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Sample records for repolarization disorder hypotheses

  1. Biological hypotheses and biomarkers of bipolar disorder.

    Science.gov (United States)

    Sigitova, Ekaterina; Fišar, Zdeněk; Hroudová, Jana; Cikánková, Tereza; Raboch, Jiří

    2017-02-01

    The most common mood disorders are major depressive disorders and bipolar disorders (BD). The pathophysiology of BD is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and for finding new biomarkers for BD. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses about the causes and pathophysiology of the BD. BD is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by: genetic and environmental factors; defects in apoptotic, immune-inflammatory, neurotransmitter, neurotrophin, and calcium-signaling pathways; oxidative and nitrosative stress; cellular bioenergetics; and membrane or vesicular transport. Current biological hypotheses of BD are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Here we also discuss the therapeutic hypotheses and mechanisms of the switch between depressive and manic state.

  2. Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome

    DEFF Research Database (Denmark)

    Petitprez, Séverine; Jespersen, Thomas; Pruvot, Etienne;

    2008-01-01

    S SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C...

  3. Test of Alternative Hypotheses Explaining the Comorbidity between Attention-Deficit/Hyperactivity Disorder and Conduct Disorder

    Science.gov (United States)

    Rhee, Soo Hyun; Willcutt, Erik G.; Hartman, Christie A.; Pennington, Bruce F.; DeFries, John C.

    2008-01-01

    There is significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). The conclusions of studies that examined the causes of comorbidity between ADHD and CD conflict, with some researchers finding support for the three independent disorders model and others finding support for the correlated risk…

  4. Test of Alternative Hypotheses Explaining the Comorbidity between Attention-Deficit/Hyperactivity Disorder and Conduct Disorder

    Science.gov (United States)

    Rhee, Soo Hyun; Willcutt, Erik G.; Hartman, Christie A.; Pennington, Bruce F.; DeFries, John C.

    2008-01-01

    There is significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). The conclusions of studies that examined the causes of comorbidity between ADHD and CD conflict, with some researchers finding support for the three independent disorders model and others finding support for the correlated risk…

  5. Sleep-specific mechanisms underlying posttraumatic stress disorder: integrative review and neurobiological hypotheses.

    Science.gov (United States)

    Germain, Anne; Buysse, Daniel J; Nofzinger, Eric

    2008-06-01

    Posttraumatic stress disorder (PTSD) is a prevalent disorder that is associated with poor clinical and health outcomes, and considerable health care utilization and costs. Recent estimates suggest that 5-20% of military personnel who serve in current conflicts in Iraq and Afghanistan meet diagnostic criteria for PTSD. Clinically, sleep disturbances are core features of PTSD that are often resistant to first-line treatments, independently contribute to poor daytime functioning, and often require sleep-focused treatments. Physiologically, these observations suggest that PTSD is partially mediated by sleep disruption and its neurobiological correlates that are not adequately addressed by first-line treatments. However, polysomnographic studies have provided limited insights into the neurobiological underpinnings of PTSD during sleep. There is an urgent need to apply state-of-the-science sleep measurement methods to bridge the apparent gap between the clinical significance of sleep disturbances in PTSD and the limited understanding of their neurobiological underpinnings. Here, we propose an integrative review of findings derived from neurobiological models of fear conditioning and fear extinction, PTSD, and sleep-wake regulation, suggesting that the amygdala and medial prefrontal cortex can directly contribute to sleep disturbances in PTSD. Testable hypotheses regarding the neurobiological underpinnings of PTSD across the sleep-wake cycle are offered.

  6. Transmural dispersion of repolarization and atrial electromechanical coupling: complementary indices for quantifying cardiac electrical heterogeneity in patients with conversion disorder

    Directory of Open Access Journals (Sweden)

    Tokatli A

    2015-07-01

    Full Text Available Alptug Tokatli,1 Omer Yiginer,2 Gokhan Degirmencioglu,2 Fethi Kilicaslan,3 Mehmet Uzun2 1Department of Cardiology, Golcuk Military Hospital, Kocaeli, 2Department of Cardiology, GATA Haydarpasa Hospital, 3Department of Cardiology, Medipol University, Istanbul, TurkeyWe read with great interest the article entitled “P-wave and QT dispersion in patients with conversion disorder” by Izci et al1 in Therapeutics and Clinical Risk Management. In this well designed research, Izci et al studied QT dispersion (QTd and P-wave dispersion (Pd in patients with conversion disorder (CD. In conclusion, they reported that corrected QT (QTc and QTd values were significantly altered in patients with CD when compared to healthy controls, but that there was no significant difference in terms of Pd.Read the original article

  7. Biomarker approaches in major depressive disorder evaluated in the context of current hypotheses

    NARCIS (Netherlands)

    Jentsch, Mike C.; Van Buel, Erin M.; Bosker, Fokko J.; Gladkevich, Anatoliy; Klein, Hans C.; Oude Voshaar, Richard; Ruhe, Eric G.; Eisel, Uli L. M.; Schoevers, Robert A.

    2015-01-01

    Major depressive disorder is a heterogeneous disorder, mostly diagnosed on the basis of symptomatic criteria alone. It would be of great help when specific biomarkers for various subtypes and symptom clusters of depression become available to assist in diagnosis and subtyping of depression, and to e

  8. A right hemisphere safety backup at work: hypotheses for deep hypnosis, post-traumatic stress disorder, and dissociation identity disorder.

    Science.gov (United States)

    Burnand, Gordon

    2013-09-01

    Problem theory points to an a priori relation between six key problems of living, to which people have adapted through evolution. Children are guided through the problems one by one, learning to switch between them automatically and unawares. The first problem of raising hope of certainty (about the environment), is dealt with in the right hemisphere (RH). The second of raising hope of freedom (or power to control), is dealt with in the left hemisphere (LH). Here adventurousness and ignoring the goodness of outcomes potentially create recklessness. When uncertainty rises the RH activates a backup with an override that substitutes immobility, takes over sensory inputs, but allows obedience to parental commands, and a cut-out that stops new work on the freedom problem. Support for the use of the backup by infants is found in the immobility that precedes the crying in strange conditions, and in childhood EEGs. The hypothesis that the backup is active in deep hypnosis imposes accord on findings that appear contradictory. For example it accounts for why observations during deep hypnosis emphasize the activity of the RH, but observations of responsive people not under hypnosis emphasize the activity of the LH. The hypothesis that the backup is active in post-traumatic stress disorder (PTSD) is supported by (a) fMRI observations that could reflect the cut-out, in that part of the precuneus has low metabolism, (b) the recall of motionlessness at the time of the trauma, (c) an argument that playing dead as a defence against predators is illogical, (d) the ease of hypnosis. With dissociative identity disorder (DID), the theory is consistent with up to six alters that have executive control and one trauma identity state where childhood traumas are re-experienced. Support for the cut-out affecting the trauma identity state comes from suppression of part of the precuneus and other parts of the parietal lobe when the trauma identity state is salient and a general script about a

  9. Early Repolarization Syndrome

    Directory of Open Access Journals (Sweden)

    Frederic Sacher

    2015-04-01

    Full Text Available The electrocardiographic pattern of early repolarization (ER is common, with a particularly high prevalence reported amongst athletes and adolescents. It has long been associated with benign outcome [1-3]. Recently, an association between inferolateral ER pattern and sudden cardiac death (SCD has been established by different groups [4-7]. Population-based studies have also reported an increased mortality rate among patients with inferolateral ER pattern compared to controls [7-9]. To bring back together these differences, it is important to focus on the definition of ER pattern used in these different studies as well as the population included. The definition of ER pattern associated with sudden cardiac death was the presence of J point elevation more than or equal to 0.1mV in at least 2 contiguous inferior and/or lateral leads of a standard 12-lead ECG and not ST elevation as it was often the case in the studies with benign outcome. Any study dealing with ER should clearly indicate the definition used. Otherwise it cannot be interpreted. Talking about definition, ER syndrome is an ER pattern (as defined above associated with symptoms (syncope or aborted SCD and/or familial history of SCD as mentioned in the last HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes [10]. It is important to recognise that having only an ER pattern is not a disease.

  10. Biomarker approaches in major depressive disorder evaluated in the context of current hypotheses.

    Science.gov (United States)

    Jentsch, Mike C; Van Buel, Erin M; Bosker, Fokko J; Gladkevich, Anatoliy V; Klein, Hans C; Oude Voshaar, Richard C; Ruhé, Eric G; Eisel, Uli L M; Schoevers, Robert A

    2015-01-01

    Major depressive disorder is a heterogeneous disorder, mostly diagnosed on the basis of symptomatic criteria alone. It would be of great help when specific biomarkers for various subtypes and symptom clusters of depression become available to assist in diagnosis and subtyping of depression, and to enable monitoring and prognosis of treatment response. However, currently known biomarkers do not reach sufficient sensitivity and specificity, and often the relation to underlying pathophysiology is unclear. In this review, we evaluate various biomarker approaches in terms of scientific merit and clinical applicability. Finally, we discuss how combined biomarker approaches in both preclinical and clinical studies can help to make the connection between the clinical manifestations of depression and the underlying pathophysiology.

  11. Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function: hypotheses and a comprehensive review.

    Science.gov (United States)

    Csermely, Peter; Sandhu, Kuljeet Singh; Hazai, Eszter; Hoksza, Zsolt; Kiss, Huba J M; Miozzo, Federico; Veres, Dániel V; Piazza, Francesco; Nussinov, Ruth

    2012-02-01

    During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into 'cumulus-type', i.e., those similar to puffy (white) clouds, and 'stratus-type', i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an 'energy transfer' mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by 'multi-trajectories'; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach 'rarely visited' but functionally-related states. We also show the role of disorder in 'spatial games' of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks.

  12. Repolarization reserve, arrhythmia and new drug development

    Directory of Open Access Journals (Sweden)

    Yang Li

    2013-05-01

    Full Text Available Repolarization-related lethal arrhythmias have led to the concept of “repolarization reserve”, which may help elucidate the relationship between K+ currents and other components of repolarization. Pharmacological manipulation as well as congenital and cardiac disease may affect repolarization and alter the repolarization reserve, leading to the development of arrhythmias. Pharmacological enhancement of outward currents or suppression of inward currents has been shown to be of therapeutic value. A number of newly found selective ion channel inhibitors or agonists have been investigated for their ability to enhance repolarization reserve and decrease the incidence of arrhythmia. In this paper we review the development, potential mechanisms, clinical application, and pharmacological significance of repolarization reserve in order to better understand, predict and prevent unexplained adverse cardiac events.

  13. Sudden cardiac death in dogs with remodeled hearts is associated with larger beat-to-beat variability of repolarization

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Truin, Michiel; van Opstal, Jurren M

    2005-01-01

    Increased proarrhythmia in dogs with chronic AV block (AVB) has been explained by ventricular remodeling causing a decrease in repolarization reserve. Beat-to-beat variability of repolarization (BVR) has been suggested to reflect repolarization reserve, in which high variability represents...... diminished reserve and larger propensity for repolarization-dependent ventricular arrhythmia. A subset of chronic AVB dogs (10%) suffers sudden cardiac death (SCD). With the assumption that repolarization defects constitute a potentially lethal proarrhythmic substrate, we hypothesized that BVR in SCD dogs...... are larger than in matched control chronic AVB dogs. From a population of 200 chronic AVB dogs, initially two groups were chosen retrospectively: 8 dogs that died suddenly (SCD) and 8 control dogs. Control dogs had a longer lifespan after AVB (10 to 18 weeks) than SCD dogs (5 to 10 weeks). All dogs had...

  14. ITSSOIN Hypotheses

    NARCIS (Netherlands)

    Anheier, H.K.; Krlev, G.; Preuss, S.; Mildenberger, G.; Bekkers, R.H.F.P.; Brink Lund, A.

    2014-01-01

    This report brings together findings from the first ITSSOIN project working steps to formulate empirically testable hypotheses on the impact of the third sector and social innovation – in particular regarding the role of the third sector in generating social innovation but also with reference to fra

  15. Ventricular repolarization measures for arrhythmic risk stratification

    Institute of Scientific and Technical Information of China (English)

    Francesco Monitillo; Marta Leone; Caterina Rizzo; Andrea Passantino; Massimo Iacoviello

    2016-01-01

    Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave(QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice.

  16. Light repolarization by scattering media

    CERN Document Server

    Sorrentini, Jacques; Soriano, Gabriel; Amra, Claude

    2011-01-01

    The polarization of a coherent depolarized incident light beam passing through a disordered medium is investigated. The local polarization of the scattered far field and the probability density function are calculated and show an excellent agreement with experiment. It is demonstrated that complex media may confer high degree of polarization (0.75 DOP average) to the incident unpolarized light.

  17. Neurophysiological Measures and Alcohol Use Disorder (AUD): Hypothesizing Links between Clinical Severity Index and Molecular Neurobiological Patterns

    Science.gov (United States)

    Vitali, Mario; Napolitano, Carmen; Berman, Marlene Oscar; Minuto, Simona Flamminii; Battagliese, Gemma; Attilia, Maria Luisa; Braverman, Eric R; Romeo, Marina; Blum, Kenneth; Ceccanti, Mauro

    2016-01-01

    Background In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics. Materials and Methods 191 alcoholics were recruited in a Day Hospital (DH) setting at the Alcohol Addiction Program Latium Region Referral Center, Sapienza University of Rome. After 7 days detoxification treatment a psychodiagnostic protocol was administered, including TCI, VAS-C, ASI and SADQ. All patients signed an Institutional Review Board (IRB) approved informed consent. Results Principally, we detected a significant positive correlation between HA-scale scores and the VAS scale: increasing in HA-scale corresponds to an increase in craving perception for both intensity (r=0.310; p ≤ 0.001) and frequency (r=0.246; p ≤ 0.001). Moreover, perception of dependence severity, measured with SADQ was also found to be significantly associated positively to both HA-scale (r=0.246; p ≤ 0.001) and NS-scale (r=0.224; p ≤ 0.01). While, for character scales, Persistence (r=−0.195; p=.008) and Self-directedness (r=−0.294; p ≤ 0.001) was negatively associated with ASI linked to alcohol problems. Self-directedness was also negatively correlated with ASI linked to family and social problems (r=−0.349; p ≤ 0.001), employment and support problems (r=−0.220; p=0.003) and psychiatric problems (r=−0.358; p ≤ 0.001). Cooperativeness was a negative correlate with Legal Problems (r=−0.173; p=0.019). and Self

  18. Na/K pump regulation of cardiac repolarization: insights from a systems biology approach

    KAUST Repository

    Bueno-Orovio, Alfonso

    2013-05-15

    The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies. © 2013 Springer-Verlag Berlin Heidelberg.

  19. Cardiac action potential repolarization re-visited: early repolarization shows all-or-none behaviour.

    Science.gov (United States)

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

    2017-08-17

    In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, action potential height and duration are key physiological variables. In addition, rate-dependent changes in ventricular action potential duration (APD), and variations in APD at a fixed heart rate, are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for Safety Pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence also draws attention to the early repolarization phase of the action potential (and the J wave of the ECG) as a biomarker for arrhythmogenesis. Here we provide mechanistic background to this Early Repolarization Syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds; and demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram as well as alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Role of abnormal repolarization in the mechanism of cardiac arrhythmia

    DEFF Research Database (Denmark)

    Osadchiy, Oleg

    2017-01-01

    impulse conduction. This review outlines the electrical activity of ventricular myocytes in normal conditions and cardiac disease, describes classical electrophysiological mechanisms of cardiac arrhythmia, and provides an update on repolarization-related surrogates currently used to assess arrhythmic...... propensity, including spatial dispersion of repolarization, activation-repolarization coupling, electrical restitution, TRIaD (triangulation, reverse use dependence, instability, and dispersion), and the electromechanical window. This is followed by a discussion of the mechanisms that account...

  1. Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of "super normal controls" in psychiatricgenetic research of complex behavioral disorders.

    Science.gov (United States)

    Chen, Thomas J H; Blum, Kenneth; Mathews, Daniel; Fisher, Larry; Schnautz, Nancy; Braverman, Eric R; Schoolfield, John; Downs, Bernard W; Comings, David E

    2005-01-01

    We hypothesize that pathological aggression, a complex behavioral disorder, in adolescents may in part involve polymorphisms of the dopaminergic system. While a number of neurotransmitter systems must be involved, due to polygenic inheritance, one major pathway should involve the dopaminergic system. Advances in our knowledge of the neurobiology of aggression and violence have given rise to rational pharmacological treatments for these behaviors. The main biological systems that are known to be involved are certain reward neurotransmitters including: serotonin, opioid peptides, gamma-aminobutyric acid, and the catecholamines (dopamine and norepinephrine). It is our notion that pathological aggressive behavior is in part similar mechanistically to other forms of impulsive behaviors such as pathological gambling. By analogy to drug dependence, it has been speculated that the underlying pathology in pathological gambling is a reduction in the sensitivity of the reward system. While studying pathological gamblers and controls during a guessing game using functional Magnetic Resonance Imaging, Reuter et al. observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that were negatively correlated with gambling severity. Subsequently, linking hypo activation of these areas to disease severity. A positive correlation of both the dopamine D2 receptor gene (DRD2) and the dopamine transporter gene (DAT1) polymorphisms were observed with pathological violence in adolescents in a blinded clinical trial. Thus, this and other cited work preliminary suggest a role for both the DRD2 and DAT genes in pathological aggressive behavior. We further hypothesize that follow-up gene research in this area, albeit premature, resulting in confirmation of positive correlations with dopaminergic polymorphisms, and utilizing highly screened controls (eliminating any addictive, compulsive and impulsive behaviors in both proband and family) may

  2. Heart rate profile during exercise in patients with early repolarization.

    Science.gov (United States)

    Cay, Serkan; Cagirci, Goksel; Atak, Ramazan; Balbay, Yucel; Demir, Ahmet Duran; Aydogdu, Sinan

    2010-09-01

    Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P heart rate increment (heart rate decrement (heart rate increment and heart rate decrement compared to higher levels, respectively. Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.

  3. Cyclical Modulation of Human Ventricular Repolarization by Respiration

    Directory of Open Access Journals (Sweden)

    Ben eHanson

    2012-09-01

    Full Text Available Background: Respiratory modulation of autonomic input to the sinus node results in cyclical modulation of heart rate, known as respiratory sinus arrhythmia. We hypothesized that the respiratory cycle may also exert cyclical modulation on ventricular repolarization, which may be separately measurable using local endocardial recordings.Methods and Results: The study included 16 subjects with normal ventricles undergoing routine clinical electrophysiological procedures for supraventricular arrhythmias. Unipolar electrograms were recorded from 10 right and 10 left ventricular endocardial sites. Breathing was voluntarily regulated at 5 fixed frequencies (6, 9, 12, 15 and 30 breaths per minute and heart rate was clamped by RV pacing. Activation-recovery intervals (ARI: a surrogate for APD exhibited significant (p<0.025 cyclical variation at the respiratory frequency in all subjects; ARI shortened with inspiration and lengthened with expiration. Peak-to-peak ARI variation ranged from 0-26 ms; the spatial pattern varied with subject. Arterial blood pressure also oscillated at the respiratory frequency (p<0.025 and lagged behind respiration by between 1.5 s and 0.65s from slowest to fastest breathing rates respectively. Systolic oscillation amplitude was significantly greater than diastolic (14±5 vs. 8±4 mmHg ± SD, p<0.001. Conclusions: Observations in humans with healthy ventricles using multiple left and right ventricular endocardial recordings showed that ARI (APD varied cyclically with respiration.

  4. Heart rate profile during exercise in patients with early repolarization

    Institute of Scientific and Technical Information of China (English)

    Serkan Cay; Goksel Cagirci; Ramazan Atak; Yucel Balbay; Ahmet Duran Demir; Sinan Aydogdu

    2010-01-01

    Background Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise.Methods A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed.Results Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrment of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P<0.05). The lower heart rate increment (<106 beats/min) and heart rate decrement (<95 beats/min) were significantly associated with the presence of early repolarization. After adjustment for age and sex, the multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95% CI 1.21-7.34) (P=0.018) and 7.73 (95% CI 2.84-21.03) (P <0.001) for the lower heart rate increment and heart rate decrement compared to higher levels, respectively.Conclusions Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.

  5. Major rapid weight loss induces changes in cardiac repolarization

    DEFF Research Database (Denmark)

    Vedel-Larsen, Esben; Iepsen, Eva Winning; Lundgren, Julie

    2016-01-01

    INTRODUCTION: Obesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology...... analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. METHODS AND RESULTS: Twenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss......A1c (pweight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight...

  6. Delayed ventricular repolarization as an anti-arrhythmic principle.

    Science.gov (United States)

    Vaughan Williams, E M

    1985-11-01

    Depolarization of cardiac muscle is achieved by 'fast inward current' through channels which are inactivated within about 1 ms. When the cells are repolarized the process of inactivation of fast channels is rapidly reversed. The class 1 anti-arrhythmic drugs delay the disappearance of inactivation until long after repolarization is complete. In theory, it should be possible to produce a similar extension of refractory period by delaying the repolarization itself. Quinidine and disopyramide caused minor delays of repolarization, but both were primarily class 1 agents, and in addition had undesirable anticholinergic activity. Amiodarone, already in use for many years as an antianginal drug, prolonged action potential duration (APD) and was shown to have an anti-arrhythmic action in rabbits, dogs and man. Although prolongation of APD lengthens QT, a long QT may be caused by phenomena other than prolonged APD, such as heterogeneity of sympathetic drive. Association of long QT with arrhythmia does not, therefore, invalidate the principle that homogeneously prolonged APD should be anti-arrhythmic. In practice, amiodarone, bretylium, sotalol, thyroidectomy, and long-term beta-blockade prolong APD, and are associated with low incidence of arrhythmia. Many mechanisms controlling cardiac repolarization have been proposed, but how repolarization is delayed by individual agents is not fully elucidated.

  7. Hypotheses and Inductive Predictions

    NARCIS (Netherlands)

    ROMEYN, J.-W.

    2008-01-01

    ABSTRACT. This paper studies the use of hypotheses schemes in generating inductive predictions. After discussing Carnap–Hintikka inductive logic, hypotheses schemes are defined and illustrated with two partitions. One partition results in the Carnapian continuum of inductive methods, the other resul

  8. Hypotheses and Inductive Predictions

    NARCIS (Netherlands)

    ROMEYN, J.-W.

    2008-01-01

    ABSTRACT. This paper studies the use of hypotheses schemes in generating inductive predictions. After discussing Carnap–Hintikka inductive logic, hypotheses schemes are defined and illustrated with two partitions. One partition results in the Carnapian continuum of inductive methods, the other resul

  9. Testing Mediators Hypothesized to Account for the Effects of a Dissonance-Based Eating Disorder Prevention Program over Longer Term Follow-Up

    Science.gov (United States)

    Stice, Eric; Marti, C. Nathan; Rohde, Paul; Shaw, Heather

    2011-01-01

    Objective: Test the hypothesis that reductions in thin-ideal internalization and body dissatisfaction mediate the effects of a dissonance-based eating disorder prevention program on reductions in eating disorder symptoms over 1-year follow-up. Method: Data were drawn from a randomized effectiveness trial in which 306 female high school students…

  10. Testing Mediators Hypothesized to Account for the Effects of a Dissonance-Based Eating Disorder Prevention Program over Longer Term Follow-Up

    Science.gov (United States)

    Stice, Eric; Marti, C. Nathan; Rohde, Paul; Shaw, Heather

    2011-01-01

    Objective: Test the hypothesis that reductions in thin-ideal internalization and body dissatisfaction mediate the effects of a dissonance-based eating disorder prevention program on reductions in eating disorder symptoms over 1-year follow-up. Method: Data were drawn from a randomized effectiveness trial in which 306 female high school students…

  11. Repolarization features as detectable from electrograms and electrocardiograms

    NARCIS (Netherlands)

    Oosterom, A. van

    2013-01-01

    This contribution discusses the feasibility of extracting the major features of repolarization: its spatio-temporal behaviour, and how much of its global or local behaviour might be deduced from signals that can be observed experimentally. The analysis presented is based on source-volume-conductor c

  12. Ventricular repolarization in a rat model of global heart failure.

    Science.gov (United States)

    Krandycheva, Valeria; Kharin, Sergey; Strelkova, Marina; Shumikhin, Konstantin; Sobolev, Aleksey; Shmakov, Dmitry

    2013-07-01

    Isoproterenol in high doses induces infarction-like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol-induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation-recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation-recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation-recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.

  13. Probing cardiac repolarization reserve in drug safety assessment

    NARCIS (Netherlands)

    Nalos, L.

    2011-01-01

    Excessive prolongation of cardiac repolarization, manifested as QT prolongation on ECG, is common unwanted side effect of many drugs and drug candidates. Prolongation of QT interval may lead to life threatening cardiac arrhythmia – Torsade de Point (TdP). Number of drugs was withdrawn from the marke

  14. The effects of sotalol on ventricular repolarization during exercise

    Institute of Scientific and Technical Information of China (English)

    LI Jian; WANG Jia-nan

    2005-01-01

    Objective: Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise. Methods: Thirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo. Results: Sotalol significantly prolonged QTc(corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001).The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate(r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo.Conclusions: These results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class Ⅲ antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise.Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.

  15. Transplantation psychoneuroimmunology: building hypotheses.

    Science.gov (United States)

    Klapheke, M M

    2000-06-01

    The research findings of psychoneuroimmunology have not yet been fully applied to the field of transplantation psychiatry. Though much study has been devoted to the impact of psychiatric disease on the immunosuppressed state and disease progression in HIV-related illness, little has yet been written on the immunology implications of psychiatric disturbances in the immunosuppressed post-transplant patient. Utilizing Medline literature searches to review relevant research data in psychoneuroimmunology and transplantation immunology, the author formulates and examines four transplantation psychoneuroimmunology hypotheses involving the potential impact of depression on post-transplant organ rejection, cancer, coronary artery disease, and infections. The author concludes that though major questions remain, it appears reasonable to include the impact of depression, and possibly other psychological states, among factors that may affect the net state of immunosuppression in transplant patients.

  16. 25 years of Eye Movement Desensitization and Reprocessing (EMDR): The EMDR therapy protocol, hypotheses of its mechanism of action and a systematic review of its efficacy in the treatment of post-traumatic stress disorder.

    Science.gov (United States)

    Novo Navarro, Patricia; Landin-Romero, Ramón; Guardiola-Wanden-Berghe, Rocio; Moreno-Alcázar, Ana; Valiente-Gómez, Alicia; Lupo, Walter; García, Francisca; Fernández, Isabel; Pérez, Víctor; Amann, Benedikt L

    2016-02-11

    Eye movement desensitization and reprocessing (EMDR) is a relatively new psychotherapy that has gradually gained popularity for the treatment of post-traumatic stress disorder. In the present work, the standardised EMDR protocol is introduced, along with current hypotheses of its mechanism of action, as well as a critical review of the available literature on its clinical effectiveness in adult post-traumatic stress disorder. A systematic review of the published literature was performed using PubMed and PsycINFO databases with the keywords «eye movement desensitization and reprocessing» and «post-traumatic stress disorder» and its abbreviations «EMDR» and «PTSD». Fifteen randomised controlled trials of good methodological quality were selected. These studies compared EMDR with unspecific interventions, waiting lists, or specific therapies. Overall, the results of these studies suggest that EMDR is a useful, evidence-based tool for the treatment of post-traumatic stress disorder, in line with recent recommendations from different international health organisations.

  17. Testing statistical hypotheses

    CERN Document Server

    Lehmann, E L

    2005-01-01

    The third edition of Testing Statistical Hypotheses updates and expands upon the classic graduate text, emphasizing optimality theory for hypothesis testing and confidence sets. The principal additions include a rigorous treatment of large sample optimality, together with the requisite tools. In addition, an introduction to the theory of resampling methods such as the bootstrap is developed. The sections on multiple testing and goodness of fit testing are expanded. The text is suitable for Ph.D. students in statistics and includes over 300 new problems out of a total of more than 760. E.L. Lehmann is Professor of Statistics Emeritus at the University of California, Berkeley. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and the recipient of honorary degrees from the University of Leiden, The Netherlands and the University of Chicago. He is the author of Elements of Large-Sample Theory and (with George Casella) he is also the author of Theory of Point Estimat...

  18. ECG-Based Measurements of Drug-induced Repolarization Changes

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed

    The purpose of this thesis is to investigate the abnormal repolarization both in the cellular and the surface ECG along with their relationship. It has been identified that the certain morphological changes of the monophasic action potential are predictor of TdP arrhythmia. Therefore the proporti......The purpose of this thesis is to investigate the abnormal repolarization both in the cellular and the surface ECG along with their relationship. It has been identified that the certain morphological changes of the monophasic action potential are predictor of TdP arrhythmia. Therefore...... the proportional changes of the surface ECG which corresponds to the arrhythmia-triggering MAP morphology is warranted to increase the confidence of determining cardiotoxicity of drugs....

  19. Lesson Twenty-two The early repolarization variant

    Institute of Scientific and Technical Information of China (English)

    鲁端; 王劲

    2007-01-01

    @@ The ST-segment elevation seen in apparently healthy and asymptomatic persons,the so-called early repolarization variant (ERPV)1.Hiss et al reported that 91% of 6014 healthy men in the US Air Force who were between 16 and 58 years old had an ST-segment elevation of 0.1 to 0.3 mV in one or more precordial leads2.The elevation was most common and marked in lead V2.

  20. Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

    Science.gov (United States)

    Jaffer, Fatima; Avbersek, Andreja; Vavassori, Rosaria; Fons, Carmen; Campistol, Jaume; Stagnaro, Michela; De Grandis, Elisa; Veneselli, Edvige; Rosewich, Hendrik; Gianotta, Melania; Zucca, Claudio; Ragona, Francesca; Granata, Tiziana; Nardocci, Nardo; Mikati, Mohamed; Helseth, Ashley R; Boelman, Cyrus; Minassian, Berge A; Johns, Sophia; Garry, Sarah I; Scheffer, Ingrid E; Gourfinkel-An, Isabelle; Carrilho, Ines; Aylett, Sarah E; Parton, Matthew; Hanna, Michael G; Houlden, Henry; Neville, Brian; Kurian, Manju A; Novy, Jan; Sander, Josemir W; Lambiase, Pier D; Behr, Elijah R; Schyns, Tsveta; Arzimanoglou, Alexis; Cross, J Helen; Kaski, Juan P; Sisodiya, Sanjay M

    2015-10-01

    Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared

  1. Molecular/genetic determinants of repolarization and their modification by environmental stress.

    Science.gov (United States)

    Rosen, M R; Cohen, I S

    2006-01-01

    Although a variety of factors, inherited or environmental, can influence expression of ion channel proteins to impact on repolarization, that environment can affect genetic determinants of repolarization for intervals of varying duration is a concept that is not as generally appreciated as it should be. In the following pages we review the molecular/genetic determinants of cardiac repolarization and summarize how pathologic events and environmental intrusions can affect these determinants. Understanding the chains of events involved should yield insights into both the causes and potential avenues of treatment for abnormalities of repolarization.

  2. An activation-repolarization time metric to predict localized regions of high susceptibility to re-entry

    Science.gov (United States)

    Child, Nicholas; Bishop, Martin J.; Hanson, Ben; Coronel, Ruben; Opthof, Tobias; Bourkens, Bastiaan; Walton, Richard; Efimov, Igor; Bostock, Julian; Hill, Yolanda; Rinaldi, Christopher A; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2015-01-01

    Background Initiation of re-entrant ventricular tachycardia (VT) involves complex interactions between activation and repolarization wavefronts. Recent experimental work has identified the time interval between S2 repolarization proximal to a line of functional block and the activation at the adjacent distal side, as a critical determinant of re-entry. Objective We hypothesized: (1) an algorithm could be developed which would generate a spatial map of this interval (designated the “re-entry vulnerability index”-RVI); (2) that this would accurately identify a pathway of re-entry as well as rotor formation in animal experiments and in a computational model; and, (3) that it would be possible to generate an RVI map in humans during routine clinical procedures and co-register with anatomical and electrophysiological features. Methods and Results An algorithm was developed which sampled all points on a multielectrode grid and calculated RVI between all pairs of electrodes within a given radius. The algorithm successfully identified the spatial region with increased susceptibility to re-entry in an established Langendorff pig heart model and the site of re-entry and rotor formation in an optically mapped sheep heart model and corresponding computational simulations. The feasibility of RVI mapping was evaluated during a clinical procedure by co-registering with the anatomy and physiology in a patient undergoing a VT ablation. Conclusions We developed an algorithm to calculate a re-entry vulnerability index from intervals between local repolarization and activation times at all adjacent points over a multielectrode grid. The algorithm accurately identified the region of re-entry in two animal models of functional re-entry. The possibility of clinical application was demonstrated in a patient with VT. PMID:25863160

  3. Diurnal modulation and sources of variation affecting ventricular repolarization in Warmblood horses

    DEFF Research Database (Denmark)

    Pedersen, Philip Juul; Moeller, Sine B; Flethøj, Mette;

    2014-01-01

    OBJECTIVES: Irregularities in cardiac repolarization are known to predispose for arrhythmias and sudden cardiac death in humans. The QT interval is a quantitative measurement of repolarization, and clinically, the QTc (QT interval corrected for heart rate) and Tpeak to Tend intervals (TpTe) are u...

  4. Early repolarization syndrome: A cause of sudden cardiac death

    Institute of Scientific and Technical Information of China (English)

    Abdi; Ali; Nida; Butt; Azeem; S; Sheikh

    2015-01-01

    Early repolarization syndrome(ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life- threatening arrhythmias and sudden cardiac death(SCD). Early repolarization characteristics associated with SCD include high-amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation(0.05 m V vs 0.1 m V) being the main determinants.ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life- threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS.

  5. Myocyte repolarization modulates myocardial function in aging dogs.

    Science.gov (United States)

    Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled; 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; Rota, Marcello

    2016-04-01

    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.

  6. [Effect of the heart electric stimulation on repolarization of fish and amphibian ventricular myocardium].

    Science.gov (United States)

    Azarov, Ia É; Kibler, N A; Vaĭshnoraĭte, M A; Tsvetkova, A S; Kharin, S N; Vitiazev, V A; Shmakov, D N

    2013-01-01

    By the method of synchronous multielectrode cartography (24-unipolar leads), distribution of durations and time of end of repolarization were studied on ventricular epicardium of pikes (Esox lucius) and frogs (Rana esculenta) and in ventricular intramural layers of toads (Bufo bufo) at the ectopic heart excitation. The time of arrival of the excitation wave and of the end of repolarization in each lead was determined from the minimum of time derivative of potential at the period of the QRS complex and by minimum of the T wave, respectively. It has been established that at the ventricle electrostimulation, alongside with deceleration and a change of sequence of the myocardium activation, there occurs redistribution of local repolarization durations: in areas of late activation the repolarization being longer than in zones of early activation (p < 0.05). At stimulation, the apicobasal gradient of repolarization is predominantly changed due to electrophysiological processes in the apical areas. In all studied species. at ectopical excitation of the heart ventricle the sequence of its repolarization repeats the depolarization sequence due to delay of activation (in fish) and redistribution of repolarization durations (in amphibians).

  7. Quinidine elicits proarrhythmic changes in ventricular repolarization and refractoriness in guinea-pig.

    Science.gov (United States)

    Osadchii, Oleg E

    2013-04-01

    Quinidine is a class Ia Na(+) channel blocker that prolongs cardiac repolarization owing to the inhibition of I(Kr), the rapid component of the delayed rectifier current. Although quinidine may induce proarrhythmia, the contributing mechanisms remain incompletely understood. This study examined whether quinidine may set proarrhythmic substrate by inducing spatiotemporal abnormalities in repolarization and refractoriness. The monophasic action potential duration (APD), effective refractory periods (ERPs), and volume-conducted electrocardiograms (ECGs) were assessed in perfused guinea-pig hearts. Quinidine was found to produce the reverse rate-dependent prolongation of ventricular repolarization, which contributed to increased steepness of APD restitution. Throughout the epicardium, quinidine elicited a greater APD increase in the left ventricular chamber compared with the right ventricle, thereby enhancing spatial repolarization heterogeneities. Quinidine prolonged APD to a greater extent than ERP, thus extending the vulnerable window for ventricular re-excitation. This change was attributed to increased triangulation of epicardial action potential because of greater APD lengthening at 90% repolarization than at 30% repolarization. Over the transmural plane, quinidine evoked a greater ERP prolongation at endocardium than epicardium and increased dispersion of refractoriness. Premature ectopic beats and monomorphic ventricular tachycardia were observed in 50% of quinidine-treated heart preparations. In summary, abnormal changes in repolarization and refractoriness contribute greatly to proarrhythmic substrate upon quinidine infusion.

  8. Evaluation of ventricular repolarization in pregnant women with intrahepatic cholestasis.

    Science.gov (United States)

    Kirbas, Ozgur; Biberoglu, Ebru Hacer; Kirbas, Ayse; Daglar, Korkut; Kurmus, Ozge; Danisman, Nuri; Biberoglu, Kutay

    2015-01-01

    Bile acids can induce arrhythmia by altering cardiomyocyte contractility or electrical conduction. The aim of this study was to investigate, by means of QT dispersion parameter detected by simple standard electrocardiogram (ECG), ventricular repolarization changes in pregnant women with and without intrahepatic cholestasis of pregnancy (ICP). In this case-control study including 75 pregnant women with cholestasis and 35 healthy, uncomplicated pregnancy cases, electrocardiographic QT interval durations and QT dispersion (QT-disp) parameters, corrected for the patients' heart rate using the Hodges formula, were investigated. Maximum corrected QT interval values were significantly higher in the severe ICP group than in the control group (p cholestasis when compared to the normal ones. This simple ECG parameter can be used to screen high-risk women, in order to better target counseling regarding lifestyle modifications and to conduct closer follow up and management of women with a history of ICP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

    Institute of Scientific and Technical Information of China (English)

    RUAN Yanfei; LIU Nian; ZHOU Qiang; LI Yang; WANG Lin

    2005-01-01

    Summary: The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P0.05). The lower IK,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

  10. Early repolarization as a predictor of premature ventricular beats.

    Science.gov (United States)

    Matoshvili, Z T; Petriashvili, Sh G; Archadze, A T; Azaladze, I G

    2015-02-01

    Early repolarization pattern (ERP) is a common ECG variant, characterized by J point elevation manifested either as terminal QRS slurring (the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on terminal QRS complex) associated with concave upward ST-segment elevation and prominent T waves in at least two contiguous leads. Aim of this observational study was to compare number of premature ventricular beats in the different groups of patients with early repolarization. The result of this observational study shows that there are: 1,74 fold higher number of premature ventricular beats in 41-74 year subgroup VS 19-40 year subgroup; 1,31 fold higher number of premature ventricular beats in male subgroup VS female subgroup (But this difference is not statistically significant, because t=1,49, p=0,141); 2,85 fold higher number of premature ventricular beats in CAD+ERP subgroup VS ERP without CAD subgroup; 1,74 fold higher number of premature ventricular beats in HF+ERP subgroup VS ERP without HF subgroup; 1,81 fold higher number of premature ventricular beats in CAD+ERP subgroup VS CAD without ERP subgroup; 1,58 fold higher number of premature ventricular beats in HF+ERP subgroup VS HF without ERP subgroup; So, CAD+ERP is very arrhythmogenic condition, after this is HF+ERP, Then Age. This study shows that ERP independently increase number of PVB in different groups (CAD, HF). This is principally new and very important result. Also the number of patients is enough to make this conclusion.

  11. Some theoretical results on the observability of repolarization heterogeneity on surface ECG.

    Science.gov (United States)

    Mainardi, Luca; Sassi, Roberto

    2013-01-01

    Assessing repolarization heterogeneity (RH) from surface ECG recording is an open issue in modern electrocardiography, despite the fact that several indexes measured on the T-wave have been proposed and tested. To understand how RH occurring at myocite level is reflected on T-wave shapes, in this paper we propose a mathematical framework that combines a simple statistical model of cardiac repolarization times with the dominant T-wave formalism. Within this framework we compare different T-wave features such as T-wave amplitude, T-wave amplitude variability or QT intervals and we describe mathematically how they are linked to the spatial and temporal components of repolarization heterogeneity.

  12. Comparison of tegaserod (HTF 919) and its main human metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart.

    Science.gov (United States)

    Drici, M D; Ebert, S N; Wang, W X; Rodriguez, I; Liu, X K; Whitfield, B H; Woosley, R L

    1999-07-01

    Tegaserod (HTF 919) is a new drug being developed for gastrointestinal motility disorders. Because other gastrointestinal prokinetic agents, such as cisapride and erythromycin, cause slowing of cardiac repolarization and have been implicated in the development of the potentially fatal ventricular arrhythmia, torsades de pointes, a study was initiated to determine whether tegaserod and its main human metabolite adversely influence cardiac repolarization. By using isolated Langendorff-perfused rabbit hearts, we show that QT intervals remain unchanged at concentrations of tegaserod from 0.5 to 10 microM. It was not until the tegaserod concentration was increased to 50 microM (roughly 500-5,000 times more concentrated than those typically found in human plasma after administration of recommended clinical dosages), that a small, but significant increase in the QT interval (12+/-4%; p 70%, respectively; p < 0.01; n = 4). Erythromycin also caused significant lengthening of QT intervals (11+/-2%; p < 0.001; n = 4), although 100 microM concentrations of this drug were required to achieve this effect. These results demonstrate that both cisapride and erythromycin can slow cardiac repolarization at therapeutic doses and that tegaserod's lack of QT prolongation at therapeutic doses suggests that it has the potential to be a safer alternative to cisapride as a gastrointestinal prokinetic agent.

  13. The Conditions for Initiating "All-or-Nothing" Repolarization in Cardiac Muscle

    Science.gov (United States)

    Noble, D.; Hall, A. E.

    1963-01-01

    Solutions have been computed for the point polarization of an infinite cable-like membrane obeying the equations used to reproduce the Purkinje fiber action potential (Noble, 1960, 1962a) in order to determine the conditions for initiating all-or-nothing repolarization during the action potential plateau. It was found that all-or-nothing repolarization would not be obtainable during the first half of the action potential in spite of the fact that the membrane current-voltage relations contain regions of negative conductance. At the point at which the all-or-nothing response is first obtained, the computed threshold is large and repolarization almost back to the resting potential would be required in order to initiate the response. The results are discussed in relation to the experimental evidence at present available on repolarization in heart muscle. PMID:19431326

  14. Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety.

    Science.gov (United States)

    Gintant, Gary A; Su, Zhi; Martin, Ruth L; Cox, Bryan F

    2006-01-01

    HERG (human-ether-a-go-go-related gene) encodes for a cardiac potassium channel that plays a critical role in defining ventricular repolarization. Noncardiovascular drugs associated with a rare but potentially lethal ventricular arrhythmia (Torsades de Pointes) have been linked to delayed cardiac repolarization and block of hERG current. This brief overview will discuss the role of hERG current in cardiac electrophysiology, its involvement in drug-induced delayed repolarization, and approaches used to define drug effects on hERG current. In addition, examples of hERG blocking drugs acting differently (i.e., overt and covert hERG blockade due to multichannel block) together with the utility and limitations of hERG assays as tools to predict the risk of delayed repolarization and proarrhythmia are discussed.

  15. Amerind taxonomy and testable hypotheses.

    Science.gov (United States)

    Pichardo, M

    1998-06-01

    The acceptance of a 30,000 yr B.P. age for Valsequillo sets new parameters for hypotheses of Paleoindian entry into America. A review of Amerind taxonomy defines the early groups as Otamid-Sundadonts. Isolation in America led to an adaptive radiation that has implications for the origin and dispersal of Pithecanthropus.

  16. The early repolarization variant--an electrocardiographic enigma with both QRS and J-STT anomalies.

    Science.gov (United States)

    Boineau, John P

    2007-01-01

    A detailed description of the electrocardiogram of the early repolarization variant, including its most common morphological variations is presented. Included is a recently identified anomaly of the QRS complex, which has not previously been reported. Ventricular activation data is presented to explain the unique QRS changes. A comparison with Wolff-Parkinson-White (preexcitation) reveals certain similarities related to a premature completion of depolarization in early repolarization variant.

  17. Procainamide and lidocaine produce dissimilar changes in ventricular repolarization and arrhythmogenicity in guinea-pig.

    Science.gov (United States)

    Osadchii, Oleg E

    2014-08-01

    Procainamide is class Ia Na(+) channel blocker that may prolong ventricular repolarization secondary to inhibition of IK r , the rapid component of the delayed rectifier K(+) current. In contrast to selective IN a blockers such as lidocaine, procainamide was shown to produce arrhythmogenic effects in the clinical setting. This study examined whether pro-arrhythmic responses to procainamide may be accounted for by drug-induced repolarization abnormalities including impaired electrical restitution kinetics, spatial gradients in action potential duration (APD), and activation-to-repolarization coupling. In perfused guinea-pig hearts, procainamide was found to prolong the QT interval on ECG and left ventricular (LV) epicardial monophasic APD, increased the maximum slope of electrical restitution, enhanced transepicardial APD variability, and eliminated the inverse correlation between the local APD and activation time values determined at distinct epicardial recording sites prior to drug infusion. In contrast, lidocaine had no effect on electrical restitution, the degree of transepicardial repolarization heterogeneities, and activation-to-repolarization coupling. Spontaneous episodes of monomorphic ventricular tachycardia were observed in 57% of procainamide-treated heart preparations. No arrhythmia was induced by lidocaine. In summary, this study suggests that abnormal changes in repolarization may contribute to pro-arrhythmic effects of procainamide.

  18. Role of the late sodium current in rate-dependent repolarization of the canine ventricle.

    Science.gov (United States)

    Zhang, Hong; Yang, Lin; Yang, Zhao; Zheng, Xiao

    2013-12-31

    Late sodium current I(NaL) is an inward current participating in maintaining the plateau of the action potential. So far its role in the repolarization of canine hearts is not well known. In this paper, by taking advantage of a computer simulation method, we developed a one-dimensional transmural tissue to study the impacts of I(NaL) on rate-dependent repolarization and its ionic basis in the canine ventricle. An OpenMP parallel algorithm was performed on a four-core personal computer to accelerate the simulation. The results demonstrated that action potential durations of midmyocytes showed greater rate dependence than the endo- and epi-myocytes. When the pacing rate was reduced, repolarization of the tissue was prolonged while the transmural dispersion of repolarization (TDR) was enlarged. The enhancement of I(NaL) further amplified this rate-dependent repolarization and TDR meanwhile increased the risk of arrhythmogenesis. I(NaL) was found highly sensitive to the pacing rate by calculating its kinetics. The study suggested that I(NaL) played an important role in the rate-dependent repolarization of the canine ventricle. Selective blockade of I(NaL) could have clinical benefits, especially for such pathological conditions with enhanced I(NaL) as long QT 3 syndrome and heart failure.

  19. The Association between Myocardial Iron Load and Ventricular Repolarization Parameters in Asymptomatic Beta-Thalassemia Patients

    Directory of Open Access Journals (Sweden)

    Mehmet Kayrak

    2012-01-01

    Full Text Available Previous studies have demonstrated impaired ventricular repolarization in patients with β-TM. However, the effect of iron overload with cardiac T2* magnetic resonance imaging (MRI on cardiac repolarization remains unclear yet. We aimed to examine relationship between repolarization parameters and iron loading using cardiac T2* MRI in asymptomatic β-TM patients. Twenty-two β-TM patients and 22 age- and gender-matched healthy controls were enrolled to the study. From the 12-lead surface electrocardiography, regional and transmyocardial repolarization parameters were evaluated manually by two experienced cardiologists. All patients were also undergone MRI for cardiac T2* evaluation. Cardiac T2* score <20 msec was considered as iron overload status. Of the QT parameters, QT duration, corrected QT interval, and QT peak duration were significantly longer in the β-TM group compared to the healthy controls. Tp−Te and Tp−Te dispersions were also significantly prolonged in β-TM group compared to healthy controls. (Tp-Te/QT was similar between groups. There was no correlation between repolarization parameters and cardiac T2* MRI values. In conclusion, although repolarization parameters were prolonged in asymptomatic β-TM patients compared with control, we could not find any relation between ECG findings and cardiac iron load.

  20. Rosuvastatin blocks hERG current and prolongs cardiac repolarization.

    Science.gov (United States)

    Plante, Isabelle; Vigneault, Patrick; Drolet, Benoît; Turgeon, Jacques

    2012-02-01

    Blocking of the potassium current I(Kr) [human ether-a-go-go related gene (hERG)] is generally associated with an increased risk of long QT syndrome (LQTS). The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, rosuvastatin, is a methanesulfonamide derivative, which shows structural similarities with several I(Kr) blockers. Hence, we assessed the effects of rosuvastatin on cardiac repolarization by using in vitro, ex vivo, and in vivo models. Patch clamp experiments on hERG-transfected human embryonic kidney (HEK) 293 cells established the potency of rosuvastatin to block hERG [half maximal inhibitory concentration (IC(50) ) = 195 nM]. We showed in isolated guinea pig hearts that 195 nM rosuvastatin prolonged (basic cycle length of 250 ms; p cancer resistance protein (BCRP), multidrug resistance gene (MDR1)] and influx [organic anion transporting polypeptide (OATP) 2B1] transporters involved in the disposition and cardiac distribution of the drug. Genetic polymorphisms observed for BCRP, MDR1, and OATP2B1, and IC(50) determined for hERG blocking lead us to propose that some patients may be at risk of rosuvastatin-induced LQTS.

  1. Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Hurtado-de-Mendoza, David; Corona-Villalobos, Celia P; Pozios, Iraklis; Gonzales, Jorge; Soleimanifard, Yalda; Sivalokanathan, Sanjay; Montoya-Cerrillo, Diego; Vakrou, Styliani; Kamel, Ihab; Mormontoy-Laurel, Wilfredo; Dolores-Cerna, Ketty; Suarez, Jacsel; Perez-Melo, Sergio; Bluemke, David A; Abraham, Theodore P; Zimmerman, Stefan L; Abraham, M Roselle

    2017-06-01

    Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias. ECG and cardiac magnetic resonance (CMR) image analyses were performed retrospectively in 112 patients with a clinical diagnosis of HCM. Replacement fibrosis was assessed by measuring late gadolinium (Gd) enhancement (LGE), using a semi-automated threshold technique. Diffuse interstitial fibrosis was assessed by measuring T1 relaxation times after Gd administration, using the Look-Locker sequence. QTc dispersion was measured digitally in the septal/anterior (V1-V4), inferior (II, III, and aVF), and lateral (I, aVL, V5, and V6) lead groups on surface ECG. All patients had evidence of asymmetric septal hypertrophy. LGE was evident in 70 (63%) patients; the median T1 relaxation time was 411±38 ms. An inverse correlation was observed between T1 relaxation time and QTc dispersion in leads V1-V4 (pdispersion in leads V1-V4 (odds ratio, 1.011 [1.004-1.0178, p=0.003). We found no correlation between presence and percentage of LGE and QTc dispersion. Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1-V4.

  2. Testing statistical hypotheses of equivalence

    CERN Document Server

    Wellek, Stefan

    2010-01-01

    Equivalence testing has grown significantly in importance over the last two decades, especially as its relevance to a variety of applications has become understood. Yet published work on the general methodology remains scattered in specialists' journals, and for the most part, it focuses on the relatively narrow topic of bioequivalence assessment.With a far broader perspective, Testing Statistical Hypotheses of Equivalence provides the first comprehensive treatment of statistical equivalence testing. The author addresses a spectrum of specific, two-sided equivalence testing problems, from the

  3. Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs.

    Science.gov (United States)

    Jost, Norbert; Virág, László; Comtois, Philippe; Ordög, Balázs; Szuts, Viktória; Seprényi, György; Bitay, Miklós; Kohajda, Zsófia; Koncz, István; Nagy, Norbert; Szél, Tamás; Magyar, János; Kovács, Mária; Puskás, László G; Lengyel, Csaba; Wettwer, Erich; Ravens, Ursula; Nánási, Péter P; Papp, Julius Gy; Varró, András; Nattel, Stanley

    2013-09-01

    The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50-100 nmol l(-1) dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 μmol l(-1) BaCl2) and IKs block (1 μmol l(-1) HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ~30% larger and ~29% smaller in human, and Na(+)-Ca(2+) exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKs α-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human-canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models for

  4. An estimate of the dispersion of repolarization times based on a biophysical model of the ECG.

    Science.gov (United States)

    Sassi, Roberto; Mainardi, Luca T

    2011-12-01

    Temporal heterogeneity of ventricular repolarization is a key quantity for the development of ventricular reentrant arrhythmia. In this paper, we introduce the V-index, a novel ECG-based estimator of the standard deviation of ventricular myocytes' repolarization times s(ϑ). Differently from other ECG metrics of repolarization heterogeneity, the V-index was derived from the analysis of a biophysical model of the ECG, where repolarization is described by the dominant T-wave (DTW) paradigm. The model explains the shape of T-waves in each lead as a projection of a main waveform (the DTW) and its derivatives weighted by scalars, the lead factors. A mathematical formula is derived to link the heterogeneity of ventricular repolarization s(ϑ) and the V-index. The formula was verified using synthetic 12-lead ECGs generated with a direct electrophysiological model for increasing values of s(ϑ) (in the range 20-70 ms). A linear relationship between the V-index and s(ϑ) was observed, V ≈ 0.675 s(ϑ) + 1.8 ms (R(2) = 0.9992). Finally, 68 ECGs from the E-OTH-12-0068-010 database of the Telemetric and Holter ECG Warehouse were analyzed. The V-index coherently increased after sotalol administration, a drug known to have QT-prolonging potential (p < 0.001).

  5. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    Science.gov (United States)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daníel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Åsa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; Ehret, Georg; Huang, Hailiang; Kao, W.H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; zu Schwabedissen, Henriette Meyer; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M.; consortium, HRGEN; den Hoed, Marcel; Loos, Ruth J.F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; de Boer, Rudolf A.; Franke, Lude; van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A.M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Fabiola Del, Greco M.; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C.M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Leach, Irene Mateo; Navis, Gerjan; van den Berg, Maarten P.; van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, André G.; Witteman, Jacqueline C.M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Gonçalo R.; Lakatta, Edward G.; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R.P.; Völker, Uwe; Snieder, Harold; Spector, Timothy D.; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T.; Viikari, Jorma S.; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W.; Pramstaller, Peter P.; Lehtimäki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Kari; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; de Bakker, Paul I.W.; Newton-Cheh, Christopher

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD. PMID:24952745

  6. Effect of Autonomic Nervous System on the Transmurai Dispersion of Ventricular Repolarization in Intact Canine

    Institute of Scientific and Technical Information of China (English)

    张存泰; 徐大文; 李泱; 刘念; 王琳; 陆再英

    2004-01-01

    Summary: The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid)and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall in 12 open-chest dogs. MAPD90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD90 of Epi, Mid and Endo before autonomic nervous stimulation were 278±11 ms,316± 16 ms and 270± 12 ms respectively, the MAPD90of Mid was significantly longer than that of Epi or Endo (P<0.01). MAPD90 of Epi, Mid and Endo were shortened by 19±4 ms, 45±6 ms,18± 3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44 ± 4 ms to 15±3 ms (P<0. 01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41 0%)during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.

  7. Calcium-activated potassium current modulates ventricular repolarization in chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Ingrid M Bonilla

    Full Text Available The role of I(KCa in cardiac repolarization remains controversial and varies across species. The relevance of the current as a therapeutic target is therefore undefined. We examined the cellular electrophysiologic effects of I(KCa blockade in controls, chronic heart failure (HF and HF with sustained atrial fibrillation. We used perforated patch action potential recordings to maintain intrinsic calcium cycling. The I(KCa blocker (apamin 100 nM was used to examine the role of the current in atrial and ventricular myocytes. A canine tachypacing induced model of HF (1 and 4 months, n = 5 per group was used, and compared to a group of 4 month HF with 6 weeks of superimposed atrial fibrillation (n = 7. A group of age-matched canine controls were used (n = 8. Human atrial and ventricular myocytes were isolated from explanted end-stage failing hearts which were obtained from transplant recipients, and studied in parallel. Atrial myocyte action potentials were unchanged by I(KCa blockade in all of the groups studied. I(KCa blockade did not affect ventricular myocyte repolarization in controls. HF caused prolongation of ventricular myocyte action potential repolarization. I(KCa blockade caused further prolongation of ventricular repolarization in HF and also caused repolarization instability and early afterdepolarizations. SK2 and SK3 expression in the atria and SK3 in the ventricle were increased in canine heart failure. We conclude that during HF, I(KCa blockade in ventricular myocytes results in cellular arrhythmias. Furthermore, our data suggest an important role for I(KCa in the maintenance of ventricular repolarization stability during chronic heart failure. Our findings suggest that novel antiarrhythmic therapies should have safety and efficacy evaluated in both atria and ventricles.

  8. Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling

    Science.gov (United States)

    Lou, Qing; Janks, Deborah L.; Holzem, Katherine M.; Lang, Di; Onal, Birce; Ambrosi, Christina M.; Fedorov, Vadim V.; Wang, I-Wen

    2012-01-01

    Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm2 field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF. PMID:23042951

  9. ECG phenomena: pseudopreexcitation and repolarization disturbances resembling ST-elevation myocardial infarction caused by an intraatrial rhabdomyoma in a newborn.

    Science.gov (United States)

    Paech, Christian; Gebauer, Roman Antonin

    2014-01-01

    As is known from other reports, a rhabdomyoma or tumor metastasis may alter intracardiac electrical conduction, producing electrical phenomena like pseudopreexcitation or repolarization disturbances resembling ST-elevation myocardial infarction or Brugada's syndrome. We present a newborn with a giant atrial rhabdomyoma and additionally multiple ventricular rhabdomyomas. He presented with several electrocardiogram (ECG) phenomena due to tumor-caused atrial depolarization and repolarization disturbances. Except from the cardiac tumors, the physical status was within normal range. Initial ECG showed a rapid atrial tachycardia with a ventricular rate of 230 bpm, which was terminated by electrical cardioversion. Afterwards, the ECG showed atrial rhythm with frequent atrial premature contractions and deformation of the PR interval with large, broad P waves and loss of discret PR segment, imposing as pseudopreexcitation. The following QRS complex was normal, with seemingly abnormal ventricular repolarization resembeling ST-elevation myocardial infarction. The atrial tumor was resected with consequent vast atrial reconstruction using patch plastic. The ventricular tumors were left without manipulation. After surgery, pseudopreexcitation and repolarization abnormalities vanished entirely and an alternans between sinus rhythm and ectopic atrial rhythm was present. These phenomena were supposably caused by isolated atrial depolarization disturbances due to tumor-caused heterogenous endocardial activation. The seemingly abnormal ventricular repolarization is probably due to repolarization of the atrial mass, superimposed on the ventricular repolarization. Recognizably, the QRS complex before and after surgical resection of the rhabdomyoma is identical, underlining the atrial origin of the repolarization abnormalities before surgery.

  10. Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Verduyn, S Cora; Stengl, Milan

    2004-01-01

    Identification of patients at risk for drug-induced torsades de pointes arrhythmia (TdP) is difficult. Increased temporal lability of repolarization has been suggested as being valuable to predict proarrhythmia. The predictive value of different repolarization parameters, including beat-to-beat v...

  11. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; Van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dorr, Marcus; Miiller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikainen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stephanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Asa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; EhreT, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Schwabedissen, Henriette Meyer Zu; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Poagek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Holm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobboll, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Hoffmann, Per; Jockel, Karl-Heinz; Kalsch, Hagen; Nothen, Markus M.; Den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Pruchal, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; De Boer, Rudolf A.; Franke, Lude; Van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardail, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Del Greco, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; Van den Berg, Maarten P.; Van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Goncalo R.; Lakatta, Edward G.; Mulas, Antonella; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Volker, Uwe; Snieder, Harold; Spector, Timothy D.; Arnlov, Johan; Lind, Lars; Sundstrom, Johan; Syvanen, Ann-Christine; Kivimaki, Mika; Kahonen, Mika; Mononen, Nina; Raitakari, I. T.; Viikari, Jorma S.; Adamkova, Vera; Kiech, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gaspariniin, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Miihleisen, Thomas W.; Pramstaller, Peter P.; Lehtimaki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; Van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Karl; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kaab, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; De Bakker, Paul I. W.; Newton-Cheh, Christopher

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using

  12. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre); T.W. Mühleisen (Thomas); P.P. Pramstaller (Peter Paul); T. Lehtimäki (Terho); A.D. Paterson (Andrew); A. Parsa (Afshin); Y. Liu (Yongmei); C.M. van Duijn (Cock); D.S. Siscovick (David); V. Gudnason (Vilmundur); Y. Jamshidi (Yalda); V. Salomaa (Veikko); S.B. Felix (Stephan); S. Sanna (Serena); M.D. Ritchie (Marylyn); B.H.Ch. Stricker (Bruno); J-A. Zwart (John-Anker); L.A. Boyer (Laurie); T.P. Cappola (Thomas); J.V. Olsen (Jesper); P. Lage (Pedro); P.J. Schwartz (Peter); S. Kääb (Stefan); A. Chakravarti (Aravinda); M. Ackerman (Margaret); A. Pfeufer (Arne); P.I.W. de Bakker (Paul); C. Newton-Cheh (Christopher)

    2014-01-01

    textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (L

  13. Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, Rikke; Høi-Hansen, Thomas; Olsen, Niels Vidiendal;

    2008-01-01

    AIMS: Activity in the renin-angiotensin system (RAS) may influence the susceptibility to cardiac arrhythmia. To study the effect of basal RAS activity on cardiac repolarization during myocardial stress induced by hypoglycaemia or hypoxaemia in healthy humans. METHODS AND RESULTS: Ten subjects...

  14. Cardiac repolarization during hypoglycaemia in type 1 diabetes: impact of basal renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, Rikke; Høi-Hansen, Thomas; Larroude, Charlotte Ellen;

    2008-01-01

    activity affects cardiac repolarization during hypoglycaemia, thereby potentially carrying prognostic information on risk of the 'dead-in-bed syndrome'. METHODS AND RESULTS: Nine subjects with high RAS activity and nine subjects with low RAS activity were subjected to single-blinded placebo...

  15. Effects of Na+ channel blockers on extrasystolic stimulation-evoked changes in ventricular conduction and repolarization.

    Science.gov (United States)

    Osadchii, Oleg E

    2014-03-01

    Antiarrhythmic agents which belong to class Ia (quinidine) and Ic (flecainide) reportedly increase propensity to ventricular tachyarrhythmia, whereas class Ib agents (lidocaine and mexiletine) are recognized as safe antiarrhythmics. Clinically, tachyarrhythmia is often initiated by a premature ectopic beat, which increases spatial nonuniformities in ventricular conduction and repolarization thus facilitating reentry. This study examined if electrical derangements evoked by premature excitation may be accentuated by flecainide and quinidine, but unchanged by lidocaine and mexiletine, which would explain the difference in their safety profile. In perfused guinea pig hearts, a premature excitation evoked over late repolarization phase was associated with prolonged epicardial activation time, reduced monophasic action potential duration (APD), and increased transepicardial dispersion of the activation time and APD. Flecainide and quinidine increased conduction slowing evoked by extrasystolic stimulation, prolonged APD, and accentuated spatial heterogeneities in ventricular conduction and repolarization associated with premature excitation. Spontaneous episodes of nonsustained monomorphic ventricular tachycardia were observed in 50% of heart preparations exposed to drug infusion. In contrast, lidocaine and mexiletine had no effect on extrasystolic stimulation-evoked changes in ventricular conduction and repolarization or arrhythmic susceptibility. These findings suggest that flecainide and quinidine may promote arrhythmia by exaggerating electrophysiological abnormalities evoked by ectopic beats.

  16. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre)

    2014-01-01

    textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome

  17. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; Van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dorr, Marcus; Miiller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikainen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stephanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Asa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; EhreT, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Schwabedissen, Henriette Meyer Zu; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Poagek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Holm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobboll, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Hoffmann, Per; Jockel, Karl-Heinz; Kalsch, Hagen; Nothen, Markus M.; Den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Pruchal, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; De Boer, Rudolf A.; Franke, Lude; Van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardail, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Del Greco, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; Van den Berg, Maarten P.; Van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Goncalo R.; Lakatta, Edward G.; Mulas, Antonella; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Volker, Uwe; Snieder, Harold; Spector, Timothy D.; Arnlov, Johan; Lind, Lars; Sundstrom, Johan; Syvanen, Ann-Christine; Kivimaki, Mika; Kahonen, Mika; Mononen, Nina; Raitakari, I. T.; Viikari, Jorma S.; Adamkova, Vera; Kiech, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gaspariniin, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Miihleisen, Thomas W.; Pramstaller, Peter P.; Lehtimaki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; Van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Karl; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kaab, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; De Bakker, Paul I. W.; Newton-Cheh, Christopher

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using

  18. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre); T.W. Mühleisen (Thomas); P.P. Pramstaller (Peter Paul); T. Lehtimäki (Terho); A.D. Paterson (Andrew); A. Parsa (Afshin); Y. Liu (Yongmei); C.M. van Duijn (Cock); D.S. Siscovick (David); V. Gudnason (Vilmundur); Y. Jamshidi (Yalda); V. Salomaa (Veikko); S.B. Felix (Stephan); S. Sanna (Serena); M.D. Ritchie (Marylyn); B.H.Ch. Stricker (Bruno); J-A. Zwart (John-Anker); L.A. Boyer (Laurie); T.P. Cappola (Thomas); J.V. Olsen (Jesper); P. Lage (Pedro); P.J. Schwartz (Peter); S. Kääb (Stefan); A. Chakravarti (Aravinda); M. Ackerman (Margaret); A. Pfeufer (Arne); P.I.W. de Bakker (Paul); C. Newton-Cheh (Christopher)

    2014-01-01

    textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (L

  19. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; Van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dorr, Marcus; Miiller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikainen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stephanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Asa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; EhreT, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Schwabedissen, Henriette Meyer Zu; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Poagek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Holm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobboll, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Hoffmann, Per; Jockel, Karl-Heinz; Kalsch, Hagen; Nothen, Markus M.; Den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Pruchal, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; De Boer, Rudolf A.; Franke, Lude; Van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardail, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Del Greco, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; Van den Berg, Maarten P.; Van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Goncalo R.; Lakatta, Edward G.; Mulas, Antonella; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Volker, Uwe; Snieder, Harold; Spector, Timothy D.; Arnlov, Johan; Lind, Lars; Sundstrom, Johan; Syvanen, Ann-Christine; Kivimaki, Mika; Kahonen, Mika; Mononen, Nina; Raitakari, I. T.; Viikari, Jorma S.; Adamkova, Vera; Kiech, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gaspariniin, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Miihleisen, Thomas W.; Pramstaller, Peter P.; Lehtimaki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; Van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Karl; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kaab, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; De Bakker, Paul I. W.; Newton-Cheh, Christopher

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using

  20. The contribution of ventricular apicobasal and transmural repolarization patterns to the development of the T wave body surface potentials in frogs (Rana temporaria) and pike (Esox lucius).

    Science.gov (United States)

    Vaykshnorayte, Marina A; Azarov, Jan E; Tsvetkova, Alena S; Vityazev, Vladimir A; Ovechkin, Alexey O; Shmakov, Dmitry N

    2011-05-01

    The study aimed at the simultaneous determination of the transmural and apicobasal differences in the repolarization timing and the comparison of the contributions of these two repolarization gradients to the development of the body surface T wave potentials in animals with the single heart ventricle (fishes and amphibians). Unipolar potentials were measured on the body surface, epicardium and in the intramural (subepicardial, Epi; midmyocardial; and subendocardial, Endo) ventricular layers of 9 pike and 8 frogs. Activation times, repolarization times and activation-recovery intervals were determined. A transmural gradient in repolarization durations in frogs (Endo>Epi, Ppike that produces a repolarization sequence from Endo to Epi (Endopike and frogs.

  1. In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism

    Directory of Open Access Journals (Sweden)

    Carducci Claudia

    2012-04-01

    Full Text Available Abstract Background The discovery of the inherited disorders of creatine (Cr synthesis and transport in the last few years disclosed the importance of blood Cr supply for the normal functioning of the brain. These putatively rare diseases share a common pathogenetic mechanism (the depletion of brain Cr and similar phenotypes characterized by mental retardation, language disturbances, seizures and movement disorders. In the effort to improve our knowledge on the mechanisms regulating Cr pool inside the nervous tissue, Cr transport and synthesis and related gene transcripts were explored in primary cultures of rat cerebellar granule cells and astrocytes. Methods Cr uptake and synthesis were explored in vitro by incubating monotypic primary cultures of rat type I astrocytes and cerebellar granule cells with: a D3-Creatine (D3Cr and D3Cr plus β-guanidinopropionate (GPA, an inhibitor of Cr transporter, and b labelled precursors of Guanidinoacetate (GAA and Cr (Arginine, Arg; Glycine, Gly. Intracellular D3Cr and labelled GAA and Cr were assessed by ESI-MS/MS. Creatine transporter (CT1, L-arginine:glycine amidinotransferase (AGAT, and S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT gene expression was assessed in the same cells by real time PCR. Results D3Cr signal was extremely high in cells incubated with this isotope (labelled/unlabelled Cr ratio reached about 10 and 122, respectively in cerebellar granule cells and astrocytes and was reduced by GPA. Labelled Arg and Gly were taken up by the cells and incorporated in GAA, whose concentration paralleled that of these precursors both in the extracellular medium and inside the cells (astrocytes. In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells and 21% (astrocytes of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells. Conclusions Our

  2. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

    Science.gov (United States)

    Storm, J F

    1987-04-01

    1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the

  3. Chronic Omega-3 Polyunsaturated Fatty Acid Treatment Variably Affects Cellular Repolarization in a Healed Post-MI Arrhythmia Model

    Science.gov (United States)

    Bonilla, Ingrid M.; Nishijima, Yoshinori; Vargas-Pinto, Pedro; Baine, Stephen H.; Sridhar, Arun; Li, Chun; Billman, George E.; Carnes, Cynthia A.

    2016-01-01

    Introduction: Over the last 40 years omega-3 polyunsaturated fatty acids (PUFAs) have been shown to be anti-arrhythmic or pro-arrhythmic depending on the method and duration of administration and model studied. We previously reported that omega-3 PUFAs do not confer anti-arrhythmic properties and are pro-arrhythmic in canine model of sudden cardiac death (SCD). Here, we evaluated the effects of chronic omega-3 PUFA treatment in post-MI animals susceptible (VF+) or resistant (VF−) to ventricular tachyarrhythmias. Methods: Perforated patch clamp techniques were used to measure cardiomyocyte action potential durations (APD) at 50 and 90% repolarization and short term variability of repolarization. The early repolarizing transient outward potassium current Ito was also studied. Results: Omega-3 PUFAs prolonged the action potential in VF− myocytes at both 50 and 90% repolarization. Short term variability of repolarization was increased in both untreated and treated VF− myocytes vs. controls. Ito was unaffected by omega-3 PUFA treatment. Omega-3 PUFA treatment attenuated the action potential prolongation in VF+ myocytes, but did not return repolarization to control values. Conclusions: Omega-3 PUFAs do not confer anti-arrhythmic properties in the setting of healed myocardial infarction in a canine model of SCD. In canines previously resistant to ventricular fibrillation (VF−), omega-3 PUFA treatment prolonged the action potential in VF− myocytes, and may contribute to pro-arrhythmic responses. PMID:27378936

  4. Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Jiang-hua ZHONG; Xiao-pan CHEN; Mei-ling YUN; Wei-jing LI; Yan-fang CHEN; Zhen YAO

    2007-01-01

    Aim: To study the effects of carvedilol on the transmural heterogeneity of ven-tricular repolarization in rabbits with congestive heart failure (CHF). Methods:Rabbits were randomly divided into 3 groups: control, CHF and carvedilol treated CHF group. Monophasic action potential duration (MAPD) in the 3 myocardial layers was simultaneously recorded. Results: All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resis-tance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold (VFT) was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization (TDR) was significantly increased in CHF.Low-dose carvedilol (0.25 mg/kg, twice daily) had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Al-though the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF. Conclusion: In the present study, the trans-mural heterogeneity of ventricular repolarization increased in the rabbits with CHF. Low-dose carvedilol decreased the transmural heterogeneity of ventricular repolarization in CHF, which may be related to its direct electrophysiological pro-perty rather than its effect on ventricular remodeling.

  5. Effects of hypokalemia on transmural dispersion of ventricular repolarization in left ventricular myocardium

    Institute of Scientific and Technical Information of China (English)

    Jiang-Hua Zhong; Shi-Juan Lu; Mo-Shui Chen; Zi-Bin Chen; Liu Wang; Ping-Sheng Wu

    2013-01-01

    Objective: To observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit, and explore the role of hypokalemia in malignant ventricular arrhythmia (MVA). Methods: A total of 20 rabbits were randomly divided into control group and hypokalemic group. Isolated hearts in the control group were simply perfused with modified Tyrode's solution, and were perfused with hypokalemic Tyrode's solution in hypokalemic group. Ventricular fibrillation threshold (VFT), 90% monophasic action potential repolarization duration (APD90) of subepicardial, midmyocardial and subendocardial myocardium, transmural dispersion of repolarization (TDR) and Cx43 protein expression in three layers of myocardium were measured in both groups. Results: VFT in the control group and the hypokalemic group were (13.40±2.95) V, and (7.00±1.49) V, respectively. There was a significant difference between two groups (P<0.01). APD90 of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group (P<0.01). APD90 in the hypokalemic group and the control group were (38.10±10.29) ms and (23.70±5.68) ms, and TDR were (52.90±14.55) ms and (36.10±12.44) ms, respectively. APD90 and TDR in the hypokalemic group were significantly higher than those in the control group (P<0.05), and the increase in APD90 of midmyocardium was more significant in the hypokalemic group. Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group (P<0.01), and Cx43 was significantly increased (P<0.05). Reduction of Cx43 protein expression was more significant in the midmyocardium. Conclusions: Hypokalemic can increase transmural heterogeneity of Cx43 expression and repolarization in left ventricular myocardium of rabbit, and decrease VFT and can induce MVA more easily.

  6. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

    2016-01-01

    in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  7. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    DEFF Research Database (Denmark)

    Arking, Dan E; Pulit, Sara L; Crotti, Lia

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Usi....... Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc....

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

    DEFF Research Database (Denmark)

    Hyltén-Cavallius, Louise; Iepsen, Eva W; Christiansen, Michael

    2017-01-01

    . RESULTS: 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 ... by ingestion of 75-g glucose caused cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients compared with control subjects....

  9. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    Science.gov (United States)

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-12-17

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission.

  10. Anti- or profibrillatory effects of Na+ channel blockade depend on the site of application relative to gradients in repolarization

    Directory of Open Access Journals (Sweden)

    Ruben Coronel

    2010-06-01

    Full Text Available Introduction. Sodium channel blockers are associated with arrhythmic sudden death, although they are considered antiarrhythmic agents. The mechanism of these opposing effects is unknown. Methods. We used a model of induction of ventricular fibrillation (VF based on selective perfusion of the vascular beds of isolated porcine hearts (n=8. One bed was perfused with sotalol (220 µM, the adjacent bed with pinacidil (80 µM, leading to repolarization heterogeneity (late repolarization in the sotalol-, early in the pinacidil-area. Premature stimulation from the area with the short action potential was performed. Epicardial activation/repolarization mapping was done. Results. In 3 of the 8 hearts VF was inducible prior to infusion of flecainide. In those hearts the Fibrillation Factor (FF, the interval between the last activation of the premature beat (S2 in the late repolarizing (sotalol domain and the earliest S2 repolarization in the early repolarizing (pinacidil domain, was significantly shorter than in the hearts without VF (33+/-22 vs 93+/-11 ms, m+/-SEM, p<0.05. In the 3 hearts with VF flecainide was infused in the pinacidil domain after defibrillation. This led to shortening of the line of block, local delay of S2 activation and repolarization, an increase in FF and failure to induce VF. In the 5 hearts without VF, flecainide was subsequently infused in the sotalol domain. This led to a local delay of S2 activation, a shortening of FF (by 47+/- 3 ms and successful induction of VF in 3 hearts. In the 2 remaining hearts FF did not decrease enough (maximally 13 ms to allow reentry. Conclusions Sodium channel blockade applied to myocardium with a short refractory period is antifibrillatory whereas sodium channel blockade of myocardium with a long refractory period is profibrillatory. Our study provides a mechanistic basis for pro- and anti-arrhythmic effects of sodium channel blockers in the absence of structural heart disease.

  11. Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major.

    Directory of Open Access Journals (Sweden)

    Chun-An Chen

    Full Text Available BACKGROUND: Patients with transfusion-dependent beta-thalassemia major (TM are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. METHODS AND RESULTS: Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc, a standard deviation of QTc (SD-QTc, and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001. Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20 compared to those with normal T2* (all p values<0.001. Loge cardiac T2* correlated with SI-QTc (r = -0.609, p<0.001, SD-QTc (r = -0.572, p<0.001, and QTc dispersion (r = -0.622, p<0.001, while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86, similar to that of cardiac T2*. CONCLUSIONS: Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.

  12. Quantitative linking hypotheses for infant eye movements.

    Directory of Open Access Journals (Sweden)

    Daniel Yurovsky

    Full Text Available The study of cognitive development hinges, largely, on the analysis of infant looking. But analyses of eye gaze data require the adoption of linking hypotheses: assumptions about the relationship between observed eye movements and underlying cognitive processes. We develop a general framework for constructing, testing, and comparing these hypotheses, and thus for producing new insights into early cognitive development. We first introduce the general framework--applicable to any infant gaze experiment--and then demonstrate its utility by analyzing data from a set of experiments investigating the role of attentional cues in infant learning. The new analysis uncovers significantly more structure in these data, finding evidence of learning that was not found in standard analyses and showing an unexpected relationship between cue use and learning rate. Finally, we discuss general implications for the construction and testing of quantitative linking hypotheses. MATLAB code for sample linking hypotheses can be found on the first author's website.

  13. Temporal complexity of repolarization and mortality in patients with implantable cardioverter defibrillators.

    Science.gov (United States)

    Perkiomaki, Juha S; Couderc, Jean-Philippe; Daubert, James P; Zareba, Wojciech

    2003-10-01

    Increased repolarization variability has been observed in various cardiac conditions. However, data on its relation to heart rate variability and on its value in predicting adverse outcomes in high risk patients are limited. Forty-seven patients with decreased left ventricular function and ICDs had high resolution 10-minute ECG recordings and were followed for 781 +/- 258 days (mean +/- SD) on average. The interval from the R peak to the T wave peak with maximum amplitude (RTmax) and from the R peak to the T wave offset (RToff) were determined automatically on a beat-to-beat basis. Temporal beat-to-beat RTmax and RToff variability were analyzed using traditional summary statistics, a complexity measure (approximate entropy [ApEn]), and the short-term scaling exponent (alpha1). Eight (17%) patients died and 16 (34%) patients experienced death/appropriate ICD shock during follow-up. RTmax-ApEn was significantly higher in patients who died compared with patients who survived (1.24 +/- 0.13 vs 1.01 +/- 0.21, respectively, P=0.008). When RTmax-ApEn was tested together with the alpha1 of the RR intervals, occurrence of ventricular arrhythmias before ICD implantation, and beta-blockers usage in the Cox regression analysis, it still independently predicted mortality; hazard ratio=3.36 (1.28-8.83, 95% CI, P=0.014) for every 0.10-increase in RTmax-ApEn. None of the repolarization variability parameters independently predicted death/appropriate ICD shocks. Increased temporal complexity of repolarization (RTmax-ApEn) independently predicts mortality in ICD patients.

  14. Double pharmacological challenge on repolarization opens new avenues for drug safety research

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard

    2007-01-01

    pointes (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are neglecting the available proarrhythmia models. In vitro studies have suggested that combined pharmacological hits on repolarization will produce a superior substrate for in vivo proarrhythmia, compared to the single......-drug assessment. By using consecutive pharmacological challenges, a simple model is proposed, in which combinatorial pharmacology is employed to provoke TdP in the conscious dog. The pharmaceutical industry interested in evaluating the proarrhythmic potential of their present and future drugs now has a simple...

  15. Reconciling Mechanistic Hypotheses About Rhizosphere Priming

    Science.gov (United States)

    Cheng, W.

    2016-12-01

    Rhizosphere priming on soil organic matter decomposition has emerged as a key mechanism regulating biogeochemnical cycling of carbon, nitrogen and other elements from local to global scales. The level of the rhizosphere priming effect on decomposition rates can be comparable to the levels of controls from soil temperature and moisture conditions. However, our understanding on mechanisms responsible for rhizosphere priming remains rudimentary and controversial. The following individual hypotheses have been postulated in the published literature: (1) microbial activation, (2) microbial community succession, (3) aggregate turnover, (4) nitrogen mining, (5) nutrient competition, (6) preferential substrate utilization, and (7) drying-rewetting. Meshing these hypotheses with existing empirical evidence tends to support a general conclusion: each of these 7 hypotheses represents an aspect of the overall rhizosphere priming complex while the relative contribution by each individual aspect varies depending on the actual plant-soil conditions across time and space.

  16. Bayesian evaluation of inequality constrained hypotheses.

    Science.gov (United States)

    Gu, Xin; Mulder, Joris; Deković, Maja; Hoijtink, Herbert

    2014-12-01

    Bayesian evaluation of inequality constrained hypotheses enables researchers to investigate their expectations with respect to the structure among model parameters. This article proposes an approximate Bayes procedure that can be used for the selection of the best of a set of inequality constrained hypotheses based on the Bayes factor in a very general class of statistical models. The software package BIG is provided such that psychologists can use the approach proposed for the analysis of their own data. To illustrate the approximate Bayes procedure and the use of BIG, we evaluate inequality constrained hypotheses in a path model and a logistic regression model. Two simulation studies on the performance of our approximate Bayes procedure show that it results in accurate Bayes factors. PsycINFO Database Record (c) 2014 APA, all rights reserved

  17. Pharmacological inhibition of I-K1 by PA-6 in isolated rat hearts affects ventricular repolarization and refractoriness

    DEFF Research Database (Denmark)

    Skarsfeldt, Mark A.; Carstensen, Helena; Skibsbye, Lasse

    2016-01-01

    The inwardly rectifying potassium current (IK1) conducted through Kir2.X channels contribute to repolarization of the cardiac action potential and to stabilization of the resting membrane potential in cardiomyocytes. Our aim was to investigate the effect of the recently discovered IK1 inhibitor PA......-6 on action potential repolarization and refractoriness in isolated rat hearts. Transiently transfected HEK-293 cells expressing IK1 were voltage-clamped with ramp protocols. Langendorff-perfused heart experiments were performed on male Sprague–Dawley rats, effective refractory period, Wenckebach...... experiments, PA-6 prolonged the ventricular action potential duration at 90% repolarization (from 41.8 6.5 msec to 72.6 21.1 msec, 74% compared to baseline, P

  18. Archaerhodopsin voltage imaging: synaptic calcium and BK channels stabilize action potential repolarization at the Drosophila neuromuscular junction.

    Science.gov (United States)

    Ford, Kevin J; Davis, Graeme W

    2014-10-29

    The strength and dynamics of synaptic transmission are determined, in part, by the presynaptic action potential (AP) waveform at the nerve terminal. The ion channels that shape the synaptic AP waveform remain essentially unknown for all but a few large synapses amenable to electrophysiological interrogation. The Drosophila neuromuscular junction (NMJ) is a powerful system for studying synaptic biology, but it is not amenable to presynaptic electrophysiology. Here, we demonstrate that Archaerhodopsin can be used to quantitatively image AP waveforms at the Drosophila NMJ without disrupting baseline synaptic transmission or neuromuscular development. It is established that Shaker mutations cause a dramatic increase in neurotransmitter release, suggesting that Shaker is predominantly responsible for AP repolarization. Here we demonstrate that this effect is caused by a concomitant loss of both Shaker and slowpoke (slo) channel activity because of the low extracellular calcium concentrations (0.2-0.5 mM) used typically to assess synaptic transmission in Shaker. In contrast, at physiological extracellular calcium (1.5 mM), the role of Shaker during AP repolarization is limited. We then provide evidence that calcium influx through synaptic CaV2.1 channels and subsequent recruitment of Slo channel activity is important, in concert with Shaker, to ensure proper AP repolarization. Finally, we show that Slo assumes a dominant repolarizing role during repetitive nerve stimulation. During repetitive stimulation, Slo effectively compensates for Shaker channel inactivation, stabilizing AP repolarization and limiting neurotransmitter release. Thus, we have defined an essential role for Slo channels during synaptic AP repolarization and have revised our understanding of Shaker channels at this model synapse.

  19. Validating Inductive Hypotheses by Mode Inference

    Institute of Scientific and Technical Information of China (English)

    王志坚

    1993-01-01

    Sme criteria based on mode inference for validating inductive hypotheses are presented in this paper.Mode inference is caried out mechanically,thus such kind of validation can result in low overhead in consistency check and high efficiency in performance.

  20. Testing inequality constrained hypotheses in SEM Models

    NARCIS (Netherlands)

    Van de Schoot, R.; Hoijtink, H.J.A.; Dekovic, M.

    2010-01-01

    Researchers often have expectations that can be expressed in the form of inequality constraints among the parameters of a structural equation model. It is currently not possible to test these so-called informative hypotheses in structural equation modeling software. We offer a solution to this probl

  1. Bayesian evaluation of inequality constrained hypotheses

    NARCIS (Netherlands)

    Gu, X.; Mulder, J.; Deković, M.; Hoijtink, H.

    2014-01-01

    Bayesian evaluation of inequality constrained hypotheses enables researchers to investigate their expectations with respect to the structure among model parameters. This article proposes an approximate Bayes procedure that can be used for the selection of the best of a set of inequality constrained

  2. Cardiac Repolarization Changes in the Children with Breath-Holding Spells

    Science.gov (United States)

    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

  3. Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings.

    Science.gov (United States)

    Stramba-Badiale, M; Locati, E H; Martinelli, A; Courville, J; Schwartz, P J

    1997-06-01

    There are gender-related differences in the QT interval measured from standard ECG tracings. However, these observations are based on a limited number of beats recorded in resting conditions. Computerized Holter techniques enable ventricular repolarization and its relationship with cardiac cycle length to be analysed long term. Previous studies used only the initial portion of the QT interval to the T wave apex (QTa) to measure ventricular repolarization; however, QTa may underestimate the total QT duration (QTe). The aims of this study were to verify whether QTa and QTe had similar rate-dependence in normal subjects and whether gender-related QTe differences observed in the resting ECG were also present in the long-term QT intervalcycle length relationship. Twenty-four hour Holter recordings were obtained in 40 healthy young subjects. 20 females and 20 males (mean age 28 +/- 9 and 26 +/- 5 years, respectively ns). Two-channel ECG digitized signals were processed using new automatic QT analysis software (Ela Medical), which converted the 24-h recordings into 2880 30-s templates. It also measured the QT apex (QTa) QT end (QTe) and the RR interval (ms) of each template, and computed the slopes of the linear regressions of QTe and QTa values plotted against the corresponding RR interval (QTe/RR and QTa/RR). Females had a shorter RR interval than males (803 +/- 129 vs 877 +/- 86 ms. P = 0.037), with longer mean QTc (420 +/- 17 vs 400 +/- 200 ms. P = 0.0005). In both genders. QTa/RR slopes were steeper than QTe/RR slopes (P = 0.0001). Both QTa/RR and QTe/RR slopes were steeper in females than in males (QTa/RR 0.20 +/- 0.04 vs 0.16 +/- 0.03, P = 0.001; QTe/RR 0.16 +/- 0.04 vs 0.13 +/- 0.03, P = 0.027). Of note, QTa and QTe at fixed long cycle lengths (1000 ms) were longer in women than in men (QTa1000 330 +/- 20 vs 309 +/- 18 ms: P = 0.002; QTe1000 410 +/- 17 vs 389 +/- 19 ms: P = 0.002), while they did not differ at fixed short cycle lengths (600 ms). This study

  4. Singularity hypotheses a scientific and philosophical assessment

    CERN Document Server

    Moor, James; Søraker, Johnny; Steinhart, Eric

    2012-01-01

    Singularity Hypotheses: A Scientific and Philosophical Assessment offers authoritative, jargon-free essays and critical commentaries on accelerating technological progress and the notion of technological singularity. It focuses on conjectures about the intelligence explosion, transhumanism, and whole brain emulation. Recent years have seen a plethora of forecasts about the profound, disruptive impact that is likely to result from further progress in these areas. Many commentators however doubt the scientific rigor of these forecasts, rejecting them as speculative and unfounded. We therefore invited prominent computer scientists, physicists, philosophers, biologists, economists and other thinkers to assess the singularity hypotheses. Their contributions go beyond speculation, providing deep insights into the main issues and a balanced picture of the debate.

  5. Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice

    DEFF Research Database (Denmark)

    Speerschneider, T; Grubb, Søren Jahn; Olesen, S P;

    2016-01-01

    AIM: In this study, we investigate the impact of altered action potential durations (APD) on ventricular repolarization time and proarrhythmia in mice with and without genetic deletion of the K(+) -channel-interacting protein 2 (KChIP2(-/-) and WT respectively). Moreover, we examine...

  6. Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts.

    Science.gov (United States)

    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.

  7. Comparison of QT dispersion during atrial fibrillation and sinus rhythm in the same patients, at normal and prolonged ventricular repolarization

    NARCIS (Netherlands)

    Houltz, B; Darpo, B; Swedberg, K; Blomstrom, P; Crijns, HJGM; Jensen, SM; Svernhage, E; Edvardsson, N

    Aims Drug-induced increase in QT dispersion has been associated with increased risk of ventricular proarrhythmia. The aim of the present study was to compare QT dispersion during atrial fibrillation and sinus rhythm in the same patients at normal and prolonged ventricular repolarization. Methods and

  8. Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts.

    Directory of Open Access Journals (Sweden)

    Oleg E Osadchii

    Full Text Available 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.

  9. Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    David Hurtado-de-Mendoza, MD

    2017-06-01

    Conclusion: Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1–V4.

  10. Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization

    DEFF Research Database (Denmark)

    Graff, Claus; Struijk, Johannes J.; Matz, J;

    2010-01-01

    This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320...

  11. Attenuated ventricular β-adrenergic response and reduced repolarization reserve in a rabbit model of chronic heart failure

    DEFF Research Database (Denmark)

    Nissen, Jakob Dahl; Thomsen, Morten Bækgaard; Bentzen, Bo Hjorth

    2012-01-01

    mortality but profound structural, functional, and electrical remodeling and compare with nonpaced controls. Pacing increased heart weight/body weight ratio and decreased left ventricular fractional shortening in tachypaced only. Electrocardiogram recordings during sinus rhythm revealed QTc prolongation...... remodeling but very low mortality. Isokalemic and hyperkalemic responses indicate downregulation of functional IKs. Increased short-term variability during hypokalemia unmasks a reduced repolarization reserve....

  12. Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice.

    Science.gov (United States)

    Farkas, Attila S; Nattel, Stanley

    2010-03-26

    Proarrhythmia, the development of new or worse arrhythmias in response to drug therapy, is a major limitation to the development and use of new drugs. There are different types of drug-induced proarrhythmia, including long-QT syndrome (LQTS), short-QT syndrome and proarrhythmia related to Na+-channel blockade/conduction impairment. By far the most important form of proarrhythmia at present is drug-induced LQTS and its associated characteristic tachyarrhythmia, torsades de pointes (TdP). TdP arises when cellular action potentials (APs) are excessively prolonged, leading to arrhythmogenic afterdepolarizations, especially early afterdepolarizations (EADs), which trigger complex re-entry in a substrate involving increased transmural dispersion of repolarization. In vitro screening, increasingly involving high-throughput assays, is used to assess potential candidate molecules and eliminate potentially problematic structures at an early stage of development. The most commonly used screening assays assess drug block of the K+ current carried by human ether-à-go-go (hERG) subunits, corresponding to the rapid delayed-rectifier K+ channel, the overwhelmingly most common target of TdP-inducing drugs. In addition, the effects of drugs on AP duration or the in vivo equivalent, QT interval, are often assessed in animal models. Methods available for repolarization-related proarrhythmic risk assessment include in vitro (Langendorff-perfused rabbit or guinea pig hearts) and in vivo models (such as alpha-adrenoceptor-stimulated rabbits, rabbits with reduced repolarization reserve due to block of slow delayed-rectifier current, animals with chronic atrioventricular block or animals with cardiac remodelling caused by congestive heart failure). In silico modelling may be helpful for molecular design of non-hERG blocking candidates and for optimization of compound selection (at the molecular and pharmacological profile levels). Finally, clinical evaluation of effects on

  13. A Principal Component Regression Approach for Estimating Ventricular Repolarization Duration Variability

    Directory of Open Access Journals (Sweden)

    Pasi A. Karjalainen

    2007-01-01

    Full Text Available Ventricular repolarization duration (VRD is affected by heart rate and autonomic control, and thus VRD varies in time in a similar way as heart rate. VRD variability is commonly assessed by determining the time differences between successive R- and T-waves, that is, RT intervals. Traditional methods for RT interval detection necessitate the detection of either T-wave apexes or offsets. In this paper, we propose a principal-component-regression- (PCR- based method for estimating RT variability. The main benefit of the method is that it does not necessitate T-wave detection. The proposed method is compared with traditional RT interval measures, and as a result, it is observed to estimate RT variability accurately and to be less sensitive to noise than the traditional methods. As a specific application, the method is applied to exercise electrocardiogram (ECG recordings.

  14. Clinical frontiers in electrocardiographic early repolarization syndrome: does a good guy turn bad now?

    Institute of Scientific and Technical Information of China (English)

    Xingpeng Liu; Ashok Shah; Frédéric Sacher; Nicolas Derval; Amir S. Jadidi; Mélèze Hocini; Michel Haissaguerre

    2010-01-01

    @@ Early repolarization pattern (ERP) is a common electrocardiographic (ECG) variant, characterized by J point elevation manifested either as QRS slurring (at the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on terminal S wave), ST-segment elevation with upper concavity and prominent T waves in at least two contiguous leads.1,2 The prevalence of ERP in normal population varies from 1 % to 13%, depending on the age (predominant in young adults), the race (highest amongst black population), and the criterion for J point elevation (0.05 mV vs. 0.1 mV).3-7 In addition, higher incidence of ERP exists in males, athletes and individuals with high vagal tone or selective loss of sympathetic tone (e.g. spinal cord injury).8

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

    DEFF Research Database (Denmark)

    Osadchii, Oleg E.

    2016-01-01

    OBJECTIVES: 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. DESIGN: 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. RESULTS: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged...

  16. Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

    Directory of Open Access Journals (Sweden)

    Tulay Akman

    2014-11-01

    Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

  17. Prognostic Value of a New Marker of Ventricular Repolarization in Cirrhotic Patients

    Science.gov (United States)

    Salgado, Angelo Antunes; Barbosa, Paulo Roberto Benchimol; Ferreira, Alinne Gimenez; Reis, Camila Aparecida de Souza Segrégio; Terra, Carlos

    2016-01-01

    Background There is still debate about the relationship between changes in ventricular repolarization on the surface electrocardiogram and cirrhosis severity. Objective To study the relationship between variables related to ventricular repolarization and the clinical severity of the cirrhotic disease. Methods We selected 79 individuals with hepatic cirrhosis, classified according to the Child-Pugh-Turcotte criteria (Child A, B, and C). We measured the QT and corrected QT (QTc) intervals, and the interval between the peak and the end of the T wave (TpTe), and we identified their minimum, maximum, and mean values in the 12-lead electrocardiogram. We also calculated the dispersion of the QT (DQT) and QTc (DQTc) intervals. Results In 12 months of clinical follow-up, nine subjects underwent hepatic transplantation (Child A: 0 [0%]; Child B: 6 [23.1%]; Child C: 3 [18.8%]; p = 0.04) and 12 died (Child A: 3 [12.0%]; Child B: 4 [15.4%]; Child C: 5 [31.3%]; p = 0.002). No significant differences were observed between the cirrhotic groups related to the minimum, maximum, and mean values for the QT, QTc, TpTe, DQT, and DQTc intervals. A minimum TpTe interval ≤ 50 ms was a predictor for the composite endpoints of death or liver transplantation with a sensitivity of 90% and a specificity of 57% (p = 0.005). In the Cox multivariate analysis, the Child groups and a minimum TpTe of ≤ 50 ms were independent predictors of the composite endpoints. Conclusion The intervals QT, QTc, DQT, DQTc, and TpTe have similar distributions between different severity stages in cirrhotic disease. The TpTe interval proved to be a prognostic marker in subjects with cirrhosis, regardless of disease severity (NCT01433848).

  18. International Conference on Harmonisation; guidance on S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals; availability. Notice.

    Science.gov (United States)

    2005-10-20

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a nonclinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization and includes information concerning nonclinical assays and an integrated risk assessment. The guidance is intended to facilitate the nonclinical assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk.

  19. Etiopathogenesis of catatonia: generalizations and working hypotheses.

    Science.gov (United States)

    Dhossche, Dirk M; Stoppelbein, Laura; Rout, Ujjwal K

    2010-12-01

    Catatonia has been rediscovered over the last 2 decades as a unique syndrome that consists of specific motor signs with a characteristic and uniform response to benzodiazepines and electroconvulsive therapy. Further inquiry into its developmental, environmental, psychological, and biological underpinnings is warranted. In this review, medical catatonia models of motor circuitry dysfunction, abnormal neurotransmitters, epilepsy, genetic risk factors, endocrine dysfunction, and immune abnormalities are discussed. Developmental, environmental, and psychological risk factors for catatonia are currently unknown. The following hypotheses need to be tested: neuroleptic malignant syndrome is a drug-induced form of malignant catatonia; Prader-Willi syndrome is a clinical GABAergic genetic-endocrine model of catatonia; Kleine-Levin syndrome represents a periodic form of adolescent catatonia; and anti-N-methyl-d-aspartate receptor encephalitis is an autoimmune type of catatonia.

  20. Idiopathic scoliosis: etiological concepts and hypotheses

    OpenAIRE

    2013-01-01

    Scoliosis is diagnosed as idiopathic in 70 % of structural deformities affecting the spine in children and adolescents, probably reflecting our current misunderstanding of this disease. By definition, a structural scoliosis should be the result of some primary disorder. The goal of this article is to give a comprehensive overview of the currently proposed etiological concepts in idiopathic scoliosis regarding genetics, molecular biology, biomechanics, and neurology, with particular emphasis o...

  1. Dental Hypotheses: Seeks to Publish Hypotheses from All Areas of Dentistry

    Directory of Open Access Journals (Sweden)

    Edward F. Rossomando

    2010-07-01

    Full Text Available Starting a new open access journal in a rapid growing scientific panorama is a severe challenge. However, the first issue of dental hypotheses is now history and the even skeptics can appreciate that dental hypotheses is a success - it is a journal of high quality that provides an outlet for publication of articles that encourage readers to question dental paradigms. But dental hypotheses readers might have noticed that the majority of the articles published in the first issue of dental hypotheses concern clinical dentistry. However, dental hypotheses editors recognize that there are many other areas in dentistry that present challenges and that our readers may offer suggestions for their solution. Some of these challenges relate to: dental education; digital dental technology; teledentistry and access to dental care; dental practice issues, such as, dental office design, dental office management, the slow rate of acceptance of innovative technology in the dental office; and issues related to innovation and dental entrepreneurship including intellectual property protection. Nevertheless, the dental profession faces many challenges - in many areas - and with the publication of dental hypotheses our profession has a venue for presentation of possible solutions. If you have developed a hypothesis that might help, please share it with your colleagues. As many have noted, the intellectual power of the global village in which we now live is formidable. The internet has provided the technology to bring us together and dental hypotheses has provided the venue. Please use it. New radical, speculative and non-mainstream scientific ideas are always welcome.

  2. Hypothesizing Dopaminergic Genetic Antecedents in Schizophrenia and Substance Seeking Behavior

    Science.gov (United States)

    Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra; Palomo, Tomas; Gold, Mark S.

    2014-01-01

    The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta- analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non- SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis.. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. PMID:24636783

  3. Early repolarization electrocardiography pattern with unexplained syncope during training in a young black African non-elite athlete: an accidental finding?

    Science.gov (United States)

    Bonny, Aimé; Ditah, Ivo; Amara, Walid; Hamdaoui, Brahim; Frank, Robert; Le Heuzey, Jean-Yves

    2009-01-01

    Until recently it was generally thought that early repolarization is benign. But a recent article in the NEJM (Haissaguerre et al.) suggests that some persons with early repolarization may be at risk of life-threatening ventricular tachyarrhythmia. Unexplained syncope or sudden death occurs mostly during sleep. However, some cases of cardiac arrest during exertion have been reported. We report the case of a 39 year-old black African male with early repolarization pattern on electrocardiogram who regularly experienced dizziness (and one episode of transient loss of consciousness) exclusively while exercising. Detailed examination was normal. Under quinidine therapy, he experienced no further episodes. Increasingly reported cases of cardiac arrest in Africans, and significant prevalence of early repolarization in this population, have to be taken into account since the Haissaguerre et al. report. Further evidence of the lethal consequences of this syndrome are needed, bearing in mind that diagnostic tools for life-threatening arrhythmias are often scarce in sub-Saharan Africa.

  4. Hypotheses testing for fuzzy robust regression parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kula, Kamile Sanli [Ahi Evran University, Department of Mathematics, 40200 Kirsehir (Turkey)], E-mail: sanli2004@hotmail.com; Apaydin, Aysen [Ankara University, Department of Statistics, 06100 Ankara (Turkey)], E-mail: apaydin@science.ankara.edu.tr

    2009-11-30

    The classical least squares (LS) method is widely used in regression analysis because computing its estimate is easy and traditional. However, LS estimators are very sensitive to outliers and to other deviations from basic assumptions of normal theory [Huynh H. A comparison of four approaches to robust regression. Psychol Bull 1982;92:505-12; Stephenson D. 2000. Available from: (http://folk.uib.no/ngbnk/kurs/notes/node38.html); Xu R, Li C. Multidimensional least-squares fitting with a fuzzy model. Fuzzy Sets and Systems 2001;119:215-23.]. If there exists outliers in the data set, robust methods are preferred to estimate parameters values. We proposed a fuzzy robust regression method by using fuzzy numbers when x is crisp and Y is a triangular fuzzy number and in case of outliers in the data set, a weight matrix was defined by the membership function of the residuals. In the fuzzy robust regression, fuzzy sets and fuzzy regression analysis was used in ranking of residuals and in estimation of regression parameters, respectively [Sanli K, Apaydin A. Fuzzy robust regression analysis based on the ranking of fuzzy sets. Inernat. J. Uncertainty Fuzziness and Knowledge-Based Syst 2008;16:663-81.]. In this study, standard deviation estimations are obtained for the parameters by the defined weight matrix. Moreover, we propose another point of view in hypotheses testing for parameters.

  5. Quantitative analysis of T-wave morphology increases confidence in drug-induced cardiac repolarization abnormalities: evidence from the investigational IKr inhibitor Lu 35-138

    DEFF Research Database (Denmark)

    Graff, Claus; Matz, Jørgen; Christensen, Ellen B;

    2009-01-01

    to determine a combined measure of repolarization morphology (morphology combination score [MCS]), based on asymmetry, flatness, and notching. Replicate measurements were used to determine reliable change and study power for both measures. Lu 35-138 increased the QTc interval with corresponding changes in T...... was 93%. As a covariate to the assessment of QT interval liability, MCS offered important additive information to the effect of Lu 35-138 on cardiac repolarization....

  6. Prevalence of Brugada-type ECG pattern and early ventricular repolarization pattern in Tunisian athletes

    Directory of Open Access Journals (Sweden)

    Ouali S

    2011-04-01

    Full Text Available Sana Ouali1, Helmi Ben Salem1, Sami Hammas1, Elyes Neffeti1, Fahmi Remedi1, Abdallah Mahdhaoui2, Essia Boughzela1, Rafik Mankai31Department of Cardiology, Sahloul Hospital, Sousse, Tunisia; 2Department of Cardiology, Farhat Hached, Sousse, Tunisia; 3Central Sports Medicine Centre of El Menzah, TunisiaIntroduction: No data regarding the prevalence of the Brugada-type electrocardiogram (ECG pattern and the early ventricular repolarization pattern (ERP in the North African population were available. The aims of this study were to determine the frequency of Brugada-type ECG pattern and ERP in Tunisia and to evaluate ECG descriptors of ventricular repolarization in a population of athletes.Methods: Over a 2-year period, resting 12-lead ECG recordings were analyzed from athletes (n = 540; 348 males; age 18.3 ± 2.4 years. Brugada-type ECG pattern was defined as Type 1, 2, or 3, and ERP was characterized by an elevation of the J point in the inferior and/or lateral leads. The population was divided into three groups of athletes: ERP group; Brugada-type ECG pattern group; and control group, with neither ERP nor Brugada ECG pattern. Clinical and electrocardiographic parameters were compared among the study groups.Results: Nine subjects (1.66% had a Brugada-type ECG pattern. None of them had the coved-type, 3 (0.6% had the Type 2, and 6 (1.1% had the Type 3. All subjects were asymptomatic. A Brugada-type ECG pattern was observed in seven males. No female had the Type 2 Brugada ECG pattern. ECG parameters were similar among Brugada-type ECG pattern and control athletes. ERP (119 subjects, 22% was obtained in 98 males. Heart rate was lower, the QRS duration shorter and QT and Tpeak–Tend intervals were longer in ERP than control groups.Conclusion: The results indicate that the frequency of the Brugada-type ECG pattern and ERP were respectively 1.66% and 22.00% in athletes, being more prevalent in males. The ERP group experienced shorter QRS duration and

  7. Two components of delayed rectifier K+ current in heart:molecular basis,functional diversity,and contribution to repolarization

    Institute of Scientific and Technical Information of China (English)

    Jian-hua CHENG; Itsuo KODAMA

    2004-01-01

    Delayed rectifier K+ current (IK) is the major outward current responsible for ventricular repolarization. Two components of IK (IKr and IKs) have been identified in many mammalian species including humans. IKr. plays a pivotal role in normal ventricular repolarization. A prolongation of action potential duration (APD) under a variety of conditions would favor the activation of IKs so that to prevent excessive repolarization delay causing early afterdepolarization. The pore-forming α subunits of IKr and IKs are composed of HERG (KCNH2) and KvLQT l (KCNQ l), respectively. KvLQT l is associated with a function-altering β subunit, minK to form IKs. HERG may be associated with minK (KCNE1) and/or minK-related protein (MiRP1) to form IKr, but the issue remains to be established. IKs is enhanced, whereas IKr is usually attenuated by β-adrenergic stimulation via cyclic adenosine 31,51-monophosphate (cAMP)/protein kinase A-dependent pathways. There exist regional differences in the density of IKr and IKs transmurally (endo-epicardial) and along the apico-basal axis, contributing to the spatial heterogeneity of ventricular repolarization. A decrease of IKr or IKs by mutations in either HERG, KvLQTl, or KCNE family results in inherited long QT syndrome (LQTS) with high risk for Torsades de pointes (TdP)-type polymorphic ventricular tachycardia and ventricular fibrillation. As to the pharmacological treatment and prevention of ventricular tachyarrhythmias, selectively block of IKs is expected to be more beneficial than selectively block of IKr in terms of homogeneous prolongation of refractoriness at high heart rates especially in diseased hearts including myocardial ischemia.

  8. The Effects of Female Sex Hormones on Ventricular Premature Beats and Repolarization Parameters in Physiological Menstrual Cycle.

    Science.gov (United States)

    Dogan, Mehmet; Yiginer, Omer; Uz, Omer; Kucuk, Ugur; Degirmencioglu, Gokhan; Isilak, Zafer; Uzun, Mehmet; Davulcu, Ezgi

    2016-05-01

    The effects of gender difference on cardiac electrophysiology have been well studied. In this study, we aimed to evaluate the effects of estradiol and progesteron changes occuring in physiological menstrual cycle on ventricular premature beats (VPBs) and cardiac repolarization parameters. Women of reproductive age with VPBs were included into the study group and healthy women were recruited as the control group. During the menstruation period, a 12-lead electrocardiography, blood samples, and 24-hour rhythm Holter were applied to the study group. Similarly, all tests were repeated in the estimated ovulation period (12-14 days before menstruation) by all cases. The study group consisted of 20 women patients with VPB, and the control group of 18 healthy women. While the number of VPB in the menstruation period was 210 beats/day (interquartile range [IQR]: 1,144), it decreased to 86 beats/day (IQR: 251) in the ovulation period with statistical significance (P < 0.05). Average heart rate in the menstruation period was 81.4 ± 10 beats/min and it significantly increased to 84.6 ± 8 beats/min in the ovulation period (P < 0.05). There were no differences in cardiac repolarization parameters in both menstruation and ovulation periods between the study and control groups. Comparing the menstruation and the ovulation periods, J-Tpeak interval, which reflects early repolarization, was shorter in the ovulation period (193 ± 27.7 ms and 201.1 ± 28.6 ms, respectively; P < 0.05). Other repolarization parameters did not show any significant difference. VPB frequency decreases with estradiol peak in the ovulation period. This suggests that estrogen may have protective effects against ventricular arrhythmias. ©2016 Wiley Periodicals, Inc.

  9. Vertical nystagmus: clinical facts and hypotheses.

    Science.gov (United States)

    Pierrot-Deseilligny, C; Milea, D

    2005-06-01

    hypoactive after pontine or caudal medullary lesions, thereby eliciting UBN, and hyperactive after floccular lesions, thereby eliciting DBN. Lastly, since gravity influences UBN and DBN and may facilitate the downward vestibular system and restrain the upward vestibular system, it is hypothesized that the excitatory SVN-VTT pathway, along with its specific floccular inhibition, has developed to counteract the gravity pull. This anatomical hyperdevelopment is apparently associated with a physiological upward velocity bias, since the gain of all upward slow eye movements is greater than that of downward slow eye movements in normal human subjects and in monkeys.

  10. Arrhythmogenic remodelling of activation and repolarization in the failing human heart.

    Science.gov (United States)

    Holzem, Katherine M; Efimov, Igor R

    2012-11-01

    Heart failure is a major cause of disability and death worldwide, and approximately half of heart failure-related deaths are sudden and presumably due to ventricular arrhythmias. Patients with heart failure have been shown to be at 6- to 9-fold increased risk of sudden cardiac death compared to the general population. (AHA. Heart Disease and Stroke Statistics-2003 Update. Heart and Stroke Facts. Dallas, TX: American Heart Association; 2002) Thus, electrophysiological remodelling associated with heart failure is a leading cause of disease mortality and has been a major investigational focus examined using many animal models of heart failure. While these studies have provided an important foundation for understanding the arrhythmogenic pathophysiology of heart failure, the need for corroborating studies conducted on human heart tissue has been increasingly recognized. Many human heart studies of conduction and repolarization remodelling have now been published and shed some light on important, potentially arrhythmogenic, changes in human heart failure. These studies are being conducted at multiple experimental scales from isolated cells to whole-tissue preparations and have provided insight into regulatory mechanisms such as decreased protein expression, alternative mRNA splicing of ion channel genes, and defective cellular trafficking. Further investigations of heart failure in the human myocardium will be essential for determining possible therapeutic targets to prevent arrhythmia in heart failure and for facilitating the translation of basic research findings to the clinical realm.

  11. Thorough QT study of the effect of fesoterodine on cardiac repolarization.

    Science.gov (United States)

    Malhotra, B; Wood, N; Sachse, R; Gandelman, K

    2010-05-01

    Fesoterodine 4 mg and 8 mg once daily are indicated for the treatment of overactive bladder. A thorough QT study was conducted to investigate the effects of fesoterodine on cardiac repolarization. In this parallel-group study, subjects were randomly assigned to receive double-blind fesoterodine 4 mg, fesoterodine 28 mg, or placebo or open-label moxifloxacin 400 mg (positive control) for 3 days. Electrocardiograms (ECGs) were obtained on Days -1 (baseline), 1, and 3. The primary analysis was the time-averaged changes from baseline for Fridericia's-corrected QT interval (QTcF) on Day 3. Among 261 subjects randomized to fesoterodine 4 mg (n = 64), fesoterodine 28 mg (n = 68), placebo (n = 65), or moxifloxacin 400 mg (n = 64), 256 completed the trial. The least squares mean changes in QTcF from baseline were 21.1, 20.5, 18.5, and 31.3 ms (maximum), and -5.1, -4.2, -5.2, and 7.6 ms (time-averaged at Day 3) for placebo, fesoterodine 4 mg, fesoterodine 28 mg, and moxifloxacin, respectively. The lower limit of the 95% confidence interval exceeded 5 ms for moxifloxacin. The results indicate that fesoterodine is not associated with QTc prolongation or other ECG abnormalities at either therapeutic or supratherapeutic doses.

  12. Profile of the cardiac repolarization in cervical spinal cord injury subjects performing physical exercise

    Directory of Open Access Journals (Sweden)

    Roberto Magalhães

    2017-08-01

    Full Text Available The aim of the study was to compare rest QT interval and QTcorrected intervals of electrocardiogram in trained men with and without cervical spinal cord injury (CSCI and investigate cardiac electrocardiogram parameters in trained men with CSCI submitted to maximal effort test. Thirty men were separated into three groups: Control without CSCI (CON, 25.3 ± 4.1 yrs, strength training: 3 days week-1; aerobic training 1day week-1; n = 10, high volume exercise (30.5 ± 4.3 yrs, 3 day week-1 rugby specific exercises, 60min. day-1; n = 12 and moderate volume of exercise (33.7 ± 5.9 yrs, 2 days week-1 specific rugby exercises, 60 min. day-1; n = 8 with incomplete CSCI (C5-C7 cervical vertrebae more than 12 months. Electrocardiogram was recorded in rest, during and after effort test. QT interval was significantly reduced (p = 0.001 in the high volume exercise group compared to control. Corrected QT interval showed no difference between moderate vs. high volume exercise group (p > 0.05. No changes were observed in QT, corrected QT, PR and QRS intervals of electrocardiogram between rest and post effort (p > 0.05. Thus, effort test does not change electrocardiogram parameters in CSCI subjects. High volume of week exercise promotes abnormalities in cardiac repolarization compared to a moderate training program.

  13. A class of Monte-Carlo-based statistical algorithms for efficient detection of repolarization alternans.

    Science.gov (United States)

    Iravanian, Shahriar; Kanu, Uche B; Christini, David J

    2012-07-01

    Cardiac repolarization alternans is an electrophysiologic condition identified by a beat-to-beat fluctuation in action potential waveform. It has been mechanistically linked to instances of T-wave alternans, a clinically defined ECG alternation in T-wave morphology, and associated with the onset of cardiac reentry and sudden cardiac death. Many alternans detection algorithms have been proposed in the past, but the majority have been designed specifically for use with T-wave alternans. Action potential duration (APD) signals obtained from experiments (especially those derived from optical mapping) possess unique characteristics, which requires the development and use of a more appropriate alternans detection method. In this paper, we present a new class of algorithms, based on the Monte Carlo method, for the detection and quantitative measurement of alternans. Specifically, we derive a set of algorithms (one an analytical and more efficient version of the other) and compare its performance with the standard spectral method and the generalized likelihood ratio test algorithm using synthetic APD sequences and optical mapping data obtained from an alternans control experiment. We demonstrate the benefits of the new algorithm in the presence of Gaussian and Laplacian noise and frame-shift errors. The proposed algorithms are well suited for experimental applications, and furthermore, have low complexity and are implementable using fixed-point arithmetic, enabling potential use with implantable cardiac devices.

  14. T-wave alternans in LQTS: repolarization-rate dynamics from digital 12-lead Holter data.

    Science.gov (United States)

    Brockmeier, K; Aslan, I; Hilbel, T; Eberle, T; Ulmer, H E; Lux, R L

    2001-01-01

    T-wave alternans (TWA) is a harbinger of ventricular vulnerability and an important prognostic indicator for torsade de pointes and likely sudden death in patients with LQTS. We analyzed the occurrence of TWA in 18 patients with LQTS (7 males, 11 females, ages ranging from 6 months to 32 years--median 8.4 years). Analysis was performed with software to investigate dynamics of cycle length mediated repolarization changes. Digital Holter ECG analysis revealed macroscopic, true TWA in 3 of 18 patients. TWA showed a variable morphological expression. One patient had continuous changes of T wave polarity, but not on a periodic beat-to-beat basis. Onsets of macroscopic TWA were preceded by long/short cycle length sequences and tachycardic rates above 130 to 140 bpm. Impact of ventricular premature beats on TWA onset was insignificant. Two of the identified patients with TWA had sudden cardiac death during follow-up (one refused PM therapy). At present, TWA cannot be detected automatically from Holter ECGs and therefore may be missed, despite the potential danger for the individuals. The observation that predominantly high beat rates and not beat rate changes, per se, triggered episodes of TWA renders difficult general therapeutic recommendations for the identified patients at risk.

  15. Early repolarization with horizontal ST segment may be associated with aborted sudden cardiac arrest: a retrospective case control study

    Directory of Open Access Journals (Sweden)

    Kim Sung

    2012-12-01

    Full Text Available Abstract Background Risk stratification of the early repolarization pattern (ERP is needed to identify malignant early repolarization. J-point elevation with a horizontal ST segment was recently suggested as a malignant feature of the ERP. In this study, the prevalence of the ERP with a horizontal ST segment was examined among survivors of sudden cardiac arrest (SCA without structural heart disease to evaluate the value of ST-segment morphology in risk stratification of the ERP. Methods We reviewed the data of 83 survivors of SCA who were admitted from August 2005 to August 2010. Among them, 25 subjects without structural heart disease were included. The control group comprised 60 healthy subjects who visited our health promotion center; all control subjects were matched for age, sex, and underlying disease (diabetes mellitus, hypertension. Early repolarization was defined as an elevation of the J point of at least 0.1 mV above the baseline in at least two continuous inferior or lateral leads that manifested as QRS slurring or notching. An ST-segment pattern of Results The SCA group included 17 men (64% with a mean age of 49.7 ± 14.5 years. The corrected QTc was not significantly different between the SCA and control groups (432.7 ± 37.96 vs. 420.4 ± 26.3, respectively; p = 0.089. The prevalence of ERP was not statistically different between the SCA and control groups (5/25, 20% vs. 4/60, 6.7%, respectively; p = 0.116. The prevalence of early repolarization with a horizontal ST segment was more frequent in the SCA than in the control group (20% vs. 3.3%, respectively; p = 0.021. Four SCA subjects (16% and one control subject (1.7% had a J-point elevation of >2 mm (p = 0.025. Four SCA subjects (16% and one (1.7% control subject had an ERP in the inferior lead (p = 0.025. Conclusion The prevalence of ERP with a horizontal ST segment was higher in patients with aborted SCA than in matched controls. This result suggests that ST morphology has

  16. Aggression among Children with ADHD, Anxiety, or Co-Occurring Symptoms: Competing Exacerbation and Attenuation Hypotheses

    Science.gov (United States)

    Becker, Stephen P.; Luebbe, Aaron M.; Stoppelbein, Laura; Greening, Leilani; Fite, Paula J.

    2012-01-01

    Competing hypotheses for explaining the role of anxiety in the relation between attention-deficit/hyperactivity disorder (ADHD) symptoms and childhood aggression were evaluated. Two studies tested whether anxiety exacerbated, attenuated, or had no effect on the relation between ADHD and aggression subtypes among psychiatrically hospitalized…

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

    Science.gov (United States)

    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.

  18. Evaluation of the effect on cardiac repolarization (QTc interval) of oncologic drugs.

    Science.gov (United States)

    Morganroth, J

    2007-01-01

    The 12-lead electrocardiograph (ECG) is the standard safety measurement used in clinical trials to identify drug-induced cardiac adverse effects. Drug-induced prolongation of the QTc interval (the measure of cardiac repolarization change), when excessive and in conjunction with the right risk factors, can degenerate into a polymorphic ventricular tachycardia called torsades de pointes and has become a new focus for new drug development. The assessment of an ECG in clinical practice using machine-defined QTc duration is intrinsically unreliable. Current regulatory concepts have focused on the need for measuring ECG intervals using manual techniques using digital processing in a central ECG laboratory. The QT interval is subject to a large degree of spontaneous variability requiring attention to basic clinical trial design issues such as sample size (use as large a cohort as possible), frequency of measurements taken (at least three to six ECGs at baseline and at many time points on therapy with pharmacokinetic samples if possible), and their accuracy. Since most oncologic products are cytotoxic, a Thorough or Dedicated ECG Trial cannot be conducted and in the usual trail, especially in phase I, all changes seen on the ECG will be attributed to the new oncology drug. For most nononcologic drugs, there is regulatory guidance on how much an effect on QTc duration might be related to the risk of cardiac toxicity. For oncology products, the central tendency magnitude and proportion of outliers needs to be well defined to construct a label if the risk-benefit analysis leads to marketing approval. Clinical cardiac findings such as syncope, ventricular tachyarrhythmias, and other cardiac effects will be important in this analysis.

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

    Science.gov (United States)

    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 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.

  20. MiRNA-1/133a clusters regulate adrenergic control of cardiac repolarization.

    Directory of Open Access Journals (Sweden)

    Johannes Besser

    Full Text Available The electrical properties of the heart are primarily determined by the activity of ion channels and the activity of these molecules is permanently modulated and adjusted to the physiological needs by adrenergic signaling. miRNAs are known to control the expression of many proteins and to fulfill distinct functions in the mammalian heart, though the in vivo effects of miRNAs on the electrical activity of the heart are poorly characterized. The miRNAs miR-1 and miR-133a are the most abundant miRNAs of the heart and are expressed from two miR-1/133a genomic clusters. Genetic modulation of miR-1/133a cluster expression without concomitant severe disturbance of general cardiomyocyte physiology revealed that these miRNA clusters govern cardiac muscle repolarization. Reduction of miR-1/133a dosage induced a longQT phenotype in mice especially at low heart rates. Longer action potentials in cardiomyocytes are caused by modulation of the impact of β-adrenergic signaling on the activity of the depolarizing L-type calcium channel. Pharmacological intervention to attenuate β-adrenergic signaling or L-type calcium channel activity in vivo abrogated the longQT phenotype that is caused by modulation of miR-1/133a activity. Thus, we identify the miR-1/133a miRNA clusters to be important to prevent a longQT-phenotype in the mammalian heart.

  1. Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

    Directory of Open Access Journals (Sweden)

    Fei Tang

    2017-07-01

    Full Text Available Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy.

  2. A survey of etiologic hypotheses among testicular cancer researchers

    DEFF Research Database (Denmark)

    Stang, A; Trabert, B; Rusner, C

    2015-01-01

    the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses......Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops...

  3. A major role for calcium-dependent potassium current in action potential repolarization in adrenal chromaffin cells.

    Science.gov (United States)

    Pancrazio, J J; Johnson, P A; Lynch, C

    1994-12-30

    To determine the extent which Ca dependent K current (IKCa) contributes during an action potential (AP), bovine chromaffin cells were voltage-clamped using a pre-recorded AP as the command voltage waveform. Based on (1) differential sensitivity of IKCa and Ca-independent K current (IK) to tetraethylammonium; (2) measurements of AP currents under conditions where Ca activation of IKCa had been abolished; and (3) blockade by charybdotoxin, IKCa comprised 70-90% of the outward K current during AP repolarization. In addition, observations are made concerning the form of AP-evoked Ca current.

  4. Assessing common classification methods for the identification of abnormal repolarization using indicators of T-wave morphology and QT interval

    DEFF Research Database (Denmark)

    Shakibfar, Saeed; Graff, Claus; Ehlers, Lars Holger;

    2012-01-01

    volunteers and LQT2 carriers were used to train classification algorithms using measures of T-wave morphology and QTc. The ability to correctly classify a third group of test subjects before and after receiving d,l-sotalol was evaluated using classification rules derived from training. As a single......Various parameters based on QTc and T-wave morphology have been shown to be useful discriminators for drug induced I(Kr)-blocking. Using different classification methods this study compares the potential of these two features for identifying abnormal repolarization on the ECG. A group of healthy...

  5. Longitudinal changes in intracardiac repolarization lability in patients with implantable cardioverter-defibrillator

    Directory of Open Access Journals (Sweden)

    Abhilash eGuduru

    2013-08-01

    Full Text Available Background─While it is known that elevated baseline intracardiac repolarization lability is associated with the risk of fast ventricular tachycardia (FVT /ventricular fibrillation (VF, the effect of its longitudinal changes on the risk of FVT/VF is unknown. Methods and Results─Near-field (NF right ventricular (RV intracardiac electrograms (EGMs were recorded every 3-6 months at rest in 248 patients with structural heart disease (mean age 61.2±13.3; 185[75%] male; 162[65.3%] ischemic cardiomyopathy and implanted cardioverter-defibrillator (ICD or cardiac resynchronization therapy defibrillator (CRT-D [201 (81% primary prevention]. Intracardiac beat-to-beat QT variability index (QTVINF was measured on NF RV EGM. During the first study phase (median 18 months, participants made on average 2.4 visits. Then remote follow-up was continued for an additional median period of 3 years. Average QTVINF did not change during the first year after ICD implantation (-0.342±0.603 at baseline vs. -0.262±0.552 at 6 months vs. -0.334±0.603 at 12 months; however, it decreased thereafter (-0.510±0.603 at 18 months; P=0.042. Adjusted population-averaged GEE model showed that the odds of developing FVT/VF increased by 75% for each 1 unit increase in QTVINF. (OR 1.75 [95%CI 1.05-2.92]; P=0.031. However, individual patient–specific QTVINF trends (increasing, decreasing, flat varied from patient to patient. For a given patient, the odds of developing FVT/VF were not associated with increasing or decreasing QTVINF over time (OR 1.27; [95%CI 0.05–30.10]; P = 0.881.Conclusion─While on average the odds of FVT/VF increased with an increase in QTVINF, patient-specific longitudinal trends in QTVINF did not affect the odds of FVT/VF.

  6. Supratherapeutic dose evaluation and effect of lesinurad on cardiac repolarization: a thorough QT/QTc study

    Directory of Open Access Journals (Sweden)

    Shen Z

    2016-10-01

    Full Text Available Zancong Shen,1 Michael Gillen,2 Kathy Tieu,1 Mai Nguyen,1 Erin Harmon,1 David M Wilson,1 Bradley Kerr,1 Caroline A Lee1 1Ardea Biosciences, Inc., San Diego, CA, 2AstraZeneca LP, Gaithersburg, MD, USA Introduction: Lesinurad is a selective uric acid reabsorption inhibitor approved in the United States and Europe for treatment of gout in combination with a xanthine oxidase inhibitor. A maximum tolerated dose study was conducted to determine the lesinurad supratherapeutic dose, followed by a thorough QTc study to characterize the effect of lesinurad on cardiac repolarization.Methods: The maximum tolerated dose study was a randomized, double-blind, placebo-controlled, single-ascending dose study that enrolled 35 healthy men and women. Lesinurad plasma exposure (maximum observed plasma concentration and area under the plasma concentration versus time curve was determined at doses of 800 mg, 1,200 mg, and 1,600 mg. The thorough QTc study was a double-blind, four-period, placebo-controlled crossover study with 54 healthy men and women who received single doses of lesinurad 1,600 mg (supratherapeutic dose, lesinurad 400 mg, moxifloxacin 400 mg, and placebo in randomized sequence. Digital 12-lead electrocardiograms were recorded at eleven time points over 24 hours in each treatment period. QT intervals were corrected for heart rate using an individual-specific correction factor (QTcI.Results: The upper bound of the one-sided 95% confidence interval for time-matched, placebo-subtracted, baseline-adjusted QTcI intervals (ΔΔQTcI was <10 ms for both the lesinurad 400 mg and 1,600 mg doses. ΔΔQTcI was independent of lesinurad concentrations. No QTcI thresholds >480 ms or QTcI increases >30 ms were observed. Moxifloxacin mean QTcI intervals were >5 ms, and the lower bounds of the 90% confidence interval were >5 ms at 2 hours, 3 hours, and 4 hours, confirming assay sensitivity.Conclusion: Lesinurad, at supratherapeutic doses, does not

  7. Evaluation of repolarization dynamics using the QT-RR regression line slope and intercept relationship during 24-h Holter ECG.

    Science.gov (United States)

    Fujiki, Akira; Yoshioka, Ryozo; Sakabe, Masao

    2015-03-01

    QT-RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT-RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT-RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.

  8. Effect of Lidocaine and Amiodarone on Transmural Heterogeneityricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

    Institute of Scientific and Technical Information of China (English)

    YOU Binquan; PU Jun; LIU Nian; YU Ronghui; RUAN Yanfei; LI Yang; WANG Lin

    2005-01-01

    To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.

  9. Eating disorder severity and functional impairment

    DEFF Research Database (Denmark)

    Davidsen, Annika Helgadóttir; Hoyt, William T.; Poulsen, Stig Bernt

    2017-01-01

    diagnosed with bulimia nervosa, binge eating disorder or eating disorder not otherwise specified. Regression analysis was applied to assess the effect of the hypothesized moderators and mediators. Eating disorder severity was measured with the Eating Disorder Examination Questionnaire, functional impairment...

  10. Pearce element ratios: A paradigm for testing hypotheses

    Science.gov (United States)

    Russell, J. K.; Nicholls, Jim; Stanley, Clifford R.; Pearce, T. H.

    Science moves forward with the development of new ideas that are encapsulated by hypotheses whose aim is to explain the structure of data sets or to expand existing theory. These hypotheses remain conjecture until they have been tested. In fact, Karl Popper advocated that a scientist's job does not finish with the creation of an idea but, rather, begins with the testing of the related hypotheses. In Popper's [1959] advocation it is implicit that there be tools with which we can test our hypotheses. Consequently, the development of rigorous tests for conceptual models plays a major role in maintaining the integrity of scientific endeavor [e.g., Greenwood, 1989].

  11. Different mechanisms underlying the repolarization of narrow and wide action potentials in pyramidal cells and interneurons of cat motor cortex.

    Science.gov (United States)

    Chen, W; Zhang, J J; Hu, G Y; Wu, C P

    1996-07-01

    Two different types of action potentials were observed among the pyramidal cells and interneurons in cat motor cortex: the narrow action potentials and the wide action potentials. These two types of action potentials had similar rising phases (528.8 +/- 77.0 vs 553.1 +/- 71.8 mV/ms for the maximal rising rate), but differed in spike duration (0.44 +/- 0.09 vs 1.40 +/- 0.39 ms) and amplitude (57.31 +/- 8.22 vs 72.52 +/- 8.31 mV), implying that the ionic currents contributing to repolarization of these action potentials are different. Here we address this issue by pharmacological manipulation and using voltage-clamp technique in slices of cat motor cortex. Raising extracellular K+ concentration (from 3 mM to 10 mM), applying a low dose of 4-aminopyridine (2-200 microM) or administering a low concentration of tetraethylammonium (0.2-1.0 mM) each not only broadened the narrow action potentials, but also increased their amplitudes. In contrast, high K+ medium or low dose of tetraethylammonium only broadened the wide action potentials, leaving their amplitudes unaffected, and 4-aminopyridine had only a slight broadening effect on the wide spikes. These results implied that K+ currents were involved in the repolarization of both types of action potentials, and that the K+ currents in the narrow action potentials seemed to activate much earlier than those in the wide spikes. This early activated K+ current may counteract the rapid sodium current, yielding the extremely brief duration and small amplitude of the narrow spikes. The sensitivity of the narrow spikes to 4-aminopyridine may not be mainly attributed to blockade of the classical A current (IA), because depolarizing the membrane potential to inactivate IA did not reproduce the effects of 4-aminopyridine. Blockade of Ca2+ influx slowed the last two-thirds repolarization of the wide action potentials. On the contrary, the narrow action potentials were not affected by Ca(2+)-current blockers, but if they were first

  12. Testing hypotheses for differences between linear regression lines

    Science.gov (United States)

    Stanley J. Zarnoch

    2009-01-01

    Five hypotheses are identified for testing differences between simple linear regression lines. The distinctions between these hypotheses are based on a priori assumptions and illustrated with full and reduced models. The contrast approach is presented as an easy and complete method for testing for overall differences between the regressions and for making pairwise...

  13. Modulation of regional dispersion of repolarization and T-peak to T-end interval by the right and left stellate ganglia

    Science.gov (United States)

    Vaseghi, Marmar; Yamakawa, Kentaro; Sinha, Arjun; So, Eileen L.; Zhou, Wei; Ajijola, Olujimi A.; Lux, Robert L.; Laks, Michael; Shivkumar, Kalyanam

    2013-01-01

    Left stellate or right stellate ganglion stimulation (LGSG or RSGS, respectively) is associated with ventricular tachyarrhythmias; however, the electrophysiological mechanisms remain unclear. We assessed 1) regional dispersion of myocardial repolarization during RSGS and LSGS and 2) regional electrophysiological mechanisms underlying T-wave changes, including T-peak to T-end (Tp-e) interval, which are associated with ventricular tachyarrhythmia/ventricular fibrillation. In 10 pigs, a 56-electrode sock was placed around the heart, and both stellate ganglia were exposed. Unipolar electrograms, to asses activation recovery interval (ARI) and repolarization time (RT), and 12-lead ECG were recorded before and during RSGS and LSGS. Both LSGS and RSGS increased dispersion of repolarization; with LSGS, the greatest regional dispersion occurred on the left ventricular (LV) anterior wall and LV apex, whereas with RSGS, the greatest regional dispersion occurred on the right ventricular posterior wall. Baseline, LSGS, and RSGS dispersion correlated with Tp-e. The increase in RT dispersion, which was due to an increase in ARI dispersion, correlated with the increase in Tp-e intervals (R2 = 0.92 LSGS; and R2 = 0.96 RSGS). During LSGS, the ARIs and RTs on the lateral and posterior walls were shorter than the anterior LV wall (P dispersion of repolarization. PMID:23893168

  14. Determinants of beat-to-beat variability of repolarization duration in the canine ventricular myocyte: a computational analysis.

    Directory of Open Access Journals (Sweden)

    Jordi Heijman

    Full Text Available Beat-to-beat variability of repolarization duration (BVR is an intrinsic characteristic of cardiac function and a better marker of proarrhythmia than repolarization prolongation alone. The ionic mechanisms underlying baseline BVR in physiological conditions, its rate dependence, and the factors contributing to increased BVR in pathologies remain incompletely understood. Here, we employed computer modeling to provide novel insights into the subcellular mechanisms of BVR under physiological conditions and during simulated drug-induced repolarization prolongation, mimicking long-QT syndromes type 1, 2, and 3. We developed stochastic implementations of 13 major ionic currents and fluxes in a model of canine ventricular-myocyte electrophysiology. Combined stochastic gating of these components resulted in short- and long-term variability, consistent with experimental data from isolated canine ventricular myocytes. The model indicated that the magnitude of stochastic fluctuations is rate dependent due to the rate dependence of action-potential (AP duration (APD. This process (the "active" component and the intrinsic nonlinear relationship between membrane current and APD ("intrinsic component" contribute to the rate dependence of BVR. We identified a major role in physiological BVR for stochastic gating of the persistent Na(+ current (INa and rapidly activating delayed-rectifier K(+ current (IKr. Inhibition of IKr or augmentation of INa significantly increased BVR, whereas subsequent β-adrenergic receptor stimulation reduced it, similar to experimental findings in isolated myocytes. In contrast, β-adrenergic stimulation increased BVR in simulated long-QT syndrome type 1. In addition to stochastic channel gating, AP morphology, APD, and beat-to-beat variations in Ca(2+ were found to modulate single-cell BVR. Cell-to-cell coupling decreased BVR and this was more pronounced when a model cell with increased BVR was coupled to a model cell with normal BVR

  15. In silico generation of alternative hypotheses using causal mapping (CMAP.

    Directory of Open Access Journals (Sweden)

    Gabriel E Weinreb

    Full Text Available Previously, we introduced causal mapping (CMAP as an easy to use systems biology tool for studying the behavior of biological processes that occur at the cellular and molecular level. CMAP is a coarse-grained graphical modeling approach in which the system of interest is modeled as an interaction map between functional elements of the system, in a manner similar to portrayals of signaling pathways commonly used by molecular cell biologists. CMAP describes details of the interactions while maintaining the simplicity of other qualitative methods (e.g., Boolean networks.In this paper, we use the CMAP methodology as a tool for generating hypotheses about the mechanisms that regulate molecular and cellular systems. Furthermore, our approach allows competing hypotheses to be ranked according to a fitness index and suggests experimental tests to distinguish competing high fitness hypotheses. To motivate the CMAP as a hypotheses generating tool and demonstrate the methodology, we first apply this protocol to a simple test-case of a three-element signaling module. Our methods are next applied to the more complex phenomenon of cortical oscillations observed in spreading cells. This analysis produces two high fitness hypotheses for the mechanism that underlies this dynamic behavior and suggests experiments to distinguish the hypotheses. The method can be widely applied to other cellular systems to generate and compare alternative hypotheses based on experimentally observed data and using computer simulations.

  16. A survey of etiologic hypotheses among testicular cancer researchers.

    Science.gov (United States)

    Stang, A; Trabert, B; Rusner, C; Poole, C; Almstrup, K; Rajpert-De Meyts, E; McGlynn, K A

    2015-01-01

    Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27 hypotheses were related to exposures during pregnancy. Hypotheses with the highest mean plausibility ratings were either related to pre-natal exposures or exposures that might have an effect during pregnancy and in post-natal life. The results of the survey may be helpful for triggering more specific etiologic hypotheses that include factors related to endocrine disruption, DNA damage, inflammation, and nutrition during pregnancy. The survey results may stimulate a multidisciplinary discussion about new etiologic hypotheses of testicular cancer.

  17. Pharmacological inhibition of I-K1 by PA-6 in isolated rat hearts affects ventricular repolarization and refractoriness

    DEFF Research Database (Denmark)

    Skarsfeldt, Mark A.; Carstensen, Helena; Skibsbye, Lasse;

    2016-01-01

    .1 14.7 msec, 67%, P ventricular fibrillation was observed in two of six hearts. Neither atrial ERP nor duration of atrial fibrillation was altered following PA-6 application. The results show that pharmacological inhibition...... cycle length, and ventricular effective refractory period were determined following 200 nmol/L PA-6 perfusion. 200 nmol/L PA-6 resulted in a significant timelatency in drug effect on the IK1 current expressed in HEK-293 cells, giving rise to a maximal effect at 20 min. In the Langendorff-perfused heart...... experiments, PA-6 prolonged the ventricular action potential duration at 90% repolarization (from 41.8 6.5 msec to 72.6 21.1 msec, 74% compared to baseline, P ventricular effective refractory period compared to baseline (from 34.8 4.6 msec to 58...

  18. Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism.

    Science.gov (United States)

    Porcello, Darrell M; Ho, Chi Shun; Joho, Rolf H; Huguenard, John R

    2002-03-01

    Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

  19. A study on stability analysis of atrial repolarization variability using ARX model in sinus rhythm and atrial tachycardia ECGs.

    Science.gov (United States)

    Sivaraman, J; Uma, G; Langley, P; Umapathy, M; Venkatesan, S; Palanikumar, G

    2016-12-01

    The interaction between the PTa and PP interval dynamics from the surface ECG is seldom explained. Mathematical modeling of these intervals is of interest in finding the relationship between the heart rate and repolarization variability. The goal of this paper is to assess the bounded input bounded output (BIBO) stability in PTa interval (PTaI) dynamics using autoregressive exogenous (ARX) model and to investigate the reason for causing instability in the atrial repolarization process. Twenty-five male subjects in normal sinus rhythm (NSR) and ten male subjects experiencing atrial tachycardia (AT) were included in this study. Five minute long, modified limb lead (MLL) ECGs were recorded with an EDAN SE-1010 PC ECG system. The number of minute ECGs with unstable segments (Nus) and the frequency of premature activation (PA) (i.e. atrial activation) were counted for each ECG recording and compared between AT and NSR subjects. The instability in PTaI dynamics was quantified by measuring the numbers of unstable segments in ECG data for each subject. The unstable segments in the PTaI dynamics were associated with the frequency of PA. The presence of PA is not the only factor causing the instability in PTaI dynamics in NSR subjects, and it is found that the cause of instability is mainly due to the heart rate variability (HRV). The ARX model showed better prediction of PTa interval dynamics in both groups. The frequency of PA is significantly higher in AT patients than NSR subjects. A more complex model is needed to better identify and characterize healthy heart dynamics. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Estimating the Proportion of True Null Hypotheses for Multiple Comparisons

    National Research Council Canada - National Science Library

    Hongmei Jiang; RW Doerge

    2008-01-01

    ...) controlling procedures are too conservative. Although false discovery rate (FDR) procedures have been suggested as having greater power, the control itself is not exact and depends on the proportion of true null hypotheses...

  1. Current hypotheses regarding the pathophysiology behind the takotsubo syndrome.

    Science.gov (United States)

    Redfors, Björn; Shao, Yangzhen; Ali, Anwar; Omerovic, Elmir

    2014-12-20

    Takotsubo syndrome is an increasingly recognized acute cardiac affliction which is characterized by severe regional left ventricular dysfunction that cannot be explained by one or more occlusive culprit lesions of a coronary artery. A preceding somatic and/or emotional stressor can be identified in a majority of these patients and older women are overrepresented among the afflicted. Catecholamine levels are elevated in patients with takotsubo and exogenous catecholamine administration may cause or exacerbate the condition. Hence, catecholamines appear implicated in the pathogenesis. However, beyond catecholamine the pathogenesis of the takotsubo syndrome is unclear. Five distinct hypotheses have been postulated which attempt to explain why specific regions within the left ventricle are affected in takotsubo. In this manuscript we critically review these hypotheses in light of the available data. We discuss how the different hypotheses may be complementary to each other and to which extent they are contradicting one another.

  2. Illustrating Bayesian evaluation of informative hypotheses for regression models

    Directory of Open Access Journals (Sweden)

    Anouck eKluytmans

    2012-01-01

    Full Text Available In the present paper we illustrate the Bayesian evaluation of informative hypotheses for regression models. This approach allows psychologists to more directly test their theories than they would using conventional statis- tical analyses. Throughout this paper, both real-world data and simulated datasets will be introduced and evaluated to investigate the pragmatical as well as the theoretical qualities of the approach. We will pave the way from forming informative hypotheses in the context of regression models to interpreting the Bayes factors that express the support for the hypotheses being evaluated. In doing so, the present approach goes beyond p-values and uninformative null hypothesis testing, moving on to informative testing and quantification of model support in a way that is accessible to everyday psychologists.

  3. Toward Valid Measurement of Stephen Pepper's World Hypotheses.

    Science.gov (United States)

    Johnson, John A.

    Two measures of the "world hypotheses" of Stephen Pepper were mailed to 100 sociobiologists, 87 behaviorists, 79 personality psychologists, and 45 human developmentalists. The World Hypothesis Scale (WHS) was designed to measure Pepper's four world views: (1) formism; (2) mechanism; (3) organicism; and (4) contextualism. The Organicism-Mechanism…

  4. Testing some common tennis hypotheses: Four years at Wimbledon

    NARCIS (Netherlands)

    Magnus, J.R.; Klaassen, F.J.G.M.

    1996-01-01

    In this paper we investigate the truth (more often the untruth) of seventeen commonly heard statements about tennis. We base our analysis on point-by-point data of almost 500 singles matches played at Wimbledon, 1992-1995. The seventeen hypotheses under consideration are: 1 A player is as good as

  5. Testing some common tennis hypotheses : Four years at Wimbledon

    NARCIS (Netherlands)

    Magnus, J.R.; Klaassen, F.J.G.M.

    1996-01-01

    In this paper we investigate the truth (more often the untruth) of seventeen commonly heard statements about tennis.We base our analysis on point-by-point data of almost 500 singles matches played at Wimbledon, 1992-1995.The seventeen hypotheses under consideration are: 1 A player is as good as

  6. Review of hypotheses for fouling during beer clarification using membranes

    NARCIS (Netherlands)

    Mepschen, A.; Sman, van der R.G.M.; Vollebregt, H.M.; Noordman, T.R.

    2012-01-01

    Hypotheses concerning the fouling of membranes during beer clarification via crossflow microfiltration are reviewed. Beer has been classified into three groups of components, each having a different kind of fouling mechanisms – but also having interactions with other modes of fouling. The membrane f

  7. Deficiency in the Opioid Hypotheses of Self-Injurious Behavior.

    Science.gov (United States)

    King, Bryan H.; And Others

    1991-01-01

    This commentary critiques two papers by Curt Sandman, pointing out interpretive problems in models explaining self-injurious behavior in terms of opioids. Withdrawal effects are emphasized as an alternative to hypotheses asserting congenital opioid excess as a cause of sensory depression or an addiction to a relative excess of opioid activity in…

  8. Relative effects at work : Bayes factors for order hypotheses

    NARCIS (Netherlands)

    Braeken, J.; Mulder, J.; Wood, S.

    2015-01-01

    Assessing the relative importance of predictors has been of historical importance in a variety of disciplines including management, medicine, economics, and psychology. When approaching hypotheses on the relative ordering of the magnitude of predicted effects (e.g., the effects of discrimination fro

  9. The Female Register: An Empirical Study of Lakoff's Hypotheses

    Science.gov (United States)

    Crosby, Faye; Nyquist, Linda

    1977-01-01

    The data support Lakoff's hypotheses that the female register is used more by women than by men, although they do not necessarily justify her further assertion that women's speech reflects, or is caused by, the low status of women in our society. (Author/HP)

  10. Editorial: hypotheses about protein folding - the proteomic code and wonderfolds

    Directory of Open Access Journals (Sweden)

    Agutter Paul S

    2009-12-01

    Full Text Available Abstract Theoretical biology journals can contribute in many ways to the progress of knowledge. They are particularly well-placed to encourage dialogue and debate about hypotheses addressing problematical areas of research. An online journal provides an especially useful forum for such debate because of the option of posting comments within days of the publication of a contentious article.

  11. The response of rodents to scent marks: four broad hypotheses.

    Science.gov (United States)

    Ferkin, Michael H

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". Many terrestrial mammals must be able to distinguish between the myriad of scent marks they encounter in order for them to facilitate or deter direct interactions with their scent donors. I review studies that examine how rodents, mainly meadow voles (Microtus pennsylvanicus), respond when they encounter the scent marks of conspecifics and heterospecifics, and how context, as well as the age and condition of senders and receivers, affect their responses. The review uses four broad hypotheses to discuss the response of rodents to scent marks. The four hypotheses are as follows: 1) Scent marks convey accurate information to the receiver about the sender's state and phenotype and genotype. 2) Scent marks are individually distinct. 3) The response of receivers to scent marks is flexible and would be modulated by the cognitive abilities of receivers. 4) Receivers respond to the information contained or conveyed by the scent mark in a manner that will increase their survival and fitness. The studies cited in this review show that scent marks signal accurate information about the sender's phenotype, genotype, and condition, which receivers use to distinguish among the scent marks of different conspecifics and heterospecifics, and by doing so, receivers tailor their response accordingly to increase their survival and fitness. Thus, the four broad hypotheses may serve as guide to increase our understanding of the response of receivers to scent marks and provide a conceptual framework for future research and the development of additional hypotheses.

  12. Testing some common tennis hypotheses: Four years at Wimbledon

    NARCIS (Netherlands)

    Magnus, J.R.; Klaassen, F.J.G.M.

    1996-01-01

    In this paper we investigate the truth (more often the untruth) of seventeen commonly heard statements about tennis. We base our analysis on point-by-point data of almost 500 singles matches played at Wimbledon, 1992-1995. The seventeen hypotheses under consideration are: 1 A player is as good as hi

  13. Testing some common tennis hypotheses : Four years at Wimbledon

    NARCIS (Netherlands)

    Magnus, J.R.; Klaassen, F.J.G.M.

    1996-01-01

    In this paper we investigate the truth (more often the untruth) of seventeen commonly heard statements about tennis.We base our analysis on point-by-point data of almost 500 singles matches played at Wimbledon, 1992-1995.The seventeen hypotheses under consideration are: 1 A player is as good as his/

  14. Causes of bat fatalities at wind turbines: Hypotheses and predictions

    Science.gov (United States)

    Cryan, P.M.; Barclay, R.M.R.

    2009-01-01

    Thousands of industrial-scale wind turbines are being built across the world each year to meet the growing demand for sustainable energy. Bats of certain species are dying at wind turbines in unprecedented numbers. Species of bats consistently affected by turbines tend to be those that rely on trees as roosts and most migrate long distances. Although considerable progress has been made in recent years toward better understanding the problem, the causes of bat fatalities at turbines remain unclear. In this synthesis, we review hypothesized causes of bat fatalities at turbines. Hypotheses of cause fall into 2 general categoriesproximate and ultimate. Proximate causes explain the direct means by which bats die at turbines and include collision with towers and rotating blades, and barotrauma. Ultimate causes explain why bats come close to turbines and include 3 general types: random collisions, coincidental collisions, and collisions that result from attraction of bats to turbines. The random collision hypothesis posits that interactions between bats and turbines are random events and that fatalities are representative of the bats present at a site. Coincidental hypotheses posit that certain aspects of bat distribution or behavior put them at risk of collision and include aggregation during migration and seasonal increases in flight activity associated with feeding or mating. A surprising number of attraction hypotheses suggest that bats might be attracted to turbines out of curiosity, misperception, or as potential feeding, roosting, flocking, and mating opportunities. Identifying, prioritizing, and testing hypothesized causes of bat collisions with wind turbines are vital steps toward developing practical solutions to the problem. ?? 2009 American Society of Mammalogists.

  15. Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology

    DEFF Research Database (Denmark)

    Graff, Claus; Andersen, Mads P; Xue, Joel Q

    2009-01-01

    BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolariz......BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal...... are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug...... with QTcF, p ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has...

  16. High-threshold, Kv3-like potassium currents in magnocellular neurosecretory neurons and their role in spike repolarization.

    Science.gov (United States)

    Shevchenko, Talent; Teruyama, Ryoichi; Armstrong, William E

    2004-11-01

    We identified Kv3-like high-threshold K+ currents in hypothalamic supraoptic neurons using whole cell recordings in hypothalamic slices and in acutely dissociated neurons. Tetraethylammonium (TEA)-sensitive currents (Kv3-like channels. In slices, tests with 0.01-0.7 mM TEA produced an IC50 of 200-300 nM for both fast and persistent currents. The fast transient current was similar to currents associated with the expression of Kv3.4 subunits, given that it was sensitive to BDS-I (100 nM). The persistent TEA-sensitive current appeared similar to those attributed to Kv3.1/3.2 subunits. Although qualitatively similar, oxytocin (OT) and vasopressin (VP) neurons in slices differed in the stronger presence of persistent current in VP neurons. In both cell types, the IC50 for TEA-induced spike broadening was similar to that observed for current suppression in voltage clamp. However, TEA had a greater effect on the spike width of VP neurons than of OT neurons. Immunochemical studies revealed a stronger expression of the Kv3.1b alpha-subunit in VP neurons, which may be related to the greater importance of this current type in VP spike repolarization. Because OT and VP neurons are not considered fast firing, but do exhibit frequency- and calcium-dependent spike broadening, Kv3-like currents may be important for maintaining spike width and calcium influx within acceptable limits during repetitive firing.

  17. Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons.

    Science.gov (United States)

    Baranauskas, Gytis; Tkatch, Tatiana; Nagata, Keiichi; Yeh, Jay Z; Surmeier, D James

    2003-03-01

    Neurons with the capacity to discharge at high rates--'fast-spiking' (FS) neurons--are critical participants in central motor and sensory circuits. It is widely accepted that K+ channels with Kv3.1 or Kv3.2 subunits underlie fast, delayed-rectifier (DR) currents that endow neurons with this FS ability. Expression of these subunits in heterologous systems, however, yields channels that open at more depolarized potentials than do native Kv3 family channels, suggesting that they differ. One possibility is that native channels incorporate a subunit that modifies gating. Molecular, electrophysiological and pharmacological studies reported here suggest that a splice variant of the Kv3.4 subunit coassembles with Kv3.1 subunits in rat brain FS neurons. Coassembly enhances the spike repolarizing efficiency of the channels, thereby reducing spike duration and enabling higher repetitive spike rates. These results suggest that manipulation of K3.4 subunit expression could be a useful means of controlling the dynamic range of FS neurons.

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

    Directory of Open Access Journals (Sweden)

    B. M. Rocha

    2015-01-01

    Full Text Available 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.

  19. Somatic membrane potential and Kv1 channels control spike repolarization in cortical axon collaterals and presynaptic boutons.

    Science.gov (United States)

    Foust, Amanda J; Yu, Yuguo; Popovic, Marko; Zecevic, Dejan; McCormick, David A

    2011-10-26

    The shape of action potentials invading presynaptic terminals, which can vary significantly from spike waveforms recorded at the soma, may critically influence the probability of synaptic neurotransmitter release. Revealing the conductances that determine spike shape in presynaptic boutons is important for understanding how changes in the electrochemical context in which a spike is generated, such as subthreshold depolarization spreading from the soma, can modulate synaptic strength. Utilizing recent improvements in the signal-to-noise ratio of voltage-sensitive dye imaging in mouse brain slices, we demonstrate that intracortical axon collaterals and en passant presynaptic terminals of layer 5 pyramidal cells exhibit a high density of Kv1 subunit-containing ion channels, which generate a slowly inactivating K(+) current critically important for spike repolarization in these compartments. Blockade of the current by low doses of 4-aminopyridine or α-dendrotoxin dramatically slows the falling phase of action potentials in axon collaterals and presynaptic boutons. Furthermore, subthreshold depolarization of the soma broadened action potentials in collaterals bearing presynaptic boutons, an effect abolished by blocking Kv1 channels with α-dendrotoxin. These results indicate that action potential-induced synaptic transmission may operate through a mix of analog-digital transmission owing to the properties of Kv1 channels in axon collaterals and presynaptic boutons.

  20. Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias.

    Science.gov (United States)

    Magyar, Janos; Banyasz, Tamas; Szentandrassy, Norbert; Kistamas, Kornel; Nanasi, Peter P; Satin, Jonathan

    2015-01-01

    The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling. Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR. Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

  1. Should unfolded histograms be used to test hypotheses?

    CERN Document Server

    Cousins, Robert D; Sun, Yipeng

    2016-01-01

    In many analyses in high energy physics, attempts are made to remove the effects of detector smearing in data by techniques referred to as "unfolding" histograms, thus obtaining estimates of the true values of histogram bin contents. Such unfolded histograms are then compared to theoretical predictions, either to judge the goodness of fit of a theory, or to compare the abilities of two or more theories to describe the data. When doing this, even informally, one is testing hypotheses. However, a more fundamentally sound way to test hypotheses is to smear the theoretical predictions by simulating detector response and then comparing to the data without unfolding; this is also frequently done in high energy physics, particularly in searches for new physics. One can thus ask: to what extent does hypothesis testing after unfolding data materially reproduce the results obtained from testing by smearing theoretical predictions? We argue that this "bottom-line-test" of unfolding methods should be studied more commonl...

  2. On Brown's and Newton's methods with convexity hypotheses

    Science.gov (United States)

    Milaszewicz, J. P.

    2003-01-01

    In the context of the monotone Newton theorem (MNT) it has been conjectured that discretised Brown iterations converge at least as fast as discretised Newton iterations, because such is the case for analytic iterations. With easily verified hypotheses, it is proved here that Brown analytic iterations converge strictly faster than Newton ones. As a consequence, the same result holds for discretised iterations with conveniently small incremental steps. However, in the general context of the MNT, it may happen that Newton's discretised method converges faster than Brown's, but this situation can be remedied in many cases by conveniently shifting the initial value, so that those hypotheses ensuring the reverse are satisfied. Thus, a fairly effective solution is given to the problem stated initially.

  3. Dissolution of hypotheses in biochemistry: three case studies.

    Science.gov (United States)

    Fry, Michael

    2016-12-01

    The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases ('the tetranucleotide hypothesis'); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts.

  4. Furious Frederich: Nietzsche's neurosyphilis diagnosis and new hypotheses.

    Science.gov (United States)

    André, Charles; Rios, André Rangel

    2015-12-01

    The causes of Friedrich Nietzsche's mental breakdown in early 1889 and of the subsequent slow decay to end-stage dementia along ten years will possibly remain open to debate. The diagnosis of syphilitic dementia paralytica, based only on medical anamnesis and physical examination, was considered indisputable by Otto Binswanger. On the other hand, taking into account recently described diseases, selectively collected evidence lend some support to alternative hypotheses: basal forebrain meningioma, CADASIL, MELAS and frontotemporal dementia.

  5. Lake Shorelines: Earth Analogs for Hypothesized Martian Coastal Features

    Science.gov (United States)

    Zimbelman, J. R.; Williams, S. H.; Johnston, A. K.; Head, James W.

    2004-01-01

    The possibility of oceans on Mars has generated a lot of interest in the science community, but conclusive evidence supporting or refuting the ocean hypothesis has remained somewhat elusive. Precise topographic measurements of fresh-appearing shorelines from glacial Lake Lahontan were collected recently in an effort to obtain well-constrained data for comparison with the hypothesized Martian shorelines. This report summarizes the first results of the on-going research project.

  6. Evaluation of seven hypotheses for metamemory performance in rhesus monkeys.

    Science.gov (United States)

    Basile, Benjamin M; Schroeder, Gabriel R; Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

    2015-02-01

    Knowing the extent to which nonhumans and humans share mechanisms for metacognition will advance our understanding of cognitive evolution and will improve selection of model systems for biomedical research. Some nonhuman species avoid difficult cognitive tests, seek information when ignorant, or otherwise behave in ways consistent with metacognition. There is agreement that some nonhuman animals "succeed" in these metacognitive tasks, but little consensus about the cognitive mechanisms underlying performance. In one paradigm, rhesus monkeys visually searched for hidden food when ignorant of the location of the food, but acted immediately when knowledgeable. This result has been interpreted as evidence that monkeys introspectively monitored their memory to adaptively control information seeking. However, convincing alternative hypotheses have been advanced that might also account for the adaptive pattern of visual searching. We evaluated seven hypotheses using a computerized task in which monkeys chose either to take memory tests immediately or to see the answer again before proceeding to the test. We found no evidence to support the hypotheses of behavioral cue association, rote response learning, expectancy violation, response competition, generalized search strategy, or postural mediation. In contrast, we repeatedly found evidence to support the memory monitoring hypothesis. Monkeys chose to see the answer when memory was poor, either from natural variation or experimental manipulation. We found limited evidence that monkeys also monitored the fluency of memory access. Overall, the evidence indicates that rhesus monkeys can use memory strength as a discriminative cue for information seeking, consistent with introspective monitoring of explicit memory.

  7. The role of observational uncertainties in testing model hypotheses

    Science.gov (United States)

    Westerberg, I. K.; Birkel, C.

    2012-12-01

    Knowledge about hydrological processes and the spatial and temporal distribution of water resources is needed as a basis for managing water for hydropower, agriculture and flood-protection. Conceptual hydrological models may be used to infer knowledge on catchment functioning but are affected by uncertainties in the model representation of reality as well as in the observational data used to drive the model and to evaluate model performance. Therefore, meaningful hypothesis testing of the hydrological functioning of a catchment requires such uncertainties to be carefully estimated and accounted for in model calibration and evaluation. The aim of this study was to investigate the role of observational uncertainties in hypothesis testing, in particular whether it was possible to detect model-structural representations that were wrong in an important way given the uncertainties in the observational data. We studied the relatively data-scarce tropical Sarapiqui catchment in Costa Rica, Central America, where water resources play a vital part for hydropower production and livelihood. We tested several model structures of varying complexity as hypotheses about catchment functioning, but also hypotheses about the nature of the modelling errors. The tests were made within a learning framework for uncertainty estimation which enabled insights into data uncertainties, suitable model-structural representations and appropriate likelihoods. The observational uncertainty in discharge data was estimated from a rating-curve analysis and precipitation measurement errors through scenarios relating the error to, for example, canopy interception, wind-driven rain and the elevation gradient. The hypotheses were evaluated in a posterior analysis of the simulations where the performance of each simulation was analysed relative to the observational uncertainties for the entire hydrograph as well as for different aspects of the hydrograph (e.g. peak flows, recession periods, and base flow

  8. Ant Abundance along a Productivity Gradient: Addressing Two Conflicting Hypotheses

    Science.gov (United States)

    Segev, Udi; Kigel, Jaime; Lubin, Yael; Tielbörger, Katja

    2015-01-01

    The number of individuals within a population or community and their body size can be associated with changes in resource supply. While these relationships may provide a key to better understand the role of abiotic vs. biotic constraints in animal communities, little is known about the way size and abundance of organisms change along resource gradients. Here, we studied this interplay in ants, addressing two hypotheses with opposite predictions regarding variation in population densities along resource gradients- the ‘productivity hypothesis’ and the ‘productivity-based thinning hypothesis’. The hypotheses were tested in two functional groups of ground-dwelling ants that are directly primary consumers feeding on seeds: specialized seed-eaters and generalist species. We examined variations in colony density and foraging activity (a size measurement of the forager caste) in six ant assemblages along a steep productivity gradient in a semi-arid region, where precipitation and plant biomass vary 6-fold over a distance of 250km. An increase in the density or foraging activity of ant colonies along productivity gradients is also likely to affect competitive interactions among colonies, and consequently clinal changes in competition intensity were also examined. Ant foraging activity increased with productivity for both functional groups. However, colony density revealed opposing patterns: it increased with productivity for the specialized seed-eaters, but decreased for the generalist species. Competition intensity, evaluated by spatial partitioning of species at food baits and distribution of colonies, was uncorrelated with productivity in the specialized seed-eaters, but decreased with increasing productivity in the generalists. Our results provide support for two contrasting hypotheses regarding the effect of resource availability on the abundance of colonial organisms- the ‘productivity hypothesis’ for specialized seed-eaters and the

  9. Radiation signature folowing the hypothesized LOCA. [BWR; PWR

    Energy Technology Data Exchange (ETDEWEB)

    Bonzon, L.L.

    1977-09-01

    The study establishes the radiation source profile following the hypothesized Loss of Coolant Accident (LOCA) as suggested by the applicable Regulatory Guides. The source is specified as time-dependent gamma and beta energy release rates and energy spectra with dose and dose rate values presented for a generic containment structure. The results of the study will provide a basis for a comparison of radiation simulators used in (radiation) qualification testing of Class I components and an evaluation of simulator ''adequacy'' in duplicating the LOCA radiation environments and resultant component damage.

  10. Hypothesized eye movements of neurolinguistic programming: a statistical artifact.

    Science.gov (United States)

    Farmer, A; Rooney, R; Cunningham, J R

    1985-12-01

    Neurolinguistic programming's hypothesized eye-movements were measured independently from videotapes of 30 subjects, aged 15 to 76 yr., who were asked to recall visual pictures, recorded audio sounds, and textural objects. chi 2 indicated that subjects' responses were significantly different from those predicted. When chi 2 comparisons were weighted by number of eye positions assigned to each modality (3 visual, 3 auditory, 1 kinesthetic), subjects' responses did not differ significantly from the expected pattern. These data indicate that the eye-movement hypothesis may represent randomly occurring rather than sensory-modality-related positions.

  11. Chaos Versus Noisy Periodicity: Alternative Hypotheses for Childhood Epidemics

    Science.gov (United States)

    Olsen, L. F.; Schaffer, W. M.

    1990-08-01

    Whereas case rates for some childhood diseases (chickenpox) often vary according to an almost regular annual cycle, the incidence of more efficiently transmitted infections such as measles is more variable. Three hypotheses have been proposed to account for such fluctuations. (i) Irregular dynamics result from random shocks to systems with stable equilibria. (ii) The intrinsic dynamics correspond to biennial cycles that are subject to stochastic forcing. (iii) Aperiodic fluctuations are intrinsic to the epidemiology. Comparison of real world data and epidemiological models suggests that measles epidemics are inherently chaotic. Conversely, the extent to which chickenpox outbreaks approximate a yearly cycle depends inversely on the population size.

  12. Vaccines and autism: a tale of shifting hypotheses.

    Science.gov (United States)

    Gerber, Jeffrey S; Offit, Paul A

    2009-02-15

    Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence.

  13. EM algorithm and its application to testing hypotheses

    Institute of Scientific and Technical Information of China (English)

    房祥忠; 陈家鼎

    2003-01-01

    The conventional method for testing hypotheses is to find an exact or asymptotic distributionof a test statistic. But when the model is complex and the sample size is small, difficulty often arises. Thispaper aims to present a method for finding maximum probability with the help of EM algorithm. For any fixedsample size, this method can be used not only to obtain an accurate test but also to check the real level ofa test which is build by large sample theory. Especially, while doing this, one needs neither the accurate norasymptotic distribution of the test statistic. So the method is easily performed and is especially useful for small samples.

  14. Conceptual change, crucial experiments and auxiliary hypotheses. A theoretical contribution.

    Science.gov (United States)

    Levinas, Marcelo Leonardo; Carretero, Mario

    2010-12-01

    Theories about conceptual change have been generally related to historical and philosophical analysis of science. Yet, there is still much debate on how ideas coming from the history of science and their implications can be applied in this field. Our study intends to investigate the complex structure of conceptual change, by making use of some particularly representative features of the History and Philosophy of science, while considering the structure of so-called crucial experiments and the specific role of implicit hypotheses. Due to their historical importance and logical reasoning aspects, examining these issues may contribute to understand how conceptual change may take place.

  15. Multivariate refutation of aetiological hypotheses in non-experimental epidemiology.

    Science.gov (United States)

    Maclure, M

    1990-12-01

    Extension of Karl Popper's logic of refutation from the realm of contingency tables to multivariate modelling leads to the conclusion that rigorously scientific multivariate analysis in non-experimental epidemiology differs from the traditional quasi-scientific approach. Instead of aiming for high sensitivity in detecting aetiological agents, the goal in refutation is high specificity--to give the best defence of the 'innocence' of every exposure hypothesized as being a cause. Instead of 'forward selection' or 'backward elimination', multivariate refutation uses the method of 'forward elimination'. This entails a likelihood approach (which may be complemented by, but should be demarcated from, Bayesian methods) not only for statistical inference but also, by analogy, for study design and conduct: one starts with the conclusion (the estimate or hypothesis) and works backwards to the observations (the likelihood of the data or the design of the study). Differences in practice can sometimes be large, as illustrated by a study of hypothesized triggers of myocardial infarction. Multivariate refutation should replace the concept of multivariate modelling in non-experimental epidemiology.

  16. Attribution of detected changes in streamflow using multiple working hypotheses

    Science.gov (United States)

    Harrigan, S.; Murphy, C.; Hall, J.; Wilby, R. L.; Sweeney, J.

    2014-05-01

    This paper revisits a widely cited study of the Boyne catchment in east Ireland that attributed greater streamflow from the mid-1970s to increased precipitation linked to a shift in the North Atlantic Oscillation. Using the method of multiple working hypotheses we explore a wider set of potential drivers of hydrological change. Rainfall-runoff models are used to reconstruct streamflow to isolate the effect of climate, taking account of both model structure and parameter uncertainty. The Mann-Kendall test for monotonic trend and Pettitt change point test are applied to explore signatures of change. Contrary to earlier work, arterial drainage and simultaneous onset of field drainage in the 1970s and early 1980s are now invoked as the predominant drivers of change in annual mean and high flows within the Boyne. However, a change in precipitation regime is also present in March, thereby amplifying the effect of drainage. This new explanation posits that multiple drivers acting simultaneously were responsible for the observed change, with the relative contribution of each driver dependant on the timescale investigated. This work demonstrates that valuable insights can be gained from a systematic application of the method of multiple working hypotheses in an effort to move towards more rigorous attribution, which is an important part of managing emerging impacts on hydrological systems.

  17. Experienced physicians benefit from analyzing initial diagnostic hypotheses.

    Science.gov (United States)

    Bass, Adam; Geddes, Colin; Wright, Bruce; Coderre, Sylvain; Rikers, Remy; McLaughlin, Kevin

    2013-01-01

    Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p vs. 70.0%, p inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.07), whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.20). Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience.

  18. Ovarian aging and menopause: current theories, hypotheses, and research models.

    Science.gov (United States)

    Wu, Julie M; Zelinski, Mary B; Ingram, Donald K; Ottinger, Mary Ann

    2005-12-01

    Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents also exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline.

  19. Impact of dosing regimen of custirsen, an antisense oligonucleotide, on safety, tolerability and cardiac repolarization in healthy subjects.

    Science.gov (United States)

    Rabinovich-Guilatt, Laura; Elgart, Anna; Erisson, Lavi; Willsie, Sandra K; Tessler, Shoshi; Barnett-Griness, Ofra; Pande, Amitkumar; Spiegelstein, Ofer

    2015-09-01

    Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects. Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated. AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration-effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience. Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen. © 2015 The British Pharmacological Society.

  20. Mouse Models of Autism: Testing Hypotheses About Molecular Mechanisms

    OpenAIRE

    2011-01-01

    Autism is a neurodevelopmental disorder that is currently diagnosed by the presence of three behavioral criteria (1) qualitative impairments in reciprocal social interactions, (2) deficits in communication, including delayed language and noninteractive conversation, and (3) motor stereotypies, repetitive behaviors, insistence on sameness, and restricted interests. This chapter describes analogous behavioral assays that have been developed for mice, including tests for social approach, recipro...

  1. Self-preservation relation to the Kolmogorov similarity hypotheses

    Science.gov (United States)

    Djenidi, Lyazid; Antonia, Robert A.; Danaila, Luminita

    2017-05-01

    The relation between self-preservation (SP) and the Kolmogorov similarity hypotheses (Kolmogorov, The local structure of turbulence in incompressible viscous fluid for very large Reynolds numbers, Dokl. Akad. Nauk SSSR 30, 301 (1941) [Proc. R. Soc. London A 434, 9 (1991), 10.1098/rspa.1991.0075]) is investigated through the transport equations for the second- and third-order moments of the longitudinal velocity increments [ δ u (r ,t )=u (x ,t )-u (x +r ,t ) , where x ,t , and r are the spatial point and the time and longitudinal separation between two points, respectively]. It is shown that the fluid viscosity ν and the mean turbulent kinetic energy dissipation rate ɛ ¯ (the overbar represents an ensemble average) emerge naturally from the equations of motion as controlling parameters for the velocity increment moments when SP is assumed. Consequently, the Kolmogorov length scale η [≡(ν3/ɛ¯) 1 /4] and velocity scale vK [≡(νɛ ¯) 1 /4] also emerge as natural scaling parameters in conformity with SP, indicating that Kolmogorov's first hypothesis is subsumed under the more general hypothesis of SP. Further, the requirement for a very large Reynolds number is also relaxed, at least for the first similarity hypothesis. This requirement however is still necessary to derive the two-thirds law (or the four-fifths law) from the analysis. These analytical results are supported by experimental data in wake, jet, and grid turbulence. An expression for the fourth-order moment of the longitudinal velocity increments (δu ) 4¯ is derived from the analysis carried out in the inertial range. The expression, which involves the product of (δu ) 2 and ∂ δ p /∂ x , does not require the use the volume-averaged dissipation ɛ¯r, introduced by Oboukhov [Oboukhov, Some specific features of atmospheric turbulence, J. Fluid Mech. 13, 77 (1962), 10.1017/S0022112062000506] on a phenomenological basis and used by Kolmogorov to derive his refined similarity hypotheses

  2. Experimentally-Based Computational Investigation into Beat-To-Beat Variability in Ventricular Repolarization and Its Response to Ionic Current Inhibition.

    Directory of Open Access Journals (Sweden)

    E Pueyo

    Full Text Available Beat-to-beat variability in repolarization (BVR has been proposed as an arrhythmic risk marker for disease and pharmacological action. The mechanisms are unclear but BVR is thought to be a cell level manifestation of ion channel stochasticity, modulated by cell-to-cell differences in ionic conductances. In this study, we describe the construction of an experimentally-calibrated set of stochastic cardiac cell models that captures both BVR and cell-to-cell differences in BVR displayed in isolated canine action potential measurements using pharmacological agents. Simulated and experimental ranges of BVR are compared in control and under pharmacological inhibition, and the key ionic currents determining BVR under physiological and pharmacological conditions are identified. Results show that the 4-aminopyridine-sensitive transient outward potassium current, Ito1, is a fundamental driver of BVR in control and upon complete inhibition of the slow delayed rectifier potassium current, IKs. In contrast, IKs and the L-type calcium current, ICaL, become the major contributors to BVR upon inhibition of the fast delayed rectifier potassium current, IKr. This highlights both IKs and Ito1 as key contributors to repolarization reserve. Partial correlation analysis identifies the distribution of Ito1 channel numbers as an important independent determinant of the magnitude of BVR and drug-induced change in BVR in control and under pharmacological inhibition of ionic currents. Distributions in the number of IKs and ICaL channels only become independent determinants of the magnitude of BVR upon complete inhibition of IKr. These findings provide quantitative insights into the ionic causes of BVR as a marker for repolarization reserve, both under control condition and pharmacological inhibition.

  3. Optimum testing of multiple hypotheses in quantum detection theory

    Science.gov (United States)

    Yuen, H. P.; Kennedy, R. S.; Lax, M.

    1975-01-01

    The problem of specifying the optimum quantum detector in multiple hypotheses testing is considered for application to optical communications. The quantum digital detection problem is formulated as a linear programming problem on an infinite-dimensional space. A necessary and sufficient condition is derived by the application of a general duality theorem specifying the optimum detector in terms of a set of linear operator equations and inequalities. Existence of the optimum quantum detector is also established. The optimality of commuting detection operators is discussed in some examples. The structure and performance of the optimal receiver are derived for the quantum detection of narrow-band coherent orthogonal and simplex signals. It is shown that modal photon counting is asymptotically optimum in the limit of a large signaling alphabet and that the capacity goes to infinity in the absence of a bandwidth limitation.

  4. Hypotheses of the origin of natural antibodies: a glycobiologist's opinion.

    Science.gov (United States)

    Khasbiullina, N R; Bovin, N V

    2015-07-01

    It is generally accepted that the generation of antibodies proceeds due to immunization of an organism by alien antigens, and the level and affinity of antibodies are directly correlated to the presence of immunogen. At the same time, vast experimental material has been obtained providing evidence of antibodies whose level remains unchanged and affinity is constant during a lifetime. In contrast to the first, adaptive immunoglobulins, the latter are named natural antibodies (nAbs). The nAbs are produced by B1 cells, whereas adaptive Abs are produced by B2. This review summarizes general data on nAbs and presents in more detail data on antigens of carbohydrate origin. Hypotheses on the origin of nAbs and their activation mechanisms are discussed. We present our thoughts on this matter supported by our experimental data on nAbs to glycans.

  5. Psychohistorical Hypotheses on Japan's History of Hostility Towards China.

    Science.gov (United States)

    Wang, Bo; Rudmin, Floyd

    2016-01-01

    The accelerating tensions and military posturing between Japan and China have created a serious crisis with a danger of a catastrophic war. The purpose of this paper is to summarize the events of the current crisis, and to put it in the context of Japan's long history of hostility to China and repeated attempts at conquest. The historical record shows that Japan has attacked China at least seven times, even though China has never attacked Japan. The irrationality of Japan's behavior is demonstrated by the repetition of this hostile behavior despite the enormous human and economic costs that Japan has suffered because of it. The irrationality of Japan's militarism suggests that psychological explanations may be required to understand this phenomenon. Several hypotheses are proposed, including 1) projected paranoid aggression, 2) collective Zeigarnik compulsion, 3) perceived weakness exciting aggression, 4) national inferiority feelings, 5) cultural narcissism, and 6) Oedipal-like hatred of a parent culture.

  6. Platinum(iv) anticancer prodrugs - hypotheses and facts.

    Science.gov (United States)

    Gibson, Dan

    2016-08-16

    In this manuscript we focus on Pt(iv) anticancer prodrugs. We explore the main working hypotheses for the design of effective Pt(iv) prodrugs and note the exceptions to the common assumptions that are prevalent in the field. Special attention was devoted to the emerging class of "dual action" Pt(iv) prodrugs, where bioactive ligands are conjugated to the axial positions of platinum in order to obtain orthogonal or complementary effects that will increase the efficacy of killing the cancer cells. We discuss the rationale behind the design of the "dual action" prodrugs and the results of the pharmacological studies obtained. Simultaneous release of two bioactive moieties inside the cancer cells often triggers several processes that together determine the fate of the cell. Pt(iv) complexes provide many opportunities for applying new concepts in targeting, synergistic cell killing and exploiting novel nanodelivery systems.

  7. From themes to hypotheses: following up with quantitative methods.

    Science.gov (United States)

    Morgan, David L

    2015-06-01

    One important category of mixed-methods research designs consists of quantitative studies that follow up on qualitative research. In this case, the themes that serve as the results from the qualitative methods generate hypotheses for testing through the quantitative methods. That process requires operationalization to translate the concepts from the qualitative themes into quantitative variables. This article illustrates these procedures with examples that range from simple operationalization to the evaluation of complex models. It concludes with an argument for not only following up qualitative work with quantitative studies but also the reverse, and doing so by going beyond integrating methods within single projects to include broader mutual attention from qualitative and quantitative researchers who work in the same field. © The Author(s) 2015.

  8. Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses.

    Science.gov (United States)

    Muzny, Christina A; Schwebke, Jane R

    2016-08-15

    In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. The discussion on the epidemiology and pathogenesis of BV is presented here, and several hypotheses on its pathogenesis are critiqued. Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV. This information is vital for the prevention and control of this important infection and its adverse public health consequences. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  9. Individualist and collectivist values: hypotheses suggested by Alexis de Tocqueville.

    Science.gov (United States)

    Watson, P J; Morris, Ronald J

    2002-05-01

    The work of Alexis de Tocqueville, the 19th-century social theorist who coined the term individualism, supplied a conceptual foundation for hypothesizing that individualism and collectivism, as value systems, should be directly correlated. In previous research (D. K.-S. Chan, 1994), individualist and collectivist values were negatively correlated in a sample of men, and in a combined sample of men and women (P. J. Watson, J. Sherbak, & R. J. Morris, 1998) these values were positively correlated. In the present study, a positive relationship was in fact observed in both men and women. Linkages with other measures of self and social functioning uncovered a few small associations of individualist values with maladjustment. Collectivist values predicted adjustment. These data confirm that individualist and collectivist values are compatible, just as Tocqueville had suggested, and that gender differences do not explain the conflicting results previously reported in this literature.

  10. Hypotheses to explain the origin of species in Amazonia

    Directory of Open Access Journals (Sweden)

    J. Haffer

    Full Text Available The main hypotheses proposed to explain barrier formation separating populations and causing the differentiation of species in Amazonia during the course of geological history are based on different factors, as follow: (1 Changes in the distribution of land and sea or in the landscape due to tectonic movements or sea level fluctuations (Paleogeography hypothesis, (2 the barrier effect of Amazonian rivers (River hypothesis, (3 a combination of the barrier effect of broad rivers and vegetational changes in northern and southern Amazonia (River-refuge hypothesis, (4 the isolation of humid rainforest blocks near areas of surface relief in the periphery of Amazonia separated by dry forests, savannas and other intermediate vegetation types during dry climatic periods of the Tertiary and Quaternary (Refuge hypothesis, (5 changes in canopy-density due to climatic reversals (Canopy-density hypothesis (6 the isolation and speciation of animal populations in small montane habitat pockets around Amazonia due to climatic fluctuations without major vegetational changes (Museum hypothesis, (7 competitive species interactions and local species isolations in peripheral regions of Amazonia due to invasion and counterinvasion during cold/warm periods of the Pleistocene (Disturbance-vicariance hypothesis and (8 parapatric speciation across steep environmental gradients without separation of the respective populations (Gradient hypothesis. Several of these hypotheses probably are relevant to a different degree for the speciation processes in different faunal groups or during different geological periods. The basic paleogeography model refers mainly to faunal differentiation during the Tertiary and in combination with the Refuge hypothesis. Milankovitch‡ cycles leading to global main hypotheses proposed to explain barrier formation separating populations and causing the differentiation of species in Amazonia during the course of geological history are based on

  11. Identifying And Weighting Integration Hypotheses On Open Data Platforms

    CERN Document Server

    Eberius, Julian; Thiele, Maik; Lehner, Wolfgang

    2012-01-01

    Open data platforms such as data.gov or opendata.socrata. com provide a huge amount of valuable information. Their free-for-all nature, the lack of publishing standards and the multitude of domains and authors represented on these platforms lead to new integration and standardization problems. At the same time, crowd-based data integration techniques are emerging as new way of dealing with these problems. However, these methods still require input in form of specific questions or tasks that can be passed to the crowd. This paper discusses integration problems on Open Data Platforms, and proposes a method for identifying and ranking integration hypotheses in this context. We will evaluate our findings by conducting a comprehensive evaluation using on one of the largest Open Data platforms.

  12. Evolutionary origins of human handedness: evaluating contrasting hypotheses.

    Science.gov (United States)

    Cochet, Hélène; Byrne, Richard W

    2013-07-01

    Variation in methods and measures, resulting in past dispute over the existence of population handedness in nonhuman great apes, has impeded progress into the origins of human right-handedness and how it relates to the human hallmark of language. Pooling evidence from behavioral studies, neuroimaging and neuroanatomy, we evaluate data on manual and cerebral laterality in humans and other apes engaged in a range of manipulative tasks and in gestural communication. A simplistic human/animal partition is no longer tenable, and we review four (nonexclusive) possible drivers for the origin of population-level right-handedness: skilled manipulative activity, as in tool use; communicative gestures; organizational complexity of action, in particular hierarchical structure; and the role of intentionality in goal-directed action. Fully testing these hypotheses will require developmental and evolutionary evidence as well as modern neuroimaging data.

  13. Hypotheses to explain the origin of species in Amazonia.

    Science.gov (United States)

    Haffer, J

    2008-11-01

    The main hypotheses proposed to explain barrier formation separating populations and causing the differentiation of species in Amazonia during the course of geological history are based on different factors, as follow: (1) Changes in the distribution of land and sea or in the landscape due to tectonic movements or sea level fluctuations (Paleogeography hypothesis), (2) the barrier effect of Amazonian rivers (River hypothesis), (3) a combination of the barrier effect of broad rivers and vegetational changes in northern and southern Amazonia (River-refuge hypothesis), (4) the isolation of humid rainforest blocks near areas of surface relief in the periphery of Amazonia separated by dry forests, savannas and other intermediate vegetation types during dry climatic periods of the Tertiary and Quaternary (Refuge hypothesis), (5) changes in canopy-density due to climatic reversals (Canopy-density hypothesis) (6) the isolation and speciation of animal populations in small montane habitat pockets around Amazonia due to climatic fluctuations without major vegetational changes (Museum hypothesis), (7) competitive species interactions and local species isolations in peripheral regions of Amazonia due to invasion and counterinvasion during cold/warm periods of the Pleistocene (Disturbance-vicariance hypothesis) and (8) parapatric speciation across steep environmental gradients without separation of the respective populations (Gradient hypothesis). Several of these hypotheses probably are relevant to a different degree for the speciation processes in different faunal groups or during different geological periods. The basic paleogeography model refers mainly to faunal differentiation during the Tertiary and in combination with the Refuge hypothesis. Milankovitch cycles leading to global main hypotheses proposed to explain barrier formation separating populations and causing the differentiation of species in Amazonia during the course of geological history are based on different

  14. Evaluating alternative stem cell hypotheses for adultcorneal epithelial maintenance

    Institute of Scientific and Technical Information of China (English)

    John D West; Natalie J Dorà; Natalie J Dorà,

    2015-01-01

    In this review we evaluate evidence for three differenthypotheses that explain how the corneal epitheliumis maintained. The limbal epithelial stem cell (LESC)hypothesis is most widely accepted. This proposes thatstem cells in the basal layer of the limbal epithelium,at the periphery of the cornea, maintain themselvesand also produce transient (or transit) amplifying cells(TACs). TACs then move centripetally to the centre ofthe cornea in the basal layer of the corneal epitheliumand also replenish cells in the overlying suprabasallayers. The LESCs maintain the corneal epitheliumduring normal homeostasis and become more active torepair significant wounds. Second, the corneal epithelialstem cell (CESC) hypothesis postulates that, duringnormal homeostasis, stem cells distributed throughoutthe basal corneal epithelium, maintain the tissue.According to this hypothesis, LESCs are present in thelimbus but are only active during wound healing. We alsoconsider a third possibility, that the corneal epithelium ismaintained during normal homeostasis by proliferationof basal corneal epithelial cells without any input fromstem cells. After reviewing the published evidence,we conclude that the LESC and CESC hypotheses areconsistent with more of the evidence than the thirdhypothesis, so we do not consider this further. The LESCand CESC hypotheses each have difficulty accountingfor one main type of evidence so we evaluate the twokey lines of evidence that discriminate between them.Finally, we discuss how lineage-tracing experimentshave begun to resolve the debate in favour of theLESC hypothesis. Nevertheless, it also seems likely thatsome basal corneal epithelial cells can act as long-termprogenitors if limbal stem cell function is compromised.Thus, this aspect of the CESC hypothesis may have alasting impact on our understanding of corneal epithelialmaintenance, even if it is eventually shown that stemcells are restricted to the limbus as proposed by the

  15. Experienced physicians benefit from analyzing initial diagnostic hypotheses

    Directory of Open Access Journals (Sweden)

    Adam Bass

    2013-03-01

    Full Text Available Background: Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. Methods: We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. Results: After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p < 0.001, and 40.0% vs. 70.0%, p < 0.001, respectively. We found a significant interaction between experience and analytic processing strategy (p = 0.002: nephrology residents had significantly increased odds of diagnostic success when using scheme-inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.007, whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.2. Discussion: Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience.

  16. Sticky Genomes: Using NGS Evidence to Test Hybrid Speciation Hypotheses.

    Directory of Open Access Journals (Sweden)

    Mary Morgan-Richards

    Full Text Available Hypotheses of hybrid origin are common. Here we use next generation sequencing to test a hybrid hypothesis for a non-model insect with a large genome. We compared a putative hybrid triploid stick insect species (Acanthoxyla geisovii with its putative paternal diploid taxon (Clitarchus hookeri, a relationship that provides clear predictions for the relative genetic diversity within each genome. The parental taxon is expected to have comparatively low allelic diversity that is nested within the diversity of the hybrid daughter genome. The scale of genome sequencing required was conveniently achieved by extracting mRNA and sequencing cDNA to examine expressed allelic diversity. This allowed us to test hybrid-progenitor relationships among non-model organisms with large genomes and different ploidy levels. Examination of thousands of independent loci avoids potential problems produced by the silencing of parts of one or other of the parental genomes, a phenomenon sometimes associated with the process of stabilisation of a hybrid genome. Transcript assembles were assessed for evidence of paralogs and/or alternative splice variants before proceeding. Comparison of transcript assemblies was not an appropriate measure of genetic variability, but by mapping reads back to clusters derived from each species we determined levels of allelic diversity. We found greater cDNA sequence diversity among alleles in the putative hybrid species (Acanthoxyla geisovii than the non-hybrid. The allelic diversity within the putative paternal species (Clitachus hookeri nested within the hybrid-daughter genome, supports the current view of a hybrid-progenitor relationship for these stick insect species. Next generation sequencing technology provides opportunities for testing evolutionary hypotheses with non-model organisms, including, as here, genomes that are large due to polyploidy.

  17. Hypotheses for Near-Surface Exchange of Methane on Mars

    Science.gov (United States)

    Hu, Renyu; Bloom, A. Anthony; Gao, Peter; Miller, Charles E.; Yung, Yuk L.

    2016-07-01

    The Curiosity rover recently detected a background of 0.7 ppb and spikes of 7 ppb of methane on Mars. This in situ measurement reorients our understanding of the martian environment and its potential for life, as the current theories do not entail any geological source or sink of methane that varies sub-annually. In particular, the 10-fold elevation during the southern winter indicates episodic sources of methane that are yet to be discovered. Here we suggest a near-surface reservoir could explain this variability. Using the temperature and humidity measurements from the rover, we find that perchlorate salts in the regolith deliquesce to form liquid solutions, and deliquescence progresses to deeper subsurface in the season of the methane spikes. We therefore formulate the following three testable hypotheses. The first scenario is that the regolith in Gale Crater adsorbs methane when dry and releases this methane to the atmosphere upon deliquescence. The adsorption energy needs to be 36 kJ mol-1 to explain the magnitude of the methane spikes, higher than existing laboratory measurements. The second scenario is that microorganisms convert organic matter in the soil to methane when they are in liquid solutions. This scenario does not require regolith adsorption but entails extant life on Mars. The third scenario is that deep subsurface aquifers produce the bursts of methane. Continued in situ measurements of methane and water, as well as laboratory studies of adsorption and deliquescence, will test these hypotheses and inform the existence of the near-surface reservoir and its exchange with the atmosphere.

  18. Effect of NIP-142 on potassium channel alpha-subunits Kv1.5, Kv4.2 and Kv4.3, and mouse atrial repolarization.

    Science.gov (United States)

    Tanaka, Hikaru; Namekata, Iyuki; Hamaguchi, Shogo; Kawamura, Taro; Masuda, Hiroyuki; Tanaka, Yoshio; Iida-Tanaka, Naoko; Takahara, Akira

    2010-01-01

    Effects of NIP-142, a benzopyran compound which terminates experimental atrial arrhythmia, on potassium channel alpha-subunits and mouse atrial repolarization were examined. NIP-142 concentration-dependently blocked the outward current through potassium channel alpha subunits Kv1.5, Kv4.2 and Kv4.3 expressed in Xenopus oocytes. In isolated mouse atrial myocardia, NIP-142 prolonged the action potential duration and effective refractory period, and increased the contractile force. These results suggest that NIP-142 blocks the potassium channels underlying the transient and sustained outward currents, which may contribute to its antiarrhythmic activity.

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

    OpenAIRE

    Liu, Pin W.; Bean, Bruce P.

    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 ...

  20. Pickles and Ice Cream! Food Cravings in Pregnancy: Hypotheses, Preliminary Evidence, and Directions for Future Research

    Directory of Open Access Journals (Sweden)

    Natalia C. Orloff

    2014-09-01

    Full Text Available Women in the United States experience an increase in food cravings at two specific times during their life, 1 perimenstrually and 2 prenatally. The prevalence of excess gestational weight gain (GWG is a growing concern due to its association with adverse health outcomes in both mothers and children. To the extent that prenatal food cravings may be a determinant of energy intake in pregnancy, a better understanding of craving etiology could be crucial in addressing the issue of excessive GWG. This paper reviews the available literature to corroborate and/or dispute some of the most commonly accepted hypotheses regarding the causes of food cravings during pregnancy, including a role of 1 hormonal changes, 2 nutritional deficits, 3 pharmacologically active ingredients in the desired foods, and 4 cultural and psychosocial factors. An existing model of perimenstrual chocolate craving etiology serves to structure the discussion of these hypotheses. The main hypotheses discussed receive little support, with the notable exception of a postulated role of cultural and psychosocial factors. The presence of cravings during pregnancy is a common phenomenon across different cultures, but the types of foods desired and the adverse impact of cravings on health may be culture-specific. Various psychosocial factors appear to correlate with excess GWG, including the presence of restrained eating. Findings strongly suggest that more research be conducted in this area. We propose that future investigations fall into one of the four following categories: 1 validation of food craving and eating-related measures specifically in pregnant populations, 2 use of ecological momentary assessment to obtain real time data on cravings during pregnancy, 3 implementation of longitudinal studies to address causality between eating disorder symptoms, food cravings, and gestational weight gain, and 4 development of interventions to ensure proper prenatal nutrition and prevent excess

  1. Pickles and ice cream! Food cravings in pregnancy: hypotheses, preliminary evidence, and directions for future research.

    Science.gov (United States)

    Orloff, Natalia C; Hormes, Julia M

    2014-01-01

    Women in the United States experience an increase in food cravings at two specific times during their life, (1) perimenstrually and (2) prenatally. The prevalence of excess gestational weight gain (GWG) is a growing concern due to its association with adverse health outcomes in both mothers and children. To the extent that prenatal food cravings may be a determinant of energy intake in pregnancy, a better understanding of craving etiology could be crucial in addressing the issue of excessive GWG. This paper reviews the available literature to corroborate and/or dispute some of the most commonly accepted hypotheses regarding the causes of food cravings during pregnancy, including a role of (1) hormonal changes, (2) nutritional deficits, (3) pharmacologically active ingredients in the desired foods, and (4) cultural and psychosocial factors. An existing model of perimenstrual chocolate craving etiology serves to structure the discussion of these hypotheses. The main hypotheses discussed receive little support, with the notable exception of a postulated role of cultural and psychosocial factors. The presence of cravings during pregnancy is a common phenomenon across different cultures, but the types of foods desired and the adverse impact of cravings on health may be culture-specific. Various psychosocial factors appear to correlate with excess GWG, including the presence of restrained eating. Findings strongly suggest that more research be conducted in this area. We propose that future investigations fall into one of the four following categories: (1) validation of food craving and eating-related measures specifically in pregnant populations, (2) use of ecological momentary assessment to obtain real time data on cravings during pregnancy, (3) implementation of longitudinal studies to address causality between eating disorder symptoms, food cravings, and GWG, and (4) development of interventions to ensure proper prenatal nutrition and prevent excess GWG.

  2. Visual hallucinations in PD and Lewy body dementias: old and new hypotheses.

    Science.gov (United States)

    Onofrj, M; Taylor, J P; Monaco, D; Franciotti, R; Anzellotti, F; Bonanni, L; Onofrj, V; Thomas, A

    2013-01-01

    Visual Hallucinations (VH) are a common non-motor symptom of Parkinson's Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.

  3. Mindfulness-based treatment to prevent addictive behavior relapse: theoretical models and hypothesized mechanisms of change.

    Science.gov (United States)

    Witkiewitz, Katie; Bowen, Sarah; Harrop, Erin N; Douglas, Haley; Enkema, Matthew; Sedgwick, Carly

    2014-04-01

    Mindfulness-based treatments are growing in popularity among addiction treatment providers, and several studies suggest the efficacy of incorporating mindfulness practices into the treatment of addiction, including the treatment of substance use disorders and behavioral addictions (i.e., gambling). The current paper provides a review of theoretical models of mindfulness in the treatment of addiction and several hypothesized mechanisms of change. We provide an overview of mindfulness-based relapse prevention (MBRP), including session content, treatment targets, and client feedback from participants who have received MBRP in the context of empirical studies. Future research directions regarding operationalization and measurement, identifying factors that moderate treatment effects, and protocol adaptations for specific populations are discussed.

  4. An automated framework for hypotheses generation using literature

    Directory of Open Access Journals (Sweden)

    Abedi Vida

    2012-08-01

    Full Text Available Abstract Background In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF finds “crisp semantic associations” among entities of interest - that is a step towards bridging such gaps. Methodology The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect “crisp” associations, and making assertions about entities (such as disease X is associated with a set of factors Z. Results Pilot studies were performed using two diseases. A comparative analysis of the computed “associations” and “assertions” with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture “crisp” direct and indirect associations, and provide knowledge

  5. Neuroinflammation in bipolar disorders

    OpenAIRE

    Georgios D. Kotzalidis; Elisa Ambrosi; Alessio Simonetti; Ilaria Cuomo; Antonio Del Casale; Matteo Caloro; Valeria Savoja; Chiara Rapinesi

    2015-01-01

    Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation, is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuro...

  6. Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8.

    Science.gov (United States)

    Barajas-Martínez, Hector; Hu, Dan; Ferrer, Tania; Onetti, Carlos G; Wu, Yuesheng; Burashnikov, Elena; Boyle, Madalene; Surman, Tyler; Urrutia, Janire; Veltmann, Christian; Schimpf, Rainer; Borggrefe, Martin; Wolpert, Christian; Ibrahim, Bassiema B; Sánchez-Chapula, José Antonio; Winters, Stephen; Haïssaguerre, Michel; Antzelevitch, Charles

    2012-04-01

    Adenosine triphosphate (ATP)-sensitive potassium cardiac channels consist of inward-rectifying channel subunits Kir6.1 or Kir6.2 (encoded by KCNJ8 or KCNJ11) and the sulfonylurea receptor subunits SUR2A (encoded by ABCC9). To examine the association of mutations in KCNJ8 with Brugada syndrome (BrS) and early repolarization syndrome (ERS) and to elucidate the mechanism underlying the gain of function of ATP-sensitive potassium channel current. Direct sequencing of KCNJ8 and other candidate genes was performed on 204 BrS and ERS probands and family members. Whole-cell and inside-out patch-clamp methods were used to study mutated channels expressed in TSA201 cells. The same missense mutation, p.Ser422Leu (c.1265C>T) in KCNJ8, was identified in 3 BrS and 1 ERS probands but was absent in 430 alleles from ethnically matched healthy controls. Additional genetic variants included CACNB2b-D601E. Whole-cell patch-clamp studies showed a 2-fold gain of function of glibenclamide-sensitive ATP-sensitive potassium channel current when KCNJ8-S422L was coexpressed with SUR2A-wild type. Inside-out patch-clamp evaluation yielded a significantly greater half maximal inhibitory concentration for ATP in the mutant channels (785.5 ± 2 vs 38.4 ± 3 μM; n = 5; P <.01), pointing to incomplete closing of the ATP-sensitive potassium channels under normoxic conditions. Patients with a CACNB2b-D601E polymorphism displayed longer QT/corrected QT intervals, likely owing to their effect to induce an increase in L-type calcium channel current (I(Ca-L)). Our results support the hypothesis that KCNJ8 is a susceptibility gene for BrS and ERS and point to S422L as a possible hotspot mutation. Our findings suggest that the S422L-induced gain of function in ATP-sensitive potassium channel current is due to reduced sensitivity to intracellular ATP. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  7. Local Left Ventricular Epicardial J Waves and Late Potentials in Brugada Syndrome Patients with Inferolateral Early Repolarization Pattern

    Science.gov (United States)

    Nagase, Satoshi; Tanaka, Masamichi; Morita, Hiroshi; Nakagawa, Koji; Wada, Tadashi; Murakami, Masato; Nishii, Nobuhiro; Nakamura, Kazufumi; Ito, Hiroshi; Ohe, Tohru; Kusano, Kengo F.

    2017-01-01

    Background: Brugada syndrome (BrS) is characterized by J-point or ST-segment elevation on electrocardiograms (ECGs) and increased risk of ventricular fibrillation (VF). In BrS, epicardial depolarization abnormality with delayed potential on the right ventricular outflow tract is reportedly the predominant mechanism underlying VF. Yet VF occurrence is also associated with early repolarization (ER) pattern in the inferolateral ECG leads, which may represent the inferior and/or left lateral ventricular myocardium. The aim of this study was to examine epicardial electrograms recorded directly at the left ventricle (LV) in BrS patients after VF episodes. Methods: In 12 BrS patients who had experienced VF episodes and 17 control subjects, a multipolar catheter was introduced into the left lateral coronary vein for unipolar and bipolar electrogram recordings at the LV epicardium. Both inferior and lateral ER patterns on ECG were observed in three BrS patients and six control subjects. Results: In the epicardium, prominent J waves were detected using unipolar recording, and potentials after the QRS complex were detected using bipolar recording in three of the 12 BrS patients. These three patients also showed both inferior and lateral ER patterns on ECG. Neither prominent J waves nor potentials after the QRS complex were recorded at the endocardium of the LV in any of these three patients; nor were they seen at the epicardium in any of the control subjects. These features were accentuated on pilsicainide administration (n = 2) but diminished on constant atrial pacing (n = 3) and isoproterenol administration (n = 1). The J waves observed through unipolar recording coincided with the potentials after QRS complex observed through bipolar recording and with the inferolateral ER patterns on ECG. Conclusions: We recorded prominent J waves in unipolar electrogram and potentials after QRS complex in bipolar electrogram at the LV epicardium in BrS patients with global ER pattern

  8. Local Left Ventricular Epicardial J Waves and Late Potentials in Brugada Syndrome Patients with Inferolateral Early Repolarization Pattern.

    Science.gov (United States)

    Nagase, Satoshi; Tanaka, Masamichi; Morita, Hiroshi; Nakagawa, Koji; Wada, Tadashi; Murakami, Masato; Nishii, Nobuhiro; Nakamura, Kazufumi; Ito, Hiroshi; Ohe, Tohru; Kusano, Kengo F

    2017-01-01

    Background: Brugada syndrome (BrS) is characterized by J-point or ST-segment elevation on electrocardiograms (ECGs) and increased risk of ventricular fibrillation (VF). In BrS, epicardial depolarization abnormality with delayed potential on the right ventricular outflow tract is reportedly the predominant mechanism underlying VF. Yet VF occurrence is also associated with early repolarization (ER) pattern in the inferolateral ECG leads, which may represent the inferior and/or left lateral ventricular myocardium. The aim of this study was to examine epicardial electrograms recorded directly at the left ventricle (LV) in BrS patients after VF episodes. Methods: In 12 BrS patients who had experienced VF episodes and 17 control subjects, a multipolar catheter was introduced into the left lateral coronary vein for unipolar and bipolar electrogram recordings at the LV epicardium. Both inferior and lateral ER patterns on ECG were observed in three BrS patients and six control subjects. Results: In the epicardium, prominent J waves were detected using unipolar recording, and potentials after the QRS complex were detected using bipolar recording in three of the 12 BrS patients. These three patients also showed both inferior and lateral ER patterns on ECG. Neither prominent J waves nor potentials after the QRS complex were recorded at the endocardium of the LV in any of these three patients; nor were they seen at the epicardium in any of the control subjects. These features were accentuated on pilsicainide administration (n = 2) but diminished on constant atrial pacing (n = 3) and isoproterenol administration (n = 1). The J waves observed through unipolar recording coincided with the potentials after QRS complex observed through bipolar recording and with the inferolateral ER patterns on ECG. Conclusions: We recorded prominent J waves in unipolar electrogram and potentials after QRS complex in bipolar electrogram at the LV epicardium in BrS patients with global ER pattern

  9. Exploration of miRNA families for hypotheses generation.

    KAUST Repository

    Kamanu, T.K.

    2013-10-15

    Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

  10. Plant reproduction systems in microgravity: experimental data and hypotheses

    Science.gov (United States)

    Kordyum, E. L.

    Elucidation of the possibilities for higher plants to realize complete ontogenesis, from seed to seed, and to propagate by seeds in microgravity, is a fundamental task of space biology connected with the working of the CELSS program. At present, there are results of only 6 spaceflight experiments with Arabidopsis thaliana, an ephemeral plant which will flower and fruit in orbit. Morphogenesis of generative organs occurs normally in microgravity, but unlike the ground control, buds and flowers mainly contain sterile elements of the androecium and gynoecium which degenerate at different stages of development in microgravity. Cytological peculiarities of male and female sterility in microgravity are similar to those occurring naturally during sexual differentiation. Many of the seed formed in microgravity are: 1) nutritional deficiency, 2) insufficient light, 3) intensification of the influence of the above-mentioned factors by microgravity, 4) disturbances of a hormonal nature, and 5) the absence of pollination and fertilization. Possible ways for testing these hypotheses and obtaining viable seeds in microgravity are discussed.

  11. Testing hypotheses about glacial cycles against the observational record

    Science.gov (United States)

    Kaufmann, Robert K.; Juselius, Katarina

    2013-01-01

    We estimate an identified cointegrated vector autoregression model of the climate system to test hypotheses about the physical mechanisms that may drive glacial cycles during the late Pleistocene. Results indicate that a permanent doubling of CO2 generates a 11.1°C rise in Antarctic temperature. Large variations in atmospheric CO2 over glacial cycles are driven by changes in sea ice and sea surface temperature in southern oceans and marine biological activity. The latter can be represented by a two-step process in which iron dust increases biological activity and the increase in biological activity reduces CO2 concentrations. Glacial variations in ice volume, as proxied by δ18O are driven by changes in CO2 concentrations, global and high latitude solar insolation, latitudinal gradients in solar insolation, and the atmospheric concentration of CO2. The model is able to quantify the effects of ice volume and temperature on sea level, such that in the long-run, sea level rises 14 m per 0.11‰ δ18O and about 17 m/°C of sea surface temperature in southern oceans. Beyond these specific results, the multivariate model suggests omitted variables may bias bivariate analyses of these mechanisms.

  12. Hypotheses for near-surface exchange of methane on Mars

    CERN Document Server

    Hu, Renyu; Gao, Peter; Miller, Charles E; Yung, Yuk L

    2016-01-01

    The Curiosity rover recently detected a background of 0.7 ppb and spikes of 7 ppb of methane on Mars. This in situ measurement reorients our understanding of the Martian environment and its potential for life, as the current theories do not entail any geological source or sink of methane that varies sub-annually. In particular, the 10-fold elevation during the southern winter indicates episodic sources of methane that are yet to be discovered. Here we suggest a near-surface reservoir could explain this variability. Using the temperature and humidity measurements from the rover, we find that perchlorate salts in the regolith deliquesce to form liquid solutions, and deliquescence progresses to deeper subsurface in the season of the methane spikes. We therefore formulate the following three testable hypotheses. The first scenario is that the regolith in Gale Crater adsorbs methane when dry and releases this methane to the atmosphere upon deliquescence. The adsorption energy needs to be 36 kJ/mol to explain the m...

  13. A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

    Directory of Open Access Journals (Sweden)

    Goldwater Paul N

    2011-05-01

    Full Text Available Abstract Several theories of the underlying mechanisms of Sudden Infant Death Syndrome (SIDS have been proposed. These theories have born relatively narrow beach-head research programs attracting generous research funding sustained for many years at expense to the public purse. This perspective endeavors to critically examine the evidence and bases of these theories and determine their plausibility; and questions whether or not a safe and reasoned hypothesis lies at their foundation. The Opinion sets specific criteria by asking the following questions: 1. Does the hypothesis take into account the key pathological findings in SIDS? 2. Is the hypothesis congruent with the key epidemiological risk factors? 3. Does it link 1 and 2? Falling short of any one of these answers, by inference, would imply insufficient grounds for a sustainable hypothesis. Some of the hypotheses overlap, for instance, notional respiratory failure may encompass apnea, prone sleep position, and asphyxia which may be seen to be linked to co-sleeping. For the purposes of this paper, each element will be assessed on the above criteria.

  14. Hypothesized evolutionary trends in zoospore ultrastructural characters in Chytridiales (Chytridiomycota).

    Science.gov (United States)

    Letcher, Peter M; Powell, Martha J

    2014-01-01

    Chytridiales is an order of zoosporic fungi currently comprising species representing 19 genera. Although morphologically and genetically diverse, these taxa have in common a zoospore with a suite of ultrastructural characters unique among Chytridiomycota. However, multiple states have been reported for almost every character that defines the Chytridiales zoospore. Two zoospore types have been recognized, each corresponding to a family. Here we examine zoospore ultrastructure of 52 isolates in Chytridiales and assess states for six characters to hypothesize evolutionary trends, using parsimony ancestral state reconstruction for evolutionary analysis. Based on suites of character states, we describe four additional zoospore types in Chytridiales. Five of the six characters ([i] location of the nucleus, [ii] morphology of the kinetosome-associated structure, [iii] complexity of the microtubular root, [iv] microbody-lipid globule complex cisterna structure and [v] thickness of the flagellar plug) revealed ancestral and derived states. The sixth character, structure of the paracrystalline inclusion, did not resolve ancestral and derived states. In each of the lineages within Chytridiales, the evolutionary trend appears to have been from a more complex zoospore to a less complex zoospore with reduced features. As we isolate and analyze additional taxa, we discover new ultrastructural character states that assist in taxon delineation and phylogenetic interpretation. © 2014 by The Mycological Society of America.

  15. Advances in the preclinical testing of cancer therapeutic hypotheses.

    Science.gov (United States)

    Caponigro, Giordano; Sellers, William R

    2011-03-01

    The genetic and epigenetic underpinnings of cancer are becoming increasingly clear owing to impressive and well-coordinated ventures occurring worldwide. As our understanding of the molecular alterations driving human cancer increases, there is an opportunity to direct the clinical application of cancer therapeutics with improved accuracy. The often empirical treatment of cancer--which was initially based on inhibiting DNA synthesis and cellular division--while having led to a number of remarkable successes, remains prone to a high rate of clinical failure that results partly from a lack of understanding of how best to implement drugs in the clinic. Consequently, it is vital that robust translational strategies be developed preclinically to both reduce failure rates in the clinic and shorten the time required to identify patient populations most likely to benefit from a given therapeutic. Here, we review both historical and current uses of preclinical model systems, being mindful that a combination of approaches will be needed to address all meritorious therapeutic hypotheses.

  16. Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release.

    Science.gov (United States)

    Hu, H; Shao, L R; Chavoshy, S; Gu, N; Trieb, M; Behrens, R; Laake, P; Pongs, O; Knaus, H G; Ottersen, O P; Storm, J F

    2001-12-15

    Large-conductance Ca(2+)-activated K(+) channels (BK, also called Maxi-K or Slo channels) are widespread in the vertebrate nervous system, but their functional roles in synaptic transmission in the mammalian brain are largely unknown. By combining electrophysiology and immunogold cytochemistry, we demonstrate the existence of functional BK channels in presynaptic terminals in the hippocampus and compare their functional roles in somata and terminals of CA3 pyramidal cells. Double-labeling immunogold analysis with BK channel and glutamate receptor antibodies indicated that BK channels are targeted to the presynaptic membrane facing the synaptic cleft in terminals of Schaffer collaterals in stratum radiatum. Whole-cell, intracellular, and field-potential recordings from CA1 pyramidal cells showed that the presynaptic BK channels are activated by calcium influx and can contribute to repolarization of the presynaptic action potential (AP) and negative feedback control of Ca(2+) influx and transmitter release. This was observed in the presence of 4-aminopyridine (4-AP, 40-100 microm), which broadened the presynaptic compound action potential. In contrast, the presynaptic BK channels did not contribute significantly to regulation of action potentials or transmitter release under basal experimental conditions, i.e., without 4-AP, even at high stimulation frequencies. This is unlike the situation in the parent cell bodies (CA3 pyramidal cells), where BK channels contribute strongly to action potential repolarization. These results indicate that the functional role of BK channels depends on their subcellular localization.

  17. Relationship between Ambient Fine Particles and Ventricular Repolarization Changes and Heart Rate Variability of Elderly People with Heart Disease in Beijing, China

    Institute of Scientific and Technical Information of China (English)

    XU Mei Mei; JIA Yu Ping; LI Guo Xing; LIU Li Qun; MO Yun Zheng; JIN Xiao Bin; PAN Xiao Chuan

    2013-01-01

    Objective To explore the effects of particulate matters less than 2.5 μm in aerodynamic diameter (PM2.5) on heart repolarization/depolarization and heart rate variability (HRV). Methods We conducted a panel study for elderly subjects with heart disease in Beijing from 2007 to 2008. PM2.5 was measured at a fixed station for 20 h continuously each day while electrocardiogram (ECG) indexes of 42 subjects were also recorded repeatedly. Meteorological data was obtained from the China Meteorological Data Sharing Service System. A mixed linear regression model was used to estimate the associations between PM2.5 and the ECG indexes. The model was adjusted for age, body mass index, sex, day of the week and meteorology. Results Significant adverse effects of PM2.5 on ECG indexes reflecting HRV were observed statistically and the strongest effect of PM2.5 on HRV was on lag 1 day in our study. However, there were no associations between PM2.5 and ECG indexes reflecting heart repolarization/depolarization. Additionally, the effects of PM2.5 on subjects with hypertension were larger than on the subjects without hypertension. Conclusion This study showed ambient PM2.5 could affect cardiac autonomic function of the elderly people with heart disease, and subjects with hypertension appeared to be more susceptive to the autonomic dysfunction induced by PM2.5.

  18. Effects of acute intravenous administration of pentamidine, a typical hERG-trafficking inhibitor, on the cardiac repolarization process of halothane-anesthetized dogs.

    Science.gov (United States)

    Yokoyama, Hirofumi; Nakamura, Yuji; Iwasaki, Hiroshi; Nagayama, Yukitoshi; Hoshiai, Kiyotaka; Mitsumori, Yoshitaka; Sugiyama, Atsushi

    2009-08-01

    Although acute treatment of pentamidine does not directly modify any ionic channel function in the heart at clinically relevant concentrations, its continuous exposure can prolong QT interval. Recent in vitro studies have indicated that hERG trafficking inhibition may play an important role in the onset of pentamidine-induced long QT syndrome. In this study, we examined acute in vivo electropharmacological effects of pentamidine using the halothane-anesthetized canine model (n = 5). The clinically relevant total dose of 4 mg/kg of pentamidine (namely, 1 mg/kg, i.v. over 10 min followed by 3 mg/kg, i.v. over 10 min with a pause of 20 min) decreased the mean blood pressure, ventricular contraction, preload to the left ventricle, and peripheral vascular resistance. Pentamidine also enhanced the atrioventricular conduction in parallel with its cardiohemodynamic actions, but it gradually prolonged both the ventricular repolarization period and effective refractory period, whereas no significant change was detected in the intraventricular conduction. Thus, acute administration of a clinically relevant dose of pentamidine can suppress cardiac function and vascular tone with reflex-mediated increase of sympathetic activity, whereas it may delay the repolarization process, suggesting that inhibition of potassium-channel trafficking might be induced more acutely in vivo than those previously expected in vitro.

  19. Mouse models of autism: testing hypotheses about molecular mechanisms.

    Science.gov (United States)

    Roullet, Florence I; Crawley, Jacqueline N

    2011-01-01

    Autism is a neurodevelopmental disorder that is currently diagnosed by the presence of three behavioral criteria (1) qualitative impairments in reciprocal social interactions, (2) deficits in communication, including delayed language and noninteractive conversation, and (3) motor stereotypies, repetitive behaviors, insistence on sameness, and restricted interests. This chapter describes analogous behavioral assays that have been developed for mice, including tests for social approach, reciprocal social interactions, olfactory communication, ultrasonic vocalizations, repetitive and perseverative behaviors, and motor stereotypies. Examples of assay applications to genetic mouse models of autism are provided. Robust endophenotypes that are highly relevant to the core symptoms of autism are enabling the search for the genetic and environmental causes of autism, and the discovery of effective treatments.

  20. Twelve testable hypotheses on the geobiology of weathering.

    Science.gov (United States)

    Brantley, S L; Megonigal, J P; Scatena, F N; Balogh-Brunstad, Z; Barnes, R T; Bruns, M A; Van Cappellen, P; Dontsova, K; Hartnett, H E; Hartshorn, A S; Heimsath, A; Herndon, E; Jin, L; Keller, C K; Leake, J R; McDowell, W H; Meinzer, F C; Mozdzer, T J; Petsch, S; Pett-Ridge, J; Pregitzer, K S; Raymond, P A; Riebe, C S; Shumaker, K; Sutton-Grier, A; Walter, R; Yoo, K

    2011-03-01

    Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby controlling the location and extent of biological weathering. (2) Biological stoichiometry drives changes in mineral stoichiometry and distribution through weathering. (3) On landscapes experiencing little erosion, biology drives weathering during initial succession, whereas weathering drives biology over the long term. (4) In eroding landscapes, weathering-front advance at depth is coupled to surface denudation via biotic processes. (5) Biology shapes the topography of the Critical Zone. (6) The impact of climate forcing on denudation rates in natural systems can be predicted from models incorporating biogeochemical reaction rates and geomorphological transport laws. (7) Rising global temperatures will increase carbon losses from the Critical Zone. (8) Rising atmospheric P(CO2) will increase rates and extents of mineral weathering in soils. (9) Riverine solute fluxes will respond to changes in climate primarily due to changes in water fluxes and secondarily through changes in biologically mediated weathering. (10) Land use change will impact Critical Zone processes and exports more than climate change. (11) In many severely altered settings, restoration of hydrological processes is possible in decades or less, whereas restoration of biodiversity and biogeochemical processes requires longer timescales. (12) Biogeochemical properties impart thresholds or tipping points beyond which rapid and irreversible losses of ecosystem health, function, and services can occur.

  1. Kidney cancer mortality in Spain: geographic patterns and possible hypotheses

    Directory of Open Access Journals (Sweden)

    Vidal Enrique

    2008-10-01

    Full Text Available Abstract Background Since the second half of the 1990s, kidney cancer mortality has tended to stabilize and decline in many European countries, due to the decrease in the prevalence of smokers. Nevertheless, incidence of kidney cancer is rising across the sexes in some of these countries, a trend which may possibly reflect the fact that improvements in diagnostic techniques are being outweighed by the increased prevalence of some of this tumor's risk factors. This study sought to: examine the geographic pattern of kidney cancer mortality in Spain; suggest possible hypotheses that would help explain these patterns; and enhance existing knowledge about the large proportion of kidney tumors whose cause remains unknown. Methods Smoothed municipal relative risks (RRs for kidney cancer mortality were calculated in men and women, using the conditional autoregressive model proposed by Besag, York and Molliè. Maps were plotted depicting smoothed relative risk estimates, and the distribution of the posterior probability of RR>1 by sex. Results Municipal maps displayed a marked geographic pattern, with excess mortality in both sexes, mainly in towns along the Bay of Biscay, including areas of Asturias, the Basque Country and, to a lesser extent, Cantabria. Among women, the geographic pattern was strikingly singular, not in evidence for any other tumors, and marked by excess risk in towns situated in the Salamanca area and Extremaduran Autonomous Region. This difference would lead one to postulate the existence of different exposures of environmental origin in the various regions. Conclusion The reasons for this pattern of distribution are not clear, and it would thus be of interest if the effect of industrial emissions on this disease could be studied. The excess mortality observed among women in towns situated in areas with a high degree of natural radiation could reflect the influence of exposures which derive from the geologic composition of the

  2. Endocardial tip cells in the human embryo - facts and hypotheses.

    Directory of Open Access Journals (Sweden)

    Mugurel C Rusu

    Full Text Available Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43-56 days were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin, CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.

  3. Cdk5 at crossroads of protein oligomerization in neurodegenerative diseases: facts and hypotheses.

    Science.gov (United States)

    Wilkaniec, Anna; Czapski, Grzegorz A; Adamczyk, Agata

    2016-01-01

    Cyclin-dependent kinase 5 (Cdk5) is involved in proper neurodevelopment and brain function and serves as a switch between neuronal survival and death. Overactivation of Cdk5 is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important link between disease-initiating factors and cell death effectors. A common hallmark of neurodegenerative disorders is incorrect folding of specific proteins, thus leading to their intra- and extracellular accumulation in the nervous system. Abnormal Cdk5 signaling contributes to dysfunction of individual proteins and has a substantial role in either direct or indirect interactions of proteins common to, and critical in, different neurodegenerative diseases. While the roles of Cdk5 in α-synuclein (ASN) - tau or β-amyloid peptide (Aβ) - tau interactions are well documented, its contribution to many other pertinent interactions, such as that of ASN with Aβ, or interactions of the Aβ - ASN - tau triad with prion proteins, did not get beyond plausible hypotheses and remains to be proven. Understanding of the exact position of Cdk5 in the deleterious feed-forward loop critical for development and progression of neurodegenerative diseases may help designing successful therapeutic strategies of several fatal neurodegenerative diseases. Cyclin-dependent kinase 5 (Cdk5) is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important factor involved in protein misfolding, toxicity and interaction. We suggest that Cdk5 may contribute to the vicious circle of neurotoxic events involved in the pathogenesis of different neurodegenerative diseases.

  4. How the mainstream limits the spreading of alternative hypotheses

    Science.gov (United States)

    Kalenda, Pavel

    2014-05-01

    that prof. Djuric had tried for more than 10 years to publish this article in various peer-reviewed journals. So, prof. Djuric got into the official book (list) of "scientific dissidents" among hundreds of other professors and doctors of science (De Climont 2012). These "scientific dissidents" do not have access to established journals and may possibly publish privately or at best on the web in marginal journals whose list was published by De Climont (2012). Such a marginal journal in the field of geophysics and geology is New Concepts in Global Tectonics. This journal has been established because the current hypothesis about the movement of the continents due to convection currents in the mantle becomes under the weight of new observation quite untenable. 4) Scientific consensus History has known many hypotheses that were accepted as proven truth but later, in the light of new knowledge, they completely failed. - No one has the right to decide which scientific hypotheses will be accepted and which will not get into print. Perhaps the worst situation is in climatology (due to global effects and impacts), when the plenary session of IPCC consensually stated that the current global warming was mainly due to the human activity. References De Climont, J. (2012): The worldwide list of dissident scientists. http://astrojan.hostei.com/droa.htm. Djurič, J. (2006): Unification Of Gravitation And Electromagnetism. http://jovandjuric.tripod.com/ David H. Douglass, John R. Christy, Benjamin D. Pearson and S. Fred Singer (2007): A comparison of tropical temperature trends with model predictions. International Journal of Climatology, Volume 28, Issue 13, 15 November 2008, Pages: 1693-1701. http://onlinelibrary.wiley.com/doi/10.1002/joc.1651/pdf. Einstein, A. : List of scientific publications by Albert Einstein. /wiki/List_of_scientific_publications_by_Albert_Einstein. Kolínský, P., Valenta, J. and Gaždová, R. (2012): Seismicity, groundwater level variations and earth tides in

  5. Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

    Science.gov (United States)

    Schlegel, T. T.; Medina, R.; Jugo, D.; Nunez, T. J.; Borrego, A.; Arellano, E.; Arenare, B.; DePalma, J. L.; Greco, E. C.; Starc, V.

    2007-01-01

    were not significantly different between groups. Patients with Chagas heart disease have increased cardiac repolarization abnormalities, especially by advanced ECG. Moreover, as a group, they have decreased uncorrected JT and QT interval durations and increased filtered QRS interval durations (versus age/gender-matched controls), all suggesting a potential loss of cardiac sodium channel function that might be mediated, in part, by cardiac autonomic damage. Overall findings support Brugada et al's recent hypothesis that the pathway leading to sudden death may often be similar in Chagas' disease and Brugada syndrome i.e., damage to the sodium channel (infectious/immunologic/autonomic in Chagas' genetic in Brugada) with consequent loss of sodium currents may facilitate a phase II-reentry based arrhythmic substrate for ventricular fibrillation in both conditions. In general, JT interval-related results have been underreported in the Chagas literature.

  6. Using asteroid families to test planetesimal differentiation hypotheses

    Science.gov (United States)

    Jacobson, S.; Campins, H.; Delbo', M.; Michel, P.; Tanga, P.; Hanuš, J.; Morbidelli, A.

    2014-07-01

    consequences of the hypothesized compositional radial gradients within the planetesimal population. The circumstantial diversity (membership number, progenitor mass, and collision energy) determines how exposed the interior of the planetesimal is. Using estimates of the progenitor mass and the mass of the largest remnant (Tanga et al. 1999, Durda et al. 2007, Broz et al. 2013), we can assess the exposed nature of different asteroid families. Those with the lowest ratio of largest remnant to planetesimal mass are more exposed since more of their mass is within the asteroid family membership as opposed to being sequestered in the largest remnant. Furthermore, models of the planetesimal differentiation process are strongly size dependent since smaller bodies cool much more effectively. Therefore, progenitor mass is also a proxy for the expected degree of differentiation. Using this set of proxies, we examine a diverse array of asteroid families to test the hypothesis of differentiation or metamorphic grading.

  7. Kv2 channel regulation of action potential repolarization and firing patterns in superior cervical ganglion neurons and hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Liu, Pin W; Bean, Bruce P

    2014-04-02

    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.

  8. The evaluation of a new marker of transmyocardial repolarization parameters in ischemic stroke patients; T peak-T end (T p-e), T p-e/QTc.

    Science.gov (United States)

    Emektar, Emine; Çorbacıoğlu, Şeref Kerem; Korucu, Osman; Ramadan, Selma; Uzunosmanoğlu, Hüseyin; Kan, Eda; Çevik, Yunsur

    2017-06-01

    The cardiovascular manifestations of acute ischemic stroke have been well known. Several electrocardiography (ECG) abnormalities have been reported in patients following acute stroke, including QT interval prolongation, ST segment deviation and T-wave changes. This study aimed to investigate the changes in transmyocardial repolarization parameters, in ischemic stroke patients. The study is a prospective, blind, and controlled clinical study. The patients without cardiac disease who received ischemic stroke diagnoses were included in the study. ECG was received from the patients in the first hour and 72 h. The P, QT, T p-e, T p-e dispersion, and the T p-e/QT ratio were calculated. Moreover, fifty-five stroke patients and 35 control subjects were included to the study. All dispersion values and T p-e/QTc ratio in patients group were higher than those of control group (p p-e/QTc ratio in ECGs on third day than ECGs on first day (p p-e dispersions values in patients who have insular lobe involvement were higher than those of patients who do not have insular lobe involvement (p P d, QTd, QTcd and new repolarization markers T p-e and T p-e/QTc, during first 24 and 72 h in acute stroke patients without cardiovascular disease compared with the control group. The physicians should be aware about ventricular dysrhythmias in patients with ischemic stroke and these patients closely observed with cardiac monitoring, especially within first 24 h, and especially patients with insular lobe involvement.

  9. Post-Pacing Abnormal Repolarization in Catecholaminergic Polymorphic Ventricular Tachycardia Associated with a Mutation in the Cardiac Ryanodine Receptor Gene (RyR2)

    Science.gov (United States)

    Nof, Eyal; Belhassen, Bernard; Arad, Michael; Bhuiyan, Zahurul A.; Antzelevitch, Charles; Rosso, Raphael; Fogelman, Rami; Luria, David; Eli-Ani, Dalia; Mannens, Marcel M.A.M.; Viskin, Sami; Eldar, Michael; Wilde, Arthur A.M.; Glikson, Michael

    2011-01-01

    Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. Objective We present a CPVT family in which marked post-pacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of RyR2 mutation carriers. Methods The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic ECG testing with epinephrine, adenosine and flecainide. Non-invasive clinical tests were normal in 10 patients evaluated, except for both epinephrine and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in LQTS as well as RyR2. Results Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent post-pacing QT changes. Conclusions M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked post-pacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family. PMID:21699856

  10. Female alcoholics: electrocardiographic changes and associated metabolic and electrolytic disorders

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    2003-01-01

    Full Text Available OBJECTIVE: To identify the electrocardiographic changes and their associations with metabolic and electrolytic changes in female alcoholics. METHODS: The study comprised 44 female alcoholics with no apparent physical disorder. They underwent the following examinations: conventional electrocardiography; serologic tests for syphilis, Chagas' disease, and hepatitis B and C viruses; urinary pregnancy testing; hematimetric analysis; biochemical measurements of albumin, fibrinogen, fasting and postprandial glycemias, lipids, hepatic enzymes, and markers for tissue necrosis and inflammation. RESULTS: Some type of electrocardiographic change was identified in 33 (75% patients. In 17 (38.6% patients, more than one of the following changes were present: prolonged QTc interval in 24 (54.5%, change in ventricular repolarization in 11(25%, left ventricular hypertrophy in 6 (13.6%, sinus bradycardia in 4 (9.1%, sinus tachycardia in 3 (6.8%, and conduction disorder in 3 (6.8%. The patients had elevated mean serum levels of creatine phosphokinase, aspartate aminotransferases, and gamma glutamyl transferase, as well as hypocalcemia and low levels of total cholesterol and LDL-cholesterol. The patients with altered electrocardiograms had a more elevated age, a lower alcohol consumption, hypopotassemia, and significantly elevated levels of triglycerides, postprandial glucose, sodium and gamma glutamyl transferase than those with normal electrocardiograms. The opposite occurred with fasting glycemia, magnesium, and alanine aminotransferase. CONCLUSION: The electrocardiographic changes found were prolonged QTc interval, change in ventricular repolarization, and left ventricular hypertrophy. Patients with normal and abnormal electrocardiograms had different metabolic and electrolytic changes.

  11. Bayesian Evaluation of Inequality and Equality Constrained Hypotheses for Contingency Tables

    Science.gov (United States)

    Klugkist, Irene; Laudy, Olav; Hoijtink, Herbert

    2010-01-01

    In this article, a Bayesian model selection approach is introduced that can select the best of a set of inequality and equality constrained hypotheses for contingency tables. The hypotheses are presented in terms of cell probabilities allowing researchers to test (in)equality constrained hypotheses in a format that is directly related to the data.…

  12. The madness of Dionysus -- six hypotheses on the illness of Nietzsche.

    Science.gov (United States)

    Tényi, Tamás

    2012-01-01

    Friedrich Nietzsche (1844-1900) is considered as one of the most influential modern thinkers of the last two centuries. The great philosopher and poet developed a mental illness at the age of 44 and died at the age of 56. Pathological examination was not undertaken. At that time Nietzsche was diagnosed as having atypical paralysis progressiva, however recently five other probable diagnoses appeared in literature. Literature search in MEDLINE and Web of Science on the illness of Nietzsche. Six hypotheses were identified: 1. Paralysis progressiva (General paralysis of the insane) 2. Bipolar affective disorder followed by vascular dementia 3. Hereditary form of frontotemporal dementia 4. Brain tumor 5. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) 6. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. Developments in neurology and molecular genetics give new perspectives to the secret of Nietzsche's illness and also there is a consensus on the questioning of the original paralysis progressiva concept. As there was no postmortem, the clinical speculations on the medical problems of the great philosopher remain a challenge.

  13. Support for major hypotheses in invasion biology is uneven and declining

    Directory of Open Access Journals (Sweden)

    Jonathan Jeschke

    2012-08-01

    Full Text Available Several major hypotheses have been proposed to explain and predict biological invasions, but the general applicability of these hypotheses is largely unknown, as most of them have not been evaluated using a standard approach across taxonomic groups and habitats. We offer such an evaluation for six selected leading hypotheses. Our global literature review reveals that those hypotheses that consider interactions of exotic invaders with their new environment (invasional meltdown, novel weapons, enemy release are better supported by empirical evidence than other hypotheses (biotic resistance, island susceptibility, tens rule. We also show that empirical support for the six hypotheses has declined over time, and that support differs among taxonomic groups and habitats. Our results have implications for basic and applied research, policy making, and invasive species management, as their effectiveness depends on sound hypotheses.

  14. Each normal logic program has a 2-valued Minimal Hypotheses semantics

    CERN Document Server

    Pinto, Alexandre Miguel

    2011-01-01

    In this paper we explore a unifying approach --- that of hypotheses assumption --- as a means to provide a semantics for all Normal Logic Programs (NLPs), the Minimal Hypotheses (MH) semantics. This semantics takes a positive hypotheses assumption approach as a means to guarantee the desirable properties of model existence, relevance and cumulativity, and of generalizing the Stable Models in the process. To do so we first introduce the fundamental semantic concept of minimality of assumed positive hypotheses, define the MH semantics, and analyze the semantics' properties and applicability. Indeed, abductive Logic Programming can be conceptually captured by a strategy centered on the assumption of abducibles (or hypotheses). Likewise, the Argumentation perspective of Logic Programs also lends itself to an arguments (or hypotheses) assumption approach. Previous works on Abduction have depicted the atoms of default negated literals in NLPs as abducibles, i.e., assumable hypotheses. We take a complementary and mo...

  15. The spreading of disorder.

    Science.gov (United States)

    Keizer, Kees; Lindenberg, Siegwart; Steg, Linda

    2008-12-12

    Imagine that the neighborhood you are living in is covered with graffiti, litter, and unreturned shopping carts. Would this reality cause you to litter more, trespass, or even steal? A thesis known as the broken windows theory suggests that signs of disorderly and petty criminal behavior trigger more disorderly and petty criminal behavior, thus causing the behavior to spread. This may cause neighborhoods to decay and the quality of life of its inhabitants to deteriorate. For a city government, this may be a vital policy issue. But does disorder really spread in neighborhoods? So far there has not been strong empirical support, and it is not clear what constitutes disorder and what may make it spread. We generated hypotheses about the spread of disorder and tested them in six field experiments. We found that, when people observe that others violated a certain social norm or legitimate rule, they are more likely to violate other norms or rules, which causes disorder to spread.

  16. Haunted hypotheses.

    Science.gov (United States)

    Albon, S

    1998-10-01

    American Pronghorn: Social Adaptations and the Ghosts of Predators Past by J.A. Byers The University of Chicago Press, 1998. $70.00/£55.95 hbk, $23.95/£19.25 pbk (xviii+300 pages) ISBN 0 226 08698 4/0 226 08699 2.

  17. Tongue Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  18. Mental Disorders

    Science.gov (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

  19. The Relationship of Personality to Eating Disorders

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Besharat

    2008-01-01

    Full Text Available This paper highlights a variety of personality disorders in individuals with eating disorder and also emphasizes the importance of identifying clinically meaningful eating disorders subtypes based on concurrent personality disorder. The relationship between personality disorders and eating disorders is an important issue as this association has implications for assessment and treatment. Different hypotheses concerning the relationship between personality disorders and eating disorders will be reviewed. The prevalence rates of concomitant personality disorder diagnoses in eating disorder patients is highlighted to illustrate some of the pertinent conceptual issues concerning the meaning of the co-occurrence of separately defined diagnostic entities. The literature review reveals a robust finding that patients with ersonality pathology have a poorer response to treatment of Axis I disorders than those without such pathology. It is also argued that therapeutic relationship deserves more attention in the assessment and treatment of eating disorder patients with a co morbid personality disorder.

  20. Synaptic and Neuronal Autoantibody-Associated Psychiatric Syndromes: Controversies and Hypotheses

    Science.gov (United States)

    Al-Diwani, Adam; Pollak, Thomas A.; Langford, Alexander E.; Lennox, Belinda R.

    2017-01-01

    Autoimmune encephalitis (AE) mediated by antibodies against synaptic and neuronal surface targets frequently presents with a psychiatric syndrome. In these patients, removal of autoantibodies treats the disease and outcomes are closely linked to early intervention. The discovery of these autoantibodies in isolated psychiatric syndromes has raised the possibility that these patients may derive similar benefits from immunotherapy, a potentially transformational approach to the treatment of mental illness. Although open-label case series suggest impressive therapeutic outcomes, the pathological relevance of these autoantibodies outside of canonical presentations is debated. The advent of diagnostic criteria for AE attempts to facilitate its prompt identification but risks prematurely neglecting the potential scientific and clinical significance of isolated syndromes that do not satisfy these criteria. Here, we propose using a syndrome-level taxonomy that has occasional, but not necessary, overlap with AE: synaptic and neuronal autoantibody-associated psychiatric syndromes or “SNAps”. This will prevent confusion with AE and act heuristically to promote active investigation into this rare example of psychopathology defined on a molecular level. We suggest that this concept would have application in other autoantibody-associated syndromes including seizure, cognitive, and movement disorders, in which similar issues arise. We review putative direct and indirect mechanisms and outline experimentally testable hypotheses that would help to determine prospectively in whom autoantibody detection is relevant, and as important, in whom it is not. We summarize a pragmatic approach to autoantibody testing and management in severe mental illness in order to promptly diagnose AE and advocate a research-orientated experimental medicine paradigm for SNAps, where there is greater equipoise. We conclude that SNAps remains a nascent area of clinical neuroscience with great potential

  1. Volume of discrete brain structures in complex dissociative disorders : preliminary findings

    NARCIS (Netherlands)

    Ehling, T.; Nijenhuis, E. R. S.; Krikke, A. P.; DeKloet, ER; Vermetten, E

    2007-01-01

    Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that (1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala

  2. Volume of discrete brain structures in complex dissociative disorders : preliminary findings

    NARCIS (Netherlands)

    Ehling, T.; Nijenhuis, E. R. S.; Krikke, A. P.; DeKloet, ER; Vermetten, E

    2007-01-01

    Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that (1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala

  3. Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Poolos, N P; Johnston, D

    1999-07-01

    Evidence is accumulating that voltage-gated channels are distributed nonuniformly throughout neurons and that this nonuniformity underlies regional differences in excitability within the single neuron. Previous reports have shown that Ca2+, Na+, A-type K+, and hyperpolarization-activated, mixed cation conductances have varying distributions in hippocampal CA1 pyramidal neurons, with significantly different densities in the apical dendrites compared with the soma. Another important channel mediates the large-conductance Ca2+-activated K+ current (IC), which is responsible in part for repolarization of the action potential (AP) and generation of the afterhyperpolarization that follows the AP recorded at the soma. We have investigated whether this current is activated by APs retrogradely propagating in the dendrites of hippocampal pyramidal neurons using whole-cell dendritic patch-clamp recording techniques. We found no IC activation by back-propagating APs in distal dendritic recordings. Dendritic APs activated IC only in the proximal dendrites, and this activation decayed within the first 100-150 micrometer of distance from the soma. The decay of IC in the proximal dendrites occurred despite AP amplitude, plus presumably AP-induced Ca2+ influx, that was comparable with that at the soma. Thus we conclude that IC activation by action potentials is nonuniform in the hippocampal pyramidal neuron, which may represent a further example of regional differences in neuronal excitability that are determined by the nonuniform distribution of voltage-gated channels in dendrites.

  4. IQGAP and mitotic exit network (MEN) proteins are required for cytokinesis and re-polarization of the actin cytoskeleton in the budding yeast, Saccharomyces cerevisiae.

    Science.gov (United States)

    Corbett, Mark; Xiong, Yulan; Boyne, James R; Wright, Daniel J; Munro, Ewen; Price, Clive

    2006-11-01

    In budding yeast the final stages of the cell division cycle, cytokinesis and cell separation, are distinct events that require to be coupled, both together and with mitotic exit. Here we demonstrate that mutations in genes of the mitotic exit network (MEN) prevent cell separation and are synthetically lethal in combination with both cytokinesis and septation defective mutations. Analysis of the synthetic lethal phenotypes reveals that Iqg1p functions in combination with the MEN components, Tem1p, Cdc15p Dbf20p and Dbf2p to govern the re-polarization of the actin cytoskeleton to either side of the bud neck. In addition phosphorylation of the conserved PCH protein, Hof1p, is dependent upon these activities and requires actin ring assembly. Recruitment of Dbf2p to the bud neck is dependent upon actin ring assembly and correlates with Hof1p phosphorylation. Failure to phosphorylate Hof1p results in the increased stability of the protein and its persistence at the bud neck. These data establish a mechanistic dependency of cell separation upon an intermediate step requiring actomyosin ring assembly.

  5. Experimental Study of the Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization under Acute Myocardial Ischemia in Vivo

    Institute of Scientific and Technical Information of China (English)

    张存泰; 徐大文; 李泱; 刘念; 钟江华; 王琳; 陆再英

    2002-01-01

    Summary: The effect of the autonomic nerves on the transmural dispersion of ventricular repolariza tion (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs.MAPD90 and TDR among three myocardial layers as well as the incidence of the early afterdepolar ization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial I~hemia, TDR was increased from 55±8.ms to 86± 15 ms during sympathetic stimulation (P<0. 01). The TDR (53± 9 ms) during parasympathetic stimulation was not significantly different from that of the control (55±8 ms) (P>0.05). The EAD was elicited in the Mid of 2 dogs (16 %) 10 min after acute myocardial ischemia,but the EAD were elicited in the Mid of 7 dogs (58 %) during sympathetic stimulation (P<0. 01).It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolari zation and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which pro-vide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.

  6. The Effects of Nicorandil and Nifekalant, Which Were Injected into the Pericardial Space, for Transmural Dispersion of Repolarization in the Pig

    Directory of Open Access Journals (Sweden)

    Hiroyuki Ito, MD

    2007-01-01

    Full Text Available Introduction: Some studies have reported that transmural dispersion of repolarization (TDR is involved in the onset of ventricular arrhythmia. We investigated the effects of nicorandil (NIC and nifekalant (NIF injected into the pericardial space, on TDR and T waves in the pig. Methods and Results: We injected NIC 4 or 8 mg and NIF 50 or 100 mg at intervals into the pericardial space for eleven pigs. The effects of these drugs were investigated on the effective refractory period (ERP between the endocardial and epicardial myocardial cells, as well as on QT time, QT peak-end (QTcpe as an index of TDR, and T waveforms, respectively. QTcpe increased from 91 ± 21 to 116 ± 19 msec, 2.8 min after injection of NIC (p < 0.01, although corrected QT (QTc interval did not changed. But 5.5 min after injection, QTc decreased while QTcpe recovered. T wave amplitude significantly increased, and epicardium ERP decreased. When NIF was injected, TDR decreased from 55 ± 10 msec to 44 ± 8 msec (p < 0.01 although QTc did not change. In a later phase, QTc increased (p < 0.01 and QTcpe recovered. T wave amplitude rapidly decreased and became negative. Conclusion: Injected into the pericardial space, NIC and NIF brought about certain changes in ERP, QT and T waveform. Furthermore, NIC increased TDR while NIF decreased TDR.

  7. Co-occurrence of dissociative identity disorder and borderline personality disorder.

    Science.gov (United States)

    Ross, Colin A; Ferrell, Lynn; Schroeder, Elizabeth

    2014-01-01

    The literature indicates that, among individuals with borderline personality disorder, pathological dissociation correlates with a wide range of impairments and difficulties in psychological function. It also predicts a poorer response to dialectical behavior therapy for borderline personality disorder. We hypothesized that (a) dissociative identity disorder commonly co-occurs with borderline personality disorder and vice versa, and (b) individuals who meet criteria for both disorders have more comorbidity and trauma than individuals who meet criteria for only 1 disorder. We interviewed a sample of inpatients in a hospital trauma program using 3 measures of dissociation. The most symptomatic group was those participants who met criteria for both borderline personality disorder and dissociative identity disorder on the Dissociative Disorders Interview Schedule, followed by those who met criteria for dissociative identity disorder only, then those with borderline personality disorder only, and finally those with neither disorder. Greater attention should be paid to the relationship between borderline personality disorder and dissociative identity disorder.

  8. Bayesian Meta-Analysis of Cronbach's Coefficient Alpha to Evaluate Informative Hypotheses

    Science.gov (United States)

    Okada, Kensuke

    2015-01-01

    This paper proposes a new method to evaluate informative hypotheses for meta-analysis of Cronbach's coefficient alpha using a Bayesian approach. The coefficient alpha is one of the most widely used reliability indices. In meta-analyses of reliability, researchers typically form specific informative hypotheses beforehand, such as "alpha of…

  9. Magnetic Field Disorder and Faraday Effects on the Polarization of Extragalactic Radio Sources

    Science.gov (United States)

    Lamee, Mehdi; Rudnick, Lawrence; Farnes, Jamie S.; Carretti, Ettore; Gaensler, B. M.; Haverkorn, Marijke; Poppi, Sergio

    2016-09-01

    We present a polarization catalog of 533 extragalactic radio sources that have a 2.3 GHz total intensity above 420 mJy from the S-band Polarization All Sky Survey, S-PASS, with corresponding 1.4 GHz polarization information from the NRAO VLA Sky Survey, NVSS. We studied the selection effects and found that fractional polarization, π, of radio objects at both wavelengths depends on the spectral index, the source magnetic field disorder, the source size, and depolarization. The relationship between depolarization, spectrum, and size shows that depolarization occurs primarily in the source vicinity. The median {π }2.3 of resolved objects in NVSS is approximately two times larger than that of unresolved sources. Sources with little depolarization are ∼2 times more polarized than both highly depolarized and re-polarized sources. This indicates that intrinsic magnetic field disorder is the dominant mechanism responsible for the observed low fractional polarization of radio sources at high frequencies. We predict that number counts from polarization surveys will be similar at 1.4 GHz and at 2.3 GHz, for fixed sensitivity, although ∼10% of all sources may currently be missing because of strong depolarization. Objects with {π }1.4≈ {π }2.3≥slant 4 % typically have simple Faraday structures, so they are most useful for background samples. Almost half of flat-spectrum (α ≥slant -0.5) and ∼25% of steep-spectrum objects are re-polarized. Steep-spectrum, depolarized sources show a weak negative correlation of depolarization with redshift in the range 0 < z < 2.3. Previous non-detections of redshift evolution are likely due the inclusion of re-polarized sources as well.

  10. [Anorexia nervosa in light of Karl Jaspers and Erich Fromm's ideas and social constructivism--hypotheses and thoughts].

    Science.gov (United States)

    Talarczyk, Małgorzata

    2012-01-01

    The point of the article is to analyse and reflect on certain symptoms of anorexia nervosa in light of Karl Jaspers and Erich Fromm's ideas and social constructivism. Contemplating the disorder in view of the philosophical ideas mentioned earlier, the author analyses such aspects of patients as: functioning on the verge of life and death, the paradoxical struggle to escape from freedom in search of independence, as well as various understandings and descriptions of anorexia in consideration of social constructivism. The author shares thoughts and poses hypotheses, trying to view anorexia in light of selected philosophical and psychological ideas, which in their general assumptions were not concerned with defining nor analysing anorexia nervosa. In view of Karl Jaspers' ideas, the author focuses on the so called 'limit-situations', in the ideas of Erich Fromm she takes notice in "Escape from Freedom" to new relations. Finally in the light of social constructivism the author focuses on the cultural context.

  11. Transitionality in addiction: A "temporal continuum" hypotheses involving the aberrant motivation, the hedonic dysregulation, and the aberrant learning.

    Science.gov (United States)

    Patrono, Enrico; Gasbarri, Antonella; Tomaz, Carlos; Nishijo, Hisao

    2016-08-01

    Addiction is a chronic compulsion and relapsing disorder. It involves several brain areas and circuits, which encode vary functions such as reward, motivation, and memory. Drug addiction is defined as a "pathological pattern of use of a substance", characterized by the loss of control on drug-taking-related behaviors, the pursuance of those behaviors even in the presence of negative consequences, and a strong motivated activity to assume substances. Three different theories guide experimental research on drug addiction. Each of these theories consider singles features, such as an aberrant motivation, a hedonic dysregulation, and an aberrant habit learning as the main actor to explain the entire process of the addictive behaviors. The major goal of this study is to present a new hypotheses of transitionality from a controlled use to abuse of addictive substances trough the overview of the three different theories, considering all the single features of each single theory together on the same "temporal continuum" from use to abuse of addictive substances. Recently, it has been suggested that common neural systems may be activated by natural and pharmacological stimuli, raising the hypotheses that binge-eating disorders could be considered as addictive behaviors. The second goal of this study is to present evidences in order to highlight a possible psycho-bio-physiological superimposition between drug and "food addiction". Finally, interesting questions are brought up starting from last findings about a theoretical/psycho-bio-physiological superimposition between drug and "food addiction" and their possibly same transitionality along the same "temporal continuum" from use to abuse of addictive substances in order to investigate new therapeutic strategies based on new therapeutic strategies based on the individual moments characterizing the transition from the voluntary intake of substances to the maladaptive addictive behavior.

  12. Study design, objectives, hypotheses, main findings, health consequences for the population exposed, rationale of future research

    Energy Technology Data Exchange (ETDEWEB)

    Trnovec, T.; Kocan, A. [Slovak Medical Univ., Bratislava (Slovakia); Bencko, V. [Charles Univ., Prague (Czech Republic); Langer, P. [Institute of Experimental Endocrinology SAS, Bratislava (Slovakia); Berg, M. van den [Rijksuniversiteit Utrecht (Netherlands); Bergman, A. [Stockholm Univ. (Sweden); Hustak, M. [Air Force Military Hospital, Kosics (Slovakia)

    2004-09-15

    In Slovakia, the Chemko Chemical Company, based in Strazske, in the Michalovce district, produced PCBs between 1959 and 1984, in the amount of more than 21,000 tons of commercial mixtures (Delor 103, 104, 105, 106, Delotherm DK and DH, Hydelor 137). PCBs were used for similar industrial purposes as in the west. Improper disposal from the Chemko plant via release of effluent directly into the Laborec River resulted in long-term contamination of sediment. As a result eastern Slovakia, the Michalovce district in particular, is recognized as one of the areas all over the world most heavily polluted with PCBs. Historical studies show that blood and adipose PCB levels were higher in Czechoslovakia than elsewhere in the 1970's and 1980's. Current data indicate that persons who eat locally raised food - pork, beef, poultry, eggs - in this district have elevated serum concentrations of PCBs. Environmental exposure to organochlorines in the Michalovce district indicate association with higher rates of certain cancers, but an inverse association with risk of breast cancer. An increased prevalence of thyroid disorders in the polluted area was also reported. This ''experimental setting in nature'' has attracted international scientific teams and two projects in the area are ongoing: Evaluating Human Health Risk from Low-dose and Long-term PCB Exposure, 5{sup th} FP Project QLK4-2000-00488, 2001- 2004; PCBRISK (http://www.pcbrisk.sk/) and Early Childhood Development and PCB Exposures in Slovakia, NCI/NIH, R01-CA96525 University of California, Davis, USA. This paper is serving as an introduction to papers of a session reporting on various health outcomes associated with PCB exposure. The objectives of the PCBRISK project were targeted at an evaluation of the human health risks of low-dose and long-term exposure to a group of persistent organochlorine pollutants, including polychlorinated biphenyls (PCBs) and their metabolites, organochlorine

  13. Regression in autistic spectrum disorders.

    Science.gov (United States)

    Stefanatos, Gerry A

    2008-12-01

    A significant proportion of children diagnosed with Autistic Spectrum Disorder experience a developmental regression characterized by a loss of previously-acquired skills. This may involve a loss of speech or social responsitivity, but often entails both. This paper critically reviews the phenomena of regression in autistic spectrum disorders, highlighting the characteristics of regression, age of onset, temporal course, and long-term outcome. Important considerations for diagnosis are discussed and multiple etiological factors currently hypothesized to underlie the phenomenon are reviewed. It is argued that regressive autistic spectrum disorders can be conceptualized on a spectrum with other regressive disorders that may share common pathophysiological features. The implications of this viewpoint are discussed.

  14. A rapid algorithm and a computer program for multiple test procedures using logical structures of hypotheses.

    Science.gov (United States)

    Hommel, G; Bernhard, G

    1994-06-01

    It is demonstrated how improvements of general multiple test procedures can be obtained using information about the logical structures among the hypotheses. Based on a procedure of Bergmann and Hommel (B. Bergmann and G. Hommel, Improvements of general multiple test procedures for redundant systems of hypotheses, in Multiple Hypothesenprüfung--Multiple Hypotheses Testing, Eds. P. Bauer, G. Hommel and E. Sonnemann, pp. 100-115 (Springer-Verlag, Berlin, 1988)), a computer program was written by Bernhard (G. Bernhard, Computerunterstützte Durchführung von multiplen Testprozeduren--Algorithmen und Powervergleich, Doctoral thesis (Mainz, 1992)) using this information. It is applicable for a general class of systems of hypotheses which can be expressed in a linear way. By means of a simulation study it is shown that the proposed procedure is often substantially more powerful than other usual multiple test procedures.

  15. Corrigendum to: Bayesian evaluation of informative hypotheses in SEM using Mplus

    NARCIS (Netherlands)

    van de Schoot, R.; Verhoeven, Marjolein; Hoijtink, H.

    2014-01-01

    This paper corrects: van de Schoot, R., Verhoeven, M., & Hoijtink, H. (2013). Bayesian evaluation ofinformative hypotheses in SEM using Mplus: A black bear story. EuropeanJournal of Developmental Psychology, 10, 81 –98.

  16. Corrigendum to: Bayesian evaluation of informative hypotheses in SEM using Mplus

    NARCIS (Netherlands)

    van de Schoot, R.; Verhoeven, Marjolein; Hoijtink, H.

    2014-01-01

    This paper corrects: van de Schoot, R., Verhoeven, M., & Hoijtink, H. (2013). Bayesian evaluation ofinformative hypotheses in SEM using Mplus: A black bear story. EuropeanJournal of Developmental Psychology, 10, 81 –98.

  17. Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones.

    Science.gov (United States)

    Kim, Jinhyun; Wei, Dong-Sheng; Hoffman, Dax A

    2005-11-15

    A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K(+) channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K(+) channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca(2)(+) imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca(2)(+) influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca(2)(+)-dependent second messenger cascades such as gene expression and synaptic plasticity.

  18. 早期复极综合征与特发性室颤及猝死%Idiopathic ventricular fibrillation and sudden death associated with early repolarization syndrome.

    Institute of Scientific and Technical Information of China (English)

    陈漠水

    2011-01-01

    Early repolarization syndrome (ERS) is a well-recognized idiopathic electrocardiographic phenomenon characterized by prominent J wave and a positive large T wave and ST-segment elevation, concave to the top, predominantly in left precordial (V3~V6 ) leads. It was generally thought that ERS is benign, but recently a growing number of case reports indicate that in some instances, ERS repeatedly induces idiopathic ventricular fibrillation which causes sudden death, suggesting that ERS is associated with idiopathic ventricular fibrillation and sudden death.However, the mechanism of its arrhythmogenic potential still remains unknown. Therefore, patients with ERS who have chest pain, unexplained syncope or other symptoms and at high risks of family history of sudden death should be automatically transferred implantable cardiac defibrillator (ICD) to improve the prognosis. This review summarizes the current state of knowledge concerning ERS associated with idiopathic ventricular fibrillation and sudden death.%早期复极综合征(ERS)是一种以心电图上表现为J波增大或J点抬高,胸前导联V3-V6弓背向下的ST段抬高和高大而直立的T波的特征性的心电改变,通常认为是一种正常心电图的良性变异,但近来报道早期复极综合征在一些情况下可诱发特发性心室颤动,导致猝死,机制尚未明确.对于有胸痛、晕厥等症状或(和)猝死家族史等的高危ERS患者,应植入型心脏自动转律除颤器(ICD)以改善预后.

  19. Effects of prulifloxacin on cardiac repolarization in healthy subjects: a randomized, crossover, double-blind versus placebo, moxifloxacin-controlled study.

    Science.gov (United States)

    Rosignoli, Maria Teresa; Di Loreto, Giorgio; Dionisio, Paolo

    2010-01-01

    Prulifloxacin, a broad-spectrum fluoroquinolone, is quantitatively transformed after oral administration into ulifloxacin, the active metabolite. On the basis of preclinical data suggesting that prulifloxacin is not likely to prolong the QT interval, a trial to assess the potential effects of prulifloxacin on QT and corrected QT (QTc) interval in humans was performed. Fifty-two healthy subjects were randomized into three groups to receive prulifloxacin 600 mg, moxifloxacin 400mg and placebo once daily for 5 days, using a crossover, double-blind versus placebo, moxifloxacin-controlled study. At baseline and days 1 and 5, three 12-lead digital ECGs were recorded before and up to 24 hours after dosing at nine predefined timepoints. Blood samples were also collected at each treatment timepoint. ECG data were analysed in a blinded manner by a centralized laboratory using skilled readers. QT values were corrected for heart rate using an individual correction method (QTcI) as the primary variable, and Fridericia's method as reference. In forty-eight subjects who completed the study, compared with placebo, prulifloxacin had no relevant effect on cardiac repolarization, with the largest mean QTcI increase being 3.97 ms (one-sided 95% CI 0.01, 7.93), whereas moxifloxacin demonstrated the expected positive effect (maximum mean QTcI increase of 12.0 ms, one-sided 95% CI 8.66, 15.34), thus demonstrating the good sensitivity of the study. A statistically significant correlation between QTcI changes and plasma concentrations was found for moxifloxacin but not for ulifloxacin. Prulifloxacin at steady state after therapeutic doses has no significant effects on the QTc interval and thus should prove to have no cardiac liability.

  20. Neuroimaging in anxiety disorders.

    Science.gov (United States)

    Engel, Kirsten; Bandelow, Borwin; Gruber, Oliver; Wedekind, Dirk

    2009-06-01

    Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, "normal anxiety" does not equal "pathological anxiety" although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors.

  1. Comparison for aphasic and control subjects of eye movements hypothesized in neurolinguistic programming.

    Science.gov (United States)

    Dooley, K O; Farmer, A

    1988-08-01

    Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.

  2. Testing Technology Transfer Hypotheses in GIS Environments Using a Case Study Approach (93-8)

    OpenAIRE

    Onsrud, Harlan J.; Jeffrey K. Pinto; Azad, Bijan

    1993-01-01

    In late 1990 and early 1991, a methodological framework was developed for testing technology transfer hypotheses within GIS operational environments. The paper reporting this work was titled "Case Study Research Methods for Geographic Information Systems" (Onsrud, Pinto, and Azad 1992). This report gathers together (1) the original foundation paper used as the basis for the case study research project, (2) the call for participation that includes a listing of the thirty hypotheses for which "...

  3. Stereo-Based Tracking-by-Multiple Hypotheses Framework for Multiple Vehicle Detection and Tracking

    Directory of Open Access Journals (Sweden)

    Young-Chul Lim

    2013-07-01

    Full Text Available In this paper, we present a tracking‐by‐multiple hypotheses framework to detect and track multiple vehicles accurately and precisely. The tracking‐by‐ multiple hypotheses framework consists of obstacle detection, vehicle recognition, visual tracking, global position tracking, data association and particle filtering. The multiple hypotheses are from obstacle detection, vehicle recognition and visual tracking. The obstacle detection detects all the obstacles on the road. The vehicle recognition classifies the detected obstacles as vehicles or non-vehicles. 3D feature‐based visual tracking estimates the current target state using the previous target state. The multiple hypotheses should be linked to corresponding tracks to update the target state. The hierarchical data association method assigns multiple tracks to the correct hypotheses with multiple similarity functions. In the particle filter framework, the target state is updated using the Gaussian motion model and the observation model with associated multiple hypotheses. The experimental results demonstrate that the proposed method enhances the accuracy and precision of the region of interest.

  4. Bipolar disorder

    Science.gov (United States)

    Manic depression; Bipolar affective disorder; Mood disorder - bipolar; Manic depressive disorder ... Fatigue or lack of energy Feelings of worthlessness, hopelessness, or guilt Loss of pleasure in activities once ...

  5. Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

    Science.gov (United States)

    Boso, M; Emanuele, E; Prestori, Francesca; Politi, P; Barale, F; D'Angelo, E

    2010-01-01

    Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

  6. [Conversion disorder : functional neuroimaging and neurobiological mechanisms].

    Science.gov (United States)

    Lejeune, J; Piette, C; Salmon, E; Scantamburlo, G

    2017-04-01

    Conversion disorder is a psychiatric disorder often encountered in neurology services. This condition without organic lesions was and still is sometimes referred as an imaginary illness or feigning. However, the absence of organic lesions does not exclude the possibility of cerebral dysfunction. The etiologic mechanisms underlying this disorder remain uncertain even today.The advent of cognitive and functional imaging opens up a field of exploration for psychiatry in understanding the neurobiological mechanisms underlying mental disorders and especially the conversion disorder. This article reports several neuroimaging studies of conversion disorder and attempts to generate hypotheses about neurobiological mechanisms.

  7. Conversion Disorder

    Science.gov (United States)

    ... Recent significant stress or emotional trauma Being female — women are much more likely to develop conversion disorder Having a mental health condition, such as mood or anxiety disorders, dissociative disorder or certain personality disorders Having ...

  8. Conduct disorder

    Science.gov (United States)

    ... Conduct disorder is often linked to attention-deficit disorder . Conduct disorder also can be an early sign of ... child or teen has a history of conduct disorder behaviors. A physical examination and blood tests can help ...

  9. Psychotic Disorders

    Science.gov (United States)

    Psychotic disorders are severe mental disorders that cause abnormal thinking and perceptions. People with psychoses lose touch ... is not there. Schizophrenia is one type of psychotic disorder. People with bipolar disorder may also have ...

  10. Neuroinflammation in bipolar disorders

    Directory of Open Access Journals (Sweden)

    Georgios D Kotzalidis

    2015-01-01

    Full Text Available Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation, is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuroinflammation-related terms and crossed them with bipolar disorder-related terms. The search produced 310 articles and the number rose to 350 after adding articles from other search engines and reference lists. Twenty papers were included that appropriately tackled the issue of the presence (but not of its pathophysiological role of neuroinflammation in bipolar disorder. Of these, 15 were postmortem and 5 were carried out in living humans. Most articles were consistent with the presence of neuroinflammation in bipolar disorder, but factors such as treatment may mask it. All studies were cross-sectional, preventing causality to be inferred. Thus, no inference can be currently made about the role of neuroinflammation in bipolar disorder, but a link is likely. The issue remains little investigated, despite an excess of reviews on this topic.

  11. Affective disorder: studies with amine precursors.

    Science.gov (United States)

    Dunner, D L; Fieve, R R

    1975-02-01

    The authors assessed the clinical antidepressant effects of L-tryptophan given alone and in combination with L-dopa in 12 patients with a diagnosis of primary affective disorder; Preliminary results did not demonstrate an antidepressant response when L-dopa was combined with L-tryptophan. Also, the results did not support the catecholamine or biogenic amine hypotheses of affective disorder.

  12. The scientific role of hypotheses and the reasoning of college students in physics problem solving

    Directory of Open Access Journals (Sweden)

    Jenaro Guisasola

    2003-08-01

    Full Text Available This paper attempts to explore how freshmen college students in engineering state hypoteses to build their own problem solving structure when dealing with physics problems. From the constructivist perspective of the teaching and learning process hypotheses stating plays a fundamental role to check the coherence of students' ideas against the theoretical framework. The main instruments to accede to students' reasoning were their written solutions to four problematic situations in which they were asked to state hypotheses. The protocols were analysed according to a standard methodology. In this paper two of such problematic situations and the corresponding cathegorization schemes are presented in addition to reseach findings and conclusions.

  13. Hypothesizing the body's genius to trigger and self-organize its healing: 25 years using a standardized neurophysics therapy.

    Science.gov (United States)

    Ross, Sara N; Ware, Ken

    2013-01-01

    We aim for this contribution to operate bi-directionally, both as a "bedside to bench" reverse-translational fractal physiological hypothesis and as a methodological innovation to inform clinical practice. In 25 years using gym equipment therapeutically in non-research settings, the standardized therapy is consistently observed to trigger universal responses of micro to macro waves of system transition dynamics in the human nervous system. These are associated with observably desirable impacts on disorders, injuries, diseases, and athletic performance. Requisite conditions are therapeutic coaching, erect posture, extremely slow movements in mild resistance exercises, and executive control over arousal and attention. To motivate research into the physiological improvements and in validation studies, we integrate from across disciplines to hypothesize explanations for the relationships among the methods, the system dynamics, and evident results. Key hypotheses include: (1) Correctly-directed system efforts may reverse a system's heretofore misdirected efforts, restoring healthier neurophysiology. (2) The enhanced information processing accompanying good posture is an essential initial condition. (3) Behaviors accompanying exercises performed with few degrees of freedom amplify information processing, triggering destabilization and transition dynamics. (4) Executive control over arousal and attention is essential to release system constraints, amplifying and complexifying information. (5) The dynamics create necessary and in many cases evidently sufficient conditions for the body to resolve or improve its own conditions within often short time periods. Literature indicates how the human system possesses material self-awareness. A broad explanation for the nature and effects of the therapy appears rooted in the cascading recursions of the systems' dynamics, which appear to trigger health-fostering self-reorganizing processes when this therapy provides catalytic initial

  14. Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: a population-based prospective cohort study (MONICA/KORA.

    Directory of Open Access Journals (Sweden)

    Moritz F Sinner

    2010-07-01

    Full Text Available BACKGROUND: Early repolarization pattern (ERP on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg] comprised of individuals of Central-European descent. METHODS AND FINDINGS: Electrocardiograms of 1,945 participants aged 35-74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9 codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005. Age-stratified analyses showed hazard ratios (HRs for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05-3.68, p = 0.035 for both sexes and 2.65 (95% CI 1.21-5.83, p = 0.015 for men between 35-54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58-6.28, p = 0.001 for both sexes and to 4.27 (95% CI 1.90-9.61, p<0.001 for men between 35-54 y. HRs for all-cause mortality were weaker but reached significance. CONCLUSIONS: We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior

  15. Tachycardia-dependent augmentation of "notched J waves" in a general patient population without ventricular fibrillation or cardiac arrest: not a repolarization but a depolarization abnormality?

    Science.gov (United States)

    Aizawa, Yoshifusa; Sato, Masahito; Kitazawa, Hitoshi; Aizawa, Yoshiyasu; Takatsuki, Seiji; Oda, Eiji; Okabe, Masaaki; Fukuda, Keiichi

    2015-02-01

    J waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood. The purpose of this study was to examine the J-wave dynamicity in a general patient population. The responses of J waves (>0.1 mV above the isoelectric line in 2 contiguous leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The J-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals. Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 ± 0.06 mV at the baseline RR interval of 853 ± 152 ms, 0.25 ± 0.11 mV at the RR interval in the conducted APB of 545 ± 133 ms (P = .0018), and 0.19 ± 0.08 mV at the RR interval of 1146 ± 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 ± 0.12 mV vs 0.42 ± 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (>0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality. J waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  16. Diagnostic and prognostic values of the V-index, a novel ECG marker quantifying spatial heterogeneity of ventricular repolarization, in patients with symptoms suggestive of non-ST-elevation myocardial infarction.

    Science.gov (United States)

    Abächerli, Roger; Twerenbold, Raphael; Boeddinghaus, Jasper; Nestelberger, Thomas; Mächler, Patrick; Sassi, Roberto; Rivolta, Massimo W; Roonizi, Ebadollah Kheirati; Mainardi, Luca T; Kozhuharov, Nikola; Rubini Giménez, Maria; Wildi, Karin; Grimm, Karin; Sabti, Zaid; Hillinger, Petra; Puelacher, Christian; Strebel, Ivo; Cupa, Janosch; Badertscher, Patrick; Roux, Isabelle; Schmid, Ramun; Leber, Remo; Osswald, Stefan; Mueller, Christian; Reichlin, Tobias

    2017-06-01

    The V-index is an ECG marker quantifying spatial heterogeneity of ventricular repolarization. We prospectively assessed the diagnostic and prognostic values of the V-index in patients with suspected non-ST-elevation myocardial infarction (NSTEMI). We prospectively enrolled 497 patients presenting with suspected NSTEMI to the emergency department (ED). Digital 12-lead ECGs of five-minute duration were recorded at presentation. The V-index was automatically calculated in a blinded fashion. Patients with a QRS duration >120ms were ruled out from analysis. The final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 24months of follow-up. NSTEMI was the final diagnosis in 14% of patients. V-index levels were higher in patients with AMI compared to other causes of chest pain (median 23ms vs. 18ms, pV-index in addition to conventional ECG-criteria improved the diagnostic accuracy for the diagnosis of NSTEMI as quantified by area under the ROC curve from 0.66 to 0.73 (p=0.001) and the sensitivity of the ECG for AMI from 41% to 86% (pV-index (pV-index remained an independent predictor of death. The V-index, an ECG marker quantifying spatial heterogeneity of ventricular repolarization, significantly improves the accuracy and sensitivity of the ECG for the diagnosis of NSTEMI and independently predicts mortality during follow-up. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Assortative mating after divorce : a test of two competing hypotheses using marginal models

    NARCIS (Netherlands)

    Gelissen, J.P.T.M.

    2004-01-01

    We analyze data from 927 remarried men and women to examine the association between spouses' educational attainment, social class, and age in their first and current union. Applying marginal homogeneity models, we test two competing hypotheses: current unions of remarried people are more homogamous

  18. Ecosystem functioning and maximum entropy production: a quantitative test of hypotheses.

    Science.gov (United States)

    Meysman, Filip J R; Bruers, Stijn

    2010-05-12

    The idea that entropy production puts a constraint on ecosystem functioning is quite popular in ecological thermodynamics. Yet, until now, such claims have received little quantitative verification. Here, we examine three 'entropy production' hypotheses that have been forwarded in the past. The first states that increased entropy production serves as a fingerprint of living systems. The other two hypotheses invoke stronger constraints. The state selection hypothesis states that when a system can attain multiple steady states, the stable state will show the highest entropy production rate. The gradient response principle requires that when the thermodynamic gradient increases, the system's new stable state should always be accompanied by a higher entropy production rate. We test these three hypotheses by applying them to a set of conventional food web models. Each time, we calculate the entropy production rate associated with the stable state of the ecosystem. This analysis shows that the first hypothesis holds for all the food webs tested: the living state shows always an increased entropy production over the abiotic state. In contrast, the state selection and gradient response hypotheses break down when the food web incorporates more than one trophic level, indicating that they are not generally valid.

  19. Delinquency and Peer Acceptance in Adolescence: A Within-Person Test of Moffitt's Hypotheses

    Science.gov (United States)

    Rulison, Kelly L.; Kreager, Derek A.; Osgood, D. Wayne

    2014-01-01

    We tested 2 hypotheses derived from Moffitt's (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. We tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent…

  20. INFLUENCES ON AND FROM THE SEGMENTATION OF NETWORKS - HYPOTHESES AND TESTS

    NARCIS (Netherlands)

    BAERVELDT, C; SNIJDERS, T

    1994-01-01

    This article discusses (a) the influence of network structure on the diffusion of (new) cultural behavior within the network and (b) the influence of external events, especially of social programs, on the diffusion of (new) cultural behavior, and on the network structure. Hypotheses are formulated a

  1. HYPERACTIVE TISSUE RENIN-ANGIOTENSIN SYSTEMS IN CARDIOVASCULAR DYSFUNCTION - EXPERIMENTAL-EVIDENCE AND CLINICAL HYPOTHESES

    NARCIS (Netherlands)

    PINTO, YM; BUIKEMA, H; VANGILST, WH

    1995-01-01

    In this review, hypotheses are discussed with regard to the role of local, tissue renin-angiotensin systems in the progression of cardiovascular dysfunction. After local renin-anglotensin systems had been described as functionally distinct systems, recent experimental studies have suggested an assoc

  2. Use of hypotheses for analysis of variance models: challenging the current practice

    NARCIS (Netherlands)

    van Wesel, F.; Boeije, H.R.; Hoijtink, H.

    2013-01-01

    In social science research, hypotheses about group means are commonly tested using analysis of variance. While deemed to be formulated as specifically as possible to test social science theory, they are often defined in general terms. In this article we use two studies to explore the current practic

  3. Delinquency and Peer Acceptance in Adolescence: A Within-Person Test of Moffitt's Hypotheses

    Science.gov (United States)

    Rulison, Kelly L.; Kreager, Derek A.; Osgood, D. Wayne

    2014-01-01

    We tested 2 hypotheses derived from Moffitt's (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. We tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent…

  4. Why Consumers Choose Managed Mutual Funds over Index Funds: Hypotheses from Consumer Behavior.

    Science.gov (United States)

    Lichtenstein, Donald R.; Kaufmann, Patrick J.; Bhagat, Sanjai

    1999-01-01

    Using the literature of psychology, consumer behavior, and behavioral finance, a series of hypotheses is presented that account for consumer choices of managed over index mutual funds. Results indicate a need for consumer education to increase awareness of the benefits of index investing. (SK)

  5. Lee Smolin Five Great Problems and Their Solution without Ontological Hypotheses

    CERN Document Server

    Quznetsov, Gunn

    2011-01-01

    Solutions of Lee Smolin Five Great Problems from his book {\\it The Trouble with Physics: the Rise of String Theory, the Fall of a Science, and What Comes Next} are described. This solutions is obtained only from the properties of probability without any ontological hypotheses.

  6. What Constrains the Accuracy of Metacomprehension Judgments? Testing the Transfer-Appropriate-Monitoring and Accessibility Hypotheses

    Science.gov (United States)

    Dunlosky, J.; Rawson, K.A.; Middleton, E.L.

    2005-01-01

    We evaluated two hypotheses-transfer appropriate monitoring (TAM) and the accessibility hypothesis-that explain why the accuracy of metacomprehension judgments is commonly low. In 2 experiments, participants read six expository texts, made global judgments about how well they would perform on a test over each text, and made term-specific judgments…

  7. Gender Relations and Economic Development: Hypotheses about the Reversal of Fortune in EurAsia

    NARCIS (Netherlands)

    de Pleijt, A.M.; van Zanden, J.L.; Carmichael, S.G.

    2016-01-01

    This paper develops an interrelated set of hypotheses about the links between gender relations, family systems and economic development in EurAsia. Firstly, we briefly discuss a number of ideas from the recent literature about the links between gender relations and economic development. Secondly, we

  8. Bullying Victimization and Adolescent Self-Harm: Testing Hypotheses from General Strain Theory

    Science.gov (United States)

    Hay, Carter; Meldrum, Ryan

    2010-01-01

    Self-harm is widely recognized as a significant adolescent social problem, and recent research has begun to explore its etiology. Drawing from Agnew's (1992) social psychological strain theory of deviance, this study considers this issue by testing three hypotheses about the effects of traditional and cyber bullying victimization on deliberate…

  9. Coping with the Stigma of Mental Illness: Empirically-Grounded Hypotheses from Computer Simulations

    Science.gov (United States)

    Kroska, Amy; Har, Sarah K.

    2011-01-01

    This research demonstrates how affect control theory and its computer program, "Interact", can be used to develop empirically-grounded hypotheses regarding the connection between cultural labels and behaviors. Our demonstration focuses on propositions in the modified labeling theory of mental illness. According to the MLT, negative societal…

  10. Williams Syndrome Hypersociability: A Neuropsychological Study of the Amygdala and Prefrontal Cortex Hypotheses

    Science.gov (United States)

    Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.

    2011-01-01

    Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…

  11. Bullying Victimization and Adolescent Self-Harm: Testing Hypotheses from General Strain Theory

    Science.gov (United States)

    Hay, Carter; Meldrum, Ryan

    2010-01-01

    Self-harm is widely recognized as a significant adolescent social problem, and recent research has begun to explore its etiology. Drawing from Agnew's (1992) social psychological strain theory of deviance, this study considers this issue by testing three hypotheses about the effects of traditional and cyber bullying victimization on deliberate…

  12. Vestigial Biological Structures: A Classroom-Applicable Test of Creationist Hypotheses

    Science.gov (United States)

    Senter, Phil; Ambrocio, Zenis; Andrade, Julia B.; Foust, Katanya K.; Gaston, Jasmine E.; Lewis, Ryshonda P.; Liniewski, Rachel M.; Ragin, Bobby A.; Robinson, Khanna L.; Stanley, Shane G.

    2015-01-01

    Lists of vestigial biological structures in biology textbooks are so short that some young-Earth creationist authors claim that scientists have lost confidence in the existence of vestigial structures and can no longer identify any verifiable ones. We tested these hypotheses with a method that is easily adapted to biology classes. We used online…

  13. Examining Preservice Science Teachers' Skills of Formulating Hypotheses and Identifying Variables

    Science.gov (United States)

    Aydogdu, Bülent

    2015-01-01

    The aim of this study is to examine preservice science teachers' skills of formulating hypotheses and identifying variables. The research has a phenomenological research design. The data was gathered qualitatively. In this study, preservice science teachers were first given two scenarios (Scenario-1 & Scenario-2) containing two different…

  14. Coping with the Stigma of Mental Illness: Empirically-Grounded Hypotheses from Computer Simulations

    Science.gov (United States)

    Kroska, Amy; Har, Sarah K.

    2011-01-01

    This research demonstrates how affect control theory and its computer program, "Interact", can be used to develop empirically-grounded hypotheses regarding the connection between cultural labels and behaviors. Our demonstration focuses on propositions in the modified labeling theory of mental illness. According to the MLT, negative societal…

  15. ADOPTING SOCIO-DEMOGRAPHIC CHARACTERISTICS IN PROFILING GREEN CONSUMERS: A REVIEW OF HYPOTHESES

    Directory of Open Access Journals (Sweden)

    Arif Hartono

    2009-02-01

    Full Text Available In the last three decades worldwide environmental consciousness has increased dramatically as well as profiling green consumers have gained tremendous attention in the past. Segmenting and targeting markets base on pro-environmental purchase behavior are essential when companies positioning their green products. Socio-demographic characteristics have gained a lot of attention as the key profiling variables. Such characteristics have been employed by many scholars more frequently for the bases of segmenting and profiling green consumers. However, most existing studies of green consumers’ socio-demographic were US based. The present article attempts to review the common hypotheses of socio-demographic characteristics in profiling green consumers. The present article reviews five general hypotheses relating to socio-demographics and environmental consciousness of green consumers, namely the gender, age, education level, income, and occupation hypotheses, as well as the theoretical explanation for each hypothesis. Most previous studies tend to have the same conclusion in the gender, age, education level, and  income characteristics. Critics to socio-demographic characteristics and a need to conduct green marketing research in Indonesia was also reviewed.Key words: profiling, socio-demographic, green consumer, hypotheses.

  16. Vestigial Biological Structures: A Classroom-Applicable Test of Creationist Hypotheses

    Science.gov (United States)

    Senter, Phil; Ambrocio, Zenis; Andrade, Julia B.; Foust, Katanya K.; Gaston, Jasmine E.; Lewis, Ryshonda P.; Liniewski, Rachel M.; Ragin, Bobby A.; Robinson, Khanna L.; Stanley, Shane G.

    2015-01-01

    Lists of vestigial biological structures in biology textbooks are so short that some young-Earth creationist authors claim that scientists have lost confidence in the existence of vestigial structures and can no longer identify any verifiable ones. We tested these hypotheses with a method that is easily adapted to biology classes. We used online…

  17. Factors that Affect the Physical Science Career Interest of Female Students: Testing Five Common Hypotheses

    Science.gov (United States)

    Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sonnert, Gerhard; Sadler, Philip M.

    2013-01-01

    There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using multivariate matching methods on national data drawn from the Persistence Research in Science and Engineering (PRiSE) project ("n" = 7505), we test the following five commonly held beliefs regarding what…

  18. Editorial: hypotheses about protein folding--the proteomic code and wonderfolds.

    Science.gov (United States)

    Agutter, Paul S

    2009-12-24

    Theoretical biology journals can contribute in many ways to the progress of knowledge. They are particularly well-placed to encourage dialogue and debate about hypotheses addressing problematical areas of research. An online journal provides an especially useful forum for such debate because of the option of posting comments within days of the publication of a contentious article.

  19. Testing Social Cognitive Interest and Choice Hypotheses across Holland Types in Italian High School Students.

    Science.gov (United States)

    Lent, Robert W.; Brown, Steven D.; Nota, Laura; Soresi, Salvatore

    2003-01-01

    Italian high school students (n=796) completed measures related to Social Cognitive Career Theory and Holland's personality types. Findings supported hypotheses that self-efficacy and outcome expectations predict interests. Whether the mediation effect of interests was full or partial varied across types. Social supports/barriers related to career…

  20. Why Consumers Choose Managed Mutual Funds over Index Funds: Hypotheses from Consumer Behavior.

    Science.gov (United States)

    Lichtenstein, Donald R.; Kaufmann, Patrick J.; Bhagat, Sanjai

    1999-01-01

    Using the literature of psychology, consumer behavior, and behavioral finance, a series of hypotheses is presented that account for consumer choices of managed over index mutual funds. Results indicate a need for consumer education to increase awareness of the benefits of index investing. (SK)

  1. Utility of Krashen's Five Hypotheses in the Saudi Context of Foreign Language Acquisition/Learning

    Science.gov (United States)

    Gulzar, Malik Ajmal; Gulnaz, Fahmeeda; Ijaz, Attiya

    2014-01-01

    In the last twenty years, the paradigm that has dominated the discipline of language teaching is the SLA theory and Krashen's five hypotheses which are still proving flexible to accommodate earlier reforms. This paper reviews second language acquisition (SLA) theory to establish an understanding of its role in the EFL/ESL classrooms. Other areas…

  2. Bipolar disorder, a precursor of Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Tânia M.S. Novaretti

    Full Text Available ABSTRACT Parkinson's disease is a neurodegenerative disorder predominantly resulting from dopamine depletion in the substantia nigra pars compacta. Some psychiatric disorders may have dopaminergic dysfunction as their substrate. We describe a well-documented case of Parkinson's disease associated with Bipolar Disorder. Although there is some knowledge about the association between these diseases, little is known about its pathophysiology and correlation. We believe that among various hypotheses, many neurotransmitters are linked to this pathophysiology.

  3. Magnetic field disorder and Faraday effects on the polarization of extragalactic radio sources

    CERN Document Server

    Lamee, Mehdi; Farnes, Jamie S; Carretti, Ettore; Gaensler, B M; Haverkorn, Marijke; Poppi, Sergio

    2016-01-01

    We present a polarization catalog of 533 extragalactic radio sources with 2.3 GHz total intensity above 420 mJy from the S-band Polarization All Sky Survey, S-PASS, with corresponding 1.4 GHz polarization information from the NRAO VLA Sky Survey, NVSS. We studied selection effects and found that fractional polarization, $\\pi$, of radio objects at both wavelengths depends on the spectral index, source magnetic field disorder, source size and depolarization. The relationship between depolarization, spectrum and size shows that depolarization occurs primarily in the source vicinity. The median $\\pi_{2.3}$ of resolved objects in NVSS is approximately two times larger than that of unresolved sources. Sources with little depolarization are $\\sim2$ times more polarized than both highly depolarized and re-polarized sources. This indicates that intrinsic magnetic field disorder is the dominant mechanism responsible for the observed low fractional polarization of radio sources at high frequencies. We predict that numbe...

  4. Familial and Temperamental Risk Factors for Social Anxiety Disorder

    Science.gov (United States)

    Hirshfeld-Becker, Dina R.

    2010-01-01

    Social anxiety disorder (SAD) is a common disorder that can lead to significant impairment. In this chapter, the author provides background on the disorder and reviews hypothesized familial and temperamental risk factors. In particular, it highlights the Massachusetts General Hospital (MGH) Longitudinal Study of Children at Risk for Anxiety, now…

  5. QT wave dispersion in patients with panic disorder

    Institute of Scientific and Technical Information of China (English)

    Murad Atmaca; Mustafa Yavuzkir; Filiz Izci; M. Gurkan Gurok; Sahin Adiyaman

    2012-01-01

    [Objective] QT dispersion (QTd),defined as the maximal inter-lead difference in QT intervals on 12 leads of the surface electrocardiogram (ECG),reflects the regional heterogeneity of ventricular repolarization and has been suggested as an important marker for risk of arrhythmia in addition to the QT interval.Some investigators proposed that it might be a predisposing factor for arrhythmic events and sudden death.Thus,we aimed to investigate whether QTd differs in patients with panic disorder from that in healthy controls.[Methods] In 40 panic disorder patients and 40 healthy controls,Qmax,Qmin,and QTd values were measured.In addition,the Hamilton depression rating scale and the panic agoraphobia scale were scored for both patients and healthy volunteers.[Results] Qmax and Qmin values in the panic disorder patients were significantly higher than those in healthy controls.The mean corrected QTd was significantly greater in the patients than in the controls.One-way analysis of covariance (ANCOVA,using left atrial size,age and heart rate as covariates) also corrected the significant difference.In addition,ANCOVA revealed a significant main effect for the diagnosis,indicating a significantly higher QTd for patients compared with controls.[Conclusion]QTd might be associated with panic disorder.Future studies in larger samples evaluating the effects of treatment are required.

  6. Schizoaffective disorder

    Science.gov (United States)

    ... cause of schizoaffective disorder is unknown. Changes in genes and chemicals in the brain (neurotransmitters) may play a role. Schizoaffective disorder is thought to be less common than schizophrenia and mood disorders. Women may have the condition ...

  7. Genetic Disorders

    Science.gov (United States)

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  8. A modular modelling framework for hypotheses testing in the simulation of urbanisation

    CERN Document Server

    Cottineau, Clementine; Chapron, Paul; Coyrehourcq, Sebastien Rey; Pumain, Denise

    2015-01-01

    In this paper, we present a modelling experiment developed to study systems of cities and processes of urbanisation in large territories over long time spans. Building on geographical theories of urban evolution, we rely on agent-based models to 1/ formalise complementary and alternative hypotheses of urbanisation and 2/ explore their ability to simulate observed patterns in a virtual laboratory. The paper is therefore divided into two sections : an overview of the mechanisms implemented to represent competing hypotheses used to simulate urban evolution; and an evaluation of the resulting model structures in their ability to simulate - efficiently and parsimoniously - a system of cities (the Former Soviet Union) over several periods of time (before and after the crash of the USSR). We do so using a modular framework of model-building and evolutionary algorithms for the calibration of several model structures. This project aims at tackling equifinality in systems dynamics by confronting different mechanisms wi...

  9. How doctors generate diagnostic hypotheses: a study of radiological diagnosis with functional magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Marcio Melo

    Full Text Available BACKGROUND: In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life. METHODOLOGY AND PRINCIPAL FINDINGS: To test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14 seconds and 1.23 (SD ±0.13 seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds. The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals. CONCLUSIONS: Generation of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of

  10. Economic and evolutionary hypotheses for cross-population variation in parochialism.

    Science.gov (United States)

    Hruschka, Daniel J; Henrich, Joseph

    2013-09-11

    Human populations differ reliably in the degree to which people favor family, friends, and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism.

  11. Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.

    Directory of Open Access Journals (Sweden)

    Karin Lundengård

    2016-06-01

    Full Text Available Functional magnetic resonance imaging (fMRI measures brain activity by detecting the blood-oxygen-level dependent (BOLD response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new

  12. Replication Requires Psychological Rather than Statistical Hypotheses: The Case of Eye Movements Enhancing Word Recollection

    Science.gov (United States)

    Phaf, R. Hans

    2016-01-01

    Can an experiment be replicated in a mechanical fashion without considering the processes underlying the initial results? Here I will consider a non-replication of Saccade Induced Retrieval Enhancement (SIRE) and argue that it results from focusing on statistical instead of on substantive process hypotheses. Particularly the theoretical integration of SIRE with Eye-Movement Desensitization and Reprocessing (EMDR) therapy, provides clues about when the memory enhancement should occur. A relatively large memory enhancement effect in participants with a consistent (i.e., extreme right or left) handedness should be observed, (a) when explicitly instructed to retrieve and imagine the memories during the eye manipulation, and (b) for emotionally negative material. A finer theoretical analysis may thus well explain the contrast between the original SIRE studies and the non-replication. Also the findings from preregistered confirmatory research (i.e., focusing solely on statistical hypotheses) should be considered preliminary, representing shifts on a gradual scale of evidence, and awaiting interpretation in terms of theoretical hypotheses. Stronger, but still not definitive, conclusions can better be postponed until after multi-study meta-analyses with theoretically motivated moderator variables have been performed. PMID:28082942

  13. Healthy migrant and salmon bias hypotheses: a study of health and internal migration in China.

    Science.gov (United States)

    Lu, Yao; Qin, Lijian

    2014-02-01

    The existing literature has often underscored the "healthy migrant" effect and the "salmon bias" in understanding the health of migrants. Nevertheless, direct evidence for these two hypotheses, particularly the "salmon bias," is limited. Using data from a national longitudinal survey conducted between 2003 and 2007 in China, we provide tests of these hypotheses in the case of internal migration in China. To examine the healthy migrant effect, we study how pre-migration self-reported health is associated with an individual's decision to migrate and the distance of migration. To test the salmon bias hypothesis, we compare the self-reported health of migrants who stay in destinations and who return or move closer to home villages. The results provide support for both hypotheses. Specifically, healthier individuals are more likely to migrate and to move further away from home. Among migrants, those with poorer health are more likely to return or to move closer to their origin communities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Using computational fluid dynamics to test functional and ecological hypotheses in fossil taxa

    Science.gov (United States)

    Rahman, Imran

    2016-04-01

    Reconstructing how ancient organisms moved and fed is a major focus of study in palaeontology. Traditionally, this has been hampered by a lack of objective data on the functional morphology of extinct species, especially those without a clear modern analogue. However, cutting-edge techniques for characterizing specimens digitally and in three dimensions, coupled with state-of-the-art computer models, now provide a robust framework for testing functional and ecological hypotheses even in problematic fossil taxa. One such approach is computational fluid dynamics (CFD), a method for simulating fluid flows around objects that has primarily been applied to complex engineering-design problems. Here, I will present three case studies of CFD applied to fossil taxa, spanning a range of specimen sizes, taxonomic groups and geological ages. First, I will show how CFD enabled a rigorous test of hypothesized feeding modes in an enigmatic Ediacaran organism with three-fold symmetry, revealing previously unappreciated complexity of pre-Cambrian ecosystems. Second, I will show how CFD was used to evaluate hydrodynamic performance and feeding in Cambrian stem-group echinoderms, shedding light on the probable feeding strategy of the latest common ancestor of all deuterostomes. Third, I will show how CFD allowed us to explore the link between form and function in Mesozoic ichthyosaurs. These case studies serve to demonstrate the enormous potential of CFD for addressing long-standing hypotheses for a variety of fossil taxa, opening up an exciting new avenue in palaeontological studies of functional morphology.

  15. Partial migration in birds: tests of three hypotheses in a tropical lekking frugivore.

    Science.gov (United States)

    Boyle, W Alice

    2008-11-01

    1. Partially migratory species provide opportunities to understand which ecological factors cause some animals to migrate when others remain resident year round. Partial migration in birds has been explained by the dominance, arrival-time, and body-size hypotheses. 2. Testing these hypotheses has proven difficult due to the similarities of the predictions they make in temperate-breeding long-distance migrants. In tropical altitudinal migrants, however, these hypotheses make different predictions regarding the sex, age, and condition of migrants and residents. 3. Among white-ruffed manakins in Costa Rica, young birds were not more likely to migrate (as predicted by the dominance hypothesis), nor were females more likely to migrate (as predicted by the arrival-time hypothesis). All condition-related variables interacted with sex, together explaining much of the variation in migratory behaviour. 4. I re-articulate the body-size hypothesis in the context of tropical altitudinal bird migration, focusing explicitly on how limited foraging opportunities and differences in individual condition affect fasting ability during torrential rains. Despite ample food, the smallest birds or those stressed by parasites or moult may risk starvation at breeding elevations due to a reduction in foraging time. These results highlight how intrinsic and extrinsic factors may interact to produce observed patterns of within- and among-species variation in migratory behaviour.

  16. Testing vs. Believing Hypotheses: Magical Ideation in the Judgement of Contingencies.

    Science.gov (United States)

    Brugger, P; Graves, R E

    1997-11-01

    This paper examines the idea that an important dimension of human cognition is the amount of objective evidence required for perception of meaningful patterns. At the clinical extreme of this dimension are patients with hallucinations and delusions who experience perception with no external evidence and see connections between objectively unrelated events. Also, normal individuals exhibit considerable variation along this continuum. The theory proposed here predicts that normal subjects with low evidential criteria will be more likely to accept causal explanations, not only for everyday ''paranormal'' coincidences, but also for random contingencies in a laboratory experiment. This prediction was confirmed when 40 students completed a differential reinforcement of low rates (DRL) task designed to induce superstitious behaviour and were then questioned about their hypotheses concerning the contingencies for successful performance. Participants scoring high on the Magical Ideation scale (indicating greater belief in paranormal phenomena) tested fewer hypotheses during the task, and they ended up believing in more hypotheses regarding illusory contingencies than did their low-scoring peers. We proposed that a continuum of hypothesis-testing behaviour underlies the schizotypy continuum, with ''positive'' schizotypal traits reflecting a Type I error bias and ''negative'' traits a Type II error bias. Differential activation patterns within frontal-limbic networks are tentatively suggested as a physiological correlate of the behavioural continuum.

  17. Using climate, energy, and spatial-based hypotheses to interpret macroecological patterns of North America chelonians

    Science.gov (United States)

    Ennen, Joshua R.; Agha, Mickey; Matamoros, Wilfredo A.; Hazzard, Sarah C.; Lovich, Jeffrey E.

    2016-01-01

    Our study investigates how factors, such as latitude, productivity, and several environmental variables, influence contemporary patterns of the species richness in North American turtles. In particular, we test several hypotheses explaining broad-scale species richness patterns on several species richness data sets: (i) total turtles, (ii) freshwater turtles only, (iii) aquatic turtles, (iv) terrestrial turtles only, (v) Emydidae, and (vi) Kinosternidae. In addition to spatial data, we used a combination of 25 abiotic variables in spatial regression models to predict species richness patterns. Our results provide support for multiple hypotheses related to broad-scale patterns of species richness, and in particular, hypotheses related to climate, productivity, water availability, topography, and latitude. In general, species richness patterns were positively associated with temperature, precipitation, diversity of streams, coefficient of variation of elevation, and net primary productivity. We also found that North America turtles follow the general latitudinal diversity gradient pattern (i.e., increasing species richness towards equator) by exhibiting a negative association with latitude. Because of the incongruent results among our six data sets, our study highlights the importance of considering phylogenetic constraints and guilds when interpreting species richness patterns, especially for taxonomic groups that occupy a myriad of habitats.

  18. Basing the treatment of stereotypic and self-injurious behaviors on hypotheses of their causes.

    Science.gov (United States)

    Repp, A C; Felce, D; Barton, L E

    1988-01-01

    Stereotypic and self-injurious behaviors are common forms of maladaptive responding demonstrated by severely handicapped persons. Various review papers suggest that no single treatment procedure is universally effective. Although there may be many reasons for this finding, one could be that people engage in these behaviors for various reasons, and that procedures that are incompatible with the cause of the behavior are unlikely to be effective. These studies also suggest many hypotheses for the development and maintenance of these behaviors, three of which are the self-stimulation, positive reinforcement, and negative reinforcement hypotheses. The purpose of this paper was to determine whether one of these hypotheses could be matched to the cause of the behavior and used as an effective treatment procedure. We therefore compared one hypothesis with one other for 3 subjects in a three-phase study. During baseline, data were taken in two classrooms for each subject, and a judgement was made about the hypothesis most likely to be related to the cause of the behavior. During the second phase, a treatment based on that hypothesis was used in one classroom, and a treatment based on another hypothesis was used in the second classroom. During the third phase, the treatment that was most effective in the second phase was used in both classrooms. Results showed that a successful treatment program can be developed on an hypothesis of why the behavior occurred during baseline. Results are discussed in terms of supporting the argument that treatment programs should be based on a functional analysis of the behavior in its environmental context.

  19. Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.

    Science.gov (United States)

    Sternberg, Michael J E; Tamaddoni-Nezhad, Alireza; Lesk, Victor I; Kay, Emily; Hitchen, Paul G; Cootes, Adrian; van Alphen, Lieke B; Lamoureux, Marc P; Jarrell, Harold C; Rawlings, Christopher J; Soo, Evelyn C; Szymanski, Christine M; Dell, Anne; Wren, Brendan W; Muggleton, Stephen H

    2013-01-09

    Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge. We study the capsular polysaccharide biosynthetic pathway of the major human gastrointestinal pathogen Campylobacter jejuni. We consider several key steps in the formation of capsular polysaccharide consisting of 15 genes of which 8 have assigned function, and we explore the extent to which functions can be hypothesised for the remaining 7. Two sources of experimental data provide the information for learning-the results of knockout experiments on the genes involved in capsule formation and the absence/presence of capsule genes in a multitude of strains of different serotypes. The machine learning uses the pathway structure as background knowledge. We propose assignments of specific genes to five previously unassigned reaction steps. For four of these steps, there was an unambiguous optimal assignment of gene to reaction, and to the fifth, there were three candidate genes. Several of these assignments were consistent with additional experimental results. We therefore show that the logic-based methodology provides a robust strategy to integrate results from different experimental approaches and propose hypotheses for the behaviour of a biological system. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. "On Clocks and Clouds:" Confirming and Interpreting Climate Models as Scientific Hypotheses (Invited)

    Science.gov (United States)

    Donner, L.

    2009-12-01

    The certainty of climate change projected under various scenarios of emissions using general circulation models is an issue of vast societal importance. Unlike numerical weather prediction, a problem to which general circulation models are also applied, projected climate changes usually lie outside of the range of external forcings for which the models generating these changes have been directly evaluated. This presentation views climate models as complex scientific hypotheses and thereby frames these models within a well-defined process of both advancing scientific knowledge and recognizing its limitations. Karl Popper's Logik der Forschung (The Logic of Scientific Discovery, 1934) and 1965 essay “On Clocks and Clouds” capture well the methodologies and challenges associated with constructing climate models. Indeed, the process of a problem situation generating tentative theories, refined by error elimination, characterizes aptly the routine of general circulation model development. Limitations on certainty arise from the distinction Popper perceived in types of natural processes, which he exemplified by clocks, capable of exact measurement, and clouds, subject only to statistical approximation. Remarkably, the representation of clouds in general circulation models remains the key uncertainty in understanding atmospheric aspects of climate change. The asymmetry of hypothesis falsification by negation and much vaguer development of confidence in hypotheses consistent with some of their implications is an important practical challenge to confirming climate models. The presentation will discuss the ways in which predictions made by climate models for observable aspects of the present and past climate can be regarded as falsifiable hypotheses. The presentation will also include reasons why “passing” these tests does not provide complete confidence in predictions about the future by climate models. Finally, I will suggest that a “reductionist” view, in

  1. Evaluating Hypotheses of Plant Species Invasions on Mediterranean Islands: Inverse Patterns between Alien and Endemic Species

    Directory of Open Access Journals (Sweden)

    Alexander Bjarnason

    2017-08-01

    Full Text Available Invasive alien species cause major changes to ecosystem functioning and patterns of biodiversity, and the main factors involved in invasion success remain contested. Using the Mediterranean island of Crete, Greece as a case study, we suggest a framework for analyzing spatial data of alien species distributions, based on environmental predictors, aiming to gain an understanding of their spatial patterns and spread. Mediterranean islands are under strong ecological pressure from invading species due to their restricted size and increased human impact. Four hypotheses of invasibility, the “propagule pressure hypothesis” (H1, “biotic resistance hypothesis vs. acceptance hypothesis” (H2, “disturbance-mediated hypothesis” (H3, and “environmental heterogeneity hypothesis” (H4 were tested. Using data from alien, native, and endemic vascular plant species, the propagule pressure, biotic resistance vs. acceptance, disturbance-mediated, and environmental heterogeneity hypotheses were tested with Generalized Additive Modeling (GAM of 39 models. Based on model selection, the optimal model includes the positive covariates of native species richness, the negative covariates of endemic species richness, and land area. Variance partitioning between the four hypotheses indicated that the biotic resistance vs. acceptance hypothesis explained the vast majority of the total variance. These results show that areas of high species richness have greater invasibility and support the acceptance hypothesis and “rich-get-richer” distribution of alien species. The negative correlation between alien and endemic species appears to be predominantly driven by altitude, with fewer alien and more endemic species at greater altitudes, and habitat richness. The negative relationship between alien and endemic species richness provides potential for understanding patterns of endemic and alien species on islands, contributing to more effective conservation

  2. Spatial overlap in a solitary carnivore: support for the land tenure, kinship or resource dispersion hypotheses?

    Science.gov (United States)

    Elbroch, L Mark; Lendrum, Patrick E; Quigley, Howard; Caragiulo, Anthony

    2016-03-01

    There are several alternative hypotheses about the effects of territoriality, kinship and prey availability on individual carnivore distributions within populations. The first is the land-tenure hypothesis, which predicts that carnivores regulate their density through territoriality and temporal avoidance. The second is the kinship hypothesis, which predicts related individuals will be clumped within populations, and the third is the resource dispersion hypothesis, which suggests that resource richness may explain variable sociality, spatial overlap or temporary aggregations of conspecifics. Research on the socio-spatial organization of animals is essential in understanding territoriality, intra- and interspecific competition, and contact rates that influence diverse ecology, including disease transmission between conspecifics and courtship behaviours. We explored these hypotheses with data collected on a solitary carnivore, the cougar (Puma concolor), from 2005 to 2012 in the Southern Yellowstone Ecosystem, Wyoming, USA. We employed 27 annual home ranges for 13 cougars to test whether home range overlap was better explained by land tenure, kinship, resource dispersion or some combination of the three. We found support for both the land tenure and resource dispersion hypotheses, but not for kinship. Cougar sex was the primary driver explaining variation in home range overlap. Males overlapped significantly with females, whereas the remaining dyads (F-F, M-M) overlapped significantly less. In support for the resource dispersion hypothesis, hunting opportunity (the probability of a cougar killing prey in a given location) was often higher in overlapping than in non-overlapping portions of cougar home ranges. In particular, winter hunt opportunity rather than summer hunt opportunity was higher in overlapping portions of female-female and male-female home ranges. Our results may indicate that solitary carnivores are more tolerant of sharing key resources with unrelated

  3. Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions.

    Science.gov (United States)

    Liester, Mitchell B; Prickett, James I

    2012-01-01

    Ayahuasca is a medicinal plant mixture utilized by indigenous peoples throughout the Amazon River basin for healing purposes. The "vine of the soul" or "vine of death," as it is known in South America, contains a combination of monoamine oxidase inhibitors and N,N-dimethyltryptamine (DMT). When ingested together, these medicines produce profound alterations in consciousness. Increasingly, ayahuasca is being utilized to treat addictions. However, the mechanism of action by which ayahuasca treats addictions remains unclear. We offer four hypotheses to explain possible biochemical, physiological, psychological, and transcendent mechanisms by which ayahuasca may exert its anti-addiction effects.

  4. Political market orientation and strategic party postures: Some hypotheses regarding profiles and relationship strengths

    DEFF Research Database (Denmark)

    Ormrod, Robert P.; Henneberg, Stephan C. M.

    2007-01-01

    in the development of political strategies and offerings with which to achieve their organizational goals. In this paper, we introduce two complementary sets of concepts, namely Strategic Political Postures (SPP) (Henneberg 2006a) and Political Market Orientation (PMO) (Ormrod 2005, 2007). Based on these, we develop......, a static level, where hypotheses regarding specific PMO profiles are related to each of the four postures. Secondly, on a dynamic level the relationship strengths between different attitudinal and behavioural constructs of PMO are hypothesised, again for each of the four SPP. Finally, we outline approaches...

  5. Change detection in INAR(p) processes against various alternative hypotheses

    CERN Document Server

    Pap, Gyula

    2011-01-01

    Change in the coefficients or in the mean of the innovation distribution of an INAR(p) process is a sign of disturbance that is important to detect. The methods of this paper can test for change in any one of these quantities separately, or in any collection of them. They are available in forms that make one-sided tests possible, furthermore, they can be used to test for a temporary change. The tests are based on a CUSUM process using conditional least squares estimators of the parameters. Under alternative hypotheses consistency of the tests is proved and the large sample properties of the change-point estimator are also explored.

  6. Molecular Data are Transforming Hypotheses on the Origin and Diversification of Eukaryotes.

    Science.gov (United States)

    Tekle, Yonas I; Parfrey, Laura Wegener; Katz, Laura A

    2009-06-01

    The explosion of molecular data has transformed hypotheses on both the origin of eukaryotes and the structure of the eukaryotic tree of life. Early ideas about the evolution of eukaryotes arose through analyses of morphology by light microscopy and later electron microscopy. Though such studies have proven powerful at resolving more recent events, theories on origins and diversification of eukaryotic life have been substantially revised in light of analyses of molecular data including gene and, increasingly, whole genome sequences. By combining these approaches, progress has been made in elucidating both the origin and diversification of eukaryotes. Yet many aspects of the evolution of eukaryotic life remain to be illuminated.

  7. Advances in the phylogenesis of Agaricales and its higher ranks and strategies for establishing phylogenetic hypotheses

    Institute of Scientific and Technical Information of China (English)

    Rui-lin ZHAO; Dennis E. DESJARDIN; Kasem SOYTONG; Kevin D. HYDE

    2008-01-01

    We present an overview of previous research results on the molecular phylogenetic analyses in Agaricales and its higher ranks (Agaricomycetes/Agaricomycotina/Basidiomycota) along with the most recent treatments of taxonomic systems in these taxa. Establishing phylogenetic hypotheses using DNA sequences, from which an understanding of the natural evolutionary relationships amongst clades may be derived, requires a robust dataset. It has been recognized that single-gene phylogenies may not truly represent organismal phylogenies, but the concordant phylogenetic genealogies from multiple-gene datasets can resolve this problem. The genes commonly used in mushroom phylogenetic research are summarized.

  8. Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons

    Science.gov (United States)

    Westmark, Cara J.

    2017-01-01

    Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition. PMID:28149839

  9. Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons.

    Science.gov (United States)

    Westmark, Cara J

    2016-01-01

    Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition.

  10. Cancer stem cell hypotheses: Impact on modern molecular physiology and pharmacology research

    Indian Academy of Sciences (India)

    Igor Pantic

    2011-12-01

    Although questioned on several occasions, the existence of cancer stem cells (CSCs) has been confirmed by a number of studies on experimental animal models. Nevertheless, it was shown that CSC hypotheses have several limitations and inconsistencies regarding the explanation of CSC origin, CSC identification and isolation, possible heterogeneity within CSC population, as well as methodology issues in some studies that were carried out in order to prove CSC existence. The aim of this article is to give a short and comprehensive review of recent advances concerning CSC hypothesis and to describe its impact on modern molecular physiology and pharmacology research.

  11. New Vehicle Detection Method with Aspect Ratio Estimation for Hypothesized Windows

    Directory of Open Access Journals (Sweden)

    Jisu Kim

    2015-12-01

    Full Text Available All kinds of vehicles have different ratios of width to height, which are called the aspect ratios. Most previous works, however, use a fixed aspect ratio for vehicle detection (VD. The use of a fixed vehicle aspect ratio for VD degrades the performance. Thus, the estimation of a vehicle aspect ratio is an important part of robust VD. Taking this idea into account, a new on-road vehicle detection system is proposed in this paper. The proposed method estimates the aspect ratio of the hypothesized windows to improve the VD performance. Our proposed method uses an Aggregate Channel Feature (ACF and a support vector machine (SVM to verify the hypothesized windows with the estimated aspect ratio. The contribution of this paper is threefold. First, the estimation of vehicle aspect ratio is inserted between the HG (hypothesis generation and the HV (hypothesis verification. Second, a simple HG method named a signed horizontal edge map is proposed to speed up VD. Third, a new measure is proposed to represent the overlapping ratio between the ground truth and the detection results. This new measure is used to show that the proposed method is better than previous works in terms of robust VD. Finally, the Pittsburgh dataset is used to verify the performance of the proposed method.

  12. One year after the Zika virus outbreak in Brazil: from hypotheses to evidence.

    Science.gov (United States)

    Brito, Carlos Alexandre Antunes de; Cordeiro, Marli Tenorio

    2016-01-01

    Zika virusis an arbovirus of the Flaviviridae family with two major strains, an Asian and an African strain. The main vectors involved in the transmission of Zika virus are the Aedes aegypti and Aedes albopictus mosquitoes. Despite its identification, discovered in 1947 in the Zika forest in Uganda, only isolated and sporadic occurrences of human infection were reported within a largely asymptomatic proportion of individuals. The first reported outbreak occurred in 2007 in the Yap Island, which belongs to the Federated States of Micronesia in the Pacific Ocean, and in French Polynesia, where high attack rates occurred and the first cases of associated Guillain-Barré syndrome were reported. From November 2014 to early 2015, the Northeast states of Brazil reported the first outbreaks of Zika virus infection, with laboratory confirmation of Zika virus circulation in April 2015. In the second quarter of 2015, the association between Zika virus infection and neurological symptoms was confirmed in adults. Moreover, in October 2015 a novel suspicion was raised based on clinical and epidemiological observations: that an association between Zika virus infection and neonatal microcephaly may exist. A year after the first reports on Zika virus in Brazil, many hypotheses and much evidence on the patterns of involvement of the disease and its complications have been produced, both in this country and others; other hypotheses still need to be clarified. This review is a synthesis of a new chapter in the history of medicine; it outlines the main results produced.

  13. Habitat structure mediates predation risk for sedentary prey: Experimental tests of alternative hypotheses

    Science.gov (United States)

    Chalfoun, A.D.; Martin, T.E.

    2009-01-01

    Predation is an important and ubiquitous selective force that can shape habitat preferences of prey species, but tests of alternative mechanistic hypotheses of habitat influences on predation risk are lacking. 2. We studied predation risk at nest sites of a passerine bird and tested two hypotheses based on theories of predator foraging behaviour. The total-foliage hypothesis predicts that predation will decline in areas of greater overall vegetation density by impeding cues for detection by predators. The potential-prey-site hypothesis predicts that predation decreases where predators must search more unoccupied potential nest sites. 3. Both observational data and results from a habitat manipulation provided clear support for the potential-prey-site hypothesis and rejection of the total-foliage hypothesis. Birds chose nest patches containing both greater total foliage and potential nest site density (which were correlated in their abundance) than at random sites, yet only potential nest site density significantly influenced nest predation risk. 4. Our results therefore provided a clear and rare example of adaptive nest site selection that would have been missed had structural complexity or total vegetation density been considered alone. 5. Our results also demonstrated that interactions between predator foraging success and habitat structure can be more complex than simple impedance or occlusion by vegetation. ?? 2008 British Ecological Society.

  14. One year after the Zika virus outbreak in Brazil: from hypotheses to evidence

    Directory of Open Access Journals (Sweden)

    Carlos Alexandre Antunes de Brito

    Full Text Available Abstract Zika virusis an arbovirus of the Flaviviridae family with two major strains, an Asian and an African strain. The main vectors involved in the transmission of Zika virus are the Aedes aegypti and Aedes albopictus mosquitoes. Despite its identification, discovered in 1947 in the Zika forest in Uganda, only isolated and sporadic occurrences of human infection were reported within a largely asymptomatic proportion of individuals. The first reported outbreak occurred in 2007 in the Yap Island, which belongs to the Federated States of Micronesia in the Pacific Ocean, and in French Polynesia, where high attack rates occurred and the first cases of associated Guillain-Barré syndrome were reported. From November 2014 to early 2015, the Northeast states of Brazil reported the first outbreaks of Zika virus infection, with laboratory confirmation of Zika virus circulation in April 2015. In the second quarter of 2015, the association between Zika virus infection and neurological symptoms was confirmed in adults. Moreover, in October 2015 a novel suspicion was raised based on clinical and epidemiological observations: that an association between Zika virus infection and neonatal microcephaly may exist. A year after the first reports on Zika virus in Brazil, many hypotheses and much evidence on the patterns of involvement of the disease and its complications have been produced, both in this country and others; other hypotheses still need to be clarified. This review is a synthesis of a new chapter in the history of medicine; it outlines the main results produced.

  15. Ethnic density effects on psychological distress among Latino ethnic groups: an examination of hypothesized pathways.

    Science.gov (United States)

    Bécares, Laia

    2014-11-01

    Studies among US Latinos provide the most consistent evidence of ethnic density effects. However, most studies conducted to date have focused on Mexican Americans, and it is not clear whether ethnic density effects differ across Latino sub-groups, generational status, or measures of ethnic density. In addition, the mechanisms behind ethnic density are not well understood. This study uses a multi-group structural equation modeling approach to analyze the Latino sample from the National Latino and Asian-American Study (n=1940) and examine ethnic density effects on psychological distress among Latino sub-groups, and explore two hypothesized mechanisms: increased neighborhood cohesion and reduced exposure to interpersonal racism. Results of the main effects between ethnic density and health, and of the hypothesized mechanisms, show clear differences across Latino ethnic groups, generational categories and measures of ethnic density. Findings highlight that ethnic density effects and their mechanisms depend on the current and historical context of Latino sub-groups, including reasons for migration and rights upon arrival.

  16. A test of Spielberger's state-trait theory of anger with adolescents: five hypotheses.

    Science.gov (United States)

    Quinn, Colleen A; Rollock, David; Vrana, Scott R

    2014-02-01

    Spielberger's state-trait theory of anger was investigated in adolescents (n = 201, ages 10-18, 53% African American, 47% European American, 48% female) using Deffenbacher's five hypotheses formulated to test the theory in adults. Self-reported experience, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) responses to anger provoking imagery scripts found strong support for the application of this theory to adolescents. Compared with the low trait anger (LTA) group, adolescents with high trait anger (HTA) produced increased HR, SBP, and DBP, and greater self-report of anger to anger imagery (intensity hypothesis) but not greater self-report or cardiovascular reactivity to fear or joy imagery (discrimination hypothesis). The HTA group also reported greater frequency and duration of anger episodes and had longer recovery of SBP response to anger (elicitation hypothesis). The HTA group was more likely to report negative health, social, and academic outcomes (consequence hypothesis). Adolescents with high hostility reported more maladaptive coping with anger, with higher anger-in and anger-out than adolescents with low hostility (negative expression hypothesis). The data on all five hypotheses supported the notion that trait anger is firmly entrenched by the period of adolescence, with few developmental differences noted from the adult literature.

  17. Testing yawning hypotheses in wild populations of two strepsirrhine species: Propithecus verreauxi and Lemur catta.

    Science.gov (United States)

    Zannella, Alessandra; Norscia, Ivan; Stanyon, Roscoe; Palagi, Elisabetta

    2015-11-01

    Yawning, although easily recognized, is difficult to explain. Traditional explanations stressed physiological mechanisms, but more recently, behavioral processes have received increasing attention. This is the first study to test a range of hypotheses on yawning in wild primate populations. We studied two sympatric strepsirrhine species, Lemur catta, and Propithecus verreauxi, of the Ankoba forest (24.99°S, 46.29°E, Berenty reserve) in southern Madagascar. Sexual dimorphism is lacking in both species. However, their differences in ecological and behavioral characteristics facilitate comparative tests of hypotheses on yawning. Our results show that within each species males and females yawned with similar frequencies supporting the Dimorphism Hypothesis, which predicts that low sexual dimorphism leads to little inter-sexual differences in yawning. In support of the State Changing Hypothesis yawning frequencies was linked to the sleep-wake cycle and punctuated transitions from one behavior to another. Accordingly, yawning frequencies were significantly higher in L. catta than in P. verreauxi, because L. catta has a higher basal level of activity and consequently a higher number of behavioral transitions. In agreement with the Anxiety Hypothesis, yawning increased significantly in the 10 min following predatory attacks or aggression. Our findings provide the first empirical evidence of a direct connection between anxiety and yawning in lemurs. Our results show that yawning in these two strepsirrhines occurs in different contexts, but more research will be necessary to determine if yawns are a single, unitary behavior. © 2015 Wiley Periodicals, Inc.

  18. Ever since Klekowski: testing a set of radical hypotheses revives the genetics of ferns and lycophytes.

    Science.gov (United States)

    Haufler, Christopher H

    2014-12-01

    There have been three periods of significant discovery in the exploration of fern and lycophyte genetics. First, during the 1930s, Andersson-Kottö conducted crossing studies on ferns. The publication of Manton's magnum opus on fern chromosomes in 1950 stimulated the second. The third emerged from Klekowski's 1973 American Journal of Botany publication that posed hypotheses linking breeding system dynamics and polyploid genetic architecture. Although Klekowski's assertions (predominant inbreeding and active polyploid genomes) were not supported, his hypotheses served as the impetus for improving our knowledge of the evolutionary mechanisms of ferns and lycophytes. It is now understood that (1) homosporous vascular plants are genetically diploid at high chromosome numbers and (2) both heterosporous and homosporous plants store and release genetic variation through a similar range of breeding systems. However, the seeming paradox of diploid genetic expression in homosporous vascular plants with high chromosome numbers remains unresolved. Ongoing and future research should include (1) more studies of gametophyte biology to elucidate the range and frequency of different breeding systems; (2) genomic analyses and new research on the mechanisms controlling bivalent formation to help discover how and why homosporous plant chromosomes appear so structurally stable; (3) considering whether the frequency of allopolyploidy in lineages can help explain why some are highly polyploid; and (4) chromosome painting studies to identify the dynamics of chromosome behavior in homosporous vascular plants. These open questions and continuing investigations demonstrate the longstanding impact of Klekowski's stimulating contribution.

  19. Confidence Intervals: From tests of statistical significance to confidence intervals, range hypotheses and substantial effects

    Directory of Open Access Journals (Sweden)

    Dominic Beaulieu-Prévost

    2006-03-01

    Full Text Available For the last 50 years of research in quantitative social sciences, the empirical evaluation of scientific hypotheses has been based on the rejection or not of the null hypothesis. However, more than 300 articles demonstrated that this method was problematic. In summary, null hypothesis testing (NHT is unfalsifiable, its results depend directly on sample size and the null hypothesis is both improbable and not plausible. Consequently, alternatives to NHT such as confidence intervals (CI and measures of effect size are starting to be used in scientific publications. The purpose of this article is, first, to provide the conceptual tools necessary to implement an approach based on confidence intervals, and second, to briefly demonstrate why such an approach is an interesting alternative to an approach based on NHT. As demonstrated in the article, the proposed CI approach avoids most problems related to a NHT approach and can often improve the scientific and contextual relevance of the statistical interpretations by testing range hypotheses instead of a point hypothesis and by defining the minimal value of a substantial effect. The main advantage of such a CI approach is that it replaces the notion of statistical power by an easily interpretable three-value logic (probable presence of a substantial effect, probable absence of a substantial effect and probabilistic undetermination. The demonstration includes a complete example.

  20. Student's tutorial on bloom hypotheses in the context of phytoplankton annual cycles.

    Science.gov (United States)

    Behrenfeld, Michael J; Boss, Emmanuel S

    2017-08-08

    Phytoplankton blooms are elements in repeating annual cycles of phytoplankton biomass and they have significant ecological and biogeochemical consequences. Temporal changes in phytoplankton biomass are governed by complex predator-prey interactions and physically-driven variations in upper water-column the growth conditions (light, nutrient, temperature). Understanding these dependencies is fundamental to assessing future change in bloom frequency, duration, and magnitude and thus represents a quintessential challenge in global change biology. A variety of contrasting hypotheses have emerged in the literature to explain phytoplankton blooms, but over time the basic tenets of these hypotheses have become unclear. Here, we provide a 'tutorial' on the development of these concepts and the fundamental elements distinguishing each hypothesis. The intent of this tutorial is to provide a useful background and set of tools for reading the bloom literature and to give some suggestions for future studies. Our tutorial is written for 'students' at all stages of their career. We hope it is equally useful and interesting to those with only a cursory interest in blooms as those deeply immersed in the challenge of understanding the temporal dynamics of phytoplankton biomass and predicting its future change. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. The evolution of parental care in insects: A test of current hypotheses

    Science.gov (United States)

    Gilbert, James D J; Manica, Andrea

    2015-01-01

    Which sex should care for offspring is a fundamental question in evolution. Invertebrates, and insects in particular, show some of the most diverse kinds of parental care of all animals, but to date there has been no broad comparative study of the evolution of parental care in this group. Here, we test existing hypotheses of insect parental care evolution using a literature-compiled phylogeny of over 2000 species. To address substantial uncertainty in the insect phylogeny, we use a brute force approach based on multiple random resolutions of uncertain nodes. The main transitions were between no care (the probable ancestral state) and female care. Male care evolved exclusively from no care, supporting models where mating opportunity costs for caring males are reduced—for example, by caring for multiple broods—but rejecting the “enhanced fecundity” hypothesis that male care is favored because it allows females to avoid care costs. Biparental care largely arose by males joining caring females, and was more labile in Holometabola than in Hemimetabola. Insect care evolution most closely resembled amphibian care in general trajectory. Integrating these findings with the wealth of life history and ecological data in insects will allow testing of a rich vein of existing hypotheses. PMID:25825047

  2. The evolution of parental care in insects: A test of current hypotheses.

    Science.gov (United States)

    Gilbert, James D J; Manica, Andrea

    2015-05-01

    Which sex should care for offspring is a fundamental question in evolution. Invertebrates, and insects in particular, show some of the most diverse kinds of parental care of all animals, but to date there has been no broad comparative study of the evolution of parental care in this group. Here, we test existing hypotheses of insect parental care evolution using a literature-compiled phylogeny of over 2000 species. To address substantial uncertainty in the insect phylogeny, we use a brute force approach based on multiple random resolutions of uncertain nodes. The main transitions were between no care (the probable ancestral state) and female care. Male care evolved exclusively from no care, supporting models where mating opportunity costs for caring males are reduced-for example, by caring for multiple broods-but rejecting the "enhanced fecundity" hypothesis that male care is favored because it allows females to avoid care costs. Biparental care largely arose by males joining caring females, and was more labile in Holometabola than in Hemimetabola. Insect care evolution most closely resembled amphibian care in general trajectory. Integrating these findings with the wealth of life history and ecological data in insects will allow testing of a rich vein of existing hypotheses. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  3. Testing hypotheses of bird extinctions at Rio Palenque, Ecuador, with informal species lists.

    Science.gov (United States)

    Pearson, David L; Anderson, Corey Devin; Mitchell, Brian R; Rosenberg, Michael S; Navarrete, Ronald; Coopmans, Paul

    2010-04-01

    Informally gathered species lists are a potential source of data for conservation biology, but most remain unused because of questions of reliability and statistical issues. We applied two alternative analytical methods (contingency tests and occupancy modeling) to a 35-year data set (1973-2007) to test hypotheses about local bird extinction. We compiled data from bird lists collected by expert amateurs and professional scientists in a 2-km(2) fragment of lowland tropical forest in coastal Ecuador. We tested the effects of the following on local extinction: trophic level, sociality, foraging specialization, light tolerance, geographical range area, and biogeographic source. First we assessed extinction on the basis of the number of years in which a species was not detected on the site and used contingency tests with each factor to compare the frequency of expected and observed extinction events among different species categories. Then we defined four multiyear periods that reflected different stages of deforestation and isolation of the study site and used occupancy modeling to test extinction hypotheses singly and in combination. Both types of analyses supported the biogeographic source hypothesis and the species-range hypothesis as causes of extinction; however, occupancy modeling indicated the model incorporating all factors except foraging specialization best fit the data.

  4. Genomic rearrangements in trypanosomatids: an alternative to the "one gene" evolutionary hypotheses?

    Directory of Open Access Journals (Sweden)

    JC Dujardin

    2000-08-01

    Full Text Available Most molecular trees of trypanosomatids are based on point mutations within DNA sequences. In contrast, there are very few evolutionary studies considering DNA (re arrangement as genetic characters. Waiting for the completion of the various parasite genome projects, first information may already be obtained from chromosome size-polymorphism, using the appropriate algorithms for data processing. Three illustrative models are presented here. First, the case of Leishmania (Viannia braziliensis/L. (V. peruviana is described. Thanks to a fast evolution rate (due essentially to amplification/deletion of tandemly repeated genes, molecular karyotyping seems particularly appropriate for studying recent evolutionary divergence, including eco-geographical diversification. Secondly, karyotype evolution is considered at the level of whole genus Leishmania. Despite the fast chromosome evolution rate, there is qualitative congruence with MLEE- and RAPD-based evolutionary hypotheses. Significant differences may be observed between major lineages, likely corresponding to major and less frequent rearrangements (fusion/fission, translocation. Thirdly, comparison is made with Trypanosoma cruzi. Again congruence is observed with other hypotheses and major lineages are delineated by significant chromosome rearrangements. The level of karyotype polymorphism within that "species" is similar to the one observed in "genus" Leishmania. The relativity of the species concept among these two groups of parasites is discussed.

  5. No evidence for bilingual cognitive advantages: A test of four hypotheses.

    Science.gov (United States)

    von Bastian, Claudia C; Souza, Alessandra S; Gade, Miriam

    2016-02-01

    The question whether being bilingual yields cognitive benefits is highly controversial with prior studies providing inconsistent results. Failures to replicate the bilingual advantage have been attributed to methodological factors such as comparing dichotomous groups and measuring cognitive abilities separately with single tasks. Therefore, the authors evaluated the 4 most prominent hypotheses of bilingual advantages for inhibitory control, conflict monitoring, shifting, and general cognitive performance by assessing bilingualism on 3 continuous dimensions (age of acquisition, proficiency, and usage) in a sample of 118 young adults and relating it to 9 cognitive abilities each measured by multiple tasks. Linear mixed-effects models accounting for multiple sources of variance simultaneously and controlling for parents' education as an index of socioeconomic status revealed no evidence for any of the 4 hypotheses. Hence, the authors' results suggest that bilingual benefits are not as broad and as robust as has been previously claimed. Instead, earlier effects were possibly due to task-specific effects in selective and often small samples.

  6. Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses

    NARCIS (Netherlands)

    Visscher, P. M.; Goddard, M. E.; Derks, E. M.; Wray, N. R.

    2012-01-01

    In this article, we review some of the data that contribute to our understanding of the genetic architecture of psychiatric disorders. These include results from evolutionary modelling (hence no data), the observed recurrence risk to relatives and data from molecular markers. We briefly discuss the

  7. Borderline disorder and attachment pathology.

    Science.gov (United States)

    West, M; Keller, A; Links, P; Patrick, J

    1993-02-01

    In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder.

  8. Autistic disorder: a neuropsychological enigma.

    Science.gov (United States)

    Huebner, R A

    1992-06-01

    Autism is increasingly viewed as an expression of an unidentified neurological disorder. Because understanding of neurological dysfunction is basic to evaluation and treatment in occupational therapy, this article provides a comprehensive and critical review of the literature since 1985 concerning the neuropsychology of autistic disorder. The research is categorized into four basic types: (a) neuropsychological testing of functional abilities, (b) treatment studies based on neuropsychological hypotheses, (c) autistic-related diseases and genetic disorders, and (d) neuroanatomical and neurophysiological studies. The research shows a spectrum of neurological impairments within the brain stem, cerebellum, midbrain, and frontal lobe. These impairments are associated with deficits in socioemotional skills, sensory processing, motor planning, and cognitive flexibility. This research suggests that persons with autistic disorder need evaluation and treatment of a wide spectrum of functional deficits.

  9. Development of working hypotheses linking management of the Missouri River to population dynamics of Scaphirhynchus albus (pallid sturgeon)

    Science.gov (United States)

    Jacobson, Robert B.; Parsley, Michael J.; Annis, Mandy L.; Colvin, Michael E.; Welker, Timothy L.; James, Daniel A.

    2016-01-20

    This report documents a process of filtering of hypotheses that relate Missouri River Scaphirhynchus albus (pallid sturgeon) population dynamics to management actions including flow alterations, channel reconfigurations, and pallid sturgeon population augmentation. The filtering process was a partnership among U.S. Geological Survey, U.S. Army Corps of Engineers, and U.S. Fish and Wildlife Service to contribute to the Missouri River Recovery Management Plan process. The objective of the filtering process was to produce a set of hypotheses with high relevance to pallid sturgeon population dynamics and decision making on the Missouri River. The Missouri River Pallid Sturgeon Effects Analysis team filtered hundreds of potential hypotheses implicit in conceptual ecological models to develop a set of 40 candidate dominant hypotheses that were identified by experts as being important in pallid sturgeon population dynamics. Using a modified Delphi process and additional expert opinion, the team reduced this set of hypotheses to 23 working dominant hypotheses. We then matched the 23 hypotheses with management actions that could influence the biotic outcomes, resulting in as many as 176 potential effects between management actions and pallid sturgeon in the Missouri River. This number was consolidated to a candidate set of 53 working management hypotheses because some management actions applied to multiple life stages of the pallid sturgeon. We used an additional round of expert surveys to identify a set of 30 working management hypotheses. Finally, the set of working management hypotheses was filtered by the U.S. Army Corps of Engineers, Missouri River Recovery Program for actions that were within the agency’s authority and jurisdiction. This round resulted in a set of 21 hypotheses for initial modeling of linkages from management to pallid sturgeon population responses.

  10. Attribution of hydrological change using the Method of Multiple Working Hypotheses

    Science.gov (United States)

    Harrigan, Shaun

    2017-04-01

    The methods we have developed for managing our long-term water supply and protection from extreme hydrological events such as droughts and floods have been founded on the assumption that the hydrological cycle operates under natural conditions. However, it increasingly recognised that humans have the potential to induce significant change in almost every component of the hydrological cycle, for example, climate change, land-use change, and river engineering. Statistical detection of change in streamflow, outside that of natural variability, is an important scientific endeavour, but it does not tell us anything about the drivers of change. Attribution is the process of establishing the most likely cause(s) of a detected change - the why. Attribution is complex due to the integrated nature of streamflow and the proliferation of multiple possible drivers. It is perhaps this complexity, combined with few proven theoretical approaches to this problem in hydrology that has led to others to call for "more efforts and scientific rigour" (Merz et al., 2012). It is easier to limit the cause of a detected change to a single driver, or use simple correlation analysis alone as evidence of causation. It is convenient when the direction of a change in streamflow is consistent with what is expected from a well-known driver such as climate change. Over a century ago, Thomas Chamberlin argued these types of issues were common in many disciplines given how the scientific method is approached in general. His 1890 article introduces the Method of Multiple Working Hypotheses (MMWH) in an attempt to limit our confirmation bias and strives for increased objectivity. This presentation will argue that the MMWH offers an attractive theoretical approach to the attribution of hydrological change in modern hydrology as demonstrated through a case study of a well-documented change point in streamflow within the Boyne Catchment in Ireland. Further Reading Chamberlin, T. C.: The Method of Multiple

  11. Anxiety disorders.

    Science.gov (United States)

    Craske, Michelle G; Stein, Murray B; Eley, Thalia C; Milad, Mohammed R; Holmes, Andrew; Rapee, Ronald M; Wittchen, Hans-Ulrich

    2017-05-04

    Anxiety disorders constitute the largest group of mental disorders in most western societies and are a leading cause of disability. The essential features of anxiety disorders are excessive and enduring fear, anxiety or avoidance of perceived threats, and can also include panic attacks. Although the neurobiology of individual anxiety disorders is largely unknown, some generalizations have been identified for most disorders, such as alterations in the limbic system, dysfunction of the hypothalamic-pituitary-adrenal axis and genetic factors. In addition, general risk factors for anxiety disorders include female sex and a family history of anxiety, although disorder-specific risk factors have also been identified. The diagnostic criteria for anxiety disorders varies for the individual disorders, but are generally similar across the two most common classification systems: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the International Classification of Diseases, Tenth Edition (ICD-10). Despite their public health significance, the vast majority of anxiety disorders remain undetected and untreated by health care systems, even in economically advanced countries. If untreated, these disorders are usually chronic with waxing and waning symptoms. Impairments associated with anxiety disorders range from limitations in role functioning to severe disabilities, such as the patient being unable to leave their home.

  12. On the particular vulnerability of face recognition to aging: A review of three hypotheses

    Directory of Open Access Journals (Sweden)

    Isabelle eBoutet

    2015-08-01

    Full Text Available Age-related face recognition deficits are characterized by high false alarms to unfamiliar faces, are not as pronounced for other complex stimuli, and are only partially related to general age-related impairments in cognition. This paper reviews some of the underlying processes likely to be implicated in theses deficits by focusing on areas where contradictions abound as a means to highlight avenues for future research. Research pertaining to three following hypotheses is presented: (i perceptual deterioration, (ii encoding of configural information, and (iii difficulties in recollecting contextual information. The evidence surveyed provides support for the idea that all three factors are likely to contribute, under certain conditions, to the deficits in face recognition seen in older adults. We discuss how these different factors might interact in the context of a generic framework of the different stages implicated in face recognition. Several suggestions for future investigations are outlined.

  13. An exploration into the home field, global advantage and liability of unfamiliarness hypotheses in multinational banking

    Directory of Open Access Journals (Sweden)

    Fadzlan Sufian

    2011-09-01

    Full Text Available This paper seeks to expand the efficiency paradigm of the eclectic theory in multinational banking within the context of a developing country banking sector. We employ the Data Envelopment Analysis (DEA method to examine the efficiency of multinational banks operating in the Malaysian banking sector from 1995 to 2007. We then employ the panel regression analysis to examine the impact of origins on bank efficiency. We find foreign banks from North America to be the most efficient banking group, providing support to the ‘limited form’ of the global advantage hypothesis. On the other hand, we do not find evidence on both the liability of unfamiliarness and home field advantage hypotheses.

  14. A dynamic procedure based on the scale-similarity hypotheses for large-eddy simulation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Bing; CUI Guixiang; CHEN Naixiang

    2007-01-01

    Current dynamic procedures in large-eddy simulation treat the two subgrid-scale stresses in the Germano identity with the same subgrid base model.Thus to get the base model coefficient,the coefficient must be assumed to be constant for test filter operation.However,since the coefficient has sharp fluctuations,this assumption causes some inconsistence.A new dynamic procedure was developed in which these two stresses are modeled by the base model and the scale-similarity hypotheses respectively.Thus the need for the assumption is removed and consistence is restored.The new procedure is tested in the large-eddy simulation of a lid-driven cavity flow at Reynolds number of 10,000.The results show that the new procedure can both improve the prediction of statistics of the flow and effectively relieve the singularity of subgrid-scale (SGS) model coefficient.

  15. Attachment and parental divorce: a test of the diffusion and sensitive period hypotheses.

    Science.gov (United States)

    Fraley, R Chris; Heffernan, Marie E

    2013-09-01

    One of the assumptions of attachment theory is that disruptions in parental relationships are prospectively related to insecure attachment patterns in adulthood. The majority of research that has evaluated this hypothesis, however, has been based on retrospective reports of the quality of relationships with parents-research that is subject to retrospective biases. In the present research, the authors examined the impact of parental divorce-an event that can be assessed relatively objectively-on attachment patterns in adulthood across two samples. The data indicate that parental divorce has selective rather than diffuse implications for insecure attachment. Namely, parental divorce was more strongly related to insecure relationships with parents in adulthood than insecure relationships with romantic partners or friends. In addition, parental insecurity was most pronounced when parental divorce took place in early childhood. This finding is consistent with hypotheses about sensitive periods in attachment development.

  16. Combining soft decision algorithms and scale-sequential hypotheses pruning for object recognition

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V.P.; Manolakos, E.S. [Northeastern Univ., Boston, MA (United States)

    1996-12-31

    This paper describes a system that exploits the synergy of Hierarchical Mixture Density (HMD) estimation with multiresolution decomposition based hypothesis pruning to perform efficiently joint segmentation and labeling of partially occluded objects in images. First we present the overall structure of the HMD estimation algorithm in the form of a recurrent neural network which generates the posterior probabilities of the various hypotheses associated with the image. Then in order to reduce the large memory and computation requirement we propose a hypothesis pruning scheme making use of the orthonormal discrete wavelet transform for dimensionality reduction. We provide an intuitive justification for the validity of this scheme and present experimental results and performance analysis on real and synthetic images to verify our claims.

  17. Comments and hypotheses on the mechanism of methane against ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    He Li

    2017-01-01

    Full Text Available As we all know, methane is a kind of fuel. Previous studies have shown that methanogens in the colon can react with carbon dioxide and hydrogen to produce methane. In a recent study, the anti-inflammatory effects of methane were shown in a dog model of small intestinal ischemia/reperfusion. The mechanism of this anti-inflammatory effect needs further investigation. Recently, studies have shown anti-inflammatory, anti-apoptotic and anti-oxidative effects of methane on different organic injuries. According to the results of these studies, we hypothesize that the initial effects of methane are to react with free radicals and enhance expression of antioxidase through forkhead box transcription factor class O pathway. The anti-inflammatory effect is following the anti-oxidative effect, and the anti-apoptotic effect relies on anti-inflammatory and anti-oxidative effects.

  18. Covariation between personalities and individual differences in coping with stress: Converging evidence and hypotheses

    Directory of Open Access Journals (Sweden)

    Claudio CARERE, Doretta CARAMASCHI, Tim W. FAWCETT

    2010-12-01

    Full Text Available In the past decade there has been a profusion of studies highlighting covariation between individual differences in stress physiology and behavioural profiles, here called personalities. Such individual differences in ways of coping with stress are relevant both in biomedicine, since different personalities may experience a different stress and disease vulnerability, and in behavioural ecology, since their adaptive value and evolutionary maintenance are the subject of debate. However, the precise way in which individual stress differences and personalities are linked is unclear. Here we provide an updated overview of this covariation across different species and taxa, consider its functional significance and present working hypotheses for how behavioural and physiological responses to stress might be causally linked, affecting life-history traits such as dispersal and life-span [Current Zoology 56 (6: 728–740, 2010].

  19. Age and motives for volunteering: testing hypotheses derived from socioemotional selectivity theory.

    Science.gov (United States)

    Okun, Morris A; Schultz, Amy

    2003-06-01

    Following a meta-analysis of the relations between age and volunteer motives (career, understanding, enhancement, protective, making friends, social, and values), the authors tested hypotheses derived from socioemotional selectivity theory regarding the effects of age on these volunteer motives. The Volunteer Functions Inventory was completed by 523 volunteers from 2 affiliates of the International Habitat for Humanity. Multiple regression analyses revealed, as predicted, that as age increases, career and understanding volunteer motivation decrease and social volunteer motivation increases. Contrary to expectations, age did not contribute to the prediction of enhancement, protective, and values volunteer motivations and the relation between age and making friends volunteer motivation was nonlinear. The results were discussed in the context of age-differential and age-similarity perspectives on volunteer motivation.

  20. Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons - a scoping review.

    Science.gov (United States)

    Bliddal, H; Leeds, A R; Christensen, R

    2014-07-01

    Obesity is widely acknowledged as a risk factor for both the incidence and progression of osteoarthritis, and has a negative influence on outcomes. Loss of at least 10% of body weight, coupled with exercise, is recognized as a cornerstone in the management of obese patients with osteoarthritis, and can lead to significant improvement in symptoms, pain relief, physical function and health-related quality of life. However, questions still remain surrounding optimal management. Given the significant health, social and economic burden of osteoarthritis, especially in obese patients, it is imperative to advance our knowledge of osteoarthritis and obesity, and apply this to improving care and outcomes. This paper overviews what is already known about osteoarthritis and obesity, discusses current key challenges and ongoing hypotheses arising from research in these areas, and finally, postulates what the future may hold in terms of new horizons for obese patients with osteoarthritis.

  1. Recruitment processes in Baltic sprat - A re-evaluation of GLOBEC Germany hypotheses

    DEFF Research Database (Denmark)

    Voss, Rudiger; Peck, M.A.; Hinrichsen, H.-H.

    2012-01-01

    , and modeling studies to re-evaluate these hypotheses for the Balticsprat stock. Recruitment success was quite different in the 2 years investigated. Despite a lower spawning stock biomass in 2003, the total number of recruits was almost 2-fold higher that year compared to 2002. The higher recruitment success...... in 2003 could be attributed to enhanced survival success during the post-larval/juvenile stage, a life phase that appears to be critical for recruitment dynamics. In the state of the Baltic ecosystem during the period of investigation, we consider bottom-up control (e.g. temperature, prey abundance......) to be more important than top-down control (predation mortality). This ranking in importance does not vary seasonally. Prevailing water circulation patterns and the transport dynamics of larval cohorts have a strong influence on spratrecruitment success. Pronounced transport to coastal areas is detrimental...

  2. Science from evaluation: testing hypotheses about differential effects of three youth-focused suicide prevention trainings.

    Science.gov (United States)

    Coleman, Daniel; Del Quest, Aisling

    2015-01-01

    As part of an evaluation component of a youth suicide prevention, a quasi-experimental repeated measures design tested hypotheses about two brief suicide prevention gatekeeper trainings (Question, Persuade, Refer [QPR] and RESPONSE) and one longer suicide intervention skills training (Applied Suicide Intervention Skills Training [ASIST]). All three trainings showed large changes in prevention attitudes and self-efficacy, largely maintained at follow-up. ASIST trainees had large increases in asking at-risk youth about suicide at follow-up. Convergent with other research, modeling and role-play in training are crucial to increased prevention behaviors. Practice and research implications are discussed, including social work roles in suicide prevention and research.

  3. Impact Of Job Analysis On Job Performance: Analysis Of A Hypothesized Model

    Directory of Open Access Journals (Sweden)

    Rehman Safdar

    2011-01-01

    Full Text Available Researchers have developed a relationship between HRM practices and organizational performance, but the relationship between HRM practice like job analysis – employee Job performance remains unexplored. This paper, based on a study of employees of Pakistan Public sector regulatory authorities of telecommunication, oil and gas, power, media, security exchange, banking sector and organizations being regulated by these authorities is an attempt to develop and test a hypothesized model linking HR importance of job analysis with employee job performance. Survey results of 568 employees indicated that practice of job analysis was strongly related to employee job performance. The findings suggest that an organisation-wide policy of job analysis is an important source of competitive advantage in its own right, and requires due attention of HR professionals. The study extends the findings of the HR–employee job performance research pursued in Western countries to a non-Western context.

  4. Testing alternative hypotheses regarding the association between behavioral inhibition and language development in toddlerhood.

    Science.gov (United States)

    Smith Watts, Ashley K; Patel, Deepika; Corley, Robin P; Friedman, Naomi P; Hewitt, John K; Robinson, JoAnn L; Rhee, Soo H

    2014-01-01

    Studies have reported an inverse association between language development and behavioral inhibition or shyness across childhood, but the direction of this association remains unclear. This study tested alternative hypotheses regarding this association in a large sample of toddlers. Data on behavioral inhibition and expressive and receptive language abilities were collected from 816 twins at ages 14, 20, and 24 months. Growth and regression models were fit to the data to assess the longitudinal associations between behavioral inhibition and language development from 14 to 24 months. Overall, there were significant associations between behavioral inhibition and expressive language, and minimal associations with receptive language, indicating that the association is better explained by reticence to respond rather than deficient language development. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

  5. Molecular group dynamics study on slip flow of thin fluid film based on the Hamaker hypotheses

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The thin fluid film was assumed to consist of a number of spherical fluid molecular groups and the attractive forces of molecular group pairs were calculated by the derived equation according to the three Hamaker homogeneous material hypotheses. Regarding each molecular group as a dynamics individual, the simulation method for the shearing motion of multilayer fluid molecular groups, which was initiated by two moving walls, was proposed based on the Verlet velocity iterative algorithm. The simulations reveal that the velocities of fluid molecular groups change about their respective mean velocities within a narrow range in steady state. It is also found that the velocity slips occur at the wall boundary and in a certain number of fluid film layers close to the wall. Because the dimension of molecular group and the number of group layers are not restricted, the hypothetical thickness of fluid film model can be enlarged from nanometer to micron by using the proposed simulation method.

  6. Cultural group selection is plausible, but the predictions of its hypotheses should be tested with real-world data.

    Science.gov (United States)

    Turchin, Peter; Currie, Thomas E

    2016-01-01

    The evidence compiled in the target article demonstrates that the assumptions of cultural group selection (CGS) theory are often met, and it is therefore a useful framework for generating plausible hypotheses. However, more can be said about how we can test the predictions of CGS hypotheses against competing explanations using historical, archaeological, and anthropological data.

  7. Organizational Learning and Innovation Performance: A Review of the Literature and the Development of a Conceptual Framework and Research Hypotheses

    Science.gov (United States)

    Wang, Yu-Lin; Ellinger, Andrea D.

    2008-01-01

    The purpose of this paper is to develop a conceptual framework and research hypotheses based upon a thorough review of the conceptual and limited published empirical research in the organizational learning and innovation performance literatures. Hypotheses indicate the relationships between organizational learning, its antecedent, perception of…

  8. Postulating hypotheses in experimental doctoral dissertations on Applied Linguistics: A qualitative investigation into rhetorical shifts and linguistic mechanisms

    Directory of Open Access Journals (Sweden)

    Jason Miin-Hwa Lim

    2014-03-01

    Full Text Available The extent to which research hypotheses need to be incorporated in experimental studies often becomes a subject of discussion among academics supervising the writing of theses and dissertations. While writers are concerned about how hypotheses can be strategically linked with other elements in research reports to effectively present an introductory chapter, instructors are considering ways of guiding learners to use the appropriate language in postulating research hypotheses. Using an analytical framework developed by Swales (1990 & 2004 and specialist informants’ qualitative data, this largely qualitative investigation looks into a corpus of experimental doctoral dissertations submitted to 32 American universities from 2001 to 2009 in order to ascertain (i the degree to which research hypotheses need to be presented in dissertation introductions, (ii how hypotheses are strategically linked with other rhetorical segments, and (iii the salient linguistic mechanisms used to achieve the communicative functions. This study has revealed (i how writers shift from pertinent communicative moves to the postulation of hypotheses, and (ii the gamut of major language choices employed to postulate these hypotheses. The findings can be used to prepare teaching materials that help learners comprehend and employ the rhetorical strategies and linguistic mechanisms needed in postulating hypotheses in research reports.

  9. Improving the scale and precision of hypotheses to explain root foraging ability.

    Science.gov (United States)

    Kembel, Steven W; De Kroon, Hans; Cahill, James F; Mommer, Liesje

    2008-06-01

    Numerous hypotheses have been proposed to explain the wide variation in the ability of plants to forage for resources by proliferating roots in soil nutrient patches. Comparative analyses have found little evidence to support many of these hypotheses, raising the question of what role resource-foraging ability plays in determining plant fitness and community structure. In the present viewpoint, we respond to Grime's (2007; Annals of Botany 99: 1017-1021) suggestion that we misinterpreted the scope of the scale-precision trade-off hypothesis, which states that there is a trade-off between the spatial scale over which plant species forage and the precision with which they are able to proliferate roots in resource patches. We use a meta-analysis of published foraging scale-precision correlations to demonstrate that there is no empirical support for the scale-precision trade-off hypothesis. Based on correlations between foraging precision and various plant morphological and ecophysiological traits, we found that foraging precision forms part of the 'fast' suite of plant traits related to rapid growth rates and resource uptake rates. We suggest there is a need not only to examine correlations between foraging precision and other plant traits, but to expand our notion of what traits might be important in determining the resource-foraging ability of plants. By placing foraging ability in the broader context of plant traits and resource economy strategies, it will be possible to develop a new and empirically supported framework to understand how plasticity in resource uptake and allocation affect plant fitness and community structure.

  10. The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions

    Directory of Open Access Journals (Sweden)

    Thiele Ines

    2011-10-01

    Full Text Available Abstract Background Metabolic network reconstructions formalize our knowledge of metabolism. Gaps in these networks pinpoint regions of metabolism where biological components and functions are "missing." At the same time, a major challenge in the post genomic era involves characterisation of missing biological components to complete genome annotation. Results We used the human metabolic network reconstruction RECON 1 and established constraint-based modelling tools to uncover novel functions associated with human metabolism. Flux variability analysis identified 175 gaps in RECON 1 in the form of blocked reactions. These gaps were unevenly distributed within metabolic pathways but primarily found in the cytosol and often caused by compounds whose metabolic fate, rather than production, is unknown. Using a published algorithm, we computed gap-filling solutions comprised of non-organism specific metabolic reactions capable of bridging the identified gaps. These candidate solutions were found to be dependent upon the reaction environment of the blocked reaction. Importantly, we showed that automatically generated solutions could produce biologically realistic hypotheses of novel human metabolic reactions such as of the fate of iduronic acid following glycan degradation and of N-acetylglutamate in amino acid metabolism. Conclusions The results demonstrate how metabolic models can be utilised to direct hypotheses of novel metabolic functions in human metabolism; a process that we find is heavily reliant upon manual curation and biochemical insight. The effectiveness of a systems approach for novel biochemical pathway discovery in mammals is demonstrated and steps required to tailor future gap filling algorithms to mammalian metabolic networks are proposed.

  11. Testing phylogenetic hypotheses of the subgenera of the freshwater crayfish genus Cambarus (Decapoda: Cambaridae.

    Directory of Open Access Journals (Sweden)

    Jesse W Breinholt

    Full Text Available BACKGROUND: The genus Cambarus is one of three most species rich crayfish genera in the Northern Hemisphere. The genus has its center of diversity in the Southern Appalachians of the United States and has been divided into 12 subgenera. Using Cambarus we test the correspondence of subgeneric designations based on morphology used in traditional crayfish taxonomy to the underlying evolutionary history for these crayfish. We further test for significant correlation and explanatory power of geographic distance, taxonomic model, and a habitat model to estimated phylogenetic distance with multiple variable regression. METHODOLOGY/PRINCIPAL FINDINGS: We use three mitochondrial and one nuclear gene regions to estimate the phylogenetic relationships for species within the genus Cambarus and test evolutionary hypotheses of relationships and associated morphological and biogeographical hypotheses. Our resulting phylogeny indicates that the genus Cambarus is polyphyletic, however we fail to reject the monophyly of Cambarus with a topology test. The majority of the Cambarus subgenera are rejected as monophyletic, suggesting the morphological characters used to define those taxa are subject to convergent evolution. While we found incongruence between taxonomy and estimated phylogenetic relationships, a multiple model regression analysis indicates that taxonomy had more explanatory power of genetic relationships than either habitat or geographic distance. CONCLUSIONS: We find convergent evolution has impacted the morphological features used to delimit Cambarus subgenera. Studies of the crayfish genus Orconectes have shown gonopod morphology used to delimit subgenera is also affected by convergent evolution. This suggests that morphological diagnoses based on traditional crayfish taxonomy might be confounded by convergent evolution across the cambarids and has little utility in diagnosing relationships or defining natural groups. We further suggest that

  12. Historical and contemporary hypotheses on the development of oral diseases: are we there yet?

    Directory of Open Access Journals (Sweden)

    Bob T. Rosier

    2014-07-01

    Full Text Available Dental plaque is an oral biofilm that much like the rest of our microbiome has a role in health and disease. Specifically, it is the cause of very common oral diseases such as caries, gingivitis and periodontitis. The ideas about oral disease development have evolved over time with the techniques to analyze these changes. In the 19th century, scientists could not identify bacteria related to disease due to the lack of technology. This led to the Non-Specific Plaque Hypothesis or the idea that the accumulation of dental plaque was responsible for oral disease without discriminating between the levels of virulence of bacteria. In the 20th century these ideas evolved with the techniques to analyze the changes from health to disease. The first common hypothesis was the Specific Plaque Hypothesis (1976 proposing that only a few species of the total microflora are actively involved in disease. Secondly, the Non-Specific Plaque Hypothesis was updated (1986 and the idea that the overall activity of the total microflora could lead to disease, was enriched by taking into account difference in virulence among bacteria. Then, a hypothesis was considered that combines key concepts of the earlier two hypotheses: the Ecological Plaque Hypothesis (1994, which proposes that disease is the result of an imbalance in the microflora by ecological stress resulting in an enrichment of certain disease-related micro-organisms. Finally, the recent Keystone-Pathogen Hypothesis (2012 proposes that certain low-abundance microbial pathogens can cause inflammatory disease by interfering with the host immune system and remodeling the microbiota. In this comprehensive review, we describe how these different hypotheses, and the ideas around them, arose and test their current applicability to the understanding of the development of oral disease. Finally, we conclude that an all-encompassing ecological hypothesis explaining the shifts from health to disease is still lacking.

  13. Phylogeny and classification of the trapdoor spider genus Myrmekiaphila: an integrative approach to evaluating taxonomic hypotheses.

    Directory of Open Access Journals (Sweden)

    Ashley L Bailey

    Full Text Available BACKGROUND: Revised by Bond and Platnick in 2007, the trapdoor spider genus Myrmekiaphila comprises 11 species. Species delimitation and placement within one of three species groups was based on modifications of the male copulatory device. Because a phylogeny of the group was not available these species groups might not represent monophyletic lineages; species definitions likewise were untested hypotheses. The purpose of this study is to reconstruct the phylogeny of Myrmekiaphila species using molecular data to formally test the delimitation of species and species-groups. We seek to refine a set of established systematic hypotheses by integrating across molecular and morphological data sets. METHODS AND FINDINGS: Phylogenetic analyses comprising Bayesian searches were conducted for a mtDNA matrix composed of contiguous 12S rRNA, tRNA-val, and 16S rRNA genes and a nuclear DNA matrix comprising the glutamyl and prolyl tRNA synthetase gene each consisting of 1348 and 481 bp, respectively. Separate analyses of the mitochondrial and nuclear genome data and a concatenated data set yield M. torreya and M. millerae paraphyletic with respect to M. coreyi and M. howelli and polyphyletic fluviatilis and foliata species groups. CONCLUSIONS: Despite the perception that molecular data present a solution to a crisis in taxonomy, studies like this demonstrate the efficacy of an approach that considers data from multiple sources. A DNA barcoding approach during the species discovery process would fail to recognize at least two species (M. coreyi and M. howelli whereas a combined approach more accurately assesses species diversity and illuminates speciation pattern and process. Concomitantly these data also demonstrate that morphological characters likewise fail in their ability to recover monophyletic species groups and result in an unnatural classification. Optimizations of these characters demonstrate a pattern of "Dollo evolution" wherein a complex character

  14. Incentivizing Blood Donation: Systematic Review and Meta-Analysis to Test Titmuss’ Hypotheses

    Science.gov (United States)

    2013-01-01

    Objectives: Titmuss hypothesized that paying blood donors would reduce the quality of the blood donated and would be economically inefficient. We report here the first systematic review to test these hypotheses, reporting on both financial and nonfinancial incentives. Method: Studies deemed eligible for inclusion were peer-reviewed, experimental studies that presented data on the quantity (as a proxy for efficiency) and quality of blood donated in at least two groups: those donating blood when offered an incentive, and those donating blood with no offer of an incentive. The following were searched: MEDLINE, EMBASE and PsycINFO using OVID SP, CINAHL via EBSCO and CENTRAL, the Cochrane Library, Econlit via EBSCO, JSTOR Health and General Science Collection, and Google. Results: The initial search yielded 1100 abstracts, which resulted in 89 full papers being assessed for eligibility, of which seven studies, reported in six papers, met the inclusion criteria. The included studies involved 93,328 participants. Incentives had no impact on the likelihood of donation (OR = 1.22 CI 95% 0.91–1.63; p = .19). There was no difference between financial and nonfinancial incentives in the quantity of blood donated. Of the two studies that assessed quality of blood, one found no effect and the other found an adverse effect from the offer of a free cholesterol test (β = 0.011 p < .05). Conclusion: The limited evidence suggests that Titmuss’ hypothesis of the economic inefficiency of incentives is correct. There is insufficient evidence to assess their likely impact on the quality of the blood provided. PMID:24001244

  15. Incentivizing blood donation: systematic review and meta-analysis to test Titmuss' hypotheses.

    Science.gov (United States)

    Niza, Claudia; Tung, Burcu; Marteau, Theresa M

    2013-09-01

    Titmuss hypothesized that paying blood donors would reduce the quality of the blood donated and would be economically inefficient. We report here the first systematic review to test these hypotheses, reporting on both financial and nonfinancial incentives. Studies deemed eligible for inclusion were peer-reviewed, experimental studies that presented data on the quantity (as a proxy for efficiency) and quality of blood donated in at least two groups: those donating blood when offered an incentive, and those donating blood with no offer of an incentive. The following were searched: MEDLINE, EMBASE and PsycINFO using OVID SP, CINAHL via EBSCO and CENTRAL, the Cochrane Library, Econlit via EBSCO, JSTOR Health and General Science Collection, and Google. The initial search yielded 1100 abstracts, which resulted in 89 full papers being assessed for eligibility, of which seven studies, reported in six papers, met the inclusion criteria. The included studies involved 93,328 participants. Incentives had no impact on the likelihood of donation (OR = 1.22 CI 95% 0.91-1.63; p = .19). There was no difference between financial and nonfinancial incentives in the quantity of blood donated. Of the two studies that assessed quality of blood, one found no effect and the other found an adverse effect from the offer of a free cholesterol test (β = 0.011 p < .05). The limited evidence suggests that Titmuss' hypothesis of the economic inefficiency of incentives is correct. There is insufficient evidence to assess their likely impact on the quality of the blood provided. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. Why is Pain Still Under-Treated in the Emergency Department? Two New Hypotheses.

    Science.gov (United States)

    Carter, Drew; Sendziuk, Paul; Eliott, Jaklin A; Braunack-Mayer, Annette

    2016-03-01

    Across the world, pain is under-treated in emergency departments (EDs). We canvass the literature testifying to this problem, the reasons why this problem is so important, and then some of the main hypotheses that have been advanced in explanation of the problem. We then argue for the plausibility of two new hypotheses: pain's under-treatment in the ED is due partly to (1) an epistemic preference for signs over symptoms on the part of some practitioners, and (2) some ED practices that themselves worsen pain by increasing patients' anxiety and fear. Our argument includes the following logic. Some ED practitioners depart from formal guidance in basing their acute pain assessments on observable features rather than on patient reports of pain. This is potentially due to an epistemic preference for signs over symptoms which aims to circumvent intentional and/or unintentional misrepresentation on the part of patients. However, conducting pain assessments in line with this epistemic preference contributes to the under-treatment of pain in at least three respects, which we detail. Moreover, it may do little to help the practitioner circumvent any intentional misrepresentation on the part of the patient, as we explain. Second, we examine at least four ED practices that may be contributing to the under-treatment of pain by increasing patient anxiety and fear, which can worsen pain. These practices include failing to provide orienting information and partially objectifying patients so as to problem-solve along lines pre-established by modern medical science. We conclude by touching on some potential solutions for ED practice.

  17. Environmental effects on vertebrate species richness: testing the energy, environmental stability and habitat heterogeneity hypotheses.

    Directory of Open Access Journals (Sweden)

    Zhenhua Luo

    Full Text Available BACKGROUND: Explaining species richness patterns is a central issue in biogeography and macroecology. Several hypotheses have been proposed to explain the mechanisms driving biodiversity patterns, but the causes of species richness gradients remain unclear. In this study, we aimed to explain the impacts of energy, environmental stability, and habitat heterogeneity factors on variation of vertebrate species richness (VSR, based on the VSR pattern in China, so as to test the energy hypothesis, the environmental stability hypothesis, and the habitat heterogeneity hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: A dataset was compiled containing the distributions of 2,665 vertebrate species and eleven ecogeographic predictive variables in China. We grouped these variables into categories of energy, environmental stability, and habitat heterogeneity and transformed the data into 100 × 100 km quadrat systems. To test the three hypotheses, AIC-based model selection was carried out between VSR and the variables in each group and correlation analyses were conducted. There was a decreasing VSR gradient from the southeast to the northwest of China. Our results showed that energy explained 67.6% of the VSR variation, with the annual mean temperature as the main factor, which was followed by annual precipitation and NDVI. Environmental stability factors explained 69.1% of the VSR variation and both temperature annual range and precipitation seasonality had important contributions. By contrast, habitat heterogeneity variables explained only 26.3% of the VSR variation. Significantly positive correlations were detected among VSR, annual mean temperature, annual precipitation, and NDVI, whereas the relationship of VSR and temperature annual range was strongly negative. In addition, other variables showed moderate or ambiguous relations to VSR. CONCLUSIONS/SIGNIFICANCE: The energy hypothesis and the environmental stability hypothesis were supported, whereas little

  18. Environmental effects on vertebrate species richness: testing the energy, environmental stability and habitat heterogeneity hypotheses.

    Science.gov (United States)

    Luo, Zhenhua; Tang, Songhua; Li, Chunwang; Fang, Hongxia; Hu, Huijian; Yang, Ji; Ding, Jingjing; Jiang, Zhigang

    2012-01-01

    Explaining species richness patterns is a central issue in biogeography and macroecology. Several hypotheses have been proposed to explain the mechanisms driving biodiversity patterns, but the causes of species richness gradients remain unclear. In this study, we aimed to explain the impacts of energy, environmental stability, and habitat heterogeneity factors on variation of vertebrate species richness (VSR), based on the VSR pattern in China, so as to test the energy hypothesis, the environmental stability hypothesis, and the habitat heterogeneity hypothesis. A dataset was compiled containing the distributions of 2,665 vertebrate species and eleven ecogeographic predictive variables in China. We grouped these variables into categories of energy, environmental stability, and habitat heterogeneity and transformed the data into 100 × 100 km quadrat systems. To test the three hypotheses, AIC-based model selection was carried out between VSR and the variables in each group and correlation analyses were conducted. There was a decreasing VSR gradient from the southeast to the northwest of China. Our results showed that energy explained 67.6% of the VSR variation, with the annual mean temperature as the main factor, which was followed by annual precipitation and NDVI. Environmental stability factors explained 69.1% of the VSR variation and both temperature annual range and precipitation seasonality had important contributions. By contrast, habitat heterogeneity variables explained only 26.3% of the VSR variation. Significantly positive correlations were detected among VSR, annual mean temperature, annual precipitation, and NDVI, whereas the relationship of VSR and temperature annual range was strongly negative. In addition, other variables showed moderate or ambiguous relations to VSR. The energy hypothesis and the environmental stability hypothesis were supported, whereas little support was found for the habitat heterogeneity hypothesis.

  19. Floral evolution in the Annonaceae: hypotheses of homeotic mutations and functional convergence.

    Science.gov (United States)

    Saunders, Richard M K

    2010-08-01

    The recent publication of hypotheses explaining the homeotic control of floral organ identity together with the availability of increasingly comprehensive and well-resolved molecular phylogenies presents an ideal opportunity for reassessing current knowledge of floral diversity and evolution in the Annonaceae. This review summarizes currently available information on selected aspects of floral structure and function, including: changes in the number of perianth whorls and the number of perianth parts per whorl; the evolution of sympetaly; the diversity and evolution of pollination chambers (with a novel classification of seven main structural forms of floral chamber based on the different arrangement, size and shape of petals); the evolution of perianth glands; floral unisexuality and hypotheses explaining the unexpectedly high frequency of occurrence of androdioecy; the origin and possible function of inner and outer staminodes; the evolution of stamen connective diversity and theca septation; and the origin of 'true' syncarpy and functionally equivalent extragynoecial compita. In each case, current ideas on the origin, evolution and function are discussed. The information presented in this review enables two main conclusions to be drawn. The first is that changes in the homeotic control of floral organ identity may have had a profound impact on floral structure in several disparate lineages in the family. This is most obvious in Fenerivia, in which a centrifugal shift of floral organ identity has occurred, and in Dasymaschalon, in which a reverse (centripetal) shift has occurred. Other genera that have gained or lost entire perianth whorls are likely to have undergone similar homeotic changes. Attention is also drawn to the extensive functional convergence in Annonaceae flowers, with widespread homoplasy in many characters that have previously been emphasized in higher-level classifications.

  20. Growth Disorders

    Science.gov (United States)

    ... because their parents are. But some children have growth disorders. Growth disorders are problems that prevent children from developing ... or other features. Very slow or very fast growth can sometimes signal a gland problem or disease. ...

  1. Metabolic Disorders

    Science.gov (United States)

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  2. Panic Disorder

    Science.gov (United States)

    ... This is the basis for a condition called agoraphobia. A person who has agoraphobia finds it difficult to leave home (or another ... Disorders Education Program Last Updated: April 2014 Tags: agoraphobia, Alprazolam, antidepressants, anxiety disorders, behavior therapy, clonazepam, klonopin, ...

  3. Anxiety Disorders

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Anxiety Disorders KidsHealth > For Teens > Anxiety Disorders A A ... Do en español Trastornos de ansiedad What Is Anxiety? Liam had always looked out for his younger ...

  4. Bipolar Disorder

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    Bipolar disorder is a serious mental illness. People who have it go through unusual mood changes. They ... The down feeling is depression. The causes of bipolar disorder aren't always clear. It runs in ...

  5. Personality Disorders

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    Personality disorders are a group of mental illnesses. They involve long-term patterns of thoughts and behaviors ... serious problems with relationships and work. People with personality disorders have trouble dealing with everyday stresses and ...

  6. Movement Disorders

    Science.gov (United States)

    ... t want them to. If you have a movement disorder, you experience these kinds of impaired movement. Dyskinesia ... movement and is a common symptom of many movement disorders. Tremors are a type of dyskinesia. Nerve diseases ...

  7. Menstrual Disorders

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    ... Issues Listen Español Text Size Email Print Share Menstrual Disorders in Teens Page Content Article Body Within ... test Measurement of gonadotropins, prolactin and androgens How Menstrual Disorders are treated with Drug Therapy: After exclusion ...

  8. Conversion disorder

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000954.htm Conversion disorder To use the sharing features on this page, please enable JavaScript. Conversion disorder is a mental condition in which a person ...

  9. Visual Hallucinations in PD and Lewy Body Dementias: Old and New Hypotheses

    Directory of Open Access Journals (Sweden)

    M. Onofrj

    2013-01-01

    Full Text Available Visual Hallucinations (VH are a common non-motor symptom of Parkinson’s Disease (PD and the Lewy body dementias (LBD of Parkinson's disease with dementia (PDD and Dementia with Lewy Bodies (DLB. The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance.

  10. Insight in Psychiatry and Neurology: State of the Art, and Hypotheses.

    Science.gov (United States)

    Landi, Paola; Marazziti, Donatella; Rutigliano, Grazia; Dell'Osso, Liliana

    2016-01-01

    In spite of the increasing number of studies on insight in psychiatry and also in neurology and psychology, its nature is still elusive. It encompasses at least three fundamental characteristics: the awareness of suffering from an illness, an understanding of the cause and source of this suffering, and an acknowledgment of the need for treatment. As such, insight is fundamental for patients' management, prognosis, and treatment. Not surprisingly, the majority of available data, which have been gathered on schizophrenia, show a relationship between low insight and poorer outcomes. For mood disorders, however, insight is associated with less positive results. For other psychiatric disorders, insight has rarely been investigated. In neurology, the impaired ability to recognize the presence of sensory, perceptual, motor, affective, or cognitive functioning-referred to as anosognosia-has been related to damage of specific brain regions. This article provides a comprehensive review of insight in different psychiatric and neurological disorders, with a special focus on brain areas and neurotransmitters that serve as the substrate for this complex phenomenon.

  11. Eating Disorders

    Science.gov (United States)

    ... Binge-eating, which is out-of-control eating Women are more likely than men to have eating disorders. They usually start in the teenage years and often occur along with depression, anxiety disorders, and substance abuse. Eating disorders can lead ...

  12. Bipolar Disorder.

    Science.gov (United States)

    Spearing, Melissa

    Bipolar disorder, a brain disorder that causes unusual shifts in a person's mood, affects approximately one percent of the population. It commonly occurs in late adolescence and is often unrecognized. The diagnosis of bipolar disorder is made on the basis of symptoms, course of illness, and when possible, family history. Thoughts of suicide are…

  13. The Involvement of Reelin in Neurodevelopmental Disorders

    OpenAIRE

    Folsom, Timothy D.; Fatemi, S. Hossein

    2012-01-01

    Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adults (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer’s disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plastici...

  14. Zebrafish: a novel research tool for cardiac (patho)electrophysiology and ion channel disorders.

    Science.gov (United States)

    Verkerk, Arie O; Remme, Carol Ann

    2012-01-01

    The zebrafish is a cold-blooded tropical freshwater teleost with two-chamber heart morphology. A major advantage of the zebrafish for heart studies is that the embryo is transparent, allowing for easy assessment of heart development, heart rate analysis and phenotypic characterization. Moreover, rapid and effective gene-specific knockdown can be achieved using morpholino oligonucleotides. Lastly, zebrafish are small in size, are easy to maintain and house, grow fast, and have large offspring size, making them a cost-efficient research model. Zebrafish embryonic and adult heart rates as well as action potential (AP) shape and duration and electrocardiogram morphology closely resemble those of humans. However, whether the zebrafish is truly an attractive alternative model for human cardiac electrophysiology depends on the presence and gating properties of the various ion channels in the zebrafish heart, but studies into the latter are as yet limited. The rapid component of the delayed rectifier K(+) current (I(Kr)) remains the best characterized and validated ion current in zebrafish myocytes, and zebrafish may represent a valuable model to investigate human I(Kr) channel-related disease, including long QT syndrome. Arguments against the use of zebrafish as model for human cardiac (patho)electrophysiology include its cold-bloodedness and two-chamber heart morphology, absence of t-tubuli, sarcoplamatic reticulum function, and a different profile of various depolarizing and repolarizing ion channels, including a limited Na(+) current density. Based on the currently available literature, we propose that zebrafish may constitute a relevant research model for investigating ion channel disorders associated with abnormal repolarization, but may be less suitable for studying depolarization disorders or Ca(2+)-modulated arrhythmias.

  15. Zebrafish: a novel research tool for cardiac (pathoelectrophysiology and ion channel disorders

    Directory of Open Access Journals (Sweden)

    Arie O Verkerk

    2012-07-01

    Full Text Available The zebrafish is a cold-blooded tropical freshwater teleost with a two-chamber heart morphology, typical for non-mammalian vertebrates. A major advantage of the zebrafish for heart studies is that the embryo is transparent, allowing for easy assessment of heart development, heart rate analysis and phenotypic characterization. Moreover, rapid and effective gene-specific knockdown can be achieved using morpholino oligonucleotides. Lastly, zebrafish are small in size, are easy to maintain and house, grow fast, and have large offspring size, making them a cost-efficient research model. Zebrafish embryonic and adult heart rates as well as action potential shape and duration and electrocardiogram morphology closely resemble those of humans. However, whether the zebrafish is truly an attractive alternative model for human cardiac electrophysiology depends on the presence and gating properties of the various ion channels in the zebrafish heart, but studies into the latter are as yet limited. The rapid component of the delayed rectifier K+ current (IKr remains the best characterized and validated ion current in zebrafish myocytes, and zebrafish may represent a valuable model to investigate human IKr channel related disease, including long QT syndrome. Arguments against the use of zebrafish as model for human cardiac (pathoelectrophysiology include its cold-bloodedness and two-chamber heart morphology, absence of t-tubuli, sarcoplamatic reticulum function, and a different profile of various depolarizing and repolarizing ion channels, including a limited Na+ current density. Based on the currently available literature, we propose that zebrafish may constitute a relevant research model for investigating ion channel disorders associated with abnormal repolarization, but may be less suitable for studying depolarization disorders or Ca2+-modulated arrhythmias.

  16. Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses.

    Science.gov (United States)

    Visscher, P M; Goddard, M E; Derks, E M; Wray, N R

    2012-05-01

    In this article, we review some of the data that contribute to our understanding of the genetic architecture of psychiatric disorders. These include results from evolutionary modelling (hence no data), the observed recurrence risk to relatives and data from molecular markers. We briefly discuss the common-disease common-variant hypothesis, the success (or otherwise) of genome-wide association studies, the evidence for polygenic variance and the likely success of exome and whole-genome sequencing studies. We conclude that the perceived dichotomy between 'common' and 'rare' variants is not only false, but unhelpful in making progress towards increasing our understanding of the genetic basis of psychiatric disorders. Strong evidence has been accumulated that is consistent with the contribution of many genes to risk of disease, across a wide range of allele frequencies and with a substantial proportion of genetic variation in the population in linkage disequilibrium with single-nucleotide polymorphisms (SNPs) on commercial genotyping arrays. At the same time, most causal variants that segregate in the population are likely to be rare and in total these variants also explain a significant proportion of genetic variation. It is the combination of allele frequency, effect size and functional characteristics that will determine the success of new experimental paradigms such as whole exome/genome sequencing to detect such loci. Empirical results suggest that roughly half the genetic variance is tagged by SNPs on commercial genome-wide chips, but that individual causal variants have a small effect size, on average. We conclude that larger experimental sample sizes are essential to further our understanding of the biology underlying psychiatric disorders.

  17. Peroxisome proliferator-activated receptor (PPAR)β/δ, a possible nexus of PPARα- and PPARγ-dependent molecular pathways in neurodegenerative diseases: Review and novel hypotheses.

    Science.gov (United States)

    Aleshin, Stepan; Strokin, Mikhail; Sergeeva, Marina; Reiser, Georg

    2013-10-01

    Peroxisome proliferator-activated receptors (PPARα, -β/δ and -γ) are lipid-activated transcription factors. Synthetic PPARα and PPARγ ligands have neuroprotective properties. Recently, PPARβ/δ activation emerged as the focus of a novel approach for the treatment of a wide range of neurodegenerative diseases. To fill the gap of knowledge about the role of PPARβ/δ in brain, new hypotheses about PPARβ/δ involvement in neuropathological processes are requested. In this paper, we describe a novel hypothesis, claiming the existence of tight interactions between the three PPAR isotypes, which we designate the "PPAR triad". We propose that PPARβ/δ has a central control of the PPAR triad. The majority of studies analyze the regulation only by one of the PPAR isotypes. A few reports describe the mutual regulation of expression levels of all three PPAR isotypes by PPAR agonists. Analysis of these studies where pairwise interactions of PPARs were described allows us to support the existence of the PPAR triad with central role for PPARβ/δ. In the present review, we propose the hypothesis that in a wide range of brain disorders, PPARβ/δ plays a central role between PPARα and PPARγ. Finally, we prove the advantages of the PPAR triad concept by describing hypotheses of PPARβ/δ involvement in the regulation of myelination, glutamate-induced neurotoxicity, and signaling pathways of reactive oxygen species/NO/Ca(2+). Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The Hydrological Open Air Laboratory (HOAL) in Petzenkirchen: a hypotheses driven observatory

    Science.gov (United States)

    Blöschl, G.; Blaschke, A. P.; Broer, M.; Bucher, C.; Carr, G.; Chen, X.; Eder, A.; Exner-Kittridge, M.; Farnleitner, A.; Flores-Orozco, A.; Haas, P.; Hogan, P.; Kazemi Amiri, A.; Oismüller, M.; Parajka, J.; Silasari, R.; Stadler, P.; Strauß, P.; Vreugdenhil, M.; Wagner, W.; Zessner, M.

    2015-07-01

    Hydrological observatories bear a lot of resemblance to the more traditional research catchment concept but tend to differ in providing more long term facilities that transcend the lifetime of individual projects, are more strongly geared towards performing interdisciplinary research, and are often designed as networks to assist in performing collaborative science. This paper illustrates how the experimental and monitoring setup of an observatory, the 66 ha Hydrological Open Air Laboratory (HOAL) in Petzenkirchen, Lower Austria, has been established in a way that allows meaningful hypothesis testing. The overarching science questions guided site selection, identifying dissertation topics and the base monitoring. The specific hypotheses guided the dedicated monitoring and sampling, individual experiments, and repeated experiments with controlled boundary conditions. The purpose of the HOAL is to advance the understanding of water related flow and transport processes involving sediments, nutrients and microbes in small catchments. The HOAL catchment is ideally suited for this purpose, because it features a range of different runoff generation processes (surface runoff, springs, tile drains, wetlands), the nutrient inputs are known, and it is convenient from a logistic point of view as all instruments can be connected to the power grid and a high speed glassfibre Local Area Network. The multitude of runoff generation mechanisms in the catchment provide a genuine laboratory where hypotheses of flow and transport can be tested, either by controlled experiments or by contrasting sub-regions of different characteristics. This diversity also ensures that the HOAL is representative of a range of catchments around the world and the specific process findings from the HOAL are applicable to a variety of agricultural catchment settings. The HOAL is operated jointly by the Vienna University of Technology and the Federal Agency for Water Management and takes advantage of the

  19. 3D tooth microwear texture analysis in fishes as a test of dietary hypotheses of durophagy

    Science.gov (United States)

    Purnell, Mark A.; Darras, Laurent P. G.

    2016-03-01

    An understanding of how extinct animals functioned underpins our understanding of past evolutionary events, including adaptive radiations, and the role of functional innovation and adaptation as drivers of both micro- and macroevolution. Yet analysis of function in extinct animals is fraught with difficulty. Hypotheses that interpret molariform teeth in fishes as evidence of durophagous (shell-crushing) diets provide a good example of the particular problems inherent in the methods of functional morphology. This is because the assumed close coupling of form and function upon which the approach is based is weakened by, among other things, behavioural flexibility and the absence of a clear one to one relationship between structures and functions. Here we show that ISO 25178-2 standard parameters for surface texture, derived from analysis of worn surfaces of molariform teeth of fishes, vary significantly between species that differ in the amount of hard-shelled prey they consume. Two populations of the Sheepshead Seabream (Archosargus probatocephalus) were studied. This fish is not a dietary specialist, and one of the populations is known to consume more vegetation and less hard-shelled prey than the other; this is reflected in significant differences in their microwear textures. The Archosargus populations differ significantly in their microwear from the specialist shell-crusher Anarhichas lupus (the Atlantic Wolffish). Multivariate analysis of these three groups of fishes lends further support to the relationship between diet and tooth microwear, and provides robust validation of the approach. Application of the multivariate models derived from microwear texture in Archosargus and Anarhichas to a third fish species—the cichlid Astatoreochromis alluaudi—successfully separates wild caught fish that ate hard-shelled prey from lab-raised fish that did not. This cross-taxon validation demonstrates that quantitative analysis of tooth microwear texture can

  20. Reactor Core Coolability Analysis during Hypothesized Severe Accidents of OPR1000

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yongjae; Seo, Seungwon; Kim, Sung Joong [Hanyang University, Seoul (Korea, Republic of); Ha, Kwang Soon; Kim, Hwan-Yeol [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    Assessment of the safety features over the hypothesized severe accidents may be performed experimentally or numerically. Due to the considerable time and expenditures, experimental assessment is implemented only to the limited cases. Therefore numerical assessment has played a major role in revisiting severe accident analysis of the existing or newly designed power plants. Computer codes for the numerical analysis of severe accidents are categorized as the fast running integral code and detailed code. Fast running integral codes are characterized by a well-balanced combination of detailed and simplified models for the simulation of the relevant phenomena within an NPP in the case of a severe accident. MAAP, MELCOR and ASTEC belong to the examples of fast running integral codes. Detailed code is to model as far as possible all relevant phenomena in detail by mechanistic models. The examples of detailed code is SCDAP/RELAP5. Using the MELCOR, Carbajo. investigated sensitivity studies of Station Black Out (SBO) using the MELCOR for Peach Bottom BWR. Park et al. conduct regulatory research of the PWR severe accident. Ahn et al. research sensitivity analysis of the severe accident for APR1400 with MELCOR 1.8.4. Lee et al. investigated RCS depressurization strategy and developed a core coolability map for independent scenarios of Small Break Loss-of-Coolant Accident (SBLOCA), SBO, and Total Loss of Feed Water (TLOFW). In this study, three initiating cases were selected, which are SBLOCA without SI, SBO, and TLOFW. The initiating cases exhibit the highest probability of transitioning into core damage according to PSA 1 of OPR 1000. The objective of this study is to investigate the reactor core coolability during hypothesized severe accidents of OPR1000. As a representative indicator, we have employed Jakob number and developed JaCET and JaMCT using the MELCOR simulation. Although the RCS pressures for the respective accident scenarios were different, the JaMCT and Ja

  1. Speech perception in children with speech output disorders.

    NARCIS (Netherlands)

    Nijland, L.

    2009-01-01

    Research in the field of speech production pathology is dominated by describing deficits in output. However, perceptual problems might underlie, precede, or interact with production disorders. The present study hypothesizes that the level of the production disorders is linked to level of perception

  2. Pelvic organ prolapse and collagen-associated disorders.

    NARCIS (Netherlands)

    Lammers, K.; Lince, S.L.; Spath, M.A.; Kempen, L.C.L.T. van; Hendriks, J.C.M.; Vierhout, M.E.; Kluivers, K.B.

    2012-01-01

    INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) and other disorders, such as varicose veins and joint hypermobility, have been associated with changes in collagen strength and metabolism. We hypothesized that these various disorders were more prevalent in both POP patients and their family

  3. Speech perception in children with speech output disorders.

    NARCIS (Netherlands)

    Nijland, L.

    2009-01-01

    Research in the field of speech production pathology is dominated by describing deficits in output. However, perceptual problems might underlie, precede, or interact with production disorders. The present study hypothesizes that the level of the production disorders is linked to level of perception

  4. Developing thresholds of potential concern for invasive alien species: Hypotheses and concepts

    Directory of Open Access Journals (Sweden)

    Llewellyn C. Foxcroft

    2009-01-01

    Full Text Available The Kruger National Park (KNP has developed and refined a system of management called ‘strategic adaptive management’ (SAM, which rests on the concept of ‘threshold of potential concern’ (TPC. TPCs represent end-points in a continuum of change. When thresholds are reached – at which point concerns of negative impacts on biodiversity are raised – management options are explicitly considered and implemented. This paper describes the TPCs developed for monitoring and managing invasive alien species (IAS. More importantly, however, it describes the conceptual understanding, principles and hypotheses adopted as the foundations for setting these TPCs. In accordance with adaptive management practices, the TPCs will be revised as the ecological and conceptual understanding of invasions grows and information is gained through research in the KNP and elsewhere.Conservation implication: In accepting that species and systems are variable, and that flux is inevitable and desirable, these TPCs developed for invasive alien species specifi cally, provide end points against which monitoring can be assessed. Once a threshold is reached, the cause of the threshold being exceeded is examined and management interventions recommended.

  5. The developmental antecedents of sexual coercion against women: testing alternative hypotheses with structural equation modeling.

    Science.gov (United States)

    Knight, Raymond A; Sims-Knight, Judith E

    2003-06-01

    A unified model of the origin of sexual aggression against women on both adult and juvenile sexual offender samples has been developed and successfully tested. This model proposed three major causal paths to sexual coercion against women. In the first path, physical and verbal abuse was hypothesized to produce callousness and lack of emotionality, which disinhibited sexual drive and sexual fantasies. These in turn disinhibited hostile sexual fantasies, and led to sexual coercion. In the second causal path, sexual abuse contributed directly to the disinhibition of sexual drive and sexual fantasies, which through hostile sexual fantasies led to sexual coercion. The third path operated through early antisocial behavior, including aggressive acts. It developed as a result of both physical/verbal abuse and callousness/lack of emotion. It in turn directly affected sexual coercion and worked indirectly through the hostile sexual fantasies path. In the present study, the anonymous responses of a group of 168 blue-collar, community males to an inventory (the Multidimensional Assessment of Sex and Aggression) were used in a structural equation model to test the validity of this model. Moreover, this model was pitted against (Malamuth's (1998)) two-path model. Whereas the three-path model had an excellent fit with the data (CFI =.951, RMSEA =.047), the two-path model fit less well (CFI =.857, RMSEA =.079). These results indicate the superiority of the three-path model and suggest that it constitutes a solid, empirically disconfirmable heuristic for the etiology of sexual coercion against women.

  6. Basal tissue structure in the earliest euconodonts: Testing hypotheses of developmental plasticity in euconodont phylogeny

    Science.gov (United States)

    Dong, X.-P.; Donoghue, P.C.J.; Repetski, J.E.

    2005-01-01

    The hypothesis that conodonts are vertebrates rests solely on evidence of soft tissue anatomy. This has been corroborated by microstructural, topological and developmental evidence of homology between conodont and vertebrate hard tissues. However, these conclusions have been reached on the basis of evidence from highly derived euconodont taxa and the degree to which they are representative of plesiomorphic euconodonts remains an open question. Furthermore, the range of variation in tissue types comprising the euconodont basal body has been used to establish a hypothesis of developmental plasticity early in the phylogeny of the clade, and a model of diminishing potentiality in the evolution of development systems. The microstructural fabrics of the basal tissues of the earliest euconodonts (presumed to be the most plesiomorphic) are examined to test these two hypotheses. It is found that the range of microstructural variation observed hitherto was already apparent among plesiomorphic euconodonts. Thus, established histological data are representative of the most plesiomorphic euconodonts. However, although there is evidence of a range in microstructural fabrics, these are compatible with the dentine tissue system alone, and the degree of variation is compatible with that seen in clades of comparable diversity. ?? The Palaeontological Association.

  7. Factors that affect the physical science career interest of female students: Testing five common hypotheses

    Science.gov (United States)

    Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sonnert, Gerhard; Sadler, Philip M.

    2013-12-01

    There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using multivariate matching methods on national data drawn from the Persistence Research in Science and Engineering (PRiSE) project (n=7505), we test the following five commonly held beliefs regarding what factors might impact females’ physical science career interest: (i) having a single-sex physics class, (ii) having a female physics teacher, (iii) having female scientist guest speakers in physics class, (iv) discussing the work of female scientists in physics class, and (v) discussing the underrepresentation of women in physics class. The effect of these experiences on physical science career interest is compared for female students who are matched on several factors, including prior science interests, prior mathematics interests, grades in science, grades in mathematics, and years of enrollment in high school physics. No significant effects are found for single-sex classes, female teachers, female scientist guest speakers, and discussing the work of female scientists. However, discussions about women’s underrepresentation have a significant positive effect.

  8. Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses and Limitations

    Directory of Open Access Journals (Sweden)

    Shruti Shukla

    2016-10-01

    Full Text Available The current scenario regarding the widespread Zika virus (ZIKV has resulted in numerous diagnostic studies, specifically in South America and in locations where there is frequent entry of travelers returning from ZIKV-affected areas, including pregnant women with or without clinical symptoms of ZIKV infection. The World Health Organization, WHO, announced that millions of cases of ZIKV are likely to occur in the United States of America in the near future. This situation has created an alarming public health emergency of international concern requiring the detection of this life-threatening viral candidate due to increased cases of newborn microcephaly associated with ZIKV infection. Hence, this review reports possible methods and strategies for the fast and reliable detection of ZIKV with particular emphasis on current updates, knowledge and new hypotheses that might be helpful for medical professionals in poor and developing countries that urgently need to address this problem. In particular, we emphasize liposome-based biosensors. Although these biosensors are currently among the less popular tools for human disease detection, they have become useful tools for the screening and detection of pathogenic bacteria, fungi and viruses because of their versatile advantageous features compared to other sensing devices. This review summarizes the currently available methods employed for the rapid detection of ZIKV and suggests an innovative approach involving the application of a liposome-based hypothesis for the development of new strategies for ZIKV detection and their use as effective biomedicinal tools.

  9. Computer-mediated communication and interpersonal attraction: an experimental test of two explanatory hypotheses.

    Science.gov (United States)

    Antheunis, Marjolijn L; Valkenburg, Patti M; Peter, Jochen

    2007-12-01

    The aims of this study were (a) to investigate the influence of computer-mediated communication (CMC) on interpersonal attraction and (b) to examine two underlying processes in the CMC-interpersonal attraction relationship. We identified two variables that may mediate the influence of CMC on interpersonal attraction: self-disclosure and direct questioning. Focusing on these potential mediating variables, we tested two explanatory hypotheses: the CMC-induced direct questioning hypothesis and the CMC-induced self-disclosure hypothesis. Eighty-one cross-sex dyads were randomly assigned to one of three experimental conditions: text-only CMC, visual CMC, and face-to-face communication. We did not find a direct effect of CMC on interpersonal attraction. However, we did find two positive indirect effects of text-only CMC on interpersonal attraction: text-only CMC stimulated both self-disclosure and direct questioning, both of which in turn enhanced interpersonal attraction. Results are discussed in light of uncertainty reduction theory and CMC theories.

  10. The relevance of the background impact flux to cyclic impact/mass extinction hypotheses

    Science.gov (United States)

    Fogg, Martyn J.

    1989-06-01

    The belief that mass extinctions of species on Earth have occurred on a ˜26- to 33-my cycle is supported by some rather equivocal geological evidence. This has prompted a search for cosmic phenomena that could subject the Earth at regular intervals to bombardment by showers of comets, with resulting damage to the biosphere. A crucial assumption that an impact-driven mass extinction cycle would automatically show up in the geological record is questioned. Might the background flux of random impacts distort the cycle and render it unrecognizable? Computer simulation of the impact bombardment of the Earth over a 250-my period, in which the background impact flux is overlaid by a 26-my comet shower cycle, showed a periodicity in the mass extinction data between 24 and 33 my in ˜40-60% of runs, dependent on the magnitude of the background flux chosen, and only ˜20-40% indicated the "true" 26-my periodicity. Thus, background impact "noise" can beidentified as an additional constraint on cyclic impact/mass extinction hypotheses.

  11. Why do niches develop in Caesarean uterine scars? Hypotheses on the aetiology of niche development.

    Science.gov (United States)

    Vervoort, A J M W; Uittenbogaard, L B; Hehenkamp, W J K; Brölmann, H A M; Mol, B W J; Huirne, J A F

    2015-12-01

    Caesarean section (CS) results in the occurrence of the phenomenon 'niche'. A 'niche' describes the presence of a hypoechoic area within the myometrium of the lower uterine segment, reflecting a discontinuation of the myometrium at the site of a previous CS. Using gel or saline instillation sonohysterography, a niche is identified in the scar in more than half of the women who had had a CS, most with the uterus closed in one single layer, without closure of the peritoneum. An incompletely healed scar is a long-term complication of the CS and is associated with more gynaecological symptoms than is commonly acknowledged. Approximately 30% of women with a niche report spotting at 6-12 months after their CS. Other reported symptoms in women with a niche are dysmenorrhoea, chronic pelvic pain and dyspareunia. Given the association between a niche and gynaecological symptoms, obstetric complications and potentially with subfertility, it is important to elucidate the aetiology of niche development after CS in order to develop preventive strategies. Based on current published data and our observations during sonographic, hysteroscopic and laparoscopic evaluations of niches we postulate some hypotheses on niche development. Possible factors that could play a role in niche development include a very low incision through cervical tissue, inadequate suturing technique during closure of the uterine scar, surgical interventions that increase adhesion formation or patient-related factors that impair wound healing or increase inflammation or adhesion formation.

  12. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  13. Inter-hemispheric competition relieved in both: hypotheses for autism and schizophrenia from problem theory.

    Science.gov (United States)

    Burnand, Gordon

    2012-07-01

    A logical relationship exists among six general problems that people face in life. Using hope about something for its subjective probability, its expected likelihood, the problems form a series where the method of assessing hope changes in a simple manner from one problem to the next. The central hypothesis is that human beings exploit this. Brain structures and predispositions have evolved accordingly, leading to the hemispheres having different predispositions. The hemispheres are effectively joined at 5 months. Infants will then find that they engage in two unrelated activities. Typical infants label the activities in detail, using visual images, as part of gaining control over them. Hypotheses are: (a) autistic children fail labelling at the start, and hence they encounter uncontrolled competition between the hemispheres; (b) with some, serotonin abnormality impairs sensory information processing and hence the labelling; (c) with some, a delay in myelination from autoimmune effects disrupts labelling; (d) the likelihood of this 'delay autism' is reduced by long chain omega oils; (e) self-pressuring, which underlies taking on challenges and play like Hide and Seek, brings relief from the competition by raising the influence of one side; (f) the same left-right competition occurs in confused episodes and schizophrenia in vulnerable people who encounter pressures to use both hemispheres at the same time; (g) some symptoms raise the influence on one side ideationally. This leads to coherent theories of autism and schizophrenia. In both competition between the hemispheres is relieved primarily by self-pressuring, which raises influence on one side.

  14. Distribution and coexistence of shrews in patchy landscapes: A field test of multiple hypotheses

    Science.gov (United States)

    Mortelliti, Alessio; Boitani, Luigi

    2009-11-01

    Despite the important role of shrews (Soricomorpha: Soricidae) in the functioning of ecosystems, as predators and prey, the effects of habitat loss and fragmentation on this guild of mammals are still unclear. We studied the distribution of 5 species (the greater white toothed shrew Crocidura leucodon; the lesser white toothed shrew Crocidura suaveolens; the pigmy shrew Sorex minutus; the Appennine shrew Sorex samniticus and the Etruscan shrew Suncus etruscus) in a fragmented landscape in central Italy. Shrews were trapped with pitfall traps made from plastic water bottles, the number of traps increased with patch size. A total of 170 individuals, of 5 species of shrews were captured. Shrews were widely distributed in our study area, however patch occupancy was determined mainly by vegetation and geometrical characteristics of the patches. Our data supports the hypotheses that patterns of habitat selection and the dynamics of seasonal abundance (habitat and temporal partitioning between similarly sized species) reduce competitive pressure, thus allowing coexistence of shrews in relatively species-rich assemblages, for such small amounts of habitat. The most important outcome of our results is the crucial role played by vegetation structure in determining distribution patterns. These results strongly suggest that measurements of the vegetation structure of habitat patches should always be included as explanatory variables when studying the distribution of shrews in fragmented landscapes.

  15. The evolution of flight in bats: narrowing the field of plausible hypotheses.

    Science.gov (United States)

    Bishop, Kristin L

    2008-06-01

    The evolution of flapping flight in bats from an arboreal gliding ancestor appears on the surface to be a relatively simple transition. However, bat flight is a highly complex functional system from a morphological, physiological, and aerodynamic perspective, and the transition from a gliding precursor may involve functional discontinuities that represent evolutionary hurdles. In this review, I suggest a framework for a comprehensive treatment of the evolution of complex functional systems that emphasizes a mechanistic understanding of the initial state, the final state, and the proposed transitional states. In this case, bats represent the final state and extant mammalian gliders are used as a model for the initial state. To explore possible transitional states, I propose a set of criteria for evaluating hypotheses about the evolution of flight in vertebrates and suggest methods by which we can advance our understanding of the transition from gliding to flapping flight. Although it is impossible ever to know with certainty the sequence of events landing to flapping flight, the field of possibilities can be narrowed to those that maintain the functional continuity of the wing and result in improved aerodynamic performance across this transition. The fundamental differences between gliding and flapping flight should not necessarily be seen as evidence that this transition could not occur; rather, these differences point out compelling aspects of the aerodynamics of animal wings that require further investigation.

  16. Developmental instability and right shift theory hypotheses concerning correlates of familial sinistrality: negative findings.

    Science.gov (United States)

    McKeever, W F; Cerone, L J; Chase-Carmichael, C

    2000-04-01

    Both the right shift (Annett, 1985) and developmental instability (Yeo & Gangestad, 1993) theories of handedness predict that familial sinistrality (FS) should relate to hand skill asymmetries (HSA) on peg-moving tasks. Annett also hypothesises that both HSA and a procedure she derived for classifying individuals according to the pattern of their hand preferences for different manual activities can index the genotypes posited in her theory, i.e. she believes these variables are highly correlated. These hypotheses were tested in a sample of 280 dextral college students. Results failed to support the finding of Gangestad and Yeo (1994) that subjects showing greater hand skill asymmetry deviations from typical asymmetry had a greater probability of having a left-handed parent. There was also no support for Annett's finding that greater dextrality, as defined by her hand preference classification system, was negatively associated with familial sinistrality. Additionally, the relationship between HSA and Annett's hand preference classes was found to be exceedingly weak, contrary to Annett's theorising. These and other failures to find highly replicable differences between FS- and FS+ dextrals cast doubt on the validity of genetic or partial-genetic theories of handedness that posit a ''penetrance'' of a recessive non-dextrality-favouring gene that causes presumed dextral heterozygotic persons to differ from presumed homozygotic dominant persons in cognitive or manual skills.

  17. Stressed out symbiotes: hypotheses for the influence of abiotic stress on arbuscular mycorrhizal fungi.

    Science.gov (United States)

    Millar, Niall S; Bennett, Alison E

    2016-11-01

    Abiotic stress is a widespread threat to both plant and soil communities. Arbuscular mycorrhizal (AM) fungi can alleviate effects of abiotic stress by improving host plant stress tolerance, but the direct effects of abiotic stress on AM fungi are less well understood. We propose two hypotheses predicting how AM fungi will respond to abiotic stress. The stress exclusion hypothesis predicts that AM fungal abundance and diversity will decrease with persistent abiotic stress. The mycorrhizal stress adaptation hypothesis predicts that AM fungi will evolve in response to abiotic stress to maintain their fitness. We conclude that abiotic stress can have effects on AM fungi independent of the effects on the host plant. AM fungal communities will change in composition in response to abiotic stress, which may mean the loss of important individual species. This could alter feedbacks to the plant community and beyond. AM fungi will adapt to abiotic stress independent of their host plant. The adaptation of AM fungi to abiotic stress should allow the maintenance of the plant-AM fungal mutualism in the face of changing climates.

  18. Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

    Directory of Open Access Journals (Sweden)

    Javier eCanales

    2014-02-01

    Full Text Available Nitrogen (N is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than two thousand genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and eleven highly co-expressed gene clusters (modules. Four of these gene network modules have robust nitrate responsive functions such as transport, signaling and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants.

  19. Evaluation of hypotheses for the cause of the 1886 Charleston earthquake

    Energy Technology Data Exchange (ETDEWEB)

    White, R.M.; Long, L.T. (Law Environmental, Inc., Kennesaw, GA (USA); Georgia Inst. of Tech., Atlanta, GA (USA))

    1989-10-01

    This report describes a geophysical/geological investigation of the earth's crust at seismogenic depths in the Charleston, South Carolina area. This investigation was made for the purpose of narrowing the range of theories that have been used to explain the historic 1886 Charleston earthquake. Since a number of these theories are based on only a portion of the available data, we have established a comprehensive data set in order to allow these hypotheses to be subjected to the entire data set. Specifically, we combined existing and new gravity, magnetic and topographic data in grids of 128 km, 256 km and 1028 km on a side centered on Charleston. Seismic, geologic and drilling data were collected and summarized. A magnetotelluric survey consisting of 12 soundings interpreted to depths of over 40 kilometers defined the bottom of the rigid crust with assistance from seismic reflection and other data. A geologic model of the crust in the area of Charleston was constructed and it defined the locations of Triassic/Jurassic basins Paleozoic plutons in greater detail than has previously been achieved. 102 refs., 75 figs.

  20. pfSNP: An integrated potentially functional SNP resource that facilitates hypotheses generation through knowledge syntheses.

    Science.gov (United States)

    Wang, Jingbo; Ronaghi, Mostafa; Chong, Samuel S; Lee, Caroline G L

    2011-01-01

    Currently, >14,000,000 single nucleotide polymorphisms (SNPs) are reported. Identifying phenotype-affecting SNPs among these many SNPs pose significant challenges. Although several Web resources are available that can inform about the functionality of SNPs, these resources are mainly annotation databases and are not very comprehensive. In this article, we present a comprehensive, well-annotated, integrated pfSNP (potentially functional SNPs) Web resource (http://pfs.nus.edu.sg/), which is aimed to facilitate better hypothesis generation through knowledge syntheses mediated by better data integration and a user-friendly Web interface. pfSNP integrates >40 different algorithms/resources to interrogate >14,000,000 SNPs from the dbSNP database for SNPs of potential functional significance based on previous published reports, inferred potential functionality from genetic approaches as well as predicted potential functionality from sequence motifs. Its query interface has the user-friendly "auto-complete, prompt-as-you-type" feature and is highly customizable, facilitating different combination of queries using Boolean-logic. Additionally, to facilitate better understanding of the results and aid in hypotheses generation, gene/pathway-level information with text clouds highlighting enriched tissues/pathways as well as detailed-related information are also provided on the results page. Hence, the pfSNP resource will be of great interest to scientists focusing on association studies as well as those interested to experimentally address the functionality of SNPs.

  1. Sleep deprivation and anxiety in humans and rodents--translational considerations and hypotheses.

    Science.gov (United States)

    Pires, Gabriel Natan; Tufik, Sergio; Andersen, Monica Levy

    2015-10-01

    The effects of acute sleep deprivation on anxiety are the focus of controversy in the literature. While clinical research studies on the effects of sleep deprivation seem to show a consistent increase in acute anxiety, rodent studies have produced inconsistent results, with some experiments pointing to anxiogenesis and others to anxiolysis. Such observations impair the translational applicability of rodent models on the paradigm between sleep deprivation and anxiety. Current studies fail in the very basic principle of biomedical translational research: to provide relevant and reliable knowledge from basic experimental science that can be applied in clinical environments. Possible explanations for the disparity between human and animal studies include the accuracy of both human and rodent research, the ability of current behavioral protocols to truly reflect the anxiety response of rodents to sleep deprivation, and the nature of sleep deprivation-induced anxiety in rodents. Based on these hypotheses, we performed a brief overview of the literature on the relationship between sleep deprivation and anxiety and propose a research agenda that could lead to a better understanding of the reasons for the discrepancies found in the literature and provide more reliable data on the translational relationship between sleep deprivation and anxiety.

  2. Test of two hypotheses explaining the size of populations in a system of cities

    CERN Document Server

    Vitanov, Nikolay K

    2015-01-01

    Two classical hypotheses are examined about the population growth in a system of cities: Hypothesis 1 pertains to Gibrat's and Zipf's theory which states that the city growth-decay process is size independent; Hypothesis 2 pertains to the so called Yule process which states that the growth of populations in cities happens when (i) the distribution of the city population initial size obeys a log-normal function, (ii) the growth of the settlements follows a stochastic process. The basis for the test is some official data on Bulgarian cities at various times. This system was chosen because (i) Bulgaria is a country for which one does not expect biased theoretical conditions; (ii) the city populations were determined rather precisely. The present results show that: (i) the population size growth of the Bulgarian cities is size dependent, whence Hypothesis 1 is not confirmed for Bulgaria; (ii) the population size growth of Bulgarian cities can be described by a double Pareto log-normal distribution, whence Hypothe...

  3. Plant defense using toxic inorganic ions: conceptual models of the defensive enhancement and joint effects hypotheses.

    Science.gov (United States)

    Boyd, Robert S

    2012-10-01

    The concept of plant defense using toxic mineral elements originated as an explanation for extremely elevated concentrations of some elements (termed hyperaccumulation) in some plant tissues. The Defensive Enhancement Hypothesis suggests that hyperaccumulation evolved because, after an initial defensive benefit accrued from a relatively low initial concentration, increased concentration of an element provided increased plant fitness and drove evolution of higher element concentrations until hyperaccumulation was achieved. The Joint Effects Hypothesis postulates that additive or synergistic effects between element-based defenses, or between toxic element and organic chemical defenses, may have contributed to the evolution of hyperaccumulation. By lessening the concentration of an element necessary to provide an initial defensive benefit to a plant, joint effects could decrease the level of an element that provides an initial defensive benefit, allowing additive or synergistic defensive enhancement to take effect. Recent experimental tests have demonstrated defense at relatively low element concentrations, and tests of metal/metal and metal/organic compound combinations have shown joint effects. These hypotheses suggest how hyperaccumulator plants may have evolved in response to plant-herbivore interactions, and suggest that toxic element levels below those used to define hyperaccumulation may be ecologically effective. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Celebrities: From Teachers to Friends : A Test of Two Hypotheses on the Adaptiveness of Celebrity Gossip.

    Science.gov (United States)

    De Backer, Charlotte J S; Nelissen, Mark; Vyncke, Patrick; Braeckman, Johan; McAndrew, Francis T

    2007-12-01

    In this paper we present two compatible hypotheses to explain interest in celebrity gossip. The Learning Hypothesis explains interest in celebrity gossip as a by-product of an evolved mechanism useful for acquiring fitness-relevant survival information. The Parasocial Hypothesis sees celebrity gossip as a diversion of this mechanism, which leads individuals to misperceive celebrities as people who are part of their social network. Using two preliminary studies, we tested our predictions. In a survey with 838 respondents and in-depth interviews with 103 individuals, we investigated how interest in celebrity gossip was related to several dimensions of the participants' social lives. In support of the Learning Hypothesis, age proved to be a strong predictor of interest in celebrities. In partial support of the Parasocial Hypothesis, media exposure, but not social isolation, was a strong predictor of interest in celebrities. The preliminary results support both theories, indicate that across our life span celebrities move from being teachers to being friends, and open up a list of future research opportunities.

  5. Violent media exposure, aggression and CU traits in adolescence: Testing the selection and socialization hypotheses.

    Science.gov (United States)

    Rydell, Ann-Margret

    2016-10-01

    We investigated the role of exposure to violent action for later aggression and for later callous-unemotional traits in a sample of Swedish adolescents (N = 77-85), testing the selection and socialization hypotheses. Adolescents reported on violent delinquency and on callous-unemotional (CU) traits at age 15, on their media habits at age 16 and on reactive and proactive aggression and CU traits at age 18. The socialization hypothesis was supported with regard to aggression, that is, violent delinquency did not affect consumption of violent action, but controlling for violent delinquency, consumption of violent action added to proactive aggression and, marginally, to reactive aggression. The selection hypothesis was supported with regard to CU traits, that is, high levels of CU traits predicted frequent consumption of violent action, but consumption of violent action did not affect later levels of CU traits. Frequent violent media use was associated with later aggression. The associations between CU traits and violent media need further study.

  6. What drove reversions to quadrupedality in ornithischian dinosaurs? Testing hypotheses using centre of mass modelling.

    Science.gov (United States)

    Maidment, Susannah C R; Henderson, Donald M; Barrett, Paul M

    2014-11-01

    The exceptionally rare transition to quadrupedalism from bipedal ancestors occurred on three independent occasions in ornithischian dinosaurs. The possible driving forces behind these transitions remain elusive, but several hypotheses-including the development of dermal armour and the expansion of head size and cranial ornamentation-have been proposed to account for this major shift in stance. We modelled the position of the centre of mass (CoM) in several exemplar ornithischian taxa and demonstrate that the anterior shifts in CoM position associated with the development of an enlarged skull ornamented with horns and frills for display/defence may have been one of the drivers promoting ceratopsian quadrupedality. A posterior shift in CoM position coincident with the development of extensive dermal armour in thyreophorans demonstrates this cannot have been a primary causative mechanism for quadrupedality in this clade. Quadrupedalism developed in response to different selective pressures in each ornithischian lineage, indicating different evolutionary pathways to convergent quadrupedal morphology.

  7. Differential invasion success of salmonids in southern Chile: patterns and hypotheses

    Science.gov (United States)

    Arismendi, Ivan; Penaluna, Brooke E.; Dunham, Jason B.; García de Leaniz, Carlos; Soto, Doris; Fleming, Ian A.; Gomez-Uchidam, Daniel; Gajardo, Gonzalo; Vargas, Pamela V.; León-Muñoz, Jorge

    2014-01-01

    Biological invasions create complex ecological and societal issues worldwide. Most of the knowledge about invasions comes only from successful invaders, but less is known about which processes determine the differential success of invasions. In this review, we develop a framework to identify the main dimensions driving the success and failure of invaders, including human influences, characteristics of the invader, and biotic interactions. We apply this framework by contrasting hypotheses and available evidence to explain variability in invasion success for 12 salmonids introduced to Chile. The success of Oncorhynchus mykiss and Salmo trutta seems to be influenced by a context-specific combination of their phenotypic plasticity, low ecosystem resistance, and propagule pressure. These well-established invaders may limit the success of subsequently introduced salmonids, with the possible exception of O. tshawytscha, which has a short freshwater residency and limited spatial overlap with trout. Although propagule pressure is high for O. kisutch and S. salar due to their intensive use in aquaculture, their lack of success in Chile may be explained by environmental resistance, including earlier spawning times than in their native ranges, and interactions with previously established and resident Rainbow Trout. Other salmonids have also failed to establish, and they exhibit a suite of ecological traits, environmental resistance, and limited propagule pressure that are variably associated with their lack of success. Collectively, understanding how the various drivers of invasion success interact may explain the differential success of invaders and provide key guidance for managing both positive and negative outcomes associated with their presence.

  8. Testing hypotheses that link wood anatomy to cavitation resistance and hydraulic conductivity in the genus Acer.

    Science.gov (United States)

    Lens, Frederic; Sperry, John S; Christman, Mairgareth A; Choat, Brendan; Rabaey, David; Jansen, Steven

    2011-05-01

    • Vulnerability to cavitation and conductive efficiency depend on xylem anatomy. We tested a large range of structure-function hypotheses, some for the first time, within a single genus to minimize phylogenetic 'noise' and maximize detection of functionally relevant variation. • This integrative study combined in-depth anatomical observations using light, scanning and transmission electron microscopy of seven Acer taxa, and compared these observations with empirical measures of xylem hydraulics. • Our results reveal a 2 MPa range in species' mean cavitation pressure (MCP). MCP was strongly correlated with intervessel pit structure (membrane thickness and porosity, chamber depth), weakly correlated with pit number per vessel, and not related to pit area per vessel. At the tissue level, there was a strong correlation between MCP and mechanical strength parameters, and some of the first evidence is provided for the functional significance of vessel grouping and thickenings on inner vessel walls. In addition, a strong trade-off was observed between xylem-specific conductivity and MCP. Vessel length and intervessel wall characteristics were implicated in this safety-efficiency trade-off. • Cavitation resistance and hydraulic conductivity in Acer appear to be controlled by a very complex interaction between tissue, vessel network and pit characteristics.

  9. Perplexities and Provocations of Eating Disorders

    Science.gov (United States)

    Halmi, Katherine A.

    2009-01-01

    Background: Etiological hypotheses of eating disorders, anorexia nervosa and bulimia nervosa have not produced informative research for predictably effective treatment. Methods: The rationale for applying a model of allostasis, a dysregulation of reward circuits with activation of brain and hormonal stress responses to maintain apparent stability,…

  10. Perplexities and Provocations of Eating Disorders

    Science.gov (United States)

    Halmi, Katherine A.

    2009-01-01

    Background: Etiological hypotheses of eating disorders, anorexia nervosa and bulimia nervosa have not produced informative research for predictably effective treatment. Methods: The rationale for applying a model of allostasis, a dysregulation of reward circuits with activation of brain and hormonal stress responses to maintain apparent stability,…

  11. On the chronobiology of seasonal affective disorder

    NARCIS (Netherlands)

    Koorengevel, Kathelijne Mara

    2002-01-01

    Chronobiological hypotheses about the pathogenesis of affective disorders have a long history. According to the modern variants, abnormalities of either a sleep-wake cycle dependent process S, or a circadian pacemaker related process C, or an abnor-mal interaction between these two processes

  12. Couples' division of employment and household chores and relationship satisfaction: A test of the specialization and equity hypotheses

    NARCIS (Netherlands)

    Blom, N.; Kraaykamp, G.L.M.; Verbakel, C.M.C.

    2017-01-01

    This article investigates associations between couples' divisions of time spent on employment and household chores and respondents’ satisfaction with their partner relationship. Theoretical notions of specialization and equity were used to derive hypotheses. Specialization relates to differentiation

  13. A Decentralized Approach to the Formulation of Hypotheses: A Hierarchical Structural Model for a Prion Self-Assembled System

    Science.gov (United States)

    Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin

    2016-07-01

    Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure.

  14. University Mentality or Community College Paranoia: A Critique of Don Morgan's Reaction to David Riesman's Tentative Hypotheses.

    Science.gov (United States)

    Vaughan, George B.

    1979-01-01

    Responds to Don Morgan's reaction (JC 502 050) to David Riesman's article, "Community Colleges: Some Tentative Hypotheses" (JC 502 056). Summarizes Riesman's major arguments and challenges Morgan's interpretations of them. (AYC)

  15. [Eating disorders].

    Science.gov (United States)

    Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

    2015-02-01

    Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

  16. [The Gioconda from the historical and medical perspective (hypotheses of pathology in her painting)].

    Science.gov (United States)

    Cruz Hermida, J

    2001-01-01

    As a preamble, some historical and biographical brushtrokes of the Gioconda, Leonardo and his painting will be outlined. Following these observations, a series of medical interpretations will be put forth regarding his painting with the aim of analysing possible pathologies related to: the skin, hair, eyes, hands and the reproductive and endocrine systems. We will conclude by observing the famous work The Smile and by extracting a hypothesis on pathologies of various natures such as: neurological, muscular, hypoacusic, asthmatic, psychoneurotic, psychiatric, ethylic, sexual, stress-related, stomatological (bruxismo) and the driving force that lies behind setting off the Stendhal Syndrome: a psychosomatic disorder known to be due to the human being's susceptibility to saturation from having received impressions of great artistic beauty.

  17. The wings before the bird: an evaluation of flapping-based locomotory hypotheses in bird antecedents

    Directory of Open Access Journals (Sweden)

    T. Alexander Dececchi

    2016-07-01

    Full Text Available Background: Powered flight is implicated as a major driver for the success of birds. Here we examine the effectiveness of three hypothesized pathways for the evolution of the flight stroke, the forelimb motion that powers aerial locomotion, in a terrestrial setting across a range of stem and basal avians: flap running, Wing Assisted Incline Running (WAIR, and wing-assisted leaping. Methods: Using biomechanical mathematical models based on known aerodynamic principals and in vivo experiments and ground truthed using extant avians we seek to test if an incipient flight stroke may have contributed sufficient force to permit flap running, WAIR, or leaping takeoff along the phylogenetic lineage from Coelurosauria to birds. Results: None of these behaviours were found to meet the biomechanical threshold requirements before Paraves. Neither was there a continuous trend of refinement for any of these biomechanical performances across phylogeny nor a signal of universal applicability near the origin of birds. None of these flap-based locomotory models appear to have been a major influence on pre-flight character acquisition such as pennaceous feathers, suggesting non-locomotory behaviours, and less stringent locomotory behaviours such as balancing and braking, played a role in the evolution of the maniraptoran wing and nascent flight stroke. We find no support for widespread prevalence of WAIR in non-avian theropods, but can’t reject its presence in large winged, small-bodied taxa like Microraptor and Archaeopteryx. Discussion: Using our first principles approach we find that “near flight” locomotor behaviors are most sensitive to wing area, and that non-locomotory related selection regimes likely expanded wing area well before WAIR and other such behaviors were possible in derived avians. These results suggest that investigations of the drivers for wing expansion and feather elongation in theropods need not be intrinsically linked to locomotory

  18. Retraining the addicted brain: a review of hypothesized neurobiological mechanisms of mindfulness-based relapse prevention.

    Science.gov (United States)

    Witkiewitz, Katie; Lustyk, M Kathleen B; Bowen, Sarah

    2013-06-01

    Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse.

  19. Tales of two similar hypotheses: the rise and fall of chemical and radiation hormesis.

    Science.gov (United States)

    Calabrese, E J; Baldwin, L A

    2000-01-01

    This paper compares the historical developments of chemical and radiation hormesis from their respective inceptions in the late 1880's for chemical hormesis and early 1900's for radiation hormesis to the mid 1930's to 1940 during which both hypotheses rose to some prominence but then became marginalized within the scientific community. This analysis documents that there were marked differences in their respective temporal developments, and the direction and maturity of research. In general, the formulation of the chemical hormesis hypothesis displayed an earlier, more-extensive and more sophisticated development than the radiation hormesis hypothesis. It was able to attract prestigious researchers with international reputations from leading institutions, to be the subject of numerous dissertations, to have its findings published in leading journals, and to have its concepts incorporated into leading microbiological texts. While both areas became the object of criticism from leading scientists, the intensity of the challenge was greatest for chemical hormesis due to its more visible association with the medical practice of homeopathy. Despite the presence of legitimate and flawed criticism, the most significant limitations of both chemical and radiation hormesis and their respective ultimate undoing were due to their: (1) lack of development of a coherent dose-response theory using data of low dose stimulation from both the chemical and radiation domains; (2) difficulty in replication of low dose stimulatory responses without an adequate study design especially with respect to an appropriate number and properly spaced doses below the toxic threshold; (3) modest degree of stimulation even under optimal conditions which was difficult to distinguish from normal variation; and (4) lack of appreciation of the practical and/or commercial applications of the concepts of low dose stimulation.

  20. The diel patterns of soil respiration in four arid California ecosystems: fluxes, sources and hypotheses

    Science.gov (United States)

    Carbone, M.; Trumbore, S.; Winston, G.; Serio, D.

    2007-12-01

    Automated measurements provide the high-resolution information that enables us to analyze potential causes for diel variability in soil respiration. These diel patterns are the complex result of biological and physical processes that determine the production and diffusion of CO2 through the soil. We examined the diel patterns of soil respiration from four arid California ecosystems: (1) a pinon-juniper woodland in at the Burns Pinon Ridge Reserve near Joshua Tree National Park, (2) a cold desert shrub community and (3) a perennial grassland near the city of Bishop in the Owens Valley, and (4) a mixed oak-pine forest at the James Reserve in the San Jacinto Mountains. In addition to automated chamber and environmental measurements at these sites, we used isotopic (14C) partitioning techniques to separate the plant and microbial sources contributing to soil respiration at certain time points. Here we present the diel cycles of soil respiration and environmental variables, the source partitioning results, and hypotheses about what processes determine these diel patterns that both span, and are specific to the studied ecosystems. In these systems dominated by Mediterranean or desert climates, we observed that factors like relative humidity can dominate the diel variations in soil respiration for sites with very dry surface litter. At other sites and times of year, diel variation in soil respiration reflects photosynthetic and VPD influence on root respiration. The combination of automated chamber measurements with isotopes provides information useful for separating the plant and heterotrophic control on diel and seasonal soil respiration fluxes.

  1. Importance of the glucocorticoid stress response in a changing world: theory, hypotheses and perspectives.

    Science.gov (United States)

    Angelier, Frédéric; Wingfield, John C

    2013-09-01

    In this perspective paper, we emphasize the importance that integrative mechanisms, and especially the GC (glucocorticoid) stress response, can play in the ability of vertebrates to cope with ongoing global change. The GC stress response is an essential mediator of allostasis (i.e., the responses of an organism to a perturbation) that aims at maintaining stability (homeostasis) despite changing conditions. The GC stress response is a complex mechanism that depends on several physiological components and aims at promoting immediate survival at the expense of other life-history components (e.g., reproduction) when a labile perturbation factor (LPF) occurs. Importantly, this mechanism is somewhat flexible and its degree of activation can be adjusted to the fitness costs and benefits that result from the GC stress response. Therefore, this GC stress response mediates life-history decisions and is involved in the regulation of important life-history trade-offs. By inducing abrupt and rapid changes in the regime of LPFs, we believe that global change can affect the efficiency of the GC stress response to maintain homeostasis and to appropriately regulate these trades-offs. This dysfunction may result in an important mismatch between new LPFs and the associated GC stress response and, thus, in the inability of vertebrates to cope with a changing world. In that context, it is essential to better understand how the GC stress response can be adjusted to new LPFs through micro-evolution, phenotypic plasticity and phenotypic flexibility (habituation and sensitization). This paper sets up a theoretical framework, hypotheses and new perspectives that will allow testing and better understanding how the GC stress response can help or constrain individuals, populations and species to adjust to ongoing global change.

  2. Childhood victimization and alcohol symptoms in females: causal inferences and hypothesized mediators.

    Science.gov (United States)

    Schuck, A M; Widom, C S

    2001-08-01

    Previous research has reported a relationship between childhood victimization experiences and alcohol problems in females. This paper has two distinct goals: (1) to determine whether it is appropriate to make a causal inference regarding the association between early child abuse and neglect and alcohol symptoms in females; and (2) to examine five potential mechanisms (depression, worthlessness, social isolation/loneliness, low self esteem, and using alcohol and/or drugs to cope) that may mediate the relationship between child abuse and neglect and alcohol symptomatology. Substantiated cases of child abuse and neglect from 1967 to 1971 were matched on sex, age, race, and approximate social class with nonabused and non-neglected children and followed prospectively into young adulthood. Subjects were administered a 2-h in-person interview, including the NIMH Diagnostic Interview Schedule (DIS-III-R) to assess alcohol use and abuse. Analyses are restricted to females in the sample (N = 582). Structural equation modeling provides support for the inference that childhood victimization plays a causal role in the development of alcohol symptoms in women. There also is support for the hypothesized mediating role of two mechanisms (depression and using alcohol/drugs to cope), but not for the other mediators. Evidence from this prospective study suggests that childhood victimization may be one of the causal factors in the development of alcohol problems in females. Interventions should bedirected at abused and neglected females of all ages to help them to deal with depression and to develop coping strategies to prevent the development of serious alcohol problems.

  3. Beta-carotene and lung cancer in smokers: review of hypotheses and status of research.

    Science.gov (United States)

    Goralczyk, Regina

    2009-01-01

    A number of epidemiological studies have reported associations of beta-carotene plasma levels or intake with decreased lung cancer risk. However, intervention studies in smokers have unexpectedly reported increased lung tumor rates after high, long-term, beta-carotene supplementation. Recently, detailed analyses by stratification for smoking habits of several large, long-term intervention or epidemiological trials are now available. The ATBC study, the CARET study, the Antioxidant Polyp Prevention trial, and the E3N study provide evidence that the adverse effects of beta-carotene supplementation are correlated with the smoking status of the study participants. In contrast, the Physician Health Study, the Linxian trial, and a pooled analysis of 7 epidemiological cohort studies have not supported this evidence. The ferret and A/J mouse lung cancer model have been used to investigate the mechanism of interaction of beta-carotene with carcinogens in the lung. Both models have specific advantages and disadvantages. There are a number of hypotheses concerning the beta-carotene/tobacco smoke interaction including alterations of retinoid metabolism and signaling pathways and interaction with CYP enzymes and pro-oxidation/DNA oxidation. The animal models consistently demonstrate negative effects only in the ferret, and following dosing with beta-carotene in corn oil at pharmacological dosages. No effects or even protective effects against smoke or carcinogen exposure were observed when beta-carotene was applied at physiological dosages or in combination with vitamins C and E, either as a mixture or in a stable formulation. In conclusion, human and animal studies have shown that specific circumstances, among them heavy smoking, seem to influence the effect of high beta-carotene intakes. In normal, healthy, nonsmoking populations, there is evidence of beneficial effects.

  4. Functional relations between locomotor performance traits in spiders and implications for evolutionary hypotheses

    Directory of Open Access Journals (Sweden)

    Taylor Phillip W

    2010-11-01

    Full Text Available Abstract Background Locomotor performance in ecologically relevant activities is often linked to individual fitness. Recent controversy over evolution of extreme sexual size dimorphism (SSD in spiders centres on the relationship between size and locomotor capacity in males. Advantages for large males running over horizontal surfaces and small males climbing vertically have been proposed. Models have implicitly treated running and climbing as functionally distinct activities and failed to consider the possibility that they reflect common underlying capacities. Findings We examine the relationship between maximum climbing and running performance in males of three spider species. Maximum running and climbing speeds were positively related in two orb-web spiders with high SSD (Argiope keyserlingi and Nephila plumipes, indicating that for these species assays of running and climbing largely reveal the same underlying capacities. Running and climbing speeds were not related in a jumping spider with low SSD (Jacksonoides queenslandica. We found no evidence of a performance trade-off between these activities. Conclusions In the web-spiders A. keyserlingi and N. plumipes good runners were also good climbers. This indicates that climbing and running largely represent a single locomotor performance characteristic in these spiders, but this was not the case for the jumping spider J. queenslandica. There was no evidence of a trade-off between maximum running and climbing speeds in these spiders. We highlight the need to establish the relationship between apparently disparate locomotor activities when testing alternative hypotheses that yield predictions about different locomotor activities. Analysis of slopes suggests greater potential for an evolutionary response on performance in the horizontal compared to vertical context in these spiders.

  5. Bivariate cumulative probit model for the comparison of neuronal encoding hypotheses.

    Science.gov (United States)

    Hillmann, Julia; Kneib, Thomas; Koepcke, Lena; Juárez Paz, León M; Kretzberg, Jutta

    2014-01-01

    Understanding the way stimulus properties are encoded in the nerve cell responses of sensory organs is one of the fundamental scientific questions in neurosciences. Different neuronal coding hypotheses can be compared by use of an inverse procedure called stimulus reconstruction. Here, based on different attributes of experimentally recorded neuronal responses, the values of certain stimulus properties are estimated by statistical classification methods. Comparison of stimulus reconstruction results then allows to draw conclusions about relative importance of covariate features. Since many stimulus properties have a natural order and can therefore be considered as ordinal, we introduce a bivariate ordinal probit model to obtain classifications for the combination of light intensity and velocity of a visual dot pattern based on different covariates extracted from recorded spike trains. For parameter estimation, we develop a Bayesian Gibbs sampler and incorporate penalized splines to model nonlinear effects. We compare the classification performance of different individual cell covariates and simple features of groups of neurons and find that the combination of at least two covariates increases the classification performance significantly. Furthermore, we obtain a non-linear effect for the first spike latency. The model is compared to a naïve Bayesian stimulus estimation method where it yields comparable misclassification rates for the given dataset. Hence, the bivariate ordinal probit model is shown to be a helpful tool for stimulus reconstruction particularly thanks to its flexibility with respect to the number of covariates as well as their scale and effect type. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The cost of wobble translation in fungal mitochondrial genomes: integration of two traditional hypotheses

    Directory of Open Access Journals (Sweden)

    Xia Xuhua

    2008-07-01

    Full Text Available Abstract Background Fungal and animal mitochondrial genomes typically have one tRNA for each synonymous codon family. The codon-anticodon adaptation hypothesis predicts that the wobble nucleotide of a tRNA anticodon should evolve towards maximizing Watson-Crick base pairing with the most frequently used codon within each synonymous codon family, whereas the wobble versatility hypothesis argues that the nucleotide at the wobble site should be occupied by a nucleotide most versatile in wobble pairing, i.e., the tRNA wobble nucleotide should be G for NNY codon families, and U for NNR and NNN codon families (where Y stands for C or U, R for A or G and N for any nucleotide. Results We here integrate these two traditional hypotheses on tRNA anticodons into a unified model based on an analysis of the wobble costs associated with different wobble base pairs. This novel approach allows the relative cost of wobble pairing to be qualitatively evaluated. A comprehensive study of 36 fungal genomes suggests very different costs between two kinds of U:G wobble pairs, i.e., (1 between a G at the wobble site of a tRNA anticodon and a U at the third codon position (designated MU3:G and (2 between a U at the wobble site of a tRNA anticodon and a G at the third codon position (designated MG3:U. Conclusion In general, MU3:G is much smaller than MG3:U, suggesting no selection against U-ending codons in NNY codon families with a wobble G in the tRNA anticodon but strong selection against G-ending codons in NNR codon families with a wobble U at the tRNA anticodon. This finding resolves several puzzling observations in fungal genomics and corroborates previous studies showing that U3:G wobble is energetically more favorable than G3:U wobble.

  7. Kinetics of cancer: a method to test hypotheses of genetic causation

    Directory of Open Access Journals (Sweden)

    Lipkin Steven M

    2005-12-01

    Full Text Available Abstract Background Mouse studies have recently compared the age-onset patterns of cancer between different genotypes. Genes associated with earlier onset are tentatively assigned a causal role in carcinogenesis. These standard analyses ignore the great amount of information about kinetics contained in age-onset curves. We present a method for analyzing kinetics that measures quantitatively the causal role of candidate genes in cancer progression. We use our method to demonstrate a clear association between somatic mutation rates of different DNA mismatch repair (MMR genotypes and the kinetics of cancer progression. Methods Most experimental studies report age-onset curves as the fraction diagnosed with tumors at each age for each group. We use such data to estimate smoothed survival curves, then measure incidence rates at each age by the slope of the fitted curve divided by the fraction of mice that remain undiagnosed for tumors at that age. With the estimated incidence curves, we compare between different genotypes the median age of cancer onset and the acceleration of cancer, which is the rate of increase in incidence with age. Results The direction of change in somatic mutation rate between MMR genotypes predicts the direction of change in the acceleration of cancer onset in all 7 cases (p ˜ 0.008, with the same result for the association between mutation rate and the median age of onset. Conclusion Many animal experiments compare qualitatively the onset curves for different genotypes. If such experiments were designed to analyze kinetics, the research could move to the next stage in which the mechanistic consequences of particular genetic pathways are related to the dynamics of carcinogenesis. The data we analyzed here were not collected to test mechanistic and quantitative hypotheses about kinetics. Even so, a simple reanalysis revealed significant insights about how DNA repair genotypes affect separately the age of onset and the

  8. Micturition disorders.

    Science.gov (United States)

    Byron, Julie K

    2015-07-01

    Evaluation of dogs and cats with micturition disorders can be challenging. It is important to determine the duration, timing, and frequency of the disorder, as well as assessing for any additional medical problems, such as neurologic or orthopedic disease, that may be affecting micturition. Observation of the patient during voiding can be particularly helpful in determining the type of disorder. Treatment of micturition disorders is varied and outcome depends on an accurate diagnosis. Patient response is also highly variable, even with appropriate therapy, and owners' expectations must be set accordingly.

  9. Volume of discrete brain structures in complex dissociative disorders: preliminary findings.

    Science.gov (United States)

    Ehling, T; Nijenhuis, E R S; Krikke, A P

    2008-01-01

    Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that (1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala than normal controls, (2) these volumes are associated with severity of psychoform and somatoform dissociative symptoms, and (3) patients who recovered from dissociative identity disorder (DID) have more hippocampal volume that patients with florid DID. The preliminary findings of the study are supportive of these hypotheses. Psychotherapy for dissociative disorders may affect hippocampal volume, but longitudinal studies are required to document this potential causal relationship.

  10. 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.

    Science.gov (United States)

    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.

  11. The Role of the Ratio of J-Point Elevation Magnitude and R-Wave Amplitude on the Same ECG Lead in the Risk Stratification of Subjects With Early Repolarization Pattern.

    Science.gov (United States)

    Chen, Xu-Miao; Ji, Cheng-Cheng; Cheng, Yun-Jiu; Liu, Li-Juan; Zhu, Wei-Qi; Huang, Ying; Chen, Wei-Ying; Wu, Su-Hua

    2016-11-01

    Just as high-risk populations for cardiac arrest exist in patients with Brugada syndrome or long QT syndrome, high-risk and low-risk populations for cardiac arrest also exist in patients with early repolarization pattern (ERP). Electrocardiographic (ECG) characteristics can aid the risk stratification of patients with ERP. Electrocardiographic parameters such as magnitude of J-point elevation and J/R ratio were measured. The magnitude of J-point elevation, leads with J points elevated, J/R ratio, morphology of the ST segment, and QT/QTc interval were used in comparative analysis in 2 groups: 57 patients with ERP and cardiac arrest (cardiac arrest group) and 100 patients with ERP but without cardiac arrest (control group). There was no statistical difference in clinical characteristics of the 2 groups. The J/R ratio in the cardiac arrest group was significantly higher than in the control group (26.8% ± 18.1% vs 16.3% ± 10.3%, respectively; P J/R ratio and horizontal/descending ST segment were independently associated with increased risk of cardiac arrest in patients with ERP. In patients with ERP and cardiac arrest, J/R ratios were relatively higher and mostly with horizontal/descending ST segments, suggesting that J/R ratio and ST-segment morphology may be used as indicators for risk stratification in patients with ERP. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2015-08-01

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

  13. White Blood Cell Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  14. Overview of Movement Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  15. Borderline Personality Disorder

    Science.gov (United States)

    ... Among U.S. Adults Any Disorder Among Children Any Anxiety Disorder Among Adults Any Anxiety Disorder Among Children Agoraphobia Among Adults Agoraphobia Among Children Generalized Anxiety Disorder Among Adults Generalized Anxiety Disorder Among Children Obsessive Compulsive Disorder ...

  16. Panic Disorder among Adults

    Science.gov (United States)

    ... Among U.S. Adults Any Disorder Among Children Any Anxiety Disorder Among Adults Any Anxiety Disorder Among Children Agoraphobia Among Adults Agoraphobia Among Children Generalized Anxiety Disorder Among Adults Generalized Anxiety Disorder Among Children Obsessive Compulsive Disorder ...

  17. Neuroimaging of tic disorders with co-existing attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Royal, Jason M; Peterson, Bradley S

    2007-01-01

    BACKGROUND: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding...... contrast these findings with those in ADHD without comorbid tic disorders. RESULTS: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory...

  18. Face-Emotion Processing in Offspring at Risk for Panic Disorder.

    Science.gov (United States)

    Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

    2005-01-01

    Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

  19. Co-morbid anxiety disorders predict early relapse after inpatient alcohol treatment

    NARCIS (Netherlands)

    Schellekens, A.F.A.; Jong, C.A.J. de; Buitelaar, J.; Verkes, R.J.

    2015-01-01

    INTRODUCTION: Alcohol dependence and anxiety disorders often co-occur. Yet, the effect of co-morbid anxiety disorders on the alcohol relapse-risk after treatment is under debate. This study investigated the effect of co-morbid anxiety disorders on relapse rates in alcohol dependence. We hypothesized

  20. Co-morbid anxiety disorders predict early relapse after inpatient alcohol treatment

    NARCIS (Netherlands)

    Schellekens, A.F.A.; Jong, C.A.J. de; Buitelaar, J.K.; Verkes, R.J.

    2015-01-01

    Introduction Alcohol dependence and anxiety disorders often co-occur. Yet, the effect of co-morbid anxiety disorders on the alcohol relapse-risk after treatment is under debate. This study investigated the effect of co-morbid anxiety disorders on relapse rates in alcohol dependence. We hypothesized

  1. Curie's hypotheses concerning radioactivity and the origin of the elements

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, P.K.

    1999-09-01

    Pierre Curie gave two hypotheses at first; (1) It can be supposed that the radioactive substances borrow the energy, which they release, from an external radiation, and their radiation would then be a secondary radiation, (2) It can be supposed that the radioactive substances draw from themselves the energy which they release. The second hypothesis has shown the more fertile in explaining the properties of the radioactive substances. Consequently, the first hypothesis became more or less forgotten. It appears, however, the first hypothesis should play an important role in explaining the phenomena concerning the origin of the elements. The Oklo Phenomenon has demonstrated that a nuclear fire had once existed on our planet earth and formation of heavy elements was occurring in nature. The author pointed out that the difference in the isotopic compositions of xenon found in meteorites, lunar samples and in the earth's atmosphere can only be explained as due to the alterations of the isotropic compositions of xenon by combined effect of (a) mass-fractionation, (b) spallation, and (c) stellar temperature neutron-capture reactions. The strange xenon components are not isotopically pure substance. Instead, xenon-HL is a mixture of the {sup 244}Pu fission xenon and the xenon whose isotopic compositions is severely altered by a combined effect of the processes (a), (b) and (c) mentioned above. These results also indicate that C1 carbonaceous chondrites, which is generally as the most primitive sample of the solar system material, began to retain its xenon 5.1 billion years ago, when the plutonium to uranium ratio in the solar system was as high as almost 0.6 (atom/atom), while the C2 carbonaceous chondrite began to retain their xenon about 150 million years later and the ordinary chondrites and achondrite about 500 to 600 million years later. This means that the birth of the solar system began soon after the last supernova exploded about 5.1 billion years ago, and the

  2. Over the top: Experiment and the testing of hypotheses in the search for the top quark

    Science.gov (United States)

    Staley, Kent Wade

    1998-07-01

    This study presents a historical account of experiments, performed by the Collider Detector at Fermilab (CDF) collaboration, which led to the discovery of the top quark, and a discussion of philosophical issues raised by that episode. The historical discussion is based on published and unpublished documents and oral history interviews, and is presented in two parts: First, the formation of the collaboration and construction of the detector are described. The activities of the collaborators during the period of detector construction are described in terms of the development of resources for a general experimental programme. Second, the development of the means of analyzing the data for the top quark search is described, particularly aspects of the analysis that were disputed. The hypothesis that collaboration researchers have come to regard the social process of resolving disputes as a matter of methodological importance is suggested. The philosophical discussion of the experiment employs the hierarchy of models approach of Patrick Suppes and Deborah Mayo in order to examine the logic of hypothesis testing and draw some conclusions regarding the nature of scientific evidence. In an extension of an argument presented by Peter Achinstein, the account of hypothesis testing given by hypothetico-deductivist philosophers such as Karl Popper and R. B. Braithwaite is examined in light of the reasoning employed in the top search, and is found wanting. The prediction based on the hypothesis being tested in the top search is found to have been inferred inductively from the experimental data. Finally, a discussion is presented of tuning on the signal, a form of bias in the testing of hypotheses. The proscription of this form of bias resembles John Worrall's requirement of use novelty, but is shown instead to serve the aim of devising a test of the hypothesis that is severe, in the sense articulated by Deborah Mayo. It is shown that the evaluation of evidence claims, as it

  3. Centripetal versus centrifugal bias in visual line bisection: focusing attention on two hypotheses.

    Science.gov (United States)

    McCourt, M E; Garlinghouse, M; Slater, J

    2000-01-01

    to the activation-orientation theory [M. Kinsbourne: Acta Psychologica 33, 193-201 (1970)]. When the range of line position exceeds the aperture of focal attention, we hypothesize that observers adopt a strategy in which attention is dynamically scanned in the direction of azimuthally displaced lines. The effects of attentional scanning on line bisection performance are quite robust. The centripetal scanning proposed to occur for widely displaced lines is consistent with the centripetal pattern of bisection error in this condition.

  4. Cyclothymic disorder

    Science.gov (United States)

    ... swings (these are less severe than in bipolar disorder or major depression) Ongoing symptoms, with no more than 2 symptom-free months in a row Exams and Tests ... Treatments for this disorder include mood-stabilizing medicine, antidepressants, talk therapy, or ...

  5. Anxiety Disorders

    Science.gov (United States)

    Klein, Rachel G.

    2009-01-01

    Because of their high prevalence and their negative long-term consequences, child anxiety disorders have become an important focus of interest. Whether pathological anxiety and normal fear are similar processes continues to be controversial. Comparative studies of child anxiety disorders are scarce, but there is some support for the current…

  6. Anxiety Disorders

    Science.gov (United States)

    Klein, Rachel G.

    2009-01-01

    Because of their high prevalence and their negative long-term consequences, child anxiety disorders have become an important focus of interest. Whether pathological anxiety and normal fear are similar processes continues to be controversial. Comparative studies of child anxiety disorders are scarce, but there is some support for the current…

  7. Conduct disorders

    NARCIS (Netherlands)

    Buitelaar, J.K.; Smeets, K.C.; Herpers, P.; Scheepers, F.; Glennon, J.; Rommelse, N.N.J.

    2013-01-01

    Conduct disorder (CD) is a frequently occurring psychiatric disorder characterized by a persistent pattern of aggressive and non-aggressive rule breaking antisocial behaviours that lead to considerable burden for the patients themselves, their family and society. This review paper updates diagnostic

  8. Personality disorders

    NARCIS (Netherlands)

    van den Bosch, L.M.C.; Verheul, R.; Verster, J.C.; Brady, K.; Galanter, M.; Conrod, P.

    2012-01-01

    Subject of this chapter is the often found combination of personality disorders and ­substance abuse disorders. The serious nature of this comorbidity is shown through the discussion of prevalence and epidemiological data. Literature shows that the comorbidity, hampering the diagnostic process, is s

  9. Calcium dysregulation, and lithium treatment to forestall Alzheimer's disease - a merging of hypotheses.

    Science.gov (United States)

    Wallace, James

    2014-03-01

    Intracellular Ca(2+) concentrations are tightly regulated, and elevated levels sustained over periods of time can cause cellular deterioration. The putative role of dysregulated intracellular Ca(2+) in Alzheimer's disease had led to the hypothesis that controlling intracellular Ca(2+) may forestall cognitive decline. Lithium has been shown to reduce intracellular Ca(2+) concentrations. Two well-characterized neuronal targets of lithium that may affect intracellular Ca(2+) levels are N-methyl-d-aspartate (NMDA) receptors and inositol monophosphatase (IMP). Results from a recent single-center placebo-controlled randomized trial suggest that long-term lithium treatment at subtherapeutic doses may have the potential to delay the progression of disease, and observational studies have shown that lithium reduces the prevalence of dementia in subjects with bipolar disorder on long-term lithium therapy. I am advancing the hypothesis that lithium may protect against cognitive decline by stabilizing intracellular Ca(2+) through a dual, synergistic mechanism of targeting both extracellular and intracellular sites, via antagonizing NMDA-receptors and inhibiting IMP. Insights derived from this hypothesis could lead to an improved understanding of the molecular pathology of Alzheimer's disease, and have implications on the evaluation and use of therapeutics that alter intracellular Ca(2+) levels.

  10. Anxiety Disorders: Support Groups

    Science.gov (United States)

    ... Disorder Specific Phobias Obsessive-Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) Depression Bipolar Disorder Suicide and Prevention Stress Related Illnesses Myth-Conceptions Find ...

  11. Screening for Panic Disorder

    Science.gov (United States)

    ... Disorder Specific Phobias Obsessive-Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) Depression Bipolar Disorder Suicide and Prevention Stress Related Illnesses Myth-Conceptions Find ...

  12. Treatment for Anxiety Disorders

    Science.gov (United States)

    ... Disorder Specific Phobias Obsessive-Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) Depression Bipolar Disorder Suicide and Prevention Stress Related Illnesses Myth-Conceptions Find ...

  13. Independence of long-term contextual memory and short-term perceptual hypotheses: Evidence from contextual cueing of interrupted search.

    Science.gov (United States)

    Schlagbauer, Bernhard; Mink, Maurice; Müller, Hermann J; Geyer, Thomas

    2017-02-01

    Observers are able to resume an interrupted search trial faster relative to responding to a new, unseen display. This finding of rapid resumption is attributed to short-term perceptual hypotheses generated on the current look and confirmed upon subsequent looks at the same display. It has been suggested that the contents of perceptual hypotheses are similar to those of other forms of memory acquired long-term through repeated exposure to the same search displays over the course of several trials, that is, the memory supporting "contextual cueing." In three experiments, we investigated the relationship between short-term perceptual hypotheses and long-term contextual memory. The results indicated that long-term, contextual memory of repeated displays neither affected the generation nor the confirmation of short-term perceptual hypotheses for these displays. Furthermore, the analysis of eye movements suggests that long-term memory provides an initial benefit in guiding attention to the target, whereas in subsequent looks guidance is entirely based on short-term perceptual hypotheses. Overall, the results reveal a picture of both long- and short-term memory contributing to reliable performance gains in interrupted search, while exerting their effects in an independent manner.

  14. [Affective disorders and eating disorders].

    Science.gov (United States)

    Fakra, Eric; Belzeaux, R; Azorin, J M; Adida, M

    2014-12-01

    Epidemiologic studies show a frequent co-occurence of affective and eating disorders. The incidence of one disorder in patients suffering from the other disorder is well over the incidence in the general population. Several causes could explain this increased comorbidity. First, the iatrogenic origin is detailed. Indeed, psychotropic drugs, and particularly mood stabilizers, often lead to modification in eating behaviors, generally inducing weight gain. These drugs can increase desire for food, reduce baseline metabolism or decrease motor activity. Also, affective and eating disorders share several characteristics in semiology. These similarities can not only obscure the differential diagnosis but may also attest of conjoint pathophysiological bases in the two conditions. However, genetic and biological findings so far are too sparse to corroborate this last hypothesis. Nonetheless, it is noteworthy that comorbidity of affective and eating disorders worsens patients'prognosis and is associated with more severe forms of affective disorders characterized by an earlier age of onset in the disease, higher number of mood episodes and a higher suicidality. Lastly, psychotropic drugs used in affective disorders (lithium, antiepileptic mood stabilizers, atypical antipsychotics, antidepressants) are reviewed in order to weigh their efficacy in eating disorders. This could help establish the best therapeutic option when confronted to comorbidity. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  15. [Dissociative disorders and affective disorders].

    Science.gov (United States)

    Montant, J; Adida, M; Belzeaux, R; Cermolacce, M; Pringuey, D; Da Fonseca, D; Azorin, J-M

    2014-12-01

    The phenomenology of dissociative disorders may be complex and sometimes confusing. We describe here two cases who were initially misdiagnosed. The first case concerned a 61 year-old woman, who was initially diagnosed as an isolated dissociative fugue and was actually suffering from severe major depressive episode. The second case concerned a 55 year-old man, who was suffering from type I bipolar disorder and polyvascular disease, and was initially diagnosed as dissociative fugue in a mooddestabilization context, while it was finally a stroke. Yet dissociative disorders as affective disorder comorbidity are relatively unknown. We made a review on this topic. Dissociative disorders are often studied through psycho-trauma issues. Litterature is rare on affective illness comorbid with dissociative disorders, but highlight the link between bipolar and dissociative disorders. The later comorbidity often refers to an early onset subtype with also comorbid panic and depersonalization-derealization disorder. Besides, unipolar patients suffering from dissociative symptoms have more often cyclothymic affective temperament. Despite the limits of such studies dissociative symptoms-BD association seems to correspond to a clinical reality and further works on this topic may be warranted. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  16. How antipsychotics impact the different dimensions of Schizophrenia: a test of competing hypotheses.

    Science.gov (United States)

    Marques, Tiago Reis; Levine, Stephen Z; Reichenberg, Avi; Kahn, Rene; Derks, Eske M; Fleischhacker, Wolfgang W; Rabinowitz, Jonathan; Kapur, Shitij

    2014-08-01

    The clinical expression of schizophrenia is generally reported to be expressed by three to five different factors (i.e. positive, negative, disorganization, excitability, anxiety-depression symptoms). It is often claimed that antipsychotic medications are particularly helpful for positive symptoms, but not for the others, suggesting a differential efficacy for different aspects of the disorder. We formally tested this claim. Using Structural Equation Modeling in two large [1884 patients] clinical trials in schizophrenia, we compared the model of a common general effect of antipsychotics to models whereby the antipsychotics have multiple and differential effects on the different factors of the illness. We validated the generalizability of the model in further trials involving antipsychotics in chronic [1460 patients] and first-episode patients [1053 patients]. Across different populations, different trials and different antipsychotics - the best-fitting model suggests that symptom response in schizophrenia is underpinned by a single general effect with secondary and minor lower-order effects on specific symptom domains. This single-factor model explained nearly 80% of the variance, was superior to the assumption of unique efficacy for specific domains; and replicated across antipsychotics and illness stages. Despite theoretical and pharmacological claims the differential efficacy of antipsychotics on the various dimensions of schizophrenia is not supported in the prevailing data. The implication of this finding for the measurement of treatment response and our understanding of the neurobiology of antipsychotic action, for clinical practice and for future drug development are discussed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  17. Eating disorders.

    Science.gov (United States)

    Treasure, Janet; Claudino, Angélica M; Zucker, Nancy

    2010-02-13

    This Seminar adds to the previous Lancet Seminar about eating disorders, published in 2003, with an emphasis on the biological contributions to illness onset and maintenance. The diagnostic criteria are in the process of review, and the probable four new categories are: anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder not otherwise specified. These categories will also be broader than they were previously, which will affect the population prevalence; the present lifetime prevalence of all eating disorders is about 5%. Eating disorders can be associated with profound and protracted physical and psychosocial morbidity. The causal factors underpinning eating disorders have been clarified by understanding about the central control of appetite. Cultural, social, and interpersonal elements can trigger onset, and changes in neural networks can sustain the illness. Overall, apart from studies reporting pharmacological treatments for binge eating disorder, advances in treatment for adults have been scarce, other than interest in new forms of treatment delivery. Copyright 2010 Elsevier Ltd. All rights reserved.

  18. The involvement of Reelin in neurodevelopmental disorders.

    Science.gov (United States)

    Folsom, Timothy D; Fatemi, S Hossein

    2013-05-01

    Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders. The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities. Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Empirical Evidence for Various Evolutionary Hypotheses on Species Demonstrating Increasing Mortality with Increasing Chronological Age in the Wild

    Directory of Open Access Journals (Sweden)

    Giacinto Libertini

    2008-01-01

    Full Text Available Many species show a significant increase in mortality with increasing chronological age in the wild. For this phenomenon, three possible general hypotheses are proposed, namely that: (1 it has no adaptive meaning; (2 it has an adaptive meaning; (3 the ancestry is the pivotal determinant. These hypotheses are evaluated according to their consistency with the empirical evidence. In particular, (1 the existence of many species with a constant, or almost constant, mortality rate, especially the so-called “animals with negligible senescence”; (2 the inverse correlation, observed in mammals and birds in the wild, between extrinsic mortality and the proportion of deaths due to intrinsic mortality; (3 the existence of highly sophisticated, genetically determined, and regulated mechanisms that limit and modulate cell duplication capacities and overall cell functionality. On the whole, the hypothesis of an adaptive meaning appears to be consistent with the empirical evidence, while the other two hypotheses hardly appear compatible.

  20. [Delusional disorders].

    Science.gov (United States)

    Garnier, Marion; Llorca, Pierre-Michel

    2015-02-01

    Delusional disorders are divided in French nosography into three clinical disease entities: paranoid delusions, psychose hallucinatoire chronique, and paraphrenia. Their common characteristics are a late start, a chronic evolution, no cognitive impairment and no dissociation. Delusio- nal syndrome is often at the forefront with a predominant mechanism characterizing each disorder (interpretation for paranoid delusions, hallucination for psychose hallucinatoire chronique and imagination for paraphrenia). Although these disorders are less sensitive to the medication than schizophrenia, care is based on second generation antipsychotic treatment, in association with psychotherapy and social care. The aim of treatment is to alleviate delusion intensity to improve global functioning and to prevent violent incidents or suicide attempt.