The atrial T wave: The elusive electrocardiographic wave exposed by a case of shifting atrial pacemaker

The atrial T wave (Ta wave) is the body surface manifestation of atrial repolarisation and, unlike the P wave (atrial depolarisation), is little recognised. We report the case of a patient with shifting pacemaker which clearly demonstrates the effect of the Ta wave on ST segment and T wave. A simple conceptual model is used to explain the observed phenomenon. The case serves as a reminder of this often forgotten ECG wave and its potential effects on other ECG features

The relative pronoun in Early Scots: a lexicographical and syntactical study

The following work is an examination of the use of the relative pronoun in Early Scots, i.e. during the period c.1375 - e.1500.It had been my intention to limit myself to an examination of the simple relative pronouns at, that, quhat, quha, quham, quho, quhom, quhilk, the asyndetic relative construction or zero form of the relative pronoun, together with the relative adverbs quhen, quhare, quhens, quhyne and quhither, including such compounds of the above as occur within the period stated. I have, however, been compelled to extend the scope of my examination in certain ways.Firstly, the simple relative use in the subjective case of the relative pronoun quha, quho can only be seen by extending the examination of the material well into the sixteenth century, since this is the one pronoun of the group of which the simple relative use was not already established by the time of the earliest extant texts.Secondly, one of the aims of this thesis was to provide a series of articles on the relative pronouns and adverbs for inclusion in the Dictionary of the Older Scottish Tongue under the appropriate headwords. I have subtitled my thesis "a lexicographical and syntactical study ", and for convenience I have labelled the D.O.S.T. articles the lexicographical part. I do not, however, mean to imply any sharp division between lexicography and syntax. A dictionary like D.O.S.T. attends to the syntax of every item included to a lesser or greater extent; and the study of a "closed system" (like that of relative pronouns) will be based on syntax rather than on lexical meaning. Thus the principal division between the two parts of the thesis will be in range and formal layout. The first part will provide a more intensive study of the simple relative construction within the period 1375 - 1500 (with the extension above noted in the case of quha, quho). The D.O.S.T. articles which comprise the second part will have the temporal range 1375 - 1700, which is the period covered by the Dictionary and will be set out according to function in the usual manner of the Dictionary

Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms

Physiologically based Pharmacokinetic (PBPK) models are used for predictions of internal or target dose from environmental and pharmacologic chemical exposures. Their use in human risk assessment is dependent on the nature of databases (animal or human) used to develop and test them, and includes extrapolations across species, experimental paradigms, and determination of variability of response within human populations. Integration of state-of-the science PBPK modeling with emerging computational toxicology models is critical for extrapolation between in vitro exposures, in vivo physiologic exposure, whole organism responses, and long-term health outcomes. This special issue contains papers that can provide the basis for future modeling efforts and provide bridges to emerging toxicology paradigms. In this overview paper, we present an overview of the field and introduction for these papers that includes discussions of model development, best practices, risk-assessment applications of PBPK models, and limitations and bridges of modeling approaches for future applications. Specifically, issues addressed include: (a) increased understanding of human variability of pharmacokinetics and pharmacodynamics in the population, (b) exploration of mode of action hypotheses (MOA), (c) application of biological modeling in the risk assessment of individual chemicals and chemical mixtures, and (d) identification and discussion of uncertainties in the modeling process

Unusual signals in a halo catheter: what is the mechanism?

In this "featured arrhythmia" article we present a set of unusual intracardiac electrode tracings that were recorded in a patient with typical clockwise flutter but a very dilated right atrium. The potential mechanism underlying this phenomenon is discussed with reference to the current literature

The PRO Program: One District’s Experience With Decentralizing Staff Development

Even today after years of restructuring and reform, when staff development is mentioned, many teachers still shudder and imagine a day of lecture that has little if anything to do with providing usable and relevant skills and information

Ventricular fibrillation in ischaemia and its defibrillation

ECG signals were recorded from isolated, Langendorff-perfused rabbit hearts to establish the relationship between dominant frequency and myocardial perfusion during ventricular fibrillation. Lower perfusion rates produced faster rates of dominant frequency decline, to lower steady state values. Optically mapping the anterior epicardial surface demonstrated heterogeneity of dominant frequency in ventricular fibrillation. During low-flow ischaemia, the dominant frequency reduction was restricted to the left ventricle. Application of individual ischaemic components during ventricular fibrillation demonstrated that raised [K+]EC, but not hypoxia or acidic pHEC, reproduced the ischaemic reduction of dominant frequency in the ECG, pseudoECG and over the left ventricular epicardial surface. In contrast, minimum defibrillation energies were increased by hypoxia and acidic pHEC, and not by raised [K+]EC. The dominant frequency heterogeneity during ventricular fibrillation in low-flow ischaemia and raised [K+]EC was not due to differential prolongation of repolarisation or post-repolarisation refractoriness in the left ventricle. Monophasic action potential studies showed that APD90 was reduced to similar degrees in each ventricle by low-flow ischaemia and raised [K+]EC. Effective refractory period was not altered in either ventricle by either condition. Low-flow ischaemia decreased conduction velocity in the left, but not the right ventricle. Conduction velocities were unaltered by raised [K+]EC in either ventricle. The activation threshold of the left ventricle was increased in low-flow ischaemia and raised [K+]EC, whilst the threshold of the right ventricle was unchanged. The increased activation threshold was associated with decreased upstroke velocity and diastolic depolarisation

Regeneration of dopaminergic neurons and other neuronal cell types in zebrafish

Unlike mammals, zebrafish have a remarkable capacity to regenerate the central nervous system. Following neuronal loss by physical injury or chemical ablation zebrafish are capable of replacing neurons through increased neurogenesis, resulting in functional recovery. In the adult zebrafish brain, certain populations of dopaminergic and noradrenergic neurons, identified by immunohistochemistry for tyrosine hydroxylase (Th+), are regenerated after ablation with 6-hydroxydopamine (6OHDA), an analogue of dopamine commonly used to specifically ablate these neurons. Here I ask where these newly formed Th+ neurons originate and which signals are involved in their regeneration. In the adult zebrafish new neurons are derived from progenitor cells, the soma of which form part of the ependyma and which have radial processes extending to the pial surface, termed ependymo-radial glial cells (ERGs). In this thesis I show that ERGs lining the diencephalic ventricle are a heterogeneous population in terms of expression of her4, gfap, and olig2. Using genetic lineage tracing and proliferation analysis I demonstrate that regenerated Th+ neurons are derived from specific ERGs at the diencephalic ventricle. In contrast to mammals, Th+ neurons are constantly generated in the adult zebrafish brain. Here I show that injection of 6OHDA elicits an immune response, and that inhibiting this immune response with the artificial glucocorticoid dexamethasone attenuates proliferation of ERGs and neurogenesis of Th+ neurons to control levels. Although stimulating an immune response increases proliferation of ERGs, an immune response is not sufficient to increase Th+ neurogenesis. This demonstrates that an immune response is necessary but not sufficient for the regeneration of Th+ neurons in the adult zebrafish brain. Following a spinal cord lesion, both larvae and adult zebrafish are capable of functional regeneration. Spinal cord regeneration has been shown to involve increased neurogenesis of motor neurons; however, the extent to which other neuronal populations are regenerated has not been fully elucidated. Here I show that glutamatergic neurons are regenerated after a spinal cord lesion in larvae, and GABAergic neurons are regenerated in both larvae and adults. Taken together, these results provide new insights into the regeneration of the central nervous system in zebrafish. I identify populations of neurons which are regenerated, progenitor cells that give rise to regenerated neurons, and I demonstrate the pivotal role of the immune response in modulating regeneration. These results could ultimately inform future attempts to promote neuroregeneration in mammals

Formation of Black Holes from Collapsed Cosmic String Loops

The fraction of cosmic string loops which collapse to form black holes is estimated using a set of realistic loops generated by loop fragmentation. The smallest radius sphere into which each cosmic string loop may fit is obtained by monitoring the loop through one period of oscillation. For a loop with invariant length $L$ which contracts to within a sphere of radius $R$, the minimum mass-per-unit length $\mu_{\rm min}$ necessary for the cosmic string loop to form a black hole according to the hoop conjecture is $\mu_{\rm min} = R /(2 G L)$. Analyzing $25,576$ loops, we obtain the empirical estimate $f_{\rm BH} = 10^{4.9\pm 0.2} (G\mu)^{4.1 \pm 0.1}$ for the fraction of cosmic string loops which collapse to form black holes as a function of the mass-per-unit length $\mu$ in the range $10^{-3} \lesssim G\mu \lesssim 3 \times 10^{-2}$. We use this power law to extrapolate to $G\mu \sim 10^{-6}$, obtaining the fraction $f_{\rm BH}$ of physically interesting cosmic string loops which collapse to form black holes within one oscillation period of formation. Comparing this fraction with the observational bounds on a population of evaporating black holes, we obtain the limit $G\mu \le 3.1 (\pm 0.7) \times 10^{-6}$ on the cosmic string mass-per-unit-length. This limit is consistent with all other observational bounds.Comment: uuencoded, compressed postscript; 20 pages including 7 figure

Amplitude Changes during Ventricular Fibrillation: A Mechanistic Insight

Introduction: Clinically in ventricular fibrillation (VF), ECG amplitude, and frequency decrease as ischemia progresses and predict defibrillation success. In vitro ECG amplitude declines without ischemia, independent of VF frequencies. This study examines the contribution of cellular electrical activity and global organization to ECG amplitude changes during VF. Methods and Results: Rabbit hearts were Langendorff-perfused (40 mL/min, Tyrode’s solution) and loaded with RH237. During VF, ECG, and epicardial optical action potentials were recorded (photodiode array; 256 sites, 15 mm × 15 mm). After 60 s of VF, perfusion was either maintained, global ischemia produced by low-flow (6 mL/min), or solution [K+]o raised to 8 mM. Peak-to-peak amplitude was determined for all signals. During VF, in control, ECG amplitude decreased to a steady-state (∼57% baseline), whereas in low-flow steady-state was not reached with the amplitude continuing to fall to 33% of baseline by 600 s. Optically, LV amplitude declined more than RV, reaching significance in control (LV vs. RV; 33 ± 5 vs. 63 ± 8%, p < 0.01). During VF in 8 mM [K+]o, amplitude changes were more complex; ECG amplitude increased with time (105 ± 13%), whilst LV amplitude decreased (60 ± 15%, p < 0.001). Microelectrode studies showed amplitude reduction in control and 8 mM [K+]o (to ∼79 and ∼93% baseline, respectively). Evaluation of electrical coordination by cross-correlation of optical signals showed as VF progressed coordination reduced in control (baseline 0.36 ± 0.02 to 0.28 ± 0.003, p < 0.01), maintained in low-flow (0.41 ± 0.03 to 0.37 ± 0.005, p = NS) and increased in 8 mM [K+]o (0.36 ± 0.02 to 0.53 ± 0.08, p < 0.05). Conclusion: ECG amplitude decline in VF is due to a combination of decreased systolic activation at the cellular level and increased desynchronization of inter-cellular electrical activity