Clayton L. Birkett

Clinical, hemodynamic and sympathetic neural correlates of heart rate variability in congestive heart failure

Heart rate (HR) variability has long been recognized as a sign of cardiac health. In the presence of heart disease, HR variability decreases, an observation that has been associated with poor prognosis in a number of recent studies. HR variability is particularly altered in congestive heart failure (CHF), a condition associated with a number of typical functional hemodynamic and neurohumoral alterations. The relation of measurements of HR variability to these abnormalities in patients with heart failure has not been carefully examined. Twenty-three patients (19 men, 4 women, mean age 49 years) with New York Heart Association class II to IV CHF were studied prospectively without cardiac medications; radionuclide ventriculography, right-sided heart catheterization, peroneal microneurography, plasma norepinephrine and 24- to 48-hour ambulatory electrocardiography were performed. Average RR interval and its standard deviation, and HR power spectrum (0 to 0.5, 0.05 to 0.15 and 0.2 to 0.5 Hz) were derived from the ambulatory electrocardiographic recordings and compared with left ventricular ejection fraction, thermodilution cardiac output, pulmonary arterial wedge pressure, New York Heart Association class, age, muscle sympathetic nerve activity (peroneal nerve) and norepinephrine level by linear regression. None of the measures of HR variability were significantly related to age, left ventricular ejection fraction, cardiac output or functional classification, whereas the 0.05 to 0.15 and 0.20 to 0.50 Hz components were weakly but significantly related to cardiac output (r = 0.49 and 0.42, p = 0.02 and 0.045, respectively). In contrast, a generally stronger and negative relation was demonstrated between spectral and nonspectral measurements of HR variability, and indicators of sympathoexcitation, muscle sympathetic nerve activity and plasma norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

ESTprep: preprocessing cDNA sequence reads

MOTIVATION High accuracy of data always governs the large-scale gene discovery projects. The data should not only be trustworthy but should be correctly annotated for various features it contains. Sequence errors are inherent in single-pass sequences such as ESTs obtained from automated sequencing. These errors further complicate the automated identification of EST-related sequencing. A tool is required to prepare the data prior to advanced annotation processing and submission to public databases. RESULTS This paper describes ESTprep, a program designed to preprocess expressed sequence tag (EST) sequences. It identifies the location of features present in ESTs and allows the sequence to pass only if it meets various quality criteria. Use of ESTprep has resulted in substantial improvement in accurate EST feature identification and fidelity of results submitted to GenBank. AVAILABILITY The program is freely available for download from http://genome.uiowa.edu/pubsoft/software.html

Three Complementary Approaches to Parallelization of Local BLAST Service on Workstation Clusters

This paper describes approaches to improving the perfor- mance of one of the most common and increasingly important aspects of the Human Genome Project (HGP) — large-volume, batch comparison of DNA sequence data. This basic comparison operation, usually carried out by the well-known BLAST program on one subject sequence against the internationally-available databases of over 3 million target sequences, is already used hundreds of thousands of times each day by researchers around the world. At present, it is still used primarily in single query, or small batch query mode. As the entire sequence of the human genome nears completion, the area of functional genomics, and the use of micro- arrays of sets of genes, is coming to the fore. These developments will demand ever more efficient means of BLASTing sets of data that will make single processor implementation on powerful workstations infea- sible. We describe the three primary parallel components to BLAST. The first is at the sequence-to-sequence comparison level. The second parallelizes a single query across a partitioned and distributed database. And finally, the set of queries themselves are partitioned across a set of servers with replicated or partitioned databases. The three methods may be employed alone or in concert. Our current implementation is described which parallelizes batch requests, and our plans for implementation of the other levels is also described. The results will ultimately be applied to hardware assistance for this soon-to-be primitive computer operation.

Interpolation over ectopic beats increases low frequency power in heart rate variability spectra

The authors compared spectra of heart rate variability (HRV) computed from 24 and 48 hour Holter tapes on 34 patients with congestive heart failure. Spectra on each patient were computed in two ways: (A) Segments with ectopic beats were included in the analysis. In this method, the intervals corresponding to ectopic beats and three beats following the last ectopic beat were computed by interpolation, and (B) Segments with ectopic beats were discarded. Spectral components of HRV in the low (0-0.05 Hz) and mid (0.05-0.15 Hz) frequency ranges were significantly (p<0.05) higher in method A than in method B. High (0.02-0.5 Hz) frequency components of the spectra were not significantly different between these two types of analysis.<<ETX>>

Is There an Optimal Electrode Pad Size to Maximize Intracardiac Current in Transthoracic Defibrillation

Achieving defibrillation depends on adequate intracardiac current. The purpose of this study was to determine, in advance of administering shocks, which parameters of body habitus can be used to select the electrode size that maximizes intracardiac current in transthoracic defibrillation. We administered direct current shocks to 18 mongrel dogs over a wide range of weight and size (weight 10–30 kg with chest circumferences 44–77 cm) using a damped sine wave defibrillator and self‐adhesive electrode pairs of various diameters (4 cm, 5.8 cm, 8 cm, and 10 cm), placed on the right and left lateral chest walls. The energy levels used were 50, 100, and 150 J. Intracardiac voltage gradient, a parameter of intracardiac current, was determined in three orthogonal planes using an intramyocardial electrode array placed in the interventricular septum. The relation between intracardiac voltage gradient magnitude [VG] and various parameters (body weight, heart weight, chest circumference, chest volume, chest radius, and heart weight divided by chest radius) was determined. The correlation (r) with the smallest P value was between [Va] and the heart weight divided by chest radius (HW/R) (r = ‐0.71). Intracardiac current was highest at intermediate pad sizes. The electrode pads that maximized [VG] tended to be large for the larger HW/R dogs, and smaller for the smaller HW/R dogs. In none of the HW/R groups did the largest electrode pads yield the highest intracardiac voltage gradient. We conclude that there is no simple way to determine in advance an electrode pad size that maximizes intracardiac current. The HW/R ratio influences but does not determine intracardiac current.

Mechanisms underlying alterations in power spectra of heart rate variability associated with ectopy

The low frequency components in heart rate variability (HRV) spectra are elevated in power spectra of segments with ectopy. The authors considered several hypothetical mechanisms which might give rise to this difference. (1) The phase of oscillations is disturbed by ectopic beats, resulting in lower coherence. (2) Reflex alterations in autonomic activity due to reduced arterial blood pressure may stimulate larger instability oscillations. (3) Underlying changes in autonomic activity give rise to elevated HRV and to increased rate of ectopy. These hypotheses were tested by computing power spectra by the method of average periodograms of segments just before, after, and centered on each ectopic beat. Spectra were not significantly different for segments before and after ectopic beats, or for segments centered on ectopic beats, suggesting that mechanisms 1 and 2 do not contribute significantly to the difference in power.<<ETX>>

A parallel/distributed architecture for hierarchically heterogeneous web-based cooperative applications

Abstract A new class of applications is described which requires cooperation among diverse users in multiple data and problem instance domains. The hierarchy of parallelism includes heterogeneity within a single instance of the problem, homogeneity among subsets of users within a problem domain, and multiple problem domains which share computational resources. The particular problem of genetic linkage analysis is used to illustrate and implement the architecture. GenoMap, the first implementation of this system is being deployed for several groups of cooperating users at multiple institutions in a study to isolate the genomic locus of the controlling gene(s) in several diseases including autism.