Accurate automatic detection of end-diastole from left ventricular pressure using peak curvature

Precise identification of end-diastole (ED), corresponding to the end of diastole and start of systole, is crucial for accurate assessment of cardiac function. The aims of this study were to develop a new algorithm based on peak curvature (kappa(p)) for detecting ED as a "corner" in left ventricular pressure (LVP) signals, and to compare this approach with "gold-standard" ED obtained by manual annotation (ED(man)) and ED calculated with previously described algorithms that use an LVP first-derivative threshold (dP/dt(0) or dP/dt(100)), the peak LVP second-derivative (d(2)P/dt(2)(p)) or ECG R-wave peak (ECG(R)). Using customized software, all algorithms were applied to data derived from 213 large animal studies spanning a wide range of animal ages (fetus to adult), heart rates, inotropic states, and loading conditions. Differences between ED(man) and each algorithm were then compared after defining an acceptance region for the ED detection based on ED(man) interobserver variability. ED detected with kappa(p) was the most accurate (p < 0.001) and least variable (p < 0.001), with 97% of measurements within the acceptance region and difference from ED(man) of (1.5 +/- 4.2) ms. By contrast, ED was often detected early with dP/dt(0) and dP/dt(100) , and late with d(2)P/dt(2)(p) and ECG(R). These results indicate that the peak curvature algorithm using LVP provides accurate and reliable detection of ED.     

Bayesian nonstationary autoregressive models for biomedical signal analysis

We describe a variational Bayesian algorithm for the estimation of a multivariate autoregressive model with time-varying coefficients that adapt according to a linear dynamical system. The algorithm allows for time and frequency domain characterization of nonstationary multivariate signals and is especially suited to the analysis of event-related data. Results are presented on synthetic data and real electroencephalogram data recorded in event-related desynchronization and photic synchronization scenarios.     

Mixtures of general linear models for functional neuroimaging

We set out a new general framework for making inferences from neuroimaging data, which includes a standard approach to neuroimaging analysis, statistical parametric mapping (SPM), as a special case. The model offers numerous conceptual and statistical advantages that derive from analyzing data at the "cluster level" rather than the "voxel level" and from explicit modeling of the shape and position of clusters of activation. This provides a natural and principled way to pool data from nearby voxels for parameter and variance-component estimation. The model can also be viewed as performing a spatio-temporal cluster analysis. The parameters of the model are estimated using an expectation maximization (EM) algorithm.     

Storage capacity of multilayer Boolean neural networks

A method for determining the statistical storage capacity of a multilayer Boolean neural network is presented. Theoretical values are compared with those obtained by computer simulation of a number of small networks.<>     

Thrombotic events and markers of oxidation and inflammation in hemodialysis

The goal of this study was to determine whether antioxidant therapy with vitamin E would alter the rate of vascular access complications or other macrovascular complications in hemodialysis (HD) patients. A secondary goal of the study was to explore the relationship between baseline pretreatment markers of oxidative stress (the advanced glycation end product pentosidine and basal levels of vitamin Eα and γ) and the subsequent development of access failure. Thirty‐five stable patients treated by HD were recruited for the study. Patients were provided with vitamin E (800 IU) or placebo capsules to be taken daily. Clinical variables, vascular access function (flow meter access flow measurements), and circulating blood markers were obtained initially and every 3 months throughout the study. Vitamin Eα levels rose in treated patients from 12.7 ± 4.4 to 25.1 ± 15.1 µg/mL at 3 months and 28.6 ± 14.8 µg/mL at 6 months. Vitamin Eγ levels fell in treated patients from 3.9 ± 1.7 to 2.3 ± 1.5 µg/mL at 3 months and 1.7 µg/mL at 6 months. Patients who subsequently developed repeated thrombotic vascular access events were characterized by higher baseline pentosidine content of circulating proteins. Patients who developed a myocardial infarction had higher pentosidine, lower vitamin Eα, and much lower vitamin Eγ than patients who did not develop thrombotic events. These findings lead to the speculation that the anti‐inflammatory effects of vitamin Eγ may play a more important role in thrombotic vascular events than the antioxidant effects of vitamin Eα. Additional studies of these interactions are in progress.     

The action of a muscle proteinase on the myofibrillar proteins of bovine muscle

Myofibrillar proteins from bovine muscle have been treated with a Ca²⁺ activated muscle proteinase and the consequent changes in these proteins have been examined by various techniques. Tropomyosin, α-actinin and troponin were substrates for the enzyme, the last losing its property of inhibiting actomyosin ATPase in the absence of Ca²⁺ ions. Actin and actomyosin were apparently not digested but the Mg²⁺-activated ATPase activity of actomyosin was less after treatment whereas the Ca²⁺-activated ATPase was unaffected. It is suggested that the observed destruction of the Z-bands of the myofibrils by this proteinase is due to its digestion of the α-actinin, rather than the actin component.     

Effect of prenatal heat stress on brain growth and serial discrimination reversal learning in the guinea pig

Exposure of pregnant guinea pigs to an environmental temperature of 42 degrees C for 1 hr daily on Days 20-24 of gestation resulted in a significant reduction in the birthweight and brainweight of newborn offspring. These deficits persisted to early maturity and were still evident at 250 days of age following behavioral testing. Although some degree of postnatal neurogenesis and brain growth had occurred, this was not sufficient to compensate for the retarding influence of prenatal hyperthermia. Heat stress was also observed to seriously impair learning performance on the original discrimination task and this tendency persisted over the subsequent 4 reversals for both initial and perseverative errors. Impaired learning performance was related to reduction in brainweight. Animals with lower brainweights made significantly more initial, perseverative and total number of errors over the 5 problems. In addition, 12 of the 14 behaviorally tested stressed progeny had brainweights that were at least 2 standard deviations below the mean of the controls and as a result were classified as micrencephalic. Although heat stressed animals showed a significant reduction in the number of amacrine synapses in the inner plexiform layer of the retina, performance differences were not atrributed to changes in synaptic organisation of the retinal circuitry or to visual or other ophthalmic defects, but brain function. Animals with higher mean maternal poststressing core temperatures gave birth to progeny which had smaller whole and part wet-brainweights. Examination of the effect of poststressing core temperature on brainweight revealed that brain growth, independent of bodyweight, was retarded when this temperature elevated above 41.5 degrees C. This represented a rise of approximately 2.1 degrees C above normal and for each 1 degree C rise above this temperature, brainweight was reduced by 0.4227 g of the control value. Analysis of the atmospheric content of the incubator during stressing sessions ruled out the possibility that changes in level of oxygen and carbon dioxide may have contributed to the retarding influence on fetal development and learning ability in the guinea pig.     

Increased apoptosis and DNA double-strand breaks in the embryonic mouse brain in response to very low-dose X-rays but not 50 Hz magnetic fields

The use of X-rays for medical diagnosis is enhancing exposure to low radiation doses. Exposure to extremely low-frequency electromagnetic or magnetic fields is also increasing. Epidemiological studies show consistent associations of childhood leukaemia with exposure to magnetic fields but any causal relationship is unclear. A limitation in assessing the consequence of such exposure is the availability of sensitive assays. The embryonic neuronal stem and progenitor cell compartments are radiosensitive tissues. Using sensitive assays, we report a statistically significant increase in DNA double-strand break (DSB) formation and apoptosis in the embryonic neuronal stem cell compartment following in utero exposure to 10–200 mGy X-rays. Both endpoints show a linear response. We also show that DSB repair is delayed following exposure to doses below 50 mGy compared with 100 mGy. Thus, we demonstrate in vivo consequences of low-dose radiation. In contrast to these impacts, we did not observe any significant induction of DSBs or apoptosis following exposure to 50 Hz magnetic fields (100 or 300 µT). We conclude that any DSB induction by treatment with magnetic fields is lower than following exposure to 10 mGy X-rays. For comparison, certain procedures involving computed tomography scanning are equivalent to 1–5 mGy X-rays.