Mathematical modeling of laser ablation in liquids with application to laser ultrasonics.

The use of laser ablation as a means of generating ultrasonic waves in liquid metals is studied in this paper. A mathematical model for predicting the onset of ablation is developed, as is a model of the ablation process based on steady state, one-dimensional gas dynamics in which the vapor phase is treated as an ideal gas. The results of this model are then used in a quasi-two-dimensional model of laser ablation that accounts for the spatial distribution of intensity in the laser beam. Model predictions are compared with experiments conducted on liquid mercury and excellent agreement is obtained. Based on these results, a simplified model is developed that shows excellent agreement with both the theory and the experiments.

Spatial variability of soil organic carbon in grasslands: implications for detecting change at different scales.

Extensive data used to quantify broad soil C changes (without information about causation), coupled with intensive data used for attribution of changes to specific management practices, could form the basis of an efficient national grassland soil C monitoring network. Based on variability of extensive (USDA/NRCS pedon database) and intensive field-level soil C data, we evaluated the efficacy of future sample collection to detect changes in soil C in grasslands. Potential soil C changes at a range of spatial scales related to changes in grassland management can be verified (alpha=0.1) after 5 years with collection of 34, 224, 501 samples at the county, state, or national scales, respectively. Farm-level analysis indicates that equivalent numbers of cores and distinct groups of cores (microplots) results in lowest soil C coefficients of variation for a variety of ecosystems. Our results suggest that grassland soil C changes can be precisely quantified using current technology at scales ranging from farms to the entire nation.

Radioimmunoguided imaging of prostate cancer foci with histopathological correlation.

PURPOSE: We have previously presented a technique that fuses ProstaScint and pelvic CT images for the purpose of designing brachytherapy that targets areas at high risk for treatment failure. We now correlate areas of increased intensity seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients to evaluate the accuracy of this technique in localizing intraprostatic disease. METHODS AND MATERIALS: The 7 patients included in this study were evaluated between June 1998 and March 29, 1999 at Metrohealth Medical Center and University Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each patient were obtained before transperineal biopsy and seed implantation. Each patient's prostate gland was biopsied at 12 separate sites determined independently of Prostascint-CT scan results. RESULTS: When correlated with biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative predictive value of 88%. CONCLUSION: The image fusion of the pelvic CT scan and ProstaScint scan helped identify foci of adenocarcinoma within the prostate that correlated well with biopsy results. These data may be useful to escalate doses in regions containing tumor by either high-dose rate or low-dose rate brachytherapy, as well as by external beam techniques such as intensity modulated radiotherapy (IMRT).

A plate-rod device for treatment of cervicothoracic disorders: comparison of mechanical testing with established cervical spine in vitro load testing data.

Posterior cervical internal fixation has long been accomplished using wires, hooks, and rods. More recently, the cervical lateral mass screw and plate or rod systems have been used effectively in unstable lower cervical spine disorders. Each form of fixation has its advantages and disadvantages. Interspinous wiring and lateral mass screw placement obviate canal penetration in the cervical region but are associated with a potential neurologic risk as a result of canal encroachment. Minor canal intrusion by laminar hooks in the thoracic spine pose a lesser neurologic risk than in the cervical region. To exploit the benefits and safety features of spinal instrumentation, a combination plate rod construct (PRC) has been developed that obviates canal penetration in the cervical region by way of lateral mass and cervical pedicle screw fixation and hooks or wires in the thoracic spine. A biomechanical analysis of the PRC device was performed and compared with the in vivo maximal load data of the cervical spine and established maximal load data of the Roy-Camille posterior cervical fixation system. The PRC has greater strength and resistance to failure than is necessary to sustain maximal in vivo cervical spine loads, and it has also compared favorably with the parameters of the Roy-Camille system. The PRC device, or variations on it, is an excellent option for spinal fixation across the cervicothoracic junction because of its superior biomechanical qualities and versatility in stabilizing a complex anatomic junction of the spine.

A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome.

Occipital horn syndrome (OHS), an X-linked connective tissue disorder, has recently been shown to result from mutations in the Menkes disease gene (MNK), which encodes a copper-transporting ATPase. By Southern analysis we detected a small deletion in a region 5' to the MNK gene in one patient with OHS. Genomic clones from an unaffected individual were isolated and sequenced, revealing three tandem 98 bp repeats situated upstream of the reported transcription start site, and analysis of the patient's DNA showed a deletion of one of the repeats. The deletion is likely to be responsible for the disease in this patient, as it was not observed in 110 unaffected individuals analyzed, and no other mutation in the patient was detected by RT-PCR and chemical cleavage mismatch analysis or by cDNA sequence analysis. The deletion is associated with a dramatic decrease in expression of a chloramphenicol acetyltransferase reporter gene, implicating the repeat sequences in regulation of MNK expression, although a quantitative analysis of MNK mRNA from a cell line derived from the patient shows no detectable reduction. Other experiments revealed no effect on the site of transcription initiation, termination or on splicing.

Estimation of regional end-systolic wall stress during exercise in coronary artery disease.

Estimating left ventricular wall stress has recognized applications, but formulae for global stress cannot be applied to ischemic ventricles. A mathematic method for estimating regional stress in infarcted ventricles has been described. The hypothesis tested was that exercise-induced ischemia increases end-systolic wall stress. Subcostal four-chamber echocardiograms were recorded at rest and during peak symptom-limited exercise in 19 controls and 41 patients with chest pain undergoing coronary arteriography. Centerline regional wall motion and regional end-systolic wall stress were measured at rest and at peak exercise. The normal controls had increased wall motion with exercise, but wall stress remained low. All 32 of the patients with coronary artery disease (> or = 50% diameter narrowing) had wall motion abnormalities with exercise, but the sensitivity of identifying right coronary artery obstructions was poor. Patients with coronary disease had higher regional stress at peak exercise than did the controls. The sensitivity of identifying lesions in all three coronary arteries (0.95 to 1.0) was better than that for wall motion (p < 0.04). The specificity of wall stress needs to be tested in a larger population. Exercise-induced ischemia causes increased regional end-systolic wall stress that reflects its distribution in patients with coronary artery disease. These changes can be measured non-invasively during exercise echocardiography.

Preliminary imaging results using In-111 labeled CYT-356 (Prostascint) in the detection of recurrent prostate cancer.

To evaluate whether In-111 capromab pendetide (an antibody conjugate directed to a glycoprotein found primarily on the cell membrane of prostate tissue) radioimmunoscintigraphy can localize residual or metastatic prostatic carcinoma in 15 patients after prostatectomy and lymphadenectomy for prostatic carcinoma with rising serum prostate-specific antigen. One patient with 0.6 ng/ml serum prostate-specific antigen had normal imaging results and 14 patients had scintigraphic evidence of residual prostatic bed or metastatic prostatic carcinoma. Two patients with borderline abnormal bone scans had abnormal activity in the same regions on In-111 capromab pendetide images. All patients had negative radiographic abdominal and pelvic cross-sectional prestudy images, and there were no adverse effects related to In-111 capromab pendetide infusion and little human antimouse antibody response.

Shoot growth dynamics and photosynthetic response to increased nitrogen availability in the alpine willow Salix glauca.

Plants subjected to increases in the supply of resource(s) limiting growth may allocate more of those resources to existing leaves, increasing photosynthetic capacity, and/or to production of more leaves, increasing whole-plant photosynthesis. The responses of three populations of the alpine willow, Salix glauca, growing along an alpine topographic sequence representing a gradient in soil moisture and organic matter, and thus potential N supply, to N amendments, were measured over two growing seasons, to elucidate patterns of leaf versus shoot photosynthetic responses. Leaf-(foliar N, photosynthesis rates, photosynthetic N-use efficiency) and shoot-(leaf area per shoot, number of leaves per shoot, stem weight, N resorption efficiency) level measurements were made to examine the spatial and temporal variation in these potential responses to increased N availability. The predominant response of the willows to N fertilization was at the shoot-level, by production of greater leaf area per shoot. Greater leaf area occurred due to production of larger leaves in both years of the experiment and to production of more leaves during the second year of fertilization treatment. Significant leaflevel photosynthetic response occurred only during the first year of treatment, and only in the dry meadow population. Variation in photosynthesis rates was related more to variation in stomatal conductance than to foliar N concentration. Stomatal conductance in turn was significantly related to N fertilization. Differences among the populations in photosynthesis, foliar N, leaf production, and responses to N fertilization indicate N availability may be lowest in the dry meadow population, and highest in the ridge population. This result is contrary to the hypothesis that a gradient of plant available N corresponds with a snowpack/topographic gradient.

Discrimination and reproducibility of an information maximizing multivariable model.

Predictor variables for multivariate rules are frequently selected by methods that maximize likelihood rather than information. We compared the discrimination and reproducibility of a prediction rule for pneumonia derived using extended dependency analysis (EDA), an information maximizing variable selection program, with that of a validated rule derived using logistic regression. Discrimination was measured by receiver-operating characteristic (ROC) analysis, and reproducibility by rederivation of the rule on 200 replicate samples of size 250 and 500, generated from a training cohort of 905 patients using Monte Carlo techniques. Four of the five predictor variables selected by EDA were identical to those selected by logistic regression. With each variable weighted by its conditional contribution to total information transmission, EDA discriminated pneumonia and nonpneumonia in the training cohort with an ROC area of 0.800 (vs 0.816 for logistic regression, p = 0.60), and in the validation cohort with an area of 0.822 (vs 0.821 for logistic regression, p = 0.98). EDA demonstrated reproducibility comparable to that of logistic regression according to most criteria for replicability. Replicate EDA models showed good discrimination in the training and testing cohorts, and met statistical criteria for validation (no significant difference in ROC areas at a one-tailed alpha level of 0.05) in 80.8% to 94.2% of cases. We conclude that extended dependency analysis selected the most important variables for predicting pneumonia, based on a validated logistic regression model. The information-theoretic model showed good discriminatory power, and demonstrated reproducibility according to clinically reasonable criteria. Information-theoretic variable selection by extended dependency analysis appears to be a reasonable basis for developing clinical prediction rules.

Non-radioactive detection of the most common mutations in the cystic fibrosis transmembrane conductance regulator gene by multiplex allele-specific polymerase chain reaction.

A rapid, simple, nonradioactive method for detection of four common mutations causing cystic fibrosis (CF) has been developed combining multiplexing with allele-specific polymerase chain reaction amplification. This approach (MASPCR) provides an easy assay for direct genotyping of normal and mutant CF alleles in homozygotes and heterozygotes. The strategy involves multiplex PCR of exons 10, 11, and 21 within the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a single reaction containing three common oligoprimers and either the four normal or four mutant oligos corresponding to the delta F508, G551D, G542X, and N1303K mutations. Primers are chosen so that the size of the four PCR products differ, thereby facilitating detection on agarose gels following amplification in the same reaction. Patient samples are primed with either four normal or four mutant oligo mixtures, and PCR products run in parallel on gels to detect band presence or absence. This approach provides a simple and potentially automated method for cost-effective population screening.

Detection of the most common mutations causing beta-thalassemia in Mediterraneans using a multiplex amplification refractory mutation system (MARMS).

A rapid, simple, cost-effective, non-radioactive method for detection of the most common mutations causing beta-thalassemia in Mediterranean people has been developed by combining multiplexing with the amplification refractory system. This approach, the multiplex amplification refractory mutation system (MARMS), provides an easy assay for direct detection of normal and mutant beta-globin genes in homozygotes and heterozygotes. The strategy involves multiplex PCR of four of the five regions of interest within the beta-globin gene in a single reaction containing a common oligoprimer and either the normal or mutant oligonucleotides corresponding to IVS-1 nucleotide 1 or IVS-1 nucleotide 6, IVS-1 nucleotide 110, codon 39, and IVS-2 nucleotide 1 regions. Primers are chosen so that the sizes of the four PCR products differ, thereby facilitating detection on agarose gels following amplification. Patient samples are primed with either four normal or four mutant oligonucleotide mixtures and the common oligoprimer, and PCR products run in parallel on gels to detect band presence or absence. This approach simplifies mutation detection and shows promise for automation employing fluorescent-tagged primers.

Reproducibility of predictor variables from a validated clinical rule.

It has been suggested that clinical prediction rules are not reproducible, and that the most important variables frequently do not appear in replicate models. The authors studied the reproducibility of a validated rule for predicting radiographic evidence of pneumonia (ROC areas for the training and validation cohorts, 0.816 and 0.821, respectively). Two hundred replicate samples of size 250 and size 500 were generated by sampling without replacement from the original training cohort of 905 patients with a 14.6% prevalence of pneumonia. Forward selection was performed among 31 candidate variables by stepwise logistic regression. Using as reproducibility criteria: 1) inclusion of all five variables from the original model in the original order; 2) inclusion of all five variables in any order; 3) inclusion of the first three variables; 4) inclusion of the first two variables; 5) inclusion of the first variable; and 6) inclusion of any of the five variables: 2.5%, 13.5%, 48.5%, 85.5%, 98.0%, and 100% of replicate models of sample size 500, respectively, met the criteria, whereas 0%, 0%, 16.5%, 49.0%, 71.5%, and 97.5% of models of sample size 250 met the criteria (all comparisons by sample size p < .0001 except for criteria 1 and 6, p = 0.07). Mean ROC areas in the training and validation samples were 0.829 and 0.791 for replicate models of sample size 500, and 0.831 and 0.779 for models of sample size 250. There was no significant difference in ROC areas between training and validation cohorts for 80.5% of models of sample size 500, and for 75.3% of models of sample size 250.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluorescence-based, multiplex allele-specific PCR (MASPCR) detection of the delta F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Cystic fibrosis (CF) is a common genetic disorder in Caucasians, and in some populations 70% of cases are associated with a 3 base pair (bp) deletion (delta F508) in the CFTR gene. We have implemented a fluorescence-based, multiplex allele-specific polymerase chain reaction (MASPCR) assay for deletion of the delta F508 mutation. Different allele-specific fluorescently-tagged primers are used in the PCR reaction to distinguish between normal and delta F508 alleles. Fluorescent PCR products are then visualized in a single lane on an agarose gel following electrophoresis combined with real-time multicolour fluorescence detection. The approach simplifies diagnosis of the most common mutation in the CFTR gene, and holds promise for a multiplex allele-specific, fluorescence-tagged gene amplification strategy for detection of additional CF mutations which may result in more cost-effective testing without increasing the risk of missed or erroneous diagnoses.

Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.

Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exercise ejection fraction (r = 0.48, p less than 0.001) at the follow-up study. Of the 32 patients who increased their left ventricular mass index greater than 7%, 18 improved their rest ejection fraction greater than 0.05 units and 17 improved their exercise ejection fraction greater than 0.05 units. Conversely, of the 13 patients who failed to increase their left ventricular mass index, only three improved their rest ejection fraction and one improved the exercise ejection fraction (Fisher's exact test, p less than 0.05). We reached three conclusions. First, in humans, significant hypertrophy of the noninfarcted myocardium can be detected by two-dimensional echocardiography, 9 months postmyocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of long-term high intensity aerobic training on left ventricular volume during maximal upright exercise.

The purpose of this study was to determine whether high intensity, long-term aerobic training causes the left ventricle to develop different mechanisms for increasing cardiac output during submaximal and maximal upright bicycle exercise. Fifteen competitive collegiate long distance runners and 14 healthy sedentary adults were studied with use of subcostal view four chamber two-dimensional echocardiography at rest and during and at peak maximal upright bicycle exercise. At rest, the athletes had a larger end-diastolic volume index (85 +/- 14 ml/m2) (mean +/- 1 SD) than that of the sedentary adults (62 +/- 14 ml/m2) and a larger end-systolic volume index (37 +/- 11 versus 21 +/- 6 ml/m2). During low and moderate intensity exercise, end-diastolic and stroke volume indexes increased in both groups, but at high intensity exercise and at peak exercise the end-diastolic volume index of both groups decreased significantly below rest value (athletes, 61 +/- 14; sedentary subjects, 46 +/- 10 ml/m2, both p less than 0.001 compared with rest). Reflecting the decreased end-diastolic volume index, at peak exercise, the stroke volume index had decreased from intermediate exercise values in both groups and was not different from rest values. Therefore, although long distance runners have a dilated left ventricle at rest, they utilize the same mechanisms as sedentary adults for increasing cardiac output during upright dynamic exercise. At low and moderate level exercise, the Frank-Starling mechanism is a dominant mechanism for increasing cardiac output, but at peak exercise, probably because of reduced diastolic left ventricular filling, enhanced contractility is the major mechanism for maintaining stroke volume.

Quantitative analysis of segmental wall motion during maximal upright dynamic exercise: variability in normal adults.

Twenty-five healthy adults underwent subcostal-view, four-chamber two-dimensional echocardiographic examination while upright at rest and at the peak of maximal bicycle exercise. The purpose of the study was to determine whether the variability in regional left ventricular endocardial motion, previously demonstrated to be present at rest, persisted at peak exercise. The rest and exercise end-diastolic and end-systolic endocardial contours were visually identified, digitized, and divided into 32 radial segments after realignment by the computer. At rest there was similar percent segmental area reduction for the septum (segments 1 to 12) (54 +/- 4%, mean +/- 1 SD), apex (segments 13 to 20) (67 +/- 3%), and lateral wall (segments 21 to 32) (67 +/- 8%). At peak exercise the percent area reduction increased significantly: septum 84 +/- 5%, apex 88 +/- 2%, lateral wall 83 +/- 6% (p less than .001 compared with rest for all areas). However, there was considerable variability in percent area reduction between different radial segments in the same individual. At rest the difference between minimal and maximal percent area reduction within the same individual was 49 +/- 17 percentage units (range 21 to 83) and that at peak exercise was 32 +/- 17 percentage units (range 0 to 66). It is concluded that, because the range of standard deviation of normal endocardial motion and the degree of variability between radial segments in the same healthy individual are significant, qualitatively determined "hypokinesis," as commonly assessed clinically, may be a normal event. However, segmental akinesis or dyskinesis, which occurred rarely at rest and never at peak exercise, must be considered abnormal events.