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Biomedical subjects

S Dillon

Publications and source records attributed to S Dillon.

At least 19 recordsLinked to original sources

Optimising parent selection in plant breeding: comparing metaheuristic algorithms for genotype building.

Stacking desirable haplotypes across the genome to develop superior genotypes has been implemented in several crop species. A major challenge in Optimal Haplotype Selection is identifying a set of parents that collectively contain all desirable haplotypes, a complex combinatorial problem with countless possibilities. In this study, we evaluated the performance of metaheuristic search algorithms (MSAs)-genetic algorithm (GA), differential evolution (DE), particle swarm optimisation (PSO), and simulated annealing (SA) for optimising parent selection under two genotype building (GB) objectives: Optimal Haplotype Selection (OHS) and Optimal Population Value (OPV). Using a diverse wheat population of 583 lines genotyped for 29,972 SNPs, forming 7645 haplotype blocks and phenotyped for stripe rust scores, we assessed each algorithm's performance across fitness optimisation, convergence speed, and computational efficiency. GA consistently achieved high fitness and rapid convergence, while DE showed robustness but required longer runtime and careful tuning. PSO performed well under the OHS criterion but was less effective for OPV. SA, although computationally lighter, was less consistent in finding optimal solutions. Simulation over 100 breeding cycles showed that OHS outperformed both OPV and GEBV-based selection in long-term genetic gain and diversity retention. OHS maintained heterozygosity and additive variance, which are key for sustainable improvement, while GEBV selection led to early allele fixation. Our findings underscore the potential of GB strategies that prioritise the collective performance of parent sets rather than individual ranking to enhance selection outcomes in genomic-assisted breeding programmes.

Plant Breeding

Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome.

Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules. Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (model pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (+/-SD) delta modal pI was -0.05 +/- 0.16, and in MCNS -0.05 +/- 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS (P < 0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P < 0.01 and for IgG1/albumin P < 0.05). For IgG4/transferrin and IgG4/albumin, P was < 0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with heavy proteinuria compared with children with MCNS with heavy proteinuria.

Adolescent

Exercise-induced mitral regurgitation is a predictor of morbid events in subjects with mitral valve prolapse.

OBJECTIVES: This study attempted to determine whether a subset of patients with mitral valve prolapse and no mitral regurgitation at rest will develop mitral regurgitation during exercise and have a higher than anticipated risk of morbid cardiovascular events. BACKGROUND: Mitral regurgitation in patients with mitral valve prolapse identifies a subset of patients at higher risk for morbid events. However, mitral regurgitation in patients with mitral valve prolapse may be intermittent and could go unrecognized. A provocative test to unmask mitral regurgitation in these patients would be useful. METHODS: Ninety-four adult patients with mitral valve prolapse and no mitral regurgitation at rest were studied during supine bicycle ergometry using color flow Doppler echocardiography in the apical four-chamber and long-axis views. Patients were prospectively followed up for morbid events. RESULTS: Thirty (32%) of 94 patients had exercise-induced mitral regurgitation. Prospective follow-up (mean 38 months) showed more morbid events in the group with than without mitral regurgitation and included, respectively, syncope (43% vs. 5%, p < 0.0001), congestive heart failure (17% vs. 0%, p < 0.005) and progressive mitral regurgitation requiring mitral valve replacement surgery (10% vs. 0%, p < 0.05). Cerebral embolic events, endocarditis or sudden death were rare and not different between groups. CONCLUSIONS: In patients with mitral valve prolapse without mitral regurgitation at rest, exercise provokes mitral regurgitation in 32% of patients and predicts a higher risk for morbid events.

Adolescent

Natural assemblages of marine bacteria exhibiting high-speed motility and large accelerations.

Natural communities of marine bacteria, an isolate (FMB-Bf3) from one marine community, and Escherichia coli were examined by video microscopy for the magnitude and uniformity of their speed. Natural communities formed tight microswarms that showed higher speeds (mean = 230 microns s-1) than did E. coli (15 microns s-1) or FMB-Bf3 (mean = 62 microns s-1). Outside the microswarms, the marine bacteria slowed to 45 microns s-1. Between turns, in mid run, and while travelling in straight lines, the natural-community bacteria accelerated up to 1,450 microns s-2 while the cultured bacteria showed maximum accelerations of 70 and 166 microns s-2. The frequency distribution of speed change for the marine bacteria was skewed towards a few large negative accelerations and a range of positive accelerations. The general pattern was one of relatively slow increases in speed followed by abrupt declines. The results indicate that the mechanical generation and energetic maintenance, as well as the environmental function, of bacterial motility need reappraisal. We conclude that the standard bacterial motility parameters of low and uniform speed, derived from culture-based studies, are not necessarily applicable to marine bacterial communities.

Escherichia coli

Activation of platelet phosphatidylinositide 3-kinase requires the small GTP-binding protein Rho.

The small GTP-binding protein Rho regulates the assembly of actin stress fibers and focal adhesions in cells responding to growth factors. ADP-ribosylation of Rho by C3 transferase blocks this function; however, an enzymatic target for Rho has not yet been defined. We now report that Rho activates phosphatidylinositide 3-kinase in soluble preparations of platelets. Activation of phosphatidylinositide 3-kinase by GTP gamma S is blocked by ADP-ribosylation of endogenous Rho, and Rho shifts to the cytoskeleton in platelets exposed to thrombin. The inhibitory effects of ADP-ribosylation are overcome by exogenous recombinant Rho but not by recombinant Rac, another member of the Ras superfamily. Exposure of platelets to thrombin has been reported to lead to activation of phosphatidylinositide 3-kinase, a shift of this enzyme to the platelet membrane skeleton, and rapid cytoskeletal reorganization. In other studies, ADP-ribosylation of Rho has been found to inhibit thrombin-induced platelet aggregation, a cytoskeletally linked event. We suggest that Rho may exert its effects on cytoskeletal reorganization via phosphatidylinositide 3-kinase.

Adenosine Diphosphate Ribose

The effect of exercise-induced myocardial ischemia on postischemic left ventricular diastolic filling.

To determine whether exercise-induced ischemia impairs left ventricular diastolic filling in the postischemic period in humans, 101 men (mean age 57 +/- 10 years) were studied before and 2 h after a symptom-limited thallium-201 tomographic treadmill with pulsed Doppler echocardiography of mitral valve inflow. In the postischemic period 2 h after exercise, diastolic filling was significantly impaired in the ischemia group (reversible thallium defect; n = 24) as reflected by a decrease in the peak early filling velocity (44.5 +/- 10.1 to 39.9 +/- 9.9 cm/s, p less than 0.01), peak early to atrial filling velocity ratio (0.91 +/- 0.27 to 0.76 +/- 0.25, p less than 0.001), and deceleration rate of early filling (281 +/- 104 to 245 +/- 86 cm/s2, p less than 0.01). Similar alterations in the postischemic period occurred in the myocardial infarction-ischemia group (partially reversible defect; n = 28) as seen by a decrease in the peak early filling velocity (47.6 +/- 11.6 to 41.8 +/- 12.0 cm/s, p less than 0.001), peak early to atrial filling velocity ratio (0.84 +/- 0.21 to 0.68 +/- 0.18, p less than 0.001), and early time-velocity integral (7.06 +/- 1.78 to 5.64 +/- 2.07 cm, p less than 0.001). In the control group (no defects; n = 33) and myocardial infarction group (fixed defect; n = 16), diastolic filling was unchanged in the postexercise period. Heart rate and blood pressure were unchanged post-exercise in all groups. Exercise-induced ischemia impairs diastolic filling in the postischemic period in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation

The influence of obesity on left ventricular filling and systolic function.

Little information on the possible influence of obesity on diastolic function is available. Thus we studied 24 asymptomatic obese volunteers (greater than 120% ideal body weight; mean 153 +/- 30%), aged 34 +/- 11 years. Each obese subject was matched for age, height, and sex, with a healthy normal-weight control subject. Isovolumic relaxation time (IVRT) and diastolic filling indexes were determined by pulsed Doppler echocardiography. The IVRT was significantly prolonged in the obese group (84 +/- 17 msec) as compared with the control group (57 +/- 13 msec; p less than 0.0002). Multiple regression analysis showed that percentage of ideal body weight was the most important predictor of peak early filling velocity (r = 0.59, p less than 0.005) and mean deceleration rate of early filling (r = 0.61, p less than 0.005) in the obese group. However, age as compared with percentage of ideal body weight was a more important determinant of the relative distribution of early and atrial filling, such as peak early-to-atrial filling velocity ratio (r = -0.75, p less than 0.0001). Ejection fraction, heart rate, and blood pressure did not differ between the obese and control groups. In conclusion, obesity is associated with preclinical abnormalities of IVRT, which may reflect impaired relaxation. The IVRT may be useful in the early detection of left ventricular dysfunction in obesity. Last, studies comparing Doppler indexes of diastolic filling among groups must control for potential differences in percentage of ideal body weight.

Adolescent

Left ventricular ejection fraction is increased during transesophageal echocardiography in patients with impaired ventricular function.

Transesophageal echocardiography (TEE) is increasingly being used to assess left ventricular function (LVF). However, little data exist on the quantitative accuracy of this technique and its influence on LVF. Thus 50 ambulatory adult patients (mean age 62 +/- 15 years) were studied with transthoracic echocardiography (TTE) immediately before, before the end, and 10 minutes after TEE. Left ventricular ejection fraction (LVEF) was calculated using the modified Simpson's method. In subjects (n = 24) with impaired LVF (LVEF less than 55% by TTE), TTE-derived LVEF increased from 37 +/- 13% to 45 +/- 15% (p less than 0.001) during TEE. In 13 of 24 subjects with abnormal LVF, LVEF significantly increased during TEE as defined by an increase in LVEF by at least 5 ejection fraction units. In four of these subjects LVF normalized during TEE. LVEF was unchanged during and after TEE in the subjects (n = 26) with normal LVF (LVEF greater than 55%). An excellent correlation was found between LVEF derived by TEE and that derived by TTE performed during TEE (r = 0.93, SEE = 6.6%, p less than 0.001). LVEF determined by TEE compared well with that derived by TTE and should be a useful measure of global left ventricular function. However, an increase in LVEF during TEE occurs in over 50% of patients with impaired LVF and may be important to consider in individual subjects.

Adult

Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis.

To determine if aortic stenosis severity could be accurately measured by two-dimensional transesophageal echocardiography (TEE), 62 adult subjects (mean age 66 +/- 12 years) with aortic stenosis had their aortic valve area (AVA) determined by direct planimetry using TEE, and with the continuity equation using combined transthoracic Doppler and two-dimensional echocardiography (TTE). Eighteen subjects had AVA calculated by the Gorlin method during catheterization. An excellent correlation (r = 0.93, SEE = 0.17 cm2) was found between AVA determined by TEE (mean 1.24 +/- 0.49 cm2; range 0.40 to 2.26 cm2) and TTE (mean 1.23 +/- 0.46 cm2; range 0.40 to 2.23 cm2). The absolute (0.13 +/- 0.12 cm2) and percent (10.8 +/- 8.9%) differences between AVA determined by TEE versus TTE were small. Excellent correlations between AVA by TEE and TTE were also found in subjects with normal systolic function (r = 0.95, SEE = 0.14 cm2; n = 38) and impaired function (r = 0.91, SEE = 0.21 cm2; n = 24). AVA determined by catheterization correlated better with AVA measured by TEE (r = 0.91, SEE = 0.15 cm2) than AVA measured with TTE (r = 0.84, SEE = 0.19 cm2). These data demonstrate that AVA can be accurately measured by direct planimetry using TEE in subjects with aortic stenosis. TEE may become an important adjunct to transthoracic echocardiography in the assessment of aortic stenosis severity.

Adult

An O antigen can interfere with the function of the Yersinia pseudotuberculosis invasin protein.

Escherichia coli strains harbouring the Yersinia pseudotuberculosis inv gene are able to enter cultured mammalial cells. We show here that this property is not shared by all enteric bacteria, since Shigella flexneri 2a cured of its virulence-associated plasmid and harbouring the inv gene is unable to enter mammalian cells efficiently. Mapping studies showed that the region of the chromosome responsible for this phenotype includes rfaB, a locus involved in the production of O antigen. S. flexneri 2a strains that express O antigen were unable to enter mammalian cells, even though invasin was efficiently expressed and localized, showing that this structure interferes with invasin activity. The O antigen either masks invasin or sterically hinders the ability of the mammalian cell receptor to bind this protein.

Adhesins, Bacterial

HIV infection, genital ulcer disease, and crack cocaine use among patients attending a clinic for sexually transmitted diseases.

BACKGROUND: Recently there has been a rise in genital ulcer disease (GUD) in urban minority heterosexuals in the United States. The impact of these increased GUD rates on HIV transmission patterns in this population is unknown. METHODS: Sexually transmitted disease (STD) diagnoses were correlated with HIV antibody status and risk factor history in 194 patients who consented to HIV testing at an STD clinic in central Brooklyn. RESULTS: Of 36 HIV-positive patients, 23 (64%) denied HIV risk factors other than heterosexual contact with persons of unknown HIV status. HIV antibody was associated with GUD (odds radio [OR] = 2.72, 95% confidence interval [CI] = 1.20-6.24), multiple concurrent STDs (OR = 2.51, 95% CI = 1.08-5.81), and a history of crack cocaine use (OR = 2.98, 95% CI = inexact-9.61). Crack use was also associated with GUD (OR = 15.15, 95% CI = 3.27-inexact) and multiple simultaneous STDs (OR = 13.87, 95% CI = 4.62-inexact). In a log-linear model analysis, HIV infection was independently associated with GUD and crack use. HIV infection, genital ulcer disease, and crack cocaine use were more common in women than men. CONCLUSIONS: The association between HIV infection and GUD seen here may be secondary to high-risk sexual behavior, which in turn may be partially attributable to crack cocaine use and drug-related prostitution. The high rate of coinfection with HIV and GUD raises a concern about the increased efficiency of sexual transmission of HIV in this population.

Comorbidity

An acousto-optically steered laser scanning system for measurement of action potential spread in intact heart.

An optical scanning device that combines a voltage-sensitive dye and an acousto-optically steered He-Ne laser beam is described. This device is capable of scanning 128 sites every 4 ms and recording and storing the fluorescence signals for a duration of up to 1 s (several beats). Comparison of an activation map constructed from laser scanning to those obtained from multiple extracellular electrodes suggests that this technique is highly reliable. Although motion-induced light scattering appears to alter the shape of the action potential, the upstroke can be distinguished quite reliably even in a vigorously contracting muscle. This technique provides high resolution (up to 50 micron) and high flexibility (i.e., the scanned sites can be concentrated over a small or very large area) in measuring the spread of activation in heart muscle. By having only one excitation and one measurement element, the approach offers simplicity and high flexibility to the user. We have shown that this system can be readily applied to the task for which it was intended--probing the mechanisms of arrhythmias in the mammalian myocardium. It has been demonstrated, for example, that arrhythmias due to automaticity can be readily distinguished from those due to reentry through the mapping capability of the laser scanner. In addition, the ability of laser scanner to measure membrane depolarization directly during arrhythmias may make this technique superior to conventional electrocardiographic mapping techniques.

Acoustic Stimulation

The diagnostic status of patients with conspicuous psychiatric morbidity in primary care.

A 7% one-year prevalence rate of conspicuous psychiatric morbidity was found in patients attending a single general practice. The nature of the morbidity was examined by a detailed assessment of mental state and personality, using interview schedules administered by a psychiatrist. Depressive disorders were presented by nearly half of the patients. The overall sex incidence of the disorders was equal, but alcohol abuse was more common in males. A personality disorder was present in 33.9% of all patients seen, although it was rarely diagnosed as the primary problem and was linked to the diagnosis of anxiety states, rather than depressive neurosis. These findings are discussed in relation to other epidemiological studies in primary care.

Alcoholism

A new laser scanning system for measuring action potential propagation in the heart.

A rapid laser scanning system was developed to map the spread of excitation in amphibian and mammalian hearts stained with fluorescent dye. Isochronic maps of conduction were constructed by timing the upstroke of the optical action potential; 128 sites could be scanned in 4 milliseconds. The accuracy of this technique was verified by recording simultaneously from 16 unipolar electrodes placed in different areas of the heart. Conducted action potentials in normal frog heart propagated at 0.1 meter per second. Propagation of action potentials was also monitored in ischemic cat heart, in which both driven and arrhythmic action potential upstrokes could be tracked. The results suggest that this system is capable of scanning the normal and abnormal spread of electrical activity in the heart.

Action Potentials