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Biomedical subjects

J D Nichols

Publications and source records attributed to J D Nichols.

At least 19 recordsLinked to original sources

Assessing spatial coupling in complex population dynamics using mutual prediction and continuity statistics.

A number of important questions in ecology involve the possibility of interactions or "coupling" among potential components of ecological systems. The basic question of whether two components are coupled (exhibit dynamical interdependence) is relevant to investigations of movement of animals over space, population regulation, food webs and trophic interactions, and is also useful in the design of monitoring programs. For example, in spatially extended systems, coupling among populations in different locations implies the existence of redundant information in the system and the possibility of exploiting this redundancy in the development of spatial sampling designs. One approach to the identification of coupling involves study of the purported mechanisms linking system components. Another approach is based on time series of two potential components of the same system and, in previous ecological work, has relied on linear cross-correlation analysis. Here we present two different attractor-based approaches, continuity and mutual prediction, for determining the degree to which two population time series (e.g., at different spatial locations) are coupled. Both approaches are demonstrated on a one-dimensional predator-prey model system exhibiting complex dynamics. Of particular interest is the spatial asymmetry introduced into the model as linearly declining resource for the prey over the domain of the spatial coordinate. Results from these approaches are then compared to the more standard cross-correlation analysis. In contrast to cross-correlation, both continuity and mutual prediction are clearly able to discern the asymmetry in the flow of information through this system.

Models, Theoretical↗

Attractor reconstruction for non-linear systems: a methodological note.

Attractor reconstruction is an important step in the process of making predictions for non-linear time-series and in the computation of certain invariant quantities used to characterize the dynamics of such series. The utility of computed predictions and invariant quantities is dependent on the accuracy of attractor reconstruction, which in turn is determined by the methods used in the reconstruction process. This paper suggests methods by which the delay and embedding dimension may be selected for a typical delay coordinate reconstruction. A comparison is drawn between the use of the autocorrelation function and mutual information in quantifying the delay. In addition, a false nearest neighbor (FNN) approach is used in minimizing the number of delay vectors needed. Results highlight the need for an accurate reconstruction in the computation of the Lyapunov spectrum and in prediction algorithms.

Algorithms↗

Quantitative evaluation of hypothermia, hyperthermia, and hemodilution on coagulation.

The purpose of this study was to investigate the effects of temperature change on the coagulation time of blood at two different hematocrit levels by using various coagulation-monitoring devices. The devices used in this study were the Bayer Rapid Point Coag Analyzers, Hemochron Jr. Signature, Hemochron Response, Medtronic ACT II, and Haemoscope Thrombelastograph. One unit of human bank blood was used in this study. The hematocrit level was adjusted to 40% and 20%. A control bath and experimental bath were set up. Control blood was maintained at 37 degrees C and tested every 45 +/- 15 min throughout the experimental period of 6 h to demonstrate the stability of the model. The experimental blood was tested at temperature points of 37, 32, 27, 32, 37, 42, and 37 degrees C. Activated clotting time (ACT) tended to increase when the temperature was initially decreased from 37 to 27 degrees C, which reached a statistically significant level when measured by the Hemochron Response at both the 20% (147 +/- 10.7 to 159.3 +/- 11.0, p < .0332) and 40% hematocrit level (130 +/- 14.9 to 152.1 +/- 19.7, p < .0148). ACT was decreased significantly (p < .05) when the temperature was increased to 42 degrees C as measured by all machines except the Hemochron Jr. Signature at the 20% hematocrit level. ACT was significantly higher (p < .05) at a 20% hematocrit level as compared to that at a 40% hematocrit level on all devices for the majority of temperature points. These data suggested that hypothermia only increased ACT when measured by a macrosample device requiring a milliliter sample (Hemochron Response). However, hemodilution induced anticoagulatory effects and hyperthermia caused an acceleration in coagulation by all devices utilized in this study.

Blood Banks↗

Effects of ultrafiltration on enoxaparin: an in vitro analysis.

The use of low molecular weight heparins (LMWH) as an anticoagulant in the heparin-resistant patient poses challenges during cardiopulmonary bypass (CPB). The ultrafiltrability of LMWH has not been previously examined. The purpose of this study was to determine the effects of continuous ultrafiltration on the concentraton of a LMWH, enoxaparin. An in vitro analysis was performed using fresh whole human blood and an extracorporeal circuit containing four parallel ultrafiltrators and a cardiotomy reservoir with an integrated heat exchanger. Constant conditions included temperature (37 degrees C), flow (0.20 L-min(-1)) transmembrane pressure (200 mmHg), and hematocrit (25 +/- 2%). Samples were collected at the inlet, outlet, and ultrafiltrate line at one and three min for one control trial and again for each of the four hemoconcentrators following the bolus of enoxaparin. Coagulation measurements included a viscoelastic monitor (TEG), activated clotting time (ACT), activated partial thromboplastin time (aPTT), and quantitative analysis utilizing a membrane-based electrode for potentiometric measurement of polyanionic concentrations of enoxaparin. Enoxaparin concentration, from inlet to outlet, increased from 2.95 +/- 0.64 to 5.89 +/- 0.95 (p < .001) at 1 min and 4.24 +/- 0.49 to 7.89 +/- 0.606 (p < .001) at 3 min. Kinetic clot activity, as assessed by the TEG index, decreased from -3.8 +/- 2.5 vs. -10.5 +/- 6.0; (p < .01) pre- to postultrafiltrator samples after 3 min. ACT and aPTT results demonstrated no significant change. In conclusion, this study demonstrates enoxaparin is concentrated with the use of continuous ultrafiltration. Functional coagulation studies also indicate a concentrating effect, primarily via the TEG.

Anticoagulants↗

The effect of volume replacement on serum protein concentration during cardiopulmonary bypass.

Although controversy exists concerning the optimal total protein and colloid osmotic pressure that should be maintained during cardiopulmonary bypass (CPB), the primary volume expanders remain albumin and 6% hetastarch. The purpose of this study was to quantify the effect of adding boluses of volume replacement agents under various conditions to total serum protein values during CPB. A standard CPB circuit was utilized in eight 45-kg swine that had a priming volume (physiologic saline solution) of 2309 +/- 245 mL. Volumetric alterations occurred throughout the CPB period by the addition of combinations of physiologic saline solution, 6% hetastarch or 5% swine albumin. Pre- and postadministration samples were assayed for total serum protein, total protein, and albumin throughout the CPB period and at pre- and postvolume administration times. There was a significant decline in total serum protein with the initiation of CPB (6.14 +/- 0.49 g/dL vs. 3.40 +/- 0.43 g/dL, p < .0001). Addition of 12.5 g of swine albumin (N = 5) to two different swine increased total serum protein significantly when compared to adding 500 mL of 6% hetastarch (N = 6) (swine albumin 12.4 +/- 6.3% vs. hetastarch 3.3 +/- 2.1%, p < .005). A reduction in total serum protein occurred after hemodilution with varying amount of physiologic saline solution: 250-450 mL (7.4 +/- 4.5%), 451-650 mL (9.6 +/- 5.6%), and 651-1050 mL (19.4 +/- 4.0%). In summary, knowledge of total serum protein concentration and estimated circulating blood volume can be used to guide albumin and hetastarch administration following hemodilution.

Albumins↗

Higher temporal variability of forest breeding bird communities in fragmented landscapes.

Understanding the relationship between animal community dynamics and landscape structure has become a priority for biodiversity conservation. In particular, predicting the effects of habitat destruction that confine species to networks of small patches is an important prerequisite to conservation plan development. Theoretical models that predict the occurrence of species in fragmented landscapes, and relationships between stability and diversity do exist. However, reliable empirical investigations of the dynamics of biodiversity have been prevented by differences in species detection probabilities among landscapes. Using long-term data sampled at a large spatial scale in conjunction with a capture-recapture approach, we developed estimates of parameters of community changes over a 22-year period for forest breeding birds in selected areas of the eastern United States. We show that forest fragmentation was associated not only with a reduced number of forest bird species, but also with increased temporal variability in the number of species. This higher temporal variability was associated with higher local extinction and turnover rates. These results have major conservation implications. Moreover, the approach used provides a practical tool for the study of the dynamics of biodiversity.

Journal Article↗

Stochastic seasonality and nonlinear density-dependent factors regulate population size in an African rodent.

Ecology has long been troubled by the controversy over how populations are regulated. Some ecologists focus on the role of environmental effects, whereas others argue that density-dependent feedback mechanisms are central. The relative importance of both processes is still hotly debated, but clear examples of both processes acting in the same population are rare. Key-factor analysis (regression of population changes on possible causal factors) and time-series analysis are often used to investigate the presence of density dependence, but such approaches may be biased and provide no information on actual demographic rates. Here we report on both density-dependent and density-independent effects in a murid rodent pest species, the multimammate rat Mastomys natalensis (Smith, 1834), using statistical capture-recapture models. Both effects occur simultaneously, but we also demonstrate that they do not affect all demographic rates in the same way. We have incorporated the obtained estimates of demographic rates in a population dynamics model and show that the observed dynamics are affected by stabilizing nonlinear density-dependent components coupled with strong deterministic and stochastic seasonal components.

Africa↗

Comparative bioavailability of aspirin and paracetamol following single dose administration of soluble and plain tablets.

In this study, the bioavailability of aspirin and paracetamol was compared in plain and soluble combination formulations in fasting, healthy volunteers. Blood samples were taken and Cmax, Tmax and AUC measured at various times following administration of single doses of the two formulations in 12 subjects. The rapidity of uptake of aspirin following administration of a soluble formulation suggests significant absorption from the stomach. There was no significant difference in the pharmacokinetic parameters of paracetamol derived from a soluble or plain formulation. A comparison of the uptake of aspirin from the soluble aspirin formulation with paracetamol from either plain or soluble tablets showed that aspirin entered the plasma and achieved peak levels significantly more quickly. However, the half life of paracetamol was significantly longer than that of aspirin. These findings suggest that onset of analgesia should be more rapid following dosing with soluble aspirin, a conclusion supported by comparative efficacy studies conducted with differing formulations of aspirin.

Acetaminophen↗

The influence of dosage form on aspirin kinetics: implications for acute cardiovascular use.

In this study, the pharmacokinetics of several formulations of aspirin were examined: soluble aspirin, mouth-dispersible aspirin, plain aspirin and enteric-coated aspirin granules. Blood samples were taken at frequent intervals for 24 hours after single dosing in 12 healthy volunteers and Tmax, Cmax and t1/2 measured. Cmax was significantly higher for soluble aspirin than for the other formulations and the t1/2 was shorter. The results show the rapid absorption of aspirin from a soluble formulation compared with that from plain aspirin or enteric-coated aspirin granules. Recommendations to treat patients suspected of having a heart attack as soon as possible with aspirin are now widely accepted and the present study would suggest that soluble aspirin should be the aspirin of choice in this situation.

Adult↗

The comparative bioavailability of cimetidine-alginate treatments.

The comparative bioavailability of cimetidine in cimetidine-alginate combinations has been investigated in twelve healthy volunteers in an open crossover study. Each volunteer received a single oral dose of a commercially available alginate-cimetidine combination tablet (Algitec) or cimetidine tablets (Tagamet), co-administered with a commercially available alginate reflux suppressant liquid or tablet (Gaviscon). No significant differences were observed between treatments for Cmax, tmax, AUC0-12 or AUC0- infinity. The study demonstrated equivalent bioavailability of cimetidine when administered separately with alginate products and as a fixed dose combination product.

Administration, Oral↗

Small mammal populations at hazardous waste disposal sites near Houston, Texas, USA.

Small mammals were trapped, tagged and recaptured in 0.45 ha plots at six hazardous industrial waste disposal sites to determine if populations, body mass and age structures were different from paired control site plots. Low numbers of six species of small mammals were captured on industrial waste sites or control sites. Only populations of hispid cotton rats at industrial waste sites and control sites were large enough for comparisons. Overall population numbers, age structure, and body mass of adult male and female cotton rats were similar at industrial waste sites and control sites. Populations of small mammals (particularly hispid cotton rats) may not suffice as indicators of environments with hazardous industrial waste contamination.

Journal Article↗

Application of a modified colorimetric enzyme assay to monitor plasma paracetamol levels following single oral doses to non-patient volunteers.

A modified enzyme-based colorimetric method has been used to determine plasma paracetamol profiles following single dose (2 x 500 mg) administration of three dosage forms to non-patient volunteers. The assay is linear over the concentration range 0.15-60 micrograms ml-1 with a coefficient of variation of 9.1% at the 1.5 micrograms ml-1 level. It is rapid, requiring small sample volumes; compares favourably with other techniques such as HPLC; and is not subject to interference from paracetamol metabolites and other drugs. Administration of paracetamol as two different dosage forms, as a solid tablet and as a dispersible tablet, resulted in no statistically significant difference in pharmacokinetic parameters between treatments.

Acetaminophen↗

Determination of underivatised efaroxan and idazoxan in blood plasma by capillary gas chromatography with mass-selective detection.

Sensitive and specific methods for the determination of efaroxan and idazoxan in blood plasma have been developed based on solvent extraction, chromatographic separation and quantification by selected-ion monitoring using a quadruple mass-selective detector. The use of a short non-polar bonded-phase capillary gas chromatography (GC) column facilitated rapid separation of the compounds of interest from internal standards, metabolites and endogenous material. Of equal significance was the ability to chromatograph these basic compounds without prior derivatisation. The application of bonded-phase capillary GC coupled to selected-ion monitoring resulted in robust analytical procedures with sub-ng ml(-1) sensitivity and high selectivity.

Adrenergic alpha-Antagonists↗

Determination of idazoxan in plasma by radioreceptor assay.

A radioreceptor assay to determine the plasma concentration of idazoxan, a potent, highly selective antagonist for the alpha(2)-adrenoreceptor, is described. The assay is based upon a technique in which plasma extracts containing idazoxan compete with radiolabelled ligand for binding sites on receptor-rich tissue prepared from beef brain cortex. Using a logistic data-fit the limit of detection is of the order of 1 ng ml(-1) and represents a 10-fold increase in sensitivity over that from an established HPLC procedure. Comparison of human plasma data from the two assays indicates a correlation coefficient of 0.92 (N = 27) although the chromatographic method gave consistently higher values than the binding assay. The binding assay requires no sample extraction or pretreatment of plasma and its accuracy, precision and inherent specificity are such that the method represents a useful alternative to HPLC for therapeutic drug monitoring.

Journal Article↗

The pharmacokinetics after intravenous and oral administration in man of the alpha 2-adrenoreceptor antagonist idazoxan (RX781094).

A high performance liquid chromatographic method was developed for the quantitative determination of idazoxan in plasma. The assay was used to study the disposition of the drug after intravenous infusion and oral administration to five normal subjects. After i.v. administration the kinetics could be described by a two compartment model with a mean elimination half life of 4.20 h. The mean calculated volume of distribution during the elimination phase was 3.20 l/kg-1 and the mean plasma clearance was 824 ml min-1. After oral administration a lag period before onset of absorption was observed in all five volunteers, the plasma levels declining monoexponentially from the peak concentration with a mean elimination half life of 5.58 h. The absolute availability varied between 26% and 41% with a mean value of 34%. In-vitro measurements produced a blood/plasma ratio of 1.3 for idazoxan.

Administration, Oral↗

Constant-parameter capture-recapture models.

Jolly (1982, Biometrics 38, 301-321) presented modifications of the Jolly-Seber model for capture-recapture data, which assume constant survival and/or capture rates. Where appropriate, because of the reduced number of parameters, these models lead to more efficient estimators than the Jolly-Seber model. The tests to compare models given by Jolly do not make complete use of the data, and we present here the appropriate modifications, and also indicate how to carry out goodness-of-fit tests which utilize individual capture history information. We also describe analogous models for the case where young and adult animals are tagged. The availability of computer programs to perform the analysis is noted, and examples are given using output from these programs.

Aging↗

Pharmacokinetics of intravenous and oral tolmesoxide.

A high pressure liquid chromatographic assay was developed for simultaneous measurement of the plasma levels of tolmesoxide and its principal metabolite, RX71112. The assay was used to study the disposition of intravenous and oral tolmesoxide in ten normotensive subjects. Two exponential terms were required to describe the disposition of the drug following intravenous administration, whilst a single exponential term sufficed to account for the decay in the plasma concentration after oral administration. The bioavailability of oral tolmesoxide from capsules averaged 84.5% and was independent of dose. The mean half-life after i.v. dosing was 2.6 h (+/- 0.3 SEM) compared to values of 1.9 h (+/- 0.1 SEM) and 2.7 h (+/- 0.5 SEM) following 200 and 400 mg oral doses respectively. In all subjects RX71112 appeared in plasma shortly after tolmesoxide following both routes of administration. The terminal half-life of the metabolite was significantly longer than tolmesoxide with a mean value of 4.9 h (+/- 0.9 SEM) following the 200 mg oral dose of tolmesoxide. The binding of tolmesoxide and RX71112 at therapeutic plasma concentration was 36.8% (+/- 0.5 SEM) and 58.5% (+/- 0.3 SEM) and this remained unchanged at higher concentrations.

Administration, Oral↗

Pharmacokinetics of fenclofenac following single and multiple doses.

The plasma concentration of the anti-inflammatory drug fenclofenac was investigated in volunteers following single oral doses of 200, 500 and 600 mg, as well as multiple doses of 600mg b.i.d. over five days, using gas chromatography with electron capture detection. The pharmacokinetic parameters derived were independent of dose, and the terminal half-life, t1/2, varied independently of dose between 20 and 38 hours (27.23 +/- 1.8 at 600mg). The apparent volume of distribution (Vd area) had similar values at doses of 200, 500 and 600mg of 15.2 +/- 2.6, 18.2 +/- 1.5 and 14.7 +/- 1.7 litres respectively. These small volumes of distribution indicate that fenclofenac distributes mainly into extracellular space. A mean peak plasma concentration of 63.5 +/- 4.6microgram/ml developed after 3 to4 hours following a single 600mg dose whilst a mean steady state plasma concentration (600mg b.i.d.) of 86.9 +/- 5.7 microgram/ml was achieved within four days, and this decayed with a mean terminal half-life of 25.9 +/- 4.2 hours.

Adult↗