Lag Time Values Research Articles

Monitoring thrombin generation: Is addition of corn trypsin inhibitor needed?

Thrombin generation monitoring has the potential to be used as a clinical diagnostic tool in the near future. However, robust preanalytical conditions may be required, and one factor that has been reported is in-vitro contact activation that might influence in-vitro measurements of thrombin generation and thereby act as an unpredictable pre-analytical variable. The aim of the current study was to investigate the influence of contact activation and the necessity of corn trypsin inhibitor (CTI) to abolish contact activation in thrombin generation measurements at low tissue factor (TF) concentrations. Thrombin generation was performed using the calibrated automated thrombinoscopy (CAT), thereby determining the endogenous thrombin potential (ETP), peak height, and the lag time, in plasma obtained from healthy volunteers. Addition of CTI after plasma preparation had no significant influence on thrombin generation triggered with 0.5 pM TF or higher, as demonstrated by unaltered ETP and lag time values between analyses with and without CTI. Addition of CTI before blood collection reduced thrombin generation triggered with 0.5 pM TF: both the ETP and peak height were significantly reduced compared to no CTI addition. In contrast, thrombin generation remained unaltered at a 1 pM TF trigger or above. This study demonstrates that addition of CTI after plasma separation is not necessary when triggering with TF concentrations of 0.5 pM and higher. Furthermore, it was demonstrated that it is not needed to pre-fill blood collecting tubes with CTI when measuring thrombin generation at TF concentrations of >/=1 pM.

PRIMARY BLADDER NECK DYSFUNCTION IN CHILDREN AND ADOLESCENTS I: PELVIC FLOOR ELECTROMYOGRAPHY LAG TIME—A NEW NONINVASIVE METHOD TO SCREEN FOR AND MONITOR THERAPEUTIC RESPONSE

One of the key findings for making the diagnosis of primary bladder neck dysfunction (PBND) on videourodynamics (VUDS) is prolongation of the time between the start of a voluntary detrusor contraction and the start of urine flow (opening time). Since normally this dynamic event is immediately preceded by pelvic floor relaxation, we determined if the interval between pelvic floor relaxation on pelvic floor electromyography (EMG) and the start of flow (pelvic floor EMG lag time), approximated opening time. Opening time measured on VUDS and pelvic floor EMG lag time measured on noninvasive uroflowmetry/EMG were compared in 22 consecutive patients with a mean age of 13.8 years diagnosed with PBND and a control group of 17 normal children. In addition, 19 patients with PBND were placed on alpha-blocker therapy, and pretreatment and on treatment uroflowmetry and pelvic floor EMG lag time values were compared. Mean opening time and mean pelvic floor EMG lag time were statistically indistinguishable from each other in the PBND and normal groups (27.4 vs 23.9 and 1.1 vs 1.3 seconds, respectively, p >0.550), but they differed significantly between the normal and PBND groups (p <0.001). On alpha-blocker therapy a decrease in mean pelvic floor EMG lag time from 24.47 to 6.67 seconds (p <0.001) corresponded with improved flow parameters, while no improvement was noted in untreated patients. Pelvic floor EMG lag time directly correlates with opening time and, when prolonged and associated with abnormal uroflowmetry, it is highly suggestive of PBND, thereby, justifying more invasive evaluation with VUDS or the initiation of empirical drug therapy. Most importantly, it provides an objective means of monitoring treatment response in a disorder that often has lingering symptoms.

Effects of cigarette smoking on the antioxidant defence in young healthy male volunteers

Cigarette smoking induces a significant oxidant effect related to variety of free radical-related diseases often affecting the upper respiratory tract, unless it is effectively compensated by the antioxidant barriers of the humans. In the present study, the evaluation of the antioxidant compensatory mechanisms, by estimating the antioxidant capacity of extracellular defence (saliva and plasma) and the intracellular resistance of peripheral lymphocytes to oxidative stress in young healthy smokers, was investigated. Twenty young healthy male smokers and 20 age-matched non-smokers with similar dietary profiles were enrolled in the study. Total saliva and plasma samples were collected from both groups, and total antioxidant capacity (TAC) and lag time were estimated. The latter was also repeated in smokers just after a cigarette smoking. Peripheral lymphocytes isolated from the subjects of both groups were also tested for their inherent DNA damage as well as for their ability to resist H2O2-induced DNA damage by using the comet assay. TAC of plasma was found significantly higher in smokers compared to non-smokers (p <0.004), whereas no difference was recorded in plasma lag time values. Lymphocytes of smokers manifested a significantly decreased oxidant resistance (increased DNA fragmentation) to H2O2, in comparison to non-smokers. Our results indicate that young smokers do not manifest different salivary antioxidant defence than non-smokers. They exhibit, however, a higher plasma antioxidant capacity, but a significantly reduced ability of blood lymphocytes, to resist to H2O2-induced DNA damage.

Temporal and spatial resolution of rainfall measurements required for urban hydrology

The objective of the paper is to provide recommendations on the temporal and spatial resolution of rainfall measurements required for urban hydrological applications, based on quantitative investigations of the space-time scales of urban catchments and rainfall. First the temporal rainfall–runoff dynamics is studied using lag time values derived from rainfall and discharge time series for a set of urban catchments. Then the temporal and spatial structure of rainfall is analysed with high resolution rain gauge and radar measurements from the HYDROMET Integrated Radar Experiment '98 experiment for three typical intense Mediterranean rain events. In particular the evolution of the structure of the rainfall field at different time steps is investigated using geostatistics. Finally the required space-time resolution of rainfall for Mediterranean regions is estimated as a function of the surface of the catchments. According to the results, hydrological applications for urban catchments of the order of 1000 ha require a temporal resolution of about 5 min and a spatial resolution of about 3 km. For urban catchments of the order of 100 ha, it becomes a resolution of about 3 min and 2 km, that common operational networks or radars cannot provide. These results complement the scarce recommendations on resolution of rainfall for urban hydrology reported in the literature.

Solid state and solution studies of a vanadium(III)- l-cysteine compound and demonstration of its antimetastatic, antioxidant and inhibition of neutral endopeptidase activities

Reaction of one equivalent of vanadium(III) chloride with three equivalents of l-cysteine(H 2Cys) in methyl alcohol affords a V III-Cys compound that is formulated as [V III(Hcys) 3] · 2HCl · 2.5H 2O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys − ligand to the V III atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and methanol by UV–visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, V IVOSO 4 · 5H 2O and l-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than l-cysteine. V IVOSO 4 · 5H 2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, V IVOSO 4 · 5H 2O and thiorphan was also measured. Compound 1, at a concentration of 10 −3 M, showed inhibition of NEP activity as potent as thiorphan at 10 −6 M, while V IVOSO 4 · 5H 2O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10 −6 M. Moreover, the antimetastatic effects of compound 1, l-cysteine and V IVOSO 4 · 5H 2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47–52% of the rats of the control group and those treated with l-cysteine and V IVOSO 4 · 5H 2O exhibited metastases.

In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation

The purpose of this study was to optimize in vitro experimental conditions for the measurement of Δ 9-tetrahydrocannabinol (Δ 9-THC) permeation across human skin using a flow-through diffusion cell system. The drug permeation rates through intact and stripped (stratum corneum (SC) removed) skin were also compared in order to determine if the SC provided significant resistance to the diffusion of hydrophobic Δ 9-THC. The receiver fluids evaluated were HEPES-buffered Hank's balanced salt solution (HHBSS) with either 4 or 6% bovine serum albumin (BSA), Polyoxyethylene 20 Oleyl Ether (Brij 98) solution (0.5 and 6.0%), and hydroxypropyl-β-cyclodextrin (HPBCD). The Δ 9-THC permeability was significantly higher into Brij 98 solutions than into 4% BSA. BSA 6% receiver solutions showed significantly higher Δ 9-THC permeation over BSA 4%. There were no significant differences in Δ 9-THC permeability or lag time values between 0.5 and 6% Brij 98 receiver solutions. HPBCD failed to work as a suitable receiver solution. The Δ 9-THC flux in the stripped skin experiments exceeded the flux in the intact skin experiments. It appears that the SC provides some resistance to the diffusion of Δ 9-THC across human skin. These experimental results have confirmed the utility of several receiver solutions for the in vitro human skin diffusion study of Δ 9-THC.

Estimation of Microbial Growth Parameters by Means of Artificial Neural Networks

An alternative method based on artificial neural networks (ANN) for the estimation of kinetic growth parameters of a microorganism is performed by applying an automatic regression on different sections of the growth curve so as to obtain more precise growth rate and lag-time values. Through the combination of genetic algorithms and pruning methods more simple neural networks are obtained, where the goodness of fitness is a combination of an error function with another function associated with the network's complexity. An interesting application of this method was the estimation of kinetic parameters in microbial growth (growth rate and lag-time) and specifically in our case, the analysis of the effect of NaCl concentration, pH level and storage temperature on the growth curves of Lactobacillus plantarum. In this study it was hoped that the architecture of the obtained model would be very simple, but still keep its adequate capacity of generalization. The comparison performed between the average standard error of predictions (SEP) obtained for the estimation of growth rate and lag-time by the automatic regression (20 and 24%, respectively) and by the Gompertz estimation (22 and 28%) showed the utility of this method. (A)

Transdermal Delivery of Nicardipine: An Approach to In Vitro Permeation Enhancement

Nicardipine hydrochloride (NC-HCl), a calcium channel blocker for the treatment of chronic stable angina and hypertension, seems to be a potential therapeutic transdermal system candidate, mainly due to its low dose, short half-life, and high first-pass metabolism. The objective of the present study was to evaluate its flux and elucidate mechanistic effects of formulation components on transdermal permeation of the drug through the skin. Solubility of NC-HCl in different solvent systems was determined using a validated HPLC method. The solubility of drug in various solvent systems was found to be in decreasing order as propylene glycol (PG)/oleic acid (OA)/dimethyl isosorbide (DMI) (80:10:10 v/v) > PG > PG/OA (90:10 v/v) > polyethylene glycol 300 > ethanol/PG (70:30 w/w) > transcutol > dimethyl isosorbide (DMI) > ethanol > water and buffer 4.7 > 2-propanol. Propylene glycol was then selected as the main vehicle in the development of a transdermal product. As a preliminary step to develop a transdermal delivery system, vehicle effect on the percutaneous absorption of NC-HCl was determined using the excised skin of a hairless guinea pig. Vehicles investigated included pure solvents alone and their selected blends, chosen based on the solubility results. In vitro permeation data were collected at 37°C, using Franz diffusion cells. The skin permeation was then evaluated by measuring the steady state permeation rate (flux) of NC-HCl, lag time, and the permeability constant. The results showed that no individual solvent was capable of promoting NC-HCl penetration. Permeation profiles of the drug through hairless guinea pig skin using saturated solutions of drug were constructed. Among the systems studied, the ternary mixture of PG/OA/DMI and binary mixture of PG/OA showed excellent flux. The flux value of the ternary system was nearly three times higher than the corresponding values obtained for the binary solvent. A similar trend also was observed for the permeation conture stant, while the values of lag time were reversed. The ternary mixindicated was then selected as a potential absorption enhancement vehicle for the transdermal delivery of drug. In general, higher fluxes were observed through hairless guinea pig skin as compared with the human stratum corneum. Based on the results obtained from the release study of NC-HCl from saturated solutions of the drug, a novel lecithin organogel (microemulsion-based gel) composed of soybean lecithin, propylene glycol, oleic acid, dimethyl isosorbide, and isopropyl myristate was developed as a possible matrix for transdermal delivery of NC-HCl. In vitro percutaneous penetration studies from this newly developed gel system through giunea pig skin and human stratum corneum revealed that the organogel system has skin-enhancing potential and could be a promising matrix for the transdermal delivery of nicardipine. Furthermore, higher permeation rates were observed when nicardipine free base was incorporated into the gel matrix instead of hydrochloride salt.

Human epidermal membrane constant conductance iontophoresis: alternating current to obtain reproducible enhanced permeation and reduced lag times of a nonionic polar permeant

An experimental protocol, using an initial 1 min direct current (DC) applied potential of 4 V followed by alternating current (AC), was established to: (a) increase conductance and permeability and decrease lag time for human epidermal membrane (HEM) relative to unaltered HEM and; (b) maintain constant conductance and permeability during flux studies. The protocol allowed specific permeation parameters of the membrane to be characterized under electrically enhanced, constant flux conditions. The permeability, lag time, and effective membrane thickness were determined using a nonionic polar permeant, urea, while the enhanced conductance was maintained at a constant level with AC. A tortuous pore pathway model was employed to analyze the data. The AC protocol increased membrane permeability, and decreased lag time and effective membrane thickness relative to similar parameters obtained in previous studies from unaltered HEM. Lag times ranged from 32.0 to 105.5 min, and permeability coefficients calculated from steady state fluxes ranged from 1.68 to 6.03×10 −7 cm/s for HEM samples with electrical resistance values during transport of 2.3–8.0 kΩ cm 2. Effective membrane thicknesses were calculated to range from 0.34 to 0.61 cm during AC iontophoresis. Significant additional results were obtained when the protocol was applied for two consecutive runs using the same HEM sample, with time for the HEM sample to recover between runs. During the second run, the applied potential was adjusted to reproduce the conductance obtained on the first run. Under these conditions, the consecutive runs yielded essentially the same lag time, permeability and effective membrane thickness values. These results suggest that constant fluxes can be achieved by keeping HEM electrical conductance constant during AC iontophoresis.

Effect of skin pretreatment with fatty acids on percutaneous absorption and skin retention of piroxicam after its topical application

The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and poly-unsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam flux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids>skin pretreatment with 5% fatty acids followed application of control gel>gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam flux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment.

Permeability of plastic films to methyl bromide: a comparative laboratory study

Abstract: The permeability of plastic Ðlms to the fumigant methyl bromide (MB)was measured by two di†erent methods, in order to facilitate the selection ofÐlms which are impermeable to the gas. Polyethylene-based Ðlms are highly per-meable to MB, as evidenced by both methods. In contrast, multilayer coextrudedÐlms which have a layer of barrier material such as polyamide (PA) or ethylene-vinyl alcohol copolymer (EVOH) were signiÐcantly less permeable to MB, asreNected by the parameters permeability rate, time to 90% concentration (TC90,by the di†usion method) and lag-time values (by the variable-volume method). AsigniÐcant correlation was found between the permeability rate assessed by thedi†usion method and that obtained with the variable-volume method. Per-meability of all Ðlms increased with temperature as evidenced by all testedparameters. This increase was more pronounced with polyethylene Ðlms, the per-meabilities of which increased Ðve- to six-fold when the temperature wasincreased from 20iC to 60iC. The e†ect of temperature on barrier-Ðlm per-meability was less signiÐcant. Permeability of Ðlms to MB was a†ected by addi-tional factors such as additives, the length of the monomer side-chain, and thethickness and density of polyethylene Ðlms. 1998 SCI(Pestic. Sci., 53, 141E148 (1998)Key words: ethylene-vinyl alcohol; polyamide; fumigation; barrier Ðlms; methylbromide

Prediction of percutaneous absorption from physicochemical data: A model based on data of in vitro experiments

Correlations between in vitro percutaneous absorption data and physicochemical properties of industrial chemicals are evaluated in order to develop predictive mathematical models based on said properties. Percutaneous diffusion of 16 compounds of occupational interest, eight of which were polycyclic aromatic hydrocarbons (acenaphthene, anthracene, benzo(a)anthracene, chrysene, phenanthrene, fluorene, naphthalene, pyrene), six organophosphorus insecticides (acephate, chlorpyrifos, dimethoate, fenitrothion, methamidophos, omethoate) and two phenoxycarboxylic herbicides (2,4-D, MCPA), were tested in vitro using monkey (Cercopithecus aetiops) skin. The test apparatus consisted of nine static diffusion cells with normal saline, gentamycin sulphate and 4% bovine serum albumin as receiving solution. Test compounds were applied at various concentrations in 30 μl of acetone solution and determined, in the receiving phase, by chemical analysis. Values for In Kow (octanol/water partition coefficient) were correlated with experimentally determined values of the permeability constant Kp (r = 0.90, P < 0.001) and lag time (r = 0.81, P < 0.01). Analysis of variance in a model of multiple linear regression between Kp, Inow and water solubility [water] of the compounds, showed that the data had a highly significant fit (P < 0.0001). A more general model which also included molecular weight (MW) and vapour pressure was evaluated as well, but the two variables made no substantial difference. Multiple regression analysis between lag time, In Kow and [water] was significant (P < 0.0001), whereas introduction of vapour pressure and MW as independent variables did not significantly improve the predictive effect on lag time. Our experimental system, therefore, enables the values of Kp and lag time to be predicted with reasonable precision on the basis of In Kow and [water] values, using the algorithm derived from the multiple linear regression equation.

Monitoring of low density lipoprotein oxidation by low-level chemiluminescence

A method for monitoring low-density lipoprotein (LDL) oxidation by low-level chemiluminescence (LL-CL) is described in this study. The kinetic indices obtained with this procedure, in particular lag-time and K value (related to prooxidant activity of Cu2+ bound to LDL) are compared with those of the established UV-absorbing conjugated diene assay. The correlation of lag-time values obtained by LL-CL and conjugated diene assay was very high both in the case of Cu2+- and peroxyl-radical-mediated oxidation (r = 0.99). By using the transient free radical scavenging activity of butylated hydroxytoluene, a calibration of LL-CL for lipid peroxyl radical and termination rate was obtained. The spectral analysis of LL-CL from oxidizing LDL shows a maximum peak between 420 and 500 nm, corresponding to the emission of triplet carbonyl compounds. LL-CL allows continuous and direct monitoring of LDL oxidation as extraction and derivatization of lipid peroxidation products are not required. Moreover, some limitations of UV spectroscopy such as by absorbing compounds need not be considered. Therefore, the present procedure represents a simple and convenient tool for continuous monitoring of LDL oxidation which may be applied to mechanistic and clinical studies.

Variability of the response of 66Listeria monocytogenesandListeria innocuastrains to different growth conditions

The growth of 58 strains ofListeria monocytogenesand eight strains ofListeria innocuaisolated from meat products (68%) and industrial sites (23%), were compared in four conditions of temperature, water activity (aw) and pH. Temperatures ranged from 10–37°C, pH from 5.6–7.0 and awfrom 0.96–1. Growths were performed in a meat broth with an automated turbidimeter (Bioscreen C, Labsystem). Growth curves were fitted using the Gompertz function, and growth parameters were calculated. The differences between strains in lag phase duration were much greater than in growth rate. The greatest differences occurred at 10°C, pH7 and aw0.96 : lag time values ranged from 4h to 4 days. the Listeria population was separated into five groups, according to the lag time and maximal growth rate values using clustering analysis. The majority of the strains isolated from industrial sites were grouped together and showed faster growth than the others in the four conditions studied. The serotype or the nature of the meat from which the strains were isolated did not influence growth. The variability observed among strains raises questions about the consequences in quantitative risk assessment and about the construction of models in predictive modelling.

Predictive modelling of growth of Escherichia coli O157:H7: the effects of temperature, pH and sodium chloride

The growth responses of Escherichia coli O157:H7 as affected by NaCl concentration, pH value and storage temperature were studied in laboratory medium. Growth curves at concentrations of NaCl in the range 0.5–6.5% ( w v ), pH values in the range 4.0–7.0 and storage temperatures in the range 10–30 °C were fitted using the Gompertz routine and the derived parameters modelled. Growth curves could then be regenerated for any set of conditions within the matrix studied and values for growth rate, generation time, lag time and time to 1000-fold increase predicted. The model was validated against data from the literature and was found to give realistic estimates for generation time in media and a range of foods including meat and poultry, milk, cheese and tempeh. All predictions were consistently ‘fail-safe’.

Predictive modelling of growth of Staphylococcus aureus: the effects of temperature, pH and sodium chloride

The growth responses of Staphylococcus aureus as affected by NaCl concentration, pH value and storage temperature were studied in laboratory medium. Growth curves at concentrations of NaCl in the range 0.5−13.5% (w/v), pH values in the range 4.0−7.0 and storage temperatures in the range 10–30°C were fitted using the Gompertz routine and derived parameters modelled. Growth curves could then be regenerated for any set of conditions within the matrix studied and values for growth rate, generation time, lag time and time to 1000-fold increase predicted. The model was validated against data from the literature and was found to give realistic estimates of generation time for media and a range of foods including milk, cheese, starch-based foods and cooked meats but not for mayonnaise or Wiltshire bacon. All predictions were consistently ‘fail-safe’.

Predictive modelling of growth of Yersinia enterocolitica: the effects of temperature, pH and sodium chloride

The growth responses of Yersinia enterocolitica as affected by NaCl concentration, pH value and storage temperature were studied in laboratory medium. Growth curves at concentrations of NaCl in the range 0.5–6.5% (w/v), pH values in the range 4.0–7.0 and storage temperatures in the range 5–30°C were fitted using the Gompertz routine and the derived parameters modelled. Growth curves could then be regenerated for any set of conditions within the matrix studied and values for growth rate, generation time, lag time and time to 1000-fold increase predicted. The model was validated against data from the literature and was found to give realistic estimates for generation time in media and a range of foods including meat and meat products, milk, eggs, fish and tofu. All predictions were consistently ‘fail-safe’.

Platelet aggregability in patients with a VVI pacemaker.

Several studies have suggested an increased incidence of thromboembolic events in patients with VVI pacemaker (VVI patients); furthermore, other authors have demonstrated that a treatment with anticoagulants or antiplatelet drugs may be effective in reducing thromboembolic events, thus suggesting an increased formation of platelet thrombi in these patients. In this respect, platelet aggregability was investigated in ten VVI patients and ten age- and sex-matched subjects. beta-thromboglobulin (beta-Tg) and platelet factor 4 (PF4) plasma levels were determined as well as platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid. Plasma beta-Tg levels were increased in the patient group (86 +/- 24 vs 24 +/- 13 ng/mL; P < 0.001) in presence of normal PF4 values (14 +/- 11 vs 13 +/- 6 ng/mL; NS). Aggregation curves showed abnormal values of maximal amplitude, slope, and lag time. In particular, maximal amplitude was significantly higher in VVI patients as compared with controls (ADP P < 0.01, collagen P < 0.001, adrenaline P < 0.01, arachidonic acid P < 0.05). These findings strongly suggest an increase of platelet activity in VVI patients.

The production of “breathy voice.”

The nature of voicing in the Hindi “voiced aspirated” phonemes has been a subject of discussion in the literature for a number of years. In particular, the question of whether or not “breathy voice” or “murmur” is present during the aspirated portion of the stop has been at issue. The present study looks at productions of the velar voiced aspirated stop (/gh/) in initial position from the speech of ten adult female speakers of Hindi. Amounts of lead time (prevoicing) and lag time (post‐release VOT) in the voiced aspirate were compared to lead and lag times in the voiced unaspirate (/g/) and the voiceless aspirate (/kh/). In addition, the presence or absence of voicing during the post‐release portion of the stop was determined. Both lead and lag time values of the voiced aspirate were found to be significantly different from those of the other velar stop types, and the presence of voicing during aspiration (breathy voice) was found to be speaker dependent. Implications of these findings for a description of voicing contrasts in various languages will be discussed.

Estimation of the bone mineral density variation associated with changes in turnover rate

Bone matrix mineral density (BMDn, fraction of maximum) is the mean mineral density of a bone sample comprising moieties of bone of varying ages/mineral densities. A method for calculating BMDn as a function of bone turnover rate is presented. The method is based on a mineralization curve defined by values for mineralization lag time, total mineralization time, and levels of primary and final mineralization. The calculations illustrate that BMDn decreases linearly in direct proportion to increases in bone turnover rate, and that the slope of the line is dependent on the assumptions used to calculate the mineralization curve. BMDn variation is important because it is reflected in whole bone density variation, independent of changes in bone mass, when bone turnover rate is altered.