bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three‐dimensional analysis of porous BaTiO3 ceramics using FIB nanotomography
Authors: HOLZER L. , INDUTNYI F. , GASSER PH. , MÜNCH B. , WEGMANN M. 
Published: September 2004

SummaryThree‐dimensional (3D) data represent the basis for reliable quantification of complex microstructures. Therefore, the development of high‐resolution tomography techniques is of major importance for many materials science disciplines. In this paper, we present a novel serial sectioning procedure for 3D analysis using a dual‐beam FIB (focused ion beam). A very narrow and reproducible spacing between the individual imaging planes is achieved by using drift correction algorithms in the automated slicing procedure. The spacing between the planes is nearly of the same magnitude as the pixel resolution on scanning electron microscopy images. Consequently, the acquired stack of images can be transformed directly into a 3D data volume with a voxel resolution of 6 × 7 × 17 nm. To demonstrate the capabilities of FIB nanotomography, a BaTiO3 ceramic with a high volume fraction of fine porosity was investigated using the method as a basis for computational microstructure analysis and the results compared with conventional physical measurements. Significant differences between the particle size distributions as measured by nanotomography and laser granulometry indicate that the latter analysis is skewed by particle agglomeration/aggregation in the raw powder and by uncertainties related to calculation assumptions. Significant differences are also observed between the results from mercury intrusion porosimetry (MIP) and 3D pore space analysis. There is strong evidence that the ink‐bottle effect leads to an overestimation of the frequency of small pores in MIP. FIB nanotomography thus reveals quantitative information of structural features smaller than 100 nm in size which cannot be acquired easily by other methods.
Habitat‐specific life‐history variation in the Caribbean termiteNasutitermes acajutlae(Isoptera: Termitidae)
Authors: Jeyasingh Punidan D. , Fuller Claire A. 
Published: September 2004

Abstract. 1. Population and individual colony characteristics ofNasutitermes acajutlaeon St John, U.S. Virgin Islands were studied over a 5‐year period.2. Four habitat types (dry forests, moist forests, sparse vegetation, and woodlands) were sampled forN. acajutlae, using quadrat‐based methods. Lying dead wood was also quantified in the same sites.3. Habitats differed significantly in the volume of lying dead wood, and total termite nest volume within quadrats was positively related to wood volume. It was hypothesised that the volume of dead wood affected growth, reproduction, and yearly survival of individual colonies.4. In a sample of > 100 colonies assessed in 1998, 2000, 2001, and 2002, no significant differences in the growth rate of colonies (= increase in nest volume) could be found between habitat types; however, colonies in sparse vegetation were smaller, less likely to survive, and reproduced at a smaller size compared with those in the other three habitats.5. Overall nest volume in sparse vegetation was high, compared with dry and moist forest, but colonies showed, on average, poorer survival (interpreted as lower fitness), and produced alates at an early stage of development. Optimum habitat characteristics forN. acajutlaemay include not only favourable microclimate but also the reliable acquisition of new dead wood after storms.
A review of relationships between interspecific competition and invasions in fruit flies (Diptera: Tephritidae)
Authors: Duyck Pierre‐Francois , David Patrice , Quilici Serge 
Published: September 2004

Abstract.  1. A number of invasions in the family Tephritidae (fruit flies) have been observed worldwide despite quarantine procedures. In this review, the potential importance of interspecific competition and competitive displacement among different tephritid species is evaluated in the context of recent invasions.2. Where polyphagous tephritid species have been introduced in areas already occupied by a polyphagous tephritid, interspecific competition has resulted in a decrease in number and niche shift of the pre‐established species. No reciprocal invasions have been observed.3. The data on tephritid invasions seem to support a hierarchical mode of competition; however, complete exclusion usually did not occur. Indeed, tephritid distribution and abundance are markedly structured by various abiotic (mostly climatic) and biotic (host plants) factors.4. The primary determinant of competitive interactions in near‐optimal conditions, such as lowlands with abundant fruit plantations, is probably the life‐history strategy. The r–K gradient could be used as a predictor of potential invaders, because K traits (such as large adult size) may favour both exploitation and interference competition.5. For future research, a better understanding of competition mechanisms seems essential. Different species competing in the same area should be compared with respect to: (i) demographic parameters, (ii) the outcome of experimental co‐infestations on the same fruit, and (iii) behavioural and chemical interference mechanisms.
The interactive effects of climate, life history, and interspecific neighbours on mortality in a population of seed harvester ants
Authors: Sanders Nathan J. , Gordon Deborah M. 
Published: September 2004

Abstract.  1. Fifteen years of census data from a population of the red harvester ant (Pogonomyrmex barbatus), 5 years of census data from populations of Aphaenogaster cockerelli and Myrmecocystus mimicus at the same site, and long‐term precipitation data from a nearby weather station were used to examine how nearest interspecific neighbours, climate, and life history influence P. barbatus colony mortality.2. It was found that more P. barbatus colonies die following dry summers than following wet summers, but there is no relationship between the establishment of new colonies and rainfall.3. Aphaenogaster cockerelli, but not M. mimicus, nearest neighbours influence P. barbatus colony mortality in some years and for some ages.4. The effects of nearest A. cockerelli neighbours are usually most severe following dry summers, when resource availability is reduced.
Pharmacokinetics of oral fumarates in healthy subjects
Authors: Litjens Nicolle H. R. , Burggraaf Jacobus , Van Strijen Elisabeth , Van Gulpen Co , Mattie Herman , Schoemaker Rik C. , Van Dissel Jaap T. , Thio H. Bing , Nibbering Peter H. 
Published: September 2004

AimsTo characterize the pharmacokinetics of fumarates in healthy subjects.MethodsTen subjects received a single fumarate tablet (containing 120 mg of dimethylfumarate and 95 mg of calcium‐monoethylfumarate) in the fasted state and after a standardized breakfast in randomized order. Prior to and at fixed intervals after the dose, blood samples were drawn and the concentrations of monomethylfumarate, the biologically active metabolite, as well as dimethylfumarate and fumaric acid were measured using high‐performance liquid chromatography.ResultsAfter a lag time, a transient increase in serum monomethylfumarate concentrations in the blood was observed, whereas dimethylfumarate and fumaric acid concentrations remained below the detection limit. The tlag was 240 min [range 60–603 min; 95% confidence interval (CI) 139, 471] shorter when the tablet was taken after an overnight fast (90 min; range 60–120 min; 95% CI 66, 107) than when taken with breakfast (300 min; range 180–723 min; 95% CI 0, 1002). The tmax was 241 min (range 60–1189 min, 95% CI 53, 781) shorter when the tablet was taken after an overnight fast (182 min; range 120–240 min; 95% CI 146, 211) than when taken with breakfast (361 min; range 240–1429 min; 95% CI 0, 1062). The mean Cmax for monomethylfumarate in the blood of fasting subjects was to 0.84 mg l−1 (range 0.37–1.29 mg l−1; 95% CI 0.52, 1.07) and did not differ from that in fed subjects (0.48 mg l−1; range 0–1.22 mg l−1; 95% CI 0, 5.55).ConclusionsThe pharmacokinetics of monomethylfumarate in healthy subjects after a single tablet of fumarate are highly variable, particularly after food intake. Further experiments exploring the pharmacokinetics of oral fumarates are warranted in order to elucidate the mechanisms underlying variability in reponse in patients.
Undeclared exposure to St. John's Wort in hospitalized patients
Authors: Martin‐Facklam Meret , Rieger Karin , Riedel Klaus‐Dieter , Burhenne Jürgen , Walter‐Sack Ingeborg , Haefeli Walter E. 
Published: September 2004

AimThe herbal medicine St. John's Wort (SJW) causes substantial decreases in the plasma concentrations of a range of co‐administered drugs. Therefore, we evaluated the extent of systemic exposure to hyperforin and hypericin, two of the main constituents of SJW, in patients on admission and during hospital stay, and compared the results with known use of SJW as documented in the drug chart and detected in additional interviews.MethodsOne hundred and fifty patients aged ≥ 18 years and admitted, between August 2000 and February 2002, to an internal medicine ward of a large German university hospital were included. Hyperforin and hypericin was determined in plasma by a sensitive liquid chromotography/mass spectometry (LC/MS/MS) method. To assess undeclared use of SJW the data were compared to information obtained from drug charts and from up to three interviews that had a particular focus on intake of herbal medicines and self‐medication during hospitalization.ResultsHyperforin was detected in 12 patients (plasma concentration on the first day of hospitalization = 12–100 ng ml−1 in five patients and <3 ng ml−1 in seven), and hypericin in five patients (0.5–4.3 ng ml−1). Nine patients (6%) were taking/had taken SJW without the knowledge of the medical team and the pharmacist, who conducted the additional interviews, and 11 (7.3%) were taking/had taken SJW without the knowledge of the medical team alone. Seven of these patients were treated concurrently with drugs that can interact with SJW.ConclusionsUnrecognized use of SJW is frequent and may have an important influence on the effectiveness and safety of drug therapy during hospital stay.
Models for time‐varying covariates in population pharmacokinetic‐pharmacodynamic analysis
Authors: Wählby Ulrika , Thomson Alison H. , Milligan Peter A. , Karlsson Mats O. 
Published: September 2004

AimIf appropriately accounted for in a pharmacokinetic (PK)–pharmacodynamic (PD) model, time‐varying covariates can provide additional information to that obtained from time‐constant covariates. The aim was to present and apply two models applicable to time‐varying covariates that capture such additional information.MethodsThe first model estimates different covariate–parameter relationships for within‐ and between‐individual variation in covariate values, by splitting the standard covariate model into a baseline covariate (BCOV) effect and a difference from baseline covariate (DCOV) effect. The second model allows the magnitude of the covariate effect to vary between individuals, by inclusion of interindividual variability in the covariate effect. The models were applied to four previously analysed data sets.ResultsThe models were applied to 10 covariate–parameter relationships and for three of these the first extended model resulted in a significant improvement of the fit. Even when this model did not improve the fit significantly, it provided useful information because the standard covariate model, which assumes within‐ and between‐patient covariate relationships of the same magnitude, was only supported by the data in four cases. The inclusion of BCOV was not supported in two cases and DCOV was unnecessary in three cases. In one case, significantly different, nonzero, relationships were found for DCOV and BCOV. The second extended model was found to be significant for four of the 10 covariate–parameter relationships.ConclusionsOn the basis of the examples presented, traditionally made simplifications of covariate–parameter relationships are often inadequate. Extensions to the covariate–parameter relationships that include time‐varying covariates have been developed, and their appropriateness and benefits have been described.
Drug interaction between St John's Wort and quazepam
Authors: Kawaguchi Atsuhiro , Ohmori Masami , Tsuruoka Shu‐ichi , Nishiki Kenta , Harada Kenichi , Miyamori Isamu , Yano Ryo‐ichi , Nakamura Toshiaki , Masada Mikio , Fujimura Akio 
Published: September 2004

AimSt John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, quazepam, which is metabolized by CYP3A4, were examined.MethodsThirteen healthy subjects took a single dose of quazepam 15 mg after treatment with SJW (900 mg day−1) or placebo for 14 days. The study was performed in a randomized, placebo‐controlled, cross‐over design with an interval of 4 weeks between the two treatments. Blood samples were obtained during a 48 h period and urine was collected for 24 h after each dose of quazepam. Pharmacodynamic effects were determined using visual analogue scales (VAS) and the digit symbol substitution test (DSST) on days 13 and 14.ResultsSJW decreased the plasma quazepam concentration. The Cmax and AUC0‐48 of quazepam after SJW were significantly lower than those after placebo [Cmax; −8.7 ng ml−1 (95% confidence interval (CI) −17.1 to −0.2), AUC0‐48; −55 ng h ml−1 (95% CI −96 to −15)]. The urinary ratio of 6β‐hydroxycortisol to cortisol, which reflects CYP3A4 activity, also increased after dosing with SJW (ratio; 2.1 (95%CI 0.85–3.4)). Quazepam, but not SJW, produced sedative‐like effects in the VAS test (drowsiness; P < 0.01, mental slowness; P < 0.01, calmness; P < 0.05, discontentment; P < 0.01). On the other hand, SJW, but not quazepam impaired psychomotor performance in the DSST test. SJW did not influence the pharmacodynamic profile of quazepam.ConclusionsThese results suggest that SJW decreases plasma quazepam concentrations, probably by enhancing CYP3A4 activity, but does not influence the pharmacodynamic effects of the drug.
Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo‐controlled, crossover study
Authors: Houghton C. M. , Langley S. J. , Singh S. D. , Holden J. , Monici Preti A. P. , Acerbi D. , Poli G. , Woodcock A. 
Published: September 2004

BackgroundIn response to the phasing out of chlorofluorocarbon (CFC) inhalers, a metered dose hydrofluoroalkane (HFA) formulation, Modulite (Chiesi Farmaceutici S.p.A, Parma, Italy), to be delivered with a pressurized metered dose inhaler (pMDI), has been developed. Modulite is a HFA formulation technology that has been designed to provide stable and uniform dose delivery of HFA‐based formulations to enable an easy transition from CFC to HFA inhalers.ObjectivesThe aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 µg of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer (dry powder inhaler, DPI) and the Foradil CFC inhalers (Novartis Health Consumer, Basel, Switzerland).MethodsThis was a double blind, double dummy, randomized, placebo‐controlled, crossover study conducted in 38 subjects with mild to moderate asthma (mean forced expiratory volume in 1 s [FEV1] 87.5% predicted). The primary endpoint was methacholine challenge provocative dose required for 20% fall in the FEV1 (PD20) 90 min post dose. Bronchodilation was assessed with spirometry (FEV1, FVC, FEF25–75) and impulse oscillometry (resistance at 5 and 20 Hz, reactance at 5 Hz and resonant frequency) over the 90 min post dose. In a subset of 12 subjects formoterol plasma levels, serum potassium and glucose were determined up to 480 min post dose.ResultsThe three formoterol formulations demonstrated significant (P ≤ 0.05) improvements in bronchoprotection compared to placebo and non‐inferiority of the HFA preparation compared to the CFC and DPI preparations was demonstrated. Geometric mean PD20 values were 0.51 mg with HFA, 0.62 mg with DPI, 0.62 mg with CFC and 0.2 mg with placebo. The log transformed mean differences in PD20 doubling dose between HFA and (a) DPI was −0.28 (95% CI −0.84–0.29, P = 0.57) (b) CFC was −0.28 (95% CI −0.84–0.28, P = 0.57) and (c) placebo was 1.38 (95% CI 0.82–1.94, P < 0.001). Serum potassium, glucose and formoterol plasma profiles were comparable for the CFC, HFA and DPI devices.ConclusionOur findings of similar efficacy, pharmacokinetics and systemic effects of the HFA formoterol inhaler compared to the CFC and DPI preparations supports the potential use of this novel formulation in the treatment of asthma.
Pharmacokinetics and renal excretion of desmopressin after intravenous administration to healthy subjects and renally impaired patients
Authors: Agersø Henrik , Seiding Larsen Lotte , Riis Anders , Lövgren Ulf , Karlsson Mats O. , Senderovitz Thomas 
Published: September 2004

ObjectiveTo evaluate the influence of renal impairment on the pharmacokinetics of desmopressin.MethodsTwenty‐four subjects were enrolled in the study, 18 with varying degrees of renal impairment and six healthy volunteers. Each subject received a single intravenous dose of 2 µg desmopressin. Blood and urine samples were collected for 24 h and assayed for desmopressin by radioimmunoassay. Plasma concentrations and the amounts of desmopressin excreted in the urine were analysed simultaneously by use of mixed effects modelling.ResultsOnly mild adverse events were observed. Both the renal and the nonrenal clearance of desmopressin were found to vary with the creatinine clearance (CrCL). A decrease of 1.67% in the CrCL (corresponding to 1 ml min−1 from 60 ml min−1) was found to cause a 1.74% decrease in the renal clearance and a 0.93% decrease in the nonrenal clearance. The fall in renal clearance caused the amount of desmopressin excreted in urine to decrease from 47% in healthy subjects to 21% in the patients with severe renal impairment. The mean systemic clearance of desmopressin was 10 litres h−1 in healthy subjects and 2.9 litres h−1 in patients with severe renal impairment (difference −7.5 litres h−1, 95% CI [−11; −4.3] litres h−1). Correspondingly, the mean terminal half‐life, was 3.7 h in healthy subjects and 10 h in patients with severe renal impairment (difference 6.7 h, 95% CI [4.0; 9.4] h).ConclusionAlthough desmopressin appears to be safe and well‐tolerated by patients with impaired renal function, great caution should be exercised when titrating towards an efficient dosage regimen if patients with moderately or severely impaired renal function are to be treated with desmopressin at all.
Pharmacokinetic/pharmacodynamic models for the depletion of Vβ5.2/5.3 T cells by the monoclonal antibody ATM‐027 in patients with multiple sclerosis, as measured by FACS
Authors: Zingmark Per‐Henrik , Edenius Charlotte , Karlsson Mats O. 
Published: September 2004

Aims(i) To model the effects of the monoclonal antibody ATM‐027 on the number of target cells and on the receptor density on the cell surface as measured by Fluorescence Activated Cell Sorter analysis, (ii) to investigate the effects of categorizing a continuous scale, and (iii) to simulate a phase II trial from phase I data in order to evaluate the predictive performance of the model by comparison with the actual trial results.MethodsBased on the data from one phase I and one phase II study in multiple sclerosis (MS) patients, models were developed to characterize the pharmacokinetics and pharmacodynamics of the monoclonal antibody ATM‐027 and its effects on Vβ5.2/5.3+ T cells. The pharmacodynamic variables were the number of target T cells and the expression of its receptor. The latter was modelled in both a categorical and continuous way. The modelling was performed with a nonlinear mixed effects approach using the software NONMEM. The joint continuous models were used to simulate the phase II trial from the phase I data.ResultsThe pharmacokinetics of ATM‐027 were characterized by a two‐compartment model with a total volume of distribution of 5.9 litres and a terminal half‐life of 22.3 days (phase II parameter estimates) in the typical patient. Continuous receptor expression was modelled using an inhibitory sigmoidal Emax‐model. Similar results from the phase I and phase II data were obtained, and EC50 was estimated to be 138 and 148 µg litre−1, respectively. Categorical receptor expression was modelled using a proportional odds model, and the EC50 values obtained were highly correlated with those from the continuous model. The numbers of target T cells were also modelled and treatment with ATM‐027 decreased the number of cells to 25.7% and 28.9% of their baseline values in the phase I and II trials, respectively. EC50s for the decrease in the number of T cells were 83 µg litre−1 and 307 µg litre−1, respectively. Simulations of the phase II trial from the phase I models gave good predictions of the dosing regimens administered in the phase II study.ConclusionAll aspects of effects of the monoclonal antibody ATM‐027 on Vβ5.2/5.3+ T cells were modelled and the phase II trial was simulated from phase I data. The effects of categorizing a continuous scale were also evaluated.
Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years‐old than cumulative high doses of inhaled terbutaline
Authors: Kaae Rikke , Agertoft Lone , Pedersen Sören , Nordvall S Lennart , Pedroletti Christophe , Bengtsson Thomas , Johannes‐Hellberg Ingegerd , Rosenborg Johan 
Published: September 2004

ObjectivesTo evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children.MethodsTwenty boys and girls (6–11 years‐old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double‐blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency.ResultsFormoterol and terbutaline had significant β2‐adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q‐Tc (heart rate corrected Q‐T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h.ConclusionsMultiple inhalations over 2.5 h of formoterol (4.5 µg) via Turbuhaler® are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 µg) in children with asthma.