bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of evaporite mobility in modifying subsidence patterns during normal fault growth and linkage, Halten Terrace, Mid‐Norway
Authors: Richardson Nick J. , Underhill John R. , Lewis Gavin 
Published: June 2005

AbstractWell‐calibrated seismic interpretation in the Halten Terrace of Mid‐Norway demonstrates the important role that structural feedback between normal fault growth and evaporite mobility has for depocentre development during syn‐rift deposition of the Jurassic–Early Cretaceous Viking and Fangst Groups. While the main rift phase reactivated pre‐existing structural trends, and initiated new extensional structures, a Triassic evaporite interval decouples the supra‐salt cover strata from the underlying basement, causing the development of two separate fault populations, one in the cover and the other confined to the pre‐salt basement.Detailed displacement–length analyses of both cover and basement fault arrays, combined with mapping of the component parts of the syn‐rift interval, have been used to reveal the spatial and temporal evolution of normal fault segments and sediment depocentres within the Halten Terrace area. Significantly, the results highlight important differences with traditional models of normal fault‐controlled subsidence, including those from parts of the North Sea where salt is absent. It can now be shown that evaporite mobility is intimately linked to the along‐strike displacement variations of these cover and basement faults. The evaporites passively move beneath the cover in response to the extension, such that the evaporite thickness becomes greatest adjacent to regions of high fault displacement. The consequent evaporite swells can become large enough to have pronounced palaeobathymetric relief in hangingwall locations, associated with fault displacement maxima– the exact opposite situation to that predicted by traditional models of normal fault growth. Evaporite movement from previous extension also affects the displacement–length relationships of subsequently nucleated or reactivated faults. Evaporite withdrawal, on the other hand, tends to be a later‐stage feature associated with the high stress regions around the propagating tips of normal faults or their coeval hangingwall release faults. The results indicate the important effect of, and structural feedback caused by, syn‐rift evaporite mobility in heavily modifying subsidence patterns produced by normal fault array evolution. Despite their departure from published models, the results provide a new, generic framework within which to interpret extensional fault and depocentre development and evolution in areas in which mobile evaporites exist.
A three‐dimensional approach to fault seal analysis: fault‐block juxtaposition & argillaceous smear modelling
Authors: Clarke Stuart M. , Burley Stuart D. , Williams Graham D. 
Published: June 2005

AbstractThree‐dimensional (3D) numerical modelling of fault displacement enables the building of geological models to represent the complex 3D geometry and geological properties of faulted sedimentary basins. Using these models, cross‐fault juxtaposition relationships are predicted in 3D space and through time, based on the geometries of strata that are cut by faults. Forward modelling of fault development allows a 3D prediction of fault‐zone argillaceous smear using a 3D application of the Shale Gouge Ratio. Numerical models of the Artemis Field, Southern North Sea, UK and the Moab Fault, Utah, USA are used to demonstrate the developed techniques and compare them to traditional one‐ and two‐dimensional solutions. These examples demonstrate that a 3D analysis leads to significant improvements in the prediction of fault seal, the analysis of the interaction of the sealing properties of multiple faults, and the interpretation of fault seal within the context of sedimentary basin geometry.
Quantifying the contribution of tectonics vs. differential compaction in the development of domes along the Mid‐Norwegian Atlantic margin
Authors: Gómez M. , Vergés J. 
Published: June 2005

AbstractA sequential restoration based on combined backstripping and unfolding methods affords the opportunity to study the Cenozoic evolution of two low amplitude domes in the Mid‐Norwegian extensional margin, the Helland Hansen Arch and the Vema Dome. The integration of growth strata geometries observed in both flanks of the domes demonstrate that the structures grew by a variable combination of tectonics and differential compaction mechanisms. Sequential restoration shows that the Helland Hansen Arch grew between Early Oligocene and earliest Late Pliocene times (33–1.9 Ma). During the first phase of growth (33–9 Ma), the tectonic compression accounted for a minimum of 27% of the total dome amplitude. During Late Miocene to Pliocene times (9–1.9 Ma), differential compaction was the mechanism for dome growth. During Late Pliocene times, the Helland Hansen Arch grew with the highest rates coinciding with initial deposition of prograding wedges (3.6–1.9 Ma). In contrast, the Vema Dome started to develop in Early Eocene times and grew at a fairly constant rate up to Early Pliocene times at 3.6 Ma. The amplification of the Vema Dome took place through both differential compaction and tectonics between Early Eocene and Late Miocene times (54.8–7 Ma). The tectonic contribution accounted for a minimum of a 37% of the total dome amplitude. During Pleistocene times, the progradation of clastic wedges led to a decrease of the amplitudes of both the Helland Hansen Arch and the Vema Dome. The different timing of tectonic growth for analysed domes and arches suggest that a small and protracted phase of compression affected the Mid‐Norwegian Margin. This agrees with well‐known widespread contractional deformation affecting the Atlantic Margin of the European Plate during the Tertiary.
Changes in availability of paediatric medicines in Australia between 1998 and 2002
Authors: Chui Jocelyn , Tordoff June , Reith David 
Published: June 2005

AimsTo determine changes in the availability of medicines for children in Australia and to determine the status of newly introduced chemical entities by age category.MethodsUsing the Australian Prescription Products Guide and the Schedule of Pharmaceutical Benefits, licensed medicines available in Australia in the calendar years 1998 and 2002 were examined.ResultsThe total number of medicines licensed in Australia increased from 1544 to 1903, the number of licensed paediatric items increased from 579 (37.5%) to 725 (38.1%), and those both licensed for paediatric use and subsidized increased from 356 (23.1%) to 441 (23.2%). The number of medicines with formulations suitable for paediatric use increased from 861 (55.7%) to 967 (50.8%), and of these 382 (24.7%) and 466 (24.5%) were licensed for paediatric use. Of the 90 new orally available chemical entities licensed for adults only 12 (13%) were licensed for children. Three (3%) were licensed for the 0–28 days and 28 days to 23 months age groups, eight (9%) for 2–11 years and 12 (13%) for 12–18 years. An additional 14 orally available chemical entities previously only licensed for adults, were licensed for children by 2002.ConclusionsThere have been some improvements in medicines licensing for older children, but not for children under the age of two years.
Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs
Authors: Björkman Sven 
Published: June 2005

Aims  To create a general physiologically based pharmacokinetic (PBPK) model for drug disposition in infants and children, covering the age range from birth to adulthood, and to evaluate it with theophylline and midazolam as model drugs.Methods  Physiological data for neonates, 0.5‐, 1‐, 2‐, 5‐, 10‐ and 15‐year‐old children, and adults, of both sexes were compiled from the literature. The data comprised body weight and surface area, organ weights, vascular and interstitial spaces, extracellular body water, organ blood flows, cardiac output and glomerular filtration rate. Tissue: plasma partition coefficients were calculated from rat data and unbound fraction (fu) of the drug in human plasma, and age‐related changes in unbound intrinsic hepatic clearance were estimated from CYP1A2 and CYP2E1 (theophylline) and CYP3A4 (midazolam) activities in vitro. Volume of distribution (Vdss), total and renal clearance (CL and CLR) and elimination half‐life (t1/2) were estimated by PBPK modelling, as functions of age, and compared with literature data.Results  The predicted Vdss of theophylline was 0.4‐0.6 l kg−1 and showed only a modest change with age. The median prediction error (MPE) compared with literature data was 3.4%. Predicted total CL demonstrated the time‐course generally reported in the literature. It was 20 ml h−1 kg−1 in the neonate, rising to 73 ml h−1 kg−1 at 5 years and then decreasing to 48 ml h−1 kg−1 in the adult. Overall, the MPE was − 4.0%. Predicted t1/2 was 18 h in the neonate, dropping rapidly to 4.6‐7.2 h from 6 months onwards, and the MPE was 24%. The predictions for midazolam were also in good agreement with literature data. Vdss ranged between 1.0 and 1.7 l kg−1 and showed only modest change with age. CL was 124 ml h−1 kg−1 in the neonate and peaked at 664 ml h−1 kg−1 at 5 years before decreasing to 425 ml h−1 kg−1 in the adult. Predicted t1/2 was 6.9 h in the neonate and attained ‘adult’ values of 2.5‐3.5 h from 1 year onwards.Conclusions  A general PBPK model for the prediction of drug disposition over the age range neonate to young adult is presented. A reference source of physiological data was compiled and validated as far as possible. Since studies of pharmacokinetics in children present obvious practical and ethical difficulties, one aim of the work was to utilize maximally already available data. Prediction of the disposition of theophylline and midazolam, two model drugs with dissimilar physicochemical and pharmacokinetic characteristics, yielded results that generally tallied with literature data. Future use of the model may demonstrate further its strengths and weaknesses.
Acute drug prescribing to children on chronic antiepilepsy therapy and the potential for adverse drug interactions in primary care
Authors: Novak Philipp H. , Ekins‐Daukes Suzie , Simpson Colin R. , Milne Robert M. , Helms Peter , McLay James S. 
Published: June 2005

AimsTo investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug–drug interactions.DesignAcute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0–17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland.SettingOne hundred and sixty‐one general practices throughout Scotland.ResultsDuring the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non‐epileptic drug therapy were eight, 11, six, and six for the 0–1, 2–4, 5–11, and 12–17‐year‐olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age‐adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0–1, 2–4, 5–11, and 12–17‐year‐old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low‐dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning.ConclusionsIn primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could give rise to clinically serious drug–drug interactions.
Allometric relationships between the pharmacokinetics of propofol in rats, children and adults
Authors: Knibbe Catherijne A. J. , Zuideveld Klaas P. , Aarts Leon P. H. J. , Kuks Paul F. M. , Danhof Meindert 
Published: June 2005

AimsAllometric equations have proven useful for the extrapolation of animal data to determine pharmacokinetic parameters in man. It has been proposed that these equations are also applicable over the human size range including the paediatric population. The aim of this work was to study the relationship between various pharmacokinetic parameters for propofol and body weight using data from rats, children and adults. Furthermore, the utility of allometric scaling is evaluated by the prediction of propofol concentrations in humans based on data obtained in the rat.MethodsThe relationship between the pharmacokinetic parameters of propofol obtained in rats, children and adults was analyzed by plotting the logarithmically transformed parameters against the corresponding logarithmically transformed body weights. In addition, based on allometric equations, pharmacokinetic parameters obtained in rats were scaled to humans. These parameters were used to simulate propofol concentrations in long‐term sedated critically ill patients using NONMEM. Simulated concentrations were then compared with actually observed concentrations in humans.ResultsThe relationship between pharmacokinetic parameters of propofol from rats, children and adults was in good agreement with those from the literature on allometric modelling. For clearance, intercompartmental clearance, central volume of distribution and peripheral volume of distribution, the power parameters were 0.78, 0.73, 0.98 and 1.1, respectively, and r2 values for the linear correlations were 0.990, 0.983, 0.977 and 0.994, respectively. On the basis of data obtained after a single bolus injection in the rat, adequate predictions of propofol concentrations in critically ill patients can be made using allometric equations, despite the long‐term nature of the use of the drug, the large number of infusion changes per day and/or differences in state of health and age.ConclusionsFor propofol, allometric scaling has proved to be valuable for cross species extrapolation. Furthermore, the use of the allometric equation between adults and children seems to be an adequate tool for the development of rational dosing schemes for children of varying body weights, and requires further study.
Effect of the Pediatric Exclusivity Provision on children's access to medicines
Authors: Grieve Joanne , Tordoff June , Reith David , Norris Pauline 
Published: June 2005

AimsTo determine the paediatric licensing status in the USA, UK, Australia and New Zealand of the 79 medicines granted paediatric exclusivity in the USA, and to assess the importance of those medicines to paediatric practice.MethodsThe medicines granted a patent extension in the USA as of 10 November 2003 were identified from the FDA website. Data on paediatric licensing were obtained from the Physicians Desk Reference (USA), the Electronic Medicines Compendium (UK), the Australian Prescription Products Guide (Australia) and the MedSafe website (New Zealand). A questionnaire was administered to seven paediatric consultants to assess the importance of the 79 PEMs for use in children. The questionnaire sought opinions on each drug, by age grouping, regarding: usefulness in patients with the condition, number of patients likely to be treated with each drug in a year, and acceptable therapeutic alternatives.ResultsFifty‐eight (73%) of the medicines had attained paediatric licensing in the USA. Sixty were licensed for adults in all four countries and of these 45 (75%) were licensed for children under 12 years in the USA compared with 31 (52%) to 33 (55%) for the other three countries. The proportion of these medicines licensed for children under 1 month, under 2 years and under 6 years of age ranged from 10% to 58% and there were no significant differences between the countries. For all four countries perceived usefulness and predicted numbers of patients both had some influence on the odds of a medicine having paediatric licensing.ConclusionsImprovements in licensing of some medicines for children have occurred in the USA, relative to the UK, Australia and New Zealand, subsequent to the Paediatric Exclusivity Provision. Improvements occurred for children over the age of six, but not for younger children.
Utility of routinely acquired primary care data for paediatric disease epidemiology and pharmacoepidemiology
Authors: Helms Peter J. , Ekins Daukes Suzie , Taylor Michael W. , Simpson Colin R. , McLay James S 
Published: June 2005

BackgroundThe majority of medicines prescribed for children are prescribed in primary care for common acute and chronic conditions. This is in contrast to prescribing in secondary care where the population of children admitted is small but where a large number of different medicines are prescribed to treat more serious and less common conditions.MethodsData on prescribing was extracted from the General Practice Administration System for Scotland (GPASS) for the year November 1999 to October 2000 and prescribing patterns for children aged 0–16 years expressed as percentages. A comparison of age specific consultations for asthma, as an example of a common paediatric condition, was also made between two separate general practice data sets, the General Practice Research Database (GRPD) and the continuous morbidity recording (CMR) subset of GPASS.ResultsOf 214 medicines investigated for unlicensed and off‐label prescribing no unlicensed prescribing was identified. Off‐label prescribing due to age was most common among younger and older children. The most common reasons for off‐label prescriptions were, in order of frequency, lower than recommended dose, higher than recommended dose, below the recommended age, and unlicensed formulation. Age and gender specific consultations for asthma were similar in the two representative databases, GPRD and CMR, both showing disappearance of the male predominance in the teenage years.ConclusionsLarge primary care data sets available within a unified health care system such as the UK National Health Service (NHS) are likely to be broadly compatible and produce similar results. The prescribing of off‐label medicines to children is common in primary care, most commonly due to prescribing out with the recommended dosage regimen.
Should domperidone be used for the treatment of gastro‐oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old
Authors: Pritchard D. S. , Baber N. , Stephenson T. 
Published: June 2005

Aim  To determine whether there is robust evidence of efficacy for domperidone in reducing the symptoms of gastro‐oesophageal reflux (GOR) and gastro‐oesophageal reflux disease (GORD) in children.Methods  Systematic review of randomized controlled trials (RCTs). A search was made of the Cochrane Library Issue 2004 (Central Register of Controlled Trials and Database of Systematic Reviews), Medline (Pub‐med) 1966 to present and Embase from 1974 to 2004, and reference citations of the RCTs that had been found electronically.Results  Four RCTs were identified. Only the two older trials showed any benefits of domperidone on clinical symptoms of GORD in older children, which were the primary outcome measures. In the trial undertaken by Clara, a good or excellent result was obtained in 93% of the domperidone group compared with 33% of the controls (P < 0.05). In the trial undertaken by de Loore, after 2 weeks of treatment 75% of patients treated with domperidone were found not to be vomiting, compared with 43% in the metoclopramide group and 7% in the placebo group. The trial by Corraccio gave no detailed results regarding the primary outcomes of effect of domperidone on symptoms but simply reported ‘cured’, ‘improved’ or ‘unchanged’. The secondary pH‐metric outcome of the number of reflux episodes, was reduced with domperidone.Conclusion  From the limited evidence available, there was no robust evidence of efficacy for the treatment of GOR with domperidone in young children. Given the usually benign nature of the condition, the widespread use of unlicensed medicines for GOR is not warranted.
Monitoring adverse drug reactions in children using community pharmacies: a pilot study
Authors: Stewart Derek , Helms Peter , McCaig Dorothy , Bond Christine , McLay James 
Published: June 2005

Aims  To determine the feasibility of a community pharmacy‐based parental adverse drug reaction (ADR) reporting system for children.Design  Prospective study of parent‐reported ADRs using a questionnaire issued to the parent or guardians of children 0–11 years of age collecting prescribed medicine for amoxicillin, and/or salbutamol, and collecting prescribed medicine for, or purchasing, paracetamol or ibuprofen suspension.Setting  Seven community pharmacies in Grampian, Scotland.Results  During a 4‐week period 360 prescriptions or purchases for the study medications occurred. Two hundred and sixty‐seven parents (85.5%) agreed to participate in the study. One hundred and six participants (40%) returned a total of 122 questionnaires. The demographics of responders and nonresponders including medication, age of child, and social status as assessed by the Depcat score were similar. There was no evidence of under‐representation of any socio‐economic group. Possible adverse events were detected using a symptom tick list and perceived ADRs using free text entry. Using the symptom tick list approach the most commonly reported symptoms were diarrhoea (28.9%) and tiredness (31.6%) for amoxicillin. The levels of diarrhoea and tiredness reported for ibuprofen, paracetamol and salbutamol were 15% and 20%, 7.4% and 18.5%, and 20% and 0%, respectively. Using the freehand section of the questionnaire 15 specific ADRs were reported by parents (12.3%). Eight children (21.2%) reported ADRs attributed to amoxicilin [diarrhoea (n = 4), fever (n = 1), anorexia (n = 1), hyperactivity (n = 1) and nonspecific (n = 1)], five to paracetamol [diarrhoea (n = 3), anorexia, irritability, crying and very angry (n = 1) and not stated (n = 1)], two to ibuprofen [diarrhoea (n = 1), not stated (n = )]. Only one off‐label prescription was identified and this was for salbutamol syrup prescribed to a child under 2 years of age.Conclusions  The prospective monitoring of paediatric ADRs, using a questionnaire issued to parents or guardians in the community pharmacies, is feasible.
Modelling approaches to dose estimation in children
Authors: Johnson Trevor N. 
Published: June 2005

IntroductionMost of the drugs on the market are originally developed for adults and dosage selection is based on an optimal balance between clinical efficacy and safety. The aphorism ‘children are not small adults’ not only holds true for the selection of suitable drugs and dosages for use in children but also their susceptibility to adverse drug reactions [1]. Since children may not be subject to dose escalation studies similar to those carried out in the adult population, some initial estimation of dose in paediatrics should be obtained via extrapolation approaches. However, following such an exercise, well‐conducted PK‐PD or PK studies will still be needed to determine the most appropriate doses for neonates, infants, children and adolescents.