bluuebunny/crossref_metadata_2025 huggingface dataset:
Informed patient consent to participation in cluster randomized trials: an empirical exploration of trials in primary care
Authors: Eldridge Sandra M , Ashby Deborah , Feder Gene S
Published: April 2005

Cluster randomized trials are increasingly common. Obtaining informed patient consent to participation in these trials raises practical challenges and ethical issues. The aims of this paper were to 1) develop a typology of interventions employed in cluster randomized trials in primary care; 2) assess whether the likelihood of seeking individual consent to participation varies by intervension type; 3) assess whether this likelihood has increased over time; 4) assess evidence for under reporting of consent procedures; 5) articulate reasons for not obtaining consent; and 6) make recommendations for future trial investigators. We collected data on trial interventions and consent procedures from reports of 152 recently published trials, and 47 unpublished trials. We develop a typology of interventions based on reasons for adopting a clustered design. We examine proportions seeking individual consent to participation among trials involving different types of intervention, in different periods, and among published and unpublished trials. Two-thirds of the trials had multifaceted interventions. Trials involving different types of intervention had different propensities to seek consent, largely because of practical obstacles to obtaining consent. Obtaining consent can compromise internal validity. More recent trials are no more likely to obtain consent than past trials. There was no evidence of under-reporting of consent procedures in publications. In conclusion, future trial investigators should consider both practical reasons and scientific arguments for not obtaining individual patient consent for all interventions in their trials. Where feasible, they should allow patients to opt out of the trial. Lay individuals should represent trial participants as part of the process of cluster consent to participation, and lay individuals could also be involved in considering ethical issues during trial planning. A more public debate may clarify the general acceptability of not obtaining consent in certain situations.
Determinants of the intracluster correlation coefficient in cluster randomized trials: the case of implementation research
Authors: Campbell Marion K , Fayers Peter M , Grimshaw Jeremy M
Published: April 2005

The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients (ICCs) in cluster randomized trials from the field of implementation research. A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size. Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research datasets, mainly from the UK. Effects of setting (primary or secondary care), type of variable (process or outcome), type of measurement (objective or subjective), prevalence of outcome and size of cluster were tested. In total, 220 ICCs were available (range 0 to 0.415). Significant differences in ICC magnitude were found. The ICCs were significantly higher for process than for outcome variables, and for secondary care outcomes compared with primary care outcomes. The effects of prevalence and size were less clear cut. There was no evidence to suggest that type of measurement affected ICC size. In conclusion, accurate estimates of ICCs are essential for sample size calculations for cluster randomized trials of professional behaviour change interventions. This study demonstrates that ICCs are sensitive to a number of trial factors, particularly setting and outcome type. These factors must be considered when planning such cluster randomized trials.
Prior distributions for the intracluster correlation coefficient, based on multiple previous estimates, and their application in cluster randomized trials
Authors: Turner Rebecca M , Thompson Simon G , Spiegelhalter David J
Published: April 2005

Numerous estimates for the intracluster correlation coefficient (ICC) are available in research databases and publications. When planning a cluster randomized trial, an anticipated value for the ICC is required; currently, researchers base their choice informally on the magnitude of previous ICC estimates. In this paper, we make use of the wealth of ICC information by formally constructing informative prior distributions, while acknowledging the varying relevance and precision of the estimates available. Typically, for a planned trial in a given clinical setting, multiple relevant ICC estimates are available from each of several completed studies. Our preferred model allows for the imprecision in each ICC estimate around its underlying true value and, separately, allows for the similarity of ICC values from the same study. The relevance of each previous estimate to the planned clinical setting is considered, and estimates corresponding to less relevant outcomes or population types are given less influence. We find that such downweighting can increase the precision of the anticipated ICC. In trial design, the prior distribution constructed allows uncertainty about the ICC to be acknowledged, and we describe how to choose a design that provides adequate power across the range of likely ICC values. Prior information on the ICC can also be incorporated in analysis of the trial data, when taking a Bayesian approach. The methods proposed enable available ICC information to be summarised appropriately by an informative prior distribution, which is of direct practical use in cluster randomized trials.
Differential recruitment in a cluster randomized trial in primary care: the experience of the UK Back pain, Exercise, Active management and Manipulation (UK BEAM) feasibility study
Authors: Farrin Amanda , Russell Ian , Torgerson David , Underwood Martin
Published: April 2005

Background Cluster randomized trials, which randomize groups of patients rather than individuals, are commonly used to evaluate healthcare interventions such as training programmes targeted at health professionals. This article reports the dangers of randomizing entire primary care practices when participants cannot be identified before randomization, as shown by a UK national trial.

Method The UK BEAM trial, a national cluster randomized 322 factorial trial, was designed to evaluate three treatments for back pain in primary care: “active management”; randomized by practice; and spinal manipulation and exercise classes, both randomized by individual.

Results Two hundred and thirty-one participants were recruited in the feasibility study, 165 (141% of expected recruitment) from active (management) practices but only 66 (54% of expected recruitment) from traditional (management) practices. The participants in active practices were significantly different from those in traditional practices, notably in suffering from milder back pain.

Conclusions The feasibility study highlighted the dangers of randomizing clusters when individuals cannot be identified beforehand. Different numbers and types of participants were recruited in the two types of cluster. This differential recruitment led us to change the main trial design by abandoning practice level randomization. Instead all practices were trained in active management to maximize recruitment. Ideally cluster randomized trials should identify patients beforehand, to minimize the chance of selection bias. If this is not possible, patient recruitment should be independent in both intervention and control clusters. Pilot studies are especially important for cluster randomized trials, to identify unforeseen problems.
Reducing selection bias in a cluster randomized trial in West African villages
Authors: Kerry Sally M , Cappuccio Francesco P , Emmett Lynsey , Plange-Rhule Jacob , Eastwood John B
Published: April 2005

Selection bias in cluster randomized trials may threaten the validity of the results. This bias may occur either at the level of the cluster or of the individual. We describe measures for maintaining comparability of intervention groups in a cluster randomized trial of a health education package to reduce dietary salt. The setting was 12 villages of the Ashanti region of Ghana. In total, 1896 villagers between 40 and 75 years of age were selected to take part in the trial using stratified random sampling, based on age and sex. Following individuals' consent and baseline measurements in a pair of villages, villages were randomized to intervention or control arms, stratified for locality (semi-urban or rural). Primary outcomes of the trial were reduction in 24-hour urinary sodium and blood pressure. Of the villagers, 1013 individuals agreed to take part, with a response rate of 53%. The groups were comparable with respect to mean (SD) systolic and diastolic blood pressure (125/74 (27/14) mmHg versus 126/75 (25/14) mmHg) and other outcomes. In conclusion, in this study blind recruitment, aided by randomization in small blocks, and stratified random sampling of the subjects within the clusters helped to ensure comparability of intervention groups, which is vital for the validity of the trial results.
Randomization inference for balanced cluster-randomized trials
Authors: Raab Gillian M , Butcherb Isabella
Published: April 2005

This paper discusses the choice of randomization tests for inferences from cluster-randomized trials that have been designed to ensure a balanced allocation of clusters to treatments. Methods for covariate-adjusted randomization tests are reviewed and their application to balanced cluster-randomized trials discussed. Two cluster-randomized trials with balanced designs are used to illustrate the choices that can be made in selecting a randomization test, and methods for obtaining confidence intervals for treatment effects are illustrated. The balance imposed by the randomization in these trials makes adjustment for covariates less beneficial than for an unbalanced design. However, the adjusted analyses do not appear generally to have worse properties than the unadjusted ones, and may provide protection against any imbalance that has not been controlled for in the design. The only case when adjustment for covariates may result in worse precision is when a large number of cluster-level covariates are included in the analysis. An expression is provided that allows the size of this effect to be calculated for any given set of cluster-level covariates.
Design and analysis of clinical trials with clustering effects due to treatment
Authors: Roberts Chris , Roberts Stephen A
Published: April 2005

Where patients receive therapy as a group, there are good theoretical reasons to believe that variation in the outcome will be smaller for patients treated in the same group than for patients treated in different groups. Similarly, where different therapists treat different groups of patients, outcome for patients treated by the same therapist may differ less than outcome for patients treated by different therapists. Clinical trials evaluating such therapies need to consider this potential lack of independence. As with cluster-randomized trials, this has implications for the precision of treatment effects estimates and statistical power. There are nevertheless differences between clustering due to the organization of treatment and that due to randomization. In cluster-randomized trials the distribution of cluster sizes in each treatment arm should be similar as a consequence of randomization unless there is differential loss to follow-up. With clustering due to therapy group or therapist, cluster size may differ systematically between treatment arms, due to size of therapy groups or differing health professional caseload. Intra-cluster correlation may also differ between treatment arms. The implications of differential cluster size and intracluster correlation for design and analysis will be illustrated by data from two trials, the first comparing nurse practitioner care with general practitioner care, and the second comparing a group therapy with individual treatment as usual. The special case where a group therapy or therapist is compared with an unclustered treatment is examined in detail using a simulation study. The implications of differential clustering effects for sample size and power are addressed. It is argued that the design and analysis of this type of trial should take account of possible heterogeneity in cluster size and intracluster correlation.
Overlap coefficient for assessing the similarity of pharmacokinetic data between ethnically different populations
Authors: Mizuno Sachiko , Yamaguchi Takuhiro , Fukushima Akira , Matsuyama Yutaka , Ohashi Yasuo
Published: April 2005

We developed a method to assess the similarity of pharmacokinetic data between ethnically different populations. An evaluation of confidence intervals for the mean difference in pharmacokinetic parameters, such as area under the concentration-versus-time curve (AUC), between populations is often used. We propose the use of the overlap coefficient (OC), which represents the proportion of overlap between two probability distributions, as a measure of the similarity between distributions. We considered five OC estimators – two parametric ones and three nonparametric ones. Simulation studies were conducted to compare the performance of the five OC estimators and their bootstrap confidence intervals. Results showed that nonparametric estimators with fixed-bandwidth kernel density estimation had a smaller mean squared error in almost all situations, and their coverage probabilities were close to the nominal level. The proposed method was applied to pharmacokinetic data from a bridging study of a combination therapy for metastatic colorectal cancer patients in the USA and Japan. From the analyses of this study, it was suggested that the distributions of the logarithmically transformed AUC for leucovorin and 5-fluorouracil were similar between the two populations.
Translational clinical trials: an entropy-based approach to sample size
Authors: Piantadosi Steven
Published: April 2005

Translational clinical trials are small studies of therapies emerging from the laboratory. These trials are essential for generating early evidence regarding the effects of treatment on specific targets in the disease pathway and for guiding the next studies to be done. The statistical properties of such studies have been neglected, in part, because they do not fit the well-known clinical trials developmental paradigm. This paper discusses the translational trial setting, and presents an information (entropy) based approach to understanding the properties and use of these trials. The combination of biological knowledge with a designed experiment (albeit a small one) is a powerful device for resolving much of the considerable uncertainty surrounding an emerging therapeutic concept. An approach to motivating the sample size for translational trials is presented.
Standardized mean differences in individually-randomized and cluster-randomized trials, with applications to meta-analysis
Authors: White Ian R , Thomas James
Published: April 2005

The magnitude of the effect of an intervention on a quantitative outcome may be expressed as a standardized mean difference by dividing the difference in means by the standard deviation of the outcome. This is useful to compare outcomes measured using different scales, especially in meta-analysis. However, uncertainty about the standard deviation leads to complicated formulae to avoid bias and to compute the correct standard error. We review approximate and exact formulae and argue for the use of the exact formulae. We then extend the formulae to cluster-randomized trials, and show how the calculations may be implemented using published results. We also describe methods for estimating the standard deviation. Various pitfalls are identified which can lead to major errors especially in the cluster-randomized setting.
The use of random effects models to allow for clustering in individually randomized trials
Authors: Lee Katherine J , Thompson Simon G
Published: April 2005

Background We describe different forms of clustering that may occur in individually randomized trials, where the observed outcomes for different individuals cannot be regarded as independent. We propose random effects models to allow for such clustering, across a range of contexts and trial designs, and investigate their effect on estimation and interpretation of the treatment effect.

Methods We apply our proposed models to two individually randomized trials with potential for clustering, a trial of teleconsultation in hospital referral (the main outcome being offer of a further hospital appointment) and a trial of exercise therapy delivered by physiotherapists for low back pain (the outcome being a back pain score). Extensions to the methods include the possibility of explaining heterogeneity between clusters using cluster level characteristics and the potential dilution of cluster effects due to noncompliance.

Results In the teleconsultation trial, the odds ratio was significant (1.52, 95% CI 1.27 to 1.82) when clustering was ignored, but smaller and nonsignificant (1.36, 95% CI 0.85 to 2.13) when clustering by hospital consultant was taken into account. The 95% range of estimated treatment effects across consultants was from 0.21 to 8.76. This variability was only partially explained by the specialty of the consultant. In the back pain trial, although there was an overall benefit of exercise (change of 20.51 points on the back pain score) and little evidence of clustering, the estimated treatment effects for different physiotherapists ranged from 21.26 to +0.26 points.

Conclusions Clustering is an important issue in many individually randomized trials. Ignoring it can lead to underestimates of the uncertainty and too extreme P-values. Even when there is little apparent heterogeneity across clusters, it can still have a large impact on the estimation and interpretation of the treatment effect.
Performance test and simulation of a reciprocating engine for long endurance miniature unmanned aerial vehicles
Authors: Shin Younggy , Chang Sung-Ho , Koo Sam-Ok
Published: April 2005

Development of an engine with good fuel economy is very important for successful implementation of long endurance miniature UAVs (unmanned aerial vehicles). In the study, a four-stroke glow-plug engine was modified to a gasoline-fuelled spark ignition engine. Engine tests measuring performance and friction losses were conducted to tune a simulation program for performance prediction. It has been found that excessive friction losses are caused by insufficient lubrication at high speeds. The simulation program predicts that engine power and fuel economy become worse with high altitude, due to an increasing portion of friction losses. The simulation results suggest quantitative guidelines for further development of a practical engine.
Neuro-fuzzy-based fault detection of the air flow sensor of an idling gasoline engine
Authors: Chen Pei-Chung
Published: April 2005

This paper presents a neuro-fuzzy-based diagnostic system for detecting the faults of an air flow sensor of an idling gasoline engine. Based on the Takagi-cSugeno fuzzy system model, the diagnostic system is formulated by the input-output relationships between symptoms and faults. The system parameters are regulated with the learning datum from experiments, using the steepest descent method and back-propagation algorithm. The proposed diagnostic system consists of two parts: one is to judge the fault of the sensor and the other is to identify the bias degree of the sensor. The experimental results show that the fault source and fault (bias) degree can be identified with the proposed diagnostic system, and indicate that the neuro-fuzzy strategy is an efficient and available approach for fault diagnosis problems of the gasoline engine system.
Objective evaluation of the rumbling sound in passenger cars based on an artificial neural network
Authors: Lee Sang-Kwon , Kim Byung-Soo , Park Dong-Chul
Published: April 2005

A rumbling sound is one of the most important sound qualities in a passenger car. In previous work, a method for objectively evaluating the rumbling sound was developed based on the principal rumble component. In the present paper, the rumbling sound was found to relate effectively not only to the principal rumble component but also to the loudness and roughness. The last two subjective parameters are sound metrics in psychoacoustics. The principal rumble component, roughness, and loudness were used as the sound metrics for the development of the rumbling index to evaluate the rumbling sound objectively. The relationship between the rumbling index and these sound metrics is identified by an artificial neural network. Interior sounds of 14 passenger cars were measured, and 21 passengers subjectively evaluated the rumbling sound qualities of these interior sounds. Through this research, it was found that the results of these evaluations and the output of a neural network have a high correlation. The rumbling index has been successfully applied to the objective evaluation of the rumbling sound quality of mass-produced passenger cars.
Aerodynamic investigations of ventilated brake discs
Authors: Parish D , MacManus D G
Published: April 2005

The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry.
Fuel design concept for improving the spray characteristics and emissions of diesel engines
Authors: Lü Xing-Cai , Zhang Wu-Gao , Qiao Xin-Qi , Huang Zhen
Published: April 2005

This work investigated the improvement of spray characteristics and exhaust emissions of diesel engines by reformulating the fuel compounds and physicochemical parameters. Three oxygenated fuels, including ethanol, dimethyl carbonate (DMC), and dimethoxymethane (DMM), were mixed with diesel. Basic properties directly related to engine parameters and those characterizing fuel quality were investigated. A laser phase Doppler anemometry analyser was applied to obtain the spray characteristics, including the Sauter mean diameter and axial mean velocity distribution, of DMM-diesel hybrid fuels. Furthermore, engine tests of oxygenated hybrid fuels were performed on a four-cylinder water-cooled high-speed direct injection diesel engine. The results show that the evaporation properties and the fuel transportation parameters could be optimized using hybrid fuel, and the engine behaviour seemed to be improved in the presence of oxygenated additives with a reduction in pollutant emissions in exhaust gas.
Effects of injector leakage on liquid propane injection engine performance
Authors: Choi Gyeung Ho , Shin Seong Keun , Bae Seok Choun , Chung Yong Jong , Han Sung Bin
Published: April 2005

This study aims to provide basic technical information for research regarding starting performance improvement by using a 2.656 cm3 V6 liquid propane injection engine to study the effects of varying the liquefied petroleum gas (LPG) leakage on starting performance and to analyse the effects of such leakage on emission characteristics. To determine the LPG injection amount that corresponds to the desired LPG leakage, 1–30 l was injected to find the critical point and, since the injected fuel was detected at the intake starting from 5.5 l, starting performance comparisons of engine speed and exhaust gases were made at 0 l, 1 l, 2 l, 3 l, 4 l, 5 l, and 6 l by measuring the desired value five times and taking the average. Also, to study the effects of a small leak, the starting performance was tested while injecting 0 l, 0.2 l, 0.4 l, 0.6 l, 0.8 l, and 1 l. The major conclusions of this work are as follows: The results of determining the critical point of starting delay for LPG leakages of 1–30 l show that the critical point is 21 l and 14 cycles. For LPG leakages of 1–6 l, the starting time and unburned hydrocarbon (HC) increases with increasing LPG leakage. At LPG leakage of 0.2 l, the starting time is much faster at 1 cycle, but unburned HC increases with increasing LPG leakage.
Human subjective response to steering wheel vibration caused by diesel engine idle
Authors: Ajovalasit M , Giacomin J
Published: April 2005

This study investigated the human subjective response to steering wheel vibration of the type caused by a four-cylinder diesel engine idle in passenger cars. Vibrotactile perception was assessed using sinusoidal amplitude-modulated vibratory stimuli of constant energy level (r.m.s. acceleration, 0.41 m/s2) having a carrier frequency of 26 Hz (i.e. engine firing frequency) and modulation frequency of 6.5 Hz (half-order engine harmonic). Evaluations of seven levels of modulation depth parameter m(0.0, 0.1, 0.2, 0.4, 0.6, 0.8, and 1.0) were performed in order to define the growth function of human perceived disturbance as a function of amplitude modulation depth. Two semantic descriptors were used (unpleasantness and roughness) and two test methods (the Thurstone paired-comparison method and the Borg CR-10 direct evaluation scale) for a total of four tests. Each test was performed using an independent group of 25 individuals. The results suggest that there is a critical value of modulation depth m = 0.2 below which human subjects do not perceive differences in amplitude modulation and above which the stimulus-response relationship increases monotonically with a power function. The Stevens power exponents suggest that the perceived unpleasantness is non-linearly dependent on modulation depth m with an exponent greater than 1 and that the perceived roughness is dependent with an exponent close to unity.
Truck tyre modelling for rolling resistance calculations under a dynamic vertical load
Authors: Miège A J P , Popov A A
Published: April 2005

This paper deals with tyre modelling to predict the rolling resistance of truck tyres under a dynamic vertical load. Several models are applied and modified to perform the desired calculations. The model predictions are compared with the available experimental data on rolling resistance under a dynamic vertical load. The analysis is extended into a larger frequency range so that the different models considered can be assessed, and recommendations are made as to which model is best suited to the desired purpose. Within the frequency range considered and based on the experimental data available, Pacejka's model appears to give the best results.
Six-degree-of-freedom three-wheeled-vehicle model validation
Authors: Gawade T R , Mukherjee S , Mohan D
Published: April 2005

A spatial six-degree-of-freedom mathematical model of a three-wheeled vehicle used in Asian countries is developed. The governing equations are derived and integrated explicitly without linearization to yield a large displacement model that can be used for parametric studies. The model includes suspension model, tyre compliance, lateral force due to cornering stiffness, and rolling resistance at the tyre. The model is validated against vertical accelerations measured when passing over a road bump. The lateral steady state response is validated through a steady state circular test procedure.
Engine valve and seat insert wear depending on speed changes
Authors: Chun Keyoung Jin , Hong Jae Soo
Published: April 2005

The minimization of valve and seat insert wear is a critical factor for consideration in the pursuit of engine performance improvement. In order to achieve this goal, an innovative simulator was developed with the ability to generate and control high temperatures up to 900°C and various frequencies up to 80 Hz during motion, just as in the case of an actual vehicle engine. This wear simulator is considered to be a valid reproduction of the engine valve and seat insert wear process operating with various speeds during engine activity.

This work focuses on the different degrees of wear at three different test frequencies (10 Hz, 25 Hz, and multi-hertz). In this study, the seat insert's exterior surface temperature was controlled at 350 °C, the number of cycles was 2.1×106and the test load was 1960 N. The wear depth was measured before and after testing using a confocal laser microscope. It was found that higher frequencies caused a greater degree of wear than lower frequencies under identical test conditions (temperature, valve displacement, number of cycles, and test load). It was intended that an actual vehicle engine be used to perform a similar test, in order that the multi-hertz test, using a combination of the 10 and 25 Hz frequencies be applied. In the wear mechanism, adhesive wear, shear strain, abrasive wear, and surface fatigue wear were observed.
An electrostatic trap for control of ultrafine particle emissions from gasoline-engined vehicles
Authors: Rubino L , Crane R I , Shrimpton J S , Arcoumanis C
Published: April 2005

Health concerns over ultrafine (< 100 nm) particles in the urban atmosphere have focused attention on measurement and control of particle number as well as mass. Gasoline-engined as well as diesel-engined vehicles are likely to be within the scope of future particulate matter (PM) emission regulations. As a potential option for after-treatment of PM emissions from gasoline engines, the trapping performance of a catalysed wire-cylinder electrostatic trap has been investigated, first in a laboratory rig with simulated PM and then in the exhaust of a direct injection spark ignition engine. In the simulation experiments, the trap achieved capture efficiencies by total particle number exceeding 90 per cent at wire voltages of 7–10 kV, gas temperatures up to 400°C, and operating durations up to one hour, with no adverse effects from a catalyst coating on the collecting electrode. In the engine tests, at moderate speeds and loads, capture efficiency was 60–85 per cent in the homogeneous combustion mode and 50–60 per cent, of a much larger number of engine-out particles, in the stratified (overall-lean) mode. Gas residence time in the trap appeared to be a major factor in determining efficiency. The electrical power requirement and the effect on engine back-pressure were both minimal.
Effect of n-heptane and n-decane on exhaust odour in direct injection diesel engines
Authors: Roy M M
Published: April 2005

This study investigated the effect of n-heptane and n-decane on exhaust odour in direct injection (DI) diesel engines. The prospect of these alternative fuels to reduce wall adherence and overleaning, major sources of incomplete combustion, as well as odorous emissions has been investigated. The n-heptane was tested as a low boiling point fuel that can improve evaporation as well as wall adherence. However, the odour is a little worse with n-heptane and blends than that of diesel fuel due to overleaning of the mixture. Also, formaldehyde (HCHO) and total hydrocarbon (THC) in the exhaust increase with increasing n-heptane content. The n-decane was tested as a fuel with a high cetane number that can improve ignition delay, which has a direct effect on wall adherence and overleaning. However, with n-decane and blends, the odour rating is about 0.5-1 point lower than for diesel fuel. Moreover, the aldehydes and THC are significantly reduced. This is due to less wall adherence and proper mixture formation.
Modelling the wet deposition of reduced nitrogen over the British Isles using a Lagrangian multi‐layer atmospheric transport model
Authors: Fournier N. , Weston K. J. , Dore A. J. , Sutton M. A.
Published: April 2005

Wet deposition of reduced nitrogen is estimated for the United Kingdom using a Lagrangian long‐term, long‐range atmospheric transport model. Such long‐range transport models are used to develop emission‐control strategies to combat environmental acidification in the sensitive regions of the United Kingdom and Europe. These models currently consider the wet deposition as a loss term using scavenging rates and a simple seeder–feeder effect. The seeder–feeder effect is assumed to be the main process producing orographic precipitation since the majority of British Isles annual rainfall falls in frontal events. This paper focuses on the analysis of different parametrizations of the removal process by wet deposition. It is shown that the seeder–feeder effect is very dependent on flow direction. Therefore, a model of directional orographic enhancement of precipitation is developed to simulate this effect. A revised formulation of the wet deposition parametrization is suggested, incorporating the directional orographic precipitation produced with this model. This new formulation also takes into account the larger concentrations of ions dissolved in rain water measured in mountainous areas. Moreover, a new representation of the wet deposition process is developed by considering explicitly the mixing layer's depth calculated in the model. The results from the atmospheric model, with these revised parametrizations of the wet deposition, are then compared with measured wet deposition of reduced nitrogen. Firstly, with the new directional orographic rainfall, the modelled United Kingdom reduced nitrogen wet deposition budget is still underestimated but an increased correlation with measurements is obtained. Secondly, the inclusion of the calculated mixing layer's depth leads to a considerable improvement in the modelled reduced nitrogen wet deposition budget compared with measurements. Copyright © 2005 Royal Meteorological Society.
Dysprealbuminemic Hyperthyroxinemia in a Patient with Hyperthyroid Graves Disease
Authors: Cameron Scott J , Hagedorn Judith C , Sokoll Lori J , Caturegli Patrizio , Ladenson Paul W
Published: April 2005

Rare mutant forms of circulating albumin and prealbumin [transthyretin (TTR)] have increased binding affinity for thyroxine (T4). Patients with these variant plasma proteins, as a result of inherited mutations or as a paraneoplastic phenomenon, typically present with increased serum total T4 and, by some assay methodologies, an increased free T4 as well. Although these individuals are, in fact, euthyroid, nonspecific symptoms may lead to inappropriate treatment for hyperthyroidism. We present a 34-year-old woman in whom a mutant form of TTR with increased T4 binding affinity and coexisting Graves disease was present. Subsequent 131I therapy led to development of postablative hypothyroidism, which was obscured by her higher serum free T4 concentration. Circulating thyroid-binding globulin (TBG), albumin, and TTR concentrations were all within their respective reference limits. A T4-binding protein panel confirmed that TTR-bound T4 was significantly increased, whereas TBG- and albumin-bound T4 was normal, indicating that this patient had euthyroid dysprealbuminemic hyperthyroxinemia, which had been masked by the initial presentation of hyperthyroidism. These findings indicate that hypothyroidism can be masked by coexisting euthyroid dysprealbuminemic hyperthyroxinemia.
Exploring the Evolution of Wolbachia Compatibility Types
Authors: Charlat Sylvain , Calmet Claire , Andrieu Olivier , Merçot Hervé
Published: April 2005

Wolbachia-induced cytoplasmic incompatibility (CI) is observed when males bearing the bacterium mate with uninfected females or with females bearing a different Wolbachia variant; in such crosses, paternal chromosomes are lost at the first embryonic mitosis, most often resulting in developmental arrest. The molecular basis of CI is currently unknown, but it is useful to distinguish conceptually the male and female sides of this phenomenon: in males, Wolbachia must do something, before it is shed from maturing sperm, that will disrupt paternal chromosomes functionality [this is usually termed “the modification (mod) function”]; in females, Wolbachia must somehow restore embryonic viability, through what is usually called “the rescue (resc) function.” The occurrence of CI in crosses between males and females bearing different Wolbachia variants demonstrates that the mod and resc functions interact in a specific manner: different mod resc pairs make different compatibility types. We are interested in the evolutionary process allowing the diversification of compatibility types. In an earlier model, based on the main assumption that the mod and resc functions can mutate independently, we have shown that compatibility types can evolve through a two-step process, the first involving drift on mod variations and the second involving selection on resc variations. This previous study has highlighted the need for simulation-based models that would include the effects of nondeterministic evolutionary forces. This study is based on a simulation program fulfilling this condition, allowing us to follow the evolution of compatibility types under mutation, drift, and selection. Most importantly, simulations suggest that in the frame of our model, the evolution of compatibility types is likely to be a gradual process, with new compatibility types remaining partially compatible with ancestral ones.
Length and Sequence Heterozygosity Differentially Affect HRAS1 Minisatellite Stability During Meiosis in Yeast
Authors: Jauert Peter A , Kirkpatrick David T
Published: April 2005

Minisatellites, one of the major classes of repetitive DNA sequences in eukaryotic genomes, are stable in somatic cells but destabilize during meiosis. We previously established a yeast model system by inserting the human Ha-ras/HRAS1 minisatellite into the HIS4 promoter and demonstrated that our system recapitulates all of the phenotypes associated with the human minisatellite. Here we demonstrate that meiotic minisatellite tract-length changes are half as frequent in diploid cells harboring heterozygous HRAS1 minisatellite tracts in which the two tracts differ by only two bases when compared to a strain with homozygous minisatellite tracts. Further, this decrease in alteration frequency is entirely dependent on DNA mismatch repair. In contrast, in a diploid strain containing heterozygous minisatellite tract alleles differing in length by three complete repeats, length alterations are observed at twice the frequency seen in a strain with homozygous tracts. Alterations consist of previously undetectable gene conversion events, plus nonparental length alteration events seen previously in strains with homozygous tracts. A strain containing tracts with both base and length heterozygosity exhibits the same level of alteration as a strain containing only length heterozygosity, indicating that base heterozygosity-dependent tract stabilization does not affect tract-length alterations occurring by gene conversion.
Effective Size of a Fluctuating Age-Structured Population
Authors: Engen Steinar , Lande Russell , Saether Bernt-Erik
Published: April 2005

Previous theories on the effective size of age-structured populations assumed a constant environment and, usually, a constant population size and age structure. We derive formulas for the variance effective size of populations subject to fluctuations in age structure and total population size produced by a combination of demographic and environmental stochasticity. Haploid and monoecious or dioecious diploid populations are analyzed. Recent results from stochastic demography are employed to derive a two-dimensional diffusion approximation for the joint dynamics of the total population size, N, and the frequency of a selectively neutral allele, p. The infinitesimal variance for p, multiplied by the generation time, yields an expression for the effective population size per generation. This depends on the current value of N, the generation time, demographic stochasticity, and genetic stochasticity due to Mendelian segregation, but is independent of environmental stochasticity. A formula for the effective population size over longer time intervals incorporates deterministic growth and environmental stochasticity to account for changes in N.
Multiple Endonucleases Function to Repair Covalent Topoisomerase I Complexes in Saccharomyces cerevisiae
Authors: Deng Changchun , Brown James A , You Dongqing , Brown J Martin
Published: April 2005

Topoisomerase I plays a vital role in relieving tension on DNA strands generated during replication. However if trapped by camptothecin or other DNA damage, topoisomerase protein complexes may stall replication forks producing DNA double-strand breaks (DSBs). Previous work has demonstrated that two structure-specific nucleases, Rad1 and Mus81, protect cells from camptothecin toxicity. In this study, we used a yeast deletion pool to identify genes that are important for growth in the presence of camptothecin. In addition to genes involved in DSB repair and recombination, we identified four genes with known or implicated nuclease activity, SLX1, SLX4, SAE2, and RAD27, that were also important for protection against camptothecin. Genetic analysis revealed that the flap endonucleases Slx4 and Sae2 represent new pathways parallel to Tdp1, Rad1, and Mus81 that protect cells from camptothecin toxicity. We show further that the function of Sae2 is likely due to its interaction with the endonuclease Mre11 and that the latter acts on an independent branch to repair camptothecin-induced damage. These results suggest that Mre11 (with Sae2) and Slx4 represent two new structure-specific endonucleases that protect cells from trapped topoisomerase by removing topoisomerase-DNA adducts.
Genetic Linkage Maps of the Red Flour Beetle, Tribolium castaneum, Based on Bacterial Artificial Chromosomes and Expressed Sequence Tags
Authors: Lorenzen Marcé D , Doyungan Zaldy , Savard Joel , Snow Kathy , Crumly Lindsey R , Shippy Teresa D , Stuart Jeffrey J , Brown Susan J , Beeman Richard W
Published: April 2005

A genetic linkage map was constructed in a backcross family of the red flour beetle, Tribolium castaneum, based largely on sequences from bacterial artificial chromosome (BAC) ends and untranslated regions from random cDNA's. In most cases, dimorphisms were detected using heteroduplex or single-strand conformational polymorphism analysis after specific PCR amplification. The map incorporates a total of 424 markers, including 190 BACs and 165 cDNA's, as well as 69 genes, transposon insertion sites, sequence-tagged sites, microsatellites, and amplified fragment-length polymorphisms. Mapped loci are distributed along 571 cM, spanning all 10 linkage groups at an average marker separation of 1.3 cM. This genetic map provides a framework for positional cloning and a scaffold for integration of the emerging physical map and genome sequence assembly. The map and corresponding sequences can be accessed through BeetleBase (http://www.bioinformatics.ksu.edu/BeetleBase/).
Model Selection in Binary Trait Locus Mapping
Authors: Coffman Cynthia J , Doerge R W , Simonsen Katy L , Nichols Krista M , Duarte Christine K , Wolfinger Russell D , McIntyre Lauren M
Published: April 2005

Quantitative trait locus (QTL) mapping methodology for continuous normally distributed traits is the subject of much attention in the literature. Binary trait locus (BTL) mapping in experimental populations has received much less attention. A binary trait by definition has only two possible values, and the penetrance parameter is restricted to values between zero and one. Due to this restriction, the infinitesimal model appears to come into play even when only a few loci are involved, making selection of an appropriate genetic model in BTL mapping challenging. We present a probability model for an arbitrary number of BTL and demonstrate that, given adequate sample sizes, the power for detecting loci is high under a wide range of genetic models, including most epistatic models. A novel model selection strategy based upon the underlying genetic map is employed for choosing the genetic model. We propose selecting the “best” marker from each linkage group, regardless of significance. This reduces the model space so that an efficient search for epistatic loci can be conducted without invoking stepwise model selection. This procedure can identify unlinked epistatic BTL, demonstrated by our simulations and the reanalysis of Oncorhynchus mykiss experimental data.
A Genetic Screen for Suppressors of Drosophila NSF2 Neuromuscular Junction Overgrowth
Authors: Laviolette Matthew J , Nunes Paula , Peyre Jean-Baptiste , Aigaki Toshiro , Stewart Bryan A
Published: April 2005

The Drosophila larval neuromuscular system serves as a valuable model for studying the genes required for synaptic development and function. N-Ethylmaleimide sensitive factor (NSF) is a molecule known to be important in vesicular trafficking but neural expression of a dominant negative form of NSF2 induces an unexpected overgrowth of the Drosophila larval neuromuscular synapse. We have taken a genetic approach to understanding this novel phenotype by conducting a gain-of-function modifier screen to isolate genes that interact with the overgrowth phenotype. Our approach was to directly visualize the neuromuscular junction (NMJ) using a GFP transgene and screen for suppressors of NMJ overgrowth using the Gene Search collection of P-element insertions. Of the 3000 lines screened, we identified 99 lines that can partially restore the normal phenotype. Analysis of the GS element insertion sites by inverse PCR and comparison of the flanking DNA sequence to the Drosophila genome sequence revealed nearby genes for all but 10 of the 99 lines. The recovered genes, both known and predicted, include transcription factors, cytoskeletal elements, components of the ubiquitin pathway, and several signaling molecules. This collection of genes that suppress the NSF2 neuromuscular junction overgrowth phenotype is a valuable resource in our efforts to further understand the role of NSF at the synapse.
Evolutionary History of Silene latifolia Sex Chromosomes Revealed by Genetic Mapping of Four Genes
Authors: Filatov Dmitry A
Published: April 2005

The sex chromosomes of dioecious white campion, Silene latifolia (Caryophyllaceae), are of relatively recent origin (10–20 million years), providing a unique opportunity to trace the origin and evolution of sex chromosomes in this genus by comparing closely related Silene species with and without sex chromosomes. Here I demonstrate that four genes that are X-linked in S. latifolia are also linked in nondioecious S. vulgaris, which is consistent with Ohno's (1967) hypothesis that sex chromosomes evolve from a single pair of autosomes. I also report a genetic map for four S. latifolia X-linked genes, SlX1, DD44X, SlX4, and a new X-linked gene SlssX, which encodes spermidine synthase. The order of the genes on the S. latifolia X chromosome and divergence between the homologous X- and Y-linked copies of these genes supports the “evolutionary strata” model, with at least three consecutive expansions of the nonrecombining region on the Y chromosome (NRY) in this plant species.