A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.

Performance evaluation of onsite wastewater treatment : field sampling and preliminary evaluation of results

Background The onsite treatment of sewage and effluent disposal within the premises is widely prevalent in rural and urban fringe areas due to the general unavailability of reticulated wastewater collection systems. Despite the seemingly low technology of the systems, failure is common and in many cases leading to adverse public health and environmental consequences. Therefore it is important that careful consideration is given to the design and location of onsite sewage treatment systems. It requires an understanding of the factors that influence treatment performance. The use of subsurface effluent absorption systems is the most common form of effluent disposal for onsite sewage treatment and particularly for septic tanks. Additionally in the case of septic tanks, a subsurface disposal system is generally an integral component of the sewage treatment process. Therefore location specific factors will play a key role in this context. The project The primary aims of the research project are: • to relate treatment performance of onsite sewage treatment systems to soil conditions at site; • to identify important areas where there is currently a lack of relevant research knowledge and is in need of further investigation. These tasks were undertaken with the objective of facilitating the development of performance based planning and management strategies for onsite sewage treatment. The primary focus of the research project has been on septic tanks. Therefore by implication the investigation has been confined to subsurface soil absorption systems. The design and treatment processes taking place within the septic tank chamber itself did not form a part of the investigation. In the evaluation to be undertaken, the treatment performance of soil absorption systems will be related to the physico-chemical characteristics of the soil. Five broad categories of soil types have been considered for this purpose. The number of systems investigated was based on the proportionate area of urban development within the Brisbane region located on each soil types. In the initial phase of the investigation, though the majority of the systems evaluated were septic tanks, a small number of aerobic wastewater treatment systems (AWTS) were also included. This was primarily to compare the effluent quality of systems employing different generic treatment processes. It is important to note that the number of different types of systems investigated was relatively small. As such this does not permit a statistical analysis to be undertaken of the results obtained. This is an important issue considering the large number of parameters that can influence treatment performance and their wide variability. The report This report is the second in a series of three reports focussing on the performance evaluation of onsite treatment of sewage. The research project was initiated at the request of the Brisbane City Council. The work undertaken included site investigation and testing of sewage effluent and soil samples taken at distances of 1 and 3 m from the effluent disposal area. The project component discussed in the current report formed the basis for the more detailed investigation undertaken subsequently. The outcomes from the initial studies have been discussed, which enabled the identification of factors to be investigated further. Primarily, this report contains the results of the field monitoring program, the initial analysis undertaken and preliminary conclusions. Field study and outcomes Initially commencing with a list of 252 locations in 17 different suburbs, a total of 22 sites in 21 different locations were monitored. These sites were selected based on predetermined criteria. To obtain house owner agreement to participate in the monitoring study was not an easy task. Six of these sites had to be abandoned subsequently due to various reasons. The remaining sites included eight septic systems with subsurface effluent disposal and treating blackwater or combined black and greywater, two sites treating greywater only and six sites with AWTS. In addition to collecting effluent and soil samples from each site, a detailed field investigation including a series of house owner interviews were also undertaken. Significant observations were made during the field investigations. In addition to site specific observations, the general observations include the following: • Most house owners are unaware of the need for regular maintenance. Sludge removal has not been undertaken in any of the septic tanks monitored. Even in the case of aerated wastewater treatment systems, the regular inspections by the supplier is confined only to the treatment system and does not include the effluent disposal system. This is not a satisfactory situation as the investigations revealed. • In the case of separate greywater systems, only one site had a suitably functioning disposal arrangement. The general practice is to employ a garden hose to siphon the greywater for use in surface irrigation of the garden. • In most sites, the soil profile showed significant lateral percolation of effluent. As such, the flow of effluent to surface water bodies is a distinct possibility. • The need to investigate the subsurface condition to a depth greater than what is required for the standard percolation test was clearly evident. On occasion, seemingly permeable soil was found to have an underlying impermeable soil layer or vice versa. The important outcomes from the testing program include the following: • Though effluent treatment is influenced by the physico-chemical characteristics of the soil, it was not possible to distinguish between the treatment performance of different soil types. This leads to the hypothesis that effluent renovation is significantly influenced by the combination of various physico-chemical parameters rather than single parameters. This would make the processes involved strongly site specific. • Generally the improvement in effluent quality appears to take place only within the initial 1 m of travel and without any appreciable improvement thereafter. This relates only to the degree of improvement obtained and does not imply that this quality is satisfactory. This calls into question the value of adopting setback distances from sensitive water bodies. • Use of AWTS for sewage treatment may provide effluent of higher quality suitable for surface disposal. However on the whole, after a 1-3 m of travel through the subsurface, it was not possible to distinguish any significant differences in quality between those originating from septic tanks and AWTS. • In comparison with effluent quality from a conventional wastewater treatment plant, most systems were found to perform satisfactorily with regards to Total Nitrogen. The success rate was much lower in the case of faecal coliforms. However it is important to note that five of the systems exhibited problems with regards to effluent disposal, resulting in surface flow. This could lead to possible contamination of surface water courses. • The ratio of TDS to EC is about 0.42 whilst the optimum recommended value for use of treated effluent for irrigation should be about 0.64. This would mean a higher salt content in the effluent than what is advisable for use in irrigation. A consequence of this would be the accumulation of salts to a concentration harmful to crops or the landscape unless adequate leaching is present. These relatively high EC values are present even in the case of AWTS where surface irrigation of effluent is being undertaken. However it is important to note that this is not an artefact of the treatment process but rather an indication of the quality of the wastewater generated in the household. This clearly indicates the need for further research to evaluate the suitability of various soil types for the surface irrigation of effluent where the TDS/EC ratio is less than 0.64. • Effluent percolating through the subsurface absorption field may travel in the form of dilute pulses. As such the effluent will move through the soil profile forming fronts of elevated parameter levels. • The downward flow of effluent and leaching of the soil profile is evident in the case of podsolic, lithosol and kransozem soils. Lateral flow of effluent is evident in the case of prairie soils. Gleyed podsolic soils indicate poor drainage and ponding of effluent. In the current phase of the research project, a number of chemical indicators such as EC, pH and chloride concentration were employed as indicators to investigate the extent of effluent flow and to understand how soil renovates effluent. The soil profile, especially texture, structure and moisture regime was examined more in an engineering sense to determine the effect of movement of water into and through the soil. However it is not only the physical characteristics, but the chemical characteristics of the soil also play a key role in the effluent renovation process. Therefore in order to understand the complex processes taking place in a subsurface effluent disposal area, it is important that the identified influential parameters are evaluated using soil chemical concepts. Consequently the primary focus of the next phase of the research project will be to identify linkages between various important parameters. The research thus envisaged will help to develop robust criteria for evaluating the performance of subsurface disposal systems.

Towards Bayesian experimental design for nonlinear models that require a large number of sampling times

The use of Bayesian methodologies for solving optimal experimental design problems has increased. Many of these methods have been found to be computationally intensive for design problems that require a large number of design points. A simulation-based approach that can be used to solve optimal design problems in which one is interested in finding a large number of (near) optimal design points for a small number of design variables is presented. The approach involves the use of lower dimensional parameterisations that consist of a few design variables, which generate multiple design points. Using this approach, one simply has to search over a few design variables, rather than searching over a large number of optimal design points, thus providing substantial computational savings. The methodologies are demonstrated on four applications, including the selection of sampling times for pharmacokinetic and heat transfer studies, and involve nonlinear models. Several Bayesian design criteria are also compared and contrasted, as well as several different lower dimensional parameterisation schemes for generating the many design points.

Collective sampling and analysis of high order tensors for chatroom communications

This work investigates the accuracy and efficiency tradeoffs between centralized and collective (distributed) algorithms for (i) sampling, and (ii) n-way data analysis techniques in multidimensional stream data, such as Internet chatroom communications. Its contributions are threefold. First, we use the Kolmogorov-Smirnov goodness-of-fit test to show that statistical differences between real data obtained by collective sampling in time dimension from multiple servers and that of obtained from a single server are insignificant. Second, we show using the real data that collective data analysis of 3-way data arrays (users x keywords x time) known as high order tensors is more efficient than centralized algorithms with respect to both space and computational cost. Furthermore, we show that this gain is obtained without loss of accuracy. Third, we examine the sensitivity of collective constructions and analysis of high order data tensors to the choice of server selection and sampling window size. We construct 4-way tensors (users x keywords x time x servers) and analyze them to show the impact of server and window size selections on the results.

Cause of Death, Trend and Disease Burden in Shandong Province, China : the Third Retrospective Sampling Survey of Cause of Death Report

This book describes the mortality for all causes of death and the trend in major causes of death since 1970s in Shandong Province, China.

Sex discrimination and non-random sampling in the Australian labour market

Historically a significant gap between male and female wages has existed in the Australian labour market. Indeed this wage differential was institutionalised in the 1912 arbitration decision which determined that the basic female wage would be set at between 54 and 66 per cent of the male wage. More recently however, the 1969 and 1972 Equal Pay Cases determined that male/female wage relativities should be based upon the premise of equal pay for work of equal value. It is important to note that the mere observation that average wages differ between males and females is not sine qua non evidence of sex discrimination. Economists restrict the definition of wage discrimination to cases where two distinct groups receive different average remuneration for reasons unrelated to differences in productivity characteristics. This paper extends previous studies of wage discrimination in Australia (Chapman and Mulvey, 1986; Haig, 1982) by correcting the estimated male/female wage differential for the existence of non-random sampling. Previous Australian estimates of male/female human capital basedwage specifications together with estimates of the corresponding wage differential all suffer from a failure to address this issue. If the sample of females observed to be working does not represent a random sample then the estimates of the male/female wage differential will be both biased and inconsistent.

Work and family : the perception of balance among female teachers in northern Malaysia

Women’s participation in paid employment has become a common scenario even in non-western developing countries. For example in Malaysia, the trend is growing although the traditional gender role remains strong in Malaysian society. Even though working, women are still expected to assume major responsibilities at home. Thus, as opposed to men, women in this society face the challenge to satisfactorily balance work and family. This study was carried out to explore how Malaysian women perceive the meaning of a balanced work-family life. Sampling women teachers, the interview findings revealed that work-family balance was mainly perceived in terms of an individual’s ‘ability to fulfill role obligation’ appropriately in both the work and family domains. A few participants also viewed balance in the context of role satisfaction and role interference. Overall, the results support the assumption in the literature that perceptions of work-family experience are not universal, rather, the construct of work-family balance is culture-specific.

Recruiting, Sampling and Data Collection with Difficult Populations: Clients of Male Sex Workers.

Although there are many potential new insights to be gained through advancing research on the clients of male sex workers, significant social, ethical and methodological challenges to accessing this population exist. This research project case explores our attempts to recruit a population that does not typically form a cohesive or coherent 'community' and often avoids self-identifying to mitigate the stigma attached to buying sex. We used an arms-length recruitment campaign that focussed on directing potential participants to our study website, which could in turn lead them to participate in an anonymous telephone interview. Barriers to reaching male sex-work clients, however, demanded the evolution of our recruitment strategy. New technologies are part of the solution to accessing a hard-to-reach population, but they only work if researchers engage responsively. We also show how we conducted an in-depth interview with a client and discuss the value of using secondary data.

Ratcheting and wear behavior of Australian rail steel: Experimental investigation of material properties and sampling method

To The ratcheting behavior of high-strength rail steel (Australian Standard AS1085.1) is studied in this work for the purpose of predicting wear and damage to the rail surface. Historically, researchers have used circular test coupons obtained from the rail head to conduct cyclic load tests, but according to hardness profile data, considerable variation exists across the rail head section. For example, the induction-hardened rail (AS1085.1) shows high hardness (400-430 HV100) up to four-millimeters into the rail head’s surface, but then drops considerably beyond that. Given that cyclic test coupons five millimeters in diameter at the gauge area are usually taken from the rail sample, there is a high probability that the original surface properties of the rail do not apply across the entire test coupon and, therefore, data representing only average material properties are obtained. In the literature, disks (47 mm in diameter) for a twin-disk rolling contact test machine have been obtained directly from the rail sample and used to validate rolling contact fatigue wear models. The question arises: How accurate are such predictions? In this research paper, the effect of rail sampling position on the ratcheting behavior of AS1085.1 rail steel was investigated using rectangular shaped specimens. Uniaxial stress-controlled tests were conducted with samples obtained at four different depths to observe the ratcheting behaviour of each. Micro-hardness measurements of the test coupons were carried out to obtain a constitutive relationship to predict the effect of depth on the ratcheting behaviour of the rail material. This work ultimately assists the selection of valid material parameters for constitutive models in the study of rail surface ratcheting.

Estimation of cosmological parameters using adaptive importance sampling

We present a Bayesian sampling algorithm called adaptive importance sampling or population Monte Carlo (PMC), whose computational workload is easily parallelizable and thus has the potential to considerably reduce the wall-clock time required for sampling, along with providing other benefits. To assess the performance of the approach for cosmological problems, we use simulated and actual data consisting of CMB anisotropies, supernovae of type Ia, and weak cosmological lensing, and provide a comparison of results to those obtained using state-of-the-art Markov chain Monte Carlo (MCMC). For both types of data sets, we find comparable parameter estimates for PMC and MCMC, with the advantage of a significantly lower wall-clock time for PMC. In the case of WMAP5 data, for example, the wall-clock time scale reduces from days for MCMC to hours using PMC on a cluster of processors. Other benefits of the PMC approach, along with potential difficulties in using the approach, are analyzed and discussed.

A note on sampling chironomids for RNA-based studies of natural populations that retains critical morphological vouchers

The rapid uptake of transcriptomic approaches in freshwater ecology has seen a wealth of data produced concerning the ways in which organisms interact with their environment on a molecular level. Typically, such studies focus either at the community level and so don’t require species identifications, or on laboratory strains of known species identity or natural populations of large, easily identifiable taxa. For chironomids, impediments still exist for applying these technologies to natural populations because they are small-bodied and often require time-consuming secondary sorting of stream material and morphological voucher preparation to confirm species diagnosis. These procedures limit the ability to maintain RNA quantity and quality in such organisms because RNA degrades rapidly and gene expression can be altered rapidly in organisms; thereby limiting the inclusion of such taxa in transcriptomic studies. Here, we demonstrate that these limitations can be overcome and outline an optimised protocol for collecting, sorting and preserving chironomid larvae that enables retention of both morphological vouchers and RNA for subsequent transcriptomics purposes. By ensuring that sorting and voucher preparation are completed within <4 hours after collection and that samples are kept cold at all times, we successfully retained both RNA and morphological vouchers from all specimens. Although not prescriptive in specific methodology, we anticipate that this paper will assist in promoting transcriptomic investigations of the sublethal impact on chironomid gene expression of changes to aquatic environments.

Sampling frequency affects estimates of annual nitrous oxide fluxes

Quantifying nitrous oxide (N(2)O) fluxes, a potent greenhouse gas, from soils is necessary to improve our knowledge of terrestrial N(2)O losses. Developing universal sampling frequencies for calculating annual N(2)O fluxes is difficult, as fluxes are renowned for their high temporal variability. We demonstrate daily sampling was largely required to achieve annual N(2)O fluxes within 10% of the best estimate for 28 annual datasets collected from three continents, Australia, Europe and Asia. Decreasing the regularity of measurements either under- or overestimated annual N(2)O fluxes, with a maximum overestimation of 935%. Measurement frequency was lowered using a sampling strategy based on environmental factors known to affect temporal variability, but still required sampling more than once a week. Consequently, uncertainty in current global terrestrial N(2)O budgets associated with the upscaling of field-based datasets can be decreased significantly using adequate sampling frequencies.

Studies on Aerosol Particle Emission, Sampling and Authenticity

Emissions of coal combustion fly ash through real scale ElectroStatic Precipitators (ESP) were studied in different coal combustion and operation conditions. Sub-micron fly-ash aerosol emission from a power plant boiler and the ESP were determined and consequently the aerosol penetration, as based on electrical mobility measurements, thus giving thereby an indication for an estimate on the size and the maximum extent that the small particles can escape. The experimentals indicate a maximum penetration of 4% to 20 % of the small particles, as counted on number basis instead of the normally used mass basis, while simultaneously the ESP is operating at a nearly 100% collection efficiency on mass basis. Although the size range as such seems to appear independent of the coal, of the boiler or even of the device used for the emission control, the maximum penetration level on the number basis depends on the ESP operating parameters. The measured emissions were stable during stable boiler operation for a fired coal, and the emissions seemed each to be different indicating that the sub-micron size distribution of the fly-ash could be used as a specific characteristics for recognition, for instance for authenticity, provided with an indication of known stable operation. Consequently, the results on the emissions suggest an optimum particle size range for environmental monitoring in respect to the probability of finding traces from the samples. The current work embodies also an authentication system for aerosol samples for post-inspection from any macroscopic sample piece. The system can comprise newly introduced new devices, for mutually independent use, or, for use in a combination with each other, as arranged in order to promote the sampling operation length and/or the tag selection diversity. The tag for the samples can be based on naturally occurring measures and/or added measures of authenticity in a suitable combination. The method involves not only military related applications but those in civil industries as well. Alternatively to the samples, the system can be applied to ink for note printing or other monetary valued papers, but also in a filter manufacturing for marking fibrous filters.

Novel Approaches to the Sampling of Atmospheric Aerosols and Determination of Chemical Composition

The Earth s climate is a highly dynamic and complex system in which atmospheric aerosols have been increasingly recognized to play a key role. Aerosol particles affect the climate through a multitude of processes, directly by absorbing and reflecting radiation and indirectly by changing the properties of clouds. Because of the complexity, quantification of the effects of aerosols continues to be a highly uncertain science. Better understanding of the effects of aerosols requires more information on aerosol chemistry. Before the determination of aerosol chemical composition by the various available analytical techniques, aerosol particles must be reliably sampled and prepared. Indeed, sampling is one of the most challenging steps in aerosol studies, since all available sampling techniques harbor drawbacks. In this study, novel methodologies were developed for sampling and determination of the chemical composition of atmospheric aerosols. In the particle-into-liquid sampler (PILS), aerosol particles grow in saturated water vapor with further impaction and dissolution in liquid water. Once in water, the aerosol sample can then be transported and analyzed by various off-line or on-line techniques. In this study, PILS was modified and the sampling procedure was optimized to obtain less altered aerosol samples with good time resolution. A combination of denuders with different coatings was tested to adsorb gas phase compounds before PILS. Mixtures of water with alcohols were introduced to increase the solubility of aerosols. Minimum sampling time required was determined by collecting samples off-line every hour and proceeding with liquid-liquid extraction (LLE) and analysis by gas chromatography-mass spectrometry (GC-MS). The laboriousness of LLE followed by GC-MS analysis next prompted an evaluation of solid-phase extraction (SPE) for the extraction of aldehydes and acids in aerosol samples. These two compound groups are thought to be key for aerosol growth. Octadecylsilica, hydrophilic-lipophilic balance (HLB), and mixed phase anion exchange (MAX) were tested as extraction materials. MAX proved to be efficient for acids, but no tested material offered sufficient adsorption for aldehydes. Thus, PILS samples were extracted only with MAX to guarantee good results for organic acids determined by liquid chromatography-mass spectrometry (HPLC-MS). On-line coupling of SPE with HPLC-MS is relatively easy, and here on-line coupling of PILS with HPLC-MS through the SPE trap produced some interesting data on relevant acids in atmospheric aerosol samples. A completely different approach to aerosol sampling, namely, differential mobility analyzer (DMA)-assisted filter sampling, was employed in this study to provide information about the size dependent chemical composition of aerosols and understanding of the processes driving aerosol growth from nano-size clusters to climatically relevant particles (>40 nm). The DMA was set to sample particles with diameters of 50, 40, and 30 nm and aerosols were collected on teflon or quartz fiber filters. To clarify the gas-phase contribution, zero gas-phase samples were collected by switching off the DMA every other 15 minutes. Gas-phase compounds were adsorbed equally well on both types of filter, and were found to contribute significantly to the total compound mass. Gas-phase adsorption is especially significant during the collection of nanometer-size aerosols and needs always to be taken into account. Other aims of this study were to determine the oxidation products of β-caryophyllene (the major sesquiterpene in boreal forest) in aerosol particles. Since reference compounds are needed for verification of the accuracy of analytical measurements, three oxidation products of β-caryophyllene were synthesized: β-caryophyllene aldehyde, β-nocaryophyllene aldehyde, and β-caryophyllinic acid. All three were identified for the first time in ambient aerosol samples, at relatively high concentrations, and their contribution to the aerosol mass (and probably growth) was concluded to be significant. Methodological and instrumental developments presented in this work enable fuller understanding of the processes behind biogenic aerosol formation and provide new tools for more precise determination of biosphere-atmosphere interactions.

Time-Instant Sampling Based Encoding of Time-Varying Acoustic Spectrum

The inner ear has been shown to characterize an acoustic stimuli by transducing fluid motion in the inner ear to mechanical bending of stereocilia on the inner hair cells (IHCs). The excitation motion/energy transferred to an IHC is dependent on the frequency spectrum of the acoustic stimuli, and the spatial location of the IHC along the length of the basilar membrane (BM). Subsequently, the afferent auditory nerve fiber (ANF) bundle samples the encoded waveform in the IHCs by synapsing with them. In this work we focus on sampling of information by afferent ANFs from the IHCs, and show computationally that sampling at specific time instants is sufficient for decoding of time-varying acoustic spectrum embedded in the acoustic stimuli. The approach is based on sampling the signal at its zero-crossings and higher-order derivative zero-crossings. We show results of the approach on time-varying acoustic spectrum estimation from cricket call signal recording. The framework gives a time-domain and non-spatial processing perspective to auditory signal processing. The approach works on the full band signal, and is devoid of modeling any bandpass filtering mimicking the BM action. Instead, we motivate the approach from the perspective of event-triggered sampling by afferent ANFs on the stimuli encoded in the IHCs. Though the approach gives acoustic spectrum estimation but it is shallow on its complete understanding for plausible bio-mechanical replication with current mammalian auditory mechanics insights.