An analysis of ethical issues in using wastewater analysis to monitor illicit drug use

Aims To discuss ethical issues that may arise in using WWA to monitor illicit drug use in the general population and in entertainment precincts, prisons, schools and work-places. Method Review current applications of WWA and identify ethical and social issues that may be raised with current and projected future uses of this method. Results Wastewater analysis (WWA) of drug residues is a promising method of monitoring illicit drug use that may overcome some limitations of other monitoring methods. When used for monitoring purposes in large populations, WWA does not raise major ethical concerns because individuals are not identified and the prospects of harming residents of catchment areas are remote. When WWA is used in smaller catchment areas (entertainment venues, prisons, schools or work-places) their results could, possibly, indirectly affect the occupants adversely. Researchers will need to take care in reporting their results to reduce media misreporting. Fears about possible use of WWA for mass individual surveillance by drug law enforcement officials are unlikely to be realized, but will need to be addressed because they may affect public support adversely for this type of research. Conclusions Using wastewater analysis to monitor illicit drug use in large populations does not raise major ethical concerns, but researchers need to minimize possible adverse consequences in studying smaller populations, such as workers, prisoners and students.

Illicit drug use between an annual key holiday and a control period: Wastewater analysis in a semi-rural, an urban and a vacation area

Introduction and Aims: Holiday periods are potentially a time for increased substance use as social events and private parties are more common. Data on community illicit drug consumption during holiday periods are limited. Besides existing methods for determining drug use, such as population surveys, one emerging method is to measure illicit drugs and/or their metabolites in wastewater samples. This study examined the change in consumption of cannabis, methamphetamine, cocaine and 3,4- methylenedioxymethamphetamine in three different types of areas (an inland semi-rural area, a coastal urban area and a vacation island) with respect to holiday times. Design and Methods: Samples were collected at the inlet of the major wastewater treatment plant in each area during a key annual holiday (i.e. the summer holiday including Christmas and New Year) and control period. Illicit drug residues in the daily composited samples were measured by liquid chromatography coupled with tandem mass spectrometry. Results: Drug use varied substantially among the three areas within each monitoring period as well as between the holiday and control period within each area. Use consistently increased and peaked over New Year particularly for cocaine and 3,4-methylenedioxymethamphetamine whereas cannabis and methamphetamine were relatively less subjected to holiday times in all the areas. Discussion and Conclusions: Wastewater sampling and analysis provides higher spatio-temporal resolution than national surveys and supplements drug epidemiology studies originating primary in metropolitan locations. Such data is essential for policy makers to plan potential intervention strategies associated with these illicit substances in regional areas and other settings besides urban areas in the future.

Challenges and opportunities in using wastewater analysis to measure drug use in a small prison facility

Introduction and Aims Wastewater analysis (WWA) is intended to be a direct and objective method of measuring substance use in large urban populations. It has also been used to measure prison substance use in two previous studies. The application of WWA in this context has raised questions as to how best it might be used to measure illicit drug use in prisons, and whether it can also be used to measure prescription misuse. We applied WWA to a small regional prison to measure the use of 12 licit and illicit substances. We attempted to measure the non-medical use of methadone and buprenorphine and to compare our findings with the results of the prison's mandatory drug testing (MDT). Design and Methods Representative daily composite samples were collected for two periods of 12 consecutive days in May to July 2013 and analysed for 18 drug metabolites. Prescription data and MDT results were obtained from the prison and compared with the substance use estimates calculated from WWA data. Results Daily use of methamphetamine, methadone, buprenorphine and codeine was detected, while sporadic detection of ketamine and methylone was also observed. Overall buprenorphine misuse appeared to be greater than methadone misuse. Discussion and Conclusions Compared with MDT, WWA provides a more comprehensive picture of prison substance use. WWA also has the potential to measure the misuse of medically prescribed substances. However, a great deal of care must be exercised in quantifying the usage of any substance in small populations, such as in prisons.

Measuring drug use patterns in Queensland through wastewater analysis

Estimating the use of illicit drugs in the general community is an important task with ramifications for law enforcement agencies, as well as health portfolios. Australia has four ongoing drug monitoring systems, including the AIC’s DUMA program, the National Drug Strategy Household Survey, the Illicit Drug Reporting System and the Ecstasy and Related Drug Reporting System. The systems vary in methods, but broadly they are reliant upon self-report data and may be subject to selection biases. The present study employed a completely different method. By chemically analysing sewerage water, the study produced daily estimates of consumption of methamphetamine, MDMA and cocaine. Samples were collected in November 2009 and November 2010 from a municipality in Queensland, with an population of over 150,000 people. Estimates were made of the average daily dose and average daily street value per 1,000 people. On the basis of estimated dose and price, the methamphetamine market appeared considerably stronger than either MDMA or cocaine. This paper explains the strengths and weaknesses of wastewater analysis. It considers the potential value of wastewater analysis in measuring net consumption of illicit drugs and the effectiveness of law enforcement agency strategies.

A novel human leucocyte antigen-DRB1 genotyping method based on multiplex primer extension reactions

We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01-16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.

A highly efficient and consistent method for harvesting large volumes of high-titre lentiviral vectors

Lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) are emerging as the vectors of choice for in vitro and in vivo gene therapy studies. However, the current method for harvesting lentivectors relies upon ultracentrifugation at 50 000 g for 2 h. At this ultra-high speed, rotors currently in use generally have small volume capacity. Therefore, preparations of large volumes of high-titre vectors are time-consuming and laborious to perform. In the present study, viral vector supernatant harvests from vector-producing cells (VPCs) were pre-treated with various amounts of poly-L-lysine (PLL) and concentrated by low speed centrifugation. Optimal conditions were established when 0.005% of PLL (w/v) was added to vector supernatant harvests, followed by incubation for 30 min and centrifugation at 10 000 g for 2 h at 4 degreesC. Direct comparison with ultracentrifugation demonstrated that the new method consistently produced larger volumes (6 ml) of high-titre viral vector at 1 x 10(8) transduction unit (TU)/ml (from about 3000 ml of supernatant) in one round of concentration. Electron microscopic analysis showed that PLL/viral vector formed complexes, which probably facilitated easy precipitation at low-speed concentration (10 000 g), a speed which does not usually precipitate viral particles efficiently. Transfection of several cell lines in vitro and transduction in vivo in the liver with the lentivector/PLL complexes demonstrated efficient gene transfer without any significant signs of toxicity. These results suggest that the new method provides a convenient means for harvesting large volumes of high-titre lentivectors, facilitate gene therapy experiments in large animal or human gene therapy trials, in which large amounts of lentiviral vectors are a prerequisite.

An accurate rating aggregation method for generating item reputation

Many websites presently provide the facility for users to rate items quality based on user opinion. These ratings are used later to produce item reputation scores. The majority of websites apply the mean method to aggregate user ratings. This method is very simple and is not considered as an accurate aggregator. Many methods have been proposed to make aggregators produce more accurate reputation scores. In the majority of proposed methods the authors use extra information about the rating providers or about the context (e.g. time) in which the rating was given. However, this information is not available all the time. In such cases these methods produce reputation scores using the mean method or other alternative simple methods. In this paper, we propose a novel reputation model that generates more accurate item reputation scores based on collected ratings only. Our proposed model embeds statistical data, previously disregarded, of a given rating dataset in order to enhance the accuracy of the generated reputation scores. In more detail, we use the Beta distribution to produce weights for ratings and aggregate ratings using the weighted mean method. Experiments show that the proposed model exhibits performance superior to that of current state-of-the-art models.

A three-dimensional hybrid smoothed finite element method (H-SFEM) for nonlinear solid mechanics problems

This paper presents a novel three-dimensional hybrid smoothed finite element method (H-SFEM) for solid mechanics problems. In 3D H-SFEM, the strain field is assumed to be the weighted average between compatible strains from the finite element method (FEM) and smoothed strains from the node-based smoothed FEM with a parameter α equipped into H-SFEM. By adjusting α, the upper and lower bound solutions in the strain energy norm and eigenfrequencies can always be obtained. The optimized α value in 3D H-SFEM using a tetrahedron mesh possesses a close-to-exact stiffness of the continuous system, and produces ultra-accurate solutions in terms of displacement, strain energy and eigenfrequencies in the linear and nonlinear problems. The novel domain-based selective scheme is proposed leading to a combined selective H-SFEM model that is immune from volumetric locking and hence works well for nearly incompressible materials. The proposed 3D H-SFEM is an innovative and unique numerical method with its distinct features, which has great potential in the successful application for solid mechanics problems.

A new method for the in vivo identification of mechanical properties in arteries from cine MRI images: Theoretical framework and validation

Quantifying the stiffness properties of soft tissues is essential for the diagnosis of many cardiovascular diseases such as atherosclerosis. In these pathologies it is widely agreed that the arterial wall stiffness is an indicator of vulnerability. The present paper focuses on the carotid artery and proposes a new inversion methodology for deriving the stiffness properties of the wall from cine-MRI (magnetic resonance imaging) data. We address this problem by setting-up a cost function defined as the distance between the modeled pixel signals and the measured ones. Minimizing this cost function yields the unknown stiffness properties of both the arterial wall and the surrounding tissues. The sensitivity of the identified properties to various sources of uncertainty is studied. Validation of the method is performed on a rubber phantom. The elastic modulus identified using the developed methodology lies within a mean error of 9.6%. It is then applied to two young healthy subjects as a proof of practical feasibility, with identified values of 625 kPa and 587 kPa for one of the carotid of each subject.

Stress analysis of carotid atheroma in a transient ischaemic attack patient using the MRI-based fluid-structure interaction method

Rupture of atherosclerotic plaque is a major cause of mortality. Plaque stress analysis, based on patient-specific multisequence in vivo MRI, can provide critical information for the understanding of plaque rupture and could eventually lead to plaque rupture prediction. However, the direct link between stress and plaque rupture is not fully understood. In the present study, the plaque from a patient who recently experienced a transient ischaemic attack (TIA) was studied using a fluid-structure interaction method to quantify stress distribution in the plaque region based on in vivo MR images. The results showed that wall shear stress is generally low in the artery with a slight increase at the plaque throat owing to minor luminal narrowing. The oscillatory shear index is much higher in the proximal part of the plaque. Both local wall stress concentrations and the relative stress variation distribution during a cardiac cycle indicate that the actual plaque rupture site is collocated with the highest rupture risk region in the studied patient.

In vivo non-invasive high resolution MR-based method for the determination of the elastic modulus of arterial vessels

The mechanical properties of arterial walls have long been recognized to play an essential role in the development and progression of cardiovascular disease (CVD). Early detection of variations in the elastic modulus of arteries would help in monitoring patients at high cardiovascular risk stratifying them according to risk. An in vivo, non-invasive, high resolution MR-phase-contrast based method for the estimation of the time-dependent elastic modulus of healthy arteries was developed, validated in vitro by means of a thin walled silicon rubber tube integrated into an existing MR-compatible flow simulator and used on healthy volunteers. A comparison of the elastic modulus of the silicon tube measured from the MRI-based technique with direct measurements confirmed the method's capability. The repeatability of the method was assessed. Viscoelastic and inertial effects characterizing the dynamic response of arteries in vivo emerged from the comparison of the pressure waveform and the area variation curve over a period. For all the volunteers who took part in the study the elastic modulus was found to be in the range 50-250 kPa, to increase during the rising part of the cycle, and to decrease with decreasing pressure during the downstroke of systole and subsequent diastole.

Comparison of active-set method deconvolution and matched-filtering for derivation of an ultrasound transit time spectrum

The quality of ultrasound computed tomography imaging is primarily determined by the accuracy of ultrasound transit time measurement. A major problem in analysis is the overlap of signals making it difficult to detect the correct transit time. The current standard is to apply a matched-filtering approach to the input and output signals. This study compares the matched-filtering technique with active set deconvolution to derive a transit time spectrum from a coded excitation chirp signal and the measured output signal. The ultrasound wave travels in a direct and a reflected path to the receiver, resulting in an overlap in the recorded output signal. The matched-filtering and deconvolution techniques were applied to determine the transit times associated with the two signal paths. Both techniques were able to detect the two different transit times; while matched-filtering has a better accuracy (0.13 μs vs. 0.18 μs standard deviation), deconvolution has a 3.5 times improved side-lobe to main-lobe ratio. A higher side-lobe suppression is important to further improve image fidelity. These results suggest that a future combination of both techniques would provide improved signal detection and hence improved image fidelity.

Efficient parameter estimation in longitudinal data analysis using a hybrid GEE method

The method of generalized estimating equations (GEEs) provides consistent estimates of the regression parameters in a marginal regression model for longitudinal data, even when the working correlation model is misspecified (Liang and Zeger, 1986). However, the efficiency of a GEE estimate can be seriously affected by the choice of the working correlation model. This study addresses this problem by proposing a hybrid method that combines multiple GEEs based on different working correlation models, using the empirical likelihood method (Qin and Lawless, 1994). Analyses show that this hybrid method is more efficient than a GEE using a misspecified working correlation model. Furthermore, if one of the working correlation structures correctly models the within-subject correlations, then this hybrid method provides the most efficient parameter estimates. In simulations, the hybrid method's finite-sample performance is superior to a GEE under any of the commonly used working correlation models and is almost fully efficient in all scenarios studied. The hybrid method is illustrated using data from a longitudinal study of the respiratory infection rates in 275 Indonesian children.

A simple method for estimating growth parameters from multiple length-frequency data in presence of continuous recruitment

The extended recruitment season for short-lived species such as prawns biases the estimation of growth parameters from length-frequency data when conventional methods are used. We propose a simple method for overcoming this bias given a time series of length-frequency data. The difficulties arising from extended recruitment are eliminated by predicting the growth of the succeeding samples and the length increments of the recruits in previous samples. This method requires that some maximum size at recruitment can be specified. The advantages of this multiple length-frequency method are: it is simple to use; it requires only three parameters; no specific distributions need to be assumed; and the actual seasonal recruitment pattern does not have to be specified. We illustrate the new method with length-frequency data on the tiger prawn Penaeus esculentus from the north-western Gulf of Carpentaria, Australia.

A quasi-likelihood method for fractal-dimension estimation

We propose a simple method of constructing quasi-likelihood functions for dependent data based on conditional-mean-variance relationships, and apply the method to estimating the fractal dimension from box-counting data. Simulation studies were carried out to compare this method with the traditional methods. We also applied this technique to real data from fishing grounds in the Gulf of Carpentaria, Australia