Health information needs and feedback of users in the online TCM community.

To improve the information service quality of the online Traditional Chinese Medicine (TCM) community, this study investigated users' information needs, feedback and the relationship between them. Using qualitative content analysis, the basic characteristics of users' needs were obtained. Logistic regression was used to explore the impact of different need characteristics of feedback. The main findings are as follows: 1) Disease consultation, health preservation, professional discussion, knowledge sharing and experience description are the major 5 types of information needs in the online TCM community; 2) Some users provided TCM-related information, such as the tongue image and the TCM four diagnosis; 3) A total of 78.8% of the posts received effective feedback, and the main types of feedback were answering, discussing, inquiring and emotional supporting; 4) Providing enough information can significantly and positively affect whether needs receive effective feedback, suggesting that users can present information about their condition in as many different formats as possible when articulating their needs.

Characteristics, sources and health risk assessment of atmospheric carbonyls during multiple ozone pollution episodes in urban Beijing: Insights into control strategies.

Carbonyls have attracted continuous attention due to their critical roles in atmospheric chemistry and their potential hazards to the ecological environment and human health. In this study, atmospheric carbonyls were measured during several ground-level-ozone (O3) pollution episodes at three urban sites (CRAES, IEP and BJUT) in Beijing in 2019 and 2020. Comparative analysis revealed that the carbonyl concentrations were 20.25 ± 6.91 ppb and 13.43 ± 5.13 ppb in 2019 and 2020 in Beijing, respectively, with a significant spatial trend from north to south, and carbonyl levels in urban Beijing were in an upper-intermediate range in China, and higher than those in other countries reported in the literature. A particularly noteworthy phenomenon is the consistency of carbonyl concentrations with variations in O3 concentrations. On O3 polluted days, the carbonyl concentrations were 1.3-1.5 times higher than those on non-O3 polluted days. Secondary formation contributed more to formaldehyde (FA) and acetaldehyde (AA) on O3 polluted days, while the anthropogenic emissions were more significant for acetone (AC) on non-O3 polluted days. Vehicle exhaust and solvent utilization were the main primary contributors to carbonyls. Due to reduced anthropogenic emissions caused by the COVID-19 lockdown and the "Program for Controlling Volatile Organic Compounds in 2020" in China, the contributions of primary emissions to carbonyls decreased in 2020 in Beijing. Human cancer risks to exposed populations from FA and AA increased with elevated O3 levels, and the risks still remained on non-O3 polluted days. The residents around the BJUT site might experience relatively higher human cancer risks than those around the other two sites. The findings in this study confirmed that atmospheric carbonyl pollution and its potential human health hazards cannot be ignored in urban Beijing; therefore, more strict control strategies for atmospheric carbonyls are urgently needed to better protect human health in Beijing in the future.

Thermochemical Liquefaction of Pomace Using Sub/Supercritical Ethanol: an Integrated Experimental and Preliminary Economic Feasibility Study.

Fossil sourced chemicals such as aromatics, are widely employed in the chemical industry for the production of commodity items. Recognizing the un-sustainability of existing approaches in the production of these chemicals, the current study investigated the valorization of apple pomace (AP) for their production. The present study assessed AP valorization by imposing variations in processing conditions of temperature (100-260 °C), time (0.5-12 h), alcohol/water ratio v/v (0:1-1:0), and Fe3+/H2O2 molar ratio (10:1-100-1), in accordance to the Box-Behnken experimental design. The optimal yield of the oil was 24.6 wt.%, at the temperature, time, alcohol/water ratio v/v, and Fe3+/H2O2 molar ratio of 260 °C, 4.7 h, 1, and 100, respectively. Notably, the application of gas chromatography-mass spectroscopy showed that the oil product contained mainly aromatics and interestingly also alkanes, indicating that the experimental conditions imposed promoted secondary hydrogenation reactions of oxygen-containing species during AP valorization. A consideration of the comparative economics of the proposed AP valorization and the existing AP management approach, using approximate estimation techniques, highlighted the potential of a ~ 59% reduction in the unit cost of AP management. The study therefore presents a compelling basis for future investigations into AP waste management using the thermochemical liquefaction technology.

Coupling and Coordinative Development of Green Finance and Industrial-Structure Optimization in China: Spatial-Temporal Difference and Driving Factors.

Although the literature has studied the direction and extent of the effect of green finance on industrial-structure optimization, quantitative analysis of the coupling coordination and spatial-temporal differences between green finance and industrial structure is relatively scarce. Therefore, in this paper, we built the theoretical framework of the coupling coordination relationship between green finance and industrial-structure optimization, and then we used the coupling coordination degree and geographic detector model to investigate the spatial-temporal evolution characteristics and influencing factors of the coupling coordination between the two based on the panel data of 31 provinces from 2012 to 2019. The results show that China's green finance and industrial-structure optimization have basically reached the primary coupling, and the coupling coordination degree is from 0.40 to 0.43, which shows a "W"-type fluctuation trend of recovery. The regional gap of the coupling coordination degree firstly decreased and then increased, showing a change law of "agglomeration, equilibrium and agglomeration". In the spatial dimension, the high-level coordination region showed an increasing trend of "fragmentation" fluctuation, while the low-level coordination region concentrated in the central and western regions with a tendency of "low value locking". The trend surface showed a spatial characteristic of "high in the north and low in the south-high in the east and west and low in the middle". We also found that the dependence of foreign trade and technological innovation are the main factors affecting the coupling coordination degree, and the interaction between government support and human capital synergistic is the crucial channel for the coevolution of green finance and industrial structure to promote green and low-carbon development.

Pollution characteristics and risk assessment of air multi-pollutants from typical e-waste dismantling activities.

This study investigated the characteristics of air multi-pollutants emitted during typical electronic waste (e-waste) dismantling processes and assessed their risks to the environment and human health. Concentrations of total volatile organic compounds (TVOCs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) in a typical e-waste dismantling workshop were 137 µg/m3, 135 ng/m3 and 42 ng/m3, respectively, which were lower than those without emission control measures. The partial removal of pollutants due to the emission control measures also decreased the ozone formation potential and non-cancer risk of volatile organic compounds (VOCs). In the workshop, the lifetime cancer risk (LCR) of VOCs (8.1 × 10-5) was close to the recommended values. Conversely, the LCR of PAHs (3.6 × 10-5) and the total exposure index of PBDEs (19 ng/d) were remarkably lower than the recommended values of 10-3 and that without emission control measures, respectively. Meanwhile, the concentrations of TVOCs, polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), PBDEs, and PAHs in the outlet were approximately 10-30 times higher than those in the workshop. In addition, the LCR of TVOCs within a 5-km radius area remained higher than the accepted value (10-6), and the inhalation exposure risk of PCDD/Fs within a 20-km radius area was five times higher than the recommended value. Therefore, the emissions from e-waste recycling processes should be considered as an important source of air pollution, and more efficient control measures should be taken in the future.

Optimization of seat allocation with fixed prices: An application of railway revenue management in China.

China Railway Corporation (CRC) has been paid more attention to passenger transportation revenue, with its increase proportion in transportation revenue. Due to the price regulation, the only way CRC can improve ticket sale profit is to find a best seat allocation scheme. This study focuses on the optimization of railway revenue management problem in China with consideration of i) customer behaviors including their arrival and purchase preferences, ii) a specific ticket booking mechanism called "seat-based control". To evaluate the performance of seat-based control, we build a Discrete-Time Markov Chain model to describe the ticket reservation process and then design a genetic algorithm to find approximate solutions. The performance of proposed method is tested in two experiments with two other benchmarks. Finally, we apply it to practical data of the Nanning-Guangzhou high-speed railway line.

Development and Qualification of a Scale-Down Mammalian Cell Culture Model and Application in Design Space Development by Definitive Screening Design.

Scale-down models are indispensable and crucial tools for process understanding and continuous process improvement in product life-cycle management. In this study, a scale-down model representing commercial-scale cell culture process of adalimumab biosimilar HS016 was first developed based on constant power per volume (P/V) principle and then qualified by multivariate data analysis (MVDA) and equivalence test method. The trajectories of the bench-scale process lie in the middle of the control range of large-scale process, built by multivariate evolution model based on nutrients, metabolites, and process performance datasets. This indicates that the small-scale process performance is comparable with that of the full-scale process. The final product titer, integrated viable cell density (iVCD), viability, aggregates, acid peak content, total afucosylation level, and high mannose content recognized as key process attributes (KPAs) or critical quality attributes (CQAs) were equivalent across the scales upon comparison using equivalence test method. The qualified scale-down model was then used for process characterization using a definitive screening design (DSD) where five independent variables including pH, shifted temperature, inoculation seeding density, viable cell density (VCD) at first feeding, VCD at temperature shift were evaluated. Three quadratic polynomial models for final product titer, aggregation, and high mannose were then established using the DSD results. The design space was finally developed using a probability-based Monte Carlo simulation method and was verified with the operation setpoint and worst-case condition. The case study presented in this report shows a feasible roadmap for cell culture process characterization.

[Establishment of VOCs Emissions Factor and Emissions Inventory from Using of Architectural Coatings in China].

Volatile organic compounds (VOCs)are important air pollutants in China, and control of their emission is an important subject of air pollution prevention and control.Architectural coatings play a significant role as sources of atmospheric VOCs in China.Due to recent economic development and increase in the levels of urbanization, the building of residences and other buildings is ongoing all the time, which results in increasing demand for architectural coatings and the VOCs pollution caused by painting operations.However, there are few studies of the VOCs emission factors and VOCs emissions due to architectural coatings.In this paper, a set of bottom-up VOCs emission inventory estimation methods for architectural coatings in China was established.The architectural coatings VOCs emission factors were gotten by actual measurement of VOCs in architectural coatings and by summarizing studies of VOCs contents in architectural coatings.Combining these results with the consumption of architectural coating sources, a VOCs emission inventory of architectural coatings in China from 2013 to 2016 was established.The results showed the following.① VOCs emission factors were 24.63 g·kg-1 for water-based interior wall coatings; 17.5 g·kg-1 and 298.8 g·kg-1 for water-based and solvent-based exterior wall coatings, respectively. They were 2.75, 87.86, and 400 g·kg-1 for water-based, reaction-type, and solvent-based waterproof coatings, respectively. For water-based, solventless, and solvent-based floor coatings, they were 86.2, 25.24, and 317 g·kg-1, respectively; and 31.95 g·kg-1 and 464.61 g·kg-1 for water-based and solvent-based anticorrosive coatings respectively. The emission factors were 59.7 g·kg-1 and 347.2 g·kg-1 for water-based and solvent-based fire retardant coatings, respectively. ② VOCs emissions from the use of architectural coatings were 255900 t, 287500 t, 319700 t, and 348000 t from 2013 to 2016 in China, with an upward trend. ③ Total VOCs emissions from architectural coatings was 348000 t in 2016, and the VOCs emissions from floor coatings was 78700 t, accounting for 22.61% with the maximum contribution rate. The VOCs emissions from exterior wall coatings were 64900 t, accounting for 18.65% (second place), and the VOCs emissions from fire retardant coatings and anticorrosive coatings (functional coatings) were 64500 t and 50800 t, accounting for 18.53% and 14.6% respectively. The VOCs emissions from waterproof coatings and interior wall coatings were 46100 t and 43000 t, accounting for 13.25% and 12.36%, respectively. ④ The consumption of water-based architectural coatings reached a total of 4889400 t in 2016 with VOCs emissions of 97900 t and average VOCs emissions factor of 20.02 g·kg-1; however, the consumption of solvent-based architectural coatings totaled 636500 t with VOCs emissions of 227200 t and average VOCs emission factor of 356.95 g·kg-1. Reducing the consumption of solvent-based coatings would be favorable for reduction of VOCs emissions. ⑤ As for the spatial distribution, architectural coating-related VOCs emissions were mainly concentrated in Shandong, Jiangsu, Zhejiang, Henan, Sichuan, Guangdong, and Hebei provinces, which have large populations. The province with the highest VOCs emissions was Shandong, with a percentage of 9.36%, and the second was Jiangsu, with a percentage of 8.54%.

Bayesian hierarchical methods for meta-analysis combining randomized-controlled and single-arm studies.

Meta-analysis of interventions usually relies on randomized controlled trials. However, when the dominant source of information comes from single-arm studies, or when the results from randomized controlled trials lack generalization due to strict inclusion and exclusion criteria, it is vital to synthesize both sources of evidence. One challenge of synthesizing both sources is that single-arm studies are usually less reliable than randomized controlled trials due to selection bias and confounding factors. In this paper, we propose a Bayesian hierarchical framework for the purpose of bias reduction and efficiency gain. Under this framework, three methods are proposed: bivariate generalized linear mixed effects models, hierarchical power prior model and hierarchical commensurate prior model. Design difference and potential biases are considered in all models, within which the hierarchical power prior and hierarchical commensurate prior models further offer to downweight single-arm studies flexibly. The hierarchical commensurate prior model is recommended as the primary method for evidence synthesis because of its accuracy and robustness. We illustrate our methods by applying all models to two motivating datasets and evaluate their performance through simulation studies. We finish with a discussion of the advantages and limitations of our methods, as well as directions for future research in this area.

A dynamic bid price approach for the seat inventory control problem in railway networks with consideration of passenger transfer.

Railway seat inventory control aims to maximize ticket sale profits by determining a selling policy on the reservation horizon. This paper introduces a dynamic bid price approach in railway seat inventory control problem. Multi-dimensional demand is taken into consideration in modeling the problem, in which passenger transfer is our main focus. A new approximate approach is designed to this problem. Numerical examples are presented to evaluate the efficiency of this approach. Simulation experiments are conducted to verify the impact of transfer under different scenarios.

Electric multiple unit circulation plan optimization based on the branch-and-price algorithm under different maintenance management schemes.

For railway operators, one of many important goals is to improve the utilization efficiency of electric multiple units (EMUs). When operators design EMU circulation plans, EMU type restrictions are critical factors when assigning EMUs to the correct depots for maintenance. However, existing studies only consider that EMUs are maintained at their home depots. However, targeting that problem, in this paper, an optimization model for the EMU circulation planning problem that allows depots to be selected for EMU maintenance is proposed. This model aims at optimizing the number of used EMUs and the number of EMU maintenance tasks and simultaneously incorporates other important constraints, including type restrictions, on EMU maintenance and night accommodation capacity at depots. In order to solve the model, a branch-and-price algorithm is also developed. A case study of a real-world high-speed railway was conducted to compare and analyze the effects of different maintenance location constraints. The results show that the number of EMUs used will decrease under the maintenance sharing scheme, the number of EMU maintenance tasks can be reduced, and the time occupied in EMU maintenance will be released. In addition, the scheme of maintenance resources sharing and increases to mileage limits can effectively decrease the number of EMU maintenance tasks significantly. The model and algorithm can be used as an effective quantitative analysis tool for railway operators' decision-making processes in the EMU circulation planning problem.

Optimization of a Coupling Process for Insulin Degludec According to a Quality by Design (QbD) Paradigm.

This case study described a successful application of the quality by design (QbD) principles to a coupling process development of insulin degludec. Failure mode effects analysis (FMEA) risk analysis was first used to recognize critical process parameters (CPPs). Five CPPs, including coupling temperature (Temp), pH of desB30 solution (pH), reaction time (Time), desB30 concentration (Conc), and molar equivalent of ester per mole of desB30 insulin (MolE), were then investigated using a fractional factorial design. The curvature effect was found significant, indicating the requirement of second-order models. Afterwards, a central composite design was built with an augmented star and center points study. Regression models were developed for the CPPs to predict the purity and yield of predegludec using above experimental data. The R2 and adjusted R2 were higher than 96 and 93% for the two models respectively. The Q2 values were more than 80% indicating a good predictive ability of models. MolE was found to be the most significant factor affecting both yield and purity of predegludec. Temp, pH, and Conc were also significant for predegludec purity, while Time appeared to remarkably influence the yield model. The multi-dimensional design space and normal operating region (NOR) with a robust setpoint were determined using a probability-based Monte-Carlo simulation method. The verified experimental results showed that the design space was reliable and effective. This study enriches the understanding of acetylation process and is instructional to other complicated operations in biopharmaceutical engineering.

Direct and potential risk assessment of exposure to volatile organic compounds for primary receptor associated with solvent consumption.

Rapid development of industrial production has stimulated the growth of consumption of raw and auxiliary materials including organic paints, among which volatile organic compounds (VOCs) are proved harmful to the population who inhale the polluted air based on epidemiologic studies. Therefore, new types of environment-friendly paints were developed to replace solvent-based paints (SBPs). Nevertheless, new types of paints containing VOCs failed to replace SBPs entirely due to certain disadvantages. Hence, five kinds of paints were employed in simulation experiments to assess the health risk of primary receptor including three kinds of water-based paints (WBPs) and two kinds of SBPs. Conclusions showed that mean TVOC concentration in breathing zone of primary receptor ranged from 9.5 to 13.6 mg/m3 and 3.4 × 103 to 1.4 × 104 mg/m3 for WBPs and SBPs, respectively. Assessments of non-cancer risk concluded that nearly one third quantified compounds exceeded corresponding thresholds for WBPs, and the maximum risk value was 101.33; for SBPs, the maximum risk value reached 50760.20, and twenty-two compounds exceeded the reference limits. The calculation of cancer risk values showed that seventeen compounds were higher than acceptable limit amongst which 1,2-dibromoethane had maximum values of 1.27 × 10-2 to 3.24 × 10-2 for WBPs; for SBPs, all quantified compounds exceeded the acceptable limit, and 82.61% VOCs were distributed in a scope larger than 1 × 10-3. Additionally, a removal efficiency of 60% was considered for primary receptor with personal protective equipment, and subsequent results confirmed its inability of lowering the risk resulted from hazardous VOCs. The calculated potential health risk could be applied to estimate the total health risk for both primary and secondary receptor based on consumed materials. The finding suggested that WBPs could improve VOCs exposure condition and reduce the direct and potential health risk significantly for primary receptor, although they might dissatisfy acceptable limit.

A quantification method for determination of racemate praziquantel and R-enantiomer in rat plasma for comparison of their pharmacokinetics.

Praziquantel is the drug of first choice for the control and treatment of all forms of schistosomiasis. Praziquantel is administered as a racemate, including R-enantiomer and S-enantiomer. Among them, R-enantiomer has main contribution to schistosomicidal activity. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry was established and validated to determine the concentration of racemate praziquantel and R-enantiomer in rat plasma after oral administration. Chromatographic separation was performed on an Agilent Zorbax SB-C18 column. An entire run time for chromatographic separation was no more than 5min. The present method for analytes manifested that high sensitivity (the lower limit of quantification was 3.0ng/mL), satisfactory accuracy (relative error ≤±15%) and precision (relative standard deviation ≤15%) were achieved. There was no obvious matrix effect found. The average recoveries of racemate praziquantel and R-enantiomer were both above 85%. Then, the developed method had a successful application to comparative pharmacokinetic study of racemate praziquantel and R-enantiomer. Meanwhile, the differences in their pharmacokinetic parameters were compared and analyzed. The present quantification method and comparative pharmacokinetic study would provide a useful reference for the drug development of enantiopure schistosomicidal R-enantiomer as a replacement of racemate praziquantel for treatment of schistosomiasis.

[Fugitive Dust Emission Characteristics from Building Construction Sites of Beijing].

Particulate matter (PM) is the primary air pollutant in Beijing, and its emission control is an important direction of air pollution prevention and control. Construction dust plays a significant role in the source of airborne particulate matter in Beijing. Due to population growth and economic development, the demand for residential and office space has been increasing which results in a high construction area in Beijing and dust pollution caused by construction activities. However, there are few studies focusing on fugitive dust emissions from construction sites and their contribution to air pollution in Beijing. Under this background, this paper established an estimation model of dust emission from construction sites, and used the localized emission factor to calculate the dust emission from 2000 to 2015 in Beijing, identified the emission characteristics and laws of construction dust emission and quantified the uncertainty range of the emissions. The WRF/CMAQ model system was used to simulate the contribution of dust pollution to quantify its influence on air quality. The results showed that the dust emission from construction sites in Beijing has been increasing, but the construction area is falling in recent years. However, the emission of PM is still high and needs to be paid enough attention. In the spatial distribution, the dust emissions in summer and autumn are larger than those in other seasons. As for spatial distribution, the construction dust is mainly concentrated in the urban function extension area and suburban area, which is related to the extension of population activities and the gradual development of urbanization. The contribution of construction dust to PM10 and PM2.5 concentration in the ambient air can reach 31.3 µg·m-3 and 9.6 µg·m-3, respectively. Through scenarios analysis, for further reduction of the emission from construction sites in 2030, more stricter standard for green construction and powerful supervision are needed.

Rapid determination of major bioactive isoflavonoid compounds during the extraction process of kudzu (Pueraria lobata) by near-infrared transmission spectroscopy.

Near-infrared (NIR) spectroscopy has been developed into an indispensable tool for both academic research and industrial quality control in a wide field of applications. The feasibility of NIR spectroscopy to monitor the concentration of puerarin, daidzin, daidzein and total isoflavonoid (TIF) during the extraction process of kudzu (Pueraria lobata) was verified in this work. NIR spectra were collected in transmission mode and pretreated with smoothing and derivative. Partial least square regression (PLSR) was used to establish calibration models. Three different variable selection methods, including correlation coefficient method, interval partial least squares (iPLS), and successive projections algorithm (SPA) were performed and compared with models based on all of the variables. The results showed that the approach was very efficient and environmentally friendly for rapid determination of the four quality indices (QIs) in the kudzu extraction process. This method established may have the potential to be used as a process analytical technological (PAT) tool in the future.

[Quality assessment of Liuwei Wuling tablet by HPLC fingerprint and quantitative analysis].

Reversed phase high performance liquid chromatography with diode array detector was employed for simultaneous determination of six components and specific chromatograms analysis in Liuwei Wuling tablets with gradient elution of acetonitrile and water containing 0.1% phosphoric acid as mobile phase. The results showed that six components containing specnuezhenide, phillyrin, schisandrin, schisantherin A, schizandrin A and schizandrin B were separated well under the analytical condition. The average recoveries ranged from 98.96% to 100.5% with RSD less than 2. 0%. Twenty-five common peaks were selected as the specific chromatograms of Liuwei Wuling tablets with schisantherin A as the reference peak. Similarities calculated by cosine of angle, correlation coefficient and peak area ratio similarity (PAR) were all above 0. 95, indicating a good similarity between the reference and twenty batches of samples. Grubbs test and cluster analysis indicated that the established HPLC fingerprints and HPLC quantitative analysis can be used efficiently in the quality control of Liuwei Wuling tablets.

Relative excess risk due to interaction: resampling-based confidence intervals.

Relative excess risk due to interaction (RERI) has been used to quantify the joint effects of 2 exposures in epidemiology. However, the construction of confidence intervals (CIs) for RERI is complicated by sparse cells. Assuming that the data contain no zero cells, here we propose constructing CIs for RERI using nonparametric and parametric bootstrap methods with a continuity correction, and compare these proposed methods to existing methods using 3 empirical examples and Monte Carlo simulations. Our results show that, when cell counts are not sparse, CIs resulting from the explored bootstrap methods are generally acceptable in terms of CI coverage and length, although computationally more demanding than existing methods. However, when cell counts are sparse, the proposed bootstrap methods using a continuity correction outperform existing methods and continue to provide acceptable CIs. The continuity correction is needed for the explored bootstrap methods to provide acceptable CIs because resampled data sets may contain zero cells even when the observed data do not.

Linear regression with an independent variable subject to a detection limit.

BACKGROUND: Linear regression with a left-censored independent variable X due to limit of detection (LOD) was recently considered by 2 groups of researchers: Richardson and Ciampi (Am J Epidemiol. 2003;157:355-363), and Schisterman et al (Am J Epidemiol. 2006;163:374-383). METHODS: Both groups obtained consistent estimators for the regression slopes by replacing left-censored X with a constant, that is, the expectation of X given X below LOD E(X|X

Estimating the odds ratio when exposure has a limit of detection.

BACKGROUND: In epidemiologic research, little emphasis has been placed on methods to account for left-hand censoring of 'exposures' due to a limit of detection (LOD). METHODS: We calculate the odds of anti-HIV therapy naiveté in 45 HIV-infected men as a function of measured log(10) plasma HIV RNA viral load using five approaches including ad hoc methods as well as a maximum likelihood estimate (MLE). We also generated simulations of a binary outcome with 10% incidence and a 1.5-fold increased odds per log increase in a log-normally distributed exposure with 25, 50 and 75% of exposure data below LOD. Simulated data were analysed using the same five methods, as well as the full data. RESULTS: In the example, the estimated odds ratio (OR) varied by 1.22-fold across methods, from 1.45 to 1.77 per log(10) copies of viral load and the standard error for the log OR varied by 1.52-fold across methods, from 0.31 to 0.47. In the simulations, use of full data or the MLE was unbiased with appropriate confidence interval (CI) coverage. However, as the proportion of exposure below LOD increased, substituting LOD, LOD/ radical 2 or LOD/2 was increasingly biased with increasingly inappropriate CI coverage. Finally, exclusion of values below LOD was unbiased but imprecise. CONCLUSIONS: In this example and the settings explored by simulation, and among methods readily available to investigators (i.e. sans full data), the MLE provided an unbiased and appropriately precise estimate of the exposure-outcome OR.