Identification of behavioural model input data sets for WWTP uncertainty analysis.

Uncertainty analysis is important for wastewater treatment plant (WWTP) model applications. An important aspect of uncertainty analysis is the identification and proper quantification of sources of uncertainty. In this contribution, a methodology to identify an ensemble of behavioural model representations (combinations of input data, model structure and parameter values) is presented and evaluated. The outcome is a multivariate conditional distribution of input data that is used for generating samples of likely inputs (such as Monte Carlo input samples) to perform WWTP model uncertainty analysis. This article presents an approach to verify uncertainty distributions of input data (otherwise often assumed) by using historical observations and actual plant data.

Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study).

AIM: To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes. MATERIALS AND METHODS: In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). RESULTS: After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks. CONCLUSION: In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes.

BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma.

INTRODUCTION: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management. METHODS: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39-59 years) and a median follow-up time of 53 months (IQR, 25-93 months). RESULTS: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15-5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80-24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan-Meier recurrence-free survival curve in low-risk PTMC. CONCLUSIONS: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.

Audit of Mental Capacity Assessment by Primary Care Physicians Versus Consultation-liaison Psychiatrists.

OBJECTIVE: To review the mental capacity assessment of in-patients referred to consultation-liaison psychiatrists and to compare the assessment first made by primary care physicians. METHODS: Medical records of in-patients who were referred to consultation-liaison psychiatrists for mental capacity assessment between May and October 2015 were retrospectively reviewed. Assessment was first made by a primary care physician; complex cases were referred to a consultation-liaison psychiatrist. Audit of each case note was conducted independently by at least two of the authors. RESULTS: Medical records of 37 female and 26 male in-patients aged 24 to 91 (mean, 68.2) years were audited. Only 33.3% of these patients had no psychiatric diagnosis. Overall, assessments by primary care physicians were suboptimal. Assessments by consultation-liaison psychiatrists were more detailed, with documentation of mental capacity (93.7%) and psychiatric diagnosis (88.9%). Nonetheless, patient wishes and beliefs were poorly documented (19.0%), as were whether the patient had a lasting power of attorney or a court-appointed deputy (6.3%) and whether the patient had made advance care planning (0%). CONCLUSION: Overall, mental capacity assessment was inadequately performed by primary care physicians and consultation-liaison psychiatrists. More work needs to be done to engage, educate, and empower all stakeholders involved.

An operational protocol for facilitating start-up of single-stage autotrophic nitrogen-removing reactors based on process stoichiometry.

Start-up and operation of single-stage nitritation-anammox sequencing batch reactors (SBRs) for completely autotrophic nitrogen removal can be challenging and far from trivial. In this study, a step-wise procedure is developed based on stoichiometric analysis of the process performance from nitrogen species measurements to systematically guide start-up and normal operation efforts (instead of trial and error). The procedure is successfully applied to laboratory-scale SBRs for start-up and maintained operation over an 8-month period. This analysis can serve as a strong decision-making tool to take appropriate actions with respect to reactor operation to accelerate start-up or ensure high-rate N removal via the nitritation-anammox pathway.

Use of continuous lactose fermentation for ethanol production by Kluveromyces marxianus for verification and extension of a biochemically structured model.

A biochemically structured model has been developed to describe the continuous fermentation of lactose to ethanol by Kluveromyces marxianus and allowed metabolic coefficients to be determined. Anaerobic lactose-limited chemostat fermentations at different dilution rates (0.02-0.35h(-1)) were performed. Species specific rates of consumption/formation, as well as yield coefficients were determined. Ethanol yield (0.655 C-mol ethanol(∗)C-mol lactose(-1)) was as high as 98% of theoretical. The modeling procedure allowed calculation of maintenance coefficients for lactose consumption and ethanol production of m(s)=0.6029 and m(e)=0.4218 (C-mol) and (C-molh)(-1), respectively. True yield coefficients for biomass, ethanol and glycerol production were calculated to be Y(true)(sx)=0.114, Y(true)(ex)=0.192 and Y(sg)=2.250 (C-mol) and (C-mol)(-1), respectively. Model calculated maintenance and true yield coefficients agreed very closely with those determined by regressions of the experimental data. The model developed provides a solid basis for the rational design of optimised fermentation of cheese whey.

Association between visceral obesity and sarcopenia and vitamin D deficiency in older Koreans: the Ansan Geriatric Study.

OBJECTIVES: To investigate whether vitamin D levels are independently associated with visceral obesity, sarcopenia, or sarcopenic obesity. DESIGN: Cross-sectional. SETTING: Population-based sample of elderly adults living in Ansan, Korea. PARTICIPANTS: Two hundred sixteen men and 268 women aged 65 and older. MEASUREMENTS: Serum 25-hydroxyvitamin D (25(OH)D) levels, visceral fat area (VFA) according to abdominal computed tomography scanning, and body composition (body fat percentage, appendicular skeletal muscle mass (ASM)) using dual-energy X-ray absorptiometry. Visceral obesity was defined as VFA of 100 cm(2) or greater and sarcopenia as ASM/height(2) more than 1 standard deviation (SD) below the sex-specific mean of a young reference group. RESULTS: The adjusted 25(OH)D level for men was negatively associated with systolic blood pressure, VFA, and body fat percentage but positively associated with ASM. In women, waist circumference, triglyceride levels, and VFA were negatively correlated with 25(OH)D levels. In the joint regression model, VFA and ASM were independently associated with 25(OH)D levels (ß = -0.078, P = .01 and ß = 0.087, P = .02, respectively) per 1SD difference in VFA and ASM in men but not women. When participants were categorized according to four visceral obesity and sarcopenia categories, adjusted mean 25(OH)D level was lower in men with visceral obesity than in men without but was not affected by the presence or absence of sarcopenia. CONCLUSION: Greater visceral fat and lower muscle mass were associated with lower 25(OH)D levels in elderly Korean men, suggesting that screening for vitamin D deficiency may be appropriate in older Koreans with visceral obesity or sarcopenia. Sarcopenic obesity as defined according to prespecified criteria did not have an additive association with 25(OH)D levels.

Application of the Morris method for screening the influential parameters of fuzzy controllers applied to wastewater treatment plants.

In this paper, we evaluate the application of a sensitivity analysis to help fine-tuning a fuzzy controller for a biological nitrogen and phosphorus removal (BNPR) plant. The Morris Screening method is proposed and evaluated as a prior step to obtain the parameter significance ranking. First, an iterative procedure has been performed in order to find out the proper repetition number of the elementary effects (r) of the method. The optimal repetition number found in this study (r = 60) is in direct contrast to previous applications of the Morris method, which usually use low repetition number, e.g. r = 10 - 20. Working with a non-proper repetition number (r) could lead to Type I error (identifying a not-important factor as significant (false positive)) as well as Type II error (identifying an important factor as not significant (false negative)), hence emphasizing the importance of finding the optimal repetition number for each study in question. With the proper r found, the Morris Screening helped identify the parameter significance ranking, thereby facilitating the calibration of fuzzy controllers, which contain many parameters that need to be adjusted for different wastewater treatment plant (WWTP) applications.

The Community Psychogeriatric Programme: a pilot project in the eastern sector of Singapore.

As the population in Singapore ages rapidly, there is a race against time to prepare for the growing psychiatric needs of this population. The Community Psychogeriatric Programme was set up in Changi General Hospital to provide community mental health services for early detection and treatment of psychogeriatric disorders in the eastern sector of Singapore. The model of care involves working closely with community partners to provide training on mental healthcare in the older person, case discussion and consultation as well as clinical home visits. Efforts to raise awareness of mental health issues faced by our greying population have been encouraging but challenging. We hope that by reducing stigma and raising awareness, early access to treatment in the community will help to keep our older persons in the community for as long as possible.

A biochemically structured model for ethanol fermentation by Kluyveromyces marxianus: A batch fermentation and kinetic study.

Anaerobic batch fermentations of ricotta cheese whey (i.e. containing lactose) were performed under different operating conditions. Ethanol concentrations of ca. 22g L(-1) were found from whey containing ca. 44g L(-1) lactose, which corresponded to up to 95% of the theoretical ethanol yield within 15h. The experimental data could be explained by means of a simple knowledge-driven biochemically structured model that was built on bioenergetics principles applied to the metabolic pathways through which lactose is converted into major products. Use of the model showed that the observed concentrations of ethanol, lactose, biomass and glycerol during batch fermentation could be described within a ca. 6% deviation, as could the yield coefficients for biomass and ethanol produced on lactose. The model structure confirmed that the thermodynamics considerations on the stoichiometry of the system constrain the metabolic coefficients within a physically meaningful range thereby providing valuable and reliable insight into fermentation processes.

Systematic model development for partial nitrification of landfill leachate in a SBR.

This study deals with partial nitrification in a sequencing batch reactor (PN-SBR) treating raw urban landfill leachate. In order to enhance process insight (e.g. quantify interactions between aeration, CO(2) stripping, alkalinity, pH, nitrification kinetics), a mathematical model has been set up. Following a systematic procedure, the model was successfully constructed, calibrated and validated using data from short-term (one cycle) operation of the PN-SBR. The evaluation of the model revealed a good fit to the main physical-chemical measurements (ammonium, nitrite, nitrate and inorganic carbon), confirmed by statistical tests. Good model fits were also obtained for pH, despite a slight bias in pH prediction, probably caused by the high salinity of the leachate. Future work will be addressed to the model-based evaluation of the interaction of different factors (aeration, stripping, pH, inhibitions, among others) and their impact on the process performance.

Wastewater treatment modelling: dealing with uncertainties.

This paper serves as a problem statement of the issues surrounding uncertainty in wastewater treatment modelling. The paper proposes a structure for identifying the sources of uncertainty introduced during each step of an engineering project concerned with model-based design or optimisation of a wastewater treatment system. It briefly references the methods currently used to evaluate prediction accuracy and uncertainty and discusses the relevance of uncertainty evaluations in model applications. The paper aims to raise awareness and initiate a comprehensive discussion among professionals on model prediction accuracy and uncertainty issues. It also aims to identify future research needs. Ultimately the goal of such a discussion would be to generate transparent and objective methods of explicitly evaluating the reliability of model results, before they are implemented in an engineering decision-making context.

Parameter subset selection for the dynamic calibration of activated sludge models (ASMs): experience versus systems analysis.

In this work we address the issue of parameter subset selection within the scope of activated sludge model calibration. To this end, we evaluate two approaches: (i) systems analysis and (ii) experience-based approach. The evaluation has been carried out using a dynamic model (ASM2d) calibrated to describe nitrogen and phosphorus removal in the Haaren WWTP (The Netherlands). The parameter significance ranking shows that the temperature correction coefficients are among the most influential parameters on the model output. This outcome confronts the previous identifiability studies and the experience based approaches which excluded them from their analysis. Systems analysis reveals that parameter significance ranking and size of the identifiable parameter subset depend on the information content of data available for calibration. However, it suffers from heavy computational demand. In contrast, although the experience-based approach is computationally affordable, it is unable to take into account the information content issue and therefore can be either too optimistic (giving poorly identifiable sets) or pessimistic (small size of sets while much more can be estimated from the data). An appropriate combinations of both approaches is proposed which offers a realistic (doable) and sound approach for parameter subset selection in activated sludge modelling.

Model-based optimisation of the biological performance of a sidestream MBR.

A model-based optimisation of the operation in view of the biological performance in terms of nitrogen (N) and phosphorus (P) removal of a pilot-scale side-stream MBR has been performed by means of a two-tier scenario analysis. The methodology uses two different scenario analyses to simulate the effect of three degrees of freedom in the MBR system: (1) DO set-point in the aerobic reactor, (2) sludge residence time and (3) internal recirculation rate. The scenarios are simulated using a calibrated ASM2d MBR model. Effluent quality, in terms of nitrate, ammonia and phosphate, is used to select the best scenario. It proved to be a compromise between nitrogen and phosphorus removal as these are linked. A 42% reduction in ammonium and a 32% reduction in nitrate concentration were achieved. Phosphate removal is partly sacrificed (39% increase) compared to the standard operation.

Evolution of an ASM2d-like model structure due to operational changes of an SBR process.

To model biological nitrogen and phosphorus removal systems with an affordable complexity, the ASM2d model structure is based on many assumptions. In this study, some of these assumptions, however, were observed to become invalid when the biological behaviour in the system altered in response to changes in the operation of the system, a pilot-scale N and P removing SBR. Particularly, the three applied operational scenarios resulted in three distinctive responses in the SBR, namely pronounced limitation of the hydrolysis of the organic nitrogen, nitrite build-up during aerobic conditions and also nitrite build-up during anoxic conditions. This shows that even for the same system with the same influent wastewater composition, the model structure of the ASM2d does not remain constant but adapts parallel to dynamic changes in the activated sludge community. On the other hand, the three calibrated ASM2d models still lacked the ability to entirely describe the observed dynamics particularly those dealing with the phosphorus dynamics and hydrolysis. Understanding the underlying reasons of this discrepancy is a challenging task, which is expected to improve the modelling of bio-P removing activated sludge systems.

Evaluation of the impacts of model-based operation of SBRs on activated sludge microbial community.

Impact of model-based operation of nutrient removing SBRs on the stability of activated sludge population was studied in this contribution. The optimal operation scenario found by the systematic model-based optimisation protocol of Sin et al. (Wat. Sci. Tech., 2004, 50(10), 97-105) was applied to a pilot-scale SBR and observed to considerably improve the nutrient removal efficiency in the system. Further, the process dynamics was observed to change under the optimal operation scenario, e.g. the nitrite route prevailed and also filamentous bulking was provoked in the SBR system. At the microbial community level as monitored by DGGE, a transient shift was observed to gradually take place parallel to the shift into the optimal operation scenario. This implies that the model-based optimisation of a nutrient removing SBR causes changes at the microbial community level. This opens future perspectives to incorporate the valuable information from the molecular monitoring of activated sludge into the model-based optimisation methodologies. In this way, it is expected that model-based optimisation approaches will better cover complex and dynamic aspects of activated sludge systems.

Application of a model-based optimisation methodology for nutrient removing SBRs leads to falsification of the model.

Recently, a model-based optimisation methodology for SBR operation has been developed and an optimal operation scenario proposed to improve N and P removal in a pilot-scale SBR. In this study, this optimal operation scenario was implemented and evaluated. The results of the implementation showed that the SBR performance was improved by approximately 50 and 40% for total nitrogen and phosphorous removal, respectively, which was better than predicted by the model. However, the long-term SBR performance was found to be unstable, particularly owing to settling problems developed after the implementation. When confronted with reality, the model used for the optimisation of the operation was found to be invalid. The model was unable to predict the nitrite build-up provoked by the optimal operation scenario. These results imply that changing the operation of an SBR system using a model may significantly change the behaviour of the system beyond the (unknown) application domain of the model. This is simply because the mechanistic models currently do not cover all the aspects of activated sludge systems, e.g. settling and adaptation of the microbial community. To further improve model-application practices, expert knowledge (not contained in the models) can be valuable and should be incorporated into model-based process optimisations.

Model-based evaluation of an on-line control strategy for SBRs based on OUR and ORP measurements.

Application of control strategies for existing wastewater treatment technologies becomes necessary to meet ever-stricter effluent legislations and reduce the associated treatment costs. In the case of SBR technology, controlling the phase scheduling is one of the key aspects of SBR operation. In this study a calibrated mechanistic model based on the ASM1 was used to evaluate an on-line control strategy for the SBR phase-scheduling and compare it with the SBR's performance using no control strategy. To evaluate the performance, reference indices relating to the effluent quality, the required energy for aeration and the treated wastewater volume were used. The results showed that it is possible to maintain optimal SBR performance in the studied system at minimal costs by on-line control of the length of the aerobic and anoxic phases.

Limitations of ASM1 and ASM3: a comparison based on batch oxygen uptake rate profiles from different full-scale wastewater treatment plants.

The two most popular models for the description of the biological COD removal are ASM1 and ASM3. However, some numerical inconsistencies arise when using these models to interpret the data obtained in short-term respirometric batch experiments. In this study, both models are fitted to four different respirometric batch profiles obtained with biomass from different WWTP. The parameter estimation results and the practical (local) identifiability are analysed, and the limitations of both models are discussed. The growth yield obtained by fitting ASM1 to the short-term respirometric batch profiles is higher than the default one, as well as the storage yield obtained by fitting ASM3 is lower than the default one. Based on these values, possible improvements to the modelling of the biological COD removal, such as the inclusion of simultaneous growth and storage on external substrate, are proposed.

Modeling of a large-scale wastewater treatment plant for efficient operation.

Environmental legislations in the Western world impose stringent effluent quality standards for ultimate protection of the environment. This is also observed in Turkey. The current paper presents efforts made to simulate an existing 0.77 million m3/day conventional activated sludge plant located at Ankara, AWTP. The ASM1 model was used for simulation in this study. The model contains numerous stoichiometric and kinetic parameters, some of which need to be determined on case by case bases. The easily degradable COD (S(S)) was determined by two methods, physical-chemical and respirometric methods, namely. The latter method was deemed unreliable and rejected in the further study. Dynamic simulation with SSSP program predicted effluent COD and MLSS values successfully while overestimating OUR. A complete fit could only be obtained by introducing a dimensionless correction factor (etaO2 = 0.58) to the oxygen term in ASM1.