Estimating the relative importance of epidemiological and behavioural parameters for epidemic mpox transmission: a modelling study.

BACKGROUND: Many European countries experienced outbreaks of mpox in 2022, and there was an mpox outbreak in 2023 in the Democratic Republic of Congo. There were many apparent differences between these outbreaks and previous outbreaks of mpox; the recent outbreaks were observed in men who have sex with men after sexual encounters at common events, whereas earlier outbreaks were observed in a wider population with no identifiable link to sexual contacts. These apparent differences meant that data from previous outbreaks could not reliably be used to parametrise infectious disease models during the 2022 and 2023 mpox outbreaks, and modelling efforts were hampered by uncertainty around key transmission and immunity parameters. METHODS: We developed a stochastic, discrete-time metapopulation model for mpox that allowed for sexual and non-sexual transmission and the implementation of non-pharmaceutical interventions, specifically contact tracing and pre- and post-exposure vaccinations. We calibrated the model to case data from Berlin and used Sobol sensitivity analysis to identify parameters that mpox transmission is especially sensitive to. We also briefly analysed the sensitivity of the effectiveness of non-pharmaceutical interventions to various efficacy parameters. RESULTS: We found that variance in the transmission probabilities due to both sexual and non-sexual transmission had a large effect on mpox transmission in the model, as did the level of immunity to mpox conferred by a previous smallpox vaccination. Furthermore, variance in the number of pre-exposure vaccinations offered was the dominant contributor to variance in mpox dynamics in men who have sex with men. If pre-exposure vaccinations were not available, both the accuracy and timeliness of contact tracing had a large impact on mpox transmission in the model. CONCLUSIONS: Our results are valuable for guiding epidemiological studies for parameter ascertainment and identifying key factors for success of non-pharmaceutical interventions.

A compartmental model for smoking dynamics in Italy: a pipeline for inference, validation, and forecasting under hypothetical scenarios.

We propose a compartmental model for investigating smoking dynamics in an Italian region (Tuscany). Calibrating the model on local data from 1993 to 2019, we estimate the probabilities of starting and quitting smoking and the probability of smoking relapse. Then, we forecast the evolution of smoking prevalence until 2043 and assess the impact on mortality in terms of attributable deaths. We introduce elements of novelty with respect to previous studies in this field, including a formal definition of the equations governing the model dynamics and a flexible modelling of smoking probabilities based on cubic regression splines. We estimate model parameters by defining a two-step procedure and quantify the sampling variability via a parametric bootstrap. We propose the implementation of cross-validation on a rolling basis and variance-based Global Sensitivity Analysis to check the robustness of the results and support our findings. Our results suggest a decrease in smoking prevalence among males and stability among females, over the next two decades. We estimate that, in 2023, 18% of deaths among males and 8% among females are due to smoking. We test the use of the model in assessing the impact on smoking prevalence and mortality of different tobacco control policies, including the tobacco-free generation ban recently introduced in New Zealand.

Investigating the effects of spatial scales on social vulnerability index: A hybrid uncertainty and sensitivity analysis approach combined with remote sensing land cover data.

Investigating the effects of spatial scales on the uncertainty and sensitivity analysis of the social vulnerability index (SoVI) model output is critical, especially for spatial scales finer than the census block group or census block. This study applied the intelligent dasymetric mapping approach to spatially disaggregate the census tract scale SoVI model into a 300-m grids resolution SoVI map in Davidson County, Nashville. Then, uncertainty analysis and variance-based global sensitivity analysis were conducted on two scales of SoVI models: (a) census tract scale; (b) 300-m grids scale. Uncertainty analysis results indicate that the SoVI model has better confidence in identifying places with a higher socially vulnerable status, no matter the spatial scales in which the SoVI is constructed. However, the spatial scale of SoVI does affect the sensitivity analysis results. The sensitivity analysis suggests that for census tract scale SoVI, the indicator transformation and weighting scheme are the two major uncertainty contributors in the SoVI index modeling stages. While for finer spatial scales like the 300-m grid's resolution, the weighting scheme becomes the uttermost dominant uncertainty contributor, absorbing uncertainty contributions from indicator transformation.

Tool for fast assessment of stormwater flood volumes for urban catchment: A machine learning approach.

Specific flood volume is an important criterion for evaluating the performance of sewer networks. Currently, mechanistic models - MCMs (e.g., SWMM) are usually used for its prediction, but they require the collection of detailed information about the characteristics of the catchment and sewer network, which can be difficult to obtain, and the process of model calibration is a complex task. This paper presents a methodology for developing simulators to predict specific flood volume using machine learning methods (DNN - Deep Neural Network, GAM - Generalized Additive Model). The results of Sobol index calculations using the GSA method were used to select the ML model as an alternative to the MCM model. It was shown that the DNN model can be used for flood prediction, for which high agreement was obtained between the results of GSA calculations for rainfall data, catchment and sewer network characteristics, and calibrated SWMM parameters describing land use and sewer retention. Regression relationships (polynomials and exponential functions) were determined between Sobol indices (retention depth of impervious area, correction factor of impervious area, Manning's roughness coefficient of sewers) and sewer network characteristics (unit density of sewers, retention factor - the downstream and upstream of retention ratio) obtaining R2 = 0. 55-0.78. The feasibility of predicting sewer network flooding and modernization with the DNN model using a limited range of input data compared to the SWMM was shown. The developed model can be applied to the management of urban catchments with limited access to data and at the stage of urban planning.

NITIRSOIL: A model that balances complexity with prediction uncertainty for improving nitrogen fertilization in agriculture.

Mismanagement of the nitrogen (N) fertilization in agriculture leads to low N use efficiency (NUE) and therefore pollution of waters and atmosphere due to NO3- leaching, and N2O and NH3 emissions. The use of N simulation models of the soil-plant system can help improve the N fertilizer management increasing NUE and decreasing N pollution issues. However, many N simulation models lack balance between complexity and uncertainty with the result that they are not applied in actual practice. The NITIRSOIL is a one-dimensional transient-state model with a monthly time step that aims at addressing this lack in the estimation of, mainly, dry matter yield (DMY), crop N uptake (Nupt), soil mineral N (Nmin), and NO3- leaching in agricultural fields. According to its global sensitivity analysis for horticulture, the NITIRSOIL simulations of the aforementioned outputs mostly depend on the critical N dilution curve, harvest index, dry matter fraction, potential fresh yield and nitrification coefficients. According to its validation for 35 nitrogen fertilization trials with 11 vegetables under semi-arid Mediterranean climate in Eastern Spain, the NITIRSOIL presents indices of agreement between 0.87 and 0.97 for the prediction of total dry matter, DMY, Nupt, NO3- leaching and soil Nmin at crop season end. Therefore, the NITIRSOIL model can be used in actual practice to improve the sustainability of the N management in, particularly horticulture, due to the balance it features between complexity and prediction uncertainty. For this aim, the NITRISOIL can be used either on its own, or in combination with "Nmin" on-site N fertilization recommendation methods, or even could be implemented as the calculation core of decision support systems.

Learning-based sensitivity analysis and feedback design for drug delivery of mixed therapy of cancer in the presence of high model uncertainties.

In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the drug delivery feedback strategy on the other hand. More precisely, a method is given that enables to extract and rank the most influent parameters that determine the probability of success/failure of a given feedback therapy for a given set of initial conditions over a cloud of realizations of uncertainties. Moreover predictors of the expectations of the amounts of drugs being used can also be derived. This enables to design an efficient stochastic optimization framework that guarantees safe contraction of the tumor while minimizing a weighted sum of the quantities of the different drugs being used. The framework is illustrated and validated using the example of a mixed therapy of cancer involving three combined drugs namely: a chemotherapy drug, an immunology vaccine and an immunotherapy drug. Finally, in this specific case, it is shown that dash-boards can be built in the 2D-space of the most influent state components that summarize the outcomes' probabilities and the associated drug usage as iso-values curves in the reduced state space.

Modeling and Global Sensitivity Analysis of Strategies to Mitigate Covid-19 Transmission on a Structured College Campus.

In response to the COVID-19 pandemic, many higher educational institutions moved their courses on-line in hopes of slowing disease spread. The advent of multiple highly-effective vaccines offers the promise of a return to "normal" in-person operations, but it is not clear if-or for how long-campuses should employ non-pharmaceutical interventions such as requiring masks or capping the size of in-person courses. In this study, we develop and fine-tune a model of COVID-19 spread to UC Merced's student and faculty population. We perform a global sensitivity analysis to consider how both pharmaceutical and non-pharmaceutical interventions impact disease spread. Our work reveals that vaccines alone may not be sufficient to eradicate disease dynamics and that significant contact with an infectious surrounding community will maintain infections on-campus. Our work provides a foundation for higher-education planning allowing campuses to balance the benefits of in-person instruction with the ability to quarantine/isolate infectious individuals.

Exploring how ecological and epidemiological processes shape multi-host disease dynamics using global sensitivity analysis.

We use global sensitivity analysis (specifically, Partial Rank Correlation Coefficients) to explore the roles of ecological and epidemiological processes in shaping the temporal dynamics of a parameterized SIR-type model of two host species and an environmentally transmitted pathogen. We compute the sensitivities of disease prevalence in each host species to model parameters. Sensitivity rankings are calculated, interpreted biologically, and contrasted for cases where the pathogen is introduced into a disease-free community and cases where a second host species is introduced into an endemic single-host community. In some cases the magnitudes and dynamics of the sensitivities can be predicted only by knowing the host species' characteristics (i.e., their competitive abilities and disease competence) whereas in other cases they can be predicted by factors independent of the species' characteristics (specifically, intraspecific versus interspecific processes or a species' roles of invader versus resident). For example, when a pathogen is initially introduced into a disease-free community, disease prevalence in both hosts is more sensitive to the burst size of the first host than the second host. In comparison, disease prevalence in each host is more sensitive to its own infection rate than the infection rate of the other host species. In total, this study illustrates that global sensitivity analysis can provide useful insight into how ecological and epidemiological processes shape disease dynamics and how those effects vary across time and system conditions. Our results show that sensitivity analysis can provide quantification and direction when exploring biological hypotheses.

A two-stages global sensitivity analysis by using the δ sensitivity index in presence of correlated inputs: application on a tumor growth inhibition model based on the dynamic energy budget theory.

Global sensitivity analysis (GSA) evaluates the impact of variability and/or uncertainty of the model parameters on given model outputs. GSA is useful for assessing the quality of Pharmacometric model inference. Indeed, model parameters can be affected by high (estimation) uncertainty due to the sparsity of data. Independence between model parameters is a common assumption of GSA methods. However, ignoring (known) correlations between parameters may alter model predictions and, then, GSA results. To address this issue, a novel two-stages GSA technique based on the δ index, which is well-defined also in presence of correlated parameters, is here proposed. In the first step, statistical dependencies are neglected to identify parameters exerting causal effects. Correlations are introduced in the second step to consider the real distribution of the model output and investigate also the 'indirect' effects due to the correlation structure. The proposed two-stages GSA strategy was applied, as case study, to a preclinical tumor-in-host-growth inhibition model based on the Dynamic Energy Budget theory. The aim is to evaluate the impact of the model parameter estimate uncertainty (including correlations) on key model-derived metrics: the drug threshold concentration for tumor eradication, the tumor volume doubling time and a new index evaluating the drug efficacy-toxicity trade-off. This approach allowed to rank parameters according to their impact on the output, discerning whether a parameter mainly exerts a causal or 'indirect' effect. Thus, it was possible to identify uncertainties that should be necessarily reduced to obtain robust predictions for the outputs of interest.

An integrated modelling approach for targeted degradation: insights on optimization, data requirements and PKPD predictions from semi- or fully-mechanistic models and exact steady state solutions.

The value of an integrated mathematical modelling approach for protein degraders which combines the benefits of traditional turnover models and fully mechanistic models is presented. Firstly, we show how exact solutions of the mechanistic models of monovalent and bivalent degraders can provide insight on the role of each system parameter in driving the pharmacological response. We show how on/off binding rates and degradation rates are related to potency and maximal effect of monovalent degraders, and how such relationship can be used to suggest a compound optimization strategy. Even convoluted exact steady state solutions for bivalent degraders provide insight on the type of observations required to ensure the predictive capacity of a mechanistic approach. Specifically for PROTACs, the structure of the exact steady state solution suggests that the total remaining target at steady state, which is easily accessible experimentally, is insufficient to reconstruct the state of the whole system at equilibrium and observations on different species (such as binary/ternary complexes) are necessary. Secondly, global sensitivity analysis of fully mechanistic models for PROTACs suggests that both target and ligase baselines (actually, their ratio) are the major sources of variability in the response of non-cooperative systems, which speaks to the importance of characterizing their distribution in the target patient population. Finally, we propose a pragmatic modelling approach which incorporates the insights generated with fully mechanistic models into simpler turnover models to improve their predictive ability, hence enabling acceleration of drug discovery programs and increased probability of success in the clinic.

An Uncertainty Model for Strain Gages Using Monte Carlo Methodology.

For the purpose of validation and identification of mechanical systems, measurements are indispensable. However, they require knowledge of the inherent uncertainty to provide valid information. This paper describes a method on how to evaluate uncertainties in strain measurement using electric strain gages for practical engineering applications. Therefore, a basic model of the measurement is deduced that comprises the main influence factors and their uncertainties. This is performed using the example of a project dealing with strain measurement on the concrete surface of a large-span road bridge under static loading. Special attention is given to the statistical modeling of the inputs, the underlying physical relationship, and the incorporation and the impact of nonlinearities for different environmental conditions and strain levels. In this regard, also experiments were conducted to quantify the influence of misalignment of the gages. The methodological approach used is Monte Carlo simulation. A subsequent variance-based sensitivity analysis reveals the degree of nonlinearity in the relationship and the importance of the different factors to the resulting probability distribution. The developed scheme requires a minimum of expert knowledge of the analytical derivation of measurement uncertainties and can easily be modified for differing requirements and purposes.

Framework for global sensitivity analysis in a complex 1D-2D coupled hydrodynamic model: Highlighting its importance on flood management over large data-scarce regions.

Sensitivity analysis determines how perturbation or variation in the values of an independent variable affects a particular dependent variable. The present study attempts to comprehend the sensitivity of the static input parameters on the accuracy of the outputs in a hydrodynamic flood model, which subsequently improves the model accuracy. Hydrodynamic flood modeling is computationally strenuous and data-intensive. Moreover, the accuracy of the flood model outputs is extremely sensitive to the quality of hydrologic and hydraulic inputs, along with a set of static parameters that are traditionally assumed and primarily used for calibration. Therefore, we focus on developing a framework for global sensitivity analysis (GSA) of static input parameters in a 1D-2D coupled hydrodynamic flood modeling system. A set of numerical experiments is conducted by perturbing various combinations of input parameters from their standard (or observed) values to generate flow hydrographs. Nonparametric probability density functions (PDFs) of the river discharge at different locations are compared to calculate the Kullback-Leibler (KL) entropy or KL-divergence, which is used to quantify the sensitivity of the input parameters. We demonstrated the proposed framework on a highly flood-prone rural catchment of the Shilabati River in West Bengal, India, and infer that the sensitivity of the static input parameters is highly dynamic, and their importance varies spatially from the upstream to the downstream of the river. However, Manning's n values of the channel and the banks are significantly sensitive irrespective of the location in the river reach. We suggest that any flood modeling exercise should accompany a GSA, which sets a guideline for the modelers to prioritize the set of sensitive static input parameters during data monitoring, collection, and retrieval. This study is the first attempt at a GSA in a 1D-2D coupled hydrodynamic flood modeling system, whose importance cannot be over-emphasized in any flood modeling platform. The proposed novel framework is generic and can be implemented prior to flood risk analyses for any floodplain management exercise. All free and commercially-available flood models can incorporate the proposed framework for a GSA as an extension toolbox.

Probabilistic assessment of failure of infiltration structures under model and parametric uncertainty.

We focus on the quantification of the probability of failure (PF) of an infiltration structure, of the kind that is typically employed for the implementation of low impact development strategies in urban settings. Our approach embeds various sources of uncertainty. These include (a) the mathematical models rendering key hydrological traits of the system and the ensuing model parametrization as well as (b) design variables related to the drainage structure. As such, we leverage on a rigorous multi-model Global Sensitivity Analysis framework. We consider a collection of commonly used alternative models to represent our knowledge about the conceptualization of the system functioning. Each model is characterized by a set of uncertain parameters. As an original aspect, the sensitivity metrics we consider are related to a single- and a multi-model context. The former provides information about the relative importance that model parameters conditional to the choice of a given model can have on PF. The latter yields the importance that the selection of a given model has on PF and enables one to consider at the same time all of the alternative models analyzed. We demonstrate our approach through an exemplary application focused on the preliminary design phase of infiltration structures serving a region in the northern part of Italy. Results stemming from a multi-model context suggest that the contribution arising from the adoption of a given model is key to the quantification of the degree of importance associated with each uncertain parameter.

Assessing runoff control of low impact development in Hong Kong's dense community with reliable SWMM setup and calibration.

Low impact development (LID) is a sustainable practice to managing urban runoff. However, its effectiveness in densely populated areas with intense rainfall, such as Hong Kong, remains unclear due to limited studies with similar climate conditions and urban patterns. The highly mixed land use and complicated drainage network present challenges for preparing a Storm Water Management Model (SWMM). This study proposed a reliable framework for setting up and calibrating SWMM by integrating multiple automated tools to address these issues. With a validated SWMM, we examined LID's effects on runoff control in a densely built catchment of Hong Kong. A designed full-scale LID implementation can reduce total and peak runoffs by around 35-45% for 2, 10 and 50-year return rainfalls. However, LID alone may not be adequate to handle the runoff in densely built areas of Hong Kong. As the rainfall return period increases, total runoff reduction increases, but peak runoff reduction remains close. Percentages of reduction in total and peak runoffs decline. The marginal control diminishes for total runoff while remaining constant for peak runoff when increasing the extent of LID implementation. In addition, the study identifies the crucial design parameters of LID facilities using global sensitivity analysis. Overall, our study contributes to accelerating the reliable application of SWMM and deepening the understanding of the effectiveness of LID in ensuring water security in densely built urban communities located near the humid-tropical climate zone, such as Hong Kong.

Environmental vulnerability assessment of the Doce River basin, southeastern Brazil.

Environmental vulnerability is an important tool to understand the natural and anthropogenic impacts associated with the susceptibility to environmental damage. This study aims to assess the environmental vulnerability of the Doce River basin in Brazil through Multicriteria Decision Analysis based on Geographic Information Systems (GIS-MCDA). Natural factors (slope, elevation, relief dissection, rainfall, pedology, and geology) and anthropogenic factors (distance from urban centers, roads, mining dams, and land use) were used to determine the environmental vulnerability index (EVI). The EVI was classified into five classes, identifying associated land uses. Vulnerability was verified in water resource management units (UGRHs) and municipalities using hot spot analysis. The study employed the water quality index (WQI) to assess the EVI and global sensitivity analysis (GSA) to evaluate the model input parameters that most influence the basin's environmental vulnerability. The results showed that the regions near the middle Doce River were considered environmentally more vulnerable, especially the UGRHs Guandu, Manhuaçu, and Caratinga; and 35.9% of the basin has high and very high vulnerabilities. Hot spot analysis identified regions with low EVI values (cold spot) in the north and northwest, while areas with high values (hot spot) were concentrated mainly in the middle Doce region. Water monitoring stations with the worst WQI values were found in the most environmentally vulnerable areas. The GSA determined that land use and slope were the primary factors influencing the model's response. The results of this study provide valuable information for supporting environmental planning in the Doce River basin.

Global sensitivity analysis in epidemiological modeling.

Operations researchers worldwide rely extensively on quantitative simulations to model alternative aspects of the COVID-19 pandemic. Proper uncertainty quantification and sensitivity analysis are fundamental to enrich the modeling process and communicate correctly informed insights to decision-makers. We develop a methodology to obtain insights on key uncertainty drivers, trend analysis and interaction quantification through an innovative combination of probabilistic sensitivity techniques and machine learning tools. We illustrate the approach by applying it to a representative of the family of susceptible-infectious-recovered (SIR) models recently used in the context of the COVID-19 pandemic. We focus on data of the early pandemic progression in Italy and the United States (the U.S.). We perform the analysis for both cases of correlated and uncorrelated inputs. Results show that quarantine rate and intervention time are the key uncertainty drivers, have opposite effects on the number of total infected individuals and are involved in the most relevant interactions.

Global Sensitivity Analysis of Background Life Cycle Inventories.

In recent years many Life Cycle Assessment (LCA) studies have been conducted to quantify the environmental performance of products and services. Some of these studies propagated numerical uncertainties in underlying data to LCA results, and several applied Global Sensitivity Analysis (GSA) to some parts of the LCA model to determine its main uncertainty drivers. However, only a few studies have tackled the GSA of complete LCA models due to the high computational cost of such analysis and the lack of appropriate methods for very high-dimensional models. This study proposes a new GSA protocol suitable for large LCA problems that, unlike existing approaches, does not make assumptions on model linearity and complexity and includes extensive validation of GSA results. We illustrate the benefits of our protocol by comparing it with an existing method in terms of filtering of noninfluential and ranking of influential uncertainty drivers and include an application example of Swiss household food consumption. We note that our protocol obtains more accurate GSA results, which leads to better understanding of LCA models, and less data collection efforts to achieve more robust estimation of environmental impacts. Implementations supporting this work are available as free and open source Python packages.

Hyperspectral response of agronomic variables to background optical variability: Results of a numerical experiment.

Understanding how biophysical and biochemical variables contribute to the spectral characteristics of vegetation canopies is critical for their monitoring. Quantifying these contributions, however, remains difficult due to extraneous factors such as the spectral variability of canopy background materials, including soil/crop-residue moisture, soil-type, and non-photosynthetic vegetation (NPV). This study focused on exploring the spectral response of two important agronomic variables (1) leaf chlorophyll content (Cab ) and (2) leaf area index (LAI) under various canopy backgrounds through a global sensitivity analysis of wheat-like canopy spectra simulated using the physically-based PROSAIL radiative transfer model. Our results reveal the following general findings: (1) the contribution of each agronomic variable to the simulated canopy spectral signature varies considerably with respect to the background optical properties; (2) the influence of the soil-type and NPV on the spectral response of canopy to Cab and LAI is more significant than that caused by soil/crop-residue moisture; (3) spectral bands at 560 and 704 nm remain sensitive to Cab while being least affected by the impacts of variations in the NPV, soil-type and moisture; (4) the near-infrared (NIR) spectral bands exhibit higher sensitivity to LAI and lower background effects only in the cases of soil/crop-residue moisture but are relatively strongly affected by soil-type and NPV. Comparative analysis of the correlations of twelve widely used vegetation indices with agronomic variables indicates that LICI (LAI-insensitive chlorophyll index) and Macc01 (Maccioni index) are more effective in estimating Cab , while OSAVI (optimized soil adjusted vegetation index) and MCARI2 (modified chlorophyll absorption ratio index 2) are better LAI predictors under the simulated background variability. Overall, our results highlight that background reflectance variability introduces considerable differences in the agronomic variables' spectral response, leading to inconsistencies in the VI- Cab /-LAI relationship. Further studies should integrate these results of spectral responsivity to develop trait-specific hyperspectral inversion models.

Global sensitivity analysis in physiologically-based pharmacokinetic/pharmacodynamic models of inhaled and opioids anesthetics and its application to generate virtual populations.

The integration between physiologically-based pharmacokinetics (PBPK) models and pharmacodynamics (PD) models makes it possible to describe the absorption, distribution, metabolism and excretion processes of drugs, together with the concentration-response relationship, being a fundamental framework with wide applications in pharmacology. Nevertheless, the enormous complexity of PBPK models and the large number of parameters that define them leads to the need to study and understand how the uncertainty of the parameters affects the variability of the models output. To study this issue, this paper proposes a global sensitivity analysis (GSA) to identify the parameters that have the greatest influence on the response of the model. It has been selected as study cases the PBPK models of an inhaled anesthetic and an analgesic, along with two PD interaction models that describe two relevant clinical effects, hypnosis and analgesia during general anesthesia. The subset of the most relevant parameters found adequately with the GSA method has been optimized for the generation of a virtual population that represents the theoretical output variability of various model responses. The generated virtual population has the potential to be used for the design, development and evaluation of physiological closed-loop control systems.

Life cycle assessment of struvite recovery and wastewater sludge end-use: A Flemish illustration.

Phosphate rock (PR) has been designated as a Critical Raw Material in the European Union (EU). This has led to increased emphasis on alternative P recovery (APR) from secondary streams like wastewater sludge (WWS). However, WWS end-use is a contentious topic, and EU member states prefer different end-use pathways (land application/incineration/valorisation in cement kilns). Previous Life Cycle Assessments (LCA) on APRs from WWS reached contrasting conclusions; while most considered WWS as waste and highlighted a net benefit relative to PR mining and beneficiation, others viewed WWS as a resource and highlighted a net burden of the treatment. We used a combined functional unit (that views WWS from a waste as well as a resource perspective) and applied it on a Flemish wastewater treatment plant (WWTP) with struvite recovery as APR technology. Firstly, a retrospective comparison was performed to measure the WWTP performance before and after struvite recovery and the analysis was complemented by uncertainty and global sensitivity analyses. The results showed struvite recovery provides marginal environmental benefits due to improved WWS dewatering and reduced polymer use. Secondly, a prospective LCA approach was performed to reflect policy changes regarding WWS end-use options in Flanders. Results indicated complete mono-incineration of WWS, ash processing to recover P and the subsequent land application appears to be less sustainable in terms of climate change, human toxicity, and terrestrial acidification relative to the status quo, i.e., co-incineration with municipal solid waste and valorisation at cement kilns. Impacts on fossil depletion, however, favour mono-incineration over the status quo.