Advancement of membrane separation technology for organic pollutant removal.

In the face of growing global freshwater scarcity, the imperative to recycle and reuse water becomes increasingly apparent across industrial, agricultural, and domestic sectors. Eliminating a range of organic pollutants in wastewater, from pesticides to industrial byproducts, presents a formidable challenge. Among the potential solutions, membrane technologies emerge as promising contenders for treating diverse organic contaminants from industrial, agricultural, and household origins. This paper explores cutting-edge membrane-based approaches, including reverse osmosis, nanofiltration, ultrafiltration, microfiltration, gas separation membranes, and pervaporation. Each technology's efficacy in removing distinct organic pollutants while producing purified water is scrutinized. This review delves into membrane fouling, discussing its influencing factors and preventative strategies. It sheds light on the merits, limitations, and prospects of these various membrane techniques, contributing to the advancement of wastewater treatment. It advocates for future research in membrane technology with a focus on fouling control and the development of energy-efficient devices. Interdisciplinary collaboration among researchers, engineers, policymakers, and industry players is vital for shaping water purification innovation. Ongoing research and collaboration position us to fulfill the promise of accessible, clean water for all.

Workflow to facilitate the detection of new psychoactive substances and drugs of abuse in influent urban wastewater.

The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open-source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.

Structured Ethical Review for Wastewater-Based Testing in Support of Public Health.

Wastewater-based testing (WBT) for SARS-CoV-2 has rapidly expanded over the past three years due to its ability to provide a comprehensive measurement of disease prevalence independent of clinical testing. The development and simultaneous application of WBT measured biomarkers for research activities and for the pursuit of public health goals, both areas with well-established ethical frameworks. Currently, WBT practitioners do not employ a standardized ethical review process, introducing the potential for adverse outcomes for WBT professionals and community members. To address this deficiency, an interdisciplinary workshop developed a framework for a structured ethical review of WBT. The workshop employed a consensus approach to create this framework as a set of 11 questions derived from primarily public health guidance. This study retrospectively applied these questions to SARS-CoV-2 monitoring programs covering the emergent phase of the pandemic (3/2020-2/2022 (n = 53)). Of note, 43% of answers highlight a lack of reported information to assess. Therefore, a systematic framework would at a minimum structure the communication of ethical considerations for applications of WBT. Consistent application of an ethical review will also assist in developing a practice of updating approaches and techniques to reflect the concerns held by both those practicing and those being monitored by WBT supported programs.

Structured Ethical Review for Wastewater-Based Testing.

Wastewater-based testing (WBT) for SARS-CoV-2 has rapidly expanded over the past three years due to its ability to provide a comprehensive measurement of disease prevalence independent of clinical testing. The development and simultaneous application of the field blurred the boundary between measuring biomarkers for research activities and for pursuit of public health goals, both areas with well-established ethical frameworks. Currently, WBT practitioners do not employ a standardized ethical review process (or associated data management safeguards), introducing the potential for adverse outcomes for WBT professionals and community members. To address this deficiency, an interdisciplinary group developed a framework for a structured ethical review of WBT. The workshop employed a consensus approach to create this framework as a set of 11-questions derived from primarily public health guidance because of the common exemption of wastewater samples to human subject research considerations. This study retrospectively applied the set of questions to peer- reviewed published reports on SARS-CoV-2 monitoring campaigns covering the emergent phase of the pandemic from March 2020 to February 2022 (n=53). Overall, 43% of the responses to the questions were unable to be assessed because of lack of reported information. It is therefore hypothesized that a systematic framework would at a minimum improve the communication of key ethical considerations for the application of WBT. Consistent application of a standardized ethical review will also assist in developing an engaged practice of critically applying and updating approaches and techniques to reflect the concerns held by both those practicing and being monitored by WBT supported campaigns. Synopsis: Development of a structured ethical review facilitates retrospective analysis of published studies and drafted scenarios in the context of wastewater-based testing.

Impact of LC-MS/MS quantification methods on analytical results by example of nationwide U.S. environmental samples.

Although different quantification methods are extensively used in environmental chemistry, the impact of the choice of method on the quality and range of analytical results is understudied. This two-part study consists of (a) in-lab evaluation and (b) a traditional meta-analysis (n = 66) of commonly used quantification methods): (i) external calibration; (ii) isotope dilution method with authentic target analogs; (iii) isotope dilution with non-target standards; and (iv) standard addition prior to LC-MS/MS in liquid chromatography tandem mass spectrometry (LC-MS/MS) by example of antibiotics in sewage sludge from across the U.S. Using method (i) as the benchmark quantification method for the antibiotic erythromycin in biosolids, other quantification methods resulted in an overestimation (110-450 %) or an underestimation (10-60 %). Using the method (iv) as the benchmark for other compounds resulted in an overestimation (101-14,700 %) or an underestimation (6-98 %). Matrix effects were also observed and were dependent on the matrix and analyte type. For example, in the case of erythromycin, all sample matrices showed signal suppression. This study showed that in the absence of isotopically labeled analogs, the most accurate alternate quantification method may need to be experimentally determined depending on the analyte. Analysis of published literature on pharmaceuticals in sewage sludge indicated that isotope dilution with authentic target analog is most commonly used, followed by non-target isotope standards, standard addition, and finally external calibration.

Three years of wastewater surveillance for new psychoactive substances from 16 countries.

The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatography - mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ketamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use.

Occurrence of Z-drugs, benzodiazepines, and ketamine in wastewater in the United States and Mexico during the Covid-19 pandemic.

Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.

Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study.

BACKGROUND: Before the COVID-19 pandemic, the US opioid epidemic triggered a collaborative municipal and academic effort in Tempe, Arizona, which resulted in the world's first open access dashboard featuring neighbourhood-level trends informed by wastewater-based epidemiology (WBE). This study aimed to showcase how wastewater monitoring, once established and accepted by a community, could readily be adapted to respond to newly emerging public health priorities. METHODS: In this population-based study in Greater Tempe, Arizona, an existing opioid monitoring WBE network was modified to track SARS-CoV-2 transmission through the analysis of 11 contiguous wastewater catchments. Flow-weighted and time-weighted 24 h composite samples of untreated wastewater were collected at each sampling location within the wastewater collection system for 3 days each week (Tuesday, Thursday, and Saturday) from April 1, 2020, to March 31, 2021 (Area 7 and Tempe St Luke's Hospital were added in July, 2020). Reverse transcription quantitative PCR targeting the E gene of SARS-CoV-2 isolated from the wastewater samples was used to determine the number of genome copies in each catchment. Newly detected clinical cases of COVID-19 by zip code within the City of Tempe, Arizona were reported daily by the Arizona Department of Health Services from May 23, 2020. Maricopa County-level new positive cases, COVID-19-related hospitalisations, deaths, and long-term care facility deaths per day are publicly available and were collected from the Maricopa County Epidemic Curve Dashboard. Viral loads of SARS-CoV-2 (genome copies per day) measured in wastewater from each catchment were aggregated at the zip code level and city level and compared with the clinically reported data using root mean square error to investigate early warning capability of WBE. FINDINGS: Between April 1, 2020, and March 31, 2021, 1556 wastewater samples were analysed. Most locations showed two waves in viral levels peaking in June, 2020, and December, 2020-January, 2021. An additional wave of viral load was seen in catchments close to Arizona State University (Areas 6 and 7) at the beginning of the fall (autumn) semester in late August, 2020. Additionally, an early infection hotspot was detected in the Town of Guadalupe, Arizona, starting the week of May 4, 2020, that was successfully mitigated through targeted interventions. A shift in early warning potential of WBE was seen, from a leading (mean of 8·5 days [SD 2·1], June, 2020) to a lagging (-2·0 days [1·4], January, 2021) indicator compared with newly reported clinical cases. INTERPRETATION: Lessons learned from leveraging an existing neighbourhood-level WBE reporting dashboard include: (1) community buy-in is key, (2) public data sharing is effective, and (3) sub-ZIP-code (postal code) data can help to pinpoint populations at risk, track intervention success in real time, and reveal the effect of local clinical testing capacity on WBE's early warning capability. This successful demonstration of transitioning WBE efforts from opioids to COVID-19 encourages an expansion of WBE to tackle newly emerging and re-emerging threats (eg, mpox and polio). FUNDING: National Institutes of Health's RADx-rad initiative, National Science Foundation, Virginia G Piper Charitable Trust, J M Kaplan Fund, and The Flinn Foundation.

Monkeypox outbreak: Wastewater and environmental surveillance perspective.

Monkeypox disease (MPXD), a viral disease caused by the monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022; 92 % (68/74) of the countries with reported MPXD cases had no historical MPXD case reports. From the One Health perspective, the spread of MPXV in the environment poses a risk not only to humans but also to small mammals and may, ultimately, spread to potent novel host populations. Wastewater-based surveillance (WBS) has been extensively utilized to monitor communicable diseases, particularly during the ongoing COVID-19 pandemic. It helped in monitoring infectious disease caseloads as well as specific viral variants circulating in communities. The detection of MPXV DNA in lesion materials (e.g. skin, vesicle fluid, crusts), skin rashes, and various body fluids, including respiratory and nasal secretions, saliva, urine, feces, and semen of infected individuals, supports the possibility of using WBS as an early proxy for the detection of MPXV infections. WBS of MPXV DNA can be used to monitor MPXV activity/trends in sewerage network areas even before detecting laboratory-confirmed clinical cases within a community. However, several factors affect the detection of MPXV in wastewater including, but not limited to, routes and duration time of virus shedding by infected individuals, infection rates in the relevant affected population, environmental persistence, the processes and analytical sensitivity of the used methods. Further research is needed to identify the key factors that impact the detection of MPXV biomarkers in wastewater and improve the utility of WBS of MPXV as an early warning and monitoring tool for safeguarding human health. In this review, we shortly summarize aspects of the MPXV outbreak relevant to wastewater monitoring and discuss the challenges associated with WBS.

Surveillance of rhinovirus diversity among a university community identifies multiple types from all three species including an unassigned rhinovirus A genotype.

We determine the presence and diversity of rhinoviruses in nasopharyngeal swab samples from 248 individuals who presented with influenza-like illness (ILI) at a university clinic in the Southwest United States between October 1, 2020 and March 31, 2021. We identify at least 13 rhinovirus genotypes (A11, A22, A23, A25, A67, A101, B6, B79, C1, C17, C36, and C56, as well a new genotype [AZ88**]) and 16 variants that contributed to the burden of ILI in the community. We also describe the complete capsid protein gene of a member (AZ88**) of an unassigned rhinovirus A genotype.

Impact of sample clarification by size exclusion on virus detection and diversity in wastewater-based epidemiology.

The use of wastewater-based epidemiology (WBE) for early detection of virus circulation and response during the SARS-CoV-2 pandemic increased interest in and use of virus concentration protocols that are quick, scalable, and efficient. One such protocol involves sample clarification by size fractionation using either low-speed centrifugation to produce a clarified supernatant or membrane filtration to produce an initial filtrate depleted of solids, eukaryotes and bacterial present in wastewater (WW), followed by concentration of virus particles by ultrafiltration of the above. While this approach has been successful in identifying viruses from WW, it assumes that majority of the viruses of interest should be present in the fraction obtained by ultrafiltration of the initial filtrate, with negligible loss of viral particles and viral diversity. We used WW samples collected in a population of ~700,000 in southwest USA between October 2019 and March 2021, targeting three non-enveloped viruses (enteroviruses [EV], canine picornaviruses [CanPV], and human adenovirus 41 [Ad41]), to evaluate whether size fractionation of WW prior to ultrafiltration leads to appreciable differences in the virus presence and diversity determined. We showed that virus presence or absence in WW samples in both portions (filter trapped solids [FTS] and filtrate) are not consistent with each other. We also found that in cases where virus was detected in both fractions, virus diversity (or types) captured either in FTS or filtrate were not consistent with each other. Hence, preferring one fraction of WW over the other can undermine the capacity of WBE to function as an early warning system and negatively impact the accurate representation of virus presence and diversity in a population.

Complete Coding Sequences of Rhinovirus Types A46, A39, C56, and C48.

We report the coding-complete sequences of rhinovirus types C48, A46, A39, and C56, determined from nasopharyngeal swabs from three individuals with influenza-like symptoms in the United States. One sample showed a coinfection of rhinovirus types A46 and C48.

Mass trends of parabens, triclocarban and triclosan in Arizona wastewater collected after the 2017 FDA ban on antimicrobials and during the COVID-19 pandemic.

Antimicrobials like parabens, triclosan (TCS), and triclocarban (TCC) are of public health concern worldwide due to their endocrine-disrupting properties and ability to promote antimicrobial drug resistance in human pathogens. The overall use of antimicrobials presumably has increased during the COVID-19 pandemic, whereas TCS and TCC may have experienced reductions in use due to their recent ban from thousands of over-the-counter (OTC) personal care products by the U.S. Food and Drug Administration (FDA). No quantitative data are available on the use of parabens or the impact the FDA ban had on TCC and TCS. Here, we use wastewater samples (n = 1514) from 10 different communities in Arizona to measure the presence of the six different antimicrobial products (TCS, TCC, and four alkylated parabens [methylparaben (MePb), ethylparaben (EtPb), propylparaben (PrPb), butylparaben (BuPb)]) collected before and during the COVID-19 pandemic using a combination of solid-phase extraction, liquid chromatography/tandem mass spectrometry (LC-MS/MS), and isotope dilution for absolute quantitation. The average mass loadings of all antimicrobials combined (1,431 ± 22 mg/day per 1,000 people) after the onset of the local epidemic (March 2020 - October 2020) were significantly higher (945 ± 62 mg/day per 1,000 people; p < 0.05) than before the pandemic (January 2019 - February 2020). Overall, parabens (∑Pbs = 999 ± 16 mg/day per 1,000 people) were the most used antimicrobials, followed by TCS (117 ± 14 mg/day per 1,000 people) and TCC (117 ± 14 mg/day per 1,000 people). After the 2017 U.S. FDA ban, we found a statistically significant (p < 0.05) reduction in the mass loadings of TCS (-89%) and TCC (-80%) but a rise in paraben use (+72%). Mass flows of 3 of a total of 4 parabens (MePb, EtPb, and PrPb) in wastewater were significantly higher upon the onset of the epidemic locally (p < 0.05). This is the first longitudinal study investigating the use of antimicrobials during the COVID-19 pandemic by employing wastewater-based epidemiology. Whereas an overall increase in the use of antimicrobials was evident from analyzing Arizona wastewater, a notable reduction in the use of TCS and TCC was evident during the pandemic, triggered by the U.S. FDA ban.

Genome Sequence of a Microvirus Recovered from Wastewater in Arizona, USA, in October 2020, Encodes a Previously Undescribed DNA-Binding Protein.

We describe the genome of Microvirus-AZ-2020, which was identified from wastewater in Arizona, USA, in October 2020. Microvirus-AZ-2020 belongs to subfamily Gokushovirinae and contains six (five known and one hypothetical) open reading frames (ORFs), each with >40 codons. HHPred analysis and Colabfold structure prediction suggest that the hypothetical ORF encodes a previously undescribed putative DNA-binding protein.

Genome Sequences of Anelloviruses, Genomovirus, and Papillomavirus Isolated from Nasal Pharyngeal Swabs.

The genome sequences of three anelloviruses (genus Alphatorquevirus), a genomovirus (genus Gemykolovirus), and an unclassified papillomavirus were identified in four human nasopharyngeal swabs, and one was positive for influenza A and one for influenza B virus. The influenza B virus-positive sample had a coinfection with an anellovirus and a papillomavirus.

Application of wastewater-based epidemiology for estimating population-wide human exposure to phthalate esters, bisphenols, and terephthalic acid.

Phthalates, bisphenols (BPs), and terephthalic acid (TPA) are widely used plasticizers and monomers in plastic manufacturing. Most of them are known to have an adverse effect on the human body, functioning as endocrine disruptors and suspected carcinogens. Access to near real-time data on population exposure to plasticizers is essential for identifying vulnerable communities and better protecting and managing public health locally. The objective of the present study was to evaluate population-level exposure to phthalates, BPs, and TPA by measuring urinary metabolites in community wastewater. Composited community wastewater (24-h samples) from five sewer sub-catchments of a southwestern city within the United States were analyzed for urinary biomarkers of phthalates, BPs, and TPA using solid-phase extraction-liquid chromatography-tandem mass spectrometry in conjunction with the isotope dilution method for absolute quantification. Ten of 16 analytes were detected at least once in community wastewater above the method detection limit (MDL), with MDLs ranging from 37 to 203 ng/L. The population normalized mass load of TPA was the highest, followed by the human metabolite of di-(2-ethylhexyl) phthalate (DEHP). Bisphenol S and monoethyl phthalate were detected with the highest frequency. Study findings suggest that analyzing municipal wastewater for chemical indicators of human exposure to plastic constituents is feasible, practicable, and informative, as long as appropriate steps are taken to determine, quantify and account for background levels of plastic analytes in the laboratory environment.

Towards a novel application of wastewater-based epidemiology in population-wide assessment of exposure to volatile organic compounds.

In this study, we investigated the feasibility of detecting 35 urinary biomarkers of volatile organic compounds (VOCs) exposure in community wastewater. 24-h composited municipal wastewater samples were collected from two communities (n = 8) in the southeastern US. Using isotope-dilution liquid chromatography-tandem mass spectrometry, results showed 16 metabolites were detected in wastewater samples, including indicators of exposure to acrolein, acrylonitrile, 1,3-butadiene, crotonaldehyde, n,n-dimethylformamide (DMF), ethylbenzene, nicotine, propylene oxide, styrene, tetrachloroethylene, toluene, and xylene. Additional metabolites qualitatively identified exposure to acrylamide and trichloroethylene. Community 1 (closer proximity to manufacturing facilities) had a greater number of detects (n = 36) and higher VOC loadings, 22,000 mg day-1 per 1000 people, as compared to Community 2 (n = 28), 7100 mg day-1 per 1000 people. Normalizing to nicotine consumption biomarkers to account for differences in smoking behaviors, Community 1 continued to have higher levels of propylene oxide, crotonaldehyde, DMF, and acrylonitrile exposures, VOCs generally sourced from manufacturing activities and vehicle emissions. This is the first study to utilize wastewater to detect urinary biomarkers of VOCs exposure. These preliminary results suggest the WBE approach as a potentially powerful tool to assess community health exposures to indoor and outdoor air pollutants.

Canine picornaviruses detected in wastewater in Arizona, USA 2019 and 2021.

Virus surveillance by wastewater-based epidemiology (WBE) in two Arizona municipalities in Maricopa County, USA (~700,000 people), revealed the presence of six canine picornavirus (CanPV) variants: five in 2019 and one in 2021. Phylogenetic analysis suggests these viruses might be from domestic dog breeds living within or around the area. Phylogenetic and pairwise identity analyses suggest over 15 years of likely enzootic circulation of multiple lineages of CanPV in the USA and possibly globally. Considering <10 CanPV sequences are publicly available in GenBank as of June 2, 2022, the results provided here constitute an increase of current knowledge on CanPV diversity and highlight the need for increased surveillance.

Opportunities and limits of wastewater-based epidemiology for tracking global health and attainment of UN sustainable development goals.

Wastewater-based epidemiology (WBE) emerged as a powerful, actionable health management tool during the COVID-19 pandemic. Hypothesizing future uses, we explored its potential for real-time, tracking of progress in attaining United Nations Sustainable Development Goals (SDGs) globally as a non-expensive method using existing infrastructure. We inventoried (i) literature-documented sewerage infrastructure, (ii) demographics of populations served, and (iii) WBE markers informative of 9 SDGs. Among the 17 different sustainable development goals listed by the UN 2030 agenda, more than half of these may be monitored by using WBE monitoring at centralized treatment infrastructure as tabulated in this study. Driven mainly by COVID-19, WBE currently is practiced in at least 55 countries, reaching about 300 million people. Expansion of WBE to 109,000 + treatment plants inventoried in 129 countries would increase global coverage 9-fold to 34.7% or 2.7 billion, leaving out 5 billion people not served by centralized sewerage systems. Associations between population demographics and present-day infrastructure are explored, and geospatial regions particularly vulnerable to infectious disease outbreaks are identified. The results suggest that difference in the differential outcomes in well-being is an outcome of the sanitation infrastructure inequalities and lack of sanitation infrastructure creates doubly disadvantaged populations at risk of poor hygiene and cut off from the early-warning benefits of conventional WBE. This is the first study to explore the feasibility and potential barriers to the use of WBE for tracking the attainment of SDGs globally with at least 9 out of 17 SDGs.

Systematic and state-of the science review of the role of environmental factors in Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's Disease.

The etiology of sporadic amyotrophic lateral sclerosis (ALS) is still unclear. We evaluate environmental factors suspected to be associated with ALS for their potential linkage to disease causality and to model geographic distributions of susceptible populations and expected cases worldwide. A PRISMA systematic literature review was performed 2021. Bradford Hill criteria were used to identify and rank environmental factors and a secondary review of ALS diagnoses in population studies and ALS case or cohort studies was conducted. Prevalence rate projection informed estimates of impacted regions and populations. Among 1710 papers identified, 258 met the inclusion criteria, of which 173 responded to at least one of nine Bradford Hill criteria among 83 literature-identified ALS environmental factors. Environmental determinants of ALS in order of decreasing significance were ß-N-methylamino-L-alanine (BMAA), formaldehyde, selenium, and heavy metals including manganese, mercury, zinc, and copper. Murine animal models were the most common methodology for exploring environmental factors. Another line of investigation of 62 population exposure studies implicated the same group of environmental agents (mean odds ratios): BMAA (2.32), formaldehyde (1.54), heavy metals (2.99), manganese (3.85), mercury (2.74), and zinc (2.78). An age-adjusted incidence model estimated current total ALS cases globally at ~85,000 people compared to only ~1600 cases projected from the reported ALS incidence in the literature. Modeling with the prevalence microscope equation forecasted an increase in U.S. ALS cases from 16,707 confirmed in 2015 to ~22,650 projected for 2040. Two orthogonal methods employed implicate BMAA, formaldehyde, manganese, mercury, and zinc as environmental factors with strong ALS associations. ALS cases likely are significantly underreported globally, and high vulnerability exists in regions with large aging populations. Recent studies on other diseases with environmental determinants suggest the need to consider additional potential triggers and mechanisms, including exposures to microbial agents and epigenetic modifications.