Wastewater and public health: the potential of wastewater surveillance for monitoring COVID-19

Pathogenic viruses represent one of the greatest threats to human well-being. As evidenced by the COVID-19 global pandemic, however, halting the spread of highly contagious diseases is notoriously difficult. Successful control strategies therefore have to rely on effective surveillance. Here, we describe how monitoring wastewater from urban areas can be used to detect the arrival and subsequent decline of pathogens, such as SARS-CoV-2. As the amount of virus shed in faeces and urine varies largely from person to person, it is very difficult to quantitatively determine the number of people who are infected in the population. More research on the surveillance of viruses in wastewater using accurate and validated methods, as well as subsequent risk analysis and modelling is paramount in understanding the dynamics of viral outbreaks

Concentration and quantification of SARS-CoV-2 RNA in wastewater using polyethylene glycol-based concentration and qRT-PCR

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Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). A review of 48 independent studies revealed that severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 102–105 gc/ml) and feces (ca. 102–107 gc/ml) is much lower than in nasopharyngeal fluids (ca. 105–1011 gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the gut and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears much lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that tens of million cases of COVID-19 have occurred globally, but exposure to feces or wastewater has never been implicated as a transmission vector

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Three numerical approaches to find mutually unbiased bases using Bell inequalities

International audienceMutually unbiased bases correspond to highly useful pairs of measurements in quantum information theory. In the smallest composite dimension, six, it is known that between three and seven mutually unbiased bases exist, with a decades-old conjecture, known as Zauner's conjecture, stating that there exist at most three. Here we tackle Zauner's conjecture numerically through the construction of Bell inequalities for every pair of integers n, d ≥ 2 that can be maximally violated in dimension d if and only if n MUBs exist in that dimension. Hence we turn Zauner's conjecture into an optimisation problem, which we address by means of three numerical methods: seesaw optimisation, non-linear semidefinite programming and Monte Carlo techniques. All three methods correctly identify the known cases in low dimensions and all suggest that there do not exist four mutually unbiased bases in dimension six, with all finding the same bases that numerically optimise the corresponding Bell inequality. Moreover, these numerical optimisers appear to coincide with the "four most distant bases" in dimension six, found through numerically optimising a distance measure in [P. Raynal, X. Lü, B.-G. Englert, Phys. Rev. A, 83 062303 (2011)]. Finally, the Monte Carlo results suggest that at most three MUBs exist in dimension ten

Alkalinity and elemental cycles in present and past ocean: Insight from geochemical modeling and alkali and alkaline earth metal isotopes

This chapter provides an overview of near-surface geochemical processes operating on Earth, with special emphasis placed on (i) marine weathering such as alteration and dissolution of silicates, carbonates and terrigenous riverine particles in the ocean, complemented by (ii) reverse weathering reactions leading to marine authigenic clay formation, and the impact of these phenomena on ocean alkalinity budget and the chemical and isotope composition of seawater. Model simulations of the above processes provide estimates of the global marine fluxes of major cations (Na+, K+, Mg2+, Ca2+) and alkalinity in the ocean induced by silicate weathering and dissolution of terrigenous material in seawater. Additional constraints on silicate vs. carbonate weathering, oceanic/coastal CaCO3 cycling, and paleo-seawater reconstructions are provided via the stable and radiogenic isotope systems of alkali and alkaline earth metals (Li, K, Mg, Ca, and Sr isotopes) that are discussed within the context of marine and reverse weathering in the present and past ocean. Key points • Impact of weathering processes on marine elemental cycles and the ocean alkalinity budget. • Alteration and dissolution of silicate minerals and riverine particles in the ocean quantified via thermodynamic equilibrium (PHREEQC) calculations, in seawater and top sediment settings. • Estimates of global ocean fluxes of dissolved cations (Na+ , K+ , Mg 2+ , Ca2+ ) and alkalinity induced by alteration and dissolution of terrigenous material in seawater and marine sediments. • Principles and mechanisms of isotope variability in nature (mass-dependent and radiogenic isotope effects) observed for alkali and alkaline earth metals. • Silicate vs. carbonate weathering and coastal carbon/carbonate cycling constrained via stable and radiogenic Ca and Sr, and Li isotopes. • Oceanic processes, marine carbonate chemistry (alkalinization vs. acidification), and paleo-seawater reconstructions constrained via d44 Ca, d88 Sr, d26 Mg proxies and numerical (MATLAB) modeling. • Emerging metal isotope proxies (d41 K) for silicate and reverse weathering in the ocean

Impact of salinity and carbonate saturation on stable Sr isotopes (δ88/86Sr) in a lagoon-estuarine system

Local carbonate cycling in lagoon-estuarine systems, involving processes such as inorganic and biogenic carbonate precipitation/dissolution, represents an important but poorly constrained component of the coastal carbon budget. This study investigates the sensitivity of stable Sr isotope tracer (δ88/86Sr) with respect to carbonate saturation and salinity of local waters in the Coorong, Lower Lakes and Murray Mouth (CLLMM) estuary in South Australia. The CLLMM has an extensive range of salinity from fresh to hypersaline (from ∼0 to over 100 PSU), with corresponding variations in water chemistry and major ion composition that in turn controls mineral saturation states, and thus CaCO3 precipitation/dissolution in local waters. Here we use the novel δ88/86Sr tracer in tandem with the more established radiogenic Sr isotope ratio (87Sr/86Sr), where the latter is a robust proxy for Sr sources and thus water provenance. We also produced a geochemical (PHREEQC) model of calcium carbonate (CaCO3) saturation changes across this unique lagoon-estuarine system. The results indicate a systematically increasing trend of δ88/86Sr (from ∼0.25‰ to ∼0.45‰) with increasing salinity and CaCO3 (aragonite, calcite) saturation indices of the coastal waters, which in turn suggest an overall control of carbonate dissolution/precipitation processes on the stable Sr isotope composition in the CLLMM system. This was further corroborated by Ca isotope data (δ44/40Ca) published previously on the same samples from the Coorong, as well as a quantitative simulation of local carbonate removal in the lagoon based on Rayleigh modelling and Sr isotope data. Overall, our results confirm that a coupled Sr isotope approach (combining 87Sr/86Sr and δ88/86Sr) can be used to constrain not only the main water sources (continental versus marine Sr) but also local CaCO3 dissolution/precipitation processes, and thus inorganic carbon and coastal carbonate cycling in the CLLMM system. Finally, this coupled δ88/86Sr and 87Sr/86Sr approach can be potentially applied to fossil carbonate archives to reconstruct paleo-hydrology and salinity changes in the CLLMM and/or other carbonate-producing coastal systems

Calcium and strontium isotope systematics in the lagoon-estuarine environments of South Australia: Implications for water source mixing, carbonate fluxes and fish migration

This study uses Ca and Sr isotopes (δ44/40Ca and87Sr/86Sr), coupled with elemental ratios, to better understand the water source apportionment and carbonate output in the Coorong, Lower Lakes and Murray Mouth Estuary, which represents the terminus of Australia\u27s longest river system. The geochemistry of waters in the Coorong (i.e., North and South Lagoon) can be explained by mixing of three major components, including: (i) the Southern Ocean seawater, (ii) local freshwaters, and (iii) hypersaline lagoon waters, the latter significantly modified by ongoing evaporation and carbonate formation. The Sr and Ca isotope composition of the North Lagoon is indistinguishable from that of the Southern Ocean (i.e., normal salinity of ∼35 PSU), with the exception of transient freshwater input events that can temporarily lower the salinity to brackish levels. Interestingly, our results from the hypersaline South Lagoon (salinity up to ∼120 PSU) confirmed that the latter is highly evaporated brackish water (with ≥40% contribution from continent-derived waters), which has been additionally modified by in-situ carbonate precipitation. Importantly, our Ca isotope and elemental constraints showed that about 15-17% of the dissolved Ca2+in the South Lagoon has been removed as CaCO3(primarily as aragonite). This in turn has implications for the local carbonate cycle and blue carbon studies, suggesting that the South Lagoon acts as a net sink for the dissolved inorganic carbon (DIC). Ca isotope data from the otoliths of smallmouth hardyhead fish species (Atherinosoma microstoma) collected in the Coorong indicate that δ44/40Ca is primarily controlled by biological processes (i.e., kinetic isotope fractionation effects related to growth rate), rather than by the Ca isotope composition of local lagoon waters. As to87Sr/86Sr in otoliths, the latter confirmed the importance of continent-derived water sources in the Coorong, recorded over the life span of the fish. Overall, with suitable fossil carbonate archives (e.g., bivalve shells, foraminifera), our calibration of87Sr/86Sr and δ44/40Ca in the modern hydrological system, with respect to a large salinity gradient (ranging from fresh to hypersaline, i.e., 0 to ∼120 PSU), implies potential future applications of these isotope tracers in carbonate-producing coastal systems, which include (i) tracing and apportioning different water sources, (ii) quantifying local carbonate outputs, and (iii) reconstructing paleo-salinity changes