Isotope tracing of nitrate : lessons from Malta

Average concentrations of nitrate in Malta’s groundwaters are probably the highest among EU member states. This compromises the quality of an important resource -almost 60% of Malta’s water supply being provided by groundwater. An 15N/14N + 18O/16O isotope study was undertaken as a core part of wide-ranging investigations into the potential sources of the nitrate pollution, its likely future trends, and possible ameliorative actions. The dual isotope (15N/14N + 18O/16O) approach was important for identifying waters affected by denitrification. Excluding these, groundwater from three physically and hydrologically distinct aquifers, with a very wide range in nitrate concentrations (24 to 410 mg NO3 L-1), had remarkably similar isotope compositions: 90% of samples lying within d15N ≈ +8 to +12‰, and d18O ≈ +3 to +6‰. The d18O values are entirely consistent with those expected for microbial nitrification in the presence of surface or groundwaters, and together with 15N values rule out nitrate derivation directly from fertilizers or sewage. In other studies the relatively high d15N values for the waters would probably have been interpreted as indicative of nitrate derived from manure. In Malta, however, cultivated soils have high d15N values, ≈ +6 to +11‰, very similar to the values for nitrate in the groundwater, and argue for a soil-derived source. The implications of a soil-source of such high nitrate levels are discussed, and the study emphasised the importance of characterising the compositions of soils in addition to other sources – a factor often neglected in isotope studies of nitrate

An exploratory study of the impact of COVID-19 vaccine spontaneous reporting on masking signal detection in EudraVigilance

Introduction: During the signal detection process, statistical methods are used to identify drug-event combinations (DECs) which are disproportionately reported when compared with other drugs and events in the entire database. We hypothesise that the high volume of COVID-19 vaccine adverse drug reaction (ADR) reports transmitted to EudraVigilance may have affected the performance of disproportionality statistics used in routine signal detection, potentially resulting in signals either being masked, or false associations being flagged as potential signals.ObjectiveOur aim was to study the impact of COVID-19 vaccine spontaneous reporting on statistical signal detection in EudraVigilance.MethodsWe recalculated the reporting odds ratio (ROR) for signals that were previously discussed at the level of the Pharmacovigilance Risk Assessment Committee, or signals that were retrieved from EudraVigilance, by omitting COVID-19 vaccine reports from the standard ROR calculation and then comparing the lower confidence interval (LCI) of the recalculated ROR to the LCI of the actual ROR in EudraVigilance.ResultsIn total, 52 signals for 38 active substances were reviewed. For 35 signals, the LCI of the recalculated ROR value was lower than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had a positive effect on the strength of the signal) while for 15 signals the LCI of the recalculated ROR value was higher than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had an attenuating effect on the strength of the signal). For two signals, no change in the ROR was observed. In our analysis, six significant results were found. Five DECs were found to be masked: bleomycin and immune thrombocytopenia (actual ROR LCI = 0.94, recalculated ROR LCI = 1.02), vortioxetine and heavy menstrual bleeding (actual ROR LCI = 0.3, recalculated ROR LCI = 1.06), caplacizumab and heavy menstrual bleeding (actual ROR LCI = 0.98, recalculated ROR LCI = 3.47), ziprasidone and amenorrhoea (actual ROR LCI = 0.84, recalculated ROR LCI = 1.67), and azacitidine and pericarditis (actual ROR LCI = 0.81, recalculated ROR LCI = 2.01). For the DEC of adalimumab and immune reconstitution inflammatory syndrome, the LCI of the actual ROR value was 1.14 and removing COVID-19 vaccine reporting resulted in an LCI of the recalculated ROR value of 0.94 (below threshold).ConclusionsWe demonstrated five cases of masking and one case of false-positive association due to the influence of COVID-19 vaccine spontaneous reporting on the ROR. This suggests that the high number of adverse drug reaction reports for COVID-19 vaccines in EudraVigilance has the potential to affect routine statistical signal detection activities. The impact of COVID-19 vaccine ADR reports on current signal detection practices requires further evaluation and solutions to tackle masking issues in EudraVigilance may need to be developed

Groundwater residence time and movement in the Maltese islands : a geochemical approach

The Maltese Islands are composed of two limestone aquifers, the Upper and Lower Coralline Limestone separated by an aquitard, the ‘Blue Clay’. The Lower Coralline Limestone is overlain in part by the poorly permeable Globigerina Limestone. The upper perched aquifers are discontinuous and have very limited saturated thickness and a short water level response time to rainfall. Frequent detections of coliforms suggest a rapid route to groundwater. However, the unsaturated zone has a considerable thickness in places and the primary porosity of the Upper Coralline Limestone is high, so there is likely to be older recharge by slow matrix flow as well as rapid recharge from fractures. Measurement of SF6 from a pumping station in a deep part of one of the perched aquifers indicated a mean saturated zone age of about 15 years. The Main Sea Level aquifers (MSL) on both Malta and Gozo have a large unsaturated thickness as water levels are close to sea level. On Malta, parts of the aquifer are capped by the perched aquifers and more extensively by the Globigerina Limestone. The limited detection of coliform bacteria suggests only some rapid recharge from the surface via fractures or karst features. Transmissivity is low and tritium and CFC/SF6 data indicate that saturated zone travel times are in the range 15-40 years. On Gozo the aquifer is similar but is more-extensively capped by impermeable Blue Clay. CFC data show the saturated zone travel time is from 25 years to possibly more than 60 years. Groundwater age is clearly related to the extent of low-permeability cover. The δ13C signature of groundwater is related to the geochemical processes which occur along the flowpath and is consistent with residence time ages in the sequence; perched aquifers<Malta MSL<Gozo MSL. The 18O and 2H enriched isotopic signature of post 1983 desalinated water can be seen in more-modern groundwater, particularly the urbanised areas of the perched and Malta MSL aquifers. In all aquifers, movement of solutes from the surface travelling slowly through the matrix provide a long term source of groundwater contaminants such as nitrate

Longitudinal Assessment of the Dynamics of Escherichia coli, Total Coliforms, Enterococcus spp., and Aeromonas spp. in Alternative Irrigation Water Sources: a CONSERVE Study.

As climate change continues to stress freshwater resources, we have a pressing need to identify alternative (nontraditional) sources of microbially safe water for irrigation of fresh produce. This study is part of the center CONSERVE, which aims to facilitate the adoption of adequate agricultural water sources. A 26-month longitudinal study was conducted at 11 sites to assess the prevalence of bacteria indicating water quality, fecal contamination, and crop contamination risk (Escherichia coli, total coliforms [TC], Enterococcus, and Aeromonas). Sites included nontidal freshwater rivers/creeks (NF), a tidal brackish river (TB), irrigation ponds (PW), and reclaimed water sites (RW). Water samples were filtered for bacterial quantification. E. coli, TC, enterococci (∼86%, 98%, and 90% positive, respectively; n = 333), and Aeromonas (∼98% positive; n = 133) were widespread in water samples tested. Highest E. coli counts were in rivers, TC counts in TB, and enterococci in rivers and ponds (P &lt; 0.001 in all cases) compared to other water types. Aeromonas counts were consistent across sites. Seasonal dynamics were detected in NF and PW samples only. E. coli counts were higher in the vegetable crop-growing (May-October) than nongrowing (November-April) season in all water types (P &lt; 0.05). Only one RW and both PW sites met the U.S. Food Safety Modernization Act water standards. However, implementation of recommended mitigation measures of allowing time for microbial die-off between irrigation and harvest would bring all other sites into compliance within 2 days. This study provides comprehensive microbial data on alternative irrigation water and serves as an important resource for food safety planning and policy setting.IMPORTANCE Increasing demands for fresh fruit and vegetables, a variable climate affecting agricultural water availability, and microbial food safety goals are pressing the need to identify new, safe, alternative sources of irrigation water. Our study generated microbial data collected over a 2-year period from potential sources of irrigation (rivers, ponds, and reclaimed water sites). Pond water was found to comply with Food Safety Modernization Act (FSMA) microbial standards for irrigation of fruit and vegetables. Bacterial counts in reclaimed water, a resource that is not universally allowed on fresh produce in the United States, generally met microbial standards or needed minimal mitigation. We detected the most seasonality and the highest microbial loads in river water, which emerged as the water type that would require the most mitigation to be compliant with established FSMA standards. This data set represents one of the most comprehensive, longitudinal analyses of alternative irrigation water sources in the United States