A year-long study of the occurrence and risk of over 140 contaminants of emerging concern in wastewater influent, effluent and receiving waters in the Republic of Ireland

Despite being a developed country in the European Union (EU), knowledge of the nature and extent of contamination of water bodies with contaminants of emerging concern (CECs) in Ireland is limited. In this study, >140 CECs including pharmaceuticals, pesticides and personal care products were monitored in monthly samples of wastewater treatment plant (WWTP) influent, effluent and receiving surface waters at both an urban and a rural location (72 samples in total) in Ireland over a 12-month period in 2018-2019. In total, 58 CECs were detected, including several EU Water Framework Directive Watch List compounds. Of all classes, the highest concentrations were measured for pharmaceuticals across all media, i.e., propranolol in surface waters (134 ng·L-1), hydrochlorothiazide in effluent (1067 ng·L-1) and venlafaxine in influent wastewater (8273 ng·L-1). Overall, high wastewater treatment removal was observed and a further reduction in CEC occurrence and concentration was measured via dilution in the receiving river environment. Lastly, an environmental risk assessment (ERA) was performed using risk quotients (RQ), which revealed that in surface waters, total RQ for all CECs was an order of magnitude lower than in effluents. The majority of CECs in surface waters posed a lower risk except E2 and EE2 which presented a medium risk (RQs of 3.5 and 1.1, respectively) in the rural area. This work represents the most comprehensive CEC monitoring dataset to date for Ireland which allowed for an ERA prioritisation to be performed for the first time

A One-Health environmental risk assessment of contaminants of emerging concern in London’s waterways throughout the SARS-CoV-2 pandemic

The SARS-CoV-2 pandemic had huge impacts on global urban populations, activity and health, yet little is known about attendant consequences for urban river ecosystems. We detected significant changes in occurrence and risks from contaminants of emerging concern (CECs) in waterways across Greater London (UK) during the pandemic. We were able to rapidly identify and monitor large numbers of CECs in n=390 samples across 2019–2021 using novel direct-injection liquid chromatography-mass spectrometry methods for scalable targeted analysis, suspect screening and prioritisation of CEC risks. At total of 10,029 measured environmental concentrations (MECs) were obtained for 66 unique CECs. Pharmaceutical MECs decreased during lockdown in 2020 in the R. Thames (p≤0.001), but then increased significantly in 2021 (p ≤0.01). For the tributary rivers, the R. Lee, Beverley Brook, R. Wandle and R. Hogsmill were the most impacted primarily via wastewater treatment plant effluent and combined sewer overflows. For the R. Hosgmill in particular, pharmaceutical MEC trends were generally correlated with NHS prescription statistics, likely reflecting limited wastewater dilution. Suspect screening of ∼1,200 compounds tentatively identified 25 additional CECs at the five impacted sites, including metabolites such as O-desmethylvenlafaxine, an EU Watch List compound. Lastly, risk quotients (RQs) ≥0.1 were calculated for 21 compounds across the whole Greater London freshwater catchment, of which 7 were of medium risk (RQ ≥1.0) and three were in the high-risk category (RQ ≥10), including imidacloprid (RQ=19.6), azithromycin (15.7) and diclofenac (10.5). This is the largest spatiotemporal dataset of its kind for any major capital city globally and the first for Greater London, representing ∼16 % of the population of England, and delivering a foundational One Health case study in the third largest city in Europe across a global pandemic

Multiscale Drivers of Water Chemistry of Boreal Lakes and Streams

The variability in surface water chemistry within and between aquatic ecosystems is regulated by many factors operating at several spatial and temporal scales. The importance of geographic, regional-, and local-scale factors as drivers of the natural variability of three water chemistry variables representing buffering capacity and the importance of weathering (acid neutralizing capacity, ANC), nutrient concentration (total phosphorus, TP), and importance of allochthonous inputs (total organic carbon, TOC) were studied in boreal streams and lakes using a method of variance decomposition. Partial redundancy analysis (pRDA) of ANC, TP, and TOC and 38 environmental variables in 361 lakes and 390 streams showed the importance of the interaction between geographic position and regional-scale variables. Geographic position and regional-scale factors combined explained 15.3% (streams) and 10.6% (lakes) of the variation in ANC, TP, and TOC. The unique variance explained by geographic, regional, and local-scale variables alone was <10%. The largest amount of variance was explained by the pure effect of regional-scale variables (9.9% for streams and 7.8% for lakes), followed by local-scale variables (2.9% and 5.8%) and geographic position (1.8% and 3.7%). The combined effect of geographic position, regional-, and local-scale variables accounted for between 30.3% (lakes) and 39.9% (streams) of the variance in surface water chemistry. These findings lend support to the conjecture that lakes and streams are intimately linked to their catchments and have important implications regarding conservation and restoration (management) endeavors

The material soul: Strategies for naturalising the soul in an early modern epicurean context

We usually portray the early modern period as one characterised by the ‘birth of subjectivity’ with Luther and Descartes as two alternate representatives of this radical break with the past, each ushering in the new era in which ‘I’ am the locus of judgements about the world. A sub-narrative called ‘the mind-body problem’ recounts how Cartesian dualism, responding to the new promise of a mechanistic science of nature, “split off” the world of the soul/mind/self from the world of extended, physical substance—a split which has preoccupied the philosophy of mind up until the present day. We would like to call attention to a different constellation of texts—neither a robust ‘tradition’ nor an isolated ‘episode’, somewhere in between—which have in common their indebtedness to, and promotion of an embodied, Epicurean approach to the soul. These texts follow the evocative hint given in Lucretius’ De rerum natura that ‘the soul is to the body as scent is to incense’ (in an anonymous early modern French version). They neither assert the autonomy of the soul, nor the dualism of body and soul, nor again a sheer physicalism in which ‘intentional’ properties are reduced to the basic properties of matter. Rather, to borrow the title of one of these treatises (L’Âme Matérielle), they seek to articulate the concept of a material soul. We reconstruct the intellectual development of a corporeal, mortal and ultimately material soul, in between medicine, natural philosophy and metaphysics, including discussions of Malebranche and Willis, but focusing primarily on texts including the 1675 Discours anatomiques by the Epicurean physician Guillaume Lamy; the anonymous manuscript from circa 1725 entitled L’Âme Matérielle, which is essentially a compendium of texts from the later seventeenth century (Malebranche, Bayle) along with excerpts from Lucretius; and materialist writings such Julien Offray de La Mettrie’s L’Homme-Machine (1748), in order to articulate this concept of a ‘material soul’ with its implications for notions of embodiment, materialism and selfhood

Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP

The Near-Infrared Spectrograph (NIRSpec) on the James Webb Space Telescope: I. Overview of the instrument and its capabilities

We provide an overview of the design and capabilities of the near-infrared spectrograph (NIRSpec) onboard the James Webb Space Telescope. NIRSpec is designed to be capable of carrying out low-resolution ($R\!=30\!-330$) prism spectroscopy over the wavelength range $0.6-5.3\!~\mu$m and higher resolution ($R\!=500\!-1340$ or $R\!=1320\!-3600$) grating spectroscopy over $0.7-5.2\!~\mu$m, both in single-object mode employing any one of five fixed slits, or a 3.1$\times$3.2 arcsec$^2$ integral field unit, or in multiobject mode employing a novel programmable micro-shutter device covering a 3.6$\times$3.4~arcmin$^2$ field of view. The all-reflective optical chain of NIRSpec and the performance of its different components are described, and some of the trade-offs made in designing the instrument are touched upon. The faint-end spectrophotometric sensitivity expected of NIRSpec, as well as its dependency on the energetic particle environment that its two detector arrays are likely to be subjected to in orbit are also discussed

The Near-Infrared Spectrograph (NIRSpec) on the James Webb Space Telescope: I. Overview of the instrument and its capabilities

We provide an overview of the design and capabilities of the near-infrared spectrograph (NIRSpec) onboard the James Webb Space Telescope. NIRSpec is designed to be capable of carrying out low-resolution ($R\!=30\!-330$) prism spectroscopy over the wavelength range $0.6-5.3\!~\mu$m and higher resolution ($R\!=500\!-1340$ or $R\!=1320\!-3600$) grating spectroscopy over $0.7-5.2\!~\mu$m, both in single-object mode employing any one of five fixed slits, or a 3.1$\times$3.2 arcsec$^2$ integral field unit, or in multiobject mode employing a novel programmable micro-shutter device covering a 3.6$\times$3.4~arcmin$^2$ field of view. The all-reflective optical chain of NIRSpec and the performance of its different components are described, and some of the trade-offs made in designing the instrument are touched upon. The faint-end spectrophotometric sensitivity expected of NIRSpec, as well as its dependency on the energetic particle environment that its two detector arrays are likely to be subjected to in orbit are also discussed

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362