The objectives of the present investigation were to determine past trends in sediment contamination and possibly predict future trends. Multiple vintages of surficial sediment metal data, from a ...quasi-decadal ‘Status and Trends’ programme, were used to provide large-scale spatial information on current status and temporal change. This information was augmented by sediment cores, specifically located to verify surface sediment data and to determine trends at major points of stormwater discharge. The data obtained indicate that surficial sediment metal concentrations have declined, since about the early 1990s, in extensive parts of the upper and central estuaries and have increased slightly in the lower estuary, due mainly to a down-estuary shift in industry and urbanisation. Declining surficial sediment metal concentrations is due to a movement of industry out of the catchment, especially from foreshore areas and the introduction of regulation, which prevent pollutants being discharged directly to the estuary. The major present-day source of metals is stormwater, with minor inputs from the main estuary channel into embayments and runoff from previously contaminated mainland sites. Modelled relaxation rates are optimistic as high metal concentrations in stormwater will slow predicted rates. Stormwater remediation should be the main managerial focus for this estuary. Multiple vintages of surficial sediment metal data covering the past 30years, supplemented by sedimentary core data, have allowed past and future contamination trends to be determined. This type of science-based information provides an important tool for strategic management of this iconic waterway.
•Multiple vintages of surficial sediment metal data provide past and future contamination trends.•Sedimentary metal concentrations are declining in the upper and central in Sydney estuaries.•Declining sediment metal levels due to reduction of industry and introduction of regulation•Major present-day source of sedimentary metals in Sydney estuary is stormwater.•Modelled relaxation rates are optimistic due to high metal stormwater concentrations.
Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and ...Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk.
The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided.
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•Ten global harbours were assessed for anthropogenic change (AC) and ecological risk (ER)•AC was high for Derwent River, Santander and Sydney estuaries•AC was moderate for Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin.•Derwent River sediment was rated at high ER, Sydney and Santander estuaries with moderate risk.•An improved technical framework for sediment quality assessment is provided.
The environmental status of three Intermittently Closed and Open Lakes and Lagoons (ICOLLs) (Manly, Curl Curl and Dee Why Lagoons) in northern Sydney (Australia) were assessed using sedimentary ...metals. Results identified the highest sedimentary metal enrichment in the Australian central east coast estuaries, with only a moderate ecological risk. A comparison with surficial sediment concentrations from 1996 to 2008 indicated declining metal concentrations, which is largely supported by subsurface metals data. Extensive low-lying areas of the catchments were historically reclaimed by infilling wetlands, which may have resulted in contaminated groundwater influx to the lagoons. An analysis of the sedimentary metals mix in lagoons surrounded by extensive infilling and estuaries with minor reclamation were statistically distinct. ICOLLs are environmentally sensitive due to large catchment/estuary ratios and restricted access to the ocean. A full set of baseline data is provided to support future monitoring of anthropogenic impacts on the system.
•Highest sedimentary metal concentrations in Australian central east coast estuaries•Extensive low-lying areas of catchments reclaimed by infilling of wetlands.•Sedimentary metals mix in urban- and groundwater-influenced lagoons statistically distinct.•Elevated metal levels possibly related to groundwater influx.•Metal enrichment is high and ecological risk moderate and metal levels maybe declining.
Clinically relevant members of the
/
species complex and Lomentospora prolificans are generally resistant against currently available systemic antifungal agents
, and infection due to these species ...is difficult to treat. We studied the
efficacy of a new fungicidal agent, olorofim (formerly F901318), against scedosporiosis and lomentosporiosis in neutropenic animals. Cyclophosphamide-immunosuppressed CD-1 mice infected by Scedosporium apiospermum, Pseudallescheria boydii (Scedosporium boydii), and Lomentospora prolificans were treated by intraperitoneal administration of olorofim (15 mg/kg of body weight every 8 h for 9 days). The efficacy of olorofim treatment was assessed by the survival rate at 10 days postinfection, levels of serum (1-3)-β-d-glucan (BG), histopathology, and fungal burdens of kidneys 3 days postinfection. Olorofim therapy significantly improved survival compared to that of the untreated controls; 80%, 100%, and 100% of treated mice survived infection by Scedosporium apiospermum, Pseudallescheria boydii, and Lomentospora prolificans, respectively, while less than 20% of the control mice (phosphate-buffered saline PBS treated) survived at 10 days postinfection. In the olorofim-treated neutropenic CD-1 mice infected with any of the three species, serum BG levels were significantly suppressed and fungal DNA detected in the target organs was significantly lower than in controls. Furthermore, histopathology of kidneys revealed no or only a few lesions with hyphal elements in the olorofim-treated mice, while numerous fungal hyphae were present in control mice. These results indicate olorofim to be a promising therapeutic agent for systemic scedosporiosis/lomentosporiosis, devastating emerging fungal infections that are difficult to treat with currently available antifungals.
•Sediments of Sydney estuary are highly enriched in Cu, Pb and Zn over extensive areas.•Cu oyster tissue concentrations exceed human consumption guidelines in all of the estuary.•Sediment quality ...guidelines are not predictive of oyster distribution, weight/size, tissue metals.•Oyster tissue metal concentrations vary greatly over temporal scales of years at a single locality.•Oysters cannot be used in Sydney estuary as a valid biomonitor due to overriding regulation.
The current study aimed to examine the relationship between metals in sediments and metal bioaccumulation in oyster tissue in a highly-modified estuary (Sydney estuary, Australia). While extensive metal contamination was observed in surficial sediments, suspended particulate matter and oyster tissue, a significant relationship between these media could not be established. No relationship was determined between sediment quality guidelines and oyster size or weight, nor with human consumption levels for metals in oyster tissue. Moreover, oyster tissue metal concentrations varied greatly at a single locality over temporal scales of years. Oyster tissue at all 19 study sites exceeded consumptions levels for Cu. Bioaccumulation of metals in oyster tissue is a useful dynamic indicator of anthropogenic influence within estuaries, however oysters cannot be used in Sydney estuary as a valid biomonitor due to overriding internal regulation (homoestasis) by the animal, or by external natural (sediment resuspension) and anthropogenic (sewer/stormwater discharges) pressures, or both.
A suite of 40 day UK Met Office Unified Model simulations over West Africa during summer 2006 are analyzed to investigate the causes of biases in the position of the rainbelt and to understand the ...role of convection in the regional water budget. The simulations include climate, global operational, and limited area runs (grid spacings from 1.5 to 40 km), including two 12 km runs, one with parameterized and one with explicit convection. The most significant errors in the water cycle terms occur in the simulations with parameterized convection, associated with the diurnal cycle and the location of the convection. Errors in the diurnal cycle increase the northward advection of moisture out of the Sahel toward the Sahara but decrease the advection of moisture into the Sahel from further south, which limits the availability of moisture for Sahelian rainfall. These biases occur within the first 24 h, showing that they originate from the representation of fast physical processes, specifically, the convection scheme. Once these rainfall regimes have been established, the terms of the water budgets act to reinforce the biases, effectively locking the rainbelt's latitude. One of the simulations with parameterized convection does, however, produce a better latitudinal distribution of rainfall because on the first day it is better able to trigger convection in the Sahel. Accurate representation of the diurnal cycle of convection and the ability to trigger convection in a high convective inhibition environment is key to capturing the water cycle of the region and will improve the representation of the West African Monsoon.
Key Points
Simulations are used to understand the West African water cycle
Errors in the convection feedback on the circulation and water cycle
Improving the diurnal cycle of convection will improve the monsoon
The emergence of azole resistance in
as well as an increasing frequency of multiresistant cryptic
spp. necessitates exploration of new classes of antifungals. Olorofim (formerly F901318) is a new ...fungicidal agent that prevents the growth of ascomycetous mold species via inhibition of
pyrimidine biosynthesis, a mechanism of action distinct from that of currently available antifungal drugs. We studied the
efficacy of olorofim intraperitoneal therapy (15 mg/kg of body weight every 8 h for 9 days) against infection with
,
, and
in both neutropenic CD-1 mice and mice with chronic granulomatous disease (CGD) (
mice). In the neutropenic mouse model, 80% to 88% of treated mice survived for 10 days, and in the CGD group, 63% to 88% of treated mice survived for 10 days, depending on the infecting species, while less than 10% of the mice in the control groups survived for 10 days. In the olorofim-treated groups, galactomannan levels were significantly suppressed, with lower organ fungal DNA burdens being seen for all three
spp. Histopathological slides revealed a limited number of inflammatory foci with or without detectable fungal elements in the kidneys of neutropenic CD-1 mice and in the lungs of CGD mice. Furthermore, the efficacy of olorofim was unrelated to the triazole MICs of the infecting
spp. These results show olorofim to be a promising therapeutic agent for invasive aspergillosis.
In common with many global models, the Met Office Unified Model (MetUM) climate simulations show large errors in Indian summer monsoon rainfall, with a wet bias over the equatorial Indian Ocean, a ...dry bias over India, and with too weak low‐level flow into India. The representation of moist convection is a dominant source of error in global models, where convection must be parametrized, with the errors growing quickly enough to affect both weather and climate simulations. Here we use the first multi‐week continental‐scale MetUM simulations over India, with grid spacings that allow explicit convection, to examine how convective parametrization contributes to model biases in the region.
Some biases are improved in the convection‐permitting simulations with more intense rainfall over India, a later peak in the diurnal cycle of convective rainfall over land, and a reduced positive rainfall bias over the Indian Ocean. The simulations suggest that the reduced rainfall over the Indian Ocean leads to an enhanced monsoon circulation and transport of moisture into India. Increases in latent heating associated with increased convection over land deepen the monsoon trough and enhance water vapour transport into the continent. In addition, delayed continental convection allows greater surface insolation and, along with the same rain falling in more intense bursts, generates a drier land surface. This increases land–sea temperature contrasts, and further enhances onshore flow. Changes in the low‐level water vapour advection into India are dominated by these changes to the flow, rather than to the moisture content in the flow. The results demonstrate the need to improve the representations of convection over both land and oceans to improve simulations of the monsoon.
•Saccostrea glomerata were exposed to 65Zn from dissolved and dietary sources.•Biokinetic model used to predict steady-state concentrations and various scenarios.•Dietary uptake is the predominant ...exposure route of Zn to Sydney rock oysters.•High dissolved Zn from stormwater may still contribute significant Zn to oysters.•Microalgae metal concentrations should be a key priority in future research.
Past studies disagree on the extent to which dissolved or dietary uptake contribute to metal bioaccumulation in the filter-feeding Sydney rock oyster (Saccostrea glomerata) in urbanized estuaries. Although most data support the assumption that fine sediments are a major route of metal uptake in these bivalves, some studies based in the Sydney estuary, Australia, have indicated a poor correlation. In the present study, seawater, sediment and microalgae were radiolabelled with 65Zn tracer and exposed to S. glomerata to assess the influence of dissolved and dietary sources to Zn bioaccumulation. Oysters in the dissolved-phase uptake experiment (5, 25 and 50μgL−1 65Zn for 4 d followed by 21 days of depuration) readily accumulated 65Zn for all three concentrations with an uptake rate constant of 0.160±0.006L dry weight g−1d−1. Oysters in the dietary assimilation experiment (1h pulse-feed of either 65Zn-radiolabelled suspended fine-fraction (<63μm) sediment or the microalgae Tetraselmis sp.) accumulated 65Zn, with assimilation efficiencies of 59 and 67% for fine sediment and microalgae, respectively. The efflux rates were low for the three experiments (0.1–0.5%d−1). A bioaccumulation kinetic model predicts that uptake of Zn will occur predominantly through the dietary ingestion of contaminated fine sediment particles and microalgae within the water column, with considerably greater metal bioaccumulation predicted if oysters ingested microalgae preferentially to sediments. However, the model predicts that for dissolved Zn concentrations greater than 40μgL−1, as observed during precipitation events, the uptake of the dissolved phase may contribute ≥50% to accumulation. Overall, the results of the present study suggest that all three sources may be important exposure routes to S. glomerata under different environmental conditions, but contributions from dietary exposure will often dominate.
Purpose
A well-defined and reliable patient-reported outcome instrument for COVID-19 is important for assessing symptom severity and supporting research studies. The InFLUenza Patient-Reported ...Outcome (FLU-PRO) instrument has been expanded to include loss of taste and smell in the FLU-PRO Plus, to comprehensively cover COVID-19 symptoms. Our studies were designed to evaluate and validate the FLU-PRO Plus among patients with COVID-19.
Methods
Two studies were conducted: (1) a qualitative, non-interventional, cross-sectional study of patients with COVID-19 involving hybrid concept elicitation and cognitive debriefing interviews; (2) a psychometric evaluation of the measurement properties of FLU-PRO Plus, using data from COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial—Intent to Care Early).
Results
In the qualitative interviews (
n
= 30), all 34 items of the FLU-PRO Plus were considered relevant to COVID-19, and participants determined the questionnaire was easily understood, well written, and comprehensive. In the psychometric evaluation (
n
= 845), the internal consistency reliability of FLU-PRO Plus total score was 0.94, ranging from 0.71 to 0.90 for domain scores. Reproducibility (Day 20–21) was 0.83 for total score, with domain scores of 0.67–0.89. Confirmatory factor analysis with the novel smell/taste domain demonstrated an acceptable fit to the data.
Conclusion
The content, reliability, validity, and responsiveness of the FLU-PRO Plus in the COVID-19 population were supported. Our results suggest that FLU-PRO Plus is a content- and psychometrically-valid, fit-for-purpose measure which is easily understood by patients. FLU-PRO Plus is a suitable PRO measure for evaluating symptoms of COVID-19 and treatment benefit directly from the patient perspective.
Trial Registration:
ClinicalTrials.Gov: NCT04545060, September 10, 2020; retrospectively registered.
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