Collecting water quality data across large lakes is often done under regulatory mandate; however, it is difficult to connect nutrient concentration observations to sources of those nutrients and to ...quantify this relationship. This difficulty arises from the spatial and temporal
separation between observations, the impact of hydrodynamic forces, and the
cost involved in discrete samples collected aboard vessels. These challenges are typified in Lake Erie, where binational agreements regulate riverine loads of total phosphorus (TP) to address the impacts from annual harmful algal blooms (HABs). While it is known that the Maumee River supplies 50 % of the nutrient load to Lake Erie, the details of how the Maumee River TP load changes Lake Erie TP concentration have not been demonstrated. We developed a hierarchical spatially referenced Bayesian state-space model with an adjacency matrix defined by surface currents. This was applied to a 2 km-by-2 km grid of nodes, to which observed lake and river TP concentrations were joined. The model generated posterior samples describing the unobserved nodes and observed nodes on unobserved days. We quantified the impact plume of the Maumee River by experimentally changing concentration data and tracking the change in in-lake predictions. Our impact plume represents the spatial and temporal variation of how river concentrations correlate with lake concentrations. We used the impact plume to scale the Maumee River spring TP load to an effective Maumee River TP spring load for each node in the lake. By assigning an effective load to each node, the relationship between load and concentration is consistent throughout our sampling locations. A linear model of annual lake node mean TP concentration and effective Maumee River load estimated that, in the absence of the Maumee River load, lake concentrations at the sampled nodes would be 23.1 µg L−1 (±1.75, 95 % CI, credible interval) and that for each 100 t of spring TP effective load delivered to Lake Erie, mean TP concentrations increase by 11 µg L−1 (±1, 95 % CI). Our proposed modeling technique allowed us to establish these quantitative connections between Maumee TP load and Lake Erie TP concentrations which otherwise would be masked by the movement of water through space and time.
Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods ...of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD −2.0; 95% CI −2.38, −1.61; p < 0.00001) and permanent (SMD −1.54; 95% CI −2.38, −1.61; p < 0.00001) focal models of ischaemia and improved neurological deficit (SMD −1.63; 95% CI −1.97, −1.29, p < 0.00001). In meta-regression, cycle length and number, dose and limb number did not interact with infarct volume, although country and physiological monitoring during anaesthesia did. In all studies, RIC was ineffective if the dose was <10 or ≥50 min. Median study quality was 7 (range 4–9/10); Egger’s test suggested publication bias (p < 0.001). RIC is most effective in experimental stroke using a dose between 10 and 45 min. Further studies using repeated dosing in animals with co-morbidities are warranted.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Within the global pharmaceutical and biotech industries, there is significant interest in identifying
in vitro screening systems that are more human-relevant—i.e., that offer greater utility in ...predicting subcellular and cellular physiological responses in humans
in vivo—and that thereby allow investigators to reduce the incidence of costly late-stage failures during pharmaceutical clinical trials, as well as to reduce the use of animals in drug testing. Currently incumbent
in vitro screening methods, such as culturing human hepatocytes in suspension, while useful, are limited by a lack of long term cellular function. In order to address this limitation, we have established an integrated, microfluidic,
in vitro platform that combines the patented HμREL
® microdevice with a hepatic coculture system. In the present report, we use this platform to study clearance and metabolite generation of a battery of molecular entities. The results show that the flow-based coculture system is capable of clearing, with improved resolution and predictive value, compounds with high, medium, and low clearance values. In addition, when coculture is coupled with flow, higher metabolite production rates are obtained than in static systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Water quality impacts to the Laurentian Great Lakes create bi-national issues that have been subject of investigation since the 1970s. However, distinguishing upgradient sources of nutrients, metals ...and legacy contaminants in rivers remains a challenge, as they are derived from multiple sources and flows typically vary throughout the region. These complications are especially pertinent in the Lake Huron to Lake Erie corridor and Detroit River. The Detroit River supplies 90% of the water to the western basin of Lake Erie (5300 m3/s) and is subject to a variety of co-occurring potential sources (e.g., agriculture, urbanization, and upgradient water bodies) of water quality indicators that limit source disaggregation. To find the source signal in the noise we used an integrative interpretation of dissolved chemical and isotopic parameters with sediment chemical, isotopic, and contaminant indicators. The approach combines archival data to distinguish point and non-point sources, and upgradient water bodies as sources of nutrients, metals and contaminants to the Detroit River and ultimately the western basin of Lake Erie. Persistent organic pollutants and metals cluster together as an urban group. Regional dissolved orthro-phosphate (PO4) in the water column also groups with urban point sources rather than agricultural sources. Urbanization as the primary source of PO4 in the Detroit River highlights the need for continued research on urban impacts and assessments of broader best management practices protecting Lake Erie.
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•Principal components & hierarchical clustering define sources of river analytes•Non-spatially derived source apportionment is powerful in noisy systems.•Dissolved phosphate groups with urban points source over agricultural non-point
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The US Food and Drug Administration (FDA) has publicly recognized the importance of improving drug development efficiency, deeming translational biomarkers a top priority. The use of imaging ...biomarkers has been associated with increased rates of drug approvals. An appropriate level of validation provides a pragmatic way to choose and implement these biomarkers. Standardizing imaging modality selection, data acquisition protocols, and image analysis (in ways that are agnostic to equipment and algorithms) have been key to imaging biomarker deployment. The best known examples come from studies done via precompetitive collaboration efforts, which enable input from multiple stakeholders and data sharing. Digital health technologies (DHTs) provide an opportunity to measure meaningful aspects of patient health, including patient function, for extended periods of time outside of the hospital walls, with objective, sensor‐based measures. We identified the areas where learnings from the imaging biomarker field can accelerate the adoption and widespread use of DHTs to develop novel treatments. As with imaging, technical validation parameters and performance acceptance thresholds need to be established. Approaches amenable to multiple hardware options and data processing algorithms can be enabled by sharing DHT data and by cross‐validating algorithms. Data standardization and creation of shared databases will be vital. Pre‐competitive consortia (public‐private partnerships and professional societies that bring together all stakeholders, including patient organizations, industry, academic experts, and regulators) will advance the regulatory maturity of DHTs in clinical trials.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Nitrification rates and ammonia-oxidizer functional gene abundance were measured in the water column of Lake Lacawac, Pennsylvania, USA, a freshwater lake on a nature sanctuary that allowed an ...investigation with minimal human impacts. Nitrification is a 2-step process consisting of ammonia oxidation followed by nitrite oxidation. Recent studies have shown that these 2 nitrification steps may be uncoupled and respond in different ways to environmental conditions. Additionally, the relative contribution of ammonia-oxidizing archea (AOA) vs ammonia-oxidizing bacteria (AOB) to nitrification rates varies widely across aquatic systems. To determine how nitrification rates are related to environmental parameters and the ammonia-oxidizing community in a nearly pristine environment, rates and gene abundance were measured over multiple seasons where in-situ environmental conditions varied. Rates of ammonia and nitrite oxidation were measured separately and summed to calculate total nitrification rates ranging from 1 to 568 nM/d. Ammonia oxidation rates generally outpaced nitrite oxidation rates, and rates of both ammonia and nitrite oxidation were higher at depth (10 m) compared with near-surface and mid water column. Ammonia oxidation, nitrite oxidation, and total nitrification rates were all strongly, positively correlated with in-situ NH4+ (Kendall’s τ > 0.35, p < 0.02). AOB ammonia monooxygenase (amoA) gene copy numbers were generally greater than AOA amoA. However, AOB gene copy numbers were not correlated with any ammonia oxidation or total nitrification rates, whereas AOA abundance was positively correlated with both ammonia oxidation and total nitrification rates (Kendall’s τ > 0.41, p < 0.01). A Bayesian generalized additive model, which accounted for sampling month, indicated that total nitrification rates were best explained by AOA and NH4+. Thus, substrate concentration and AOA likely play key roles in regulating rates of nitrification in this small, nearly pristine freshwater lake. These reported relationships between rates of ammonia and nitrite oxidation (and, thus, total nitrification), in-situ environmental parameters, and the ammonia-oxidizer community in a protected environment establish a reference for evaluating the impact of a changing environment on mesotrophic lake water quality.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Filter-feeders play an important role in regulating nutrient availability in coastal systems, with important implications for phytoplankton community composition, primary production, and food web ...structure. The role of filter-feeding bivalves in the nitrogen and phosphorus cycles is relatively well established, but their impact on coastal silicon (Si) cycling remains poorly understood. To help reduce this uncertainty, we quantified rates of Si recycling and the size of various Si pools at an oyster (
Crassostrea virginica
) farm. We found that oysters drive rapid recycling of dissolved Si (DSi) to the water column, primarily by altering rates of sediment Si flux. Sediments beneath oyster aquaculture recycled DSi to the water column at more than twice the rate (2476.06 µmol DSi m
-2
h
-1
) of nearby bare sediments (998.75 µmol DSi m
-2
h
-1
). Oysters consume DSi at a low rate (-0.06 µmol DSi ind.
-1
h
-1
), and, while we were unable to determine the fate of that Si, we hypothesize that at least some of it may be stored in the shell and tissue, which are both small Si pools (0.55 and 0.13% Si by mass respectively). Si held in oysters is removed from the system when oysters are harvested, but this removal is small compared to oyster-mediated enhancements in sediment Si recycling. In a broader context, coastal systems with larger oyster populations are likely to have a more rapid Si cycle, with more Si available to primary producers in the water column than those with no oysters.
Accessing the venous bloodstream to deliver fluids or obtain a blood sample is the most common clinical routine practiced in the U.S. Practitioners continue to rely on manual venipuncture techniques, ...but success rates are heavily dependent on clinician skill and patient physiology. In the U.S., failure rates can be as high as 50% in difficult patients, making venipuncture the leading cause of medical injury. To improve the rate of first-stick success, we have developed a portable autonomous venipuncture device that robotically servos a needle into a suitable vein under image guidance. The device operates in real time, combining near-infrared and ultrasound imaging, image analysis, and a 7-degree-of-freedom (DOF) robotic system to perform the venipuncture. The robot consists of a 3-DOF gantry to image the patient's peripheral forearm veins and a miniaturized 4-DOF serial arm to guide the cannula into the selected vein under closed-loop control. In this paper, we present the system architecture of the robot and evaluate the accuracy and precision through tracking, free-space positioning, and in vitro phantom cannulation experiments. The results demonstrate submillimeter accuracy throughout the operating workspace of the manipulator and a high rate of success when cannulating phantom veins in a skin-mimicking tissue model.
Geographic variability in abundance can be driven by multiple physical and biological factors operating at multiple scales. To understand the determinants of larval trematode prevalence within ...populations of the marine snail host Littorina littorea, we quantified many physical and biological variables at 28 New England interidal sites. A hierarchical, mixed-effects model identified the abundance of gulls (the final hosts and dispersive agents of infective trematode stages) and snail size (a proxy for time of exposure) as the primary factors associated with trematode prevalence. The predominant influence of these variables coupled with routinely low infection rates (21 of the 28 populations exhibited prevalence <12%) suggest broad-scale recruitment limitation of trematodes. Although infection rates were spatially variable, formal analyses detected no regional spatial gradients in either trematode prevalence or independent environmental variables. Trematode prevalence appears to be predominantly determined by local site characteristics favoring high gull abundance.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
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