Perfluoroalkyl Substances in Seabird Eggs from Canada's Pacific Coast: Temporal Trends (1973-2019) and Interspecific Patterns.

Whether perfluoroalkyl sulfonates (PFSAs) and perfluoroalkyl carboxylates (PFCAs) are responding to legislative restrictions and showing decreasing trends in top marine predators that range across the eastern North Pacific Ocean is unclear. Here, we examined longer-term temporal trends (1973-2019) of 4 PFSAs and 13 PFCAs, as well stable isotopes of δ13C and δ15N, in the eggs of 4 seabird species sampled along a nearshore-offshore gradient; double-crested cormorants (Nannopterum auritum), pelagic cormorants (Urile pelagicus), rhinoceros auklets (Cerorhinca monocerata), and Leach's storm-petrels (Hydrobates leucorhous) from the Pacific coast of British Columbia, Canada. PFOS was the most abundant PFSA (79-94%) detected in all eggs regardless of colony and year, with the highest concentrations, on average, measured in auklet eggs (mean = 58 ng g-1, range = 11-286 ng g-1 ww). Perfluoroundecanoic acid (PFUdA) and perfluorotridecanoic acid (PFTriDA) were the dominant long-chain PFCAs (≥30% combined). The majority of PFSAs (including PFOS) are statistically declining (p < 0.001) in the eggs of all 4 species with PFOS half-lives ranging from 2.6 to 7.8 years. Concentrations of long-chain PFCAs exhibited a trajectory comprised of linear increases and second-order declines, suggesting that the rate of uptake of PFCAs is slowing or leveling off. These trends are consistent with the voluntarily ceased production of PFSAs by 3M circa 2000-2003 and are among the first from the northeast Pacific to indicate a positive response to several regulations and restrictions on PFCAs from facility emissions and product content.

Developing Methods for Assessing Trophic Magnification of Perfluoroalkyl Substances within an Urban Terrestrial Avian Food Web.

We investigated the trophic magnification potential of perfluoroalkyl substances (PFAS) in a terrestrial food web by using a chemical activity-based approach, which involved normalizing concentrations of PFAS in biota to their relative biochemical composition in order to provide a thermodynamically accurate basis for comparing concentrations of PFAS in biota. Samples of hawk eggs, songbird tissues, and invertebrates were collected and analyzed for concentrations of 18 perfluoroalkyl acids (PFAAs) and for polar lipid, neutral lipid, total protein, albumin, and water content. Estimated mass fractions of PFCA C8-C11 and PFSA C4-C8 predominantly occurred in albumin within biota samples from the food web with smaller estimated fractions in polar lipids > structural proteins > neutral lipids and insignificant amounts in water. Estimated mass fractions of longer-chained PFAS (i.e., C12-C16) mainly occurred in polar lipids with smaller estimated fractions in albumin > structural proteins > neutral lipids > and water. Chemical activity-based TMFs indicated that PFNA, PFDA, PFUdA, PFDoA, PFTrDA, PFTeDA, PFOS, and PFDS biomagnified in the food web; PFOA, PFHxDA, and PFHxS did not appear to biomagnify; and PFBS biodiluted. Chemical activity-based TMFs for PFCA C8-C11 and PFSA C4-C8 were in good agreement with corresponding TMFs derived with concentrations normalized to only total protein in biota, suggesting that concentrations normalized to total protein may be appropriate proxies of chemical activity-based TMFs for PFAS, which predominantly partition to albumin. Similarly, TMFs derived with concentrations normalized to albumin may be suitable proxies of chemical activity-based TMFs for longer-chained PFAS, which predominantly partition to polar lipids.

Development of a Cell-Based SARS-CoV-2 Pseudovirus Neutralization Assay Using Imaging and Flow Cytometry Analysis.

COVID-19 is an ongoing, global pandemic caused by the novel, highly infectious SARS-CoV-2 virus. Efforts to mitigate the effects of SARS-CoV-2, such as mass vaccination and development of monoclonal therapeutics, require precise measurements of correlative, functional neutralizing antibodies that block virus infection. The development of rapid, safe, and easy-to-use neutralization assays is essential for faster diagnosis and treatment. Here, we developed a vesicular stomatitis virus (VSV)-based neutralization assay with two readout methods, imaging and flow cytometry, that were capable of quantifying varying degrees of neutralization in patient serum samples. We tested two different spike-pseudoviruses and conducted a time-course assay at multiple multiplicities of infection (MOIs) to optimize the assay workflow. The results of this assay correlate with the results of previously developed serology and surrogate neutralization assays. The two pseudovirus readout methods produced similar values of 50% neutralization titer values. Harvest-free in situ readouts for live-cell imaging and high-throughput analysis results for flow cytometry can provide unique capabilities for fast evaluation of neutralization, which is critical for the mitigation of future pandemics.

A Sensitive and Controlled Data-Independent Acquisition Method for Proteomic Analysis of Cell Therapies.

Mass spectrometry (MS)-based proteomic measurements are uniquely poised to impact the development of cell and gene therapies. With the adoption of rigorous instrumental performance qualifications (PQs), large-scale proteomics can move from a research to a manufacturing control tool. Especially suited, data-independent acquisition (DIA) approaches have distinctive qualities to extend multiattribute method (MAM) principles to characterize the proteome of cell therapies. Here, we describe the development of a DIA method for the sensitive identification and quantification of proteins on a Q-TOF instrument. Using the improved acquisition parameters, we defined a control strategy and highlighted some metrics to improve the reproducibility of SWATH acquisition-based proteomic measurements. Finally, we applied the method to analyze the proteome of Jurkat cells that here serves as a model for human T-cells. Raw and processed data were deposited in PRIDE (PXD029780).

A model for harmonizing flow cytometry in clinical trials.

Complexities in sample handling, instrument setup and data analysis are barriers to the effective use of flow cytometry to monitor immunological parameters in clinical trials. The novel use of a central laboratory may help mitigate these issues.

Stable Mercury Trends Support a Long-Term Diet Shift Away from Marine Foraging in Salish Sea Glaucous-Winged Gulls over the Last Century.

Marine predators are monitored as indicators of pollution, but such trends can be complicated by variation in diet. Glaucous-winged gulls (Larus glaucescens) have experienced a dietary shift over the past century, from mainly marine to including more terrestrial/freshwater inputs, with unknown impacts on mercury (Hg) trends. We examined 109-year trends in total mercury (THg) and methylmercury (MeHg) concentrations in glaucous-winged gull feathers (1887-1996) from the Salish Sea. Adult flank feathers had higher MeHg concentrations than immature feathers, and males head feathers had higher THg concentrations than females. Overall, we found no evidence of a trend in feather MeHg or THg concentrations over time from 1887 to 1996. In the same individuals, δ15N, δ13C, and δ34S declined over time in gull feathers. In comparison, egg THg concentrations declined from 1970 to 2019 in two species of cormorants, likely reflecting decreases in local Hg sources. We conclude that diet shifts through time may have countered increased Hg deposition from long-range transport in glaucous-winged gulls. The lack of Hg trends over time in glaucous-winged gull feathers provides additional support that these gulls have decreased the amount of marine forage fish in their diet.

Outcomes of Continuous Renal Replacement Therapy in a Community Health System.

OBJECTIVE: Continuous renal replacement therapy (CRRT) is commonly used in critically ill, hemodynamically unstable patients with acute kidney injury (AKI). This procedure is resource intensive with reported high in-hospital mortality. We evaluated mortality with CRRT in our healthcare system and markers associated with decreased survival. METHODS: A retrospective cohort study collected data on patients 18 years or older, without prior history of end stage kidney disease (ESKD), who received CRRT in the intensive care units at one of three hospitals in our health system in Columbus, OH from July 1, 2016 to July 1, 2019. Data included demographics, presenting diagnosis, comorbidities, laboratory markers, and patient disposition. In-hospital mortality rates and sequential organ failure assessment (SOFA) scores were calculated. We then compared information between two groups (patients who died during hospitalization and survivors) using univariate comparisons and multivariate logistic regression models. RESULTS: In-hospital mortality was 56.8% (95%CI: 53.4-60.1) among patients who received CRRT. Mean SOFA scores did not differ between survival and mortality groups. The odds for in-patient mortality were increased for patients age ≥60 (OR = 1.74, 95%CI: 1.23-2.44), first bilirubin >2 mg/dL (OR = 1.73, 95%CI: 1.12-2.69), first creatinine < 2 mg/dL (OR = 1.57, 95%CI: 1.04-2.37), first lactate > 2 mmol/L (OR = 2.08, 95%CI: 1.43-3.04). The odds for in-patient mortality were decreased for patients with cardiogenic shock (OR = .32, 95%CI: .17-.58) and hemorrhagic shock (OR = .29, 95%CI: .13-.63). CONCLUSIONS: We report in-hospital mortality rates of 56.8% with CRRT. Unlike prior studies, higher mean SOFA scores were not predictive of higher in-hospital mortality in patients utilizing CRRT.

Bioaccumulation and effects of selenium from surface coal mining in an aquatic songbird.

Open-pit mining operations are hailed for safe working conditions for miners as well as economically and logistically favourable outcomes for mining companies. However, ecological impacts of these operations may persist for decades. Expansions of open-pit coal mining in British Columbia of Western Canada are planned. Governmental regulation of background contaminants leached from these mines into nearby water systems were established to mitigate environmental impacts associated with these operations. We analyzed water, periphyton, invertebrate, and American dipper (Cinclus mexicanus) blood, egg, and feather samples for selenium and mercury exposure related to mining operations in the Elk Valley. We also quantified effects associated with exposure on clutch size and hatching success. Selenium concentrations in water, periphyton, and invertebrates were significantly higher downstream of mines compared to reference sites within and outside of the Elk River watershed. Selenium concentrations in water from exposed sites exceeded current regulatory levels established to protect wildlife by up to 20 times. Mercury concentrations were below toxic levels for birds in all media and did not factor into determination of selenium exposure or effects. Egg selenium concentrations were on average 0.9 times the regulatory threshold. Our stable isotope analyses showed that diets of nesting females included a negligible proportion of higher order consumers. We did not detect a significant effect of selenium on the rate of hatching success or clutch size of dippers nesting in exposed sites. We conclude that at the time of the investigation, selenium exposure was not impairing hatching of American dippers at the sampled locations.

Effects of diluted bitumen exposure on the survival, physiology, and behaviour of zebra finches (Taeniopygia guttata).

Diluted bitumen (dilbit) is an unconventional crude petroleum increasingly being extracted and transported to market by pipeline and tanker. Despite the transport of dilbit through terrestrial, aquatic, and coastal habitat important to diverse bird fauna, toxicity data are currently only available for fish and invertebrates. We used the zebra finch (Taeniopygia guttata) as a tractable, avian model system to investigate exposure effects of lightly weathered Cold Lake blend dilbit on survival, tissue residue, and a range of physiological and behavioural endpoints. Birds were exposed via oral gavage over 14-days with dosages of 0, 2, 4, 6, 8, 10, or 12 mL dilbit/kg bw/day. We identified an LD50 of 9.4 mL/kg/d dilbit, with complete mortality at 12 mL/kg/d. Mortality was associated with mass loss, external oiling, decreased pectoral and heart mass, and increased liver mass. Hepatic ethoxyresorufin-O-deethylase activity (EROD) was elevated in all dilbit-dosed birds compared with controls but there was limited evidence of sublethal effects of dilbit on physiological endpoints at doses < 10 mL/kg/d (hematocrit, hemoglobin, total antioxidants, and reactive oxygen metabolites). Dilbit exposure affected behavior, with more dilbit-treated birds foraging away from the feeder, more birds sleeping or idle at low dilbit doses, and fewer birds huddling together at high dilbit doses. Naphthalene, dibenzothiophene, and their alkylated congeners in particular (e.g. C2-napthalene and C2-dibenzothiophene) accumulated in the liver at greater concentrations in dilbit-treated birds compared to controls. Although directly comparable studies in the zebra finch are limited, our mortality data suggest that dilbit is more toxic than the well-studied MC252 conventional light crude oil with this exposure regime. A lack of overt sublethal effects at lower doses, but effects on body mass and composition, behaviour, high mortality, and elevated PAC residue at doses ≥ 10 mL/kg/d suggest a threshold effect.

Mercury toxicity risk and corticosterone levels across the breeding range of the Yellow-breasted Chat.

Mercury (Hg) is an environmental contaminant that can negatively impact human and wildlife health. For songbirds, Hg risk may be elevated near riparian habitats due to the transfer of methylmercury (MeHg) from aquatic to terrestrial food webs. We measured Hg levels in tail feathers sampled across the breeding range of the Yellow-breasted Chat (Icteria virens), a riparian songbird species of conservation concern. We assessed the risk of Hg toxicity based on published benchmarks. Simultaneously, we measured corticosterone, a hormone implicated in the stress response system, released via the hypothalamus-pituitary-adrenal axis. To better understand range-wide trends in Hg and corticosterone, we examined whether age, sex, subspecies, or range position were important predictors. Lastly, we examined whether Hg and corticosterone were correlated. Hg levels in chats were relatively low: 0.30 ± 0.02 µg/g dry weight. 148 out of 150 (98.6%) had Hg levels considered background, and 2 (1.6%) had levels considered low toxicity risk. Hg levels were similar between sexes and subspecies. Younger chats (<1 year) had higher Hg levels than older chats (>1 year). Hg levels were lowest in the northern and central portion of the eastern subspecies' range. Corticosterone concentrations in feathers averaged 3.68 ± 0.23 pg/mm. Corticosterone levels were similar between ages and sexes. Western chats had higher levels of corticosterone than eastern chats. Hg and corticosterone were not correlated, suggesting these low Hg burdens did not affect the activity of the hypothalamus-pituitary-adrenal axis. Altogether, the chat has low Hg toxicity risk across its breeding range, despite living in riparian habitats.

Practical application of microsphere samples for benchmarking a quantitative phase imaging system.

Quantitative phase imaging (QPI) provides an approach for monitoring the dry mass of individual cells by measuring the optical pathlength of visible light as it passes through cells. A distinct advantage of QPI is that the measurements result in optical path length quantities that are, in principle, instrument independent. Reference materials that induce a well-defined optical pathlength shift and are compatible with QPI imaging systems will be valuable in assuring the accuracy of such measurements on different instruments. In this study, we evaluate seven combinations of microspheres embedded in index refraction matching media as candidate reference materials for benchmarking the performance of a QPI system and as calibration standards for the optical pathlength measurement. Poly(methyl metharylate) microspheres and mineral oil were used to evaluate the range of illumination apertures, signal-to-noise ratios, and focus positions that allow an accurate quantitative optical pathlength measurement. The microsphere-based reference material can be used to verify settings on an instrument that are suitable for obtaining an accurate pathlength measurement from biological cells. The microsphere/media reference material is applied to QPI-based dry mass measurements of a population of HEK293 cells to benchmark and provide evidence that the QPI image data are accurate.

How measurement science can improve confidence in research results.

The current push for rigor and reproducibility is driven by a desire for confidence in research results. Here, we suggest a framework for a systematic process, based on consensus principles of measurement science, to guide researchers and reviewers in assessing, documenting, and mitigating the sources of uncertainty in a study. All study results have associated ambiguities that are not always clarified by simply establishing reproducibility. By explicitly considering sources of uncertainty, noting aspects of the experimental system that are difficult to characterize quantitatively, and proposing alternative interpretations, the researcher provides information that enhances comparability and reproducibility.

Biomarkers of ageing in New Zealand VLBW young adults and controls.

BACKGROUND: There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight < 1500 g) young adults may have less satisfactory measurements on some physiological parameters than term controls. We hypothesized that a summation score of physiological biomarkers that change with age would show VLBW adults to have a more advanced physiologic age than controls. METHODS: VLBW adults (229; 71% survivors of a national VLBW cohort) and term-born controls (100) were clinically assessed at 26-30 years. Ten measured physiological biomarkers were selected and measurements converted to z-scores using normative reference data. Between-group comparisons were tested for statistical significance for individual biomarker z-scores and a summation score. RESULTS: Nine of 10 biomarkers showed a mean z-score suggestive of older physiological age in the VLBW group versus controls. The observed mean difference in the summation score was highly significant (p < 0.001), representing a mean shift of 0.47 SD in the distribution of test scores for VLBW relative to controls. CONCLUSIONS: Utilizing a 10-biomarker score, VLBW young adults have a score indicative of poorer physiological functioning than term-born controls. Repeating these measures after an interval could provide insights into the comparative pace of ageing between VLBW and term-born adults. IMPACT: A summation score of 10 physiological biomarkers that are known to change with age shows that former very low birthweight adults have significantly poorer physiological functioning by the end of their third decade than term-born controls. This result adds to existing literature showing very preterm and very low birthweight young adults often have physiological and metabolic test results that are less satisfactory than those from term controls, despite mostly being in the normal range for age; for instance, higher systolic blood pressure. Although the pace of ageing in later years is yet to be established, the implications of this study are that preventative measures and lifestyle choices that impact on physiological ageing might have even greater importance for very preterm and very low birthweight graduates.

Establishing a reference focal plane using beads for trypan-blue-based viability measurements.

Trypan blue dye exclusion-based cell viability measurements are highly dependent upon image quality and consistency. In order to make measurements repeatable, one must be able to reliably capture images at a consistent focal plane, and with signal-to-noise ratio within appropriate limits to support proper execution of image analysis routines. Imaging chambers and imaging systems used for trypan blue analysis can be inconsistent or can drift over time, leading to a need to assure the acquisition of images prior to automated image analysis. Although cell-based autofocus techniques can be applied, the heterogeneity and complexity of the cell samples can make it difficult to assure the effectiveness, repeatability and accuracy of the routine for each measurement. Instead of auto-focusing on cells in our images, we add control beads to the images, and use them to repeatedly return to a reference focal plane. We use bead image features that have stable profiles across a wide range of focal values and exposure levels. We created a predictive model based on image quality features computed over reference datasets. Because the beads have little variation, we can determine the reference plane from bead image features computed over a single-shot image and can reproducibly return to that reference plane with each sample. The achieved accuracy (over 95%) is within the limits of the actuator repeatability. We demonstrate that a small number of beads (less than 3 beads per image) is needed to achieve this accuracy. We have also developed an open-source Graphical User Interface called Bead Benchmarking-Focus And Intensity Tool (BB-FAIT) to implement these methods for a semi-automated cell viability analyser.

It is critical for the manufacturing and release of living cell-based therapies to determine the viability, the ratio of living cells to the total number of cells (live and dead), in the therapy. Dead cells can be a safety concern for the patient, and dosing is often based on the number of living cells which are the active ingredient of the drug product. Currently, the most common approach to evaluating cell viability is based on the staining of cell samples with the trypan blue marker of cell membrane integrity: a loss in cell membrane integrity with cell death allows the dye into the cell, which can be seen using brightfield microscopy. To classify cells as live/dead, the brightness of the cells is evaluated and cells with bright centres are considered live, while those with dark centres are considered dead. Unfortunately, this approach of staining, imaging and classification is very sensitive to image acquisition settings, including image focus and brightness. This paper introduces a method to establish the required image quality for image viability analysis, providing a tool to return to image acquisition settings that will ensure image quality even when there is variability from sample to sample. In this method, polymeric beads are added to each cell sample prior to cell viability analysis. Using image processing, we extract key features from the beads in the image such as sharpness of the edges of the beads. The image features of the cells can vary significantly from sample to sample and under different cell conditions, but image features of beads have proved to be consistent across samples. We are thus able to collect reference datasets quantifying bead features over a wide range of image acquisition settings (brightness and focus), allowing us to establish a reference focal plan for image acquisition for any cell sample based on bead features. We show that with as few as three beads per image, the reference focal plane can be found from a single acquisition of beads image data over a wide range of image focuses and brightness, allowing users to consistently acquire images for cell viability that meet pre-defined quality requirements.

Fugacity-Based Trophic Magnification Factors Characterize Bioaccumulation of Cyclic Methyl Siloxanes within an Urban Terrestrial Avian Food Web: Importance of Organism Body Temperature and Composition.

Trophic magnification of cyclic volatile methyl siloxanes (cVMS) in a terrestrial food web was investigated by measuring concentrations of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) and two reference chemicals within air and biota samples from an avian food web located in a mixed urban-agricultural landscape. Terrestrial trophic magnification factors derived from lipid normalized concentrations (TMFLs) for D5 and D6 were 0.94 (0.17 SE) and 1.1 (0.23 SE) and not statistically different from 1 (p > 0.05); however, the TMFL of D4 was 0.62 (0.11 SE) and statistically less than 1 (p < 0.001). TMFLs of PCB-153 and p,p'-DDE were 5.6 (2.2 SE) and 6.1 (2.8 SE) and statistically greater than 1 (p < 0.001). TMFLs of cVMS in this terrestrial system were similar to those reported in aquatic systems. However, trophic magnification factors derived on a fugacity basis (TMFFs), which recognize differences in body temperature and lipid composition between organisms, were greater than corresponding TMFLs primarily because a temperature-induced thermodynamic biomagnification of hydrophobic chemicals occurs when endothermic organisms consume poikilothermic organisms. Therefore, we recommend that biomagnification studies of food webs including endothermic and poikilothermic organisms incorporate differences in body temperature and tissue composition to accurately characterize the biomagnification potential of chemicals.

Review of petroleum toxicity in marine reptiles.

Worldwide petroleum exploration and transportation continue to impact the health of the marine environment through both catastrophic and chronic spillage. Of the impacted fauna, marine reptiles are often overlooked. While marine reptiles are sensitive to xenobiotics, there is a paucity of petroleum toxicity data for these specialized fauna in peer reviewed literature. Here we review the known impacts of petroleum spillage to marine reptiles, specifically to marine turtles and iguanas with an emphasis on physiology and fitness related toxicological effects. Secondly, we recommend standardized toxicity testing on surrogate species to elucidate the mechanisms by which petroleum related mortalities occur in the field following catastrophic spillage and to better link physiological and fitness related endpoints. Finally, we propose that marine reptiles could serve as sentinel species for marine ecosystem monitoring in the case of petroleum spillage. Comprehensive petroleum toxicity data on marine reptiles is needed in order to serve as a foundation for future research with newer, unconventional crude oils of unknown toxicity such as diluted bitumen.

Trends in the Detection, Management and 30-Day Outcomes of Spontaneous Coronary Artery Dissection: A Six-Year, New Zealand Centre Experience.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important but under-recognised cause of acute coronary syndrome (ACS), particularly in younger women. We assessed trends in the detection, management and outcomes of all patients with SCAD over 6 consecutive years. METHODS: All patients with first diagnosis of SCAD at Christchurch Public Hospital, New Zealand, between January 2014 and January 2020 were included. Patient management and outcomes were determined by retrospective review of medical records. SCAD presentations were compared to total ACS presentations, obtained from a national ACS (ANZACS-QI) database. RESULTS: We identified 113 patients with angiographic diagnosis of SCAD. Median age was 54 years (88% female). The detection of SCAD increased over the period, both as a total number (Kendall's τ 0.87, p=0.015) and as a proportion of all ACS (p value for trend <0.0001). In 2019, SCAD represented 2.4% of all ACS and 18% of ACS in females aged less than 60 years. The most common presentation was non-ST elevation myocardial infarction (NSTEMI) in 72%; and, there was an increase in NSTEMI compared with STEMI over the period (p=0.023). Initial strategy of percutaneous coronary intervention (PCI) was undertaken in 12% of patients, with a significant trend towards a more conservative approach over the study period (p=0.019). The rate of 30-day major adverse cardiovascular events (MACE) was 8.8% overall, and significantly reduced over the study period to 3% in 2019 (p value for trend, 0.006). CONCLUSIONS: The detection of SCAD has increased and is a particularly important cause of ACS in younger women. This increase has been largely driven by an increasing number of NSTEMI patients diagnosed with SCAD, associated with a significant improvement in 30-day MACE.

Cardiovascular Outcomes in Young Adulthood in a Population-Based Very Low Birth Weight Cohort.

OBJECTIVES: To assess differences in left heart structure and function, and endothelial function in a national cohort of very low birth weight (VLBW) young adults and term-born controls. STUDY DESIGN: The New Zealand VLBW study is a prospective, population-based, longitudinal cohort study which included all infants born <1500 g in 1986. The VLBW cohort (n = 229; 71% of survivors) and term-born controls (n = 100), were assessed at age 26-30 years. Measures of left heart structure and function were evaluated by echocardiography, vascular function was assessed using blood pressure, reactive hyperemia index, and arterioventricular coupling by calculating left ventricular (LV) and arterial elastance. RESULTS: Compared with controls, those born VLBW had smaller LVs, even when indexed for body surface area (mean LV mass, 89.7 ± 19.3 g/m2 vs 95.0 ± 22.3 g/m2 [P = .03]; LV end-diastolic volume, 58.3 ± 10.9 mL/m2 vs 62.4 ± 12.4 mL/m2 [P = .002]; and LV end-systolic volume, 20.8 ± 4.9 mL/m2 vs 22.6 ± 5.8 mL/m2 [P = .004]). VLBW participants had lower stroke volume (median, 37.2 mL/m2 [IQR, 33-42 mL/m2] vs median, 40.1 mL/m2 [IQR, 34-45 mL/m2]; P = .0059) and cardiac output (mean, 4.8 ± 1.2 L/min vs 5.1 ± 1.4 L/min; P = .03), but there was no difference in ejection fraction. The VLBW group had higher LV elastance (3.37 ± 0.88 mm Hg/mL vs 2.86 ± 0.75 mm Hg/mL; P < .0001) and arterial elastance (1.84 ± 0.4 vs 1.6 ± 0.4; P < .0001) and lower reactive hyperemia index (0.605 ± 0.28 vs 0.688 ± 0.31; P = .041). These measures were influenced by birth weight and sex, but we found limited associations with other perinatal factors. CONCLUSIONS: Being born preterm and VLBW is associated with differences in cardiovascular structure and function in adulthood. This population may be more vulnerable to cardiovascular pathology as they age. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12612000995875.

Cause-and-Effect Analysis as a Tool To Improve the Reproducibility of Nanobioassays: Four Case Studies.

One of the challenges in using in vitro data to understand the potential risks of engineered nanomaterials (ENMs) is that results often differ or are even contradictory among studies. While it is recognized that numerous factors can influence results produced by nanobioassays, there has not yet been a consistently used conceptual framework to identify key sources of variability in these assays. In this paper, we use cause-and-effect analysis to systematically describe sources of variability in four key in vitro nanobioassays: the 2',7'-dichlorofluorescein assay, an enzyme-linked immunosorbent assay for measuring interleukin-8, a flow cytometry assay (Annexin V/propidium iodide), and the Comet assay. These assays measure end points that can occur in cells impacted by ENMs through oxidative stress, a principle mechanism for ENM toxicity. The results from this analysis identify control measurements to test for potential artifacts or biases that could occur during conduct of these assays with ENMs. Cause-and-effect analysis also reveals additional measurements that could be performed either in preliminary experiments or each time the assay is run to increase confidence in the assay results and their reproducibility within and among laboratories. The approach applied here with these four assays can be used to support the development of a broad range of nanobioassays.

Decreases in cardiac catheter laboratory workload during the COVID-19 level 4 lockdown in New Zealand.

An increase in coronavirus disease (COVID-19) infections prompted Level 4 lockdown throughout New Zealand from 25 March 2020. We have investigated trends in coronary and electrophysiology (EP) procedures before and during this lockdown. The number of acute procedures for ST elevation myocardial infarction remained stable. In contrast, the number of in-patient angiograms and percutaneous intervention procedures fell by 53% compared with the previous 4 weeks in 2020 and by 56% compared with the corresponding period in 2019. Further study is required to determine the reasons for these trends.