Proof-of­‐Concept : Automated high­‐frequency measurements of PCO₂ and TCO₂ and real­‐time monitoring of the saturation state of calcium carbonate

The rapid increase in atmospheric carbon dioxide (CO₂) over the last 250 years has led to the absorption of approximately 550 billion tons of anthropogenic CO₂ by the global ocean. This oceanic uptake of CO₂ has resulted in decreasing pH and alterations to carbonate chemistry, threatening many ecologically and economically important marine species. The majority of biological production takes place on highly dynamic coastal margins, which require instrumentation capable of high-frequency measurements. In practice, measurements of sufficient resolution often do not include all required analytical parameters necessary to constrain the carbonate chemistry in order to investigate biogeochemical processes relevant to ocean acidification. This report provides a proof-of-concept for the development of an instrument designed to make autonomous measurements of the partial pressure of CO₂ (PCO₂) and total CO₂ (TCO₂) in a continuous sample stream at high frequency, based on combination of two existing measurement techniques. The objective is to provide measurements sufficient to constrain the carbonate chemistry in ocean waters while capturing the variability seen over short timescales in estuaries and on coastal margins. By constraining the carbonate chemistry and performing real time calculations of the saturation state of calcium carbonate and other carbonate parameters, this instrument can be utilized as a monitoring tool for fisheries in need of high resolution time series carbonate data. In our combined system, PCO₂ is determined by measuring the infrared absorbance due to CO₂ in the re-circulated gaseous headspace of a shower-type equilibrator. For TCO₂ analysis, a low-flowing seawater sample stream is acidified and passed through a microporous membrane contactor. The evolved CO₂ diffuses into a high-flowing CO₂-free strip-gas stream and is measured by infrared absorbance in the same manner as the PCO₂ method. The results of laboratory testing indicated the instrument is able to resolve TCO₂ changes with 0.5% precision. The system responds to changes in TCO₂ with a time constant of 12 seconds. TCO₂ analysis of gravimetrically prepared liquid carbonate standards and discrete field samples that were cross-analyzed at the Hales lab at Oregon State University indicated the internal accuracy of the system is better than 1%. PCO₂ measurements made with the combined PCO₂/TCO₂ system were within 3.5% of measurements made on synchronously-collected discrete samples preserved with HgCl₂ and subsequently analyzed in the Hales lab. However, absolute accuracy has yet to be validated for both PCO2 and TCO₂ measurements. Field observations carried out at Whiskey Creek Shellfish Hatchery at Netarts Bay on the Oregon coast illustrate the instrument’s ability to capture the high variability seen in the bay. The maximum rates of change seen in carbonate conditions were 123μM hr⁻¹ for TCO₂ and 103μatm hr⁻¹ for PCO₂, corresponding to environmental changes of 2.4°C hr⁻¹ in temperature, and 2.6 psu hr⁻¹ in salinity. Our interpolation method developed to model alkalinity between synchronized TCO₂ and PCO₂ measurements predicts the saturation of calcium carbonate minerals with an internal precision of 1.6%. The error of the resultant high-resolution time series of calcium carbonate saturation is estimated to be less than 3.6%. I conclude that this instrument is capable of producing quality time series of carbonate data at sufficient resolution to be a powerful tool for coastal biogeochemical research and deepening our understanding of the impacts of ocean acidification

DNA Evidence of a Croatian and Sephardic Jewish Settlement on the North Carolina Coast Dating from the Mid to Late 1500s

While the British origins of North American colonization currently are widely accepted, there is new evidence that other countries and non-Christians may have been earlier in establishing permanent settlements on the North Atlantic coast. Using the new research tool of human genomics, this paper provides DNA evidence that Croatians and Sephardic Jews were absorbed into the ancestral population of the Lumbee Native American tribe of North Carolina during the mid- to late-1500s. We further propose that these Sephardic Jews originated, in part, from a subgroup of the Roanoke colonists of 1586. Given this, a new historical narrative of early European colonization in North America during the 1500s is proposed

Small-Area Estimation for the USDA Forest Service, National Woodland Owner Survey: Creating a Fine-Scale Land Cover and Ownership Layer to Support County-Level Population Estimates

Small area estimation is a powerful modeling technique in which ancillary data can be utilized to “borrow” additional information, effectively increasing sample sizes in small spatial, temporal, or categorical domains. Though more commonly applied to biophysical variables within the study of forest inventory analyses, small area estimation can also be implemented in the context of understanding social values, behaviors, and trends among types of forest landowners within small domains. Here, we demonstrate a method for deriving a continuous fine-scale land cover and ownership layer for the state of Delaware, United States, and an application of that ancillary layer to facilitate small-area estimation of several variables from the USDA Forest Service’s National Woodland Owner Survey. Utilizing a proprietary parcel layer alongside the National Land Cover Database, we constructed a continuous layer with 10-meter resolution depicting land cover and land ownership classes. We found that the National Woodland Owner Survey state-level estimations of total acreage and total ownerships by ownership class were generally within one standard error of the population values calculated from the raster layer, which supported the direct calculation of several population-level summary variables at the county levels. Subsequently, we compare design-based and model-based methods of predicting commercial harvesting by family forest ownerships in Delaware in which forest ownership acreage, taken from the parcel map, was utilized to inform the model-based approach. Results show general agreement between the two modes, indicating that a small area estimation approach can be utilized successfully in this context and shows promise for other variables, especially if additional variables, e.g., United States Census Bureau data, are also incorporated

Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy)

Purpose: There is currently no true macrophage cell line and in vitro experiments requiring these cells currently require mitogenic stimulation of a macrophage precursor cell line (THP-1) or ex vivo maturation of circulating primary monocytes. In this study, we characterise a human macrophage cell line, derived from THP-1 cells, and compare its phenotype to the THP-1 cells. Methods: THP-1 cells with and without mitogenic stimulation were compared to the newly derived macrophage-like cell line (Daisy) using microscopy, flow cytometry, phagocytosis assays, antigen binding assays and gene microarrays. Results: We show that the cell line grows predominantly in an adherent monolayer. A panel of antibodies were chosen to investigate the cell surface phenotype of these cells using flow cytometry. Daisy cells expressed more CD11c, CD80, CD163, CD169 and CD206, but less CD14 and CD11b compared with mitogen-stimulated THP-1 cells. Unlike stimulated THP-1 cells which were barely able to bind immune complexes, Daisy cells showed large amounts of immune complex binding. Finally, although not statistically significant, the phagocytic ability of Daisy cells was greater than mitogen-stimulated THP-1 cells, suggesting that the cell line is more similar to mature macrophages. Conclusions: The observed phenotype suggests that Daisy cells are a good model of human macrophages with a phenotype similar to human alveolar macrophages

Comparing pediatric gastroenteritis emergency department care in Canada and the United States

BACKGROUND: Between-country variation in health care resource use and its impact on outcomes in acute care settings have been challenging to disentangle from illness severity by using administrative data. METHODS: We conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to,48 months with,72 hours of gastroenteritis were recruited in pediatric EDs in the United States (N = 10 sites; 588 participants) and Canada (N = 6 sites; 827 participants). The primary outcome was an unscheduled health care provider visit within 7 days; the secondary outcomes were intravenous fluid administration and hospitalization at or within 7 days of the index visit. RESULTS: In adjusted analysis, unscheduled revisits within 7 days did not differ (adjusted odds ratio [aOR]: 0.72; 95% confidence interval (CI): 0.50 to 1.02). At the index ED visit, although participants in Canada were assessed as being more dehydrated, intravenous fluids were administered more frequently in the United States (aOR: 4.6; 95% CI: 2.9 to 7.1). Intravenous fluid administration rates did not differ after enrollment (aOR: 1.4; 95% CI: 0.7 to 2.8; US cohort with Canadian as referent). Overall, intravenous rehydration was higher in the United States (aOR: 3.8; 95% CI: 2.5 to 5.7). Although hospitalization rates during the 7 days after enrollment (aOR: 1.1; 95% CI: 0.4 to 2.6) did not differ, hospitalization at the index visit was more common in the United States (3.9% vs 2.3%; aOR: 3.2; 95% CI: 1.6 to 6.8). CONCLUSIONS: Among children with gastroenteritis and similar disease severity, revisit rates were similar in our 2 study cohorts, despite lower rates of intravenous rehydration and hospitalization in Canadian-based EDs

Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer’s disease

Background Simultaneous consideration of two neuropathological traits related to Alzheimer’s disease (AD) has not been attempted in a genome-wide association study. Methods We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs. control brains using gene expression data. Results Genome-wide significant pleiotropic associations were observed for the joint model of NP and NFT (NP + NFT) with the single-nucleotide polymorphism (SNP) rs34487851 upstream of C2orf40 (alias ECRG4, P = 2.4 × 10−8) and for the joint model of NFT and CAA (NFT + CAA) with the HDAC9 SNP rs79524815 (P = 1.1 × 10−8). Gene-based testing revealed study-wide significant associations (P ≤ 2.0 × 10−6) for the NFT + CAA outcome with adjacent genes TRAPPC12, TRAPPC12-AS1, and ADI1. Risk alleles of proxy SNPs for rs79524815 were associated with significantly lower expression of HDAC9 in the brain (P = 3.0 × 10−3), and HDAC9 was significantly downregulated in subjects with AD compared with control subjects in the prefrontal (P = 7.9 × 10−3) and visual (P = 5.6 × 10−4) cortices. Conclusions Our findings suggest that pleiotropy analysis is a useful approach to identifying novel genetic associations with complex diseases and their endophenotypes. Functional studies are needed to determine whether ECRG4 or HDAC9 is plausible as a therapeutic target

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

BACKGROUND: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. METHODS: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. RESULTS: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P \u3c .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P \u3c .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). CONCLUSIONS: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Genetic variants and functional pathways associated with resilience to Alzheimer\u27s disease.

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer\u27s disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer\u27s disease and three longitudinal cohort studies of cognitive ageing. All analyses were run across all participants and repeated restricting the sample to individuals with unimpaired cognition to identify variants at the earliest stages of disease. As expected, all resilience metrics were genetically correlated with cognitive performance and education attainment traits (P-values \u3c 2.5 × 10-20), and we observed novel correlations with neuropsychiatric conditions (P-values \u3c 7.9 × 10-4). Notably, neither resilience metric was genetically correlated with clinical Alzheimer\u27s disease (P-values \u3e 0.42) nor associated with APOE (P-values \u3e 0.13). In single variant analyses, we observed a genome-wide significant locus among participants with unimpaired cognition on chromosome 18 upstream of ATP8B1 (index single nucleotide polymorphism rs2571244, minor allele frequency = 0.08, P = 2.3 × 10-8). The top variant at this locus (rs2571244) was significantly associated with methylation in prefrontal cortex tissue at multiple CpG sites, including one just upstream of ATPB81 (cg19596477; P = 2 × 10-13). Overall, this comprehensive genetic analysis of resilience implicates a putative role of vascular risk, metabolism, and mental health in protection from the cognitive consequences of neuropathology, while also providing evidence for a novel resilience gene along the bile acid metabolism pathway. Furthermore, the genetic architecture of resilience appears to be distinct from that of clinical Alzheimer\u27s disease, suggesting that a shift in focus to molecular contributors to resilience may identify novel pathways for therapeutic targets