Contaminant Levels in Eggs of American White Pelicans, Pelecanus erythrorhynchos, from Chase Lake, North Dakota

American White Pelicans (Pelecanus erythrorhynchos) are colonial nesters, making them susceptible to site-specific mortality factors. One of the largest known breeding colonies is at Chase Lake National Wildlife Refuge in North Dakota. In 2004, this colony suffered total reproductive failure. In 2005, we collected abandoned eggs from this colony to test for environmental contaminants. Nine eggs were analyzed for 28 organochlorine pesticides, total polychlorinated biphenyls, and 26 inorganic elements. Based on concentrations in this sample of eggs and levels linked to reproductive problems in birds, adult pelicans in the Chase Lake breeding colony are not at known risk from any of the environmental contaminants we measured

Multi-omics responses in tree swallow (\u3ci\u3eTachycineta bicolor\u3c/i\u3e) nestlings from the Maumee Area of Concern, Maumee River, Ohio

A multi-omics approach was utilized to identify altered biological responses and functions, and to prioritize contaminants to assess the risks of chemical mixtures in the Maumee Area of Concern (AOC), Maumee River, OH, USA. The Maumee AOC is designated by the United States Environmental Protection Agency as having significant beneficial use impairments, including degradation of fish and wildlife populations, bird or animal deformities or reproduction problems, and loss of fish and wildlife habitat. Tree swallow (Tachycineta bicolor) nestlings were collected at five sites along the Maumee River, which included wastewater treatment plants (WWTPs) and industrial land-use sites. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo p dioxins and furans (PCDD/Fs), and chlorinated pesticide concentrations were elevated in Maumee tree swallows, relative to a remote reference site, Star Lake, WI, USA. Liver tissue was utilized for non-targeted transcriptome and targeted metabolome evaluation. A significantly differentially expressed gene cluster related to a downregulation in cell growth and cell cycle regulation was identified when comparing all Maumee River sites with the reference site. There was an upregulation of lipogenesis genes, such as PPAR signaling (HMGCS2, SLC22A5), biosynthesis of unsaturated fatty acids (FASN, SCD, ELOVL2, and FADS2), and higher lipogenesis related metabolites, such as docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) at two industrial land-use sites, Ironhead and Maumee, relative to WWTP sites (Perrysburg and SideCut), and the reference site. Toledo Water, in the vicinity of the other two industrial sites and also adjacent to a WWTP, showed a mix of signals between industrial land-use and WWTP land-use. PAHs, oxychlordane, and PBDEs were determined to be the most likely causes of the differentiation in biological responses, including de novo lipogenesis and biosynthesis of unsaturated fatty acids

Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial

IMPORTANCE Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. OBJECTIVE To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. INTERVENTIONS Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200mg (n = 588), or placebo (n = 587). MAIN OUTCOMES AND MEASURES The primary outcomewas incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase–polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. RESULTS The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5%vs 15.2%; odds ratio, 0.43 [95%CI, 0.28-0.68]; P < .001; absolute risk difference, −6.6 [95%CI, −10.7 to −2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). CONCLUSIONS AND RELEVANCE Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing

Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency

The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10−7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10−9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

BIOAVAILABILITY AND EXPOSURE ASSESSMENT OF PETROLEUM HYDROCARBONS AND TRACE ELEMENTS IN BIRDS NESTING NEAR THE NORTH PLATTE RIVER, CASPER, WYOMING

The objectives of this study were to compare refinery-related petroleum hydrocarbon concentrations in nestling tree swallows (Tachycineta bicolor) and nestling house wrens (Troglodytes aedon) at sites along the North Platte River Casper, Wyoming in 1997 and 1998; and to determine if contaminants were present in concentrations that could adversely affect the birds. Because trace element concentrations, mixed function oxidase activity, and the variation in DNA are often associated with petroleum hydrocarbon concentrations in birds, each was measured as indicators of petroleum contamination. Sediment and aquatic invertebrates were also sampled for characterizing a possible contaminant source to the birds. Sampling areas included sites upstream (Game & Fish, Patterson-Zonta Park), adjacent to (Amoco Park, Texaco Refinery), and downstream (EKW State Park) of the former Amoco and Texaco oil refineries. We also sampled one site between the Amoco and Texaco Refineries (Crossroads Park). Additional samples were taken using adult cliff swallows (Hirundo pyrrhonota) nesting under various bridges along the North Platte River in 1998. Several aliphatic hydrocarbons were detected in sediment, aquatic invertebrates, and carcasses and gastrointestinal contents of house wren and tree swallow nestlings and adult barn and cliff swallows from all sites but differences among sites were not significant. The low pristane to n-C17 ratio in avian diet and tissues did not suggest chronic or acute exposure of birds to petroleum at any of the locations. However, the high phytane to n-C18 ratios of the gastrointestinal contents may indicate that some of the dietary items consumed by the birds were recently or chronically exposed to petroleum products. Most polycyclic aromatic hydrocarbons (PAHs) were not detected in aquatic insect larvae but some were detected in sediments. Concentrations of total PAHs were detected in nestling carcasses of tree swallows, house wrens, and a bank swallow. Differences in PAH concentrations were not significant among sites for tree swallow nestlings but were for house wren nestlings. In gastrointestinal contents of both tree swallow and house wren nestlings, PAH concentrations tended to be higher at the Texaco Refinery site when compared to the Game & Fish site. Two hepatic monooxygenase activities, benzyloxyresorufin-O-dealkylase (BROD) and ethoxyresorufin-Odealkylase (EROD), in tree swallow livers also tended to be higher at the Texaco Refinery site than at the Game & Fish sites and their induction may be related to PAH exposure. Because of the small sample size, results of the flow cytometry analysis, which measured DNA content, were inconclusive. Adult cliff swallow carcasses showed significant differences in total PAHs among sites with the highest concentrations occurring at the Texaco Refinery site and the upstream Patterson-Zonta Park site. PAHs were not detected in gastrointestinal contents of the cliff swallows. The predominance of unsubstituted PAHs and the general lack of alkyl-PAHs in all samples suggests that most of the PAHs were combustion-derived. Most trace elements were not elevated in any of the samples. Chromium and selenium were elevated in aquatic insect larvae but differences among sites were not significant. Chromium was not detected in avian eggs or most nestling livers but was detected in nestling tree swallow and wren carcasses and one adult barn swallow carcass. Mercury was detected in one bank swallow egg and all tree swallow eggs. Mercury was significantly higher in tree swallow eggs collected at the EKW State Park site when compared to the Game & Fish site. Mercury was detected in wren eggs from EKW State Park but was not detected in eggs from the Game & Fish site or in two of the three eggs from the Texaco Refinery site. In tree swallow and wren nestling livers from EKW State Park and the Texaco Refinery site, mercury concentrations were significantly higher than from the Game & Fish site. Mercury was also detected in tree swallow nestling carcasses from both the Texaco Refinery and EKW State Park but not from the Game & Fish site or in any of the house wrens. Differences were not significant among sites and the source of the mercury is unknown. Concentrations of mercury were detected in adult barn and cliff swallow livers and carcasses. Selenium was detected in house wren and tree swallow eggs, livers, and nestling carcasses. Selenium was also detected in adult barn and cliff swallow livers and carcasses. Differences were not significant but selenium concentrations, probably the result of irrigation return flows, tended to decrease downstream. This study demonstrates that some refinery-related contaminants are bioavailable and birds are being exposed. However, the data do not exhibit any pattern that can be linked to the refineries. Our small sample size and limited statistical power do not allow us to determine if any of the contaminants are adversely affecting the birds; and, the data collected on adult birds are inconclusive because exposure to contaminants may have occurred outside the sampling area. Additionally, for several contaminants detected, the upstream Game & Fish site appears to have concentrations similar to the study sites. Finally, we were unable to determine the influence of yearly variation on the results of the petroleum hydrocarbon or trace element analyses from 1997 and 1998; but, the 1997 data from the EKW State Park were not critical to the overall conclusions of the manuscript

NONTARGET BIRD EXPOSURE TO DRC-1339 DURING FALL IN NORTH DAKOTA AND SPRING IN SOUTH DAKOTA

Blackbirds frequently use ripening sunflower (Helianthus annuus)as a food source in the northern Great Plains. In 1999 and 2000, the avicide DRC-1339 (3-chloro-4-methylaniline hydrochloride) was used experimentally on fall-ripening sunflower fields in North Dakota so researchers could evaluate its effectiveness for reducing crop depredations by blackbirds DRC-1339 was applied to rice and broadcast on the ground in a confined area within ripening sunflower fields. One objective of this study was to determine if nontarget birds, birds other than blackbirds, were eating rice and were exposed to DRC 1339. In 1999, 8 of 11(73%) sparrows collected by shotgun in sunflower fields treated with DRC-1339 had rice in their gastrointestinal (GI) tracts. In 2000, 5 mourning doves (Zenaida macroura) and 3 sparrows were collected by shotgun in sunflower fields treated with DRC-1339 Three doves had rice in their GI tracts, 4 doves and all 3 sparrows had measurable DRC- 1339 concentrations in their GI tracts, and 3 mourning doves and 1 savannah sparrow (Passerculus sandwichensis) exhibited histopathological signs of kidney damage. In April 2002, untreated rice was applied to corn stubble plots in South Dakota to determine which bird species ate rice. In 2002, 3 of 3 song sparrows (Melospiza melodia) collected by shotgun had rice in their GI tracts. Our results demonstrate that the use of DRC-1339 to control blackbirds in the northern Great Plains will likely expose nontarget birds to the DRC-1339 bait

Radio Telemetry Documents 24-Hour Feeding Activity of Wintering Lesser Scaup

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