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Evidence linking calcium to increased organo-mineral association in soils

Geochemical indicators are emerging as important predictors of soil organic carbon (SOC) dynamics, but evidence concerning the role of calcium (Ca) is scarce. This study investigates the role of Ca prevalence in SOC accumulation by comparing otherwise similar sites with (CaCO 3 -bearing) or without carbonates (CaCO 3 -free). We measured the SOC content and indicators of organic matter quality (C stable isotope composition, expressed as δ 13 C values, and thermal stability) in bulk soil samples. We then used sequential sonication and density fractionation (DF) to separate two occluded pools from free and mineral-associated SOC. The SOC content, mass, and δ 13 C values were determined in all the fractions. X-ray photoelectron spectroscopy was used to investigate the surface chemistry of selected fractions. Our hypothesis was that occlusion would be more prevalent at the CaCO 3 -bearing site due to the influence of Ca on aggregation, inhibiting oxidative transformation, and preserving lower δ 13 C values. Bulk SOC content was twice as high in the CaCO 3 -bearing profiles, which also had lower bulk δ 13 C values, and more occluded SOC. Yet, contrary to our hypothesis, occlusion only accounted for a small proportion of total SOC (< 10%). Instead, it was the heavy fraction (HF), containing mineral-associated organic C, which accounted for the majority of total SOC and for the lower bulk δ 13 C values. Overall, an increased Ca prevalence was associated with a near-doubling of mineral-associated SOC content. Future investigations should now aim to isolate Ca-mediated complexation processes that increase organo-mineral association and preserve organic matter with lower δ 13 C values.

58 GEOSCIENCES↗

Structure-guided design of a broadly cross-reactive multivalent group a streptococcal vaccine

The M protein of group A streptococci (Strep A) is a major virulence determinant and protective antigen. The N-terminal region of the M protein is variable in sequence, defines the M/emm type, and contains epitopes that elicit opsonic antibodies that protect animals from challenge infections. Although there are >200 M types of Strep A, there is now evidence that structurally related M proteins can be grouped into clusters and that immunity may be cluster-specific in addition to M type-specific. This observation has led to recent studies of structure-based design of multivalent M peptide vaccines to select peptides predicted to cross-react with heterologous M types to improve vaccine coverage. In the current study, we have applied a refined series of peptide structural algorithms to predict immunological cross-reactivity among 117N-terminal M peptides representing the most prevalent M types of Strep A. Based on the results of the structural analyses, in combination with global M type prevalence data, we constructed a 32-valent vaccine containing 19 cross-reactive vaccine candidates predicted to cross-react with 37 heterologous M peptides to which were added 13 type-specific M peptides. Further, the 4-protein recombinant vaccine was immunogenic in rabbits and elicited significant levels of antibodies against 31/32 (97%) vaccine peptides and 28/37 (76%) peptides predicted to cross-react. The vaccine antisera also promoted opsonophagocytic killing of vaccine and cross-reactive M types of Strep A. Based on a recent analysis of M type prevalence of Strep A, the potential global coverage of the 32-valent vaccine is ~90%, ranging from 68% in Africa to 95% in North America. Our results indicate the utility of structure-based design that may be applied to future studies of broadly protective M peptide vaccines.

60 APPLIED LIFE SCIENCES↗

Deep neural network improves the estimation of polygenic risk scores for breast cancer

Polygenic risk scores (PRS) estimate the genetic risk of an individual for a complex disease based on many genetic variants across the whole genome. Here, we compared a series of computational models for estimation of breast cancer PRS. A deep neural network (DNN) was found to outperform alternative machine learning techniques and established statistical algorithms, including BLUP, BayesA, and LDpred. In the test cohort with 50% prevalence, the Area Under the receiver operating characteristic Curve (AUC) were 67.4% for DNN, 64.2% for BLUP, 64.5% for BayesA, and 62.4% for LDpred. BLUP, BayesA, and LPpred all generated PRS that followed a normal distribution in the case population. However, the PRS generated by DNN in the case population followed a bimodal distribution composed of two normal distributions with distinctly different means. This suggests that DNN was able to separate the case population into a high-genetic-risk case subpopulation with an average PRS significantly higher than the control population and a normal-genetic-risk case subpopulation with an average PRS similar to the control population. This allowed DNN to achieve 18.8% recall at 90% precision in the test cohort with 50% prevalence, which can be extrapolated to 65.4% recall at 20% precision in a general population with 12% prevalence. Interpretation of the DNN model identified salient variants that were assigned insignificant p values by association studies, but were important for DNN prediction. These variants may be associated with the phenotype through nonlinear relationships.

59 BASIC BIOLOGICAL SCIENCES↗

Mapping brucellosis risk in Kenya and its implications for control strategies in sub-Saharan Africa

In Sub-Saharan Africa (SSA), effective brucellosis control is limited, in part, by the lack of long-term commitments by governments to control the disease and the absence of reliable national human and livestock population-based data to inform policies. Therefore, we conducted a study to establish the national prevalence and develop a risk map for Brucella spp. in cattle to contribute to plans to eliminate the disease in Kenya by the year 2040. We randomly generated 268 geolocations and distributed them across Kenya, proportionate to the area of each of the five agroecological zones and the associated cattle population. Cattle herds closest to each selected geolocation were identified for sampling. Up to 25 cattle were sampled per geolocation and a semi-structured questionnaire was administered to their owners. We tested 6,593 cattle samples for Brucella immunoglobulin G (IgG) antibodies using an Enzyme-linked immunosorbent assay (ELISA). We assessed potential risk factors and performed spatial analyses and prevalence mapping using approximate Bayesian inference implemented via the integrated nested Laplace approximation (INLA) method. The national Brucella spp. prevalence was 6.8% (95% CI: 6.2–7.4%). Exposure levels varied significantly between agro-ecological zones, with a high of 8.5% in the very arid zone with the lowest agricultural potential relative to a low of 0.0% in the agro-alpine zone with the highest agricultural potential. Additionally, seroprevalence increased with herd size, and the odds of seropositivity were significantly higher for females and adult animals than for males or calves. Similarly, animals with a history of abortion, or with multiple reproductive syndromes had higher seropositivity than those without. At the herd level, the risk of Brucella spp. transmission was higher in larger herds, and herds with a history of reproductive problems such as abortion, giving birth to weak calves, or having swollen testes. Geographic localities with high Brucella seroprevalence occurred in northern, eastern, and southern regions of Kenya all primarily characterized by semi-arid or arid agro-ecological zones dominated by livestock pastoralism interspersed with vast areas with mixed livestock-wildlife systems. The large spatial extent of our survey provides compelling evidence for the widespread geographical distribution of brucellosis risk across Kenya in a manner easily understandable for policymakers. Our findings can provide a basis for risk-stratified pilot studies aiming to investigate the cost-effectiveness and efficacy of singular and combined preventive intervention strategies that seek to inform Kenya’s Brucellosis Control Policy.

60 APPLIED LIFE SCIENCES↗

Recent aspects on epidemiology, clinical disease, and genetic diversity of Toxoplasma gondii infections in Australasian marsupials

Toxoplasma gondii infections are common in humans and animals worldwide. Among all intermediate hosts of T. gondii, captive marsupials from Australia and New Zealand are highly susceptible to clinical toxoplasmosis. However, most free-range marsupials establish chronic T. gondii infection. Infected marsupial meat may serve as a source of T. gondii infection for humans. Differences in mortality patterns in different species of kangaroos and other marsupials are not fully understood. Lifestyle, habitat, and the genotype of T. gondii are predicted to be risk factors. For example, koalas are rarely exposed to T. gondii because they live on treetops whereas wallabies on land are frequently exposed to infection. The present review summarizes worldwide information on the prevalence of clinical and subclinical infections, epidemiology, and genetic diversity of T. gondii infecting Australasian marsupials in their native habitat and among exported animals over the past decade. The role of genetic types of T. gondii and clinical disease is discussed. Fatal toxoplasmosis has been diagnosed in captive Australasian marsupials in Argentina, Chile, China, Germany, Hungary, Japan, Spain, Turkey, and the USA. Most deaths occurred because of disseminated toxoplasmosis. Genetic characterization of T. gondii strains isolated from fatal marsupial infections identified Type III as well as atypical, nonclonal genotypes. Fatal toxoplasmosis was also diagnosed in free-ranging wombats (Vombatus ursinus) in Australia. Genetic characterization of DNA amplified directly from host tissues of subclinical culled kangaroos at slaughter identified many mixed-strain infections with both atypical and recombinant genotypes of T. gondii. Most Australasian marsupials in their native land, Australia and New Zealand, have high prevalence of T. gondii, and kangaroo meat can be a source of infection for humans if consumed uncooked/undercooked. The genotypes prevalent in kangaroos in Australia and New Zealand were genetically distinct from those isolated or genotyped from most macropods in the USA and other countries. Thus, clinical toxoplasmosis in marsupials imported from Australia is most likely to occur from infections acquired after importation.

59 BASIC BIOLOGICAL SCIENCES↗

A fast comparative genome browser for diverse bacteria and archaea

Genome sequencing has revealed an incredible diversity of bacteria and archaea, but there are no fast and convenient tools for browsing across these genomes. It is cumbersome to view the prevalence of homologs for a protein of interest, or the gene neighborhoods of those homologs, across the diversity of the prokaryotes. We developed a web-based tool, fast . genomics , that uses two strategies to support fast browsing across the diversity of prokaryotes. First, the database of genomes is split up. The main database contains one representative from each of the 6,377 genera that have a high-quality genome, and additional databases for each taxonomic order contain up to 10 representatives of each species. Second, homologs of proteins of interest are identified quickly by using accelerated searches, usually in a few seconds. Once homologs are identified, fast . genomics can quickly show their prevalence across taxa, view their neighboring genes, or compare the prevalence of two different proteins. Fast . genomics is available at https://fast.genomics.lbl.gov .

59 BASIC BIOLOGICAL SCIENCES↗

ComStock Measure Documentation: Heat Pump Rooftop Units with Standard Performance

This documentation focuses on a single end-use savings shape measure - heat pump rooftop units (HP-RTUs) with standard efficiencies that are prevalent in the current market. Today, these products are claimed as standard efficiency by the manufacturers and are most commonly installed. This document will primarily discuss the additional changes of performance and configuration of the standard efficiency HP-RTUs while a comprehensive overview of the fundamental modeling methodology and background of the HP-RTU measure, including applicability, sizing scheme, and other key assumptions can be found in the original documentation: Heat Pump RTU. The definition of "standard efficiency" can be a bit vague when considering detailed specifics other than efficiency metrics of a heat pump. Thus, we have focused on reflecting products where manufacturers claim as standard efficiency and products that are not top-of-the-line in their model lineup. Based on gathering information from eight products from four major manufacturers, there are some common (or relatively prevalent) characteristics and we have defined standard efficiency product as follows: direct drive outdoor unit fan, two stages of heat pump cooling, single stage heat pump heating (i.e., all compressors running at the same time), heat pump minimum lockout temperature of 0°F (-17.8°C), backup electric resistance heating, backup heating runs at the same time as heat pump heating , heat pump heating locking out below minimum operating temperature, IEER in between 11-13, and HSPF in between 8-8.9. There are cases where some of these products have other variations: a variable frequency drive fan, dual fuel (i.e., gas backup heating) option, three or more cooling stages, two stages of heat pump heating, no backup heating as default , etc. However, this work tried to reflect the most common and prevalent options for a standard efficiency product.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Epidemiological investigation of coccidiosis and associated risk factors in broiler chickens immunized with live anticoccidial vaccines in China

Coccidiosis is a costly intestinal disease of chickens caused by Eimeria species. This infection is associated with high mortality, reduced feed efficiency, and slowed body weight gain. The diagnosis and control of coccidiosis becomes challenging due to the fact that chickens can be infected by seven different Eimeria species and often occur mixed-species co-infections. Grasping the epidemiology of Eimeria species is crucial to estimate the efficiency of poultry management. This study aimed to explore the distribution of Eimeria species in broiler chickens in China after administering live anticoccidial vaccines. A total of 634 samples were obtained, and the survey results showed that the prevalence of Eimeria was 86.12% (546/634), and the most common species were E. acervulina (65.62%), E. necatrix (50.95%), E. mitis (50.79%), E. tenella (48.42%), and E. praecox (41.80%). Most samples indicated mixed-species infections (an average of 3.29 species per positive sample). Notably, 63.98% of samples contain 3 to 5 Eimeria species within a single fecal sample. The most prevalent combinations were E. acervulina – E. tenella (38.96%) and E. acervulina – E. necatrix (37.22%). Statistical analysis showed that flocks vaccinated with trivalent vaccines were significantly positive for E. necatrix in grower chickens (OR = 3.30, p < 0.05) compared with starter chickens, and tetravalent vaccinated flocks showed that starter chickens demonstrated a higher susceptibility to E. tenella – E. brunetti (OR = 2.03, p < 0.05) and E. acervulina – E. maxima (OR = 2.05, p < 0.05) compared with adult chickens. Geographically, in the case of tetravalent vaccine-immunized flocks, a substantial positive association was observed between E. necatrix infection rates and flocks from eastern (OR = 3.88, p < 0.001), central (OR = 2.65, p = 0.001), and southern China (OR = 3.17, p < 0.001) compared with southwestern China. This study also found a positive association between E. necatrix (OR = 1.64, p < 0.05), E. acervulina (OR = 1.59, p < 0.05), and E. praecox (OR = 1.81, p < 0.05) infection and coccidiosis occurrence compared with non-infected flocks in tetravalent vaccinated flocks. This molecular epidemiological investigation showed a high prevalence of Eimeria species in the field. The emergent species, E. brunetti and E. praecox , might be incorporated into the widely-used live vaccines in the future. These insights could be useful in refining coccidiosis control strategies in the poultry industry.

Liao, Shenquan↗

Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence

There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03 - 0.80 Gy). Female CB6F1 mice were irradiated with low single doses of either oxygen, silicon, titanium, or iron ions at various energies to cover a range of dose-averaged LET values from 0.2 - 193 keV/µm, using 137Cs γ-rays as the reference radiation. Sham-treated controls were included in each individual experiment totally 398 animals across the 5 studies reported. Based on power calculations, between 40 - 156 mice were included in each of the treatment groups. Tumor prevalence at 16 months after radiation exposure was determined and compared to the age-matched, sham-treated animals. Results indicate that lung tumor prevalence is non-linear as a function of dose with suggestions of threshold doses depending on the LET of the beams. Histopathological evaluations of the tumors showed that the majority of tumors were benign bronchioloalveolar adenomas with occasional carcinomas or lymphosarcomas which may have resulted from metastases from other sites.

60 APPLIED LIFE SCIENCES↗

Racoons ( Procyon Lotor ) Show Higher Trypanosoma Cruzi Detection Rates than Virginia Opossums ( Didelphis Virginiana ) in South Carolina, USA

Chagas disease, a significant public health concern in the Americas, is caused by a protozoan parasite, Trypanosoma cruzi. The life cycle of T. cruzi involves kissing bugs (Triatoma spp.) functioning as vectors and mammalian species serving as hosts. Raccoons (Procyon lotor) and opossums (Didelphis virginiana) have been identified as important reservoir species in the life cycle of T. cruzi, but prevalence in both species in the southeastern US is currently understudied. We quantified T. cruzi prevalence in these two key reservoir species across our study area in South Carolina, US, and identified factors that may influence parasite detection. We collected whole blood from 183 raccoons and 126 opossums and used PCR to detect the presence of T. cruzi. We then used generalized linear models with parasite detection status as a binary response variable and predictor variables of land cover, distance to water, sex, season, and species. Our analysis indicated that raccoons experienced significantly higher parasite detection rates than Virginia opossums, with T. cruzi prevalence found to be 26.5% (95% confidence interval [CI], 20.0–33.8) in raccoons and 10.5% (95% CI, 5.51–17.5) in opossums. Altogether, our results concur with previous studies, in that T. cruzi is established in reservoir host populations in natural areas of the southeastern US.

60 APPLIED LIFE SCIENCES↗

Factors Predicting Apparent Ophidiomycosis in Wild Brown Watersnakes ( Nerodia Taxispilota )

Ophidiomycosis, also known as snake fungal disease, is caused by Ophidiomyces ophidiicola and is a threat to snake conservation worldwide. Ophidiomycosis has been reported throughout much of the eastern US, and outbreaks have been associated with local population declines of already strained populations. Previous studies report significant variability in ophidiomycosis among species sampled, with higher prevalence typically observed in Nerodia spp. Although ophidiomycosis can lead to morbidity and mortality in affected individuals, little is known about disease dynamics in free-ranging populations. Herein, we examine how individual-specific factors (e.g., life stage [immature, mature], contaminant status, sex, hemograms) may be associated with ophidiomycosis status in the brown watersnake (Nerodia taxispilota). During 2018–19, we sampled 97 N. taxispilota from five locations along the Savannah River in South Carolina and Georgia, US. Ophidiomyces ophidiicola DNA was detected in 66 snakes for a prevalence of 68% (95% confidence interval, 59–77). Mature snakes had a significantly higher risk of apparent ophidiomycosis (skin lesions present and quantitative PCR [qPCR], positive) relative to immature snakes. Snakes classified as having possible (skin lesions present, but qPCR negative) or apparent ophidiomycosis exhibited a relative azurophilia and heterophilia compared with individuals classified as negative (P≤0.037). Nerodia taxispilota in this region appear to have a high prevalence of apparent ophidiomycosis (22%; 95% CI, 14–31), similar to previous reports from the southeastern US. Furthermore, additional epidemiologic investigations are warranted to further elucidate other individual-specific and environmental factors that may dictate disease risk and outcomes in affected populations.

59 BASIC BIOLOGICAL SCIENCES↗

Restrictive spirometry pattern among construction trade workers

Spirometry-based studies of occupational lung disease have mostly focused on obstructive or mixed obstructive/restrictive outcomes. We wanted to determine if restrictive spirometry pattern (RSP) is associated with occupation and increased mortality. Study participants included 18,145 workers with demographic and smoking data and repeatable spirometry. The mortality analysis cohort included 15,445 workers with known vital status and cause of death through December 31, 2016. Stratified analyses explored RSP prevalence by demographic and clinical variables and trade. Log-binomial regression models explored RSP risk factors while controlling for important confounders such as smoking, obesity, and comorbidities. Cox regression models explored mortality risk by spirometry category. Prevalence of RSP was very high (28.6%). Mortality hazard ratios for RSP were 1.50 for all causes, 1.86 for cardiovascular diseases, 2.31 for respiratory diseases, and 1.66 for lung cancer. All construction trades except painters, machinists, and roofers had significantly elevated risk for RSP compared to our internal reference group. RSP was significantly associated with both parenchymal and pleural changes seen by chest X-ray. Construction trade workers are at significantly increased risk for RSP independent of obesity. Individuals with RSP are at increased risk for all-cause mortality as well as mortality attributable to respiratory diseases, cardiovascular diseases, and lung cancer. RSP deserves greater attention in occupational medicine and epidemiology.

60 APPLIED LIFE SCIENCES↗

Associations between cumulative environmental quality and ten selected birth defects in Texas

Abstract Background Causes of most birth defects are largely unknown. Genetics, maternal factors (e.g., age, smoking) and environmental exposures have all been linked to some birth defects, including neural tube, oral cleft, limb reduction, and gastroschisis; however, the contribution of cumulative exposures across several environmental domains in association with these defects is not well understood. Methods The Environmental Quality Index (EQI) and its domains (air, water, land, sociodemographic, built) were used to estimate county‐level cumulative environmental exposures from 2006–2010 and matched to birth defects identified from Texas Birth Defects Registry and live birth records from births in years 2007–2010 ( N = 1,610,709). Poisson regression models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for associations between 10 birth defects and the EQI. Results We observed some positive associations between worst environmental quality and neural tube, anencephaly, spina bifida, oral cleft, cleft palate, cleft lip with and without cleft palate, and gastroschisis [PR range: 1.12–1.55], but near null associations with limb reduction defects. Among domain specific results, we observed the strongest positive associations with the sociodemographic domain across birth defects but varied positive associations among the air and water domains, and negative or null associations with the land and built domains. Overall, few exposure‐response patterns were evident. Conclusions Our results highlight the complexities of cumulative, simultaneous environmental exposures in the prevalence rates of 10 selected birth defects. We were able to explore the impact of overall and domain specific environmental quality on birth defects and identify potential domain specific drivers of these associations.

Krajewski, Alison K.↗

Stream and ocean hydrodynamics mediate partial migration strategies in an amphidromous Hawaiian goby

Abstract Partial migration strategies, in which some individuals migrate but others do not, are widely observed in populations of migratory animals. Such patterns could arise via variation in migratory behaviors made by individual animals, via genetic variation in migratory predisposition, or simply by variation in migration opportunities mediated by environmental conditions. Here we use spatiotemporal variation in partial migration across populations of an amphidromous Hawaiian goby to test whether stream or ocean conditions favor completing its life cycle entirely within freshwater streams rather than undergoing an oceanic larval migration. Across 35 watersheds, microchemical analysis of otoliths revealed that most adult Awaous stamineus were freshwater residents (62% of n = 316 in 2009, 83% of n = 274 in 2011), but we found considerable variation among watersheds. We then tested the hypothesis that the prevalence of freshwater residency increases with the stability of stream flows and decreases with the availability of dispersal pathways arising from ocean hydrodynamics. We found that streams with low variation of daily discharge were home to a higher incidence of freshwater residents in each survey year. The magnitude of the shift in freshwater residency between survey years was positively associated with predicted interannual variability in the success of larval settlement in streams on each island based on passive drift in ocean currents. We built on these findings by developing a theoretical model of goby life history to further evaluate whether mediation of migration outcomes by stream and ocean hydrodynamics could be sufficient to explain the range of partial migration frequency observed across populations. The model illustrates that the proportion of larvae entering the ocean and differential survival of freshwater‐resident versus ocean‐going larvae are plausible mechanisms for range‐wide shifts in migration strategies. Thus, we propose that hydrologic variation in both ocean and stream environments contributes to spatiotemporal variation in the prevalence of migration phenotypes in A. stamineus . Our empirical and theoretical results suggest that the capacity for partial migration could enhance the persistence of metapopulations of diadromous fish when confronted with variable ocean and stream conditions.

54 ENVIRONMENTAL SCIENCES↗

Paradox of sustainability in tobacco control in Thailand: A comprehensive assessment of three-decade experiences

Background: Over the past three decades of tobacco control, Thailand has gained international recognition as a middle-income country with sustained achievement of declining smoking prevalence. However, the number of key FCTC measures implementation is still far away from the highest-level implementation. As a result, we aim to explore explanatory factors for the paradoxical phenomenon of sustainability in tobacco control in Thailand, to understand what the paradox means, why it happens, and how to take further steps in minimizing the paradox. Methods: We used a mixed-method approach comprising qualitative (review of literature and documents plus Program Sustainability Assessment Tool (PSAT) guided key informant interviews) and semi-quantitative methods (PSAT scoring, Theory of change (TOC), and causal-loop diagram (CLD)) to synthesize all the findings from the qualitative data. Results: Across all eight domains, sustainability scores at the local level are lower than the national level. The highest total score was in three domains: political support, partnership, and organizational capacity. The lowest total score was for the strategic planning domain. We propose a set of key strategic elements and drivers for future strategic planning. Discussion: Using CLD, we capture a high-level view of tobacco control with dynamic interactions between contexts, mechanisms, interventions, and outcomes. Finally, we believe the deep understanding of tobacco control and the proposed strategy to counteract transnational tobacco companies in Thailand will guide future sustainable actions to reduce the prevalence of smoking, especially in the strategic planning domain that has the lowest PSAT score.

60 APPLIED LIFE SCIENCES↗

Mercury bioaccumulation and Hepatozoon spp. infections in two syntopic watersnakes in South Carolina

Mercury (Hg) is a ubiquitous environmental contaminant known to bioaccumulate in biota and biomagnify in food webs. Parasites occur in nearly every ecosystem and often interact in complex ways with other stressors that their hosts experience. Hepatozoon spp. are intraerythrocytic parasites common in snakes. The Florida green watersnake (Nerodia floridana) and the banded watersnake (Nerodia fasciata) occur syntopically in certain aquatic habitats in the Southeastern United States. The purpose of this study was to investigate relationships among total mercury (THg) concentrations, body size, species,habitat type and prevalence and parasitemia of Hepatozoon spp. infections in snakes. In the present study, we sampled N. floridana and N. fasciata from former nuclear cooling reservoirs and isolated wetlands of the Savannah River Site in South Carolina. We used snake tail clips to quantify THg and collected blood samples for hemoparasite counts. Our results indicate a significant, positive relationship between THg and snake body size in N. floridana and N. fasciata in both habitats. Average THg was significantly higher for N. fasciata compared to N. floridana in bays (0.22 ± 0.02 and 0.08 ± 0.006 mg/kg, respectively; p < 0.01), but not in reservoirs (0.17 ± 0.02 and 0.17 ± 0.03 mg/kg, respectively; p = 0.29). Sex did not appear to be related to THg concentration or Hepatozoon spp. infections in either species. In conclusion, we found no association between Hg and Hepatozoon spp. prevalence or parasitemia; however, our results suggest that species and habitat type play a role in susceptibility to Hepatozoon spp. infection.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

A Comprehensive Scientific Survey of Excipients Used in Currently Marketed, Therapeutic Biological Drug Products

The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations. Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020. We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug’s recommended pH range, concentration ranges for excipients, and route of administration. The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.

60 APPLIED LIFE SCIENCES↗