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At least 55 records · Page 3

Modeling Pancreatic Tumor Motion Using 4-Dimensional Computed Tomography and Surrogate Markers

Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Teal Cycle Ergometer Vibration Isolation and Stabilization System Human-in-the-Loop Ground Evaluation for Long-Duration Spaceflight

Purpose: To counter the deleterious effects of weightlessness on the cardiopulmonary system, astronauts living on the International Space Station exercise on a variety of countermeasure equipment including the Cycle Ergometer Vibration Isolation and Stabilization System (CEVIS). Operational since 2001, the onboard CEVIS will be replaced by a new model, known as Teal CEVIS (TC). As a part of ground evaluation, TC hardware underwent human-in-the-loop (HITL) testing to verify the TC hardware produces workloads that elicit physiologic responses comparable to a laboratory cycle ergometer (LAB). Methods: Seven subjects (5 M/2 F) performed submaximal cycle ergometer testing with indirect calorimetry measures on TC and LAB on separate test days. Testing consisted of graded 30 watt increases in workload until subjects reached 85% of age-predicted max heart rate (HR). Exercise outcomes included rate of oxygen uptake (VO2; liters/min), rate of energy expenditure (REE; kcal/min), and HR (beats/min). Linear mixed models (LMM) were fitted to compare VO2, REE, and HR responses between devices across power outputs with fixed effects for power (P) and device (D) and with random effects for subject. LMM effect coefficients (β), std errors (SE), pseudo-partial R2 of effects (pR2), and model likelihood ratio statistics (χ2, Pr(> chisq); α<.05) are provided. Results: LMM main effects for P and D were observed for VO2 (βp=.0107, SE = .0002, pR2=0.97; βd = -0.075, SE = 0.019, pR2=0.14; χ2(1)= 13.57, p<.001), such that VO2 was higher across stages on TC. Main effects of P and D were observed for REE (βp= .0586, SE = 0.001, pR2= 0.97; βd = -0.33208, SE = 0.099, pR2= 0.056; χ2(1)=10.481, p < .01), such that REE was higher across power outputs on TC. A P x D interaction was observed for HR, along with main effects for P and D (βp x d =-0.048, SE = 0.02, pR2=0.048; βp= 0.42, SE = 0.016, pR2=0.87; χ2(1) = 5.398, p = 0.02), such that higher workloads elicited a greater difference in HR between devices. Conclusions: HITL results show, TC elicits greater physiologic responses across power outputs compared to LAB. However, pR2 for device effects show small differences between devices. Therefore, TC can be expected to provide appropriate physiological stimulus across workloads and be considered a reliable tool to mitigate the effects of weightlessness.

Cycle Ergometer Vibration and Isolation System↗

Verification of Data-Driven Models of Physical Phenomena using Interpretable Approximation

Machine-learned models, specifically neural networks, are increasingly used as “closures” or “constitutive models” in engineering simulators to represent fine-scale physical phenomena that are too computationally expensive to resolve explicitly. However, these neural net models of unresolved physical phenomena tend to fail unpredictably and are therefore not used in mission-critical simulations. In this report, we describe new methods to authenticate them, i.e., to determine the (physical) information content of their training datasets, qualify the scenarios where they may be used and to verify that the neural net, as trained, adhere to physics theory. We demonstrate these methods with neural net closure of turbulent phenomena used in Reynolds Averaged Navier-Stokes equations. We show the types of turbulent physics extant in our training datasets, and, using a test flow of an impinging jet, identify the exact locations where the neural network would be extrapolating i.e., where it would be used outside the feature-space where it was trained. Using Generalized Linear Mixed Models, we also generate explanations of the neural net (à la Local Interpretable Model agnostic Explanations) at prototypes placed in the training data and compare them with approximate analytical models from turbulence theory. Finally, we verify our findings by reproducing them using two different methods.

42 ENGINEERING↗

Vertical variation of turbulent entrainment mixing processes in marine stratocumulus clouds using high-resolution digital holography

Marine stratocumulus clouds contribute signi?cantly to the Earth’s radiation budget due to their extensive coverage and high albedo. Yet, subgrid variability in cloud properties such as aerosol concentration, droplet number and precipitation rates lead to considerable errors in global climate models. While these clouds usually have small vertical ex-tent, turbulent entrainment-mixing and precipitation can generate signi?cant variations in droplet number, size and relative dispersion with altitude. In this paper, we analyze turbulent entrainment-mixing processes and the variability in cloud microphysical properties as a function of height within a warm marine stratocumulus cloud layer over the Eastern North Atlantic. We use high resolution airborne holographic measurements and compare them with local turbulence measurements. We ?nd that entrainment-mixing is primarily inhomogeneous near cloud top leading to larger droplet sizes and homogeneous near cloud base leading to smaller droplet sizes. Further analysis of Damk¨ohler number measurements are able to explain the mixing mechanisms at di?erent cloud heights, reinforcing the importance of turbulent mixing and microphysical time scales in deter-mining cloud microphysics.

Desai, Neel↗

Explicit modeling of abiotic and landscape factors reveals precipitation and forests associated with aphid abundance

Abstract Increases in natural or noncrop habitat surrounding agricultural fields have been shown to be correlated with declines in insect crop pests. However, these patterns are highly variable across studies suggesting other important factors, such as abiotic drivers, which are rarely included in landscape models, may also contribute to variability in insect population abundance. The objective of this study was to explicitly account for the contribution of temperature and precipitation, in addition to landscape composition, on the abundance of a widespread insect crop pest, the soybean aphid ( Aphis glycines Matsumura), in Wisconsin soybean fields. We hypothesized that higher soybean aphid abundance would be associated with higher heat accumulation (e.g., growing degree days) and increasing noncrop habitat in the surrounding landscape, due to the presence of the overwintering primary hosts of soybean aphid. To evaluate these hypotheses, we used an ecoinformatics approach that relied on a large dataset collected across Wisconsin over a 9‐year period (2003–2011), for an average of 235 sites per year ( n = 2,110 fields total). We determined surrounding landscape composition (1.5‐km radius) using publicly available satellite‐derived land cover imagery and interpolated daily temperature and precipitation information from the National Weather Service COOP weather station network. We constructed linear mixed models for soybean aphid abundance based on abiotic and landscape explanatory variables and applied model averaging for prediction using an information theoretic framework. Over this broad spatial and temporal extent in Wisconsin, we found that variation in growing season precipitation was positively related to soybean aphid abundance, while higher precipitation during the nongrowing season had a negative effect on aphid populations. Additionally, we found that aphid populations were higher in areas with proportionally more forest but were lower in areas where minor crops, such as small grains, were more prevalent. Thus, our findings support our hypothesis that including abiotic drivers increases our understanding of crop pest abundance and distribution. Moreover, by explicitly modeling abiotic factors, we may be able to explore how variable climate in tandem with land cover patterns may affect current and future insect populations, with potentially critical implications for crop yields and agricultural food webs.

Stack Whitney, Kaitlin↗

Evaluation of partial volume correction and analysis of longitudinal [ 18 F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models

Purpose: We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [ 18 F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM). Methods: We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates. Results: The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability. Conclusion: The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [ 18 F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability. Clinical trial registration: NCT02640092 and NCT03289143.

60 APPLIED LIFE SCIENCES↗

Mapping of the Ronda peridotite massif (Spain) from AVIRIS spectro-imaging survey: A first attempt

In both AVIRIS and ISM data, through the use of mixing models, geological boundaries of the Ronda massif are identified with respect to the surrounding rocks. We can also yield first-order vegetation maps. ISM and AVIRIS instruments give consistent results. On the basis of endmember fraction images, it is then possible to discard areas highly vegetated or not belonging to the peridotite massif. Within the remaining part of the mosaic, spectro-mixing analysis reveals spectral variations in the peridotite massif between the well-exposed areas. Spatially organized units are depicted, related to differences in the relative depth of the absorption band at 1 micron, and it may be due to a different pyroxene content. At this stage, it is worth noting that, although mineralogical variations observed in the rocks are at a sub-pixel scale for the airborne analysis, we see an emerging spatial pattern in the distribution of spectral variations across the massif which might be prevailingly related to mineralogy. Although it is known from fieldwork that the Ronda peridotite massif exhibits mineralogical variations at local scale in the content of pyroxene, and at regional scale in different mineral facies, ranging from garnet-, to spinel- to plagioclase-lherzolites, no attempt has been done yet to produce a synoptic map relating the two scales of analysis. The present work is a first attempt to reach this objective, though a lot more work is still required. In particular, for the purpose of mineralogical interpretation, it is critical to relate the airborne observation to field work and laboratory spectra of Ronda rocks already obtained, with the use of image endmembers and associated reference endmembers. Also, the pretty rough linear mixing model used here is taken as a 'black-box' process which does not necessarily apply correctly to the physical situation at the sub-pixel level. One may think of using the ground-truth observations bearing on the sub-pixel statistical characteristics (texture, structural pattern, surface distribution and vegetation contribution (grass,..)) to produce a more advanced mixing model, physically appropriate to the geologic and environmental contexts.

Pinet, P. C.↗

Association of Cortical ß-Amyloid Protein in the Absence of Insoluble Deposits With Alzheimer Disease.

IMPORTANCE: ß-Amyloid deposits are a pathologic hallmark of Alzheimer disease (AD). However, the extent to which cortical ß-amyloid protein in the absence of insoluble deposits is associated with classic features of AD appear to be unknown. OBJECTIVE: To examine the associations of cortical ß-amyloid protein in the absence of insoluble deposits with cognitive decline, neurofibrillary tangles, other age-associated neuropathologic conditions, and APOE. DESIGN, SETTING, AND PARTICIPANTS: This analysis combines data from 2 community-based clinicopathologic cohort studies of aging. The Religious Orders Study started in 1994, and the Rush Memory and Aging Project started in 1997. Both studies are ongoing. Participants without known dementia were enrolled and agreed to annual clinical evaluations and brain donation after death. Primary analyses focused on individuals without ß-amyloid deposits. Data analyses occurred in mid-September 2018. MAIN OUTCOMES AND MEASURES: ß-Amyloid protein abundance was measured by targeted proteomics using selected reaction monitoring. ß-Amyloid deposits were detected using immunohistochemistry. Other neuropathologic indices were quantified via uniform structured evaluation. Linear mixed models were used to examine the association of ß-amyloid protein with cognitive decline. Regression models examined the protein associations with neuropathologic outcomes and the APOE genotype. RESULTS: By mid-September 2018, 3575 older persons were enrolled, and 1559 had died and undergone brain autopsy. Proteomic data were collected in 1208 individuals, and 5 with missing cognitive scores were excluded. Of the remaining 1203, primary analyses focused on 148 individuals (12.3%) without ß-amyloid deposits. In this group, the mean (SD) age at death was 87.0 (7.0) years, and 84 individuals (56.8%) were women. In the absence of ß-amyloid deposits, we did not observe an association of ß-amyloid protein with decline in episodic memory, but the protein was associated with faster rates of decline in processing speed (mean [SE] change, -0.014 [0.005]; P?=?.008) and visuospatial abilities (mean [SE] change, -0.013 [0.005]; P?=?.006). We did not observe protein association with paired helical filament tau tangle density. The protein was associated with amyloid angiopathy (odds ratio, 1.38 [95% CI, 1.15-1.67]; P?<?.001) but no other brain pathology. The associations with cognitive decline were unchanged after controlling for amyloid angiopathy. Neither APOE e4 nor a polygenic Alzheimer risk score was associated with ß-amyloid protein. CONCLUSIONS AND RELEVANCE: Cortical ß-amyloid protein was associated with faster cognitive decline in the absence of ß-amyloid deposits, which supports the role of cortical soluble ß-amyloid as a neurotoxic agent in aging. The lack of protein association with paired helical filament tau tangles, episodic memory decline, or strong genetic drivers of deposited ß-amyloid suggests an underlying neuropathologic change that may differ from that of AD.

Alzheimer’s disease, Insoluble deposits↗

Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia

Objective Previous gene expression analysis identified a network of coexpressed genes that is associated with β‐amyloid neuropathology and cognitive decline in older adults. The current work targeted influential genes in this network with quantitative proteomics to identify potential novel therapeutic targets. Methods Data came from 834 community‐based older persons who were followed annually, died, and underwent brain autopsy. Uniform structured postmortem evaluations assessed the burden of β‐amyloid and other common age‐related neuropathologies. Selected reaction monitoring quantified cortical protein abundance of 12 genes prioritized from a molecular network of aging human brain that is implicated in Alzheimer's dementia. Regression and linear mixed models examined the protein associations with β‐amyloid load and other neuropathological indices as well as cognitive decline over multiple years preceding death. Results Average age at death was 88.6 years. Overall, 349 participants (41.9%) had Alzheimer's dementia at death. A higher level of PLXNB1 abundance was associated with more β‐amyloid load ( p = 1.0 × 10 −7 ) and higher PHFtau tangle density ( p = 2.3 × 10 −7 ), and the association of PLXNB1 with cognitive decline is mediated by these known Alzheimer's disease pathologies. On the other hand, higher IGFBP5, HSPB2, and AK4 and lower ITPK1 levels were associated with faster cognitive decline, and, unlike PLXNB1, these associations were not fully explained by common neuropathological indices, suggesting novel mechanisms leading to cognitive decline. Interpretation Using targeted proteomics, this work identified cortical proteins involved in Alzheimer's dementia and begins to dissect two different molecular pathways: one affecting β‐amyloid deposition and another affecting resilience without a known pathological footprint. Ann Neurol 2018;83:78–88

Yu, Lei↗

The toughest animals of the Earth versus global warming: Effects of long‐term experimental warming on tardigrade community structure of a temperate deciduous forest

Abstract Understanding how different taxa respond to global warming is essential for predicting future changes and elaborating strategies to buffer them. Tardigrades are well known for their ability to survive environmental stressors, such as drying and freezing, by undergoing cryptobiosis and rapidly recovering their metabolic function after stressors cease. Determining the extent to which animals that undergo cryptobiosis are affected by environmental warming will help to understand the real magnitude climate change will have on these organisms. Here, we report on the responses of tardigrades within a five‐year‐long, field‐based artificial warming experiment, which consisted of 12 open‐top chambers heated to simulate the projected effects of global warming (ranging from 0 to 5.5°C above ambient temperature) in a temperate deciduous forest of North Carolina (USA). To elucidate the effects of warming on the tardigrade community inhabiting the soil litter, three community diversity indices (abundance, species richness, and Shannon diversity) and the abundance of the three most abundant species ( Diphascon pingue , Adropion scoticum , and Mesobiotus sp.) were determined. Their relationships with air temperature, soil moisture, and the interaction between air temperature and soil moisture were tested using Bayesian generalized linear mixed models. Despite observed negative effects of warming on other ground invertebrates in previous studies at this site, long‐term warming did not affect the abundance, richness, or diversity of tardigrades in this experiment. These results are in line with previous experimental studies, indicating that tardigrades may not be directly affected by ongoing global warming, possibly due to their thermotolerance and cryptobiotic abilities to avoid negative effects of stressful temperatures, and the buffering effect on temperature of the soil litter substrate.

54 ENVIRONMENTAL SCIENCES↗

Resident and transient coyotes exhibit differential patterns of movement behavior across heterogeneous landscapes in the southeastern United States

Coyotes (Canis latrans) are a highly adaptable canid species whose behavioral plasticity has allowed them to persist in a wide array of habitats throughout North America. As generalists, coyotes can alter movement patterns and change territorial strategies between residency (high site fidelity) and transiency (low site fidelity) to maximize fitness. Uncertainty remains about resident and transient coyote movement patterns and habitat use because research has reached conflicting conclusions regarding patterns of habitat use by both groups. We quantified effects of habitat on resident and transient coyote movement behavior using first passage time (FPT) analysis, which assesses recursive movement along an individual's movement path to delineate where they exhibit area-restricted search (ARS) behaviors relative to habitat attributes. We quantified monthly movement rates for 171 coyotes (76 residents and 53 transients) and then used estimated FPT values in generalized linear mixed models to quantify monthly habitat use for resident and transient coyotes. Transients had greater movement rates than residents across all months except January. Resident FPT values were positively correlated with agricultural land cover during fall and winter, but negatively correlated with agriculture during spring. Resident FPT values were also negatively correlated with developed habitats during May–August, deciduous land cover during June–August, and wetlands during September–January except November. FPT values of transient coyotes were positively correlated with developed areas throughout much of the year and near wetlands during July–September. Transient FPT values were negatively correlated with agriculture during all months except June and July. High FPT values (ARS behavior) of residents and transients were generally correlated with greater densities of edge habitat. Although we observed high individual variation in space use, our study found substantive differences in habitat use between residents and transients, providing further evidence that complexity and plasticity of coyote habitat use is influenced by territorial strategy.

54 ENVIRONMENTAL SCIENCES↗

Effective dose and persistence of Rhodamine-B in wild pig Vibrissae

Due to substantial ecological and economic damage attributed to wild pigs (Sus scrofa), there is international interest in using pharmaceutical baits to control populations. To assess the efficacy and specificity of baiting programs, one may use chemical biomarkers to evaluate uptake of pharmaceutical baits. In particular, Rhodamine B (RB) is known to be an effective biomarker in wild pigs. However, significant data gaps exist regarding the minimum effective dosage and the persistence of RB in wild pigs. To investigate this we used a controlled double-blind study, administering a one-time dose of RB at three treatment levels (5, 15, or 30 mg/kg) to 15 pigs, with five pigs per treatment group. Facial vibrissae were collected pre-RB ingestion as a control and every 2 weeks post-RB ingestion for 12 weeks. We examined samples for RB presence and used a generalized linear mixed model (GLMM) to determine the influence of treatment dose on persistence of RB. Additionally, we measured distance moved by the RB mark away from the vibrissae root and used a GLMM to assess movement rates of RB bands along growing vibrissae. Here, we found consistently greater persistence of RB in the 15 and 30 mg/kg treatments across the sampling period (p = 0.005 and p = <0.0001, respectively). A significant, positive movement trend in RB bands was observed within the 15 and 30mg/kg groups. Based on our results, a 15 mg/kg dosage can be considered a minimum effective dose for wild pigs and will reliably produce a detectable RB mark up to and likely beyond 12 weeks post-ingestion.

59 BASIC BIOLOGICAL SCIENCES↗

Real-world outcomes in patients with unresected stage III non-small cell lung cancer

This study examined real-world clinical outcomes such as progression-free survival (PFS), time to metastasis (TTM), overall survival (OS), and health-related quality of life (HRQOL) in patients with unresected stage III non-small cell lung cancer (NSCLC) treated in the community setting. A retrospective review of medical records extracted from 10 US community oncology practices was conducted. Eligible patients were adults diagnosed with stage III NSCLC from 1/1/2011 to 3/1/2016 without evidence of surgical resection within 6 months after stage III NSCLC diagnosis (index date). PFS, OS, and TTM were assessed from the index date, and were analyzed using Kaplan–Meier and Cox regression analyses. HRQOL was assessed for a subset of patients using a patient-reported measure, the 86-item Patient Care Monitor (PCM). Linear mixed models (LMM) were used to assess the impact of patient characteristics and change in PCM scores associated with progression. Among the sample of 478 patients, median PFS (95% confidence interval) was 10 months (9–11), median OS was 20 months (17–22), and median TTM was 30 months (23–45). Most patients (58.2%) experienced disease progression, which the LMM showed to be associated with significant worsening of physical symptoms and psychological states (p < 0.001). This study documented PFS and OS consistent with published literature. The majority of patients experienced disease progression, which was associated with worsening of HRQOL. These findings highlighted the need for better therapeutic options in patients with unresected stage III NSCLC with potential to improve patient outcomes and HRQOL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Differing behavioral changes in crayfish and bluegill under short- and long-chain PFAS exposures: Field study in Northern Michigan, USA

The emergent contaminant family, per- and poly-fluorinated alkyl substances (PFAS) has gained research attention due to their widespread detection and stability within the environment. Despite the growing amount of research on perfluorooctanesulfonic acid (PFOS) and perfluoro-n-octanoic acid (PFOA) in aquatic organisms, investigations detailing behavioral and physiological effects of aquatic organisms exposed to a mixture of PFAS analytes in the wild have been limited. The objective of this study was to evaluate the potential behavioral and histological effects of environmental exposure to PFAS compounds within multiple trophic levels of aquatic ecosystems. The current study investigates effects of environmentally relevant PFAS concentration exposures in crayfish (Faxonius immunis, F. rusticus, F. virilis) and bluegill (Lepomis macrochirus) sourced from four water bodies in Northern Michigan. Antipredator response and foraging behavioral assays were used to investigate potential effects on crayfish; a swimming speed behavioral assay and liver and gill histology analysis were used to investigate potential effects on fish. Linear mixed model and multiple regression analyses resulted in significant relationships between tissue accumulation levels of long chain PFAS compounds and crayfish foraging and fish critical swimming speed responses. Crayfish foraging decreased and fish critical swim speeds increased with PFAS exposure which may lead to energetic and population concerns. Antipredator response in crayfish and liver and gill histology in fish were not significantly related to PFAS tissue or water concentrations. The sensitivity of crayfish and bluegill behavior contributes to the growing body of research regarding the differential toxicity of short-chain and long-chain PFAS compounds. The sensitivity of some aquatic organism behaviors to PFAS accumulated in tissue may have implications for PFAS transfer and alterations to ecosystem functioning; based on the results of this field study, further laboratory research is recommended to further evaluate these relationships.

59 BASIC BIOLOGICAL SCIENCES↗

Personal and environmental predictors of polycyclic aromatic hydrocarbon exposure identified through repeated silicone wristband sampling

This study integrates quantitative data on personal exposure to polycyclic aromatic hydrocarbons (PAHs) in 162 silicone wristbands with demographics, behavioral information, and housing characteristics to explore contributions to residential exposure in a superfund-adjacent community over the course of a year. Forty-six residents completed questionnaires and wore silicone wristbands as personal passive samplers for seven consecutive days on up to four separate occasions in alternating months between November 2022 and June 2023. It was hypothesized that individual behaviors and housing characteristics are sources of dependence and correlation between personal PAH exposures. 50 PAHs were detected at least once, 17 of which were alkylated PAHs. Exposure to PAHs of similar molecular weight was often correlated, notably between naphthalenes (2-rings) and higher molecular weight PAHs (3 or more rings). Generalized linear mixed models identified flooring type, participant age, and sampling month as important predictors of increased PAH exposure, and flooring type, and use of wood stoves or heavy machinery as predictors of increased naphthalene exposure relative to higher molecular weight PAHs. Individual chemical models based on concentration data and detection frequencies corroborated these findings across multiple PAHs. We demonstrate that personal exposure is not static and the degree of variability in personal exposure is individual. Hence, identification of influential exposure factors through repeated measures of chemical exposure and characterization of variability in personal exposure as performed in this study, is important in the development of exposure mitigation strategies.

Bonner, Emily↗

Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer, was introduced commercially in 2002 as an alternative to ortho-phthalate esters because of its favorable toxicological profile. However, the potential health effects from DINCH exposure remain largely unknown. We explored the associations between urinary concentrations of metabolites of DINCH on markers of ovarian response among women undergoing in vitro fertilization (IVF) treatments. Between 2011 and 2015, 113 women enrolled a prospective cohort study at the Massachusetts General Hospital Fertility Center and provided up to two urine samples prior to oocyte retrieval. The urinary concentrations of two DINCH metabolites, cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) and cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), were quantified by isotope dilution tandem mass spectrometry. We used generalized linear mixed models to evaluate the association between urinary metabolite concentrations and markers of ovarian response, accounting for multiple IVF cycles per woman via random intercepts. On average, women with detectable urinary MHiNCH concentrations, as compared to those below LOD, had a lower estradiol levels (−325 pmol/l, p=0.09) and number of retrieved oocytes (−1.8, p=0.08), with a stronger association among older women. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness. In conclusion, we found suggestive negative associations between urinary MHiNCH concentrations and peak estradiol levels and number of total oocyte yields. This is the first study evaluating the effect of DINCH exposure on human reproductive health and raises the need for further experimental and epidemiological studies to better understand the potential effects of this chemical on health. - Highlights: • Women with detectable urinary MHiNCH concentrations had a lower estradiol levels and number of retrieved oocytes. • The negative association between urinary MHiNCH concentrations and total oocyte yield was stronger in older women. • Urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness.

54 ENVIRONMENTAL SCIENCES↗

Blood lead levels and hypothalamic-pituitary-adrenal function in middle-aged individuals

Highlights: • We assessed cortisol secretions (CS) in adults aged 50–67 years. • We reported changes in CS in relation to blood lead levels. • At low-levels, lead does not impact the global trend of salivary CS. Experimental and epidemiological studies suggested that exposure to lead (Pb) may influence the hypothalamic-pituitary-adrenal (HPA) axis. However, previous studies have yielded mixed results. We evaluated changes in basal salivary cortisol levels and acute cortisol responsivity to psychological stress in relation with blood Pb levels (BPb), in Caucasian individuals 50–67 years of age. Data were collected through the Study of Genetics, Stress and Cognitive Development (2004–2006). Diurnal basal and stress-reactive salivary cortisol levels were collected and BPb levels were determined using inductively coupled plasma mass spectroscopy. A total of 65 participants were included in the current study. General linear mixed models were used to assess the association between BPb level and change in cortisol secretion over time, for diurnal basal pattern and stress-reactive pattern, respectively. The geometric mean BPb was 2.70 μg/dL (± 1.44) and two exposure groups were created based on the median value of 2.48 µg/dL. No difference in geometric mean of salivary cortisol (µg/dL) at awakening was observed between High and Low BPb groups (0.23 (± 0.11) vs 0.20 (± 0.11), p = 0.36). The overall pattern of change in both diurnal basal (from the awakening to bedtime) and reactive salivary cortisol (during the stress induction protocol) did not differ between groups. In these middle-aged and older adults, we concluded that Pb exposure, within the range observed in the current study, was associated with neither diurnal nor stress-reactive cortisol secretion. Further investigation with larger datasets are needed to confirm our observations.

54 ENVIRONMENTAL SCIENCES↗