Final Report: BUI Delisting Studies in the Rochester Embayment AOC, 2013-2014

Substantial evidence of live mink was observed along the shoreline of the Genesee River portion of the RE AOC, which supports delisting the “mink are present and are reproducing” criterion of the Degradation of Fish and Wildlife Populations and the Loss of Fish and Wildlife Habitat BUIs. According to the USFWS Habitat Suitability Index Model, habitat appears to be highly suitable (85%) for mink along the Genesee River shoreline of the RE AOC, which supports delisting of the Loss of Fish and Wildlife Habitat BUI.For total mercury chemical analysis: a. No amphibian, crayfish and lower trophic level fish samples exceeded the published dietary lowest observed adverse effect level (LOAEL) for mink. b. All upper trophic level fish samples exceeded the published dietary LOAEL for mink (500 ng/g), by 13% on average. For PAH, PCB and dioxin (CDD)/furan (CDF) chemical analyses: a. None of the 12 composited mink prey samples exceeded dietary LOAELs for total PCBs (960,000 pg/g) and TEQ for CDD/CDF (9.2 pg/g). b. Ten of the 12 samples did not exceed the dietary LOAEL for PAHs, co-planar PCBs, and CDD/CDF combined (9.2 pg/g). c. One upper trophic level fish sample exceeded the dietary LOAEL for PAHs by 147% because it contained ~100 times more PAHs (which accounted for 95% of total TEQ in that sample) than the other two samples. d. One lower trophic level fish sample exceeded the dietary LOAEL for PCB TEQ by 4% because it contained ~90 times more PCB 126 (which accounted for 93% of total TEQ in that sample) than the other two samples. Mink hazard assessment: a. Using the “highest exposure” mink diet found in published literature (92% from aquatic sources), and using mean concentrations of BUI contaminants found in 2 potential mink prey in the Genesee River portion of the RE AOC, the maximum dietary exposure of mink would be 81% of the LOAEL for total mercury, 23% of the LOAEL for total PCBs, and 69% of the LOAEL for total TEQ (PAHs + CDD/CDF + co-planar PCBs). This is the “worst case” diet scenario. b. Using the average of six mink diets reported in published literature (65% from aquatic sources) comparable to what mink would eat in the Genesee River portion of the RE AOC, and using mean concentrations of BUI contaminants found in potential mink prey in the study area, the dietary exposure of mink would be 48% of the LOAEL for total mercury, 13% of the LOAEL for total PCBs, and 40% of the LOAEL for total TEQ. This is the “likely” diet scenario. It would be reasonable to delist the Bird or Animal Deformities or Reproductive Problems BUI in the RE AOC because: a. Except for total mercury (13% above) and total TEQ (3.4% below; CDD/CDF, PAH and co-planar PCB TEQ combined) in upper trophic level fish, mean concentrations of BUI contaminants in the other three mink prey groups (crayfish, amphibians, lower trophic level fish) were far below dietary LOAELs for mink. b. Using a worst case diet (92% aquatic) for mink, and the analytically-determined mean concentrations of BUI contaminants in potential prey, a hazard assessment showed that the dietary LOAELs for total mercury, total PCBs, and total TEQ would not be exceeded for mink in the Genesee River portion of the RE AOC

Diel Activity Patterns of Mink, Neovison vison, Change with Habitat

Using video traps, we tested the commonly held view that Mink, Neovison vison, are mostly nocturnal. We compared Mink passages during daylight and darkness in two habitats. Mink were significantly more nocturnal in uplands with streams and significantly more diurnal in wetlands. Assuming that uplands have a higher proportion of terrestrial prey active at night and wetlands have a higher proportion of aquatic prey, the observed difference in activity periods may be related to the difficulty of seeing aquatic prey at night and suggests a dynamic interaction between food visibility and diel activity in Mink

Diel Activity Patterns of Mink, Neovison vison, Change with Habitat

Using video traps, we tested the commonly held view that Mink, Neovison vison, are mostly nocturnal. We compared Mink passages during daylight and darkness in two habitats. Mink were significantly more nocturnal in uplands with streams and significantly more diurnal in wetlands. Assuming that uplands have a higher proportion of terrestrial prey active at night and wetlands have a higher proportion of aquatic prey, the observed difference in activity periods may be related to the difficulty of seeing aquatic prey at night and suggests a dynamic interaction between food visibility and diel activity in Mink

Total PCBs, Dioxin-Furan TEQs and Total Mercury Concentrations in Mink In and Out of the Rochester Embayment Area of Concern Near and Inland from the Shore of Lake Ontario

In terms of reproductive and other adverse outcomes after exposure to polychlorinated biphenyls (PCBs), dioxins and furans, the mink (Mustela vison) is one of the most sensitive mammals. Our objective was to determine if there are differences in the concentrations of total mercury (Hg), total PCBs, and dioxin-furan toxic equivalents (TEQs) between mink living in and out of the Rochester Embayment of Lake Ontario (RELO) Area of Concern (AOC) and between mink living near the shore of Lake Ontario and inland. Concentrations of total Hg in brain, total PCB and dioxin-furan TEQ in adipose, and total PCB in liver were significantly higher for mink living near the shore of Lake Ontario than inland. For mink living in and out of the AOC, differences in total PCB and dioxin-furan TEQ in adipose and liver were substantial but not significant. Correlations between concentrations of total Hg, total PCB, and dioxin-furan TEQ in mink were high. Our results suggest that contamination of mink living near the southern shore of Lake Ontario primarily comes from contact with the Lake Ontario food web, not from sources in the RELO AOC

Model Estimates Bioaccumulation of Total PCBs, Dioxin-Furan TEQs, and Total Mercury in Mink Liver Based on Concentrations in Lake Ontario Water

We used stable isotope analysis and a bioaccumulation model to estimate concentrations of total polychlorinated biphenyls (PCB), dioxin-furan toxic equivalents (TEQ), and total mercury (Hg) in mink and to compare predicted ranges with their chemical concentrations in mink liver (PCB, TEQ) and brain (Hg). Actual concentrations were within predicted bounds for total PCB, dioxin-furan TEQ, and Hg except in two cases (lowest PCB and highest Hg) which were very close to predicted bounds. Based on 15N analysis, the trophic level of mink ranged from 3.4 to 3.9. Animals at the upper end of the range were exposed to Lake Ontario water and its food web while those at the lower end were captured at inland locations. Because of the complexity of wetland (an important habitat for mink in this study) food webs with pelagic, littoral, and terrestrial carbon sources and overlapping 13C signatures, whether the origins of mink diets were aquatic or terrestrial could not be determined. We have established a non-destructive biomonitoring tool to reasonably estimate concentrations of total PCB, TEQ and total Hg in mink tissues as concentrations of these chemicals change in their water supply

Histological Lesions in Mink Jaws are a Highly Sensitive Biomarker of Effect after Exposure to TCDD-like Chemicals: Field and Literature-based Confirmations

The mink (Mustela vison) is one of the most sensitive mammals to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-like chemicals. By literature review we established that a histological lesion of the jaw bone of mink, evidenced by squamous epithelial hyperplasia in the gingival tissue that forms nests or cords that infiltrate the periodontal ligament and alveolar bone causing osteolysis of the mandible and maxilla that could lead to squamous cell carcinoma, is the most sensitive known biomarker of effect following exposure of mink to TCDD-like chemicals. Lesions have been observed when total TCDD toxic equivalents (TEQ: dioxins, furans, co-planar polychlorinated biphenyls or PCBs) in liver exceed 40 ng/kg-ww or when total PCB exceeds 1,698 ng/g-ww. This is the second report of histological evidence of this lesion in wild-caught mink, and it is the first report of the lesion being grossly detectable in naturally exposed mink. Some mink living near the south shore of Lake Ontario (exposed to the lake’s food web) but not inland mink (not exposed to the lake’s food web) accumulate more than 40 ng total TEQ/kg or 2 1,698 ng total PCB/kg in liver. Because of its sensitivity, the jaw lesion biomarker is very useful for assessing the health of wildlife populations exposed to TCDD-like chemicals

The Large-Scale Polarization Explorer (LSPE)

The LSPE is a balloon-borne mission aimed at measuring the polarization of the Cosmic Microwave Background (CMB) at large angular scales, and in particular to constrain the curl component of CMB polarization (B-modes) produced by tensor perturbations generated during cosmic inflation, in the very early universe. Its primary target is to improve the limit on the ratio of tensor to scalar perturbations amplitudes down to r = 0.03, at 99.7% confidence. A second target is to produce wide maps of foreground polarization generated in our Galaxy by synchrotron emission and interstellar dust emission. These will be important to map Galactic magnetic fields and to study the properties of ionized gas and of diffuse interstellar dust in our Galaxy. The mission is optimized for large angular scales, with coarse angular resolution (around 1.5 degrees FWHM), and wide sky coverage (25% of the sky). The payload will fly in a circumpolar long duration balloon mission during the polar night. Using the Earth as a giant solar shield, the instrument will spin in azimuth, observing a large fraction of the northern sky. The payload will host two instruments. An array of coherent polarimeters using cryogenic HEMT amplifiers will survey the sky at 43 and 90 GHz. An array of bolometric polarimeters, using large throughput multi-mode bolometers and rotating Half Wave Plates (HWP), will survey the same sky region in three bands at 95, 145 and 245 GHz. The wide frequency coverage will allow optimal control of the polarized foregrounds, with comparable angular resolution at all frequencies.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibite

Developing the Diagnostic Adherence to Medication Scale (the DAMS) for use in clinical practice

There is a need for an adherence measure, to monitor adherence services in clinical practice, which can distinguish between different types of non-adherence and measure changes over time. In order to be inclusive of all patients it needs to be able to be administered to both patients and carers and to be suitable for patients taking multiple medications for a range of clinical conditions. A systematic review found that no adherence measure met all these criteria. We therefore wished to develop a theory based adherence scale (the DAMS) and establish its content, face and preliminary construct validity in a primary care population

Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice.

Introduction: Alzheimer\u27s disease (AD) is the most common form of dementia. Beta-secretase (BACE) inhibitors have been proposed as potential therapeutic interventions; however, initiating treatment once disease has significantly progressed has failed to effectively stop or treat disease. Whether BACE inhibition may have efficacy when administered prophylactically in the early stages of AD has been under-investigated. The present studies aimed to evaluate prophylactic treatment of the BACE inhibitor verubecestat in an AD mouse model using the National Institute on Aging (NIA) resources of the Model Organism Development for Late-Onset Alzheimer\u27s Disease (MODEL-AD) Preclinical Testing Core (PTC) Drug Screening Pipeline. Methods: 5XFAD mice were administered verubecestat ad libitum in chow from 3 to 6 months of age, prior to the onset of significant disease pathology. Following treatment (6 months of age), in vivo imaging was conducted with 18F-florbetapir (AV-45/Amyvid) (18F-AV45) and 18-FDG (fluorodeoxyglucose)-PET (positron emission tomography)/MRI (magnetic resonance imaging), brain and plasma amyloid beta (Aβ) were measured, and the clinical and behavioral characteristics of the mice were assessed and correlated with the pharmacokinetic data. Results: Prophylactic verubecestat treatment resulted in dose- and region-dependent attenuations of 18F-AV45 uptake in male and female 5XFAD mice. Plasma Aβ40 and Aβ42 were also dose-dependently attenuated with treatment. Across the dose range evaluated, side effects including coat color changes and motor alterations were reported, in the absence of cognitive improvement or changes in 18F-FDG uptake. Discussion: Prophylactic treatment with verubecestat resulted in attenuated amyloid plaque deposition when treatment was initiated prior to significant pathology in 5XFAD mice. At the same dose range effective at attenuating Aβ levels, verubecestat produced side effects in the absence of improvements in cognitive function. Taken together these data demonstrate the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provide insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD