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Abstract Introduction Clinical trials involving patients with Alzheimer's disease (AD) continue to try to identify disease‐modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods A systematic review sought research that elicited information from people with AD, their caregivers, and health‐care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.

The abundances of migratory shark species observed throughout the Mid-Atlantic Bight (MAB) during productive summer months suggest that this region provides critical habitat and prey resources to these taxa. However, the principal prey assemblages sustaining migratory shark biomass in this region are poorly defined. We applied high-throughput DNA metabarcoding to shark feces derived from cloacal swabs across nine species of Carcharhinid and Lamnid sharks to (1) quantify the contribution of broad taxa (e.g., invertebrates, fishes) supporting shark biomass during seasonal residency in the MAB and (2) determine whether the species displayed distinct dietary preference indicative of resource partitioning. DNA metabarcoding resulted in high taxonomic (species-level) resolution of shark diets with actinopterygian and elasmobranch fishes as the dominant prey categories across the species. DNA metabarcoding identified several key prey groups consistent across shark taxa that are likely integral for sustaining their biomass in this region, including Atlantic menhaden (Brevoortia tyrannus), Atlantic mackerel (Scomber scombrus), and benthic elasmobranchs, including skates. Our results are consistent with previously published stomach content data for the shark species of similar size range in the Northwest Atlantic Ocean, supporting the efficacy of cloacal swab DNA metabarcoding as a minimally invasive diet reconstruction technique. The high reliance of several shark species on Atlantic menhaden could imply wasp-waist food-web conditions during the summer months, whereby high abundances of forage fishes sustain a diverse suite of migratory sharks within a complex, seasonal food web., (© 2023 Fisheries Society of the British Isles.)

Recent spikes in interactions between humans and sharks in the New York Bight have sparked widespread reporting of possible causalities, many of which lack empirical support. Here we comment on the current state of knowledge regarding shark biology and management in New York waters emphasizing that the possible drivers of increased human-shark interactions are confounded by a lack of historical monitoring data. We outline several key research avenues that should be considered to ensure the safe and sustainable coexistence of humans, sharks, and their prey, in an era of accelerated environmental change., (© 2023 Fisheries Society of the British Isles.)

Understanding how intraspecific variation in the use of prey resources impacts energy metabolism has strong implications for predicting long-term fitness and is critical for predicting population-to-community level responses to environmental change. Here, we examine the energetic consequences of variable prey resource use in a widely distributed marine carnivore, juvenile sand tiger sharks (Carcharias taurus). We used carbon and nitrogen isotope analysis to identify three primary prey resource pools-demersal omnivores, pelagic forage, and benthic detritivores and estimated the proportional assimilation of each resource using Bayesian mixing models. We then quantified how the utilization of these resource pools impacted the concentrations of six plasma lipids and how this varied by ontogeny. Sharks exhibited variable reliance on two of three predominant prey resource pools: demersal omnivores and pelagic forage. Resource use variation was a strong predictor of energetic condition, whereby individuals more reliant upon pelagic forage exhibited higher blood plasma concentrations of very low-density lipoproteins, cholesterol, and triglycerides. These findings underscore how intraspecific variation in resource use may impact the energy metabolism of animals, and more broadly, that natural and anthropogenically driven fluctuations in prey resources could have longer term energetic consequences., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Coastal ecosystems are essential for absorbing and bouncing back from the impacts of climate change, yet accelerating climate change is causing anthropogenically-derived stressors in these ecosystems to grow. The effects of stressors are more difficult to foresee when they act simultaneously, however, predicting these effects is critical for understanding ecological change. Spartina alterniflora (Spartina), a foundational saltmarsh plant key to coastal resilience, is subject to biological stress such as herbivory, as well as anthropogenic stress such as chemical pollution. Using saltmarsh mesocosms as a model system in a fully factorial experiment, we tested whether the effects of herbivory and two chemicals (oil and dispersant) were mediated or magnified in combination. Spartina responded to stressors asynchronously; ecophysiology responded negatively to oil and herbivores in the first 2-3 weeks of the experiment, whereas biomass responded negatively to oil and herbivores cumulatively throughout the experiment. We generally found mixed multi-stressor effects, with slightly more antagonistic effects compared to either synergistic or additive effects, despite significant reductions in Spartina biomass and growth from both chemical and herbivore treatments. We also observed an indirect positive effect of oil on Spartina, via a direct negative effect on insect herbivores. Our findings suggest that multi-stressor effects in our model system, 1) are mixed but can be antagonistic more often than expected, a finding contrary to previous assumptions of primarily synergistic effects, 2) can vary in duration, 3) can be difficult to discern a priori, and 4) can lead to ecological surprises through indirect effects with implications for coastal resilience. This leads us to conclude that understanding the simultaneous effects of multiple stressors is critical for predicting foundation-species persistence, discerning ecosystem resilience, and managing and mitigating impacts on ecosystem services., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Nitrogen isotope (δ 15 N) analysis of bulk tissues and individual amino acids (AA) can be used to assess how consumers maintain nitrogen balance with broad implications for predicting individual fitness. For elasmobranchs, a ureotelic taxa thought to be constantly nitrogen limited, the isotopic effects associated with nitrogen-demanding events such as prolonged gestation remain unknown. Given the linkages between nitrogen isotope variation and consumer nitrogen balance, we used AA δ 15 N analysis of muscle and liver tissue collected from female bonnethead sharks (Sphyrna tiburo, n = 16) and their embryos (n = 14) to explore how nitrogen balance may vary across gestation. Gestational stage was a strong predictor of bulk tissue and AA δ 15 N values in pregnant shark tissues, decreasing as individuals neared parturition. This trend was observed in trophic (e.g., Glx, Ala, Val), source (e.g., Lys), and physiological (e.g., Gly) AAs. Several potential mechanisms may explain these results including nitrogen conservation, scavenging, and bacterially mediated breakdown of urea to free ammonia that is used to synthesize AAs. We observed contrasting patterns of isotopic discrimination in embryo tissues, which generally became enriched in 15 N throughout development. This was attributed to greater excretion of nitrogenous waste in more developed embryos, and the role of physiologically sensitive AAs (i.e., Gly and Ser) to molecular processes such as nucleotide synthesis. These findings underscore how AA isotopes can quantify shifts in nitrogen balance, providing unequivocal evidence for the role of physiological condition in driving δ 15 N variation in both bulk tissues and individual AAs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mercury (Hg) concentrations in fishes from the NW Atlantic Ocean pose concern due to the importance of this region to U.S. fisheries harvest. In this study, total Hg (THg) concentrations and nitrogen stable isotope (δ 15 N) values were quantified in muscle tissues sampled from Golden (Lopholatilus chamaeleonticeps) and Blueline (Caulolatilus microps) Tilefish collected during a fishery-independent survey conducted in the NW Atlantic to compare bioaccumulation patterns between these species. Total Hg concentrations averaged (±SD) 0.4 ± 0.4 μg/g dry weight (d.w.) for L. chamaeleonticeps and 1.1 ± 0.7 μg/g d.w. for C. microps with <2% of all sampled fish, those >70 cm fork length, exceeding the most restrictive USEPA regulatory guidelines for human consumption (THg > 0.46 μg/g w.w.), when converted to wet weight concentrations. The THg concentrations reported here for individuals from the NW Atlantic stock are comparable to those reported for similarly sized individuals collected from the SW Atlantic stock but notably lower than those reported for Gulf of Mexico L. chamaeleonticeps, indicating different Hg exposure and assimilation kinetics for fish from the NW Atlantic, and highlights the broad geographic variability of Hg bioaccumulation among Tilefish stocks. Caulolatilus microps had higher δ 15 N values relative to L. chamaeleonticeps and a pattern of decreasing THg concentrations was also present from south to north across the study range. It is concluded that this trophic difference and spatial pattern in Tilefish THg concentrations emphasizes the habitat and resource partitioning mechanisms described for these sympatric species that permits their coexistence in the continental shelf environment. Importantly, regional variability in THg concentrations accentuate the possible roles of fine-scale biotic and abiotic processes that can act to regulate Hg bioaccumulation among individuals and species., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Bioindicator species are commonly used as proxies to help identify the ecological effects of oil spills and other stressors. However, the utility of taxa as bioindicators is dependent on understanding their trophic niche and life history characteristics, as these factors mediate their ecological responses. Seaside sparrows ( Ammospiza maritima) and marsh rice rats ( Oryzomys palustris ) are two ubiquitous terrestrial vertebrates that are thought to be bioindicators of oil spills in saltmarsh ecosystems. To improve the utility of these omnivorous taxa as bioindicators, we used carbon and nitrogen stable isotope analysis to quantify their trophic niches at saltmarshes in coastal Louisiana with differing oiling histories. We found that rats generally had lower trophic positions and incorporated more aquatic prey relative to seaside sparrows. The range of resources used (i.e.,trophic niche width) varied based on oiling history. Seaside sparrows had wider trophic niches than marsh rice rats at unoiled sites, but not at oiled sites. Trophic niche widths of conspecifics were less consistent at oiled sites, although marsh rice rats at oiled sites had wider trophic niches than rats at unoiled sites. These results suggest that past oiling histories may have imparted subtle, yet differing effects on the foraging ecology of these two co-occurring species. However, the temporal lag between initial oiling and our study makes identifying the ultimate drivers of differences between oiled and unoiled sites challenging. Even so, our findings provide a baseline quantification of the trophic niches of sympatric seaside sparrows and marsh rice rats that will aid in the use of these species as indicators of oiling and other environmental stressors in saltmarsh ecosystems., Competing Interests: The authors declare there are no competing interests., (©2021 Moyo et al.)

Golden and Blueline Tilefish ( Lopholatilus chamaeleonticeps and Caulolatilus microps ) are keystone taxa in northwest (NW) Atlantic continental shelf-edge environments due to their biotic (trophic-mediated) and abiotic (ecosystem engineering) functional roles combined with high-value fisheries. Despite this importance, the ecological niche dynamics (i.e., those relating to trophic behavior and food-web interactions) of these sympatric species are poorly understood, knowledge of which may be consequential for maintaining both ecosystem function and fishery sustainability. We used stable isotope ratios of carbon (δ 13 C) and nitrogen (δ 15 N) to build realized ecological niche hypervolumes to serve as proxies for diet and production use patterns of L .  chamaeleonticeps and C. microps . We hypothesized that: (a) species exhibit ontogenetic shifts in diet and use of production sources; (b) species acquire energy from spatially distinct resource pools that reflect a sedentary life-history and differential use of the continental shelf-edge; and (c) species exhibit differentiation in one or more measured niche axes. We found evidence for ontogenetic shifts in diet (δ 15 N) but not production source (δ 13 C) in both species, suggesting a subtle expansion of measured ecological niche axes. Spatial interpolation of stable isotope ratios showed distinct latitudinal gradients; for example, individuals were 13 C enriched in northern and 15 N enriched in southern regions, supporting the assertion that tilefish species acquire energy from regional resource pools. High isotopic overlap was observed among species (≥82%); however, when hypervolumes included depth and region of capture, overlap among species substantially decreased to overlap estimates of 15%-77%. This suggests that spatial segregation could alleviate potential competition for resources among tilefish species inhabiting continental shelf-edge environments. Importantly, our results question the consensus interpretation of isotopic overlap estimates as representative of direct competition among species for shared resources or habitats, instead identifying habitat segregation as a possible mechanism for coexistence of tilefish species in the NW Atlantic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

A multinational demersal longline survey was conducted on the Gulf of Mexico continental shelf over the years 2015 and 2016 to generate a Gulf-wide baseline of polycyclic aromatic hydrocarbon (PAH) concentrations in demersal fishes. Tilefish (Lopholatilus chamaeleonticeps) were sampled in all regions of the Gulf of Mexico for biometrics, bile, and liver. Tilefish liver was also obtained from surveys in the northwest Atlantic Ocean for comparison. Liver tissues (n = 305) were analyzed for PAHs and select alkylated homologs using QuEChERS extractions and gas chromatography tandem mass spectrometry. Bile samples (n = 225) were analyzed for biliary PAH metabolites using high-performance liquid chromatography with fluorescence detection. Spatial comparisons indicate the highest levels of PAH exposure and hepatic accumulation in the north central Gulf of Mexico, with decreasing concentrations moving from the north central Gulf counterclockwise, and an increase on the Yucatán Shelf. Hepatic PAH concentrations were similar between the Gulf of Mexico and the northwest Atlantic, however, Tilefish from the northwest Atlantic had higher concentrations and more frequent detection of carcinogenic high molecular weight PAHs. Overall, results demonstrate that PAH pollution was ubiquitous within the study regions, with recent exposure and hepatic accumulation observed in Tilefish from both the Gulf of Mexico and northwest Atlantic., Competing Interests: Declaration of competing interest Declare no conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Determining the flow of energy from primary producers to higher trophic levels in complex systems remains an important task for ecologists. Biomarkers can be used to trace carbon or energy sources contributing to an organism's tissues. However, different biomarkers vary in their ability to trace carbon sources based on how faithfully they transfer between trophic levels. Comparing emerging biomarker techniques with more commonly used techniques can demonstrate the relative efficacy of each in specific systems., Methods: Two common biomarker techniques, fatty acid analysis (FAA) and bulk stable isotope analysis (SIA), and one emerging biomarker technique, compound-specific stable isotope analysis of amino acids (CSIA-AA), were compared to assess their ability to characterize and quantify basal carbon sources supporting the seaside sparrow (Ammodramus maritimus), a common salt marsh species. Herbivorous insect and deposit-feeding fiddler crab biomarker values were analyzed as proxies of major terrestrial and aquatic basal carbon sources, respectively., Results: All three biomarker techniques indicated that both terrestrial and aquatic carbon sources were important to seaside sparrows. However, FAA could only be evaluated qualitatively, due to a currently limited understanding of trophic modification of fatty acids between primary producer and this consumer's tissues. Quantitative stable isotope (SIA or CSIA-AA) mixing models predicted nearly equal contributions of terrestrial and aquatic carbon sources supporting seaside sparrows, yet estimates based on CSIA-AA had greater precision., Conclusions: These findings support the use of CSIA-AA as an emerging tool to quantify the relative importance of basal carbon sources in salt marsh consumers. Integrating multiple biomarker techniques, with their differing benefits and limitations, will help to constrain models of carbon and energy flow in future ecosystem studies., (© 2019 John Wiley & Sons, Ltd.)

Measures of trophic position (TP) are critical for understanding food web interactions and human-mediated ecosystem disturbance. Nitrogen stable isotopes (δ(15) N) provide a powerful tool to estimate TP but are limited by a pragmatic assumption that isotope discrimination is constant (change in δ(15) N between predator and prey, Δ(15) N = 3.4‰), resulting in an additive framework that omits known Δ(15) N variation. Through meta-analysis, we determine narrowing discrimination from an empirical linear relationship between experimental Δ(15) N and δ(15) N values of prey consumed. The resulting scaled Δ(15) N framework estimated reliable TPs of zooplanktivores to tertiary piscivores congruent with known feeding relationships that radically alters the conventional structure of marine food webs. Apex predator TP estimates were markedly higher than currently assumed by whole-ecosystem models, indicating perceived food webs have been truncated and species-interactions over simplified. The scaled Δ(15) N framework will greatly improve the accuracy of trophic estimates widely used in ecosystem-based management., (© 2013 The Authors. Ecology Letters published by John Wiley & Sons Ltd and CNRS.)

Polychlorinated biphenyls (PCBs) were quantified in liver tissues of bull sharks (Carcharhinus leucas) ranging in age from <4 wk to >3 yr. Summed values of PCBs (ΣPCBs) ranged from 310 ng/g to 22 070 ng/g (lipid wt) across age classes with ΣPCB concentrations for the youngest sharks in the present study (<4 wk; 5230 ± 2170 ng/g lipid wt) determined to not significantly differ from those quantified in >3-yr-old sharks, highlighting the extent of exposure of this young life stage to this class of persistent organic pollutants (POPs). Age normalization of PCB congener concentrations to those measured for the youngest sharks demonstrated a significant hydrophobicity (log octanol/water partition coefficient [KOW ]) effect that was indicative of maternal offloading of highly hydrophobic (log KOW ≥6.5) congeners to the youngest individuals. A distinct shift in the PCB congener profiles was also observed as these young sharks grew in size. This shift was consistent with a transition from the maternally offloaded signal to the initiation of exogenous feeding and the contributions of mechanisms including growth dilution and whole-body elimination. These results add to the growing pool of literature documenting substantially high concentrations of POPs in juvenile sharks that are most likely attributable to maternal offloading. Collectively, such results underscore the potential vulnerability of young sharks to POP exposure and pose additional concerns for shark-conservation efforts., (© 2013 SETAC.)

The application of stable isotopes to characterize the complexities of a species foraging behavior and trophic relationships is dependent on assumptions of δ(15)N diet-tissue discrimination factors (∆(15)N). As ∆(15)N values have been experimentally shown to vary amongst consumers, tissues and diet composition, resolving appropriate species-specific ∆(15)N values can be complex. Given the logistical and ethical challenges of controlled feeding experiments for determining ∆(15)N values for large and/or endangered species, our objective was to conduct an assessment of a range of reported ∆(15)N values that can hypothetically serve as surrogates for describing the predator-prey relationships of four shark species that feed on prey from different trophic levels (i.e., different mean δ(15)N dietary values). Overall, the most suitable species-specific ∆(15)N values decreased with increasing dietary-δ(15)N values based on stable isotope Bayesian ellipse overlap estimates of shark and the principal prey functional groups contributing to the diet determined from stomach content analyses. Thus, a single ∆(15)N value was not supported for this speciose group of marine predatory fishes. For example, the ∆(15)N value of 3.7‰ provided the highest percent overlap between prey and predator isotope ellipses for the bonnethead shark (mean diet δ(15)N = 9‰) whereas a ∆(15)N value < 2.3‰ provided the highest percent overlap between prey and predator isotope ellipses for the white shark (mean diet δ(15)N = 15‰). These data corroborate the previously reported inverse ∆(15)N-dietary δ(15)N relationship when both isotope ellipses of principal prey functional groups and the broader identified diet of each species were considered supporting the adoption of different ∆(15)N values that reflect the predators' δ(15)N-dietary value. These findings are critical for refining the application of stable isotope modeling approaches as inferences regarding a species' ecological role in their community will be influenced with consequences for conservation and management actions.

Stable-isotope analysis (SIA) can act as a powerful ecological tracer with which to examine diet, trophic position and movement, as well as more complex questions pertaining to community dynamics and feeding strategies or behaviour among aquatic organisms. With major advances in the understanding of the methodological approaches and assumptions of SIA through dedicated experimental work in the broader literature coupled with the inherent difficulty of studying typically large, highly mobile marine predators, SIA is increasingly being used to investigate the ecology of elasmobranchs (sharks, skates and rays). Here, the current state of SIA in elasmobranchs is reviewed, focusing on available tissues for analysis, methodological issues relating to the effects of lipid extraction and urea, the experimental dynamics of isotopic incorporation, diet-tissue discrimination factors, estimating trophic position, diet and mixing models and individual specialization and niche-width analyses. These areas are discussed in terms of assumptions made when applying SIA to the study of elasmobranch ecology and the requirement that investigators standardize analytical approaches. Recommendations are made for future SIA experimental work that would improve understanding of stable-isotope dynamics and advance their application in the study of sharks, skates and rays., (© 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.)

Stable isotopes of neonatal vertebrates reflect those of their mother's diet and foraging location. Evaluating feeding strategies and habitat use of neonates is consequently complicated by the maternal isotopic signal and its subsequent elimination with growth. Thus, methods that measure the loss of the maternal signal, i.e. when the isotopic signal of a neonate reflects its own diet, are needed. Values of δ(13)C and δ(15)N were measured in liver and muscle tissues of <1 year old bull (Carcharhinus leucas) and Atlantic sharpnose (Rhizoprionodon terraenovae) sharks and related to age using, total length, date sampled and umbilical scar stage (USS). We observed a decline in δ(13)C and δ(15)N values with age that was different among species, similar among isotopes, and greater in liver than in muscle; highlighting that retention of the maternal signal is dependent on species-specific life history and tissue characteristics. USS was most effective for assessing the loss of the maternal isotopic signal in the faster growing Atlantic sharpnose shark, but was less effective for the slower growing bull shark. Total length and date sampled were overall less effective and may be more informative for slower growing species when coupled with USS, as variable size at birth and misclassification of animals >1 year old, which remain in nursery habitats, increase the variability of the isotopic values. Consideration of the maternal signal and measuring its loss are thus necessary when analyzing the stable isotopes of young animals, as there is potential to misinterpret feeding strategies, over-estimate trophic position and incorrectly assign carbon source., (Copyright © 2011 John Wiley & Sons, Ltd.)

Stable nitrogen (delta(15)N) and carbon (delta(13)C) isotopes of Atlantic sharpnose shark Rhizoprionodon terraenovae embryos and mothers were analysed. Embryos were generally enriched in (15)N in all studied tissue relative to their mothers' tissue, with mean differences between mother and embryo delta(15)N (i.e. Deltadelta(15)N) being 1.4 per thousand for muscle, 1.7 per thousand for liver and 1.1 per thousand for cartilage. Embryo muscle and liver were enriched in (13)C (both Deltadelta(13)C means = 1.5 per thousand) and embryo cartilage was depleted (Deltadelta(13)C mean = -1.01 per thousand) relative to corresponding maternal tissues. While differences in delta(15)N and delta(13)C between mothers and their embryos were significant, muscle delta(15)N values indicated embryos to be within the range of values expected if they occupied a similar trophic position as their respective mothers. Positive linear relationships existed between embryo total length (L(T)) and Deltadelta(15)N for muscle and liver and embryo L(T) and Deltadelta(13)C for muscle, with those associations possibly resulting from physiological differences between smaller and larger embryos or differences associated with the known embryonic nutrition shift (yolk feeding to placental feeding) that occurs during the gestation of this placentatrophic species. Together these results suggest that at birth, the delta(15)N and delta(13)C values of R. terraenovae are likely higher than somewhat older neonates whose postpartum feeding habits have restructured their isotope profiles to reflect their postembryonic diet.

This article describes the architectural design of a secure forensic state psychiatric hospital. The project combined input from staff at all levels of the client organization, outside consultants, and a team of experienced architects. The design team was able to create a design that maximized patient dignity and privacy on one hand, and the ability of staff to observe all patient activity on the other. The design centers around 24-bed units, broken into smaller living wings of eight beds each. Each eight-bed living wing has its own private bathrooms (two) and showers (two), as well as a small living area solely reserved for these eight patients and their guests. An indoor-outdoor dayroom allows patients to go outside whenever they choose, while allowing staff to continue observing them. The heart of the facility is a large treatment mall, designed to foster the acquisition of social, emotional, cognitive, and behavioral skills that will help patients to safely return to their communities., (Copyright 2002 John Wiley & Sons, Ltd.)

To clarify the relationship between dissociative symptoms and obsessive-compulsive disorder (OCD), 100 patients with OCD were assessed with standardized instruments measuring symptoms of OCD, dissociation, and depression. Diagnoses of personality disorders and dissociative disorders were made using structured interviews. Compared with a previous study, OCD patients had dissociation scores slightly higher than normal controls and comparable to patients with other anxiety disorders. Patients with elevated dissociation scores had more severe OCD symptoms, were more depressed, and were more likely to have a personality disorder than patients with low dissociation scores. Although dissociative symptoms were frequently reported by OCD patients, symptoms of OCD may also mimic dissociation in some patients.