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• Individual based model simulates Calanus hyperboreus multi-year life cycle in GSL. • Dormancy entry and exit occur dynamically based on individual lipid content. • Model building generated insights into C. hyperboreus biological processes. • Second reproduction females reproduce earlier & over wider time window. • Eggs spawned earlier align growth with spring bloom, allowing CIV dormancy entry. Calanus hyperboreus is a large-bodied, biomass dominant species that performs a crucial ecosystem energy transfer by converting the spring phytoplankton bloom into lipid reserves that fuel the higher trophic levels of the Gulf of St. Lawrence (GSL) pelagic ecosystem, including the critically endangered North Atlantic right whale (Eubalena glacialis). Given that the GSL, the southernmost core habitat of C. hyperboreus , is undergoing rapid warming, developing a population model allows us to synthesize existing knowledge of the species, and to examine the species response to environmental conditions. To simulate the multi-year life cycle in the northwest GSL, model equations are implemented for ingestion, assimilation, respiration, egg production, stage development, mortality, and vertical migration behaviors including dormancy entry and exit. The 1-D particle-based model predicts the evolution of individual stage, structural mass, lipid, age, sex, abundance, and egg production, as well as the seasonal evolution of the population structure in the northwest GSL. Individual lipid-based thresholds inform the timing of ontogenetic vertical migration. Life cycle targets defined from a literature review are used to guide model parameterization and assess its performance. The simulated population structure, phenology, and size at stage are generally consistent with observations. Under 10 years of repeat year forcing, the model simulates a quasi-stable overwintering population composed of late stages CIV, CV and CVI. Observations suggest that stage CIV is the first overwintering stage in the GSL, and point to the occurrence of iteroparous females. Using the model, the relative success of diverse dormancy and reproductive phenotypes are explored. Second reproduction females reproduce earlier in winter than first reproduction females, with implications for the ability of the new generation to match the spring bloom and accumulate sufficient lipid to overwinter as stage CIV. Without iteroparity, the time window of reproduction contracts and the population is reduced, underscoring the role of a flexible multi-year life cycle in population success. [ABSTRACT FROM AUTHOR]

• This study examined the seasonal and interannual variability of phenology and relative distribution of C. hyperboreus biomass in the southern Gulf of St. Lawrence using a 3-D coupled biophysical model. • Our study confirmed that C. hyperboreus distribution in the sGSL is mainly influenced by transport from adjacent deeper areas through interactions between ocean circulation and early copepodite stages during the spring. • Model results indicated that various number of C. hyperboreus individuals were transported annually from the Laurentian Channel to the sGSL during their active stages and were retained near the seafloor in late-spring early-summer. • Biophysical simulation outputs contributed to assess the locations of NARW potential foraging habitat formation and improve understanding NARW seasonal dynamics in the sGSL in spring and early-summer. Since 2015, North Atlantic right whale (NARW) occurrences have considerably increased in the Gulf of St. Lawrence (GSL), likely driven by a decrease in the availability of their historically preferred prey, the lipid-rich Calanus spp. (Copepoda), in their traditional foraging habitats. In the southern GSL (sGSL) where most NARW sightings occurred in recent years, the large bodied and lipid-rich Calanus hyperboreus dominates the Calanus spp. biomass in the spring and early summer, with important interannual variability hypothesized to be driven by variations in phenology and transport. This study examined the seasonal and interannual variability of phenology and relative distribution of C. hyperboreus biomass in the sGSL during the spring and early summer from 2016 to 2019, using a 3-D coupled biophysical model. We simulated the development and advection of the new cohort of C. hyperboreus from first copepodite (CI) stages in early spring to mid-July, a period during which they enter diapause as lipid-rich fourth copepodite (CIV) stages. Our study confirmed that C. hyperboreus distribution in the sGSL is mainly influenced by transport from adjacent deeper areas through interactions between ocean circulation and early copepodite stages during the spring. Model results indicated variable numbers of simulated individuals from the Laurentian Channel were transported annually to the sGSL during their active stages, entered diapause, and were retained near the seafloor in the summer. Biophysical simulation outputs could therefore contribute to seasonal-scale advice on locations of NARW potential foraging habitat formation and improve understanding NARW seasonal dynamics in the sGSL. [ABSTRACT FROM AUTHOR]

Highlights • New model represents Calanus life history, vertical behavior & ocean circulation. • Model simulates high surface layer prey abundance in the sGSL in summer & fall. • Transport of active stages is important to late stage Calanus abundance in sGSL. • Model intercomparison & groundtruthing identify future coupled model improvements. Abstract Two copepod species, Calanus finmarchicus and Calanus hyperboreus , constitute the main prey of endangered North Atlantic right whales in eastern Canadian shelf waters. Estimating the spatial distribution of Calanus spp. and understanding how it changes in response to environmental variability are crucial information requirements for mitigating risks to the right whale population. Here we present a new coupled dynamic model that builds on observations from the Atlantic Zone Monitoring Program (AZMP) and statistical modelling of copepod spatial distributions using Generalized Additive Models (GAMs). The coupled model is initialized with the GAMs climatological abundance and explicitly represents transport of the two species C. finmarchicus and C. hyperboreus via particle tracking, considering Calanus vertical swimming behavior and along-track mortality and temperature-dependent development. Assessment of model performance and the role of advection in determining the modelled Calanus distributions is focused on the southern Gulf of St. Lawrence (sGSL), an area regularly visited by right whales, and where local Calanus abundance is likely dependent on the seasonal transport from deep upstream areas. The coupled model simulates high Calanus abundance in the sGSL in summer and fall, distinct from the spatial distribution estimated by GAMs, which do not consider the effect of transport in the region. The exercise of building and testing this model allows us to investigate the factors producing high concentrations of late stage Calanus , and in the cases of model-data mismatch, infer important processes that are not adequately represented in the model. The model constitutes an important step forward in the ongoing effort to improve estimates of Calanus availability in the region, guiding future modelling efforts (e.g., a population development model) and potentially informing North Atlantic right whale management. [ABSTRACT FROM AUTHOR]

• Prey transport to sGSL right whale foraging habitat shaped by runoff, wind, warming. • Model simulates Cool & Warm Year C. finmarchicus & C. hyperboreus spatial patterns. • Advection dominates southern GSL Calanus influx variability in spring-early summer. • GSL C. finmarchicus population declines drive late summer-fall variability. • Large upstream population declines on the Scotian Shelf dominate at Roseway Basin. Starting ~2010, declines in Calanus finmarchicus and Calanus hyperboreus , the biomass dominant copepods on the northwest Atlantic shelf, coincide with notable ocean warming and a northward shift in endangered North Atlantic right whale (Eubalena glacialis) foraging habitat from the Bay of Fundy/Western Scotian Shelf to the southern Gulf of St. Lawrence (sGSL). Abundance changes in right whales' prey , lipid-rich Calanus late stages , are known to relate to shifts in Calanus demography and changes in Calanus transport. Our objective was to investigate how these mechanistic drivers shaped potential whale preyscapes during the relatively cooler, high-abundance 2000′s vs the warmer, lower abundance 2010′s. Here, bio-physical Calanus model "Cool Year" and "Warm Year" simulations are used to quantify relative effects of the physical environment vs population level. Analysis is focused on the western sGSL, where right whales have recently been observed foraging in high numbers. Simulations indicate that Calanus variability is most strongly influenced by changes in advection from upstream areas, linked to river runoff and winds on the coastal Gaspé Current in late spring and summer. In the simulated Cool Year (2008), high runoff is associated with a strong Gaspé Current hugging the coastline and advection of Calanus into the western sGSL. Conversely, in the simulated Warm Year (2012), lower runoff led to a separation of the Gaspé Current from the coast, transporting Calanus eastward along the Laurentian Channel, away from Shediac Valley. Variation in population size drives changes in late stage Calanus delivery to the western sGSL in late summer and fall. Complementary analyses on the Western Scotian Shelf indicate that the source of Calanus to Roseway Basin can shift between the coastal Nova Scotia Current and Scotian Shelf slope water, but large declines in upstream population drive lower Warm Year abundance. Our findings inform marine managers about how Calanus high abundance areas may continue to change in the future. [ABSTRACT FROM AUTHOR]

Problems with emotional attachment to objects (i.e., object attachment) are a key component of hoarding disorder (HD) in the cognitive-behavioral model of HD. We hypothesized that excessive object attachment is an attempt to compensate for unmet relatedness needs. We tested this hypothesis in two studies by examining whether object attachment mediates the relationship between loneliness and HD using bootstrapped multiple regression analyses in a community sample (Study 1; n = 213) and an undergraduate sample of individuals with high hoarding symptoms (Study 2: n = 91). Participants in both studies completed self-report measures of loneliness, object attachment, and hoarding symptoms. Study 2 also accounted for the possible confounding effects of age and depressive symptoms. Results from both studies showed that loneliness and object attachment were positively associated with HD symptoms. Study 1 showed that object attachment mediated the relationship between loneliness and HD symptoms, and Study 2 showed a significant mediation even after accounting for age and depression. Results provide justification for further experimental and longitudinal research into loneliness as both a cause and consequence of object attachment and HD. Further investigation may be warranted into the possibility that addressing loneliness in HD might result in lower object attachment. • Loneliness and object attachment were positively associated with hoarding. • Object attachment mediated the relationship between loneliness and hoarding. • Object attachment might be an attempt at compensating for loneliness. [ABSTRACT FROM AUTHOR]

Abstract: 17β-Hydroxysteroid dehydrogenase II (17β-HSD II) antagonists may provide an important way into preventing the onset of osteoporosis. The discovery of 4,5-disubstituted cis-pyrrolidinones as 17β-HSD II inhibitors led to the development of an efficient intramolecular Michael addition, followed by catalytic hydrogenation to obtain the desired cis configuration. [Copyright &y& Elsevier]

Abstract: Novel anthranilamides were surprisingly found to exert additional activity on B-RAF. Corresponding thiophene, pyrazole, and thiazole core analogs were prepared as VEGFR-2 inhibitors with c-KIT, and B-RAF activity. Compounds in the phenyl, thiophene, and thiazole series are in vivo active. [Copyright &y& Elsevier]

Abstract: A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors of 17β-HSD II for the treatment of osteoporosis. Biochemical data for several compounds are given. Compound 42 was selected as the lead candidate. [Copyright &y& Elsevier]

Abstract: 4,5-Disubstituted cis-pyrrolidinones were investigated as inhibitors of type II 17β-hydroxysteroid dehydrogenase (17β-HSD). Early structure–activity relationship patterns for this class of compounds are discussed. [Copyright &y& Elsevier]