Use of island and mainland shorelines by woodland caribou during the nursery period in two northern Ontario parks

Predation is considered a primary limiting factor of woodland caribou (Rangifer tarandus caribou) populations across North America. Caribou are especially vulnerable to predation during their first few weeks of life and have evolved space-use strategies to reduce predation risk through habitat selection during the critical calving and nursery period. We assessed landscape-scale physical characteristics and landcover types associated with caribou nursery sites in Wabakimi and Woodland Caribou Provincial Parks in northern Ontario to better understand nursery site selection in relatively undisturbed landscapes. Although free from industrial activity, these protected areas may subject caribou to human recreational disturbance, so our secondary objective was to evaluate female caribou nursery site selection relative to human recreational activities. We determined that parturient caribou selected landscape characteristics at multiple spatial scales that may reduce predation risk during the calving and nursery period. Generally, female caribou in both parks selected larger lakes with larger than average sized islands configured within shorter than average distances to other islands or landforms that might facilitate escape from predators. The majority of caribou nursery areas in both parks occurred on islands rather than the mainland shoreline of lakes that were surveyed. The nearest landform for escape from these nursery sites on islands was typically another island, and most often 2-3 islands, suggesting parturient caribou may choose islands clustered together as part of their escape strategy. In Woodland Caribou Provincial Park, caribou nursery sites occurred more often in coniferous landcover than expected from availability, while in Wabakimi Provincial Park caribou used sparse, mixed and coniferous forests for nursery activity. Caribou cow-calf pairs typically used areas for nursery activity that were 9.1 km (± 1.0 km, range 2.3-20.6 km) in Wabakimi Provincial Park and 10.2 km (± 0.7 km, range 0.7-32.6 km) in Woodland Caribou Provincial Park from any human recreational disturbance. These landscape-scale physical characteristics and landcover types associated with caribou nursery sites may be used to predict locations of potential caribou nursery areas both outside and within protected areas for the provision of adequate protection and to ensure the persistence of this valued species

Tectonic motion site survey of the National Radio Astronomy Observatory, Green Bank, West Virginia

A geological and geophysical site survey was made of the area around the National Radio Astronomy Observatory (NRAO) to determine whether there are at present local tectonic movements that could introduce significant errors to Very Long Baseline Interferometry (VLBI) geodetic measurements. The site survey consisted of a literature search, photogeologic mapping with Landsat and Skylab photographs, a field reconnaissance, and installation of a seismometer at the NRAO. It is concluded that local tectonic movement will not contribute significantly to VLBI errors. It is recommended that similar site surveys be made of all locations used for VLBI or laser ranging

Molecular determinants of a competent bovine corpus luteum: first vs final wave dominant follicles

Reproductive management in cattle requires the synchrony of follicle development and oestrus before insemination. However, ovulation of follicles that have not undergone normal physiological maturation can lead to suboptimal luteal function. Here, we investigated the expression of a targeted set of 47 genes in (a) a first-wave vs final-wave dominant follicle (DF; the latter destined to ovulate spontaneously) and (b) 6-day-old corpora lutea (CLs) following either spontaneous ovulation or induced ovulation of a first-wave DF to ascertain their functional significance for competent CL development. Both the mass and progesterone-synthesising capacity of a CL formed following induced ovulation of a first-wave DF were impaired. These impaired CLs had reduced expression of steroidogenic enzymes (e.g. STAR and HSD3B1), luteotrophic receptors (LHCGR) and angiogenic regulators (e.g. VEGFA) and increased expression of BMP2 (linked to luteolysis). Relative to final-wave DFs, characteristic features of first-wave DFs included reduced oestradiol concentrations and a reduced oestradiol:progesterone ratio in the face of increased expression of key steroidogenic enzymes (i.e. CYP11A1, HSD3B1 and CYP19A1) in granulosa cells and reduced expression of the HDL receptor SCARB1 in thecal cells. Transcripts for further components of the TGF and IGF systems (e.g. INHA, INHBA, IGF2R and IGFBP2) varied between the first- and final-wave DFs. These results highlight the importance of hormones such as progesterone interacting with local components of both the TGF and IGF systems to affect the maturation of the ovulatory follicle and functional competency of the subsequent CL

Global projections of flash drought show increased risk in a warming climate

Flash drought, characterized by unusually rapid drying, can have substantial impact on many socioeconomic sectors, particularly agriculture. However, potential changes to flash drought risk in a warming climate remain unknown. In this study, projected changes in flash drought frequency and cropland risk from flash drought are quantified using global climate model simulations. We find that flash drought occurrence is expected to increase globally among all scenarios, with the sharpest increases seen in scenarios with higher radiative forcing and greater fossil fuel usage. Flash drought risk over cropland is expected to increase globally, with the largest increases projected across North America (change in annual risk from 32% in 2015 to 49% in 2100) and Europe (32% to 53%) in the most extreme emissions scenario. Following low-end and medium scenarios compared to high-end scenarios indicates a notable reduction in annual flash drought risk over cropland

Pharmacokinetic and behavioral characterization of a longterm antipsychotic delivery system in rodents and rabbits

Rationale: Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel long-term delivery systems. Objectives: The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits. Materials and methods: Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits. Results: Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits. Conclusions: The current study suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a degree of reversibility not available with depot formulations

Applied Personality Assessment: A 'Cronbachian' Perspective in Open Peer Commentary and Author's Response

Lievens's proposal that personality psychology would benefit from using applied tools of assessment—situation judgement tests and assessment centre exercises—was appropriate, especially as these tools focus on real-world criteria in high-stakes situations. Their use would help to integrate (specific) situationally influenced intra-individual differences (variability) and (general) inter-individual differences (diversity). Lievens's proposal also raised a broader issue: each assessment tool yields unique information, and together they have potential to provide a truly comprehensive model of personality based on the ‘Cronbachian’ perspective that has, so far, not been realized. Copyright © 2017 European Association of Personality Psycholog

Use of Quantitative Pharmacology in the Development of HAE1, a High-Affinity Anti-IgE Monoclonal Antibody

HAE1, a high-affinity anti-IgE monoclonal antibody, is discussed here as a case study in the use of quantitative pharmacology in the development of a second-generation molecule. In vitro, preclinical, and clinical data from the first-generation molecule, omalizumab, were heavily leveraged in the HAE1 program. A preliminary mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for HAE1 was developed using an existing model for omalizumab, together with in vitro binding data for HAE1 and omalizumab. When phase I data were available, the model was refined by simultaneously modeling PK/PD data from omalizumab studies with the available HAE1 phase I data. The HAE1 clinical program was based on knowledge of the quantitative relationship between a pharmacodynamic biomarker, suppression of free IgE, and clinical response (e.g., lower exacerbation rates) obtained in pivotal studies with omalizumab. A clinical trial simulation platform was developed to predict free IgE levels and clinical responses following attainment of a target free IgE level (≤10 IU/ml). The simulation platform enabled selection of four doses for the phase II dose-ranging trial by two independent methods: dose-response non-linear fitting and linear mixed modeling. Agreement between the two methods provided confidence in the doses selected. Modeling and simulation played a large role in supporting acceleration of the HAE1 program by enabling data-driven decision-making, often based on confirmation of projections and/or learning from incoming new data

Human Embryonic Stem Cells Express Elevated Levels of Multiple Pro-Apoptotic BCL-2 Family Members

Two of the greatest challenges in regenerative medicine today remain (1) the ability to culture human embryonic stem cells (hESCs) at a scale sufficient to satisfy clinical demand and (2) the ability to eliminate teratoma-forming cells from preparations of cells with clinically desirable phenotypes. Understanding the pathways governing apoptosis in hESCs may provide a means to address these issues. Limiting apoptosis could aid scaling efforts, whereas triggering selective apoptosis in hESCs could eliminate unwanted teratoma-forming cells. We focus here on the BCL-2 family of proteins, which regulate mitochondrial-dependent apoptosis. We used quantitative PCR to compare the steady-state expression profile of all human BCL-2 family members in hESCs with that of human primary cells from various origins and two cancer lines. Our findings indicate that hESCs express elevated levels of the pro-apoptotic BH3-only BCL-2 family members NOXA, BIK, BIM, BMF and PUMA when compared with differentiated cells and cancer cells. However, compensatory expression of pro-survival BCL-2 family members in hESCs was not observed, suggesting a possible explanation for the elevated rates of apoptosis observed in proliferating hESC cultures, as well as a mechanism that could be exploited to limit hESC-derived neoplasms