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The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the clinical trial paradigm from a site‐centric to a patient‐centric model. Merck’s (Kenilworth, NJ) digitally enabled clinical trial initiative is focused on introduction of digital technologies into the clinical trial paradigm to reduce patient burden, improve drug adherence, provide a means of more closely engaging with the patient, and enable higher quality, faster, and more frequent data collection. This paper will describe the following four key areas of focus from Merck’s digitally enabled clinical trials initiative, along with corresponding enabling technologies: (i) use of technologies that can monitor and improve drug adherence (smart dosing), (ii) collection of pharmacokinetic (PK), pharmacodynamic (PD), and biomarker samples in an outpatient setting (patient‐centric sampling), (iii) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (iv) use of data platforms that integrate digital data streams, visualize data in real‐time, and provide a means of greater patient engagement during the trial (digital platform). Furthermore, this paper will discuss the synergistic power in implementation of these approaches jointly within a trial to enable better understanding of adherence, safety, efficacy, PK, PD, and corresponding exposure‐response relationships of investigational therapies as well as reduced patient burden for clinical trial participation. Obstacle and challenges to adoption and full realization of the vision of patient‐centric, digitally enabled trials will also be discussed.

Abstract How intensely animals use habitat features depends on their functional properties (i.e., how the feature influences fitness) and the spatial and temporal scale considered. For herbivores, habitat use is expected to reflect the competing risks of starvation, predation, and thermal stress, but the relative influence of each functional property is expected to vary in space and time. We examined how a dietary and habitat specialist, the pygmy rabbit (Brachylagus idahoensis), used these functional properties of its sagebrush habitat—food quality, security, and thermal refuge—at two hierarchical spatial scales (microsite and patch) across two seasons (winter and summer). At the microsite and patch scales, we determined which plant functional traits predicted the number of bites (i.e., foraging) by pygmy rabbits and the number of their fecal pellets (i.e., general habitat use). Pygmy rabbits used microsites and patches more intensely that had higher crude protein and aerial concealment cover and were closer to burrows. Food quality was more influential when rabbits used microsites within patches. Security was more influential in winter than summer, and more at Cedar Gulch than Camas. However, the influence of functional properties depended on phytochemical and structural properties of sagebrush and was not spatiotemporally consistent. These results show function‐dependent habitat use that varied according to specific activities by a central‐place browsing herbivore. Making spatially explicit predictions of the relative value of habitat features that influence different types of habitat use (i.e., foraging, hiding, and thermoregulating) will improve how we predict patterns of habitat use by herbivores and how we monitor and manage functional traits within habitats for wildlife.

Abstract Sympatric species that are ecologically similar must either segregate through habitat disassociation or engage in biotic interactions with one another. Mule (Odocoileus hemionus) and white‐tailed deer (Odocoileus virginianus) are similar ungulate species that are distributed across North America in both areas of sympatry and allopatry. Over many decades, white‐tailed deer have been expanding their range into areas historically used allopatrically by mule deer, potentially leading to increased interactions between the species. However, the degree to which the two species segregate spatio‐temporally or engage in agonistic interactions is yet unclear. Therefore, to compare their realized habitat niches in an area of sympatry, we determined presence and absence of both deer species at 312 camera traps during the summers of 2018–2019 across a range of elevations and habitats in the Colville National Forest (CNF) in northeastern Washington. We compared characteristics of habitats used by the two species using single‐species occupancy models and found that topography was the strongest predictor of differing habitat use. Mule deer were more likely to occupy steep slopes and higher elevations and white‐tailed deer more likely to occupy shallower slopes and lower elevations. Using conditional, two‐species occupancy modeling, we found that after accounting for differences in habitat selection between the species, mule and white‐tailed deer occurred independently of one another in the CNF during summer. We found no evidence for temporal segregation, with ˜90% overlap in daily activity patterns and similar elapsed time between subsequent intra‐ and interspecies detections at the 21% of camera sites where both species were detected. Niche segregation along topographic gradients in our study system likely reduces the potential for current interspecies interactions, positive or negative, to occur in this system. However, we did not find any evidence of ongoing spatio‐temporal avoidance, even in areas of the landscape where both species were detected (e.g., sharing habitat). Therefore, although our observational study cannot rule out that contemporaneous habitat segregation is evidence of past competitive interactions between the species, our research does not strongly support the contention that agonistic interactions are currently occurring between mule and white‐tailed deer.

Although an important part of the ecosystem, large wild herbivores (LWH), especially red deer (Cervus elaphus L.), cause significant damage to economically valuable timber in forests of Central Europe. Recent work has demonstrated that less valuable softwood broadleaved trees can act as “biological control” that helps reduce bark browsing on more valuable trees in a mixed stand. To better understand the factors that influence how much bark area and mass are removed by LWH from these broadleaved trees, we took advantage of a novel “natural” experiment that occurred after a breach in a herbivory exclosure surrounding a 10-year old mixed broadleaved/conifer stand in the Western Carpathians in north-western Slovakia. We measured the area of old (up to 2 years previously) and new browsed patches on stems of common aspen (Populus tremula L.), common rowan (Sorbus aucuparia L.) and goat willow (Salix caprea L.), and their position along the vertical profile of the stem. The browsed bark area (cm2) was then converted to the bark mass (g) removed and the proportion of browsed bark to total bark (%) using conversion equations. Our models demonstrated that the amount of bark removed was influenced by tree species, stem diameter, age of browsing (old vs. new), and stem section along the vertical profile. LWH removed the most bark area from willow but the most bark mass from aspen because aspen had thicker bark than the other tree species. Bark browsing was greater on trees > 6 cm basal diameter. The distribution of bark browsing along the vertical profile was symmetrical (unimodal) with maximum intensity at 101–125 cm from the ground, which corresponds with the height most optimal for feeding by red deer. However, previous browsing in 2019 and 2020 caused new browsing on willow in 2021 to be focused in stem sections lower (51–75 cm) and higher (126–150 cm) than that optima. By quantifying browsing patterns and the amount of bark that is accessible to LWH for forage on the most attractive softwood broadleaved trees, our work will contribute to developing better methods for protecting commercially important species such as European beech (Fagus sylvatica L.) and Norway spruce (Picea abies L. Karst.) in areas of Central Europe that are greatly affected by increasing population density of LWH, especially red deer.

In heterogeneous landscapes, large herbivores employ plastic behavioral strategies to buffer themselves against negative effects of environmental variation on fitness. Yet, the mechanisms by which individual responses to such variation scale up to influence population performance remain uncertain. Analyses of space-use behaviors exemplify this knowledge gap, because such behaviors are often assumed, but rarely demonstrated, to have direct fitness consequences. We combined fine-scale data on forage biomass and quality with movement data and measures of somatic energy reserves to determine whether variation in use (the quantity of resource units, e.g., pixels on a landscape, that receive some level of investment by an animal during a specific sampling period) or selection (use of a resource unit relative to its availability to the animal during the same sampling period) of the nutritional landscape predicted early winter body condition of mule deer (Odocoileus hemionus). At the population level, mule deer exhibited stronger selection for high forage biomass at the landscape scale than at the home-range scale, and during summer than during spring. Use of the nutritional landscape varied among individual deer and had important consequences for early winter condition (an important determinant of survival and reproduction in capital-breeding ungulates). Females that consistently used vegetation communities that provided high biomass of preferred forage plants throughout spring and summer entered winter in better condition than females that used those vegetation communities less frequently. In contrast, selection (i.e., use relative to availability) of the nutritional landscape by individual deer was not significantly related to early winter condition at either the landscape or home-range scales. Our results highlight the value of using mechanistic, nutritional approaches to understand the potential fitness consequences of individual variation in behavior. In addition, our study suggests that patterns of forage use by ungulates may sometimes correlate more strongly with fitness than patterns of forage selection, which are scale-dependent and more vulnerable to biases stemming from the need to accurately quantify availability.

Abstract Mule (Odocoileus hemionus) and white‐tailed deer (Odocoileus virginianus) are congeneric and share similar life histories, yet their distribution is segregated across much of North America. Extensive research on both species within and outside their zone of co‐occurrence has not fully explained these distribution patterns, especially the potential role of diet and foraging behavior. Therefore, we used a common garden experiment to compare diet composition, diet quality, foraging behavior, and intake of tractable mule and white‐tailed deer foraging together within the dry Douglas‐fir (Pseudotsuga menziesii)/ponderosa pine (Pinus ponderosa) forests of northeastern Washington. We sampled at 21 0.5‐ha sites from June to August 2016. We used standard bite count techniques coupled with forage biomass sampling, behavioral observations, and nutritional analyses to compare the foraging ecology of the two species. Mule and white‐tailed deer had similar activity patterns. However, mule deer took larger bites and harvested food faster than white‐tailed deer, and white‐tailed deer consumed more diverse but higher‐quality diets than mule deer. These differences resulted in mule deer acquiring ~25% more dry matter and digestible energy per day. About 90% of the diets consumed by both deer species consisted of deciduous shrubs and forbs, and they selected many of the same plant species. However, overall diet composition was 38% dissimilar, with mule deer consuming diets that were more likely to contain shrubs with higher levels of tannins and lower levels of dry matter digestibility than diets eaten by white‐tailed deer. Dietary overlap was greatest at both very low and very high forage biomass, indicating potential for modest resource competition or partitioning. Our research provides evidence that differences in diet composition of mule and white‐tailed deer do not merely reflect differences in habitat selection, but also suggest the species differ in their fundamental nutritional niches.

Small mammals in habitats with strong seasonal variation in the thermal environment often exhibit physiological and behavioral adaptations for coping with thermal extremes and reducing thermoregulatory costs. Burrows are especially important for providing thermal refuge when above-ground temperatures require high regulatory costs (e.g., water or energy) or exceed the physiological tolerances of an organism. Our objective was to explore the role of burrows as thermal refuges for a small endotherm, the pygmy rabbit (Brachylagus idahoensis), during the summer and winter by quantifying energetic costs associated with resting above and below ground. We used indirect calorimetry to determine the relationship between energy expenditure and ambient temperature over a range of temperatures that pygmy rabbits experience in their natural habitat. We also measured the temperature of above- and below-ground rest sites used by pygmy rabbits in eastern Idaho, USA, during summer and winter and estimated the seasonal thermoregulatory costs of resting in the two microsites. Although pygmy rabbits demonstrated seasonal physiological acclimatization, the burrow was an important thermal refuge, especially in winter. Thermoregulatory costs were lower inside the burrow than in above-ground rest sites for more than 50% of the winter season. In contrast, thermal heterogeneity provided by above-ground rest sites during summer reduced the role of burrows as a thermal refuge during all but the hottest periods of the afternoon. Our findings contribute to an understanding of the ecology of small mammals in seasonal environments and demonstrate the importance of burrows as thermal refuge for pygmy rabbits.

ABSTRACT We used both experimental and observational approaches to investigate sub‐lethal effects of capture and radiocollaring on pygmy rabbits (Brachylagus idahoensis) in Idaho and Washington during 2004–2008. We expected that attachment of collars would increase rates of grooming behaviors and alter patterns of space use. Frequency of grooming was >3 times higher following attachment of radiocollars on captive rabbits; however, the grooming rate declined rapidly and returned to within 5% of pre‐collaring levels after 7 days. Free‐ranging rabbits exhibited relatively longer distance movements immediately following and during the 2 weeks after capture and attachment of radiocollars, but those movements decreased during weeks 3–4 post‐collaring. Rabbits also shifted use areas away from capture locations. Our results suggest that: 1) rabbits became habituated to the presence of collars with respect to grooming; and 2) although, magnitude of movements following capture and collaring in the field attenuated with time, some animals continued to avoid capture areas up to 4 weeks after collaring. A better understanding of potential effects of telemetry on wildlife can help to improve the quality of data collected, design ways to mitigate the impacts on animals, and enhance the ethical conduct of wildlife research. © 2014 The Wildlife Society.

Understanding the responses of foragers to patchy distributions of resources has formed a fundamental challenge in behavioral ecology. Two currencies have been used to assess the patch preferences of herbivores—intake rate maximization and risk sensitivity. We wished to understand if small mammalian foragers, collared lemmings (Dichrostonyx groenlandicus), choose patches to maximize food intake rate or to reduce risk of starvation in “variable” environments. Moreover, we examined the possibility that maximizing intake rate depends on the spatial scale of patchiness. We designed an experiment offering two alternative patches of food, varying the predictability of food rewards and the “potential intake rate” at different spatial scales. Collared lemmings did not consistently select patches that maximized their intake rate at either scale studied. Instead, they chose patches offering the least variation in food reward over the course of the experiment. Collared lemmings used prior knowledge gained from previous foraging bouts to assess food variability. We interpret these results as evidence for risk-averse foraging strategies, which are predicted for continuous foragers aiming to minimize risk of starvation. [ABSTRACT FROM AUTHOR]

BackgroundMachine learning–based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis and severity. Demonstrating utility and validity of remote and automated assessments conducted outside of controlled experimental or clinical settings can facilitate scaling such measurement tools to aid in risk assessment and tracking of treatment response in populations that are difficult to engage. ObjectiveThis study aimed to determine the accuracy of machine learning–based facial and vocal measurements acquired through automated assessments conducted remotely through smartphones. MethodsMeasurements of facial and vocal characteristics including facial expressivity, vocal acoustics, and speech prevalence were assessed in 20 patients with schizophrenia over the course of 2 weeks in response to two classes of prompts previously utilized in experimental laboratory assessments: evoked prompts, where subjects are guided to produce specific facial expressions and speech; and spontaneous prompts, where subjects are presented stimuli in the form of emotionally evocative imagery and asked to freely respond. Facial and vocal measurements were assessed in relation to schizophrenia symptom severity using the Positive and Negative Syndrome Scale. ResultsVocal markers including speech prevalence, vocal jitter, fundamental frequency, and vocal intensity demonstrated specificity as markers of negative symptom severity, while measurement of facial expressivity demonstrated itself as a robust marker of overall schizophrenia symptom severity. ConclusionsEstablished facial and vocal measurements, collected remotely in schizophrenia patients via smartphones in response to automated task prompts, demonstrated accuracy as markers of schizophrenia symptom severity. Clinical implications are discussed.

Forested lands in the western USA have undergone changes in management and condition that are resulting in a shift towards climax vegetation. These changes can influence the quality and quantity of forage for herbivores that rely on early-seral plants. To evaluate how management of forested landscapes might affect nutrition for Shiras moose (A. a. shirasi) at large spatial scales, we focused on shrubs and evaluated summer diet composition, forage availability, and forage quality across 21 population management units encompassing >36,000 km2 in northern Idaho, USA. We identified 17 shrub species in the diets of moose, 11 of which comprised the bulk of the diets. These forage shrubs varied markedly in both energy (mean digestible energy for leaves ranged from 9.62 to 12.89 kJ/g) and protein (mean digestible protein for leaves ranged from 1.73 to 7.90%). By adapting established field sampling methods and integrating recent advances in remote sensing analyses in a modeling framework, we predicted approximations of current and past (i.e., 1984) quantities of forage shrubs across northern Idaho. We also created a qualitative index of population trend for moose across population management units using harvest data. Predicted quantities of forage shrubs varied widely across the study area with generally higher values at more northern latitudes. The quantity of forage shrubs was estimated to have declined over the past 30 years in about half of the population management units, with the greatest declines predicted for high-energy forage species. The population trend index was correlated with the percent change in availability of moderate-energy forage shrubs, indicating that availability of forage shrubs and change in availability over time might be affecting population dynamics for moose in northern Idaho. Our study highlights the importance of assessing how changes in forest management across broad spatiotemporal extents could affect wildlife and their habitats.

GPS telemetry markedly enhances the temporal and spatial resolution of animal location data, and recent advances in micro-GPS receivers permit their deployment on small mammals. One such technological advance, snapshot technology, allows for improved battery life by reducing the time to first fix via postponing recovery of satellite ephemeris (satellite location) data and processing of locations. However, no previous work has employed snapshot technology for small, terrestrial mammals. We evaluated performance of two types of micro-GPS (< 20 g) receivers (traditional and snapshot) on a small, semi-fossorial lagomorph, the pygmy rabbit (Brachylagus idahoensis), to understand how GPS errors might influence fine-scale assessments of space use and habitat selection. During stationary tests, microtopography (i.e., burrows) and satellite geometry had the largest influence on GPS fix success rate (FSR) and location error (LE). There was no difference between FSR while animals wore the GPS collars above ground (determined via light sensors) and FSR generated during stationary, above-ground trials, suggesting that animal behavior other than burrowing did not markedly influence micro-GPS errors. In our study, traditional micro-GPS receivers demonstrated similar FSR and LE to snapshot receivers, however, snapshot receivers operated inconsistently due to battery and software failures. In contrast, the initial traditional receivers deployed on animals experienced some breakages, but a modified collar design consistently functioned as expected. If such problems were resolved, snapshot technology could reduce the tradeoff between fix interval and battery life that occurs with traditional micro-GPS receivers. Our results suggest that micro-GPS receivers are capable of addressing questions about space use and resource selection by small mammals, but that additional techniques might be needed to identify use of habitat structures (e.g., burrows, tree cavities, rock crevices) that could affect micro-GPS performance and bias study results.