Poor Cardiac Output Reserve in Pulmonary Arterial Hypertension is Associated With Right Ventricular Stiffness and Impaired Interventricular Dependence.

BACKGROUND: Pulmonary arterial hypertension is characterized by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (p-V) loop analysis to characterize the impact of RV diastology on poor flow augmentation during exercise in PAH. METHODS: RV p-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance, Eed) and ventricular interdependence (left ventricular transmural pressure, LVTMP) were compared at matched exercise stages. RESULTS: Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 ml·m-2, p=0.0001), with higher associated exercise afterload (Ea 1.76 versus 0.90 mmHg·mL-1, p<0.0001), RV stiffness (Eed 0.68 versus 0.26 mmHg·mL-1, p=0.003), and right-sided pressures (RA 14 versus 8 mmHg, p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg, p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. CONCLUSIONS: Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness, and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiologic PAH differences unapparent at rest.

Metabolic profiling of in vivo right ventricular function and exercise performance in pulmonary arterial hypertension.

Right ventricular (RV) adaptation is the principal determinant of outcomes in pulmonary arterial hypertension (PAH), however, RV function is challenging to assess. RV responses to hemodynamic stressors are particularly difficult to interrogate without invasive testing. This study sought to identify metabolomic markers of in vivo right ventricular function and exercise performance in PAH. Consecutive subjects with PAH (n = 23) underwent rest and exercise right heart catheterization with multibeat pressure volume loop analysis. Pulmonary arterial blood was collected at rest and during exercise. Mass spectrometry-based targeted metabolomics were performed, and metabolic associations with hemodynamics and comprehensive measures of RV function were determined using sparse partial least squares regression. Metabolite profiles were compared with N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurements for accuracy in modeling ventriculo-arterial parameters. Thirteen metabolites changed in abundance with exercise, including metabolites reflecting increased arginine bioavailability, precursors of catecholamine and nucleotide synthesis, and branched-chain amino acids. Higher resting arginine bioavailability predicted more favorable exercise hemodynamics and pressure-flow relationships. Subjects with more severe PAH augmented arginine bioavailability with exercise to a greater extent than subjects with less severe PAH. We identified relationships between kynurenine pathway metabolism and impaired ventriculo-arterial coupling, worse RV diastolic function, lower RV contractility, diminished RV contractility with exercise, and RV dilation with exercise. Metabolite profiles outperformed NT-proBNP in modeling RV contractility, diastolic function, and exercise performance. Specific metabolite profiles correspond to RV functional measurements only obtainable via invasive pressure-volume loop analysis and predict RV responses to exercise. Metabolic profiling may inform discovery of RV functional biomarkers.NEW & NOTEWORTHY In this cohort of patients with pulmonary arterial hypertension (PAH), we investigate metabolomic associations with comprehensive right ventricular (RV) functional measurements derived from multibeat RV pressure-volume loop analysis. Our results show that tryptophan metabolism, particularly the kynurenine pathway, is linked to intrinsic RV function and PAH pathobiology. Findings also highlight the importance of arginine bioavailability in the cardiopulmonary system's response to exercise stress. Metabolite profiles selected via unbiased analysis outperformed N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) in predicting load-independent measures of RV function at rest and cardiopulmonary system performance under stress. Overall, this work suggests the potential for select metabolites to function as disease-specific biomarkers, offers insights into PAH pathobiology, and informs discovery of potentially targetable RV-centric pathways.

Wherever I may roam-Human activity alters movements of red deer (Cervus elaphus) and elk (Cervus canadensis) across two continents.

Human activity and associated landscape modifications alter the movements of animals with consequences for populations and ecosystems worldwide. Species performing long-distance movements are thought to be particularly sensitive to human impact. Despite the increasing anthropogenic pressure, it remains challenging to understand and predict animals' responses to human activity. Here we address this knowledge gap using 1206 Global Positioning System movement trajectories of 815 individuals from 14 red deer (Cervus elaphus) and 14 elk (Cervus canadensis) populations spanning wide environmental gradients, namely the latitudinal range from the Alps to Scandinavia in Europe, and the Greater Yellowstone Ecosystem in North America. We measured individual-level movements relative to the environmental context, or movement expression, using the standardized metric Intensity of Use, reflecting both the directionality and extent of movements. We expected movement expression to be affected by resource (Normalized Difference Vegetation Index, NDVI) predictability and topography, but those factors to be superseded by human impact. Red deer and elk movement expression varied along a continuum, from highly segmented trajectories over relatively small areas (high intensity of use), to directed transitions through restricted corridors (low intensity of use). Human activity (Human Footprint Index, HFI) was the strongest driver of movement expression, with a steep increase in Intensity of Use as HFI increased, but only until a threshold was reached. After exceeding this level of impact, the Intensity of Use remained unchanged. These results indicate the overall sensitivity of Cervus movement expression to human activity and suggest a limitation of plastic responses under high human pressure, despite the species also occurring in human-dominated landscapes. Our work represents the first comparison of metric-based movement expression across widely distributed populations of a deer genus, contributing to the understanding and prediction of animals' responses to human activity.

Case Report: When Two Is Worse Than One-Stereo Imbalance in a Case of Wavefront-guided Scleral Lenses.

SIGNIFICANCE: Wavefront-guided scleral lenses (WGSLs) reduce visually debilitating residual higher-order aberrations. Although reduced higher-order aberrations lead to improvement in monocular high-contrast visual acuity (VA), the success of the lenses in everyday life depends on additional factors such as retinal contrast, binocular balance, and stereoacuity. PURPOSE: This report describes a case where WGSLs provided improved monocular vision compared with scleral lenses (SLs) but reduced binocularity and stereoacuity. CASE REPORT: A 48-year-old woman with moderate keratoconus right eye (OD) and severe left eye (OS) was fitted with SLs and WGSLs. Visual acuity with best SLs was 20/20 -2 OD and 20/25 -2 OS. Residual higher-order root-mean-square (HORMS) wavefront error (6 mm pupil) was 0.56 µm OD and 1.38 µm OS. Visual acuity with WGSLs was 20/16 -2 OD and 20/25 +2 OS, and residual HORMS was 0.41 µm OD and 0.98 µm OS. Monocularly, WGSLs were reported to provide better VA. However, binocularly, the patient reported an "imbalanced feeling" and preferred the SLs over WGSLs. Binocular VA at distance was 20/25 with SLs and 20/25 -2 with WGSL. To investigate, the Worth Four-Dot test was performed, and the outcomes reported fusion with SLs but suppression OS at distance with WGSLs. Stereoacuity was 160 arc seconds at near and 120 arc seconds at distance with SLs and 400 arc seconds at near and >1200 arc seconds at distance with WGSLs. Dichoptic contrast balancing showed a balance point of 0.48 with SLs and 0.17 with WGSLs, indicating a strong preference toward OD. Simulation of the patient's retinal image revealed a greater difference in image contrast between the two eyes with WGSLs. CONCLUSIONS: Wavefront-guided scleral lenses reduced HORMS and improved VA compared with SLs. However, in this case, it inadvertently caused binocular imbalance. As WGSLs become more widely available, future work should include methods to optimize binocular balance to maximize overall patient satisfaction.

Migrating bison engineer the green wave.

Newly emerging plants provide the best forage for herbivores. To exploit this fleeting resource, migrating herbivores align their movements to surf the wave of spring green-up. With new technology to track migrating animals, the Green Wave Hypothesis has steadily gained empirical support across a diversity of migratory taxa. This hypothesis assumes the green wave is controlled by variation in climate, weather, and topography, and its progression dictates the timing, pace, and extent of migrations. However, aggregate grazers that are also capable of engineering grassland ecosystems make some of the world's most impressive migrations, and it is unclear how the green wave determines their movements. Here we show that Yellowstone's bison (Bison bison) do not choreograph their migratory movements to the wave of spring green-up. Instead, bison modify the green wave as they migrate and graze. While most bison surfed during early spring, they eventually slowed and let the green wave pass them by. However, small-scale experiments indicated that feedback from grazing sustained forage quality. Most importantly, a 6-fold decadal shift in bison density revealed that intense grazing caused grasslands to green up faster, more intensely, and for a longer duration. Our finding broadens our understanding of the ways in which animal movements underpin the foraging benefit of migration. The widely accepted Green Wave Hypothesis needs to be revised to include large aggregate grazers that not only move to find forage, but also engineer plant phenology through grazing, thereby shaping their own migratory movements.

Body size and digestive system shape resource selection by ungulates: A cross-taxa test of the forage maturation hypothesis.

The forage maturation hypothesis (FMH) states that energy intake for ungulates is maximised when forage biomass is at intermediate levels. Nevertheless, metabolic allometry and different digestive systems suggest that resource selection should vary across ungulate species. By combining GPS relocations with remotely sensed data on forage characteristics and surface water, we quantified the effect of body size and digestive system in determining movements of 30 populations of hindgut fermenters (equids) and ruminants across biomes. Selection for intermediate forage biomass was negatively related to body size, regardless of digestive system. Selection for proximity to surface water was stronger for equids relative to ruminants, regardless of body size. To be more generalisable, we suggest that the FMH explicitly incorporate contingencies in body size and digestive system, with small-bodied ruminants selecting more strongly for potential energy intake, and hindgut fermenters selecting more strongly for surface water.

Life-history theory provides a framework for detecting resource limitation: a test of the Nutritional Buffer Hypothesis.

For ungulates and other long-lived species, life-history theory predicts that nutritional reserves are allocated to reproduction in a state-dependent manner because survival is highly conserved. Further, as per capita food abundance and nutritional reserves decline (i.e., density dependence intensifies), reproduction and recruitment become increasingly sensitive to weather. Thus, the degree to which weather influences vital rates should be associated with proximity to nutritional carrying capacity-a notion that we refer to as the Nutritional Buffer Hypothesis. We tested the Nutritional Buffer Hypothesis using six moose (Alces alces) populations that varied in calf recruitment (33-69 calves/100 cows). We predicted that populations with high calf recruitment were nutritionally buffered against the effects of unfavorable weather, and thus were below nutritional carrying capacity. We applied a suite of tools to quantify habitat and nutritional condition of each population and found that increased browse condition, forage quality, and body fat were associated with increased pregnancy and calf recruitment, thereby providing multiple lines of evidence that declines in calf recruitment were underpinned by resource limitation. From 2001 to 2015, recruitment was more sensitive to interannual variation in weather (e.g., winter severity, drought) and plant phenology (e.g., duration of spring) for populations with reduced browse condition, forage quality, and body fat, suggesting these populations lacked the nutritional reserves necessary to buffer demographic performance against the effects of unfavorable weather. Further, average within-population calf recruitment was determined by regional climatic variation, suggesting that the pattern of reduced recruitment near the southern range boundary of moose stems from an interaction between climate and resource limitation. When coupled with information on habitat, nutrition, weather, and climate, life-history theory provides a framework to estimate nutritional limitation, proximity to nutritional carrying capacity, and impacts of climate change for ungulates.

Drivers of site fidelity in ungulates.

While the tendency to return to previously visited locations-termed 'site fidelity'-is common in animals, the cause of this behaviour is not well understood. One hypothesis is that site fidelity is shaped by an animal's environment, such that animals living in landscapes with predictable resources have stronger site fidelity. Site fidelity may also be conditional on the success of animals' recent visits to that location, and it may become stronger with age as the animal accumulates experience in their landscape. Finally, differences between species, such as the way memory shapes site attractiveness, may interact with environmental drivers to modulate the strength of site fidelity. We compared inter-year site fidelity in 669 individuals across eight ungulate species fitted with GPS collars and occupying a range of environmental conditions in North America and Africa. We used a distance-based index of site fidelity and tested hypothesized drivers of site fidelity using linear mixed effects models, while accounting for variation in annual range size. Mule deer Odocoileus hemionus and moose Alces alces exhibited relatively strong site fidelity, while wildebeest Connochaetes taurinus and barren-ground caribou Rangifer tarandus granti had relatively weak fidelity. Site fidelity was strongest in predictable landscapes where vegetative greening occurred at regular intervals over time (i.e. high temporal contingency). Species differed in their response to spatial heterogeneity in greenness (i.e. spatial constancy). Site fidelity varied seasonally in some species, but remained constant over time in others. Elk employed a 'win-stay, lose-switch' strategy, in which successful resource tracking in the springtime resulted in strong site fidelity the following spring. Site fidelity did not vary with age in any species tested. Our results provide support for the environmental hypothesis, particularly that regularity in vegetative phenology shapes the strength of site fidelity at the inter-annual scale. Large unexplained differences in site fidelity suggest that other factors, possibly species-specific differences in attraction to known sites, contribute to variation in the expression of this behaviour. Understanding drivers of variation in site fidelity across groups of organisms living in different environments provides important behavioural context for predicting how animals will respond to environmental change.

Drought reshuffles plant phenology and reduces the foraging benefit of green-wave surfing for a migratory ungulate.

To increase resource gain, many herbivores pace their migration with the flush of nutritious plant green-up that progresses across the landscape (termed "green-wave surfing"). Despite concerns about the effects of climate change on migratory species and the critical role of plant phenology in mediating the ability of ungulates to surf, little is known about how drought shapes the green wave and influences the foraging benefits of migration. With a 19 year dataset on drought and plant phenology across 99 unique migratory routes of mule deer (Odocoileus hemionus) in western Wyoming, United States, we show that drought shortened the duration of spring green-up by approximately twofold (2.5 weeks) and resulted in less sequential green-up along migratory routes. We investigated the possibility that some routes were buffered from the effects of drought (i.e., routes that maintained long green-up duration irrespective of drought intensity). We found no evidence of drought-buffered routes. Instead, routes with the longest green-up in non-drought years also were the most affected by drought. Despite phenological changes along the migratory route, mule deer closely followed drought-altered green waves during migration. Migrating deer did not experience a trophic mismatch with the green wave during drought. Instead, the shorter window of green-up caused by drought reduced the opportunity to accumulate forage resources during rapid spring migrations. Our work highlights the synchronization of phenological events as an important mechanism by which climate change can negatively affect migratory species by reducing the temporal availability of key food resources. For migratory herbivores, climate change poses a new and growing threat by altering resource phenology and diminishing the foraging benefit of migration.

A test of the Niche Variation Hypothesis in a ruminant herbivore.

Despite the shared prediction that the width of a population's dietary niche expands as food becomes limiting, the Niche Variation Hypothesis (NVH) and Optimal Foraging Theory (OFT) offer contrasting views about how individuals alter diet selection when food is limited. Classical OFT predicts that dietary preferences do not change as food becomes limiting, so individuals expand their diets as they compensate for a lack of preferred foods. In contrast, the NVH predicts that among-individual variation in cognition, physiology or morphology create functional trade-offs in foraging efficiency, thereby causing individuals to specialize on different subsets of food as food becomes limiting. To evaluate (a) the predictions of the NVH and OFT and (b) evidence for physiological and cognitive-based functional trade-offs, we used DNA microsatellites and metabarcoding to quantify the diet, microbiome and genetic relatedness (a proxy for social learning) of 218 moose Alces alces across six populations that varied in their degree of food limitation. Consistent with both the NVH and OFT, dietary niche breadth increased with food limitation. Increased diet breadth of individuals-rather than increased diet specialization-was strongly correlated with both food limitation and dietary niche breadth of populations, indicating that moose foraged in accordance with OFT. Diets were not constrained by inheritance of the microbiome or inheritance of diet selection, offering support for the little-tested hypothesis that functional trade-offs in food use (or lack thereof) determine whether populations adhere to the predictions of the NVH or OFT. Our results indicate that both the absence of strong functional trade-offs and the digestive physiology of ruminants provide contexts under which populations should forage in accordance with OFT rather than the NVH. Also, because dietary niche width increased with increased food limitation, OFT and the NVH provide theoretical support for the notion that plant-herbivore interaction networks are plastic rather than static, which has important implications for understanding interspecific niche partitioning. Lastly, because population-level dietary niche breadth and calf recruitment are correlated, and because calf recruitment can be a proxy for food limitation, our work demonstrates how diet data can be employed to understand a populations' proximity to carrying capacity.

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.

Efectos del Tamaño Corporal sobre la Estimación de los Requerimientos de Área de Mamíferos Resumen La cuantificación precisa de los requerimientos de área de una especie es un prerrequisito para que la conservación basada en áreas sea efectiva. Esto comúnmente implica la recolección de datos de rastreo de la especie de interés para después realizar análisis de la distribución local. De manera problemática, la autocorrelación en los datos de rastreo puede resultar en una subestimación grave de las necesidades de espacio. Con base en trabajos previos, formulamos una hipótesis en la que supusimos que la magnitud de la subestimación varía con la masa corporal, una relación que podría tener implicaciones serias para la conservación. Para probar esta hipótesis en mamíferos terrestres, estimamos las áreas de distribución local con las ubicaciones en GPS de 757 individuos de 61 especies de mamíferos distribuidas mundialmente con una masa corporal entre 0.4 y 4,000 kg. Después aplicamos una validación cruzada en bloque para cuantificar el sesgo en estimaciones empíricas de la distribución local. Los requerimientos de área de los mamíferos <10 kg fueron subestimados por una media ∼15% y las especies con una masa ∼100 kg fueron subestimadas en ∼50% en promedio. Por lo tanto, encontramos que la estimación del área estaba sujeta al sesgo inducido por la autocorrelación, el cual era peor para las especies de talla grande. En combinación con el hecho de que el riesgo de extinción incrementa conforme aumenta la masa corporal, el escalamiento alométrico del sesgo que observamos sugiere que la mayoría de las especies amenazadas también tienen la probabilidad de ser aquellas especies con las estimaciones de distribución local menos acertadas. Como corrección, probamos si la reducción de datos o la estimación de la distribución local informada por la autocorrelación minimizan el efecto de escalamiento que tiene la autocorrelación sobre las estimaciones de área. La reducción de datos requirió una pérdida de datos del ∼93% para lograr la independencia estadística con un 95% de confianza y por lo tanto no fue una solución viable. Al contrario, la estimación de la distribución local informada por la autocorrelación resultó en estimaciones constantemente precisas sin importar la masa corporal. Cuando relacionamos la masa corporal con el tamaño de la distribución local, detectamos que la corrección de la autocorrelación resultó en un exponente de escalamiento significativamente >1, lo que significa que el escalamiento de la relación cambió sustancialmente en el extremo superior del espectro de la masa corporal.

Case Report: What Are We Doing for Our "20/20 Unhappy" Scleral Lens Patients?

SIGNIFICANCE: Scleral lenses (SLs) partially mask higher-order aberrations (HOAs) in highly aberrated eyes. Although visual acuity (VA) may show satisfactory quantitative clinical outcomes during SL wear, residual (uncorrected) HOAs can leave subjective visual quality goals unmet. PURPOSE: The purpose of this study was to report a case where a "20/20 unhappy" patient with SLs was able to meet visual goals with wavefront-guided SLs. CASE REPORT: A 40-year-old male with bilateral keratoconus, whose Snellen VA with SLs was 20/20 right eye (OD) 20/16 left eye (OS), reported halos and glare at night and perceptual smearing. When viewing a point of light, a "Ferris wheel" shadowing was observed OD and a U-shaped shadowing OS. Residual higher-order root mean square wavefront error was 0.49 µm OD and 0.39 µm OS; visual image quality measured by visual Strehl ratio was 0.067 OD and 0.092 OS (pupil size, 4.00 mm). Wavefront-guided SLs reduced residual higher-order root mean square to 0.19 µm OD and 0.25 µm OS, VA improved to 20/10 OD and 20/13 OS, and visual Strehl improved to 0.150 OD and 0.121 OS. The patient reported reduced smearing, shadowing, and night vision concerns, meeting his visual expectations and goals. CONCLUSIONS: Wavefront sensing quantifies both lower and HOAs, which can cause visual dissatisfaction in individuals with highly aberrated eyes, despite sometimes reaching typical levels of VA. As wavefront-guided SLs targeting these residual aberrations to improve visual image quality become more available, they should be considered for 20/20 unhappy patients when conventional clinical options are unsatisfactory.

The Impact of Misaligned Wavefront-guided Correction in a Scleral Lens for the Highly Aberrated Eye.

SIGNIFICANCE: To achieve maximum visual benefit, wavefront-guided scleral lens corrections (WGCs) are aligned with the underlying wavefront error of each individual eye. This requirement adds complexity to the fitting process. With a view toward simplification in lens fitting, this study quantified the consequences of placing WGCs at two pre-defined locations. PURPOSE: This study aimed to quantify performance reduction accompanying the placement of the WGC at two locations: (1) the average decentered location (ADL; average decentration observed across individuals wearing scleral lenses) and (2) the geometric center (GC) of the lens. METHODS: Deidentified residual aberration and lens translation data from 36 conventional scleral lens-wearing eyes with corneal ectasia were used to simulate WGC correction in silico. The WGCs were decentered from the eye-specific pupil position to both the ADL and GC locations. The impact of these misalignments was assessed in terms of change (from the aligned, eye-specific pupil position) in higher-order root mean square (HORMS) wavefront error, change in log of the visual Strehl ratio (logVSX), and predicted change in logMAR visual acuity (VA). RESULTS: As expected, HORMS increased, logVSX decreased, and predicted VA was poorer at both ADL and GC compared with the aligned condition (P < .001). Thirty-four of 36 eyes had greater residual HORMS, and 33 of 36 eyes had worse logVSX values at the GC than at the ADL. In clinical terms, 19 of 36 eyes at the ADL and 35 of 36 eyes at the GC had a predicted loss in VA of three letters or greater. CONCLUSIONS: The placement of the WGC at either ADL or GC is predicted to lead to a noticeable reduction in VA for more than half of the eyes studied, suggesting the simplification of the fitting process is not worth the cost in performance.

Quantifying the Optical and Physical Consequences of Daily Cleaning on Conventional and Wavefront-guided Scleral Lenses.

SIGNIFICANCE: An equivalent 12 months of cleaning did not induce significant changes in the optical aberrations or base curves of scleral lenses. PURPOSE: This study aimed to test whether an equivalent of 12 months of manual cleaning alters the optical and physical properties of conventional and wavefront-guided scleral lenses. METHODS: Twelve scleral lenses (four repeats of three designs, termed A, B, and C) were manufactured in Boston XO material: design A, -5.00 D defocus; design B, -5.00 D defocus with -0.153-µm vertical coma; and design C, -5.00 D defocus with a full custom wavefront-guided correction (second to fifth Zernike radial orders) of an eye with severe keratoconus. One lens of each design group served as a control and was not cleaned. To simulate a year of cleaning, seven individuals cleaned nine lenses (three from each group) twice a day for 27 days using the palm technique and commercially available cleaners, resulting in 378 cleanings of each lens. Lens aberrations were optically profiled and base curve radii were measured at baseline and after every 42nd cleaning. Differences in higher-order root mean square (HORMS) wavefront error and base curve radii associated with cleaning were compared with clinical benchmarks and using sign tests. RESULTS: For the experimental lenses, median change in Seidel spherical dioptric power was +0.01 D (maximum, +0.025 D). Median change in HORMS wavefront error was 0.013 µm (maximum, 0.019 µm). All lenses exhibited HORMS changes less than one-eighth equivalent diopters (P = .002). Median percentage change in HORMS wavefront error in the three wavefront-guided lenses was 0.96% (maximum, 1.25%). Median change in base curve radii was 0.00 mm, with all lenses exhibiting changes (P = .002), less than the American National Standards Institute tolerance of 0.05 mm. CONCLUSIONS: Cleaning over an equivalent 12-month period did not induce clinically significant changes in the optical or base curve properties of conventional or wavefront-guided scleral lenses.

Spatial memory shapes migration and its benefits: evidence from a large herbivore.

From fine-scale foraging to broad-scale migration, animal movement is shaped by the distribution of resources. There is mounting evidence, however, that learning and memory also guide movement. Although migratory mammals commonly track resource waves, how resource tracking and memory guide long-distance migration has not been reconciled. We examined these hypotheses using movement data from four populations of migratory mule deer (n = 91). Spatial memory had an extraordinary influence on migration, affecting movement 2-28 times more strongly than tracking spring green-up or autumn snow depth. Importantly, with only an ability to track resources, simulated deer were unable to recreate empirical migratory routes. In contrast, simulated deer with memory of empirical routes used those routes and obtained higher foraging benefits. For migratory terrestrial mammals, spatial memory provides knowledge of where seasonal ranges and migratory routes exist, whereas resource tracking determines when to beneficially move within those areas.

Plasticity in elk migration timing is a response to changing environmental conditions.

Migration is an effective behavioral strategy for prolonging access to seasonal resources and may be a resilient strategy for ungulates experiencing changing climatic conditions. In the Greater Yellowstone Ecosystem (GYE), elk are the primary ungulate, with approximately 20,000 individuals migrating to exploit seasonal gradients in forage while also avoiding energetically costly snow conditions. How climate-induced changes in plant phenology and snow accumulation are influencing elk migration timing is unknown. We present the most complete record of elk migration across the GYE, spanning 9 herds and 414 individuals from 2001 to 2017, to evaluate the drivers of migration timing and test for temporal shifts. The timing of elk departure from winter range involved a trade-off between current and anticipated forage conditions, while snow melt governed summer range arrival date. Timing of elk departure from summer range and arrival on winter range were both influenced by snow accumulation and exposure to hunting. At the GYE scale, spring and fall migration timing changed through time, most notably with winter range arrival dates becoming almost 50 days later since 2001. Predicted herd-level changes in migration timing largely agreed with observed GYE-wide changes-except for predicted winter range arrival dates which did not reflect the magnitude of change detected in the elk telemetry data. Snow melt, snow accumulation, and spring green-up dates all changed through time, with different herds experiencing different rates and directions of change. We conclude that elk migration is plastic, is a direct response to environmental cues, and that these environmental cues are not changing in a consistent manner across the GYE. The impacts of changing elk migration timing on predator-prey dynamics, carnivore-livestock conflict, disease ecology, and harvest management across the GYE are likely to be significant and complex.

Comparison of Wavefront-guided and Best Conventional Scleral Lenses after Habituation in Eyes with Corneal Ectasia.

SIGNIFICANCE: Visual performance with wavefront-guided (WFG) contact lenses has only been reported immediately after manufacture without time for habituation, and comparison has only been made with clinically unrefined predicate conventional lenses. We present comparisons of habitual corrections, best conventional scleral lenses, and WFG scleral lenses after habituation to all corrections. PURPOSE: The purpose of this study was to compare, in a crossover design, optical and visual performance of eyes with corneal ectasias wearing dispensed best conventional scleral lens corrections and dispensed individualized WFG scleral lens corrections. METHODS: Ten subjects (20 eyes) participated in a randomized crossover study where best conventional scleral lenses and WFG scleral lenses (customized through the fifth radial order) were worn for 8 weeks each. These corrections, as well as each subject's habitual correction and normative data for normal eyes, were compared using (1) residual higher-order aberrations (HORMS), (2) visual acuity (VA), (3) letter contrast sensitivity (CS), and (4) visual image quality (logarithm of the visual Strehl ratio, or logVSX). Correlations were performed between Pentacam biometric measures and gains provided by WFG lenses. RESULTS: Mean HORMS was reduced by 48% from habitual to conventional and 43% from conventional to WFG. Mean logMAR VA improved from habitual (+0.12) to conventional (-0.03) and further with WFG (-0.09); six eyes gained greater than one line with WFG over conventional. Area under the CS curve improved by 26% from habitual to conventional and 14% from conventional to WFG. The percentage of the eyes achieving normal levels were as follows: HORMS, 40% for conventional and 85% for WFG; VA, 50% for conventional and 85% for WFG; and CS, 60% for conventional and 90% for WFG. logVSX improved by 16% from habitual to conventional and 25% further with WFG. Reduction in aberrations with WFG lenses best correlated with posterior cornea radius of curvature. CONCLUSIONS: Visual performance was superior to that reported with nonhabituated WFG lens wear. With WFG lenses, HORMS and logVSX significantly improved, allowing more eyes to reach normal levels of optical and visual performance compared with conventional lenses.

Functional attributes of ungulate migration: landscape features facilitate movement and access to forage.

Long-distance migration by terrestrial mammals is a phenomenon critical to the persistence of populations, but such migrations are declining globally because of over-harvest, habitat loss, and movement barriers. Increasingly, there is a need to improve existing routes, mitigate route segments affected by anthropogenic disturbance, and in some instances, determine whether alternative routes are available. Using a hypothesis-driven approach, we identified landscape features associated with the primary functional attributes, stopovers and movement corridors, of spring migratory routes for mule deer in two study areas using resource selection functions. Patterns of selection for landscape attributes of movement corridors and stopovers mostly were similar; however, landscape features associated with movement corridors aligned better with areas that facilitated movement, whereas selection of stopovers was consistent with sites offering early access to spring forage. For movement corridors, deer selected for dry sites, low elevation, and low anthropogenic disturbance. For stopovers, deer selected for dry sites, with consistently early green-up across years, south-southwesterly aspects, low elevation, and low anthropogenic disturbance. Stopovers and movement corridors of a migratory route presumably promote different functions, but for a terrestrial migrant, patterns of habitat selection indicate that the same general habitat attributes may facilitate both movement and foraging in spring. Our findings emphasize the roles of topographical wetness, vegetation phenology, and anthropogenic disturbance in shaping use of the landscape during migration for this large herbivore. Avoiding human disturbance and tracking ephemeral forage resources appear to be a consistent pattern during migration, which reinforces the notion that movement during migration has a nutritional underpinning and disturbance potentially alters the net benefits of migration.

Demographic drivers of a refugee species: large-scale experiments guide strategies for reintroductions of hirola.

Effective reintroduction strategies require accurate estimates of vital rates and the factors that influence them. The hirola (Beatragus hunteri) is the rarest antelope on Earth, with a global population size of <500 individuals restricted to the Kenya-Somali border. We estimated vital rates of hirola populations exposed to varying levels of predation and rangeland quality from 2012 to 2015, and then built population matrices to estimate the finite rate of population change (λ) and demographic sensitivities. Mean survival for all age classes and population growth was highest in the low-predation-high-rangeland-quality setting (λ = 1.08 ± 0.03 [mean ± SE]), and lowest in the high-predation-low-rangeland-quality setting (λ = 0.70 ± 0.22). Retrospective demographic analyses revealed that increased fecundity (the number of female calves born to adult females annually) and female calf survival were responsible for higher population growth where large carnivores were absent. In contrast, variation in adult female survival was the primary contributor to differences in population growth attributable to rangeland quality. Our analyses suggest that hirola demography is driven by a combination of top-down (predation) and bottom-up (rangeland quality) forces, with populations in the contemporary geographic range impacted both by declining rangeland quality and predation. To enhance the chances of successful reintroductions, conservationists can consider rangeland restoration to boost both the survival and fecundity of adult females within the hirola's historical range.