Values of lifelong learners and their pursuits of happiness and whole-person wellness.

Objectives: In this study, we explored the lived experiences of older adults engaged in lifelong learning programs using the Orientations to Happiness (OTH) framework.Methods: Semi-structured interviews employing a phenomenological approach were conducted with Midwestern older adults (aged 65 years and older) who participated in lifelong learning programs. Interviews were transcribed and collaboratively coded using pattern coding.Results: Six themes were identified that described the values expressed by participants: 1) need for novelty, 2) generativity, 3) spirituality, 4) hedonism, 5) active lifestyle, and 6) family. We created a novel diagram representing the intersectionality of the three OTH components (e.g.meaning, engagement, and pleasure) and explored how the six themes fit within our diagram. In doing so, we elucidated various OTH intersections that highlight a variety of happiness-promoting pathways that lifelong learning programs offer older adults.Discussion: Results suggest that these values and experiences can play an important role in maintaining an engaged lifestyle and providing opportunities for achieving and maintaining happiness and whole-person wellness.

Automated, Resin-Based Method to Enhance the Specific Activity of Fluorine-18 Clicked PET Radiotracers.

Radiolabeling of substrates with 2-[18F]fluoroethylazide exploits the rapid kinetics, chemical selectivity, and mild conditions of the copper-catalyzed azide-alkyne cycloaddition reaction. While this methodology has proven to result in near-quantitative labeling of alkyne-tagged precursors, the relatively small size of the fluoroethylazide group makes separation of the 18F-labeled radiotracer and the unreacted precursor challenging, particularly with precursors >500 Da (e.g., peptides). We have developed an inexpensive azide-functionalized resin to rapidly remove unreacted alkyne precursor following the fluoroethylazide labeling reaction and integrated it into a fully automated radiosynthesis platform. We have carried out 2-[18F]fluoroethylazide labeling of four different alkynes ranging from <300 Da to >1700 Da and found that >98% of the unreacted alkyne was removed in less than 20 min at room temperature to afford the final radiotracers at >99% radiochemical purity with specific activities up to >200 GBq/µmol. We have applied this technique to label a novel cyclic peptide previously evolved to bind the Her2 receptor with high affinity, and demonstrated tumor-specific uptake and low nonspecific background by PET/CT. This resin-based methodology is automated, rapid, mild, and general allowing peptide-based fluorine-18 radiotracers to be obtained with clinically relevant specific activities without chromatographic separation and with only a minimal increase in total synthesis time.

Directed Evolution of Scanning Unnatural-Protease-Resistant (SUPR) Peptides for in Vivo Applications.

Peptides typically have poor biostabilities, and natural sequences cannot easily be converted into drug-like molecules without extensive medicinal chemistry. We have adapted mRNA display to drive the evolution of highly stable cyclic peptides while preserving target affinity. To do this, we incorporated an unnatural amino acid in an mRNA display library that was subjected to proteolysis prior to selection for function. The resulting "SUPR (scanning unnatural protease resistant) peptide" showed ≈500-fold improvement in serum stability (t1/2 =160 h) and up to 3700-fold improvement in protease resistance versus the parent sequence. We extended this approach by carrying out SUPR peptide selections against Her2-positive cells in culture. The resulting SUPR4 peptide showed low-nanomolar affinity toward Her2, excellent specificity, and selective tumor uptake in vivo. These results argue that this is a general method to design potent and stable peptides for in vivo imaging and therapy.

Behavioral responses associated with a human-mediated predator shelter.

Human activities in protected areas can affect wildlife populations in a similar manner to predation risk, causing increases in movement and vigilance, shifts in habitat use and changes in group size. Nevertheless, recent evidence indicates that in certain situations ungulate species may actually utilize areas associated with higher levels of human presence as a potential refuge from disturbance-sensitive predators. We now use four-years of behavioral activity budget data collected from pronghorn (Antilocapra americana) and elk (Cervus elephus) in Grand Teton National Park, USA to test whether predictable patterns of human presence can provide a shelter from predatory risk. Daily behavioral scans were conducted along two parallel sections of road that differed in traffic volume--with the main Teton Park Road experiencing vehicle use that was approximately thirty-fold greater than the River Road. At the busier Teton Park Road, both species of ungulate engaged in higher levels of feeding (27% increase in the proportion of pronghorn feeding and 21% increase for elk), lower levels of alert behavior (18% decrease for pronghorn and 9% decrease for elk) and formed smaller groups. These responses are commonly associated with reduced predatory threat. Pronghorn also exhibited a 30% increase in the proportion of individuals moving at the River Road as would be expected under greater exposure to predation risk. Our findings concur with the 'predator shelter hypothesis', suggesting that ungulates in GTNP use human presence as a potential refuge from predation risk, adjusting their behavior accordingly. Human activity has the potential to alter predator-prey interactions and drive trophic-mediated effects that could ultimately impact ecosystem function and biodiversity.

The effect of human activities and their associated noise on ungulate behavior.

BACKGROUND: The effect of anthropogenic noise on terrestrial wildlife is a relatively new area of study with broad ranging management implications. Noise has been identified as a disturbance that has the potential to induce behavioral responses in animals similar to those associated with predation risk. This study investigated potential impacts of a variety of human activities and their associated noise on the behavior of elk (Cervus elaphus) and pronghorn (Antilocapra americana) along a transportation corridor in Grand Teton National Park. METHODOLOGY/PRINCIPAL FINDINGS: We conducted roadside scan surveys and focal observations of ungulate behavior while concurrently recording human activity and anthropogenic noise. Although we expected ungulates to be more responsive with greater human activity and noise, as predicted by the risk disturbance hypothesis, they were actually less responsive (less likely to perform vigilant, flight, traveling and defensive behaviors) with increasing levels of vehicle traffic, the human activity most closely associated with noise. Noise levels themselves had relatively little effect on ungulate behavior, although there was a weak negative relationship between noise and responsiveness in our scan samples. In contrast, ungulates did increase their responsiveness with other forms of anthropogenic disturbance; they reacted to the presence of pedestrians (in our scan samples) and to passing motorcycles (in our focal observations). CONCLUSIONS: These findings suggest that ungulates did not consistently associate noise and human activity with an increase in predation risk or that they could not afford to maintain responsiveness to the most frequent human stimuli. Although reduced responsiveness to certain disturbances may allow for greater investment in fitness-enhancing activities, it may also decrease detections of predators and other environmental cues and increase conflict with humans.

Interpersonal contribution to outcome: The relation of interpersonal distress and symptomatic improvement as a result of psychotherapy.

The study utilized a 32-item brief measure of interpersonal problems (IIP) to examine interpersonal distress in relation to symptomology and treatment outcome as assessed by the Outcome Questionnaire-45 (OQ-45). The study included a community sample of 210 individuals receiving psychotherapy at a mental health training facility. A number of significant correlations were found between interpersonal distresses with symptomology. The highest correlations were found between levels of general interpersonal distress and symptoms relating to psychiatric and social distress at the onset of therapy; in general the IIP did not differentiate between symptomology types. The study failed to replicate previous research indicating a relation between facets of interpersonal problems with treatment outcome.

An examination of the "interpersonalness" of the outcome questionnaire.

This study examined whether the Outcome Questionnaire-45 (OQ) and its subscales assessed unique interpersonal distress. The Inventory of Interpersonal Problems (IIP) was used to assess discriminant validity for unique interpersonal distress. Participants (N = 121) were recruited from a southwestern university counselor training center. Significant correlations emerged between OQ and IIP scores supporting the OQ as a measure of general interpersonal distress. However, the OQ subscales do not significantly assess unique types of interpersonal distress.

A comparison of data sets varying in spatial accuracy used to predict the occurrence of wildlife-vehicle collisions.

Wildlife-vehicle collisions (WVCs) pose a significant safety and conservation concern in areas where high-traffic roads are situated adjacent to wildlife habitat. Improving transportation safety, accurately planning highway mitigation, and identifying key habitat linkage areas may all depend on the quality of WVC data collection. Two common approaches to describe the location of WVCs are spatially accurate data derived from global positioning systems (GPS) or vehicle odometer measurements and less accurate road-marker data derived from reference points (e.g., mile-markers or landmarks) along the roadside. In addition, there are two common variable types used to predict WVC locations: (1) field-derived, site-specific measurements and (2) geographic information system (GIS)-derived information. It is unclear whether these different approaches produce similar results when attempting to identify and explain the location of WVCs. Our first objective was to determine and compare the spatial error found in road-marker data (in our case the closest mile-marker) and landmark-referenced data. Our second objective was to evaluate the performance of models explaining high- and low-probability WVC locations, using congruent, spatially accurate (<3-m) and road-marker (<800-m) response variables in combination with field- and GIS-derived explanatory variables. Our WVC data sets were comprised of ungulate collisions and were located along five major roads in the central Canadian Rocky Mountains. We found that spatial error (mean +/- SD) was higher for WVC data referenced to nearby landmarks (516 +/- 808 m) than for data referenced to the closest mile-marker data (401 +/- 219 m). The top-performing model using the spatially accurate WVC locations contained all explanatory variable types, whereas GIS-derived variables were only influential in the best road-marker model and the spatially accurate reduced model. Our study showed that spatial error and sample size, using road-marker data for ungulate species, are important to consider for model output interpretation, which will impact the appropriate scale on which to apply modeling results. Using road-marker references <1.6 km or GPS-derived data locations may represent an optimal compromise between data acquisition costs and analytical performance.

An assessment of road impacts on wildlife populations in U.S. national parks.

Current United States National Park Service (NPS) management is challenged to balance visitor use with the environmental and social consequences of automobile use. Wildlife populations in national parks are increasingly vulnerable to road impacts. Other than isolated reports on the incidence of road-related mortality, there is little knowledge of how roads might affect wildlife populations throughout the national park system. Researchers at the Western Transportation Institute synthesized information obtained from a system-wide survey of resource managers to assess the magnitude of their concerns on the impacts of roads on park wildlife. The results characterize current conditions and help identify wildlife-transportation conflicts. A total of 196 national park management units (NPS units) were contacted and 106 responded to our questionnaire. Park resource managers responded that over half of the NPS units' existing transportation systems were at or above capacity, with traffic volumes currently high or very high in one quarter of them and traffic expected to increase in the majority of units. Data is not generally collected systematically on road-related mortality to wildlife, yet nearly half of the respondents believed road-caused mortality significantly affected wildlife populations. Over one-half believed habitat fragmentation was affecting wildlife populations. Despite these expressed concerns, only 36% of the NPS units used some form of mitigation method to reduce road impacts on wildlife. Nearly half of the respondents expect that these impacts would only worsen in the next five years. Our results underscore the importance for a more systematic approach to address wildlife-roadway conflicts for a situation that is expected to increase in the next five to ten years.

Prolonged signal-averaged P-wave duration as an intermediate phenotype for familial atrial fibrillation.

OBJECTIVES: This study sought to perform a genome-wide linkage analysis in a large atrial fibrillation (AF) kindred using AF and abnormally prolonged signal-averaged (SA) P-wave duration as the phenotype. BACKGROUND: Although inherited forms of AF exist, phenotypic complexity has limited efforts to ascertain mutation carriers and thus identify causal genes. The identification of intermediate or endophenotypes may accelerate this effort. METHODS: A genome-wide linkage analysis was performed in a 4-generation AF kindred of 27 individuals, 8 with AF documented by electrocardiogram. The analysis was performed using AF as the phenotype, and repeated using an abnormally prolonged SA P-wave duration as the phenotype. RESULTS: Linkage analysis and fine mapping generated a maximum multipoint logarithm of the odds (LOD) score of 3.0 at chromosome 5p15 between markers D5S406 and D5S635. Importantly, 8 heterozygous carriers had a prolonged SA P-wave (203 +/- 21 ms) compared with 17 noncarriers (116 +/- 12 ms, p < 0.00001). Using prolonged SA P-wave (conventionally defined as >155 ms) as an endophenotype, a maximum LOD score of 3.6 was obtained in the same region of chromosome 5p15, a span of 5.75 centi-Morgans. CONCLUSIONS: In a large AF kindred, we have identified a novel AF locus on chromosome 5p15 and shown that affected individuals with AF and mutation carriers can be identified by a prolonged SA P-wave duration. Importantly, identification of an endophenotype in this kindred not only aided ascertainment of additional family members but also increased the LOD score, providing increased support for linkage at this locus. Identification of the causal gene, mapped to chromosome 5p15, will advance our understanding of the molecular basis of AF.

Behavioral responses of bison and elk in Yellowstone to snowmobiles and snow coaches.

Managers of public lands are charged with protecting some of our most important natural resources and ecosystems, while providing for their use and enjoyment by visitors. Almost one million visitors entered Yellowstone National Park by motorized means on snowmobiles (87%) or snow coaches (13%) during 1992-2003. Most vehicles toured the central portion of the park where bison (Bison bison) and elk (Cervus elaphus) concentrate in geothermal areas. We sampled >6500 interactions between groups of these species and groups of snowmobiles and snow coaches (collectively, OSV, over-snow vehicles) during five winters (1999-2000, 2002-2004). Multinomial logits models were used to identify conditions leading to behavioral responses. Elk responded three times as often (52%) as bison (19%) during interactions with groups of snowmobiles and snow coaches due to increased vigilance responses (elk, 44%; bison, 10%). However, the frequency of higher-intensity movement responses by bison and elk were similar (6-7% travel, 1-2% flight, <1% defense) and relatively low compared to other studies of ungulates and snowmobile disturbance. The likelihood of active responses by bison and elk increased significantly if animals were on or near roads, groups were smaller, or humans approached. The likelihood of an active response by bison decreased within winters having the largest visitation, suggesting some habituation to snowmobiles and snow coaches. There was no evidence that snowmobile use during the past 35 years affected the population dynamics or demography of bison or elk. Thus, we suggest that regulations restricting levels and travel routes of over-snow vehicles (OSVs) were effective at reducing disturbances to bison and elk below a level that would cause measurable fitness effects. We recommend park managers consider maintaining OSV traffic levels at or below those observed during our study. Regardless, differing interpretations of the behavioral and physiological response data will continue to exist because of the diverse values and beliefs of the many constituencies of Yellowstone.