"I was screaming hallelujah": Patient and provider perceptions of blood-based testing for colorectal cancer screening.

BACKGROUND: Blood-based tests for colorectal cancer (CRC) screening can offer many advantages over stool-based tests such as FIT. Yet, we know little about patients' and providers' perceptions of this type of test. We report findings from a qualitative study comparing patient and provider perceptions of blood-based testing for CRC screening. METHODS: Patient participants were aged 45-75 years and members of a large, integrated health system. Participants were mailed, but did not complete, a FIT through an organized FIT-screening program and were scheduled for a health-care encounter at any of nine clinical sites. Participants were consented to complete a blood draw. We used purposive sampling to select and recruit patients (who did and did not complete the blood test) and providers/specialists who would be involved in offering the blood test to patients or explaining results. We administered telephone interviews using a semi-structured interview guide and recorded and transcribed all interviews, then coded and analyzed content. RESULTS: We interviewed 15 patients (11 completed and 4 did not complete the blood test) and 5 providers (3 primary care providers, one gastroenterologist (GI), and one GI medical assistant). Patients were enthusiastic about completing a blood test, citing the simplicity, ease, convenience, and high perceived accuracy of the test. Providers were also receptive to a blood-based option, if adequate test performance could be achieved and if they have information that informs patients about the pros and cons of blood-based screening versus other screening tests. CONCLUSIONS: Patients and providers were willing and enthusiastic about blood-based CRC screening tests. Future research focusing on performance and communication is needed.

Climate-informed forecasts reveal dramatic local habitat shifts and population uncertainty for northern boreal caribou.

Most research on boreal populations of woodland caribou (Rangifer tarandus caribou) has been conducted in areas of high anthropogenic disturbance. However, a large portion of the species' range overlaps relatively pristine areas primarily affected by natural disturbances, such as wildfire. Climate-driven habitat change is a key concern for the conservation of boreal-dependent species, where management decisions have yet to consider knowledge from multiple ecological domains integrated into a cohesive and spatially explicit forecast of species-specific habitat and demography. We used a novel ecological forecasting framework to provide climate-sensitive projections of habitat and demography for five boreal caribou monitoring areas within the Northwest Territories (NWT), Canada, over 90 years. Importantly, we quantify uncertainty around forecasted mean values. Our results suggest habitat suitability may increase in central and southwest regions of the NWT's Taiga Plains ecozone but decrease in southern and northwestern regions driven by conversion of coniferous to deciduous forests. We do not project that boreal caribou population growth rates will change despite forecasted changes to habitat suitability. Our results emphasize the importance of efforts to protect and restore northern boreal caribou habitat despite climate uncertainty while highlighting expected spatial variations that are important considerations for local people who rely on them. An ability to reproduce previous work, and critical thought when incorporating sources of uncertainty, will be important to refine forecasts, derive management decisions, and improve conservation efficacy for northern species at risk.

Protecting boreal caribou habitat can help conserve biodiversity and safeguard large quantities of soil carbon in Canada.

Boreal caribou require large areas of undisturbed habitat for persistence. They are listed as threatened with the risk of extinction in Canada because of landscape changes induced by human activities and resource extraction. Here we ask: Can the protection of habitat for boreal caribou help Canada meet its commitments under the United Nations Convention on Biological Diversity and United Nations Framework Convention on Climate Change? We identified hotspots of high conservation value within the distribution of boreal caribou based on: (1) three measures of biodiversity for at risk species (species richness, unique species and taxonomic diversity); (2) climate refugia or areas forecasted to remain unchanged under climate change; and, (3) areas of high soil carbon that could add to Canada's greenhouse gas emissions if released into the atmosphere. We evaluated the overlap among hotspot types and how well hotspots were represented in Canada's protected and conserved areas network. While hotspots are widely distributed across the boreal caribou distribution, with nearly 80% of the area falling within at least one hotspot type, only 3% of the distribution overlaps three or more hotspots. Moreover, the protected and conserved areas network only captures about 10% of all hotspots within the boreal caribou distribution. While the protected and conserved areas network adequately represents hotspots with high numbers of at risk species, areas occupied by unique species, as well as the full spectrum of areas occupied by different taxa, are underrepresented. Climate refugia and soil carbon hotspots also occur at lower percentages than expected. These findings illustrate the potential co-benefits of habitat protection for caribou to biodiversity and ecosystem services and suggest caribou may be a good proxy for future protected areas planning and for developing effective conservation strategies in regional assessments.

Multi-objective optimization can balance trade-offs among boreal caribou, biodiversity, and climate change objectives when conservation hotspots do not overlap.

The biodiversity and climate change crises have led countries-including Canada-to commit to protect more land and inland waters and to stabilize greenhouse gas concentrations. Canada is also obligated to recover populations of at-risk species, including boreal caribou. Canada has the opportunity to expand its protected areas network to protect hotspots of high value for biodiversity and climate mitigation. However, co-occurrence of hotspots is rare. Here we ask: is it possible to expand the network to simultaneously protect areas important for boreal caribou, other species at risk, climate refugia, and carbon stores? We used linear programming to prioritize areas for protection based on these conservation objectives, and assessed how prioritization for multiple, competing objectives affected the outcome for each individual objective. Our multi-objective approach produced reasonably strong representation of value across objectives. Although trade-offs were required, the multi-objective outcome was almost always better than when we ignored one objective to maximize value for another, highlighting the risk of assuming that a plan based on one objective will also result in strong outcomes for others. Multi-objective optimization approaches could be used to plan for protected areas networks that address biodiversity and climate change objectives, even when hotspots do not co-occur.

Functional response of wolves to human development across boreal North America.

AIM: The influence of humans on large carnivores, including wolves, is a worldwide conservation concern. In addition, human-caused changes in carnivore density and distribution might have impacts on prey and, indirectly, on vegetation. We therefore tested wolf responses to infrastructure related to natural resource development (i.e., human footprint). LOCATION: Our study provides one of the most extensive assessments of how predators like wolves select habitat in response to various degrees of footprint across boreal ecosystems encompassing over a million square kilometers of Canada. METHODS: We deployed GPS-collars on 172 wolves, monitored movements and used a generalized functional response (GFR) model of resource selection. A functional response in habitat selection occurs when selection varies as a function of the availability of that habitat. GFRs can clarify how human-induced habitat changes are influencing wildlife across large, diverse landscapes. RESULTS: Wolves displayed a functional response to footprint. Wolves were more likely to select forest harvest cutblocks in regions with higher cutblock density (i.e., a positive functional response to high-quality habitats for ungulate prey) and to select for higher road density in regions where road density was high (i.e., a positive functional response to human-created travel routes). Wolves were more likely to use cutblocks in habitats with low road densities, and more likely to use roads in habitats with low cutblock densities, except in winter when wolves were more likely to use roads regardless of cutblock density. MAIN CONCLUSIONS: These interactions suggest that wolves trade-off among human-impacted habitats, and adaptively switch from using roads to facilitate movement (while also risking encounters with humans), to using cutblocks that may have higher ungulate densities. We recommend that conservation managers consider the contextual and interacting effects of footprints when assessing impacts on carnivores. These effects likely have indirect impacts on ecosystems too, including on prey species.

Overall and minority-focused recruitment strategies in the PREMIER multicenter trial of lifestyle interventions for blood pressure control.

Recruitment strategies employed by four clinical centers across the US and a coordinating center were examined to identify successful overall and minority-focused recruitment strategies for the PREMIER multicenter trial of lifestyle changes for blood pressure control. The goal was to recruit 800 adults (40% African Americans) with systolic blood pressure of 120-159 mm Hg and diastolic of 80-95 mm Hg, not taking antihypertensive medication. Clinical centers used combinations of mass distribution of brochures, mass media, email distribution lists, screening events, and a national website. Culturally appropriate strategies for African Americans were designed by a Minority Implementation (MI) committee. Diversity training was provided for study staff, and African Americans were included in the study design process. Main recruitment outcomes were number overall and number of African Americans recruited by each strategy. Of the 810 randomized PREMIER participants, 279 (34%) were African American with site-specific percentages of 56%, 46%, 27%, and 8%. Of African Americans recruited, 151 (54%) were from mass distribution of brochures (mailed letter, flyer included in Val-Pak coupons, or other), 66 (24%) from mass media (printed article, radio, TV story or ads, 52 (19%) from word of mouth, and 10 (3%) from email/website and screening events combined. Yields for Non-Hispanic Whites were 364 (69%) from brochures, 71 (13%) from mass media, 49 (9%) from word of mouth and 47 (9%) from email/website and screening events. Mass distribution of brochures was relatively more effective with Non-Hispanic Whites, while African Americans responded relatively better to other recruitment strategies.

Mortality risk increases with natal dispersal distance in American martens.

The assumption that mortality risk increases with dispersal distance has rarely been tested. We compared patterns of natal dispersal in the American marten (Martes americana) between a large regenerating forest landscape and an uncut landscape that was dominated by more mature forest to test whether mortality risk increased with dispersal distance, and whether variation in mortality risk influenced dispersal distance. Mortality risk increased with dispersal distance in both landscape treatments, but the distance-dependent increase in mortality in the regenerating landscape was twice that in the uncut landscape. Differences in body condition, supported by other data on foraging efficiency, suggested that juveniles from the regenerating landscape were less able to cope with the energetic demands of dispersal compared with juveniles from older forests. Juveniles travelled shorter distances in the regenerating versus uncut landscape. These results implied that dispersal was costly in terms of juvenile survival and that mean dispersal distance was shaped, in part, by mortality risk.

Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution.

The crystal structures of two human dihydrofolate reductase (hDHFR) ternary complexes, each with bound NADPH cofactor and a lipophilic antifolate inhibitor, have been determined at atomic resolution. The potent inhibitors 6-([5-quinolylamino]methyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (SRI-9439) and (Z)-6-(2-[2,5-dimethoxyphenyl]ethen-1-yl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (SRI-9662) were developed at Southern Research Institute against Toxoplasma gondii DHFR-thymidylate synthase. The 5-deazapteridine ring of each inhibitor adopts an unusual puckered conformation that enables the formation of identical contacts in the active site. Conversely, the quinoline and dimethoxybenzene moieties exhibit distinct binding characteristics that account for the differences in inhibitory activity. In both structures, a salt-bridge is formed between Arg70 in the active site and Glu44 from a symmetry-related molecule in the crystal lattice that mimics the binding of methotrexate to DHFR.