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RET tyrosine kinase is necessary for enteric nervous system development. Loss-of-function RET mutations cause Hirschsprung disease (HSCR), in which infants are born with aganglionic bowel. Despite surgical correction, patients with HSCR often experience chronic defecatory dysfunction and enterocolitis, suggesting that RET is important after development. To test this hypothesis, we determined the location of postnatal RET and its significance in gastrointestinal (GI) motility. Ret CFP/+ mice and human transcriptional profiling data were studied to identify the enteric neuronal and epithelial cells that express RET. To determine whether RET regulates gut motility in vivo, genetic, and pharmacologic approaches were used to disrupt RET in all RET-expressing cells, a subset of enteric neurons, or intestinal epithelial cells. Distinct subsets of enteric neurons and enteroendocrine cells expressed RET in the adult intestine. RET disruption in the epithelium, rather than in enteric neurons, slowed GI motility selectively in male mice. RET kinase inhibition phenocopied this effect. Most RET+ epithelial cells were either enterochromaffin cells that release serotonin or L-cells that release peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), both of which can alter motility. RET kinase inhibition exaggerated PYY and GLP-1 release in a nutrient-dependent manner without altering serotonin secretion in mice and human organoids. PYY receptor blockade rescued dysmotility in mice lacking epithelial RET. RET signaling normally limits nutrient-dependent peptide release from L-cells and this activity is necessary for normal intestinal motility in male mice. These effects could contribute to dysmotility in HSCR, which predominantly affects males, and uncovers a mechanism that could be targeted to treat post-prandial GI dysfunction. [Display omitted] Signaling by the RET growth factor receptor in intestinal epithelial cells is important for regulating gut hormone release and propulsive activity, offering a new therapeutic target for motility disorders. [ABSTRACT FROM AUTHOR]

Background: Continuing professional development fosters advancement in knowledge and skills and can support changes in practice. Research suggests that pharmacists perceive the need for additional training to take on expanded roles. However, the types of professional development and preferred learning methods are unclear.Objective: To identify pharmacists' professional learning needs in order to support expanded roles in practice.Methods: A mixed-methods approach was used. In focus groups made up of pharmacists and pharmacy students, learning needs associated with their perceptions of pharmacists' roles were examined. A web-based survey of Albertan pharmacists determined the knowledge, experience, and confidence required to engage in professional activities, preferred learning methods, and professional development needed to support pharmacists currently and in future.Results: Analysis of data obtained from 5 focus groups (n = 42) revealed learning needs related to changes in pharmacists' roles. Pharmacists valued the social aspect of learning as well as the role of certification in building confidence. Survey data (n = 416) indicated that a high proportion of pharmacists reported training needs in the areas of physical assessment, interpreting laboratory tests, and making decisions about complex drug therapy. Community pharmacists and those with bachelor degrees were more likely to indicate a need for additional training in various patient care skills. Pharmacists reported a preference for learning with peers and learning at work within teams.Conclusion: Meeting various learning needs will foster pharmacists in their current and future professional roles, including situated learning in the workplace. These findings will be of interest to employers and educators in supporting pharmacists' evolving roles in practice. [ABSTRACT FROM AUTHOR]

Objective: To describe experiences with development and implementation of a compensation plan for pharmacy services delivered by pharmacists in community pharmacies.Setting: Community pharmacy practice in Alberta, Canada.Practice Description: Pharmacists in Alberta have one of the most progressive scopes of practice in North America. They have authority to prescribe drugs independently, administer drugs by injection, access electronic health records, and order laboratory tests.Practice Innovation: A publicly funded compensation plan for pharmacy services was implemented in 2012. Principles that guided development of the compensation plan aimed to 1) ensure payment for pharmacy services, 2) support pharmacists in using their full scope of practice, 3) enable the development of long-term relationships with patients, 4) facilitate expansion of services delivered by pharmacists, and 5) provide access to pharmacy services for all eligible Albertans. Services covered by the compensation plan include care planning, prescribing, and administering drugs by injection.Evaluation: The guiding principles were used to evaluate experiences with the compensation plan.Results: Claims for pharmacy services covered by the compensation plan increased from 30,000 per month in July 2012 to 170,000 per month in March 2016. From September 2015 to August 2016, 1226 pharmacies submitted claims for services provided by 3901 pharmacists. The number of pharmacists with authorization to prescribe and administer injections continued to increase following implementation of the plan.Conclusion: Alberta's experiences with the development and implementation of the compensation plan will be of interest to jurisdictions considering implementation of remunerated pharmacy services. The potential impact of the plan on health and economic outcomes, in addition to the value of the services as perceived by the public, patients, pharmacists, and other health care providers, should also be explored. [ABSTRACT FROM AUTHOR]

Background: Alberta was the first province in Canada to enact legislative changes to permit expansion of pharmacists' scope of practice, including allowing pharmacists to prescribe. However, such changes to the scope of practice can blur professional boundaries and obscure the roles of pharmacists. Understanding perceptions about the pharmacist's role may provide insight into recent and historical changes in pharmacy practice. This study clarifies perceptions held by pharmacists and other stakeholders concerning the role of the pharmacist in society.Objective: To understand the perceptions of pharmacists, pharmacy students, technicians, other health care professionals, and the public of the pharmacist's role in Alberta.Methods: A mixed methods approach was used: focus group sessions (n = 9) and individual interviews (n = 4) of pharmacists and other stakeholders were conducted and analyzed using qualitative-descriptive approach. A web-based survey of Alberta pharmacists (n = 416) explored pharmacists' perceptions of their own roles.Results: Data analysis revealed the following: participants perceived that the pharmacist's role was transitioning to focus more on patient care; consistency in pharmacist uptake of this new role shaped the public's expectations; pharmacists with expanded scopes of practice were assuming greater responsibility; collaboration and relationships with other health care professionals were essential. The survey confirmed that changes in the roles of pharmacists were primarily related to patient care.Conclusion: Following legislative changes and implementation of a compensation framework for pharmacy services, pharmacists and other stakeholders perceived the pharmacist's role to be shifting toward patient care. Periodic revisiting of pharmacists' roles and professional activities is needed to evaluate changes over time. [ABSTRACT FROM AUTHOR]

K-Ras is a monomeric GTPase that controls cellular and tissue homeostasis. Prior studies demonstrated that mutationally activated K-Ras (K-Ras G12D ) signals through MEK to promote expansion and hyperproliferation of the highly mitotically active transit-amplifying cells (TACs) in the intestinal crypt. Its effect on normally quiescent stem cells was unknown, however. Here, we have used an H2B-Egfp transgenic system to demonstrate that K-Ras G12D accelerates the proliferative kinetics of quiescent intestinal stem cells. As in the TAC compartment, the effect of mutant K-Ras on the quiescent stem cell is dependent upon activation of MEK. Mutant K-Ras is also able to increase self-renewal potential of intestinal stem cells following damage. These results demonstrate that mutant K-Ras can influence intestinal homeostasis on multiple levels. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To evaluate clinical and imaging features associated with adequacy of the hepatocyte phase (HP) in gadoxetate disodium–enhanced liver magnetic resonance imaging (MRI) in patients without chronic liver disease (CLD). Materials and Methods: This was a retrospective institutional review board–approved study of 97 patients who underwent liver MRI examinations with gadoxetate disodium and had no history of CLD. Available late dynamic and HP sequences (3–20 minutes postinjection) were independently analyzed by four radiologists for perceived image adequacy and level of biliary enhancement. Signal intensity ratios (SIRs) of liver/inferior vena cava (IVC), liver/spleen, and liver/muscle were measured. The Spearman ρ and receiver operating characteristic analyses were performed correlating various factors with HP adequacy. A rule for predicting HP adequacy was also derived and tested to determine whether overall examination time could be shortened. Results: A visually adequate HP was observed in 12% of subjects by 10 minutes, 80% by 15 minutes, and 93% by 20 minutes. An SIRliver/IVC > 1.8 was the imaging feature that had the strongest correlation with an adequate HP (ρ = 0.813, P < .001), and was more predictive of adequacy of the HP than the time postinjection (ρ = 0.5, P < .001). The time at which an adequate HP was first observed did not correlate with any tested demographic or laboratory values. Stopping imaging when an SIRliver/IVC > 1.8 would have successfully reduced mean postcontrast time to 15:39 ± 4:02 from 20:00 (P < .001), although maintaining HP adequacy. Conclusions: Most patients without CLD undergoing gadoxetate-enhanced liver MRI achieve adequate HP at 20 minutes. However, a shorter postcontrast stopping time can be used in most patients. [Copyright &y& Elsevier]

Objective: To obtain an understanding of how community pharmacists self-describe their professional role, in order to begin understanding some of the assumptions underlying pharmacy culture. Design: Cross-sectional qualitative study. Setting: Edmonton, Canada, and surrounding area. Participants: 115 community pharmacists. Intervention: Brief telephone interview Main outcomes measure: Pharmacists' self-description/perception of their professional role and its relation to underlying assumptions of pharmacy culture. Results: 100 pharmacists provided usable responses. The majority of pharmacists practiced in a community chain setting (76%) and within the city of Edmonton (81%). The median length of time in practice was 15 years. A total of 278 separate response items were obtained. Of these responses, 45% were categorized as product focused, 29% as patient centered, and 26% as ambiguous. The first response of 52 of the 100 pharmacists was a product-focused description of their role. Overall, in either their first or second response, 57% of the pharmacists used the term "dispensing" or dispensing-related terms to describe their professional role. Conclusion: The results of this study seem to suggest that, community pharmacists who participated viewed themselves primarily as "dispensers of medication," not patient-centered practitioners. Sustainable pharmacy practice change will be possible only if the current culture aligns with change initiatives. Our findings may suggest that pharmacists self-perception of what they do and, perhaps by extension, the culture of pharmacy itself, could be important barriers to implementing practice change initiatives. We need to better understand the culture of pharmacy to foster meaningful practice change. [ABSTRACT FROM AUTHOR]

• Apex mesocarnivores important to conservation of island ecosystems. • Ecology of Pacific marten not well understood across intensively managed forests. • Marten associated with habitat containing some component of forest edge and road. • Foraging likely adapted to invasive Sitka black-tailed deer and forest management. • Competition and predation may contribute to regulation of species at risk on Haida Gwaii. Apex mesocarnivores can have a large influence on the functioning of plant and animal communities. Such effects can be more pronounced in relatively depauperate island ecosystems, especially in the context of a legacy of landscape change and introduced species. One such ecosystem is Haida Gwaii, British Columbia, Canada, where a long history of introduced species and forest harvesting has greatly influenced the composition of the plant and animal communities. Most notably, Sitka black-tailed deer (Odocoileus hemionus sitkensis), an introduced and unchecked invasive species, has interacted with forest harvesting to greatly change the understory structure and composition of those temperate rainforests. Little is known of the habitat ecology of Pacific marten (Martes caurina), the small-bodied apex predator on those islands. We used camera traps to monitor the distribution and habitat ecology of marten across 2 winters. We used mixed-effects logistic regression to test 14 a priori hypotheses represented by statistical models formulated at two spatial scales (100 and 1000 m), with four categories of explanatory factors: sampling bias, forest structure, topography, and human disturbance. Relationships between detections and covariates from the top models revealed that at the 100-m scale, marten were more likely to use habitat that was closer to streams and marine shorelines and that contained a small area of forest harvesting. Marten detections were associated with habitat containing some component of forest edge and road, suggesting foraging behavior adapted to invasive deer, an important source of carrion for marten during winter. The broad use of habitats by Pacific marten suggests that intraguild competition and predation might occur with several species at risk including the endemic Haida ermine (Mustela ermine haidarum). Those two species would likely overlap in diet and distribution when co-occurring across low-elevation coastal habitats. Conservation planning on Haida Gwaii should consider measures that decrease the potential for competition or predation between marten and species at risk. [ABSTRACT FROM AUTHOR]

• Automatic quest generation can be accomplished with an input world state and a planning algorithm. • An explicit ontology of character motivation can allow for a variety of quest kinds. • The CONAN system can do procedural generation of quests. • An automated classifier system can measure the breadth of quest types generated This work proposes an engine for the Creation Of Novel Adventure Narrative (CONAN), which is a procedural quest generator that uses a planning approach. The engine is tested on its ability to create quests, which are sets of actions that must be performed in order to achieve a certain goal. The engine takes in a world description represented as a set of facts, including characters, locations, and items, and generates quests according to the state of the world and the preferences of the characters in it. We evaluate quests through the classification of the motivations behind the quests. We also compare world descriptions of two different sizes. Compared to human structural quest classification, the current engine was found to be able to replicate the quest structures found in commercial video game quests. [ABSTRACT FROM AUTHOR]

Objectives: To describe the comprehensive annual care plan (CACP) process and to conceptualize how remunerated CACP services were implemented by community pharmacists.Design: A comparative, multiple case study approach with data comprising document review, observation, and semistructured interviews.Setting and Participants: Pharmacists, pharmacy technicians and staff, and student pharmacists from 4 different community pharmacy sites in Alberta, Canada, including independent, franchise, and corporate chain pharmacies. In addition, patients and other health care providers were included in the interviews.Outcome Measures: Constructivist grounded theory was used to understand how care planning services were implemented in the real-world context of community pharmacies and how pharmacists provided CACPs within their practice.Results: Between May 2016 and January 2018, a total of 77 interviews and 94 hours of observations were completed at the 4 pharmacy sites, and 61 documents were collected. The CACP service required adaptation of the workflow at each of the sites. However, pharmacists and other pharmacy staff recognized benefits of the service with respect to pharmacists' role expansion. The overarching grounded theory concept was changing the status quo. The following 4 themes emerged representing how the service was implemented: engaging patients, professional development and learning from experience, creating a supportive environment, and building community connections.Conclusion: This study found that practice change or changing the status quo was needed to implement remunerated care planning services in community pharmacies. The results of this study may be of interest to community pharmacists, pharmacy managers, and policy makers who are implementing remunerated care planning services in other jurisdictions. [ABSTRACT FROM AUTHOR]

The article reports on the compensation plan for the pharmacy services in Alberta, with topics including the importance of patient care services in pharmacy profession, the management of health care expenditures, and the importance of compensation plans.