Appealing to Different Appetites? A Comparative Analysis of Visitors and Residents to a Culinary Festival

This study presents a comparative analysis of visitors and local residents attending selected events at a month-long culinary festival. The primary purposes of this study were to compare the motivations, spending behaviours, and satisfaction levels of these two groups. Consideration was also given to the information sources used to learn about the Festival Findings are based on an on-line survey of festival attendees; in total 460 surveys were collected and used. Research findings highlighted differences between visitor and resident groups with respect to motivations for attending a culinary events, spending behaviours and information sources used. An examination of satisfaction rating revealed significant variance across individual events. These results offer valuable insights for culinary festival organizers and marketers, who may wish to consider the differing motivations and information sources used by these two groups when developing advertising campaigns and on-site food and shopping experiences

Motivations and Preferred Activities of Tourists to Rural Destinations: A Comparative Analysis of Rural and Urban Residents

The primary purposes of this study were to identify the perceived importance of motivations and activities for travel to a rural destination, and to determine whether these variables were influenced by the tourist’s place of residence. The study is based on an on-line survey completed by 1,048 individuals. A series of independent t-tests were used to determine whether there were differences in the motivations and preferred activities of rural residents versus urban residents, while canonical correlation analysis revealed relationships between the two sets of variables (motivations and activities). Findings suggest that rural destinations appeal to both rural and urban residents. In some instances, differences with regards to the motivations and activity preferences of these two groups were identified. Correlations between the motivations and activity preferences of respondents also suggest that rural tourists are interested in activities that are aligned with their initial motivations for deciding to travel to a rural area

Vetting Online Resources that Support Teachers' Promotion of Mathematical Habits of Mind

In this report, four secondary school mathematics teachers and one university mathematics teacher educator present an instrument designed to evaluate the usefulness and relevance of online resources at helping teachers develop practical conceptions of mathematical habits of mind as described by the Common Core’s Standards for Mathematical Practice. Descriptions for how the instrument was developed, its components parts, and an example of its use are provided in detail

Beyond planning tools: Experiential learning in climate adaptation planning and practices

In the past decade, several dedicated tools have been developed to help natural resources professionals integrate climate science into their planning and implementation; however, it is unclear how often these tools lead to on-the-ground climate adaptation. Here, we describe a training approach that we developed to help managers effectively plan to execute intentional, climate-informed actions. This training approach was developed through the Climate Change Response Framework (CCRF) and uses active and focused work time and peer-to-peer interaction to overcome observed barriers to using adaptation planning tools. We evaluate the effectiveness of this approach by examining participant evaluations and outlining the progress of natural resources projects that have participated in our trainings. We outline a case study that describes how this training approach can lead to place and context-based climate-informed action. Finally, we describe best practices based on our experience for engaging natural resources professionals and helping them increase their comfort with climate-informed planning

Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo

Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals with a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer’s disease (AD). These observations suggest that abnormal glucose metabolism likely plays a role in some aspects of AD pathogenesis, leading us to investigate the link between aberrant glucose metabolism, T2DM, and AD in murine models. Here, we combined two techniques — glucose clamps and in vivo microdialysis — as a means to dynamically modulate blood glucose levels in awake, freely moving mice while measuring real-time changes in amyloid-β (Aβ), glucose, and lactate within the hippocampal interstitial fluid (ISF). In a murine model of AD, induction of acute hyperglycemia in young animals increased ISF Aβ production and ISF lactate, which serves as a marker of neuronal activity. These effects were exacerbated in aged AD mice with marked Aβ plaque pathology. Inward rectifying, ATP-sensitive potassium (K(ATP)) channels mediated the response to elevated glucose levels, as pharmacological manipulation of K(ATP) channels in the hippocampus altered both ISF Aβ levels and neuronal activity. Taken together, these results suggest that K(ATP) channel activation mediates the response of hippocampal neurons to hyperglycemia by coupling metabolism with neuronal activity and ISF Aβ levels

Methionine Antagonizes para-Aminosalicylic Acid Activity via Affecting Folate Precursor Biosynthesis in Mycobacterium tuberculosis

para-Aminosalicylic acid (PAS) is a second-line anti-tubercular drug that is used for the treatment of drug-resistant tuberculosis (TB). PAS efficacy in the treatment of TB is limited by its lower potency against Mycobacterium tuberculosis relative to many other drugs in the TB treatment arsenal. It is known that intrinsic metabolites, such as, para-aminobenzoic acid (PABA) and methionine, antagonize PAS and structurally related anti-folate drugs. While the basis for PABA-mediated antagonism of anti-folates is understood, the mechanism for methionine-based antagonism remains undefined. In the present study, we used both targeted and untargeted approaches to identify factors associated with methionine-mediated antagonism of PAS activity. We found that synthesis of folate precursors as well as a putative amino acid transporter, designated MetM, play crucial roles in this process. Disruption of metM by transposon insertion resulted in a ≥30-fold decrease in uptake of methionine in M. bovis BCG, indicating that metM is the major facilitator of methionine transport. We also discovered that intracellular biotin confers intrinsic PAS resistance in a methionine-independent manner. Collectively, our results demonstrate that methionine-mediated antagonism of anti-folate drugs occurs through sustained production of folate precursors

Heterogenous Lung Inflammation CT Patterns Distinguish Pneumonia and Immune Checkpoint Inhibitor Pneumonitis and Complement Blood Biomarkers in Acute Myeloid Leukemia: Proof of Concept

BACKGROUND: Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers. MATERIALS AND METHODS: We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ( habitats ). We validated the model and compared it with a clinical-blood model to determine whether imaging can add diagnostic value. RESULTS: Habitat imaging revealed intrinsic lung inflammation patterns by identifying 5 distinct subregions, correlating to lung parenchyma, consolidation, heterogenous ground-glass opacity (GGO), and GGO-consolidation transition. Consequently, our proposed habitat model (accuracy of 79%, sensitivity of 48%, and specificity of 88%) outperformed the clinical-blood model (accuracy of 68%, sensitivity of 14%, and specificity of 85%) for classifying pneumonia versus pneumonitis. Integrating imaging and blood achieved the optimal performance (accuracy of 81%, sensitivity of 52% and specificity of 90%). Using this imaging-blood composite model, the post-test probability for detecting pneumonitis increased from 23% to 61%, significantly ( CONCLUSION: Habitat imaging represents a step forward in the image-based detection of pneumonia and pneumonitis, which can complement known blood biomarkers. Further work is needed to validate and fine tune this imaging-blood composite model and further improve its sensitivity to detect pneumonitis

Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.This work was supported in part by The Leukemia & Lymphoma Society Beat AML Program, the V Foundation for Cancer Research, the Gabrielle’s Angel Foundation for Cancer Research and the National Cancer Institute (1R01CA183947–01; 1U01CA217862–01; 1U54CA224019-01; 3P30CA069533-18S5). H.Z. received a Collins Medical Trust research grant. S.D.B. was supported by the National Cancer Institute (5R01CA138744-08)

Expedition 392 summary

During International Ocean Discovery Program Expedition 392, three sites were drilled on the Agulhas Plateau and one site was drilled in the Transkei Basin in the Southwest Indian Ocean. This region was positioned at paleolatitudes of ~53°–61°S during the Late Cretaceous (van Hinsbergen et al., 2015) (100–66 Ma) and within the new and evolving gateway between the South Atlantic, Southern Ocean, and southern Indian Ocean basins. Recovery of basement rocks and sedimentary sequences from the Agulhas Plateau sites and a thick sedimentary sequence in the Transkei Basin provides a wealth of new data to (1) determine the nature, origin, and bathymetric evolution of the Agulhas Plateau; (2) significantly advance the understanding of how Cretaceous temperatures, ocean circulation, and sedimentation patterns evolved as CO2 levels rose and fell and the breakup of Gondwana progressed; (3) document long- and short-term paleoceanographic variability through the Late Cretaceous and Paleogene; and (4) investigate geochemical interactions between igneous rocks, sediments, and pore waters through the life cycle of a large igneous province (LIP). Importantly, postcruise analysis of Expedition 392 drill cores will allow testing of competing hypotheses concerning Agulhas Plateau LIP formation and the role of deep ocean circulation changes through southern gateways in influencing Late Cretaceous–early Paleogene climate evolution