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In the context of sport events, several stakeholders' reputations could be impacted by critical incidents, including event organizers, athletes, teams, countries represented by athletes, and sponsors. The purposes of this study were to develop an understanding of (a) how an event organizer, media, and the public framed a critical incident in a rhetorical arena and (b) how frames were connected with the reputations of event stakeholders immediately following a critical incident. A three-phase approach was employed that involved collecting and analyzing data from X/Twitter about a bus crash at the 2013 Tour de France. The critical incident was framed in nine different ways, many of which were emergent. Findings demonstrated that critical incidents at a sport event are interpreted and framed in multiple ways and can have an impact on the reputations of the event and other event stakeholders. [ABSTRACT FROM AUTHOR]

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) have gained substantial attention because they represent one of the only radiographically identifiable precursors of invasive pancreatic ductal adenocarcinoma. Although most of these neoplasms have low-grade dysplasia and will remain indolent, a subset of IPMNs will progress to invasive cancer. The role of the immune system in the progression of IPMNs is unclear, but understanding its role could reveal the mechanism of neoplastic progression and targets for immunotherapy to inhibit progression or treat invasive disease. The available evidence supports a shift in the immune composition of IPMNs during neoplastic progression. Although low-grade lesions contain a high proportion of effector T cells, high-grade IPMNs, and IPMNs with an associated invasive carcinoma lose the T-cell infiltrate and are characterised by a predominance of immunosuppressive elements. Several possible therapeutic strategies emerge from this analysis that are unique to IPMNs and its microbiome.

In this paper, we use narrative analysis to examine the case study of "Nicole" (pseudonym), a student in a science, technology, engineering, and mathematics (STEM) program who transferred from a 2-year college (TYC) to a 4-year college (FYC). We draw from longitudinal qualitative data that follow Nicole's experience pre- and posttransfer, while acknowledging the impact of her experience at the TYC. We use an anti-deficit lens by highlighting the role of supporting characters for Nicole, especially at the TYC. Narrative analysis of Nicole's experiences highlights differences in her sense of community at the two different institutions. Organizing our data in these narrative components revealed how impactful supporting characters are in Nicole's story and how drastically they can shape the outcome of scenes in her story. Instructors and programmatic staff at FYCs who aim to better support transfer students in their transition can learn from the kinds of scenes Nicole cited as helpful in her time at the TYC as well as the FYC. It is our aim in sharing Nicole's story to provide guidelines for how faculty and program directors could be impactful supporting characters to create welcoming settings for transfer students.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common malignancy, with little improvement in patient outcomes over the past decades. Recently, subtypes of pancreatic cancer with different prognoses have been elaborated; however, the inability to model these subtypes has precluded mechanistic investigation of their origins. Here, we present a xenotransplantation model of PDAC in which neoplasms originate from patient-derived organoids injected directly into murine pancreatic ducts. Our model enables distinction of the two main PDAC subtypes: intraepithelial neoplasms from this model progress in an indolent or invasive manner representing the classical or basal-like subtypes of PDAC, respectively. Parameters that influence PDAC subtype specification in this intraductal model include cell plasticity and hyperactivation of the RAS pathway. Finally, through intratumoral dissection and the direct manipulation of RAS gene dosage, we identify a suite of RAS-regulated secreted and membrane-bound proteins that may represent potential candidates for therapeutic intervention in patients with PDAC. SIGNIFICANCE: Accurate modeling of the molecular subtypes of pancreatic cancer is crucial to facilitate the generation of effective therapies. We report the development of an intraductal organoid transplantation model of pancreatic cancer that models the progressive switching of subtypes, and identify stochastic and RAS-driven mechanisms that determine subtype specification.See related commentary by Pickering and Morton, p. 1448.This article is highlighted in the In This Issue feature, p. 1426.

The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p

Children with complex congenital heart defects often show delays and deficits in cognitive, language, motor, and social-emotional functioning. As such, the American Academy of Pediatrics and the American Heart Associated recommend ongoing monitoring and support of development. In conjunction with the formal therapeutic supports frequently recommended for young children with CHD, caregivers are instrumental in providing an enriching environment to enhance development in the hospital, at home, and in early childhood settings. In this article, we review the common developmental sequelae associated with CHD, underlying causes, and ways in which parents, family members, and professional caregivers can support development for children with CHD from birth to three years old. [ABSTRACT FROM AUTHOR]

Transformations in health care and attendant social work responses have eroded a health-care social work role grounded in holism and social justice. Tracing events at the intersection of social work, the labor movement, and health-care provision, this paper examines the evolution of social work's gravitation to micro-level practice and professionalism at the expense of macro practice, including labor organizing. It argues that engagement between health-care social work and labor unions is mutually beneficial and indispensable in preserving a role that reflects social work values in the face of massive socioeconomic inequality and health-care corporatization. [ABSTRACT FROM AUTHOR]

This review explores the progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma through a dual lens of intrinsic molecular alterations and extrinsic microenvironmental influences. PanIN development begins with Kirsten rat sarcoma viral oncogene (KRAS) mutations driving PanIN initiation. Key additional mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53 (TP53), and mothers against decapentaplegic homolog 4 (SMAD4) disrupt cell cycle control and genomic stability, crucial for PanIN progression from low-grade to high-grade dysplasia. Additional molecular alterations in neoplastic cells, including epigenetic modifications and chromosomal alterations, can further contribute to neoplastic progression. In parallel with these alterations in neoplastic cells, the microenvironment, including fibroblast activation, extracellular matrix remodeling, and immune modulation, plays a pivotal role in PanIN initiation and progression. Crosstalk between neoplastic and stromal cells influences nutrient support and immune evasion, contributing to tumor development, growth, and survival. This review underscores the intricate interplay between cell-intrinsic molecular drivers and cell-extrinsic microenvironmental factors, shaping PanIN predisposition, initiation, and progression. Future research aims to unravel these interactions to develop targeted therapeutic strategies and early detection techniques, aiming to alleviate the severe impact of pancreatic cancer by addressing both genetic predispositions and environmental influences. [ABSTRACT FROM AUTHOR]

Rationale/purpose: The purpose of this study was to explore the role that event cognitions (aesthetics, evaluation, fantasy, flow, personalities) and inspiration play in generating a demonstration effect for spectators at one elite-level swimming competition, while controlling for spectators having other physical activity preferences, age, and current swimming participation status. Design/methodology/approach: Data were collected from spectators (N = 258) via a questionnaire at one elite swimming competition in Canada. Structural equation modeling was used to analyze the data. Findings: Results indicated that inspiration had a direct association with intentions. Furthermore, inspiration mediated the positive relationships that fantasy and aesthetics had with intentions. All of the significant relationships were able to form notwithstanding the influence of the control variables. Practical Implications: Suggestions to inspire spectators and increase post-event intentions are offered, including a focus on stimulating spectators to fantasize they are part of the action and highlighting the aesthetics of the sport. Research Contribution: Although previous research has indicated that non-swimmers or those who prefer other physical activities are less likely to participate in the sport post-event, results suggest that those conditions might not have an effect on the formation of inspiration. [ABSTRACT FROM AUTHOR]

The Daily Life Experiences -- Frequency scale (DLE-F) measures the frequency of 18 racial discrimination experiences. Bifactor exploratory and confirmatory analyses indicated that the DLE-F is a unidimensional scale that yields valid and reliable scores. The DLE-F also showed evidence of measurement invariance by gender, convergent evidence, and criterion-related validity.

Background & aimsMutations at hotspots in GNAS, which encodes stimulatory G-protein, α subunits, are detected in approximately 60% of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. We generated mice with KRAS-induced IPMNs that also express a constitutively active form of GNAS in pancreas and studied tumor development.MethodsWe generated p48-Cre; LSL-KrasG12D; Rosa26R-LSL-rtTA-TetO-GnasR201C mice (Kras;Gnas mice); pancreatic tissues of these mice express activated KRAS and also express a mutant form of GNAS (GNASR201C) upon doxycycline administration. Mice that were not given doxycycline were used as controls, and survival times were compared by Kaplan-Meier analysis. Pancreata were collected at different time points after doxycycline administration and analyzed by histology. Pancreatic ductal adenocarcinomas (PDACs) were isolated from mice and used to generate cell lines, which were analyzed by reverse transcription polymerase chain reaction, immunoblotting, immunohistochemistry, and colony formation and invasion assays. Full-length and mutant forms of yes-associated protein (YAP) were expressed in PDAC cells. IPMN specimens were obtained from 13 patients with IPMN undergoing surgery and analyzed by immunohistochemistry.ResultsAll Kras;Gnas mice developed pancreatic cystic lesions that resemble human IPMNs; the grade of epithelial dysplasia increased with time. None of the control mice developed cystic lesions. Approximately one third of Kras;Gnas mice developed PDACs at a median of 30 weeks after doxycycline administration, whereas 33% of control mice developed PDACs. Expression of GNASR201C did not accelerate the development of PDACs compared with control mice. However, the neoplasms observed in Kras;Gnas mice were more differentiated, and expressed more genes associated with ductal phenotypes, than in control mice. PDACs isolated from Kras;Gnas mice had activation of the Hippo pathway; in cells from these tumors, phosphorylated YAP1 was sequestered in the cytoplasm, and this was also observed in human IPMNs with GNAS mutations. Sequestration of YAP1 was not observed in PDAC cells from control mice.ConclusionsIn mice that express activated KRAS in the pancreas, we found expression of GNASR201C to cause development of more differentiated tumors, with gene expression pattern associated with the ductal phenotype. Expression of mutant GNAS caused phosphorylated YAP1 to be sequestered in the cytoplasm, altering tumor progression.

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.