Characterization of Mentorship Programs in Departments of Surgery in the United States

Importance Mentorship is considered a key element for career satisfaction and retention in academic surgery. Stakeholders of an effective mentorship program should include the mentor, the mentee, the department, and the institution. Objective The objective of this study was to characterize the status of mentorship programs in departments of surgery in the United States, including the roles of all 4 key stakeholders, because to our knowledge, this has never been done. Design, Setting, and Participants A survey was sent to 155 chairs of departments of surgery in the United States in July 2014 regarding the presence and structure of the mentorship program in their department. The analysis of the data was performed in November 2014 and December 2014. Main Outcomes and Measures Presence and structure of a mentorship program and involvement of the 4 key stakeholders. Results Seventy-six of 155 chairs responded to the survey, resulting in a 49% response rate. Forty-one of 76 of department chairs (54%) self-reported having an established mentorship program. Twenty-five of 76 departments (33%) described no formal or informal pairing of mentors with mentees. In 62 (82%) and 59 (78%) departments, no formal training existed for mentors or mentees, respectively. In 42 departments (55%), there was no formal requirement for the frequency of scheduled meetings between the mentor and mentee. In most departments, mentors and mentees were not required to fill out evaluation forms, but when they did, 28 of 31 were reviewed by the chair (90%). In 70 departments (92%), no exit strategy existed for failed mentor-mentee relationships. In more than two-thirds of departments, faculty mentoring efforts were not recognized formally by either the department or the institution, and only 2 departments (3%) received economic support for the mentoring program from the institution. Conclusions and Relevance These data show that only half of departments of surgery in the United States have established mentorship programs, and most are informal, unstructured, and do not involve all of the key stakeholders. Given the importance of mentorship to career satisfaction and retention, development of formal mentorship programs should be considered for all academic departments of surgery

Neurotensin Receptor 3/Sortilin Contributes to Tumorigenesis of Neuroendocrine Tumors Through Augmentation of Cell Adhesion and Migration

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels of NTSR3/sortilin were noted in the majority of human clinical NETs (n = 21) by immunohistochemical analyses compared with normal tissues (n = 12). Expression of NTS and NTSR3/sortilin was also noted in all tested NET cell lines. In addition, small interfering RNA–mediated knockdown of NTSR3/sortilin decreased cell number without alteration of cell cycle progression and apoptosis induction in NET cell lines BON and QGP-1. Moreover, silencing of NTSR3/sortilin significantly suppressed cell adhesion and cell migration with inhibition of focal adhesion kinase and Src phosphorylation in the NET cells. Our results demonstrate increased expression of NTSR3/sortilin in NET patient tissues and a critical role of NTSR3/sortilin on NET cell adhesion and migration suggesting that NTSR3/sortilin contributes to NET tumorigenesis

Differential Expression and Tumorigenic Function of Neurotensin Receptor 1 in Neuroendocrine Tumor Cells

Neurotensin (NTS), localized predominantly to the small bowel, stimulates the growth of a variety of cancers, including neuroendocrine tumors (NETs), mainly through its interaction with the high-affinity NTS receptor 1 (NTSR1). Here, we observed increased expression of NTSR1 in almost all tested clinical NET samples, but not in normal tissues. Through RT-PCR analysis, we found that the expression of NTSR1 and NTSR2 was either variable (NTSR1) or absent (NTSR2) in human NET cell lines. In contrast, NTSR3 and NTS were expressed in all NET cells. Treatment with 5-aza-2\u27-deoxycytidine, a demethylating agent, increased levels of NTSR1 and NTSR2 suggesting that DNA methylation contributes to NTSR1/2 expression patterns, which was confirmed by methylation analyses. In addition, we found that knockdown of NTSR1 decreased proliferation, expression levels of growth-related proteins, and anchorage-independent growth of BON human carcinoid cells. Moreover, stable silencing of NTSR1 suppressed BON cell growth, adhesion, migration and invasion. Our results show that high expression of NTSR1 is found in clinical NETs and that promoter methylation is an important mechanism controlling the differential expression of NTSR1 and silencing of NTSR2 in NET cells. Furthermore, knockdown of NTSR1 in BON cells suppressed oncogenic functions suggesting that NTSR1 contributes to NET tumorigenesis

Kinase Suppressor of Ras 1 and Exo70 Promote Fatty Acid-Stimulated Neurotensin Secretion Through ERK1/2 Signaling

Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal–regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal–regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal–regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates neurotensin secretion and extracellular signal–regulated kinase 1 and 2 signaling in human endocrine cells. Conversely, we show that overexpression of kinase suppressor of Ras 1 enhances neurotensin secretion and extracellular signal–regulated kinase 1 and 2 signaling. We also show that inhibition of extracellular signal–regulated kinase 2 and exocyst complex component 70, a substrate of extracellular signal–regulated kinase 2 and mediator of secretory vesicle exocytosis, potently inhibits basal and docosahexaenoic acid-stimulated neurotensin secretion, whereas overexpression of exocyst complex component 70 enhances basal and docosahexaenoic acid-stimulated neurotensin secretion. Together, our findings demonstrate a role for kinase suppressor of Ras 1 as a positive regulator of neurotensin secretion from human endocrine cells and indicate that this effect is mediated by the extracellular signal–regulated kinase 1 and 2 signaling pathway. Moreover, we reveal a novel role for exocyst complex component 70 in regulation of neurotensin vesicle exocytosis through its interaction with the extracellular signal–regulated kinase 1 and 2 signaling pathway

PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors

Patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor overall prognosis despite chemotherapy and radiotherapy (e.g., peptide receptor radionuclide therapy (PRRT)). Better treatment options are needed to improve disease regression and patient survival. The purpose of this study was to examine a new treatment strategy by combining PI3K/mTOR dual inhibition and radiotherapy. First, we assessed the efficacy of two PI3K/mTOR dual inhibitors, PF-04691502 and PKI-402, to inhibit pAkt and increase apoptosis in NET cell lines (BON and QGP-1) and patient-derived tumor spheroids as single agents or combined with radiotherapy (XRT). Treatment with PF-04691502 decreased pAkt (Ser473) expression for up to 72 h compared with the control; in contrast, decreased pAkt expression was noted for less than 24 h with PKI-402. Simultaneous treatment with PF-04691502 and XRT did not induce apoptosis in NET cells; however, the addition of PF-04691502 48 h after XRT significantly increased apoptosis compared to PF-04691502 or XRT treatment alone. Our results demonstrate that schedule-dependent administration of a PI3K/mTOR inhibitor, combined with XRT, can enhance cytotoxicity by promoting the radiosensitivity of NET cells. Moreover, our findings suggest that radiotherapy, in combination with timed PI3K/mTOR inhibition, may be a promising therapeutic regimen for patients with GEP-NET

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Disability and participation in breast and bowel cancer screening in England: a large prospective study.

BACKGROUND: There is limited information about participation in organised population-wide screening programmes by people with disabilities. METHODS: Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants. RESULTS: Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62-0.65) and in bowel cancer screening (RR=0.75, 0.73-0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation. CONCLUSION: Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability

McNair Research Journal - Summer 2015

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program Table of Contents Biography of Dr. Ronald E. McNair Statements: Dr. Neal J. Smatresk, UNLV President Dr. Juanita P. Fain, Vice President of Student Affairs Dr. William W. Sullivan, Associate Vice President for Retention and Outreach Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach McNair Scholars Institute Staf

Monazite trumps zircon: applying SHRIMP U–Pb geochronology to systematically evaluate emplacement ages of leucocratic, low-temperature granites in a complex Precambrian orogen

Although zircon is the most widely used geochronometer to determine the crystallisation ages of granites, it can be unreliable for low-temperature melts because they may not crystallise new zircon. For leucocratic granites U–Pb zircon dates, therefore, may reflect the ages of the source rocks rather than the igneous crystallisation age. In the Proterozoic Capricorn Orogen of Western Australia, leucocratic granites are associated with several pulses of intracontinental magmatism spanning ~800 million years. In several instances, SHRIMP U–Pb zircon dating of these leucocratic granites either yielded ages that were inconclusive (e.g., multiple concordant ages) or incompatible with other geochronological data. To overcome this we used SHRIMP U–Th–Pb monazite geochronology to obtain igneous crystallisation ages that are consistent with the geological and geochronological framework of the orogen. The U–Th–Pb monazite geochronology has resolved the time interval over which two granitic supersuites were emplaced; a Paleoproterozoic supersuite thought to span ~80 million years was emplaced in less than half that time (1688–1659 Ma) and a small Meso- to Neoproterozoic supersuite considered to have been intruded over ~70 million years was instead assembled over ~130 million years and outlasted associated regional metamorphism by ~100 million years. Both findings have consequences for the duration of associated orogenic events and any estimates for magma generation rates. The monazite geochronology has contributed to a more reliable tectonic history for a complex, long-lived orogen. Our results emphasise the benefit of monazite as a geochronometer for leucocratic granites derived by low-temperature crustal melting and are relevant to other orogens worldwide