Partners in the Parks: Field Guide to an Experiential Program in the National Parks (1st edition)

When Joan Digby first proposed taking collegiate honors students into our national parks, I jumped at the chance. Within minutes of reading her email, I not only responded with an enthusiastic “Yes!” but went so far as to volunteer the resources of the Southern Utah University Honors Program to get things started. Nestled among 5 national parks in southwestern Utah, I felt our campus would be a natural focal point for the kind of program Joan envisioned. Within weeks we had laid the groundwork for a proof-of-concept pilot project at nearby Bryce Canyon National Park. Little did I know at the time, but I was taking the first steps on a nationwide journey that would introduce me to 11 amazing national parks, some 47 park rangers, and over 100 outstanding college students—with the prospect of these numbers growing annually. The aim of Partners in the Parks (PITP) from its inception has been to introduce, or reintroduce, collegiate honors students to this country: not the transformed environment that we have constructed on its surface but the bedrock world upon which it rests. Like de Toqueville, Jefferson, Thoreau, Emerson, and so many others, we recognized that the unique place that is America cannot be separated from the land upon which it was built. One valuable way to study and understand it, then, is to visit places where the bones of America lie exposed, often without the veneer of civilization, cultivation, or modernization: places protected by the people to preserve for this and future generations, original American landscapes, and important historical landmarks that illustrate and define what America was, is, and can be. PITP takes students deep into America’s national parks. PITP is a see-America-first program. While we recognize the importance of a global perspective in an overall honors education, our goal is to help students see and understand America before or in addition to going abroad. Indeed, for students without the desire or resources to leave the country, PITP offers many of the same kinds of personal development that make study abroad so valuable. In the Field Notes to Chapter 2, “Growing from Within,” Bill Atwill and Kathleen King, share their experience in Acadia National Park, observing how their students demonstrated valuable growth in the same four key areas that researchers of study abroad programs have identified in their alumni: personal discovery, academic commitment, cultural development, and career development. The student writings in this volume, such as Andy Grube’s “soul expanding” talk with Juste Gatari on the rocky coast of Mount Desert Island, aptly illustrate this important facet of the PITP experience. (See the Field Notes to Chapter 5, “Sitting There in Silence.”

Percutaneous treatment of patients with heart diseases: selection, guidance and follow-up. A review

Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Trna-Dependent Alanylation Of Diacylglycerol And Phosphatidylglycerol In Corynebacterium Glutamicum

Aminoacyl-phosphatidylglycerol synthases (aaPGSs) are membrane proteins that utilize aminoacylated tRNAs to modify membrane lipids with amino acids. Aminoacylation of membrane lipids alters the biochemical properties of the cytoplasmic membrane and enables bacteria to adapt to changes in environmental conditions. aaPGSs utilize alanine, lysine and arginine as modifying amino acids, and the primary lipid recipients have heretofore been defined as phosphatidylglycerol (PG) and cardiolipin. Here we identify a new pathway for lipid aminoacylation, conserved in many Actinobacteria, which results in formation of Ala-PG and a novel alanylated lipid, Alanyl-diacylglycerol (Ala-DAG). Ala-DAG formation in Corynebacterium glutamicum is dependent on the activity of an aaPGS homolog, whereas formation of Ala-PG requires the same enzyme acting in concert with a putative esterase encoded upstream. The presence of alanylated lipids is sufficient to enhance the bacterial fitness of C.glutamicum cultured in the presence of certain antimicrobial agents, and elucidation of this system expands the known repertoire of membrane lipids acting as substrates for amino acid modification in bacterial cells. In this study, we revealed a new aa-tRNA-dependent pathway for lipid aminoacylation in Corynebacterium glutamicum, which is conserved in various Actinobacteria. This pathway produces alanyl-diacylglycerol (Ala-DAG) in addition to alanyl-phosphatidylglycerol (Ala-PG). While Ala-DAG is synthesized by a homolog (Ala-DAGS) of the gene MprF, synthesis of Ala-PG is dependent on the presence of a putative esterase (PesT). We showed that this pathway enhances the fitness of C. glutamicum when challenged by certain antimicrobial compounds. AlaRS: Alanyl-tRNA synthetase

Immunoadsorption and subsequent immunoglobulin substitution decreases myocardial gene expression of desmin in dilated cardiomyopathy

Cardiac autoantibodies play a pathogenic role in dilated cardiomyopathy (DCM). Removal of antibodies by immunoadsorption (IA) induces hemodynamic improvement in DCM patients. The present study investigated the effects of IA on myocardial gene expression of the intermediate cytoskeletal filament desmin, which is upregulated in heart failure. RNA was isolated from five explanted non-failing hearts and five explanted failing hearts of DCM patients, and myocardial gene expression of desmin was estimated by real-time polymerase chain reaction (PCR). In a case-control study in six DCM patients (LVEF < 40%, NYHA II-III), IA and subsequent IgG substitution were performed at monthly intervals until month 3. Endomyocardial biopsies (EMBs) were obtained before and after IA (after 3-6 months). From six DCM patients without IA therapy (controls), EMBs were also obtained over a comparable time interval. Expression of the desmin gene was analyzed in these EMBs by real-time PCR. In failing explanted hearts, expression of desmin was significantly increased (0.88±0.12 vs 0.45±0.15 in non-failing hearts, P < 0.05). After IA, myocardial gene expression of desmin was significantly decreased (from 0.26±0.05 [baseline] to 0.14±0.04 [P < 0.05] vs baseline and controls). Removal of antibodies by IA modulates myocardial gene expression of desmin in DCM patients