Emerging as a Major Carrier: A Case Study of America West Airlines

The increasing concentration and turbulent financial environment of the U.S. airline industry raise serious questions regarding the efficacy of airline deregulation. The deregulatory experience has brought into question many of the critical assumptions of entry freedom and contestable markets upon which much of deregulation was based. The current environment poses the important question: How does a smaller or new carrier compete with today\u27s increasingly global megacarriers? The evolution of America West Airlines in its struggle to build a strong market niche provides an interesting case study of one start-up carrier\u27s strategies and policies

Graduate Education in Airport Administration: Preparing Airport Managers for the 21st Century

Growing numbers of students pursuing management careers in aviation are seeking graduate degrees to prepare for the complex and evolving challenges in the aviation industry. This study questioned members of the American Association of Airport Executives (AAAE) about their profession and the appropriateness of current education opportunities in aviation administration. The purpose of this study was to identify the knowledge and skills that the next generation of airport administrators will need to effectively contend with the new industrial environment

Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas

2019 EAST PODIUM PAPER Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas Harmon, Laura A. MD; Haase, Daniel J. MD; Kufera, Joseph A. MA; Adnan, Sakib BS; Cabral, Donna BNS; Lottenberg, Lawrence MD; Cunningham, Kyle W. MD, MPH; Bonne, Stephanie MD; Burgess, Jessica MD; Etheridge, James MD; Rehbein, Jennifer L. MD; Semon, Gregory DO; Noorbakhsh, Matthew R. MD; Cragun, Benjamin N. MD; Agrawal, Vaidehi PhD; Truitt, Michael MD; Marcotte, Joseph MD; Goldenberg, Anna DO; Behbahaninia, Milad MD; Keric, Natasha MD; Hammer, Peter M. MD; Nahmias, Jeffry MD; Grigorian, Areg MD; Turay, Dave MD; Chakravarthy, Vikram MD; Lalchandani, Priti MD; Kim, Dennis MD; Chapin, Trinette; Dunn, Julie MD; Portillo, Victor MD; Schroeppel, Thomas MD, MS; Stein, Deborah M. MD, MPH Author Information Journal of Trauma and Acute Care Surgery 87(1):p 61-67, July 2019. | DOI: 10.1097/TA.0000000000002327 Buy CME Test Erratum Abstract BACKGROUND Fatality rates following penetrating traumatic brain injury (pTBI) are extremely high and survivors are often left with significant disability. Infection following pTBI is associated with worse morbidity. The modern rates of central nervous system infections (INF) in civilian survivors are unknown. This study sought to determine the rate of and risk factors for INF following pTBI and to determine the impact of antibiotic prophylaxis. METHODS Seventeen institutions submitted adult patients with pTBI and survival of more than 72 hours from 2006 to 2016. Patients were stratified by the presence or absence of infection and the use or omission of prophylactic antibiotics. Study was powered at 85% to detect a difference in infection rate of 5%. Primary endpoint was the impact of prophylactic antibiotics on INF. Mantel-Haenszel χ2 and Wilcoxon\u27s rank-sum tests were used to compare categorical and nonparametric variables. Significance greater than p = 0.2 was included in a logistic regression adjusted for center. RESULTS Seven hundred sixty-three patients with pTBI were identified over 11 years. 7% (n = 51) of patients developed an INF. Sixty-six percent of INF patients received prophylactic antibiotics. Sixty-two percent of all patients received one dose or greater of prophylactic antibiotics and 50% of patients received extended antibiotics. Degree of dural penetration did not appear to impact the incidence of INF (p = 0.8) nor did trajectory through the oropharynx (p = 0.18). Controlling for other variables, there was no statistically significant difference in INF with the use of prophylactic antibiotics (p = 0.5). Infection was higher in patients with intracerebral pressure monitors (4% vs. 12%; p = \u3c0.001) and in patients with surgical intervention (10% vs. 3%; p \u3c 0.001). CONCLUSION There is no reduction in INF with prophylactic antibiotics in pTBI. Surgical intervention and invasive intracerebral pressure monitoring appear to be risk factors for INF regardless of prophylactic use. LEVEL OF EVIDENCE Therapeutic, level IV

Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas

2019 EAST PODIUM PAPER Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas Harmon, Laura A. MD; Haase, Daniel J. MD; Kufera, Joseph A. MA; Adnan, Sakib BS; Cabral, Donna BNS; Lottenberg, Lawrence MD; Cunningham, Kyle W. MD, MPH; Bonne, Stephanie MD; Burgess, Jessica MD; Etheridge, James MD; Rehbein, Jennifer L. MD; Semon, Gregory DO; Noorbakhsh, Matthew R. MD; Cragun, Benjamin N. MD; Agrawal, Vaidehi PhD; Truitt, Michael MD; Marcotte, Joseph MD; Goldenberg, Anna DO; Behbahaninia, Milad MD; Keric, Natasha MD; Hammer, Peter M. MD; Nahmias, Jeffry MD; Grigorian, Areg MD; Turay, Dave MD; Chakravarthy, Vikram MD; Lalchandani, Priti MD; Kim, Dennis MD; Chapin, Trinette; Dunn, Julie MD; Portillo, Victor MD; Schroeppel, Thomas MD, MS; Stein, Deborah M. MD, MPH Author Information Journal of Trauma and Acute Care Surgery 87(1):p 61-67, July 2019. | DOI: 10.1097/TA.0000000000002327 Buy CME Test Erratum Abstract BACKGROUND Fatality rates following penetrating traumatic brain injury (pTBI) are extremely high and survivors are often left with significant disability. Infection following pTBI is associated with worse morbidity. The modern rates of central nervous system infections (INF) in civilian survivors are unknown. This study sought to determine the rate of and risk factors for INF following pTBI and to determine the impact of antibiotic prophylaxis. METHODS Seventeen institutions submitted adult patients with pTBI and survival of more than 72 hours from 2006 to 2016. Patients were stratified by the presence or absence of infection and the use or omission of prophylactic antibiotics. Study was powered at 85% to detect a difference in infection rate of 5%. Primary endpoint was the impact of prophylactic antibiotics on INF. Mantel-Haenszel χ2 and Wilcoxon\u27s rank-sum tests were used to compare categorical and nonparametric variables. Significance greater than p = 0.2 was included in a logistic regression adjusted for center. RESULTS Seven hundred sixty-three patients with pTBI were identified over 11 years. 7% (n = 51) of patients developed an INF. Sixty-six percent of INF patients received prophylactic antibiotics. Sixty-two percent of all patients received one dose or greater of prophylactic antibiotics and 50% of patients received extended antibiotics. Degree of dural penetration did not appear to impact the incidence of INF (p = 0.8) nor did trajectory through the oropharynx (p = 0.18). Controlling for other variables, there was no statistically significant difference in INF with the use of prophylactic antibiotics (p = 0.5). Infection was higher in patients with intracerebral pressure monitors (4% vs. 12%; p = \u3c0.001) and in patients with surgical intervention (10% vs. 3%; p \u3c 0.001). CONCLUSION There is no reduction in INF with prophylactic antibiotics in pTBI. Surgical intervention and invasive intracerebral pressure monitoring appear to be risk factors for INF regardless of prophylactic use. LEVEL OF EVIDENCE Therapeutic, level IV

Rigid-body Ligand Recognition Drives Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) Receptor Triggering

The inhibitory T-cell surface-expressed receptor, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which belongs to the class of cell surface proteins phosphorylated by extrinsic tyrosine kinases that also includes antigen receptors, binds the related ligands, B7-1 and B7-2, expressed on antigen-presenting cells. Conformational changes are commonly invoked to explain ligand-induced “triggering” of this class of receptors. Crystal structures of ligand-bound CTLA-4 have been reported, but not the apo form, precluding analysis of the structural changes accompanying ligand binding. The 1.8-Å resolution structure of an apo human CTLA-4 homodimer emphasizes the shared evolutionary history of the CTLA-4/CD28 subgroup of the immunoglobulin superfamily and the antigen receptors. The ligand-bound and unbound forms of both CTLA-4 and B7-1 are remarkably similar, in marked contrast to B7-2, whose binding to CTLA-4 has elements of induced fit. Isothermal titration calorimetry reveals that ligand binding by CTLA-4 is enthalpically driven and accompanied by unfavorable entropic changes. The similarity of the thermodynamic parameters determined for the interactions of CTLA-4 with B7-1 and B7-2 suggests that the binding is not highly specific, but the conformational changes observed for B7-2 binding suggest some level of selectivity. The new structure establishes that rigid-body ligand interactions are capable of triggering CTLA-4 phosphorylation by extrinsic kinase(s)

Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers

Nuclear 3’-end-polyadenylation is essential for the transport, stability and translation of virtually all eukaryotic mRNAs. Poly(A) tail extension can also occur in the cytoplasm, but the transcripts involved are incompletely understood, particularly in cancer. Here we identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma. CPEB4 is upregulated early in melanoma progression, as defined by computational and histological analyses. Melanoma cells are distinct from other tumour cell types in their dependency on CPEB4, not only to prevent mitotic aberrations, but to progress through G1/S cell cycle checkpoints. RNA immunoprecipitation, sequencing of bound transcripts and poly(A) length tests link the melanoma-specific functions of CPEB4 to signalling hubs specifically enriched in this disease. Essential in these CPEB4-controlled networks are the melanoma drivers MITF and RAB7A, a feature validated in clinical biopsies. These results provide new mechanistic links between cytoplasmic polyadenylation and lineage specification in melanoma.M.S.S. was funded by Marató TVE and Consolider RNAREG (CSD2009-00080), and SAF2014-56868-R (Spanish Ministry of Economy and Innovation). R.M. was supported by Fundación Botín, by the Banco Santander through its Santander Universities Global Division, and by grants from the Spanish Ministry of Economy and Innovation (BFU2011–30121 and Consolider RNAREG (CSD2009-00080). J.L.R.-P. was funded by grant FIS 2014/1737 from the Spanish Ministry of Health, P.L.O.-R. by FIS 14/1784; and N.B. and E.E. by MINECO and FEDER (BIO2014-52566-R), as well as by Consolider RNAREG (CSD2009-00080), by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013). C.R.G was funded by Ludwig Institute for Cancer Research. E.P.-G., D.A.-C. and R.M.-H. are recipients of Scientists in Training predoctoral fellowships from the Spanish Ministry of Science and Innovation. P.K and M.C. are funded by a predoctoral fellowship from Fundación La Caixa. E.R.-F. is the recipient of a postdoctoral fellowship from ‘Fundación Científica de la Asociación Española Contra el Cáncer’ and supported by FMM-2013/0075 of Fundacion Mutua Madrileña