An Investigation of Certified Flight Instructor Competencies

The research literature documents distinct differences in teaching skills among instructors in a variety of fields. Some seem to be naturally skilled, whereas others seem to face more challenges in the instructional setting. Although several investigators have addressed a variety of questions concerning flight instructor training, more research is needed to elucidate the instructional competencies associated with successful instruction in this critical field. The proposed poster will present the preliminary results of an observational study designed to identify flight instructor competencies and patterns of instructional behavior. A preliminary set of essential instructor skills was developed based on instructor competencies as defined by the International Board of Standards for Training, Performance and Instruction (Klein, Spector, Grabowski, & de la Teja, 2004). Behaviors specific to flight instruction were then identified. During the Fall semester of 2006, 17 Certified Flight Instructor students were videotaped as they were instructing other students on a flight simulator. The researchers coded the student instructor behaviors using a data collection software product, Noldus Observer. Initial analyses revealed several distinct patterns in flight instructor behaviors. The poster will present the behavioral patterns observed in this study. The ways in which these data may be used to develop further studies to investigate methods of enhancing instructor performance will also be discussed

Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea

Primary cilia have been implicated in the generation of planar cell polarity (PCP). However, variations in the severity of polarity defects in different cilia mutants, coupled with recent demonstrations of non-cilia-related actions of some cilia genes, make it difficult to determine the basis of these polarity defects. To address this issue, we evaluated PCP defects in cochlea from a selection of mice with mutations in cilia-related genes. Results indicated notable PCP defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and Ift20 single mutants that are more severe than in other cilia gene knockouts. In addition, deletion of either Bbs8 or Ift20 results in disruptions in asymmetric accumulation of the core PCP molecule Vangl2 in cochlear cells, suggesting a role for Bbs8 and/or Ift20, possibly upstream of core PCP asymmetry. Consistent with this, co-immunoprecipitation experiments indicate direct interactions of Bbs8 and Ift20 with Vangl2. We observed localization of Bbs and Ift proteins to filamentous actin as well as microtubules. This could implicate these molecules in selective trafficking of membrane proteins upstream of cytoskeletal reorganization, and identifies new roles for cilia-related proteins in cochlear PCP

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men

What Can a Pilot Congestive Heart Failure Disease Management Program Tell Us about Likely Return on Investment?: A Case Study from a Program Offered to Federal Employees

In 1999, the Blue Cross and Blue Shield Federal Employee Program (FEP) implemented a pilot disease management program to manage congestive heart failure (CHF) among members. The purpose of this project was to estimate the financial return on investment in the pilot CHF program, prior to a full program rollout. A cohort of 457 participants from the state of Maryland was matched to a cohort of 803 nonparticipants from a neighboring state where the CHF program was not offered. Each cohort was followed for 12 months before the program began and 12 months afterward. The outcome measures of primary interest were the differences over time in medical care expenditures paid by FEP and by all payers. Independent variables included indicators of program participation, type of heart disease, comorbidity measures, and demographics. From the perspective of the funding organization (FEP), the estimated return on investment for the pilot CHF disease management program was a savings of $1.08 in medical expenditure for every dollar spent on the program. Adding savings to other payers as well, the return on investment was a savings of$1.15 in medical expenditures per dollar spent on the program. The amount of savings depended upon CHF risk levels. The value of a pilot initiative and evaluation is that lessons for larger-scale efforts can be learned prior to full-scale rollout. (Disease Management 2005;8:346-360)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63402/1/dis.2005.8.346.pd

Towards quantifying the increasing role of oceanic heat in sea ice loss in the new Arctic

The loss of Arctic sea ice has emerged as a leading signal of global warming. This, together with acknowledged impacts on other components of the Earth system, has led to the term “the new Arctic.” Global coupled climate models predict that ice loss will continue through the twenty-first century, with implications for governance, economics, security, and global weather. A wide range in model projections reflects the complex, highly coupled interactions between the polar atmosphere, ocean, and cryosphere, including teleconnections to lower latitudes. This paper summarizes our present understanding of how heat reaches the ice base from the original sources—inflows of Atlantic and Pacific Water, river discharge, and summer sensible heat and shortwave radiative fluxes at the ocean/ice surface—and speculates on how such processes may change in the new Arctic. The complexity of the coupled Arctic system, and the logistic and technological challenges of working in the Arctic Ocean, require a coordinated interdisciplinary and international program that will not only improve understanding of this critical component of global climate but will also provide opportunities to develop human resources with the skills required to tackle related problems in complex climate systems. We propose a research strategy with components that include 1) improved mapping of the upper- and middepth Arctic Ocean, 2) enhanced quantification of important process, 3) expanded long-term monitoring at key heat-flux locations, and 4) development of numerical capabilities that focus on parameterization of heat-flux mechanisms and their interactions.publishedVersio

Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies

Studying monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combine patient-derived and genetically engineered iPSCs with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene Tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural, and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS “heart on chip” tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies, and advances iPSC-based in vitro modeling of cardiomyopathy

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts