Targeting Oncogenic BRAF: Past, Present, and Future.

Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a "precision medicine" paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies

The Electronic Flight Bag Generation

More pilots depend on Electronic Flight Bags for flight planning, charts, weather, airport information, document management, hazard awareness, than ever before. These pilot companions have advanced from just a chart replacement to a comprehensive toolset helping pilots plan, fly, and debrief more efficiently. A review of Electronic Flight Bags latest advances and how they are shaping the flight training environment

Zenélés a „víg gettóban”. A cseh underground 1968 és 1989 között

ArticleText in HungarianThis study presents an empirical case study of the Czech Underground community, focusing on actors’ entrance into, and experience within, the Underground from the late 1960s to 1980s. The Underground can be conceived as a network of alternative dispositions toward social and cultural life in Czechoslovakia that emerged through non-official musicking practices. The author uses this case to focus on the non-official uses and reinventions of ‘music-as-resource’ in the Underground in a simultaneous, two-fold manner: 1) to understand music as a transformative aspect in the activities and processes of community-building and 2) to think more specifically about music’s role in collective agency and how collective phenomena begin and grow. The article explores how ‘music-asresource’ takes shape in relation to what is described as ‘creative constriction’: the paradoxical situation whereby suppression generates new opportunities for creative action. The ‘creative constriction’ – censorship, banning, state-consolidation of the music industry, auditions/reviews – is situated in the production of music, subsequent consumption of these products, their embodied practices, and how actors articulate meaning to musical materials. Through non-official musicking in the Underground, the author illustrates how ‘music-as-resource’ afforded new and socially important cultural practices that were informally learned in and through musical experience. These ‘lessons’ in turn provided a springboard for alternative, non-official, or ‘underground’ modes of being, permitting us to see the creation of an imaginative cultural space and how this collectively coalesces into a community

Doctor of Philosophy

dissertationFew instruments have been developed to assess patient physical activity (PA) in primary healthcare, nor assessed for validity. The purpose of these studies was to provide evidence of validity for a PA "vital sign" (PAVS) self-reported by clinic staff and patients and for the PA portion of the Speedy Nutrition and PA assessment (SNAP). Criterion validity of the PAVS and SNAP was assessed in clinic staff by agreement with accelerometry (accel). Construct validity of the PAVS was assessed by using electronic health records (EHRs) to examine odds of BMI and Charlson Comorbidity Index categories for patients reporting to the PAVS as not meeting 2008 Aerobic PA Guidelines for Americans (PAG) compared to patients meeting PAG. Concurrent validity of the PAVS was assessed by associating patient responses to the PAVS with concurrent responses to a Modifiable Activity Questionnaire (MAQ). The PAVS and SNAP correlated moderately strongly with accel identifying days/week clinic staff (N = 45) achieved ≥30 minutes (min) of moderate-vigorous PA (MVPA) performed at least 10 min. at a time (PAVS, r 0.52, p < 0.001; SNAP, r 0.31, p < 0.05). Of 34,712 eligible outpatient visits, patients who did not meet PAG according to the PAVS were more likely than normal weight patients to have a higher BMI (BMI 25.0-29.9, OR = 1.19, p = 0.001; BMI 30-34.9, OR = 1.39, p < 0.0001; BMI 35.0-39.9, OR = 2.42, p < 0.0001; BMI ≥ 40, OR = 3.7, p < 0.0001). Likewise, patients who did not meet PAG were also significantly more likely to have a higher disease burden (above 50th Charlson percentile, OR = 1.8, p < 0.0001). Of 269 eligible patient-participants, the PAVS agreed with the MAQ 89.6% of the time identifying insufficiently active patients and demonstrated good agreement with the MAQ identifying patients meeting/not meeting PAG (k = .55, rho = 0.57; p < 0.0001). Usual min·wk-1 MVPA reported to the PAVS correlated strongly with the same construct reported to the MAQ (r = 0.71; p < 0.0001). The PAVS appears to be a useful and valid tool particularly for identifying patients who most need counseling for PA. The PAVS should be evaluated further for validity and repeatability with criterion measures of PA. The PAVS could be used within EHRs to improve estimates of PA-disease relationships and interventions aimed to improve patient PA

Design, construction, and testing of a research quality electric machine testbed

With energy demands and costs growing every day, the need for improving energy efficiency in electrical devices has become very important. Research into various methods of improving efficiency for all electrical components will be a key to meet future energy needs. This report documents the design, construction, and testing of a research quality electric machine dynamometer and test bed. This test cell system can be used for research in several areas including: electric drives systems, electric vehicle propulsion systems, power electronic converters, load/source element in an AC Microgrid, as well as many others. The test cell design criteria, and decisions, will be discussed in reference to user functionality and flexibility. The individual power components will be discussed in detail to how they relate to the project, highlighting any feature used in operation of the test cell. A project timeline will be discussed, clearly stating the work done by the different individuals involved in the project. In addition, the system will be parameterized and benchmark data will be used to provide the functional operation of the system. With energy demands and costs growing every day, the need for improving energy efficiency in electrical devices has become very important. Research into various methods of improving efficiency for all electrical components will be a key to meet future energy needs. This report documents the design, construction, and testing of a research quality electric machine dynamometer and test bed. This test cell system can be used for research in several areas including: electric drives systems, electric vehicle propulsion systems, power electronic converters, load/source element in an AC Microgrid, as well as many others. The test cell design criteria, and decisions, will be discussed in reference to user functionality and flexibility. The individual power components will be discussed in detail to how they relate to the project, highlighting any feature used in operation of the test cell. A project timeline will be discussed, clearly stating the work done by the different individuals involved in the project. In addition, the system will be parameterized and benchmark data will be used to provide the functional operation of the system

Providing Rational for Further Funding Additive Manufacturing Efforts in the Air Force

Extremely long lead times for legacy aircraft replacement parts often exceed 120 days and cost 3 to 4 times the original price drives a search for alternative manufacturing methods such as additive manufacturing. Currently, the method to procuring a legacy replacement for aircraft such as the C-130 is daunting and at times, impossible. Through a comprehensive knowledge collection of organizational data the Air Force body of knowledge increases and provides actionable data to decision makers which has the potential of dramatically decreasing part wait times and procurement. The proposed, intuitive decision analysis framework mapped out in this research provides relevant direction for potential candidates considering additive manufacturing alternatives within their organizations. As result of this study, interested parties now have an abridged guide to costs, expenses, and challenges of setting up an Additive Manufacturing facility within their establishments

Ridge preservation comparing a flap vs. a flapless technique using a demineralized bone matrix allograft plus mineralized particulate allograft and covered with a calcium sulfate barrier.

Aims . The primary aim of this study is to compare the clinical and histologic results of a flap vs. a flapless technique of ridge preservation after 4 months of healing. Both groups received an intrasocket graft of demineralized bone matrix mixed with mineralized particulate allograft that was covered with a calcium sulfate barrier. Methods . Twelve test patients received ridge preservation using the flapless technique while 12 positive control patients were treated with a flap technique. All sockets were grafted with a mixture of demineralized bone matrix and a mineralized particulate allograft. Following tooth extraction horizontal ridge dimensions were measured with a digital caliper and vertical ridge dimensions were measured from a stent. Each site was re-entered for implant placement at about 4 months. Prior to implant placement a 2 X 6 mm trephine core was obtained and preserved in formalin for histologic analysis. Results . The horizontal ridge width of the flapless group at the crest decreased from 8.3 ± 1.3 mm to 7.0 ± 1.9 mm for a mean loss of 1.3 ± 0.9 mm (p \u3c 0.05) while the flap group decreased from 8.5 ± 1.5 mm to 7.5 ± 1.5 mm for a mean loss of 1.0 ± 1.1 mm (p \u3c; 0.05). There were no statistically significance differences between the two groups (p \u3e 0.05). The mean mid-buccal vertical change for the flap group was a loss of 0.9 ± 1.3 mm (p \u3c 0.05) vs. a loss of 0.5 ± 0.9 mm (p \u3c 0.05) for the flap group. There were no statistically significant differences between groups for vertical change (p \u3e 0.05). Histologic analysis revealed 44 ± 10% vital bone for the flapless group and 35 ± 15% for the flap group. Non-vital bone was 17 ±13% for the flapless group and 19 ± 12% for the flap group. Conclusions . Crestal ridge width following treatment with a flapless ridge preservation procedure using a demineralized bone matrix plug allograft and a calcium sulfate barrier was not significantly different than a flap ridge preservation technique using the same materials. There was a trend toward less loss of ridge height when the flapless procedure was used, although the difference was not statistically significant (p \u3e 0.05)

Selected Barriers and Incentives for Participation in a University Wellness Program

Evidence supporting the benefits of worksite health promotion (WHP) programs is extensive. Research shows these programs can improve the health of participants, lower health care costs, and improve the bottom line of employers. Although the evidence of these benefits is vast, reported participation in WHP is not optimal. Little published data exists on employees\u27 perceived incentives and barriers for participation in WHP. The purpose of this study was to determine perceived barriers and incentives for participation in an existing WHP program at a large land-grant university. Opinions of eligible WHP participants were collected using a web-based questionnaire (n = 321). The questionnaire was adapted from questions used in the 2004 HealthStyles survey. Overall percentages and odds ratios of responses were calculated and stratified by demographics. Respondents were 68.5% female, 76.6% were college graduates, 47% were active, and 32.7% had a BMI ≥ 30. The most common reported barrier to using employee wellness services was no time during work day (60.2%). Women were more likely than men to report lack of energy (OR, 4.5; 95% CI, 1.7-11.9) and no time during work day (OR, 2.6; 95% CI, 1.4-4.8) as barriers to participation. Respondents who were underweight and overweight were less likely to report lack of energy than respondents who were obese (OR, 0.2; 95% CI, 0.1-0.6; OR, 0.4; 95% CI, 0.2-0.9). The most common reported incentive was having programs at a convenient time (66.6%). Younger respondents were much more likely to report paid time off work to attend as incentive to participate than respondents 60 or more years (18-29 years OR, 10.8; 95% CI, 2.9-40.1; 30-34 years OR, 4.2; 95% CI, 1.5-11.7; 35-44 years OR, 3.1; 95% CI, 1.3-7.4). Most preferred wellness service or policies were available fitness center (75.9%), health screening tests (75.6%), and paid time to exercise at work (69.6%). The results of this study, combined with an employer\u27s own employee needs assessment, may help universities, and other employers with similar characteristics, design more attractive employee wellness programs. Making employee wellness programs attractive to their potential participants may improve program participation

Force Transducer for Inventory Management

Inventory management for small parts such as electronic components remains time consuming and costly to implement, yet required for efficient business operations. Currently there exists no solution to this problem that is both automated and inexpensive. This project provides a solution by developing an accurate and wireless force transducer for automated inventory management systems. The device works by laying on the bottom of an inventory storage container and measuring the total weight of the items. The device then wirelessly transmits this weight to a receiver where it is stored in a database. Afterwards, the database compares the most recent weight with the known weight of an item and calculates the quantity of items in stock. The project accomplished a proof of concept inventory system that accurately measures up to the weight of 1.5 grams. However the cost of the device needs to be significantly reduced to provide market feasible product. Cost improvements are discussed in the conclusion