Design of Automotive Center Pillar Reinforcement to Resist Roof Crush

ME450 Capstone Design and Manufacturing Experience: Fall 2007A major role of automotive engineers is to improve fuel efficiency and vehicle safety. However, it is very difficult to improve both of these requirements at the same time. Our team was asked to aid with the design of structural reinforcements in hopes to improve the roof crush strength, but minimize the weight of the automobile body center pillar, also known as the B-pillar. This design would be able to resist roof crush during vehicle rollover accidents when subjected to forces defined by the United States government regulation FMVSS 216. In addition, the design will be able to resist larger forces. Our group focused on the Ford F-150 Crew Cab.Ford Motor Companyhttp://deepblue.lib.umich.edu/bitstream/2027.42/57954/1/me450f07project24_report.pd

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Self-confidence and level of knowledge after cardiopulmonary resuscitation training in 14 to 18-year-old schoolchildren A randomised-interventional controlled study in secondary schools in Germany

BACKGROUND Education of schoolchildren in cardiopulmonary resuscitation (CPR) is a strategic goal for improvement of bystander CPR in society. OBJECTIVE(S) The primary objective was to analyse the impact of CPR training on the resuscitation knowledge and self-confidence of secondary schoolchildren. In addition, independent predictors of improved CPR knowledge and self-confidence were investigated. DESIGN Randomised-interventional controlled study. SETTING Four secondary schools in Germany. PARTICIPANTS Four hundred and twenty-four schoolchildren aged from 14 to 18 years were included into the study. Fifty-one percent were female, and 33% had an immigrant background. INTERVENTION The intervention group received a 90-min CPR training session, whereas controls had no intervention. Levels of knowledge and self-confidence in initiating CPR were analysed by a study questionnaire before (t(0)), 90 min after (t(1)) and 6 months after training (t(2)). MAIN OUTCOME MEASURES Based on the evaluation of study questionnaires, the primary endpoint was to determine the development of resuscitation knowledge and self- confidence in initiating cardiopulmonary resuscitation at survey time-points t(0), t(1) and t(2). RESULTS Schoolchildren in the intervention group (n=207) showed a significantly higher level of knowledge (P < 0.001) and self-confidence (P< 0.001) at t(1) and t(2) compared with controls (n=217). Age was a predictor for long-term self-confidence [odds ratio (OR), 1.20; 95% confidence interval (95% CI), 1.02 to 1.41; P=0.032]. The long-term benefit in the level of knowledge and self-confidence were significantly higher in native compared with immigrant schoolchildren: (OR, 1.79; 95% CI, 1.14 to 2.82; P= 0.011) and (OR, 1.67; 95% CI, 1.07 to 2.60; P= 0.024), respectively. CONCLUSION Guideline compliant (90 min) theoretical and practical CPR training improves the level of knowledge and self-confidence in 14 to 18-year-old schoolchildren. Older schoolchildren are more likely to have increased self-confidence with respect to initiating CPR. Schoolchildren with an immigrant background showed a significantly lower increase in their level of knowledge and self-confidence compared with native children. Adaptation and simplification of teaching materials and further research on educational methods for CPR are urgently needed to enable a sustainable approach to teaching CPR, which also produces a long-lasting effect in the entire population

Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy

The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-b superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.Stem Cell and Regenerative Biolog

Genomic Profiling Identifies Outcome-Relevant Mechanisms of Innate and Acquired Resistance to Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Lung Cancer

PURPOSE Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective in acquired resistance (AR) to early-generation EGFR TKIs in EGFR-mutant lung cancer. However, efficacy is marked by interindividual heterogeneity. We present the molecular profiles of pretreatment and post-treatment samples from patients treated with third-generation EGFR TKIs and their impact on treatment outcomes. METHODS Using the databases of two lung cancer networks and two lung cancer centers, we molecularly characterized 124 patients with EGFR p. T790M-positive AR to early-generation EGFR TKIs. In 56 patients, correlative analyses of third-generation EGFR TKI treatment outcomes and molecular characteristics were feasible. In addition, matched post-treatment biopsy samples were collected for 29 patients with progression to third-generation EGFR TKIs. RESULTS Co-occurring genetic aberrations were found in 74.4% of EGFR p. T790-positive samples (n = 124). Mutations in TP53 were the most frequent aberrations detected (44.5%; n = 53) and had no significant impact on third-generation EGFR TKI treatment. Mesenchymal-epithelial transition factor (MET) amplifications were found in 5% of samples (n = 6) and reduced efficacy of third-generation EGFR TKIs significantly (eg, median progression-free survival, 1.0 months; 95% CI, 0.37 to 1.72 v 8.2 months; 95% CI, 1.69 to 14.77 months; P <= .001). Genetic changes in the 29 samples with AR to third-generation EGFR TKIs were found in EGFR (eg, p.T790M loss, acquisition of p.C797S or p.G724S) or in other genes (eg, MET amplification, KRAS mutations). CONCLUSION Additional genetic aberrations are frequent in EGFR-mutant lung cancer and may mediate innate and AR to third-generation EGFR TKIs. MET amplification was strongly associated with primary treatment failure and was a common mechanism of AR to third-generation EGFR TKIs. Thus, combining EGFR inhibitors with TKIs targeting common mechanisms of resistance may delay AR. (C) 2019 by American Society of Clinical Oncolog