Development of Procedures for Accurate Finite Element Modeling of the Dynamic and Quasi-Static Performance of Automotive Chassis Components Incorporating Hyperelastic Materials

Finite element models of the vehicle for crashworthiness have traditionally included simplified representations of isolators intended to improve noise and vibration. However, the low stiffness of the hyperelastic material employed in such components allows for large deformations under impact conditions with a significant effect upon the accelerations experienced by the occupant. Modeling these components is challenging due to the non-linear behaviour of the material and the large deformations. The purpose of this research was to identify practices for developing accurate and efficient finite element models of chassis components incorporating hyperelastic materials. To maximize the comprehensiveness of this process, this research included quasi-static and dynamic material characterization; material model selection and implementation; finite element modeling techniques; quasi-static and dynamic component characterization; and model validation. Conclusions included the importance of comprehensive material characterization, material model selection, variation in results due to solver updates, and methodologies for model validation through component characterization

Mechanical Characterization of Direct/In-line Compounded, Compression Molded Polyamide / Carbon Fibre Long Fibre Thermoplastic

Direct compounded compression molded carbon fibre long fibre thermoplastic (LFT-D) combines the high strength and stiffness of carbon fibre with a mass production manufacturing process intended to maximize fibre length. However, this process is more commonly used in industry with glass fibre. Extensive characterization of mechanical properties, spanning fundamental tensile tests to impact characterization of standard specimens and a complex automotive component, was completed to understand the strengths and deficiencies of this novel material formulation for engineering applications: fundamental uniaxial tension (quasi-static and intermediate strain rate) and three-point bending tests, tensile stress-life fatigue characterization, ISO 6603-2 instrumented impact of standard specimens, and quasi-static/low velocity impact loading of an automotive seating component. These studies provide the data necessary to advance commercial adoption of direct compounded long carbon fibre thermoplastic. Uniaxial tension and three-point bending characterization of 9% to 25% weight fraction compression molded carbon fibre LFT-D polyamide-6 was completed with orientations of 0°, ±45°, and 90°. A novel finding that has importance for process modelling was that uniaxial tension and flexural properties were higher in the +45° direction compared to –45° (tensile modulus: 20%, strength: 10%, flexural modulus: 8%). Correspondingly, engineering strain at failure for uniaxial tensile tests was 18% lower in the +45° direction. These observations are hypothesized to be the result of fibre orientation asymmetry in the compression molding charge due to the screw of the compounder. Tensile fatigue characterization was carried out for 40% (by weight) carbon fiber/polyamide 66 LFT-D composites. This characterization yielded fatigue stress-life curves (23 °C, dry as molded, R = 0.1, 3 Hz) for 0°, 45°, and 90° orientations with respect to flow. Peak stresses at which the samples achieved 1E6 cycles were 105 MPa for samples oriented in the flow direction, 72 MPa for samples oriented 45° to the flow direction, and 53 MPa for samples oriented 90° to flow. Poorly dispersed fibre with little to no wet-out were identified by SEM at the fracture surfaces for those specimens with fatigue properties near the stress-life lower bound. Further development of the direct compounding process is needed for carbon fibre. Direct/in-line compounded PA6/CF long fibre thermoplastic was also characterized under low velocity impact consistent with ISO standard 6603-2. Additionally, a quasi-static variant of the ISO method was employed to assess rate sensitivity. At quasi-static loading rates, flow region specimens were notably more brittle considering the force-deflection response. However, the energy absorption did not differ significantly between charge and flow region specimens. In terms of rate sensitivity, puncture energy under low velocity impact decreased by 18% on average with respect to quasi-static loading. Tensile specimens were extracted from an automotive seatback structure compression molded from PA66/CF. Additionally, quasi-static and low velocity impact loading of seatback components was completed. Under low velocity impact loading a local force maxima was observed for seatbacks produced with a longitudinal charge orientation. No local maxima were consistently observed for transverse charge seatbacks. In terms of rate effects: initial stiffness was 550% higher for low velocity impact with respect to quasi-static loading. Digital image correlation identified localized deformation at the hemispherical indenter for low-velocity impact indicating an inertial component to the rate sensitivity. Catastrophic failure occurred at larger deflections for low velocity impact (36% increase for longitudinal charge placement, 24% for transverse). A study of specimen size effect for quasi-static uniaxial tension puncture test was completed for compression molded direct compounded carbon fibre LFT. No significant size effects were observed for the elastic modulus or tensile strength obtained from tensile specimens with four different gauge lengths (6.25 mm to 57 mm). The failure strain decreased by 27.5% and 29.9%, respectively, across the gauge length range for the 0°/90° directions. This material was also characterized at intermediate strain rates (10 s–1 to 100 s–1) through uniaxial tension tests on a novel apparatus and ISO 6603-2 puncture tests. Intermediate strain rate tensile tests showed little to no strain rate sensitivity for the 0° and 90° directions. However, initial stiffness was approximately 50% higher for ISO 6603-2 impact tests compared to quasi-static puncture tests

Ezetimibe is effective when added to maximally tolerated lipid lowering therapy in patients with HIV

To determine the efficacy and safety of adding ezetimibe to maximally tolerated lipid lowering therapy in patients with HIV dyslipidemia

Are HIV positive patients resistant to statin therapy?

<p>Abstract</p> <p>Background</p> <p>Patients with HIV are subject to development of HIV metabolic syndrome characterized by dyslipidemia, lipodystrophy and insulin resistance secondary to highly active antiretroviral therapy (HAART). Rosuvastatin is a highly potent HMG-CoA reductase inhibitor. Rosuvastatin is effective at lowering LDL and poses a low risk for drug-drug interaction as it does not share the same metabolic pathway as HAART drugs. This study sought to determine the efficacy of rosuvastatin on lipid parameters in HIV positive patients with HIV metabolic syndrome.</p> <p>Results</p> <p>Mean TC decreased from 6.54 to 4.89 mmol/L (25.0% reduction, p < 0.001). Mean LDL-C decreased from 3.39 to 2.24 mmol/L (30.8% reduction, p < 0.001). Mean HDL rose from 1.04 to 1.06 mmol/L (2.0% increase, p = ns). Mean triglycerides decreased from 5.26 to 3.68 mmol/L (30.1% reduction, p < 0.001). Secondary analysis examining the effectiveness of rosuvastatin monotherapy (n = 70) vs. rosuvastatin plus fenofibrate (n = 43) showed an improvement of 21.3% in TG and a decrease of 4.1% in HDL-C in the monotherapy group. The rosuvastatin plus fenofibrate showed a greater drop in triglycerides (45.3%, p < 0.001) and an increase in HDL of 7.6% (p = 0.08).</p> <p>Conclusion</p> <p>This study found that rosuvastatin is effective at improving potentially atherogenic lipid parameters in HIV-positive patients. The lipid changes we observed were of a smaller magnitude compared to non-HIV subjects. Our results are further supported by a small, pilot trial examining rosuvastatin effectiveness in HIV who reported similar median changes from baseline of -21.7% (TC), -22.4% (LDL-C), -30.1% (TG) with the exception of a 28.5% median increase in HDL. In light of the results revealed by this pilot study, clinicians may want to consider a possible resistance to statin therapy when treating patients with HIV metabolic syndrome.</p

Introduction de carnets d’apprentissage expérientiel portant sur la responsabilité sociale à l’externat au doctorat de premier cycle en médecine

Implication Statement Medical schools have a responsibility to ensure students meet and advocate for the needs of the community. However, addressing the social determinants of health is not always emphasized in clinical learning objectives. Learning logs are useful tools that can engage students to reflect on clinical encounters and direct students in their learning to target the development of highlighted skills. Despite their efficacy, the use of learning logs in medical education is largely applied towards biomedical knowledge and procedural skills. Thus, students may lack competence to address the psychosocial challenges involved in comprehensive medical care. Social accountability experiential logs were developed for third year medical students at the University of Ottawa to address and intervene on the social determinants of health. Students completed quality improvement surveys and results demonstrated this initiative to be beneficial to their learning and contributed to greater clinical confidence. Experiential logs in clinical training can be adapted across other medical schools and tailored to fit the needs and priorities of each institution’s local communities.Énoncé des implications de la recherche Les facultés de médecine ont la responsabilité de s’assurer que les étudiants répondent aux besoins de la collectivité et militent pour leur satisfaction. Or, les objectifs d’apprentissage clinique ne sont pas toujours axés sur les déterminants sociaux de la santé. L’utilité des carnets d’apprentissage est d’inciter les étudiants à réfléchir sur les rencontres cliniques et de les orienter dans leur apprentissage vers le développement des compétences ciblées. Malgré leur efficacité, les carnets d’apprentissage sont surtout appliqués aux connaissances biomédicales et aux compétences procédurales. Par conséquent, les étudiants pourraient ne pas disposer des compétences nécessaires pour relever les enjeux psychosociaux, qui sont à considérer aux fins d’une prise en charge médicale globale. Des carnets d’apprentissage expérientiel portant sur la responsabilité sociale ont été élaborés pour les étudiants en médecine de troisième année de l’Université d’Ottawa afin d’aborder et d’intervenir sur les déterminants sociaux de la santé. Les étudiants ont participé à des sondages sur l’amélioration de la qualité et les résultats de ceux-ci ont montré que cette initiative était bénéfique pour leur apprentissage et qu’elle contribuait à améliorer leur confiance en eux en tant que cliniciens. Les carnets expérientiels en formation clinique peuvent être adaptés par les diverses facultés de médecine pour qu’ils correspondent aux besoins et aux priorités des collectivités locales qu’elles desservent

Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.

Repurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types. We demonstrate that cells pre-engineered with anti-CRISPR molecules become resistant to gene editing, thus providing a means to generate "write-protected" cells that prevent future gene editing. We further show that anti-CRISPRs can be used to control CRISPR-based gene regulation circuits, including implementation of a pulse generator circuit in mammalian cells. Our work suggests that anti-CRISPR proteins should serve as widely applicable tools for synthetic systems regulating the behavior of eukaryotic cells

Implementing experiential learning logs addressing social accountability into undergraduate medical clerkship education

Implication Statement Medical schools have a responsibility to ensure students meet and advocate for the needs of the community. However, addressing the social determinants of health is not always emphasized in clinical learning objectives. Learning logs are useful tools that can engage students to reflect on clinical encounters and direct students in their learning to target the development of highlighted skills. Despite their efficacy, the use of learning logs in medical education is largely applied towards biomedical knowledge and procedural skills. Thus, students may lack competence to address the psychosocial challenges involved in comprehensive medical care. Social accountability experiential logs were developed for third year medical students at the University of Ottawa to address and intervene on the social determinants of health. Students completed quality improvement surveys and results demonstrated this initiative to be beneficial to their learning and contributed to greater clinical confidence. Experiential logs in clinical training can be adapted across other medical schools and tailored to fit the needs and priorities of each institution’s local communities

Sex Differences in the Fecal Microbiome and Hippocampal Glial Morphology Following Diet and Antibiotic Treatment

Rising obesity rates have become a major public health concern within the United States. Understanding the systemic and neural effects of obesity is crucial in designing preventive and therapeutic measures. In previous studies, administration of a high fat diet has induced significant weight gain for mouse models of obesity. Interestingly, sex differences in high-fat diet-induced weight gain have been observed, with female mice gaining significantly less weight compared to male mice on the same high-fat diet. It has also been observed that consumption of a high-fat diet can increase neurogliosis, but the mechanism by which this occurs is still not fully understood. Recent research has suggested that the gut microbiome may mediate diet-induced glial activation. The current study aimed to (1) analyze changes to the gut microbiome following consumption of a high fat (HF) diet as well as antibiotic treatment, (2) evaluate hippocampal microgliosis and astrogliosis, and (3) identify sex differences within these responses. We administered a low fat (Research Diets D12450 K) or high fat diet (Research Diets D12451) to male and female C57Bl/6 mice for sixteen weeks. Mice received an antibiotic cocktail containing 0.5g/L of vancomycin, 1.0 g/L ampicillin, 1.0 g/L neomycin, and 1.0 g/L metronidazole in their drinking water during the last six weeks of the study and were compared to control mice receiving normal drinking water throughout the study. We observed a significant reduction in gut microbiome diversity for groups that received the antibiotic cocktail, as determined by Illumina next-generation sequencing. Male mice fed the HF diet (± antibiotics) had significantly greater body weights compared to all other groups. And, female mice fed the low fat (LF) diet and administered antibiotics revealed significantly decreased microgliosis and astrogliosis in the hippocampus compared to LF-fed females without antibiotics. Interestingly, male mice fed the LF diet and administered antibiotics revealed significantly increased microgliosis, but decreased astrogliosis, compared to LF-fed males without antibiotics. The observed sex differences in LF-fed mice given antibiotics brings forward questions about sex differences in nutrient metabolism, gut microbiome composition, and response to antibiotics

Associations among ancestry, geography and breast cancer incidence, mortality, and survival in Trinidad and Tobago

Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates (Incidence: 66.96; Mortality: 30.82 per 100,000) compared to women of East Indian (Incidence: 41.04, Mortality: 14.19 per 100,000) or mixed ancestry (Incidence: 36.72, Mortality: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT

Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (,0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned