A healthy herd: addressing the justifications for vaccine denial and applying the health belief model to the current anti-vaccination movement

The purpose of this thesis is to explore and analyze the existing literature regarding the refusal to receive vaccinations designed specifically to prevent Measles-Mumps-Rubella (MMR), which has spurred a serious public health issue that puts every unvaccinated person at risk. It will investigate the reasons people refuse to get vaccinations for themselves or their children. The analysis of the current situation and the application of the Health Belief Model to the related factors will provide potential explanations regarding how the decision-making process may strengthen efforts towards increasing vaccination rates

Multiphasic Growth Factor Release from Fibrin Microthreads

Biomaterial scaffolds are used to aid in regeneration of tissue for volumetric muscle loss (VML) where natural regeneration fails. Fibrin microthreads are beneficial due to their mechanical properties, uniaxial cell alignment, and low cytotoxicity. We designed a composite system of a microthread bundle coated with a hydrogel to meet the unmet need of delivering two factors in different time domains to mimic natural healing and assist the regeneration process. Release from the microthreads and hydrogels was quantified with a protein assay and microthread release was validated semi-qualitatively with fluorescence microscopy. Results demonstrated that we created a dual factor, multi-phase release system to aid in skeletal muscle regeneration to potentially heal patients with VML injuries

Barriers to and facilitators of implementing complex workplace dietary interventions: Process evaluation results of a cluster controlled trial

Background: Ambiguity exists regarding the effectiveness of workplace dietary interventions. Rigorous process evaluation is vital to understand this uncertainty. This study was conducted as part of the Food Choice at Work trial which assessed the comparative effectiveness of a workplace environmental dietary modification intervention and an educational intervention both alone and in combination versus a control workplace. Effectiveness was assessed in terms of employees’ dietary intakes, nutrition knowledge and health status in four large manufacturing workplaces. The study aimed to examine barriers to and facilitators of implementing complex workplace interventions, from the perspectives of key workplace stakeholders and researchers involved in implementation. Methods: A detailed process evaluation monitored and evaluated intervention implementation. Interviews were conducted at baseline (27 interviews) and at 7–9 month follow-up (27 interviews) with a purposive sample of workplace stakeholders (managers and participating employees). Topic guides explored factors which facilitated or impeded implementation. Researchers involved in recruitment and data collection participated in focus groups at baseline and at 7–9 month follow-up to explore their perceptions of intervention implementation. Data were imported into NVivo software and analysed using a thematic framework approach. Results: Four major themes emerged; perceived benefits of participation, negotiation and flexibility of the implementation team, viability and intensity of interventions and workplace structures and cultures. The latter three themes either positively or negatively affected implementation, depending on context. The implementation team included managers involved in coordinating and delivering the interventions and the researchers who collected data and delivered intervention elements. Stakeholders’ perceptions of the benefits of participating, which facilitated implementation, included managers’ desire to improve company image and employees seeking health improvements. Other facilitators included stakeholder buy-in, organisational support and stakeholder cohesiveness with regards to the level of support provided to the intervention. Anticipation of employee resistance towards menu changes, workplace restructuring and target-driven workplace cultures impeded intervention implementation. Conclusions: Contextual factors such as workplace structures and cultures need to be considered in the implementation of future workplace dietary interventions. Negotiation and flexibility of key workplace stakeholders plays an integral role in overcoming the barriers of workplace cultures, structures and resistance to change

The chemical structure and phosphorothioate content of hydrophobically modified siRNAs impact extrahepatic distribution and efficacy

Small interfering RNAs (siRNAs) have revolutionized the treatment of liver diseases. However, robust siRNA delivery to other tissues represents a major technological need. Conjugating lipids (e.g. docosanoic acid, DCA) to siRNA supports extrahepatic delivery, but tissue accumulation and gene silencing efficacy are lower than that achieved in liver by clinical-stage compounds. The chemical structure of conjugated siRNA may significantly impact invivo efficacy, particularly in tissues with lower compound accumulation. Here, we report the first systematic evaluation of the impact of siRNA scaffold-i.e. structure, phosphorothioate (PS) content, linker composition-on DCA-conjugated siRNA delivery and efficacy in vivo. We found that structural asymmetry (e.g. 5- or 2-nt overhang) has no impact on accumulation, but is a principal factor for enhancing activity in extrahepatic tissues. Similarly, linker chemistry (cleavable versus stable) altered activity, but not accumulation. In contrast, increasing PS content enhanced accumulation of asymmetric compounds, but negatively impacted efficacy. Our findings suggest that siRNA tissue accumulation does not fully define efficacy, and that the impact of siRNA chemical structure on activity is driven by intracellular re-distribution and endosomal escape. Fine-tuning siRNA chemical structure for optimal extrahepatic efficacy is a critical next step for the progression of therapeutic RNAi applications beyond liver

A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing

OBJECTIVES: Anti-TIF1γ is an important autoantibody in the diagnosis of cancer-associated dermatomyositis and the most common autoantibody in juvenile onset dermatomyositis. Its reliable detection is important to instigate further investigations into underlying malignancy in adults. We previously showed that commercial assays using line and dot blots do not reliably detect anti-TIF1γ. We aimed to test a new commercial ELISA and compare with previously obtained protein immunoprecipitation. METHODS: Radio-labelled immunoprecipitation had previously been used to determine the autoantibody status of patients with immune-mediated inflammatory myopathies and several healthy controls. ELISA was undertaken on healthy control and anti-TIF1γ sera and compared to previous immunoprecipitation data. RESULTS: A total of 110 serum samples were analysed: 42 myositis patients with anti- TIF1γ and 68 autoantibody negative healthy control sera. Anti-TIF1γ was detected by ELISA in 41 out of 42 of the anti-TIF1γ-positive samples by immunoprecipitation, and in none of the healthy controls, giving a sensitivity of 97.6% and specificity of 100%. The false negative rate was 2%. CONCLUSION: ELISA is an affordable and time-efficient method which is accurate in detecting anti-TIF1γ