Research Design and Methods. Patients
Research Design and Methods. Subjects and design
Research Design and Methods. A randomized, placebo-controlled double-blind trial was performed in 250 patients with DM2 without manifest cardiovascular disease. Patients were given 0.4 mg cerivastatin or placebo daily. The primary endpoint was the change in high sensitivity CRP after 2 years. CRP in the statin group was 1.58 mg/L at baseline and 1.69 mg/L at 2 years (p= 0.413), in the placebo group it increased from 2.03 mg/L at baseline to 2.54 mg/L at 2 years (p = 0.058) (p= 0.269 for comparison between the groups). In a high-risk subgroup with the metabolic syndrome and LDL levels > 2.6 mmol/L (40 % of the cohort) CRP levels increased significantly in the placebo group (from 2.97 mg/L at baseline to 3.99 mg/L at 2 years, p=0.036) in com- parison to the statin group (from 2.13 mg/L at baseline to 2.10 mg/L at 2 years, p=0.885) (p=0.042 for comparison between the groups) There was no effect of two year statin therapy on CRP in patients with DM2 without manifest cardiovascular disease, except in a subgroup with the metabolic syndrome and LDL > 2.6 mmol/L. Studies supporting risk stratified therapy in primary prevention in DM2 are needed. Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes mellitus (DM2)1. C-reactive protein (CRP) is a marker for the chronic inflammatory process in atherosclerotic plaques, and probably has pro-atherogenic properties of its own2-4. When measured with high sensitivity assays, CRP levels are highly reproducible, unaffected by food intake and with no circadian variation. CRP is a strong predictor of future cardiovas- cular events, independent of traditional risk factors such as LDL cholesterol5-7. CRP levels are associated with components of the metabolic syndrome (MS) such as triglycerides, obesity and insulin sensitivity8,9. Finally, CRP might be predictive of incident DM210-12. In DM2 without coronary artery disease, levels of CRP are higher than in non-diabetic controls13. CRP levels independently predict future cardiovascular events in DM2 in some studies14,15. Importantly, in the Hoorn study16, the association of CRP with future CVD events in DM2 was not independent of classical risk factors. A meta-analysis of intervention studies with statins in the setting of secondary prevention after a cardiovascular event has shown a correlation between reduced cardiovascular events and reduction in CRP, independent of LDL cholesterol lowering17. Results from intervention studies on the effects of statin therap...
Research Design and Methods. Study design Patients Definition of MS criteria cut-off values and low-grade chronic systemic inflammation
Research Design and Methods. Using baseline data from a clinical trial we provide an initial description of vascular param- eters in AI-DM2 compared to Europid Caucasian controls (ECs) matched for age and gender. Endpoints of the study were endothelial function, low-grade systemic inflammation (CRP) and carotid intima-media thickness (CIMT). AIs had longer duration of diabetes, worse glycemic control and more microangiopathy. Both groups demonstrated marked endothelial dysfunction. CRP levels were similar: 1.7 (4.9) mg/L in AIs and 2.8 (3.6) mg/L in ECs. CIMT values were significantly lower in AI-DM2 than EC-DM2 (0.655 mm (0.12) versus 0.711 mm (0.15), p = 0.03). Multiple regression analysis showed that variability in CRP was mainly determined by waist circumference, not by ethnicity. In contrast, ethnicity was a significantly explanatory variable for CIMT.
Research Design and Methods. The research program outlined herein builds upon the combined experience of the collaborators to develop technologies to accelerate the completion of the human genome sequence as well as to enable more routine genome sequencing. As outlined before, the HGP has evolved to the point where its completion is tractable. This project plans to hasten that timeline in stages:
Research Design and Methods. [***] In the past, we have successfully overexpressed functional human synthetases in E. coli. In order to enhance protein expression and solubility, all 6 human genes have been codon-optimized for translation in E. coli using the proprietary algorithms developed by CODA Genomics, Inc (xxxx://xxx.xxxxxxxxxxxx.xxx/). We have cloned the genes into pBAD vectors. Five out of the 6 genes have been expressed, and of these, two have good solubility. Aminoacyl-tRNA synthetases have modular structures with distinct domains that are joined together (Xxxxx, Xxxxx et al. 1983). Each domain is responsible for a specific task—for example, the catalytic domain for aminoacylation, anti-codon recognition domain for recognition of the triplet anti-codon embedded in the tRNA, and editing domain for clearance of the misactivated non-cognate amino acids or the mischarged tRNAs. Mammalian tRNA synthetases usually have acquired additional domains, each of which belongs to one of 3 types of structures; glutathione S-transferase (GST), helix-turn-helix (HTH), and endothelial monocyte activating peptide II (EMAP II). The extra domains often are dispensable for aminoacylation, and may provide a regulatory mechanism for non-canonical functions, as demonstrated for TyrRS and TrpRS. In addition, the extra domains may be involved with specific interactions between members of the multi-synthetase complex. With these considerations, we have also cloned domain fragments from the above 6 genes. As an additional benefit, most of the fragments have better expressions and improved solubility relative to the full-length proteins. Gene Fragment Tag MW (KD) Expression Solubility [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] * Confidential Information, indicated by [***], has been omitted from this filing and filed separately with the Securities and Exchange Commission [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Research Design and Methods. Research Design The study will use a Quasi Experimental research design study with African American participants who are already pre-hypertensive and between the ages of 18-35. The two group pretest posttest design will assign the participants into two groups; a study group and a control group. One group will receive detailed dietary advice in a community educational setting with special emphasis on sodium reduction in diet by following the “DASH” diet, advice on how to lower sodium in food and ways to modify recipes and shop smart to include less sodium in the diet coupled with a technological component with a smartphone app called the “eDiet” app which they can use to monitor dietary sodium levels and receive recommendations for dietary modifications. The control group will receive general hypertension prevention advice coupled with dietary recommendations according to the “DASH” diet plan, of how to eat a healthy and balanced diet. The information will be distributed in the form of study material and pamphlets without any specific sodium reduction means or any technological component associated to it. The two groups will be monitored throughout a period of 18 months at 3,6,9,12 and 18 month intervals for changes in blood pressure and results will be analyzed at the end of the experiment. The rationale for focusing African-American individuals is the high incidence of Hypertension and cardiovascular disease amongst them and by focusing on pre-hypertensive individuals, the study will explore how significant of a role diet can play in the prevention of developing Hypertension in the future. Research Questions
Research Design and Methods. This study used an explanatory cross-sectional sequential mixed methods design, which consisted of first collecting quantitative data (that provide a general picture of the research problem) and then collecting qualitative data to help explain or elaborate on the quantitative results, which will refine and extend the general picture (Xxxxxxxx, 2014, p. 572). Quantitative data were collected via an online survey and qualitative data were collected through semi-structured interviews. This research design aligned with the research questions as a way to understand the general picture regarding the support for play in the state kindergartens in Xxx-Xxxxxx, but also to explore the deeper explanations from individual practitioners to clarify the broader picture. In the field of educational research, both quantitative and qualitative methods have been used to understand play and playful learning. In this study, for example, conducting a quantitative survey was necessary to see the situation in general, but also to identify potential candidates for further qualitative study. As Xxxxxxxx (2013) noted: We conduct qualitative research because a problem or issue needs to be explored. This exploration is needed, in turn, because of a need to study a group or population, identify variables which cannot be easily measured, or hear silenced voices … We also conduct qualitative research because we need a complex, detailed understanding of the issue. (pp. 47-48) Thus, qualitative research is one of the tools that helps to explore and understand in depth the issues that cannot be easily measured and hear the voices that are not often heard. Therefore, a qualitative approach is also appropriate for the exploration of complex situations where individuals can offer their perspectives. In this research, a qualitative approach was used since the study focused on early childhood educators’ perceptions of play and learning and their support for play in a natural setting—the state kindergarten. This study adapted Xxxxxx’x (2017) doctoral study where a multiple case study approach was used to understand the support of play in US kindergartens. However, apart from a survey and face-to-face interviews, Xxxxxx’x study (2017) also included classroom observations, which could not be replicated due to both time constraints and the COVID-19 pandemic restrictions in early childhood education (ECE) organisations. Both quantitative and qualitative data were collected. The quantitative data were...
