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. Specific Aim 1: To determine, during a one-year school-based telehealth pilot asthma program, whether students will experience decreased absenteeism, adhere to individualized plan of care, and experience an improved health quality-of-life.
Research Design and Methods. We propose to develop, test and clinically validate a delivery system that is optimized for MR guided DBS implantation. In collaboration with our research partner, Surgi-Vision, Inc, we have identified the limitations of our present approach and defined the requirements for an ideal delivery system. These specifications address many of the issues identified in Section 2.3.3 and should substantially improve our methodology. We initially intend to evaluate the safety and efficacy of the novel delivery platform in phantom models. We will subsequently apply the technique to patients receiving DBS for treatment of Xxxxxxxxx’x disease and dystonia. We will seek clinical validation of the technique, including immediate evaluation of the technical success of the surgical procedure, as well as delayed evaluation of the neurological benefits of DBS.
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 Nur-Sultan, 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. Data Collection Instruments and Procedures Both quantitative and qualitative data...
Research Design and Methods. Design A descriptive, cross sectional design was selected to examine correlates of diet quality among women with previous gestational diabetes (pGDM). This design was selected for its utility in the exploratory and descriptive focus of this initial pilot study examining variables that have not been studied previously in this population and to generate hypotheses for future studies. Individual beliefs, along with social support and family-level factors were examined in association with diet quality as defined by the Alternate Healthy Eating Index (AHEI). Questionnaires were completed for a single time point. Clinical and anthropometric factors were measured at one study visit and assessed in relation to diet quality. Before the start of any recruitment or data collection, Institutional Review Board (IRB) approval was granted from Emory University. The approval for this study (#IRB00046666) included a partial HIPAA waiver to allow for medical chart reviews to identify potential participants. All recruitment sites, strategies, forms, and instruments were approved by the Emory IRB. Additional approvals were granted by the Xxxxx Research Oversight Committee and the Hall County Health Department. All IRB- specific documents, including approval letters, consent forms and waivers are included in Appendix A. The Emory University IRB stipulates that any patient contact must come from the patient’s individual provider. The PI collaborated with providers at each site to design site-specific recruitment tools to contact patients.
Research Design and Methods. Patients Patients were recruited from the departments of internal medicine at two nonacademic teaching hospitals, the Leyenburg Hospital and the Red Cross Hospital, the Hague, the Neth- erlands. Subjects were eligible for the study if they had been diagnosed with type 2 diabetes for at least 1 year, were aged 30–80 years, and were without a history of CVD (defined as CAD, electrocardiographic criteria for a past myocardial infarction, ischemic stroke, peripheral artery bypass surgery, percutaneous transluminal angioplasty, or amputation because of atherosclerotic disease). At a screening visit, fasting blood samples were drawn and a resting electrocardiogram performed. Patients with fasting total cholesterol > 6.9 mmol/l or < 4.0 mmol/l, triglycerides > 6.0 mmol/l, creatinine kinase values more than three times and alanine aminotransferase (ALT) more than two times the upper limit of normal, or creatinine clearance < 30 ml/min were excluded. Any lipid-lowering therapy had to be discontinued 8 weeks before the screening visit. The study was approved by the medical ethics committees of both hospitals and performed in accordance with the Declaration of Helsinki.
Research Design and Methods. Subjects and design The study design and baseline characteristics of the original patient population have been described elsewhere 27. Briefly, 250 patients with DM2 for at least one year, aged 30-80 years, without CVD were included in this randomized, double-blind, clinical trial. Patients were given 0.4 mg cerivastatin (Bayer B.V., Mijdrecht , The Netherlands) or placebo daily for 2 years. After the withdrawal of cerivastatin from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin (Merck Sharp & Dome, Haarlem, the Netherlands), without deblinding the study. Only patients who completed the study were included in the present analysis. There were no significant differences in demographic or lipid parameters between the full cohort (n=250) and the patients in this study (n=182), except for race, as more Caucasians than non-Caucasians completed the study (data not shown). Eligible patients gave their written informed consent. The study was performed at the Leyenburg Hospital, The Hague. The study was approved by the hospital’s Medical Ethics Committee.
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. Results 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) Conclusions 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. INTRODUCTION 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 studie...
