Coronary artery disease (CAD) is one of the leading causes of death in the US and a substantial health-care burden in all industrialized societies. In recent years we have witnessed a constant strive towards the development and the clinical application of novel or improved detection methods as well as therapies. Particularly, noninvasive imaging is a decisive component in the cardiovascular field. Image fusion is the ability of combining into a single integrated display the anatomical as well as the physiological data retrieved by separated modalities. Clinical evidence suggests that it represents a promising strategy in CAD assessment and risk stratification by significantly improving the diagnostic power of each modality independently considered and of the traditional side-by-side interpretation. Numerous techniques and approaches taken from the image registration field have been implemented and validated in the context of CAD assessment and management. Although its diagnostic power is widely accepted, additional technical developments are still needed to become a routinely used clinical tool.
Objective
Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI.
Methods
Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters.
Results
The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing.
Conclusion
The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI.
The Insulin-like Growth Factor 1 (IGF-1) signaling pathway activates several downstream signals important to lung cancer development and survival. IGF-1R activation has been linked to cancer risk in epidemiological studies and tumorigenesis in preclinical models. Several inhibitors of the insulin-like growth factor 1 receptor (IGF-1R) have been tested in clinical trials. Despite promising data in early phase studies, most studies of IGF-1R antagonists in combination with chemotherapy or with epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer (NSCLC) yielded disappointing results. Biomarker studies of clinical trials have identified IGF-1 levels as a potential marker of sensitivity to IGF-1R inhibition. Further study will need to focus on selection of NSCLC patients most likely to benefit from the addition of IGF-1R antagonists to standard therapy and the development of rational strategies for combination therapy in NSCLC.
Background: A cohort of community residents and workers is the basis for a series of epidemiologic studies of a Mid-Ohio Valley population with substantial perfluorooctanoic acid (PFOA) exposure due to releases from a chemical plant.
Objectives: We describe study design, methods, and study participants for a longitudinal cohort study of associations between PFOA exposure and adult chronic diseases.
Methods: Two cohorts were formed, one recruited from community residents who participated in a previous community-wide survey, and one from plant workers. Study participants were interviewed during 2008–2011 regarding demographics, health-related behaviors, and personal history of chronic diseases. Reported diseases were validated through medical records review and registry matching. Here we describe cohort characteristics, compare survey respondents and nonrespondents, provide data on the number of diseases reported and validated, and describe historical estimates of serum PFOA concentrations over time.
Results: The final combined cohort included 32,254 participants (28,541 community; 3,713 worker). Participation rates were high (community, 81.5%; worker, 72.9% of target population). The final population from each cohort was representative of the target population in terms of demographic characteristics and measured serum PFOA concentrations in 2005–2006. The study had a wide exposure range and the number of reported cases of chronic diseases was high, resulting in greater power to detect associations than has been the case for many previous studies.
Conclusions: This is the largest study to date of the health effects of PFOA. The information from this cohort is being used to examine associations between PFOA exposure and multiple adult chronic diseases.
Type 1 diabetes (T1DM) affects one in every 400 children and adolescents in the US. Due to the limitations of exogenous insulin therapy and whole pancreas transplantation, pancreatic islet transplantation has emerged as a promising therapy for T1DM. However, this therapy is severely limited by donor islet availability and poor islet engraftment and function. We engineered an injectable bio-synthetic, polyethylene glycol-maleimide hydrogel to enhance vascularization and engraftment of transplanted pancreatic islets in a mouse model of T1DM. Controlled presentation of VEGF-A and cell-adhesive peptides within this engineered material significantly improved the vascularization and function of islets delivered to the small bowel mesentery, a metabolically relevant site for insulin release. Diabetic mice receiving islets transplanted in proteolytically degradable hydrogels incorporating VEGF-A exhibited complete reversal of diabetic hyperglycemia with a 40% reduction in the number of islets required. Furthermore, hydrogel-delivered islets significantly improved weight gain, regulation of a glucose challenge, and intra-islet vascularization and engraftment compared to the clinical standard of islet infusion through the hepatic portal vein. This study establishes a simple biomaterial strategy for islet transplantation to promote enhanced islet engraftment and function.
Background: Little is known about environmental determinants of autoimmune diseases.
Objectives: We studied autoimmune diseases in relation to level of exposure to perfluorooctanoic acid (PFOA), which was introduced in the late 1940s and is now ubiquitous in the serum of residents of industrialized countries.
Methods: In 2008–2011 we interviewed 32,254 U.S. adults with high serum PFOA serum levels (median, 28 ng/mL) associated with drinking contaminated water near a chemical plant. Disease history was assessed retrospectively from 1952 or birth (if later than 1952) until interview. Self-reported history of autoimmune disease was validated via medical records. Cumulative exposure to PFOA was derived from estimates of annual mean serum PFOA levels during follow-up, which were based on plant emissions, residential and work history, and a fate-transport model. Cox regression models were used to estimate associations between quartiles of cumulative PFOA serum levels and the incidence of autoimmune diseases with ≥ 50 validated cases, including ulcerative colitis (n = 151), Crohn’s disease (n = 96), rheumatoid arthritis (n = 346), insulin-dependent diabetes (presumed to be type 1) (n = 160), lupus (n = 75), and multiple sclerosis (n = 98).
Results: The incidence of ulcerative colitis was significantly increased in association with PFOA exposure, with adjusted rate ratios by quartile of exposure of 1.00 (referent), 1.76 (95% CI: 1.04, 2.99), 2.63 (95% CI: 1.56, 4.43), and 2.86 (95% CI: 1.65, 4.96) (ptrend < 0.0001). A prospective analysis of ulcerative colitis diagnosed after the baseline 2005–2006 survey (n = 29 cases) suggested a positive but non-monotonic trend (ptrend = 0.21).
Discussion: To our knowledge, this is the first study of associations between this common environmental exposure and autoimmune diseases in humans. We found evidence that PFOA is associated with ulcerative colitis.
Objective
To develop a toolset to monitor and assess laboratory biosafety program performance and cost
Introduction
Laboratory biosafety – a component of biosecurity – has specific elements that together, comprise a facility’s capability to both protect employees and the surrounding public and environment. Measuring these elements permits assessment and the costing of program-specific safety interventions. In the absence of a strategy and toolset, we developed a conceptual framework and toolset that monitors and assesses laboratory biosafety programs (LBPs) and provides useful information (e.g., return on investment [ROI]) for decision makers.
Methods
We conducted academic and open source literature reviews of LBPs and affiliated organizations laboratory manuals to identify objectives, goals, and indicators. These findings were aligned to laboratory biosafety-specific inputs, activities, outputs, and outcomes to create a strategic, conceptual framework (logic models) used to assess performance and measure the cost and ROI. Indicators were identified in existing literature or developed and mapped to the logic model elements.
Results
Six logic models were created: laboratory biosafety, biosurety, procedural, biocontainment, information security, and training. The laboratory biosafety logic model served as the overall framework for the remaining five sub-logic models. We also established a database containing 161 indicators mapped to each of the logic model elements.
Conclusions
We developed a strategic framework that monitors and evaluates LBPs. While evaluation of cost-impacts in LBPs provides business intelligence for resource planning, this integrated approach also provides information about gaps. We plan to pilot this toolset and refine indicators using principal component analysis.
Introduction: Students aged 16-24 years are at greatest risk for interpersonal violence and the resulting short and long-term health consequences. Electronic survey methodology is well suited for research related to interpersonal violence. Yet methodological questions remain about best practices in using electronic surveys. While researchers often indicate that potential participants receive multiple emails as reminders to complete the survey, little mention is made of the sender of the recruitment email. The purpose of this analysis is to describe the response rates from three violence-focused research studies when the recruitment emails are sent from a campus office, researcher or survey sampling firm. Methods: Three violence-focused studies were conducted about interpersonal violence among college students in the United States. Seven universities and a survey sampling firm were used to recruit potential participants to complete an electronic survey. The sender of the recruitment emails varied within and across the each of the studies depending on institutional review boards and university protocols. Results: An overall response rate of 30% was noted for the 3 studies. Universities in which researcherinitiated recruitment emails were used had higher response rates compared to universities where campus officials sent the recruitment emails. Researchers found lower response rates to electronic surveys at Historically Black Colleges or Universities and that other methods were needed to improve response rates. Conclusion: The sender of recruitment emails for electronic surveys may be an important factor in response rates for violence-focused research. For researchers identification of best practices for survey methodology is needed to promote accurate disclosure and increase response rates.