Mechanical and Cellular Changes During Compaction of a Collagen-Sponge-Based Corneal Stromal Equivalent

The need for corneas suitable for transplantation, combined with the decreasing supply, has fueled interest in the development of a corneal replacement. In this study, a collagen-sponge-based stromal equivalent, consisting of human corneal fibroblasts cultured on a type I collagen sponge, was maintained in culture for up to 21 days and characterized with respect to mechanical properties and cellular behavior. The Young's modulus of the stromal equivalent varied from 95 to 370 Pa, and its permeability varied from 5.3 x 10(-8) - 4.2 x 10(-7) m4 N(-1) s(-1). The greatest changes occurred during the first few days in culture, but the mechanical properties continued to change during the entire 21 days. Cell traction stress, determined from sponge compaction and DNA count, decreased during the compaction process with the maximum traction value the initial value of 6.6 +/- 2.9 x 10(-3) Pacm3 cell(-1). Microarray data showed that the expression level of fibronectin, decorin sulfate, collagenase, and gelatinase A was upregulated at day 14 in the sponge. This suggested that the repair fibroblast phenotype was being expressed by the fibroblasts. Additional analysis suggested that a subpopulation of cells expressed the myofibroblast phenotype.     

Roadmap for the development of the University of North Carolina at Chapel Hill Genitourinary OncoLogy Database—UNC GOLD

BackgroundThe management of genitourinary malignancies requires a multidisciplinary care team composed of urologists, medical oncologists, and radiation oncologists. A genitourinary (GU) oncology clinical database is an invaluable resource for patient care and research. Although electronic medical records provide a single web-based record used for clinical care, billing, and scheduling, information is typically stored in a discipline-specific manner and data extraction is often not applicable to a research setting. A GU oncology database may be used for the development of multidisciplinary treatment plans, analysis of disease-specific practice patterns, and identification of patients for research studies. Despite the potential utility, there are many important considerations that must be addressed when developing and implementing a discipline-specific database.Methods and materialsThe creation of the GU oncology database including prostate, bladder, and kidney cancers with the identification of necessary variables was facilitated by meetings of stakeholders in medical oncology, urology, and radiation oncology at the University of North Carolina (UNC) at Chapel Hill with a template data dictionary provided by the Department of Urologic Surgery at Vanderbilt University Medical Center. Utilizing Research Electronic Data Capture (REDCap, version 4.14.5), the UNC Genitourinary OncoLogy Database (UNC GOLD) was designed and implemented.ResultsThe process of designing and implementing a discipline-specific clinical database requires many important considerations. The primary consideration is determining the relationship between the database and the Institutional Review Board (IRB) given the potential applications for both clinical and research uses. Several other necessary steps include ensuring information technology security and federal regulation compliance; determination of a core complete dataset; creation of standard operating procedures; standardizing entry of free text fields; use of data exports, queries, and de-identification strategies; inclusion of individual investigators' data; and strategies for prioritizing specific projects and data entry.ConclusionsA discipline-specific database requires a buy-in from all stakeholders, meticulous development, and data entry resources to generate a unique platform for housing information that may be used for clinical care and research with IRB approval. The steps and issues identified in the development of UNC GOLD provide a process map for others interested in developing a GU oncology database.     

Reliability across studies from the functional assessment of cancer therapy-general (FACT-G) and its subscales: a reliability generalization

PURPOSE: The aim of this study was to conduct a reliability generalization of the Functional Assessment of Cancer Therapy-General (FACT-G) and its subscales to examine variation in score reliability across all published studies. METHODS: We reviewed 344 publications based on predetermined criteria. About 78 published studies reported Cronbach's Alpha reliability coefficients from their study in which data were collected. Sample size based weights were applied, and studies were coded on several scale and demographic characteristics. Using independent samples t tests, we examined associations between study characteristics and internal consistency variability. RESULTS: Average FACT-G score reliability was .88 (subscales ranged between .71-.83). Three variables produced small, statistically significant (P < or = .05) eta squared effects (ranging between .06-.21) due to different sources of variation in the FACT-G and subscales: ethnicity, cancer type, and study type-all of which appeared to be related to disproportionate representation of studies with the majority including Caucasian samples, mixed cancer samples, and validation type studies. CONCLUSIONS: The FACT-G and its subscales demonstrated acceptable reliability evidence across observed studies, without substantial variability due to scale or demographic characteristics.     

A boussinesq model of natural convection in the human eye and the formation of Krukenberg's spindle

The cornea of the human eye is cooled by the surrounding air and by evaporation of the tear film. The temperature difference between the cornea and the iris (at core body temperature) causes circulation of the aqueous humor in the anterior chamber of the eye. Others have suggested that the circulation pattern governs the shape of the Krukenberg spindle, a distinctive vertical band of pigment on the posterior cornea surface in some pathologies. We modeled aqueous humor flow the human eye, treating the humor as a Boussinesq fluid and setting the corneal temperature based on infrared surface temperature measurements. The model predicts convection currents in the anterior chamber with velocities comparable to those resulting from forced flow through the gap between the iris and lens. When paths of pigment particles are calculated based on the predicted flow field, the particles circulate throughout the anterior chamber but tend to be near the vertical centerline of the eye for a greatest period of time. Further, the particles are usually in close proximity to the cornea only when they are near the vertical centerline. We conclude that the convective flow pattern of aqueous humor is consistent with a vertical pigment spindle. © 2002 Biomedical Engineering Society. PAC2002: 4266Ew, 8710+e, 8719Pp     

Computer Simulation of Convective and Diffusive Transport of Controlled-Release Drugs in the Vitreous Humor

Purpose. Biodistribution of drugs in the eye is central to the efficacy of pharmaceutical ocular therapies. Of particular interest to us is the effect of intravitreal transport on distribution of controlled-released drugs within the vitreous. Methods. A computer model was developed to describe the three-dimensional convective-diffusive transport of drug released from an intravitreal controlled release source. Unlike previous studies, this work includes flow of aqueous from the anterior to the posterior of the vitreous. The release profile was based on in vitro release of gentamicin from poly(L-lactic acid) microspheres into vitreous. Results. For small drugs, convection plays a small role, but for large (slower diffusing) drugs, convection becomes more important. For the cases studied, the predicted ratio of drug reaching the retina to drug cleared by the aqueous humor was 2.4 for a small molecule but 13 for a large molecule. Transport in neonatal mouse eye, in contrast, was dominated by diffusion, and the ratio decreased to 0.39. Conclusions. The interaction among convection, diffusion, and geometry causes significant differences in biodistribution between large and small molecules or across species. These differences should be considered in the design of delivery strategies or animal studies.     

Intelligence quotient scores of 4-year-old children: social-environmental risk factors

Verbal IQ scores in a socially heterogeneous sample of 215 4-year-old children were highly related to a cumulative environmental risk index composed of maternal, family and cultural variables. Different combinations of equal numbers of risk factors produced similar effects on IQ, providing evidence that no single factor identified here uniquely enhances or limits early intellectual achievement and that cumulative effects from multiple risk factors increase the probability that development will be compromised. The multiple risk index predicted substantially more variance in the outcome measure than did any single risk factor alone, including socioeconomic status. High-risk children were more than 24 times as likely to have IQs below 85 than low-risk children.     

Acute Intrusive and Avoidant PTSD Symptoms as Predictors of Chronic PTSD Following Burn Injury

Several studies have endeavored to learn if acute PTSD symptoms are predictive of chronic PTSD, with equivocal results. In the present study, acute intrusive and avoidant PTSD symptoms were analyzed as possible predictors of chronic PTSD following burn injury. Results showed that baseline IES scores, within one week of injury, were significantly different for those who were later diagnosed with chronic PTSD. Additional analyses, undertaken to assess the relative importance of each symptom group in predicting chronic PTSD, indicated that both the presence, per se, and severity of acute avoidant symptoms predicted chronic PTSD.