Depth- and direction-dependent changes in solute transport following cross-linking with riboflavin and UVA light in ex vivo porcine cornea.

Diffusion is an important mechanism of transport for nutrients and drugs throughout the avascular corneal stroma. The purpose of this study was to investigate the depth- and direction-dependent changes in stromal transport properties and their relationship to changes in collagen structure following ultraviolet A (UVA)-riboflavin induced corneal collagen cross-linking (CXL). After cross-linking in ex vivo porcine eyes, fluorescence recovery after photobleaching (FRAP) was performed to measure fluorescein diffusion in the nasal-temporal (NT) and anterior-posterior (AP) directions at corneal depths of 100, 200, and 300 µm. Second harmonic generation (SHG) imaging was also performed at these three corneal depths to quantify fiber alignment. For additional confirmation, an electrical conductivity method was employed to quantify ion permeability in the AP direction in corneal buttons and immunohistochemistry (IHC) was used to image collagen structure. Cross-linked corneas were compared to a control treatment that received the riboflavin solution without UVA light (SHAM). The results of FRAP revealed that fluorescein diffusivity decreased from 23.39 ± 11.60 µm2/s in the SHAM group to 19.87 ± 10.10 µm2/s in the CXL group. This change was dependent on depth and direction: the decrease was more pronounced in the 100 µm depth (P = 0.0005) and AP direction (P = 0.001) when compared to the effect in deeper locations and in the NT direction, respectively. Conductivity experiments confirmed a decrease in solute transport in the AP direction (P < 0.0001). FRAP also detected diffusional anisotropy in the porcine cornea: the fluorescein diffusivity in the NT direction was higher than the diffusivity in the AP direction. This anisotropy was increased following CXL treatment. Both SHG and IHC revealed a qualitative decrease in collagen crimping following CXL. Analysis of SHG images revealed an increase in coherency in the anterior 200 µm of CXL treated corneas when compared to SHAM treated corneas (P < 0.01). In conclusion, CXL results in a decrease in stromal solute transport, and this decrease is concentrated in the most anterior region and AP direction. Solute transport in the porcine cornea is anisotropic, and an increase in anisotropy with CXL may be explained by a decrease in collagen crimping.

Acculturation and Health Beliefs: Interactions Between Host and Heritage Culture Underlie Latina/o Caregivers' Beliefs About HPV Vaccination.

This study examined the interactive effects of acculturation (host culture acquisition) and enculturation (heritage culture retention) on Latina/o caregivers' beliefs about their child completing the human papillomavirus vaccine series. Participants were 161 caregiver-child dyads from Florida. Using multiple regression, caregiver knowledge and health beliefs (perceived threat, benefits, barriers, subjective norms, and self-efficacy) about series completion were predicted from caregivers' scores on acculturation, enculturation, and their interaction, controlling for sociodemographics. Acculturation and enculturation interacted to predict knowledge, benefits, barriers, and self-efficacy. Caregivers with high acculturation scores generally supported series completion, regardless of their enculturation score. However, when acculturation was low, caregivers who retained more (vs. less) of their heritage culture were more knowledgeable and held more favorable beliefs about series completion. Findings highlight the importance of independently assessing acculturation and enculturation in Latina/o immigrant populations. Overlooking enculturation may lead to incomplete conclusions about acculturation and health.

Temporomandibular Joint Condyle-Disc Morphometric Sexual Dimorphisms Independent of Skull Scaling.

PURPOSE: Approximately 2 to 4% of the US population have been estimated to seek treatment for temporomandibular symptoms, predominately women. The study purpose was to determine whether sex-specific differences in temporomandibular morphometry result from scaling with sex differences in skull size and shape or intrinsic sex-specific differences. MATERIALS AND METHODS: A total of 22 (11 male [aged 74.5 ± 9.1 years]; 11 female [aged 73.6 ± 12.8 years]) human cadaveric heads with no history of temporomandibular disc derangement underwent cone beam computed tomography and high-resolution magnetic resonance imaging scanning to determine 3-dimensional cephalometric parameters and temporomandibular morphometric outcomes. Regression models between morphometric outcomes and cephalometric parameters were developed, and intrinsic sex-specific differences in temporomandibular morphometry normalized by cephalometric parameters were determined. Subject-specific finite element (FE) models of the extreme male and extreme female conditions were developed to predict variations in articular disc stress-strain under the same joint loading. RESULTS: In some cases, sex differences in temporomandibular morphometric parameters could be explained by linear scaling with skull size and shape; however, scaling alone could not fully account for some differences between sexes, indicating intrinsic sex-specific differences. The intrinsic sex-specific differences in temporomandibular morphometry included an increased condylar medial length and mediolateral disc lengths in men and a longer anteroposterior disc length in women. Considering the extreme male and female temporomandibular morphometry observed in the present study, subject-specific FE models resulted in sex differences, with the extreme male joint having a broadly distributed stress field and peak stress of 5.28 MPa. The extreme female joint had a concentrated stress field and peak stress of 7.37 MPa. CONCLUSIONS: Intrinsic sex-specific differences independent of scaling with donor skull size were identified in temporomandibular morphometry. Understanding intrinsic sex-specific morphometric differences is critical to determining the temporomandibular biomechanics given the effect of anatomy on joint contact mechanics and stress-strain distributions and requires further study as one potential factor for the increased predisposition of women to temporomandibular disc derangement.

Predictors of Human Papillomavirus Vaccine Completion Among Low-Income Latina/o Adolescents.

PURPOSE: The purpose of this longitudinal study was to identify individual and interpersonal factors associated with human papillomavirus (HPV) vaccine series completion in a sample of low-income Latina/o adolescent girls and boys. METHODS: Caregiver-adolescent dyads (N = 161) were recruited from a rural Federally Qualified Health Center in southwest Florida when the adolescent (aged 11-17 years) received the first dose of HPV vaccine. Dyads completed a baseline assessment that measured demographic and cultural characteristics, past medical history, provider-patient communication, HPV knowledge, health beliefs about completing the series, and the adolescent's experience receiving the first dose. Using multivariable logistic regression, we identified caregiver- and adolescent-related factors associated with series completion (receipt of three doses of HPV vaccine within 1 year of initiation) as indicated in the adolescent's medical record and state immunization registry. RESULTS: Within 1 year of initiation, 57% (n = 92) completed the three-dose series. Missed opportunities for completion were observed for 20% of the sample who returned to the clinic. Caregiver-related predictors of completion included education, self-efficacy to complete the series, and knowledge of the required number of doses. Adolescent-related predictors included age, influenza vaccination within the past 2 years, having a chronic medical condition, reason for the baseline visit, and receipt of written information about HPV vaccination from a health care provider. CONCLUSIONS: Findings highlight important opportunities for improving completion of the HPV vaccine series among Latina/o adolescents. Intervention efforts should involve health care providers and parent-adolescent dyads and prioritize evidence-based strategies for reducing missed opportunities for series completion.

Influencing cardiovascular health habits in the rural, deep south: results of a cluster randomized trial.

Cardiovascular disease (CVD) is a major cause of death among people living in the United States. Populations, especially minorities, living in the rural South are disproportionately affected by CVD and have greater CVD risk, morbidity and mortality. Culturally relevant cardiovascular health programs implemented in rural community settings can potentially reduce CVD risk and facilitate health behavior modification. The purpose of this study was to examine the effects of a cardiovascular health promotion intervention on the health habits of a group of rural African American adults. The study had a cluster randomized controlled trial design involving 12 rural churches that served as statistical clusters. From the churches (n = 6) randomized to the intervention group, 115 participants were enrolled, received the 6-week health program and completed pretest-posttest measures. The 114 participants from the control group churches (n = 6) did not receive the health program and completed the same pretest-posttest measures. The linear mixed model was used to compare group differences from pretest to posttest. The educational health intervention positively influenced select dietary and confidence factors that may contribute toward CVD risk reduction.

Differential expression of mitogen activating protein kinases in periodontitis.

AIM: Following toll-like receptor (TLR) engagement, lipopolysaccharide (LPS) can stimulate the expression of pro-inflammatory cytokines thus activating the innate immune response. The production of inflammatory cytokines results, in part, from the activation of kinase-induced signalling cascades and transcriptional factors. Of the four distinct classes of mitogen-activated protein kinases (MAPK) described in mammals, p38, c-Jun N-terminal activated kinases (JNK1-3) and extracellular activated kinases (ERK1,2) are the best studied. Previous data have established that p38 MAPK signalling is required for inflammation and bone loss in periodontal disease pre-clinical animal models. MATERIALS & METHODS: In this study, we obtained healthy and diseased periodontal tissues along with clinical parameters and microbiological parameters. Excised fixed tissues were immunostained with total and phospho-specific antibodies against p38, JNK and ERK kinases. RESULTS: Intensity scoring from immunostained tissues was correlated with clinical periodontal parameters. Rank correlations with clinical indices were statistically significantly positive (p-value < 0.05) for total p38 (correlations ranging 0.49-0.68), phospho-p38 (range 0.44-0.56), and total ERK (range 0.52-0.59) levels, and correlations with JNK levels also supported association (range 0.42-0.59). Phospho-JNK and phospho-ERK showed no significant positive correlation with clinical parameters of disease. CONCLUSION: These data strongly implicate p38 MAPK as a major MAPK involved in human periodontal inflammation and severity.

Bayesian analysis of recurrent event with dependent termination: an application to a heart transplant study.

For a heart transplant patient, the risk of graft rejection and risk of death are likely to be associated. Two fully specified Bayesian models for recurrent events with dependent termination are applied to investigate the potential relationships between these two types of risk as well as association with risk factors. We particularly focus on the choice of priors, selection of the appropriate prediction model, and prediction methods for these two types of risk for an individual patient. Our prediction tools can be easily implemented and helpful to physicians for setting heart transplant patients' biopsy schedule.

LBoost: A boosting algorithm with application for epistasis discovery.

Many human diseases are attributable to complex interactions among genetic and environmental factors. Statistical tools capable of modeling such complex interactions are necessary to improve identification of genetic factors that increase a patient's risk of disease. Logic Forest (LF), a bagging ensemble algorithm based on logic regression (LR), is able to discover interactions among binary variables predictive of response such as the biologic interactions that predispose individuals to disease. However, LF's ability to recover interactions degrades for more infrequently occurring interactions. A rare genetic interaction may occur if, for example, the interaction increases disease risk in a patient subpopulation that represents only a small proportion of the overall patient population. We present an alternative ensemble adaptation of LR based on boosting rather than bagging called LBoost. We compare the ability of LBoost and LF to identify variable interactions in simulation studies. Results indicate that LBoost is superior to LF for identifying genetic interactions associated with disease that are infrequent in the population. We apply LBoost to a subset of single nucleotide polymorphisms on the PRDX genes from the Cancer Genetic Markers of Susceptibility Breast Cancer Scan to investigate genetic risk for breast cancer. LBoost is publicly available on CRAN as part of the LogicForest package, http://cran.r-project.org/.

Reduction in postoperative high-density lipoprotein cholesterol levels in children undergoing the Fontan operation.

Despite the emerging relevance of high-density lipoprotein (HDL) in the inflammatory cascade and vascular barrier integrity, HDL levels in children undergoing cardiac surgery are unexplored. As a measure of HDL levels, the HDL-cholesterol (HDL-C) in single-ventricle patients was quantified before and after the Fontan operation, and it was determined whether relationships existed between the duration and the type of postoperative pleural effusions. The study prospectively enrolled 12 children undergoing the Fontan operation. Plasma HDL-C levels were measured before and after cardiopulmonary bypass. The outcome variables of interest were the duration and type of chest tube drainage (chylous vs. nonchylous). The Kendall rank correlation coefficient and the Wilcoxon rank sum test were used. There were 11 complete observations. The median preoperative HDL-C level for all the subjects was 30 mg/dl (range, 24-53 mg/dl), and the median postcardiopulmonary bypass level was 21 mg/dl (range, 14-46 mg/dl) (p = 0.004). There was a tendency toward a moderate inverse correlation (-0.42) between the postcardiopulmonary bypass HDL-C level and the duration of chest tube drainage, but the result was not statistically significant (p = 0.07). In the chylous effusion group, the median postcardiopulmonary bypass HDL-C tended to be lower (16 vs. 23 mg/dl; p = 0.09). After the Fontan operation, the plasma HDL-C levels in children are significantly reduced. It is reasonable to conclude that the reduction in HDL-C reflects reduced plasma levels of HDL particles, which may have pertinent implications in postoperative pleural effusions given the antiinflammatory and endothelial barrier functions of HDL.

Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior.

BACKGROUND: To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets. RESULTS: We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as AMIGO2, Gem, and CXCL11 that have not been shown to associate with, but may play roles in, metastasis. CONCLUSIONS: CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray experiments. AVAILABILITY: CDEP is implemented in R and freely available at: http://genomebioinfo.musc.edu/CDEP/. CONTACT: zhengw@musc.edu.

Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer.

The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 microg/d (n = 47), or 800 microg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 microg/d and 800 microg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 microg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations.

Bayesian Adaptation of the Summary ROC Curve Method for Meta-analysis of Diagnostic Test Performance.

Meta-analytic methods for diagnostic test performance, Bayesian methods in particular, have not been well developed. The most commonly used method for meta-analysis of diagnostic test performance is the Summary Receiver Operator Characteristic (SROC) curve approach of Moses, Shapiro and Littenberg. In this paper, we provide a brief summary of the SROC method, then present a case study of a Bayesian adaptation of their SROC curve method that retains the simplicity of the original model while additionally incorporating uncertainty in the parameters, and can also easily be extended to incorporate the effect of covariates. We further derive a simple transformation which facilitates prior elicitation from clinicians. The method is applied to two datasets: an assessment of computed tomography for detecting metastases in non-small-cell lung cancer, and a novel dataset to assess the diagnostic performance of endoscopic ultrasound (EUS) in the detection of biliary obstructions relative to the current gold standard of endoscopic retrograde cholangiopancreatography (ERCP).

Factors associated with oral problems among adults with spinal cord injury.

OBJECTIVE: To explore factors associated with self-reported current oral (tooth and gum) problems and oral pain in the past 12 months among adults with spinal cord injury. METHODS: An online oral health survey on the South Carolina Spinal Cord Injury Association website. Respondents were 192 adult residents of the US who identified themselves as having spinal cord injury at least 1 year before the survey date. RESULTS: Approximately 47% of respondents reported having oral problems at the time of the survey, and 42% reported experiencing oral pain in the 12 months before the survey date. Multiple predictor analyses (controlling for age, gender, income, and dental insurance) indicated that current oral problems were positively associated with dry mouth symptoms, financial barriers to dental care access, smoking, and paraplegia. Oral pain experienced in the past 12 months was positively associated with dry mouth symptoms, financial barriers to dental care access, minority race, and paraplegia. CONCLUSIONS: Adults with spinal cord injury reported a high prevalence of oral problems and oral pain. Those with paraplegia were more likely to report problems than those with tetraplegia. Because dry mouth and smoking were significantly associated with these problems, patient education from both dental and medical providers should emphasize awareness of the side effects of xerostomia-causing medications, dry mouth management, and smoking cessation. Findings also indicate unmet needs for low-cost preventive and treatment dental services for this vulnerable population.

Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation.

Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA reductase inhibitor, effectively inhibited LPS-stimulated MMP-1 as well as MMP-8 and MMP-9 expression by U937 mononuclear cells. Our studies showed that the geranylgeranyl transferase inhibitor inhibited LPS-stimulated MMP-1 expression, and addition of isoprenoid intermediate geranylgeranyl pyrophosphate (GGPP) reduced the inhibitory effect of simvastatin on LPS-stimulated MMP-1 expression. We also demonstrated that simvastatin inhibited the activation of Ras and Rac, and the inhibition was abolished by addition of GGPP. The above results indicate that protein isoprenylation is involved in the regulation of MMP-1 expression by LPS and simvastatin. Moreover, we showed that simvastatin inhibited LPS-stimulated nuclear AP-1, but not NF-kappaB activity, and the inhibition was reversed by addition of GGPP. Simvastatin also inhibited LPS-stimulated ERK but not p38 MAPK and JNK. Finally, we showed that the inhibition of LPS-stimulated ERK activation by simvastatin was reversed by GGPP. Taken together, this study showed that simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by targeting protein isoprenylation-mediated ERK activation.

Joint spatial survival modeling for the age at diagnosis and the vital outcome of prostate cancer.

Prostate cancer (PrCA) is the most common malignancy in men and a leading cause of cancer mortality among males in the United States. Large geographical variation and racial disparities exist in both the incidence of PrCA and the survival rate after diagnosis. In this population-based study, a joint spatial survival model is constructed to investigate factors that affect the age at diagnosis of PrCA and the subsequent survival. The joint model for these two time-to-event outcomes is specified through parametric models for age at diagnosis and survival time conditional on diagnosis age. To account for possible correlation in these outcomes among men from the same geographical region, frailty terms are included in the survival model. Both spatially correlated and uncorrelated frailties are incorporated in each model considered. The deviance information criterion is used to select a best-fitting model within the Bayesian framework. The results from our final best-fitting model indicate that race, marital status at diagnosis, and cancer stage are significantly associated with both of the two time-to-event outcomes. No pattern emerged in the geographical distribution of age at PrCA diagnosis. In contrast, a spatially clustered pattern was observed in the geographic distribution of survival experience post diagnosis.

A Bayesian hierarchical modeling approach for studying the factors affecting the stage at diagnosis of prostate cancer.

We extend the baseline-category logits model for categorical response data to accommodate two distinct kinds of clustering. Our extension introduces random effects that have one component exhibiting spatial dependence and a second component that is distributed independently. We use this enhanced categorical logits model for investigating the factors that affect the geographical distribution of the diagnostic stage of prostate cancer (PrCA) in South Carolina (SC). Using incidence data from the SC registry, we fit three types of models: the baseline-category logits model, the proportional odds model, and the adjacent-categories logits model, each incorporating our two-component random effects. The deviance information criterion (DIC) is used for selecting the best-fitting model. The results from the best model are presented and interpreted. The county-specific random effects are mapped to characterize the spatial distribution pattern of diagnostic stage of PrCA in the study region. In terms of spatial distribution of the diagnostic stage of PrCA, an area of excess (unexplained) risk was found in the north-west area, and an area of low excess risk in the north-east area for regional-stage cancer in SC was identified through the analysis of the cancer registry data.

Semiparametric Inference for a General Class of Models for Recurrent Events.

Procedures for estimating the parameters of the general class of semiparametric models for recurrent events proposed by Peña and Hollander (2004) are developed. This class of models incorporates an effective age function encoding the effect of changes after each event occurrence such as the impact of an intervention, it models the impact of accumulating event occurrences on the unit, it admits a link function in which the effect of possibly time-dependent covariates are incorporated, and it allows the incorporation of unobservable frailty components which induce dependencies among the inter-event times for each unit. The estimation procedures are semiparametric in that a baseline hazard function is nonparametrically specified. The sampling distribution properties of the estimators are examined through a simulation study, and the consequences of mis-specifying the model are analyzed. The results indicate that the flexibility of this general class of models provides a safeguard for analyzing recurrent event data, even data possibly arising from a frailtyless mechanism. The estimation procedures are applied to real data sets arising in the biomedical and public health settings, as well as from reliability and engineering situations. In particular, the procedures are applied to a data set pertaining to times to recurrence of bladder cancer and the results of the analysis are compared to those obtained using three methods of analyzing recurrent event data.

Modelling intervention effects after cancer relapses.

This article addresses the problem of incorporating information regarding the effects of treatments or interventions into models for repeated cancer relapses. In contrast to many existing models, our approach permits the impact of interventions to differ after each relapse. We adopt the general model for recurrent events proposed by Peña and Hollander, in which the effect of interventions is represented by an effective age process acting on the baseline hazard rate function. To accommodate the situation of cancer relapse, we propose an effective age function that encodes three possible therapeutic responses: complete remission, partial remission, and null response. The proposed model also incorporates the effect of covariates, the impact of previous relapses, and heterogeneity among individuals. We use our model to analyse the times to relapse for 63 patients with a particular subtype of indolent lymphoma and compare the results to those obtained using existing methods.

Combining longitudinal studies of PSA.

Prostate-specific antigen (PSA) is a biomarker commonly used to screen for prostate cancer. Several studies have examined PSA growth rates prior to prostate cancer diagnosis. However, the resulting estimates are highly variable. In this article we propose a non-linear Bayesian hierarchical model to combine longitudinal data on PSA growth from three different studies. Our model enables novel investigations into patterns of PSA growth that were previously impossible due to sample size limitations. The goals of our analysis are twofold: first, to characterize growth rates of PSA accounting for differences when combining data from different studies; second, to investigate the impact of clinical covariates such as advanced disease and unfavorable histology on PSA growth rates.

Flap thickness accuracy: comparison of 6 microkeratome models.

PURPOSE: To determine the flap thickness accuracy of 6 microkeratome models and determine factors that might affect flap thickness. SETTING: Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This multicenter prospective study involved 18 surgeons. Six microkeratomes were evaluated: AMO Amadeus, Bausch & Lomb Hansatome, Moria Carriazo-Barraquer, Moria M2, Nidek MK2000, and Alcon Summit Krumeich-Barraquer. Eyes of 1061 consecutive patients who had laser in situ keratomileusis were included. Age, sex, surgical order (first or second cut), keratometry (flattest, steepest, and mean), white-to-white measurement, laser used, plate thickness, head serial number, blade lot number, and occurrence of epithelial defects were recorded. Intraoperative pachymetry was obtained just before the microkeratome was placed on the eye. Residual bed pachymetry was measured after the microkeratome cut had been created and the flap lifted. The estimated flap thickness was determined by subtraction (ie, mean preoperative pachymetry measurement minus mean residual bed pachymetry). RESULTS: A total of 1634 eyes were reviewed. Sex distribution was 54.3% women and 45.7% men, and the mean age was 39.4 years +/- 10.6 (SD). In addition, 54.5% of the procedures were in first eyes and 45.5%, in second eyes. The mean preoperative pachymetry measurement was 547 +/- 34 microm. The mean keratometry was 43.6 +/- 1.6 diopters (D) in the flattest axis and 44.6 +/-1.5 D in the steepest axis. The mean white-to-white measurement was 11.7 +/- 0.4 mm. The mean flap thickness created by the devices varied between head designs, and microkeratome heads had significant differences (P<.05). Factors that explained 78.4% of the variability included microkeratome model, plate thickness, mean preoperative pachymetry, Kmin, surgery order, head serial number, blade lot number, and surgeon. Factors such as age, sex, Kmax, Kaverage, white to white, and laser had no significant correlation to flap thickness. CONCLUSIONS: The results demonstrated variability between the 6 microkeratome models. Device labeling did not necessarily represent the mean flap thickness obtained, nor was it uniform or consistent. Thinner corneas were associated with thinner flaps and thicker corneas with thicker flaps. In addition, first cuts were generally associated with thicker flaps when compared to second cuts in bilateral procedures.