Symmetric inverse consistent nonlinear registration driven by mutual information.

A nonlinear viscoelastic image registration algorithm based on the demons paradigm and incorporating inverse consistent constraint (ICC) is implemented. An inverse consistent and symmetric cost function using mutual information (MI) as a similarity measure is employed. The cost function also includes regularization of transformation and inverse consistent error (ICE). The uncertainties in balancing various terms in the cost function are avoided by alternatively minimizing the similarity measure, the regularization of the transformation, and the ICE terms. The diffeomorphism of registration for preventing folding and/or tearing in the deformation is achieved by the composition scheme. The quality of image registration is first demonstrated by constructing brain atlas from 20 adult brains (age range 30-60). It is shown that with this registration technique: (1) the Jacobian determinant is positive for all voxels and (2) the average ICE is around 0.004 voxels with a maximum value below 0.1 voxels. Further, the deformation-based segmentation on Internet Brain Segmentation Repository, a publicly available dataset, has yielded high Dice similarity index (DSI) of 94.7% for the cerebellum and 74.7% for the hippocampus, attesting to the quality of our registration method.

Generalized fuzzy clustering for segmentation of multi-spectral magnetic resonance images.

An integrated approach for multi-spectral segmentation of MR images is presented. This method is based on the fuzzy c-means (FCM) and includes bias field correction and contextual constraints over spatial intensity distribution and accounts for the non-spherical cluster's shape in the feature space. The bias field is modeled as a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of intensity are added into the FCM cost functions. To reduce the computational complexity, the contextual regularizations are separated from the clustering iterations. Since the feature space is not isotropic, distance measure adopted in Gustafson-Kessel (G-K) algorithm is used instead of the Euclidean distance, to account for the non-spherical shape of the clusters in the feature space. These algorithms are quantitatively evaluated on MR brain images using the similarity measures.

Molecular and biochemical analysis of the {\it Drosophila\/} segmentation gene {\it runt\/}

Genetic evidence has indicated that the segmentation gene runt plays a key role in regulating gene expression of the pair-rule genes hairy, even-skipped, and fushi tarazu. In contrast to other pair-rule genes, sequence data of the runt open reading frame did not reveal homologies to DNA-binding motifs of known transcriptional regulatory proteins. This thesis project examined several properties of the runt gene based on the sequence of the transcription unit, including the subcellular localization of the protein in vivo, its ability to bind DNA, and the functionality of a putative nucleotide binding domain.^ A runt-specific antibody was generated and used to demonstrate that runt is localized in the nucleus. Since the precise overlap of the pair-rule stripes is thought to be critical for the determination of cellular identity along the anterior-posterior axis, phasing of early runt expression in the blastoderm was examined with regard to the segmentation genes hairy, even-skipped, and fushi tarazu. runt was also expressed at later stages of embryogenesis, including expression in neuroblasts, and ganglion mother cells of the developing nervous system. Expression at this stage was required for the subsequent formation of specific neurons and runt was extensively expressed in the central and peripheral nervous systems.^ Several experiments were done to address the biochemical function of the runt protein. A direct interaction of runt with DNA was first examined. Although bacterial expressed runt was found to bind dsDNA-cellulose, subsequent experiments failed to detect sequence-specific interactions with DNA. Inter-species conservation of the putative nucleotide binding domain suggested that this region was functionally important, and runt protein bound a labeled ATP analog with high affinity in vitro. Finally, the effect of substitution of a critical residue of the nucleotide binding domain on runt activity was examined in vivo. Ectopic expression of the mutant protein indicated that this conserved substitution altered, but did not eliminate, runt activity as evaluated by segmentation phenotype and viability. ^

Cost-effectiveness analysis of a 2-stage community-based hepatocellular carcinoma screening program in Taiwan

Hepatocellular carcinoma (HCC) has been ranked as the top cause of death due to neoplasm malignancy in Taiwan for years. The high incidence of HCC in Taiwan is primarily attributed to high prevalence of hepatitis viral infection. Screening the subjects with liver cirrhosis for HCC was widely recommended by many previous studies. The latest practice guideline for management of HCC released by the American Association for the Study of Liver Disease (AASLD) in 2005 recommended that the high risk groups, including cirrhotic patients, chronic HBV/HCV carriers, and subjects with family history of HCC and etc., should undergo surveillance.^ This study aims to investigate (1) whether the HCC screening program can prolong survival period of the high risk group, (2) what is the incremental cost-effectiveness ratio of the HCC screening program in Taiwan, as compared with a non-screening strategy from the payer perspective, (3) which high risk group has the lowest ICER for the HCC screening program from the insurer's perspective, in comparison with no screening strategy of each group, and (4) the estimated total cost of providing the HCC screening program to all high risk groups.^ The high risk subjects in the study were identified from the communities with high prevalence of hepatitis viral infection and classified into three groups (cirrhosis group, early cirrhosis group, and no cirrhosis group) at different levels of risk to HCC by status of liver disease at the time of enrollment. The repeated ultrasound screenings at an interval of 3, 6, and 12 months were applied to cirrhosis group, early cirrhosis group, and no cirrhosis group, respectively. The Markov-based decision model was constructed to simulate progression of HCC and to estimate the ICER for each group of subjects.^ The screening group had longer survival in the statistical results and the model outcomes. Owing to the low HCC incidence rate in the community-based screening program, screening services only have limited effect on survival of the screening group. The incremental cost-effectiveness ratio of the HCC screening program was $3834 per year of life saved, in comparison with the non-screening strategy. The estimated total cost of each group from the screening model over 13.5 years approximately consumes 0.13%, 1.06%, and 0.71% of total amount of adjusted National Health Expenditure from Jan 1992 to Jun 2005. ^ The subjects at high risk of developing HCC to undergo repeated ultrasound screenings had longer survival than those without screening, but screening was not the only factor to cause longer survival in the screening group. The incremental cost-effectiveness ratio of the 2-stage community-based HCC screening program in Taiwan was small. The HCC screening program was worthy of investment in Taiwan. In comparison with early cirrhosis group and no cirrhosis group, cirrhosis group has the lowest ICER when the screening period is less than 19 years. The estimated total cost of providing the HCC screening program to all high risk groups consumes approximately 1.90% of total amount of adjusted 13.5-year NHE in Taiwan.^

Disparities in medical expenditure and utilization among hypertensive men and women in the U.S.: Cross-section and lifetime analysis

Objectives. To investigate procedural gender equity by assessing predisposing, enabling and need predictors of gender differences in annual medical expenditures and utilization among hypertensive individuals in the U.S. Also, to estimate and compare lifetime medical expenditures among hypertensive men and women in the U.S. ^ Data source. 2001-2004 the Medical Expenditure Panel Survey (MEPS);1986-2000 National Health Interview Survey (NHIS) and National Health Interview Survey linked to mortality in the National Death Index through 2002 (2002 NHIS-NDI). ^ Study design. We estimated total medical expenditure using four equations regression model, specific medical expenditures using two equations regression model and utilization using negative binomial regression model. Procedural equity was assessed by applying the Aday et al. theoretical framework. Expenditures were estimated in 2004 dollars. We estimated hypertension-attributable medical expenditure and utilization among men and women. ^ To estimate lifetime expenditures from ages 20 to 85+, we estimated medical expenditures with cross-sectional data and survival with prospective data. The four equations regression model were used to estimate average annual medical expenditures defined as sum of inpatient stay, emergency room visits, outpatient visits, office based visits, and prescription drugs expenditures. Life tables were used to estimate the distribution of life time medical expenditures for hypertensive men and women at different age and factors such as disease incidence, medical technology and health care cost were assumed to be fixed. Both total and hypertension attributable expenditures among men and women were estimated. ^ Data collection. We used the 2001-2004 MEPS household component and medical condition files; the NHIS person and condition files from 1986-1996 and 1997-2000 sample adult files were used; and the 1986-2000 NHIS that were linked to mortality in the 2002 NHIS-NDI. ^ Principal findings. Hypertensive men had significantly less utilization for most measures after controlling predisposing, enabling and need factors than hypertensive women. Similarly, hypertensive men had less prescription drug (-9.3%), office based (-7.2%) and total medical (-4.5%) expenditures than hypertensive women. However, men had more hypertension-attributable medical expenditures and utilization than women. ^ Expected total lifetime expenditure for average life table individuals at age 20, was $188,300 for hypertensive men and $254,910 for hypertensive women. But the lifetime expenditure that could be attributed to hypertension was $88,033 for men and $40,960 for women. ^ Conclusion. Hypertensive women had more utilization and expenditure for most measures than hypertensive men, possibly indicating procedural inequity. However, relatively higher hypertension-attributable health care of men shows more utilization of resources to treat hypertension related diseases among men than women. Similar results were reported in lifetime analyses.^ Key words: gender, medical expenditures, utilization, hypertension-attributable, lifetime expenditure ^

Systematic review of worksite-based behavior change programs that target metabolic syndrome risk factors

Approximately one-third of US adults have metabolic syndrome, the clustering of cardiovascular risk factors that include hypertension, abdominal adiposity, elevated fasting glucose, low high-density lipoprotein (HDL)-cholesterol and elevated triglyceride levels. While the definition of metabolic syndrome continues to be much debated among leading health research organizations, the fact is that individuals with metabolic syndrome have an increased risk of developing cardiovascular disease and/or type 2 diabetes. A recent report by the Henry J. Kaiser Family Foundation found that the US spent $2.2 trillion (16.2% of the Gross Domestic Product) on healthcare in 2007 and cited that among other factors, chronic diseases, including type 2 diabetes and cardiovascular disease, are large contributors to this growing national expenditure. Bearing a substantial portion of this cost are employers, the leading providers of health insurance. In lieu of this, many employers have begun implementing health promotion efforts to counteract these rising costs. However, evidence-based practices, uniform guidelines and policy do not exist for this setting in regard to the prevention of metabolic syndrome risk factors as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Therefore, the aim of this review was to determine the effects of worksite-based behavior change programs on reducing the risk factors for metabolic syndrome in adults. Using relevant search terms, OVID MEDLINE was used to search the peer-reviewed literature published since 1998, resulting in 23 articles meeting the inclusion criteria for the review. The American Dietetic Association's Evidence Analysis Process was used to abstract data from selected articles, assess the quality of each study, compile the evidence, develop a summarized conclusion, and assign a grade based upon the strength of supporting evidence. The results revealed that participating in a worksite-based behavior change program may be associated in one or more improved metabolic syndrome risk factors. Programs that delivered a higher dose (>22 hours), in a shorter duration (<2 years) using two or more behavior-change strategies were associated with more metabolic risk factors being positively impacted. A Conclusion Grade of III was obtained for the evidence, indicating that studies were of weak design or results were inconclusive due to inadequate sample sizes, bias and lack of generalizability. These results provide some support for the continued use of worksite-based health promotion and further research is needed to determine if multi-strategy, intense behavior change programs targeting multiple risk factors are able to sustain health improvements in the long-term.^