Inverse modeling and experimental validation for reconstructing wave sources on a 2D solid from surficial measurement.

This paper discusses a source inversion method for the reconstruction of moving or stationary wave sources on the top surface of a two-dimensional (2D) linear elastic solid. This adjoint-gradient-based source inversion method uses vibrational measurements from sensors at the top surface of the solid, which can be heterogeneous and damped, to reconstruct temporal and spatial distributions of the wave sources. The finite element method (FEM) is used to obtain wave solutions with the high-resolution discretization of source functions in space and time leading the number of inversion parameters to range in the millions. Numerical experiments, in which the iterative inversion procedure begins with an initial guess of zero loading at all points in space and time, show that the presented approach is effective at reconstructing horizontal and vertical components of force (i.e., normal and shear tractions) for multiple simultaneous moving dynamic distributed loads without any prior knowledge about the loads except that all loading is applied along the top surface of the solid. Provided that moving loads on roadways are applied to the top surface, it is shown that updating the guessed loading at just surface nodes, rather than at all nodes in space, greatly improves the inversion results. The inversion is shown to be as effective at reconstructing loads on the top surface of a solid when the solid is horizontally layered with multiple materials as when the solid it is homogeneous. Reducing the distance between sensors improves the accuracy of the inversion while reducing the width of distributed loads leads to less accurate results. The authors also validate the presented inversion method by using experimental data obtained from lab-scale tests at a high frequency (100 kHz) for a stationary load on a homogeneous solid.

Coach, sports medicine, and parent influence on concussion care seeking intentions and behaviors in collegiate student-athletes.

BACKGROUND: Sport is a socio-ecological framework where student-athletes are part of a larger community of stakeholders, including coaches, sports medicine professionals (SMPs), and parents. This framework may hold influence over whether student-athletes seek care for a concussion. AIM: We aimed to describe, compare, and determine the influence of stakeholder concussion knowledge, attitudes, and concussion scenario responses. MATERIALS AND METHODS: We recruited a sample of 477 student-athletes and their 27 coaches (response rate=46.6%), 24 SMPs (48.7%), and 31 parents/guardians (4.8%). Stakeholder surveys assessed their concussion knowledge, attitudes toward care seeking, and concussion scenario responses. Surveys administered to student-athletes assessed their concussion care seeking intentions and behaviors. Kruskal-Wallis tests were used to compare responses between stakeholder groups and to determine the differences in student-athlete intentions and behaviors (alpha=0.05). RESULTS: SMPs had significantly better knowledge (p<0.001) and concussion scenario responses (p<0.001) compared to both coaches and parents. SMPs also had significantly better attitudes compared to parents, but not coaches (p=0.038). Coach concussion scenario responses (p=0.044) and SMP knowledge positively influenced student-athletes' concussion care seeking intentions (p=0.049). Parent responses were not associated with their child's concussion care seeking intentions and behaviors. CONCLUSIONS: The gap in coach and parent concussion knowledge and concussion scenario response relative to SMPs is a preliminary target for stakeholder concussion education and supports the current sports medicine model where SMPs primarily disseminate concussion education. Stakeholders, specifically coaches and SMPs, do hold influence over collegiate athlete concussion care seeking intentions and behaviors. RELEVANCE FOR PATIENTS: Stakeholders should be addressed within educational efforts aimed at student-athletes and should also complete stakeholder-specific concussion education.

A Multi-method Investigation of the Personality Correlates of Functional Ability in Older Adults.

OBJECTIVES: This study evaluated the role of personality in predicting functional ability (FA) in older adults using self-report, collateral report, and performance-based measures of FA. METHODS: Participants included older adults (N = 131) who completed a personality measure (NEO-FFI), a self-report of FA (OARS ADL), and participated in a performance-based assessment of FA (DAFS-R). In addition, each participant had a collateral complete a collateral report of FA (OARS ADL). Bivariate correlations were computed to assess how Five Factor Model traits were related to self-report, collateral, and performance-based measures of FA. RESULTS: Neuroticism was negatively related to self-reported FA (r = - .27) and collateral-reported FA (r = - .18) and Conscientiousness was positively related to self-reported FA (r = .25). None of the traits were significantly related to the performance-based measure of FA. CONCLUSIONS: These results suggest that personality traits can impact self-reported FA in older adults and underscore the importance of assessing FA in older adults using multiple methods, particularly performance-based measures. CLINICAL IMPLICATIONS: Clinicians should consider how personality may impact FA in older adults and multiple methods of FA performance should be examined to better tailor recommendations.

The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer.

Pimozide, an antipsychotic drug of the diphenylbutylpiperidine class, has been shown to suppress cell growth of breast cancer cells in vitro. In this study we further explore the inhibitory effects of this molecule in cancer cells. We found that Pimozide inhibited cell proliferation in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells and A549 lung cancer cells. Furthermore, we found that Pimozide also promoted apoptosis as demonstrated by cell cycle arrest and induction of double-strand DNA breaks but did not result in any effect in the non-transformed MCF10A breast cell line. In order to shed new lights into the molecular pathways affected by Pimozide, we show that Pimozide downregulated RAN GTPase and AKT at both protein and mRNA levels and inhibited the AKT signaling pathway in MDA-MB-231 breast cancer cells. Pimozide also inhibited the epithelial mesenchymal transition and cell migration and downregulated the expression of MMPs. Administration of Pimozide showed a potent in vivo antitumor activity in MDA-MB-231 xenograft animal model and reduced the number of lung metastases by blocking vascular endothelial growth factor receptor 2. Furthermore, Pimozide inhibited myofibroblast formation as evaluated by the reduction in α-smooth muscle actin containing cells. Thus, Pimozide might inhibit tumor development by suppressing angiogenesis and by paracrine stimulation provided by host reactive stromal cells. These results demonstrate a novel in vitro and in vivo antitumor activity of Pimozide against breast and lung cancer cells and provide the proof of concept for a putative Pimozide as a novel approach for cancer therapy.

Lutein and Zeaxanthin Are Positively Associated with Visual-Spatial Functioning in Older Adults: An fMRI Study.

Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L and Z in cognition, neural structure, and neural efficiency. The present study aimed to better understand the mechanisms by which L and Z relate to cognition, in particular, visual-spatial processing and decision-making in older adults. We hypothesized that markers of higher levels of L and Z would be associated with better neural efficiency during a visual-spatial processing task. L and Z were assessed via standard measurement of blood serum and retinal concentrations. Visual-spatial processing and decision-making were assessed via a judgment of line orientation task (JLO) completed during a functional magnetic resonance imaging (fMRI) scan. The results demonstrated that individuals with higher concentrations of L and Z showed a decreased blood-oxygen-level dependent (BOLD) signal during task performance (i.e., "neural efficiency") in key areas associated with visual-spatial perception, processing, decision-making, and motor coordination, including the lateral occipital cortex, occipital pole, superior and middle temporal gyri, superior parietal lobule, superior and middle frontal gyri, and pre- and post-central gyri. To our knowledge, this is the first investigation of the relationship of L and Z to visual-spatial processing at a neural level using in vivo methodology. Our findings suggest that L and Z may impact brain health and cognition in older adults by enhancing neurobiological efficiency in a variety of regions that support visual perception and decision-making.

A healthy lifestyle index is associated with reduced risk of colorectal adenomatous polyps among non-users of non-steroidal anti-inflammatory drugs.

In a Columbia, South Carolina-based case-control study, we developed a healthy lifestyle index from five modifiable lifestyle factors (smoking, alcohol intake, physical activity, diet, and body mass index), and examined the association between this lifestyle index and the risk of colorectal adenomatous polyps (adenoma). Participants were recruited from a local endoscopy center and completed questionnaires related to lifestyle behaviors prior to colonoscopy. We scored responses on each of five lifestyle factors as unhealthy (0 point) or healthy (1 point) based on current evidence and recommendations. We added the five scores to produce a combined lifestyle index for each participant ranging from 0 (least healthy) to 5 (healthiest), which was dichotomized into unhealthy (0-2) and healthy (3-5) lifestyle scores. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for adenoma with adjustment for multiple covariates. We identified 47 adenoma cases and 91 controls. In the main analyses, there was a statistically nonsignificant inverse association between the dichotomous (OR 0.54; 95% CI 0.22, 1.29) and continuous (OR 0.75; 95% CI 0.51, 1.10) lifestyle index and adenoma. Odds of adenoma were significantly modified by the use of non-steroidal anti-inflammatory drugs (NSAIDs) (p(interaction) = 0.04). For participants who reported no use of NSAIDs, those in the healthy lifestyle category had a 72% lower odds of adenoma as compared to those in the unhealthy category (OR 0.28; 95% CI 0.08, 0.98), whereas a one-unit increase in the index significantly reduced odds of adenoma by 53% (OR 0.47; 95% CI 0.26, 0.88). Although these findings should be interpreted cautiously given our small sample size, our results suggest that higher scores from this index are associated with reduced odds of adenomas, especially in non-users of NSAIDs. Lifestyle interventions are required to test this approach as a strategy to prevent colorectal adenomatous polyps.

Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation.

Clock genes are expressed in a self-perpetuating, circadian pattern in virtually every tissue including the human gastrointestinal tract. They coordinate cellular processes critical for tumor development, including cell proliferation, DNA damage response and apoptosis. Circadian rhythm disturbances have been associated with an increased risk for colon cancer and other cancers. This mechanism has not been elucidated, yet may involve dysregulation of the 'period' (PER) clock genes, which have tumor suppressor properties. A variable number tandem repeat (VNTR) in the PERIOD3 (PER3) gene has been associated with sleep disorders, differences in diurnal hormone secretion, and increased premenopausal breast cancer risk. Susceptibility related to PER3 has not been examined in conjunction with adenomatous polyps. This exploratory case-control study was the first to test the hypothesis that the 5-repeat PER3 VNTR sequence is associated with increased odds of adenoma formation. Information on demographics, medical history, occupation and lifestyle was collected prior to colonoscopy. Cases (n=49) were individuals with at least one histopathologically confirmed adenoma. Controls (n=97) included patients with normal findings or hyperplastic polyps not requiring enhanced surveillance. Unconditional multiple logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), after adjusting for potential confounding. Adenomas were detected in 34% of participants. Cases were more likely to possess the 5-repeat PER3 genotype relative to controls (4/5 OR, 2.1; 95% CI, 0.9-4.8; 5/5 OR, 5.1; 95% CI, 1.4-18.1; 4/5+5/5 OR, 2.5; 95% CI, 1.7-5.4). Examination of the Oncomine microarray database indicated lower PERIOD gene expression in adenomas relative to adjacent normal tissue. Results suggest a need for follow-up in a larger sample.

Cognitive reserve moderates relation between global cognition and functional status in older adults.

The ability to perform instrumental activities of daily living (IADLs) is necessary for independent living. Research suggests that community-dwelling older adults are at risk for experiencing subtle decrements in the performance of IADLs. Neuropsychological tests have been used to account for differences in IADL status. Studies of the relationship between cognitive ability and functional status have produced variable results, however, and cognitive ability appears to be only a moderate predictor. Several studies of normal aging have revealed cognitive and functional benefits of higher cognitive reserve (CR) in healthy, nondemented older adults. The purposes of the present study were to: (a) examine the relationship between global cognitive ability and IADL performance among 53 community-dwelling older adults, and (b) determine whether formal education, as a proxy of CR, significantly moderates this relationship. Consistent with previous findings, global cognitive ability accounted for a considerable portion of variance in IADL performance [ΔR(2) = .54; ΔF(2, 53) = 67.96; p < .001]. Additionally, CR modestly but significantly attenuated this relationship [ΔR(2) = .044; ΔF(4, 53) = 5.98; p = .018; total R(2) = .65]. This finding suggests that community-dwelling older adults with lower levels of formal education may be at greater risk for functional decrements associated with age-related cognitive decline.

e-Labs and the stock of health method for simulating health policies.

Regional outcomes of national health policies are difficult to forecast. This is partly due to a lack of realistically complex models that can be used to appraise policy options and partly a lack of accessible and adaptable tools that can be used to simulate the consequences of policy decisions. These barriers might be overcome by exploiting the commoditization of massively parallel computing architectures, advances in machine learning, and the increased availability of large-scale linked healthcare data. This paper presents a novel modelling methodology, The Stock of Health, for harnessing emerging data and computational resources to simulate health policy, with application initially to coronary heart disease. We detail the use of multi-core graphical processing architectures to facilitate a micro-simulation approach. The simulation tools have been deployed through the IMPACT Framework. We explore how this framework can be extended to support the sharing and reuse of policy models and simulations based on the digital publishing concept of e-Lab.

Sources of variation on the mini-mental state examination in a population-based sample of centenarians.

Centenarians represent a rare but rapidly growing segment of the oldest-old. This study presents item-level data from the Mini-Mental State Examination (MMSE) in a cross-sectional, population-based sample of 244 centenarians and near-centenarians (aged 98-108, 16% men, 21% African-American, 38% community dwelling) from the Georgia Centenarian Study (2001-2008) according to age, education, sex, race, and residential status. Multiple-Indicator Multiple-Cause (MIMIC) models were used to identify systematic domain-level differences in MMSE scores according to demographic characteristics in this age group. Indirect effects of age, educational attainment, race, and residential status were found on MMSE scores. Direct effects were limited to concentration for education and race and orientation for residential status. Mean levels of cognitive functioning in centenarians were low, with mean values below most commonly-used cutoffs. Overall scores on the MMSE differed as a function of age, education, race, and residential status, with differences in scale performance limited primarily to concentration and orientation and no evidence of interactions between centenarian characteristics. Adjusting for education was not sufficient to account for differences according to race, and adjusting for residential status was not sufficient to account for differences according to age.

Racial disparities in colon cancer. Primary care endoscopy as a tool to increase screening rates among minority patients.

Colon cancer is a condition whose far-reaching effects have been well documented nationally and within the state of South Carolina. Fortunately, the disease is amenable to both primary and secondary prevention through screening colonoscopy. Despite the conceptual simplicity of recommending colonoscopy, barriers exist to universal (or even widespread) screening. Currently the infrastructure necessary to achieve screening goals set by the American Cancer Society (ACS), the American College of Gastroenterology (ACG), and the South Carolina Department of Health and Environmental Control (DHEC) has not been established. At current rates of training gastroenterologists, the medical community will not be able to come close to achieving widespread screening. Given the discrepancy between the public health benefit of achieving the goals and the deaths that have occurred because of the resource shortfall, we propose alternative measures to screen the at-risk population for consideration. This need is most acute in the black community, in which where screening rates tend to be lower and polyps have been found to progress more quickly than among white populations. In South Carolina, one model has used primary care physicians as the labor force to provide routine screening colonoscopy for their own patients. This model makes screening much more accessible to minority patients, as the wait is shorter and the cost typically lower. In combination with a faith-based partnership with minority religious organizations, this model has begun to make needed inroads toward addressing the disparities associated with colon cancer. Cancer 2007. (c) 2006 American Cancer Society.

Multilayered materials: a palette for the materials artist.

Developments in the understanding of how materials behave enable us to design material structures to display specified properties. We introduce multilayered materials as systems in which new properties, not found in their constituents in bulk form, can emerge. The importance of transmission electron microscopy to determine structure-property relationships in nanoscale multilayers through characterization of their atomic and electronic structure is emphasized. Two examples of technologically useful multilayer systems are considered in more detail: hard coatings made from nitride multilayer films and the new structures and magnetic properties that are found in some metal multilayer systems. Finally, we discuss the future developments that are required to fully exploit the novel properties found in multilayered materials.