Estimating youth locomotion ground reaction forces using an accelerometer-based activity monitor.

To address a variety of questions pertaining to the interactions between physical activity, musculoskeletal loading and musculoskeletal health/injury/adaptation, simple methods are needed to quantify, outside a laboratory setting, the forces acting on the human body during daily activities. The purpose of this study was to develop a statistically based model to estimate peak vertical ground reaction force (pVGRF) during youth gait. 20 girls (10.9 ± 0.9 years) and 15 boys (12.5 ± 0.6 years) wore a Biotrainer AM over their right hip. Six walking and six running trials were completed after a standard warm-up. Average AM intensity (g) and pVGRF (N) during stance were determined. Repeated measures mixed effects regression models to estimate pVGRF from Biotrainer activity monitor acceleration in youth (girls 10-12, boys 12-14 years) while walking and running were developed. Log transformed pVGRF had a statistically significant relationship with activity monitor acceleration, centered mass, sex (girl), type of locomotion (run), and locomotion type-acceleration interaction controlling for subject as a random effect. A generalized regression model without subject specific random effects was also developed. The average absolute differences between the actual and predicted pVGRF were 5.2% (1.6% standard deviation) and 9% (4.2% standard deviation) using the mixed and generalized models, respectively. The results of this study support the use of estimating pVGRF from hip acceleration using a mixed model regression equation

Synaptophysin-Ki67 double stain: a novel technique that improves interobserver agreement in the grading of well-differentiated gastrointestinal neuroendocrine tumors.

A common problem in the assessment of Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors is distinguishing tumor from non-tumor. This is because background stromal lymphocytes, entrapped non-neoplastic glands, and the delicate vascular network characteristic of neuroendocrine tumors frequently contain a subset of proliferating cells. Furthermore, in small biopsies, crush and cautery artifact can alter the morphologic appearance of tumor cells, making the Ki67 proliferative index more difficult to assess. To address these issues, we developed a synaptophysin-Ki67 double stain using a commercially available immunohistochemistry kit, allowing simultaneous visualization of tumor and proliferating nuclei. To test this method, three gastrointestinal pathologists individually graded 50 gastrointestinal neuroendocrine tumors first using synaptophysin-Ki67 double-stained slides and then, after a washout period, using Ki67-only stained slides (along with routine hematoxylin- and eosin-stained slides). Interobserver agreement on Ki67 proliferative index was moderate using the Ki67-only stained slides (intraclass correlation 0.51, 95% confidence interval: 0.35-0.66) and improved using the synaptophysin-Ki67 double stain (intraclass correlation 0.79, 95% confidence interval: 0.69-0.86). Similarly, interobserver agreement on tumor grade was fair with Ki67-only stained slides (κ=0.39, P<0.001) and improved with the double stain (κ=0.58, P<0.001). Analysis of individual pathologists' scores revealed that fewer total number of tumor cells counted correlated with higher grade designation and appeared to contribute to grade discordance. In tumors cited as particularly challenging to assess by the pathologists, three of four tumors were grade discordant with the Ki67-only stain, whereas all four tumors were grade concordant with the synaptophysin-Ki67 stain. The synaptophysin-Ki67 double stain is the first technique to address specifically the histomorphologic challenges of evaluating Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors. Although further validation is needed, this study provides evidence that the synaptophysin-Ki67 double stain can improve interobserver agreement

Age differences in the use of serving size information on food labels: numeracy or attention?

ObjectiveThe ability to use serving size information on food labels is important for managing age-related chronic conditions such as diabetes, obesity and cancer. Past research suggests that older adults are at risk for failing to accurately use this portion of the food label due to numeracy skills. However, the extent to which older adults pay attention to serving size information on packages is unclear. We compared the effects of numeracy and attention on age differences in accurate use of serving size information while individuals evaluated product healthfulness.DesignAccuracy and attention were assessed across two tasks in which participants compared nutrition labels of two products to determine which was more healthful if they were to consume the entire package. Participants' eye movements were monitored as a measure of attention while they compared two products presented side-by-side on a computer screen. Numeracy as well as food label habits and nutrition knowledge were assessed using questionnaires.SettingSacramento area, California, USA, 2013-2014.SubjectsStratified sample of 358 adults, aged 20-78 years.ResultsAccuracy declined with age among those older adults who paid less attention to serving size information. Although numeracy, nutrition knowledge and self-reported food label use supported accuracy, these factors did not influence age differences in accuracy.ConclusionsThe data suggest that older adults are less accurate than younger adults in their use of serving size information. Age differences appear to be more related to lack of attention to serving size information than to numeracy skills

Relationships among food label use, motivation, and dietary quality.

Nutrition information on packaged foods supplies information that aids consumers in meeting the recommendations put forth in the US Dietary Guidelines for Americans such as reducing intake of solid fats and added sugars. It is important to understand how food label use is related to dietary intake. However, prior work is based only on self-reported use of food labels, making it unclear if subjective assessments are biased toward motivational influences. We assessed food label use using both self-reported and objective measures, the stage of change, and dietary quality in a sample of 392 stratified by income. Self-reported food label use was assessed using a questionnaire. Objective use was assessed using a mock shopping task in which participants viewed food labels and decided which foods to purchase. Eye movements were monitored to assess attention to nutrition information on the food labels. Individuals paid attention to nutrition information when selecting foods to buy. Self-reported and objective measures of label use showed some overlap with each other (r=0.29, p<0.001), and both predicted dietary quality (p<0.001 for both). The stage of change diminished the predictive power of subjective (p<0.09), but not objective (p<0.01), food label use. These data show both self-reported and objective measures of food label use are positively associated with dietary quality. However, self-reported measures appear to capture a greater motivational component of food label use than do more objective measures

Misunderstanding of Front-Of-Package Nutrition Information on US Food Products.

Front-of-package nutrition symbols (FOPs) are presumably readily noticeable and require minimal prior nutrition knowledge to use. Although there is evidence to support this notion, few studies have focused on Facts Up Front type symbols which are used in the US. Participants with varying levels of prior knowledge were asked to view two products and decide which was more healthful. FOPs on packages were manipulated so that one product was more healthful, allowing us to assess accuracy. Attention to nutrition information was assessed via eye tracking to determine what if any FOP information was used to make their decisions. Results showed that accuracy was below chance on half of the comparisons despite consulting FOPs. Negative correlations between attention to calories, fat, and sodium and accuracy indicated that consumers over-relied on these nutrients. Although relatively little attention was allocated to fiber and sugar, associations between attention and accuracy were positive. Attention to vitamin D showed no association to accuracy, indicating confusion surrounding what constitutes a meaningful change across products. Greater nutrition knowledge was associated with greater accuracy, even when less attention was paid. Individuals, particularly those with less knowledge, are misled by calorie, sodium, and fat information on FOPs

Impact of an Interactive On-line Tool on Therapeutic Decision-Making for Patients with Advanced Non-Small-Cell Lung Cancer

Background:Treatment guidelines provide recommendations but cannot account for the wide variability in patient-tumor characteristics in individual patients. We developed an on-line interactive decision tool to provide expert recommendations for specific patient scenarios in the first-line and maintenance settings for advanced non–small-cell lung cancer. We sought to determine how providing expert feedback would influence clinical decision-making.Method:Five lung cancer experts selected treatment for 96 different patient cases based on patient and/or tumor-specific features. These data were used to develop an on-line decision tool. Participant physicians entered variables for their patient scenario with treatment choices, and then received expert treatment recommendations for that scenario. To determine the impact on decision-making, users were asked whether the expert feedback impacted their original plan.Results:A total of 442 individual physicians, of which 88% were from outside the United States, entered 653 cases, with report on impact in 389 cases. Expert feedback affected treatment choice in 73% of cases (23% changed and 50% confirmed decisions). For cases with epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion, all experts selected targeted therapy whereas 51% and 58% of participants did not. Greater variability was seen between experts and participants for cases involving EGFR or ALK wild-type tumors. Participants were 2.5-fold more likely to change to expert recommended therapy for ALK fusions than for EGFR mutations (p = 0.017).Conclusion:This online tool for treatment decision-making resulted in a positive influence on clinician's decisions. This approach offers opportunities for improving quality of care and meets an educational need in application of new therapeutic paradigms

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells

Abstract Introduction Previous studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells. Methods MUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells. Results Immunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis. Conclusions Our observations suggest that after an initial loss of MUC4 levels during the transition of normal breast tissue to primary tumor, the re-establishment of elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by promoting the acquisition of cellular properties associated with malignancy

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

INTRODUCTION: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. METHODS: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. RESULTS: Multimodal analyses will provide insight into AD pathophysiology and disease progression. DISCUSSION: ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments