Abstract Background An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. Methods Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web‐platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. Results The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001). Conclusions The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.
The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share
Abstract Background: Nitrate and nitrite are precursors of N-nitroso compounds, known animal and human carcinogens. Nitrate and nitrite are common in foods, such as vegetables and processed meats, and nitrate is a contaminant of drinking water. We previously reported an increased ovarian cancer risk associated with higher nitrate intake in public water supplies in the Iowa Women's Health Study. Here, we report results based on an additional 12 years of follow-up and we present results for dietary nitrate and nitrite intake. Methods: Among 28,555 postmenopausal women aged 55–69 y at baseline, we identified 315 incident epithelial ovarian cancers between 1986 and 2010. Dietary nitrate and nitrite intakes were assessed using a food frequency questionnaire at baseline. Information on drinking water source was obtained in 1989. Nitrate-nitrogen (NO3-N) levels in public water supplies (average level 1955-1988) and water sources (finished surface or ground water) were from a database of monitoring data for Iowa water utilities. Cox proportional hazards regression generated hazard ratios (HR) and 95% confidence intervals (CI). Because disinfection by-products (DBP) are higher in surface water and have been associated with increased risk for certain cancers, we determined whether the association between nitrate intake from drinking water and ovarian cancer risk differed by water source. Results: Neither total dietary nitrate nor nitrite intake was associated with ovarian cancer risk after adjusting for age, energy intake, family history of ovarian cancer, number of live births, and history of unilateral oophorectomy. Nitrate and nitrite intakes from animal or plant sources, or processed meats were not associated with ovarian cancer risk. Among women who drank public water, we observed an increased risk for ovarian cancer with higher average levels of NO3-N (ptrend=0.004). Compared with women in the lowest quartile of NO3-N levels (<0.36 mg/L), risk was 1.81 (95% CI=1.08-3.05) and 2.02 (95% CI=1.21-3.36) times higher in the third (1.0-2.5 mg/L) and fourth (>2.5 mg/L) quartiles, respectively. Ovarian cancer risk among private well water drinkers was elevated (HR=1.52, 95% CI=0.91-2.53) but not statistically significantly different from the referent group. When stratified by water source, the positive association between NO3-N levels in public water and ovarian cancer risk was confined to women who drank water from surface sources (ptrend=0.007; pinteraction=0.04). Conclusions: Dietary nitrate or nitrite intake was not associated with ovarian cancer risk. Our findings for nitrate intake from public water supplies suggest that nitrate intake from drinking water may increase ovarian cancer risk, particularly in the likely presence of other contaminants found in surface water. Further evaluation of DBP and other water contaminant levels on ovarian cancer risk in this population is warranted. Citation Format: Maki Inoue-Choi, Kristin E. Anderson, James R. Cerhan, Peter J. Weyer, Mary H. Ward. Dietary intake of nitrate and nitrite, nitrate in drinking water, and ovarian cancer risk among postmenopausal women in Iowa. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 149. doi:10.1158/1538-7445.AM2013-149
A Structurally Distinct Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union
Easy M Our immune systems can produce a vastly diverse repertoire of antibody molecules that each recognize and bind to a specific foreign antigen via a hypervariable region. However, there are a few bacterial antigens—such as Protein A, Protein G, and Protein L—that instead bind to the antibody's conserved regions and can bind to a large number of different antibodies. These high-affinity broad-spectrum antibody-binding properties have been widely exploited both in the laboratory and in industry for purifying, immobilizing, and detecting antibodies. Grover et al. (p. 656 ) have now identified Protein M found on the surface of human mycoplasma, which displays even broader antibody-binding specificity. The crystal structure of Protein M revealed how Protein-M binding blocks the antibody's antigen binding site. This mechanism may be exploited by mycoplasma to escape the humoral immune response.
Survival outcomes in patients with early stage, resected pancreatic cancer - a comparison of gemcitabine- and 5-fluorouracil-based chemotherapy and chemoradiation regimens
AbstractAlzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant discussion, including potential next steps to move this area of research forward.
Telemedicine Barriers Associated with Regional Quality Measures
Telemedicine practitioners are familiar with multiple barriers to delivering care at a distance. Licensing and reimbursement barriers are well known and are being addressed at national and state levels by the American Telemedicine Association. Another telemedicine barrier comes in the form of quality measures for diabetes. Minnesota medical practices are currently being compared on the proportion of their patients with diabetes who have attained goals for blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1C. The quality measure for blood pressure specifically excludes measurements taken by the patient, thus precluding blood pressure telemonitoring as a way to meet the blood pressure goal. To counter this barrier, advocacy in telemedicine is needed so that telemonitoring as a data collection tool is included in quality measures.