The possibility of an infectious etiology for Alzheimer's disease (AD) has been repeatedly postulated over the past three decades. We provide the first meta-analysis to address the relationship between bacterial infection and AD. Studies examining the association between AD and spirochetal bacteria or Chlamydophila pneumoniae (Cpn) were identified through a systematic search of the databases MEDLINE, EMBASE, PubMed, and Google Scholar. Data combined from 25 relevant, primarily case-control studies demonstrated a statistically significant association between AD and detectable evidence of infection of either bacterial group. We found over a ten-fold increased occurrence of AD when there is detectable evidence of spirochetal infection (OR: 10.61; 95% CI: 3.38-33.29) and over a four-fold increased occurrence of AD in a conservative risk estimate (OR: 4.45; 95% CI: 2.33-8.52). We found over a five-fold increased occurrence of AD with Cpn infection (OR: 5.66; 95% CI: 1.83-17.51). This study shows a strongly positive association between bacterial infection and AD. Further detailed investigation of the role of bacterial infection is warranted.

The fetal modified myocardial performance index (Mod-MPI) is a noninvasive, pulsed-wave Doppler-derived measure of global myocardial function. This review assesses the progress in technical refinements of its measurement and the potential for automation to be the crucial next step. The Mod-MPI is a ratio of isovolumetric to ejection time cardiac time intervals, and the potential for the left ventricular Mod-MPI as a tool to clinically assess fetal cardiac function is well-established. However, there are wide variations in published reference ranges, as (1) a standardised method of selecting cardiac time intervals used in Mod-MPI calculation has not been established; (2) cardiac time interval measurement currently requires manual, inherently subjective placement of callipers on Doppler ultrasound waveforms; and (3) ultrasound machine settings and ultrasound system type have been found to affect Mod-MPI measurement. Collectively these factors create potential for significant inter- and intraobserver measurement variability. Automated measurement of the Mod-MPI may be the next key development which propels the Mod-MPI into routine clinical use. A novel automated system of Mod-MPI measurement is briefly presented and its implications for the future of the Mod-MPI in fetal cardiology are discussed.

Objectives: 1. To develop an automated system for calculating the fetal myocardial performance index (MPI), a non-invasive, pulsed-wave Doppler derived measure of global myocardial function, from raw ultrasound waveform data. 2. To compare automation with human evaluation of the fetal left MPI using an international team of fetal cardiology experts. Methods: A multicentre international study was undertaken using online technology to compare automated and manual MPIs. Images were used from a prior study of women with uncomplicated, morphologically normal singleton pregnancies at 16-38 weeks gestation. Individual Doppler ultrasound cardiac cycle images from the left ventricle of 25 cases were selected. Each waveform was used in triplicate and placed into a random order (n = 75). One senior observer blinded to this repetition at each of six centres manually calculated the MPI for the 75 waveforms online. The automated system was used to also measure the MPI for those waveforms. Intraobserver repeatability and interobserver reproducibility of MPI measurements were assessed using intraclass correlation coefficients (ICC) and 95% confidence intervals (95%CI). Bland-Altman plots, ICC and 95%CI were used to evaluate agreement between each observer's manual MPI measurements and corresponding automated measurements. Results: Automated measurements had superior repeatability (ICC = 1.00) compared to manual intraobserver repeatability (ICC ranging from 0.692-0.967) and manual interobserver reproducibility (ICC = 0.777). There was good agreement between automated and manual measurements of MPI (ICC 0.78-0.95). Conclusions: Automated fetal MPI provides superior repeatability and reproducibility to manual methodology. Universal application of this technique could facilitate translation of the MPI into a clinically useful tool. OC21.03 Beat-to-beat variability of the fetal myocardial performance index (MPI) Objectives: To determine whether there is beat-to-beat variability in the fetal left MPI as evaluated by an automated MPI measurement system and whether there is a correlation between the MPI and fetal heart rate (FHR). Methods: In this prospective cross-sectional study, women at 20-38 weeks gestation with uncomplicated, morphologically normal singleton pregnancies were recruited to undergo 2D Doppler ultrasound examinations. Multiple cineloops of waveforms suitable for measurement of the left MPI were acquired during a single examination in each fetus. Raw cineloop data was analysed by our automated MPI system (with established ICC of 1.0 for any given waveform) to produce a set of MPIs. The corresponding instantaneous FHR for each individual cycle that the MPI was calculated for was also measured. Results: Data from examinations of 29 fetuses was analysed, yielding a mean MPI of 0.52 and a mean FHR of 151. The median number of cycles examined per fetus was 70 (interquartile range: 31-115). There was marked beat-to-beat variability noted. When expressed as coefficient of variation, the median CoV was 8.7% (range 4.9% to 13....

There is significant BTB variability in fetal left MPI, which has an overall weak correlation with FHR. This could be a factor affecting the consistency of MPI values reported by different research groups. Variability would be reduced by averaging 4-5 cardiac cycles per fetus. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.