Purpose

Machine learning methods could better improve the detection of specific types of physical activities and sedentary behaviors from accelerometer data. No studies in older populations have developed and tested algorithms for walking and sedentary time in free-living daily life. Our goal was to rectify this gap by leveraging access to data from two studies in older women.

Methods

In study 1, algorithms were developed and tested in a sample of older women (N = 39, age range = 55-96 yr) in the field. Women wore accelerometers and SenseCam (ground truth annotation) devices for 7 d, yielding 3191 h and 320 d of data. Images were annotated and time matched to accelerometer data, and random forest classifiers labeled behaviors (sitting, riding in a vehicle, standing still, standing moving, and walking/running). In study 2, we examined the concurrent validity of the algorithms using accelerometer data from an observed 400-m walk test (2983 min of data available) and 6 d of wearing both accelerometers and global positioning systems devices in a sample of 222 women (age range = 67-100; 313,290 min of data available). Analyses included sensitivity, specificity balanced accuracy, and precision, as appropriate, averaged over each test participant at the minute level for each behavior.

Results

In study 1, the algorithms had 82.2% balanced accuracy. In study 2, the classifier had 87.9% accuracy for predicting walking. Overall machine learning classifiers and global positioning systems had 88.6% agreement.

Conclusions

Free-living algorithms for walking and sedentary time yielded high levels of accuracy and concurrent validity and can be applied to existing accelerometer data from older women.

Novel bis-1,2,4-triazine compounds with potent in vitro activity against Plasmodium falciparum parasites were recently identified. The bis-1,2,4-triazines represent a unique antimalarial pharmacophore and are proposed to act by a novel but as-yet-unknown mechanism of action. This study investigated the activity of the bis-1,2,4-triazine MIPS-0004373 across the mammalian life cycle stages of the parasite and profiled the kinetics of activity against blood and transmission stage parasites in vitro and in vivo. MIPS-0004373 demonstrated rapid and potent activity against P. falciparum, with excellent in vitro activity against all asexual blood stages. Prolonged in vitro drug exposure failed to generate stable resistance de novo, suggesting a low propensity for the emergence of resistance. Excellent activity was observed against sexually committed ring stage parasites, but activity against mature gametocytes was limited to inhibiting male gametogenesis. Assessment of liver stage activity demonstrated good activity in an in vitro P. berghei model but no activity against Plasmodium cynomolgi hypnozoites or liver schizonts. The bis-1,2,4-triazine MIPS-0004373 efficiently cleared an established P. berghei infection in vivo, with efficacy similar to that of artesunate and chloroquine and a recrudescence profile comparable to that of chloroquine. This study demonstrates the suitability of bis-1,2,4-triazines for further development toward a novel treatment for acute malaria.