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1. A Pilot Study to Assess the Reliability of Sensing Joint Acoustic Emissions of the Wrist

   https://doi.org/10.3390/s20154240  

   Hochman, Daniel M. ; Gharehbaghi, Sevda ; Whittingslow, Daniel C. ; Inan, Omer T. ( August 2020 , Sensors)

   Joint acoustic emission (JAE) sensing has recently proven to be a viable technique for non-invasive quantification indicating knee joint health. In this work, we adapt the acoustic emission sensing method to measure the JAEs of the wrist—another joint commonly affected by injury and degenerative disease. JAEs of seven healthy volunteers were recorded during wrist flexion-extension and rotation with sensitive uniaxial accelerometers placed at eight locations around the wrist. The acoustic data were bandpass filtered (150 Hz–20 kHz). The signal-to-noise ratio (SNR) was used to quantify the strength of the JAE signals in each recording. Then, nine audio features were extracted, and the intraclass correlation coefficient (ICC) (model 3,k), coefficients of variability (CVs), and Jensen–Shannon (JS) divergence were calculated to evaluate the interrater repeatability of the signals. We found that SNR ranged from 4.1 to 9.8 dB, intrasession and intersession ICC values ranged from 0.629 to 0.886, CVs ranged from 0.099 to 0.241, and JS divergence ranged from 0.18 to 0.20, demonstrating high JAE repeatability and signal strength at three locations. The volunteer sample size is not large enough to represent JAE analysis of a larger population, but this work will lay a foundation for future work in using wrist JAEsmore »to aid in diagnosis and treatment tracking of musculoskeletal pathologies and injury in wearable systems.« less
2. Predictive models of pregnancy based on data from a preconception cohort study

   https://doi.org/10.1093/humrep/deab280  

   Yland, Jennifer J. ; Wang, Taiyao ; Zad, Zahra ; Willis, Sydney K. ; Wang, Tanran R. ; Wesselink, Amelia K. ; Jiang, Tammy ; Hatch, Elizabeth E. ; Wise, Lauren A. ; Paschalidis, Ioannis Ch ( January 2022 , Human Reproduction)

   Can we derive adequate models to predict the probability of conception among couples actively trying to conceive?

   Leveraging data collected from female participants in a North American preconception cohort study, we developed models to predict pregnancy with performance of ∼70% in the area under the receiver operating characteristic curve (AUC).

   Earlier work has focused primarily on identifying individual risk factors for infertility. Several predictive models have been developed in subfertile populations, with relatively low discrimination (AUC: 59–64%).

   Study participants were female, aged 21–45 years, residents of the USA or Canada, not using fertility treatment, and actively trying to conceive at enrollment (2013–2019). Participants completed a baseline questionnaire at enrollment and follow-up questionnaires every 2 months for up to 12 months or until conception. We used data from 4133 participants with no more than one menstrual cycle of pregnancy attempt at study entry.

   On the baseline questionnaire, participants reported data on sociodemographic factors, lifestyle and behavioral factors, diet quality, medical history and selected male partner characteristics. A total of 163 predictors were considered in this study. We implemented regularized logistic regression, support vector machines, neural networks and gradient boosted decisionmore »trees to derive models predicting the probability of pregnancy: (i) within fewer than 12 menstrual cycles of pregnancy attempt time (Model I), and (ii) within 6 menstrual cycles of pregnancy attempt time (Model II). Cox models were used to predict the probability of pregnancy within each menstrual cycle for up to 12 cycles of follow-up (Model III). We assessed model performance using the AUC and the weighted-F1 score for Models I and II, and the concordance index for Model III.

   Model I and II AUCs were 70% and 66%, respectively, in parsimonious models, and the concordance index for Model III was 63%. The predictors that were positively associated with pregnancy in all models were: having previously breastfed an infant and using multivitamins or folic acid supplements. The predictors that were inversely associated with pregnancy in all models were: female age, female BMI and history of infertility. Among nulligravid women with no history of infertility, the most important predictors were: female age, female BMI, male BMI, use of a fertility app, attempt time at study entry and perceived stress.

   Reliance on self-reported predictor data could have introduced misclassification, which would likely be non-differential with respect to the pregnancy outcome given the prospective design. In addition, we cannot be certain that all relevant predictor variables were considered. Finally, though we validated the models using split-sample replication techniques, we did not conduct an external validation study.

   Given a wide range of predictor data, machine learning algorithms can be leveraged to analyze epidemiologic data and predict the probability of conception with discrimination that exceeds earlier work.

   The research was partially supported by the U.S. National Science Foundation (under grants DMS-1664644, CNS-1645681 and IIS-1914792) and the National Institutes for Health (under grants R01 GM135930 and UL54 TR004130). In the last 3 years, L.A.W. has received in-kind donations for primary data collection in PRESTO from FertilityFriend.com, Kindara.com, Sandstone Diagnostics and Swiss Precision Diagnostics. L.A.W. also serves as a fibroid consultant to AbbVie, Inc. The other authors declare no competing interests.

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3. Kinematic Design and Evaluation of a Six-Bar Knee-Ankle-Foot Orthosis

   https://doi.org/10.1115/1.4046474  

   Ghosh, Shramana ; Robson, Nina P. ; McCarthy, J. Michael ( May 2020 , Journal of Engineering and Science in Medical Diagnostics and Therapy)

   Abstract This paper presents a new two-step design procedure and preliminary kinematic evaluation of a novel, passive, six-bar knee-ankle-foot orthosis (KAFO). The kinematic design and preliminary kinematic gait analysis of the KAFO are based on motion capture data from a single healthy male subject. Preliminary kinematic evaluation shows that the designed passive KAFO is capable of supporting flexion and extension of the knee joint during stance and swing phases of walking. The two-step design procedure for the KAFO consists of (1) computational synthesis based on user's motion data and (2) performance optimization. In the computational synthesis step, first the lower leg (knee-ankle-foot) of the subject is approximated as a 2R kinematic chain and its target trajectories are specified from motion capture data. Six-bar linkages are synthesized to coordinate the angular movements of knee and ankle joints of the 2R chain at 11 accuracy points. The first step of the design procedure yields 332 six-bar KAFO design candidates. This is followed by a performance optimization step in which the KAFO design candidates are optimally modified to satisfy specified constraints on end-effector trajectory and shape. This two-step process yields an optimally designed passive six-bar KAFO that shows promising kinematic results at themore »knee joint of the user during walking. The preliminary prototype manufactured is cost effective, easy to operate, and suitably demonstrates the feasibility of the proposed concept.« less
4. Ensemble Machine Learning for Alzheimer’s disease Classification from Retinal Vasculature

   Lin, Hely ; Fang, Ruogu ( October 2021 , Biomedical Engineering Society Annual Meeting)

   Introduction: Alzheimer’s disease (AD) causes progressive irreversible cognitive decline and is the leading cause of dementia. Therefore, a timely diagnosis is imperative to maximize neurological preservation. However, current treatments are either too costly or limited in availability. In this project, we explored using retinal vasculature as a potential biomarker for early AD diagnosis. This project focuses on stage 3 of a three-stage modular machine learning pipeline which consisted of image quality selection, vessel map generation, and classification [1]. The previous model only used support vector machine (SVM) to classify AD labels which limited its accuracy to 82%. In this project, random forest and gradient boosting were added and, along with SVM, combined into an ensemble classifier, raising the classification accuracy to 89%. Materials and Methods: Subjects classified as AD were those who were diagnosed with dementia in “Dementia Outcome: Alzheimer’s disease” from the UK Biobank Electronic Health Records. Five control groups were chosen with a 5:1 ratio of control to AD patients where the control patients had the same age, gender, and eye side image as the AD patient. In total, 122 vessel images from each group (AD and control) were used. The vessel maps were then segmented from fundusmore »images through U-net. A t-test feature selection was first done on the training folds and the selected features was fed into the classifiers with a p-value threshold of 0.01. Next, 20 repetitions of 5-fold cross validation were performed where the hyperparameters were solely tuned on the training data. An ensemble classifier consisting of SVM, gradient boosting tree, and random forests was built and the final prediction was made through majority voting and evaluated on the test set. Results and Discussion: Through ensemble classification, accuracy increased by 4-12% relative to the individual classifiers, precision by 9-15%, sensitivity by 2-9%, specificity by at least 9-16%, and F1 score by 712%. Conclusions: Overall, a relatively high classification accuracy was achieved using machine learning ensemble classification with SVM, random forest, and gradient boosting. Although the results are very promising, a limitation of this study is that the requirement of needing images of sufficient quality decreased the amount of control parameters that can be implemented. However, through retinal vasculature analysis, this project shows machine learning’s high potential to be an efficient, more cost-effective alternative to diagnosing Alzheimer’s disease. Clinical Application: Using machine learning for AD diagnosis through retinal images will make screening available for a broader population by being more accessible and cost-efficient. Mobile device based screening can also be enabled at primary screening in resource-deprived regions. It can provide a pathway for future understanding of the association between biomarkers in the eye and brain.« less
5. Fecundability in relation to use of mobile computing apps to track the menstrual cycle

   https://doi.org/10.1093/humrep/deaa176  

   Stanford, Joseph B ; Willis, Sydney K ; Hatch, Elizabeth E ; Rothman, Kenneth J ; Wise, Lauren A ( September 2020 , Human Reproduction)

   Abstract STUDY QUESTION To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence fecundability among women trying to conceive? SUMMARY ANSWER After adjusting for potential confounders, use of any of several different apps was associated with increased fecundability ranging from 12% to 20% per cycle of attempt. WHAT IS KNOWN ALREADY Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive. STUDY DESIGN, SIZE, DURATION The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21–45 years, trying to conceive and not using contraception or fertility treatment at baseline. PARTICIPANTS/MATERIALS, SETTING, METHODS We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reportedmore »whether they used mobile computing apps to track their menstrual cycles (‘cycle apps’) and, if so, which one(s). We estimated fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent use of fertility indicators: basal body temperature, cervical fluid, cervix position and/or urine LH. MAIN RESULTS AND THE ROLE OF CHANCE Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as ‘selected apps’). The use of any app at baseline was associated with 20% increased fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12–15% increased fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3–6 cycles) or cycle regularity. For use of the selected apps, we observed higher fecundability among women with a history of subfertility: FR 1.33 (1.05–1.67). LIMITATIONS, REASONS FOR CAUTION Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations. WIDER IMPLICATIONS OF THE FINDINGS Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase fecundability (per-cycle pregnancy probability) by about 12–20% for couples trying to conceive. We did not find consistent evidence of improved fecundability resulting from use of one specific app over another. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A.« less