ROC confidence bands

Analysis of high-throughput proteomic/genomic data, in particular, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) data and microarray data, has led to a multitude of techniques aimed at identifying potential biomarkers. Most of the statistical techniques for comparing two groups are based on qualitative measures such as P-value. A quantitative way such as interval estimation for the contrasts of two groups is more appealing. We have devised a simultaneous confidence bands method capable of detecting potential biomarkers, while controlling for overall confidence coverage level, in high-dimensional datasets that discriminate two treatment groups using a permutation scheme. For example, for the SELDI-TOF MS data, we deal with the entire spectrum simultaneously and construct (1 - alpha) confidence bands for the mean differences between groups. Furthermore, peaks were identified based on the maximal differences between the groups as determined by the confidence bands. The analysis method herein described gives both qualitative (P-value) and quantitative data (magnitude of difference). The Clinical Proteomics Programs Databank's ovarian cancer dataset and data from in-house samples containing known spiked-in proteins were analyzed. We were able to identify potential biomarkers similar to those described in previous analysis of the ovarian cancer data, however, while these markers are highly significant between cancer and normal groups, our analysis indicated the absolute difference between the two groups was minimal. In addition, we found additional markers than those previously described with greater differences in average intensities. The proposed confidence bands method successfully detected the spiked-in peaks, as well as, secondary peaks generated by adducts and double-charged species. We also illustrate our method utilizing paired gene expression data from a prostate cancer microarray experiment by constructing confidence bands for the fold changes between cancer and normal samples. R-package, 'seie.zip' (license: GNU GPL), is publiclly available at http://research2.dfci.harvard.edu/dfci/MS_spike-in_data/

Chemical heuristics have been fundamental to the advancement of chemistry and materials science. These heuristics are typically established by scientists using knowledge and creativity to extract patterns from limited datasets. Machine learning offers opportunities to perfect this approach using computers and larger datasets. Here, we discuss the relationships between traditional heuristics and machine learning approaches. We show how traditional rules can be challenged by large-scale statistical assessment and how traditional concepts commonly used as features are feeding the machine learning techniques. We stress the waste involved in relearning chemical rules and the challenges in terms of data size requirements for purely data-driven approaches. Our view is that heuristic and machine learning approaches are at their best when they work together.

Finding a new drug which is both safe and efficient is an expensive and time-consuming endeavour. In particular, establishing the ‘dose-effect relationship’ – how beneficial a drug is at different dosages – can be challenging. Predicting this curve requires gathering experimental data by exposing and recording how cells respond to various levels of the drug. However, extreme values are often observed at low and high dosages, potentially introducing errors that are hard to correct in the prediction process. Yet, these extreme observations are sometimes genuine so researchers cannot just ignore them. To improve dose-effect estimation, Zhou, Liu, Fang et al. developed a new general-purpose approach. It uses advanced statistical modelling to account for extremes in lab data. This strategy outperformed other methods when dealing with these observations while also providing higher efficiency in data analysis with more uniform data in experiments. To facilitate implementation, Zhou, Liu, Fang et al. set up a user-friendly tool baptized ‘REAP’; this free online resource allows scientists without advanced statistical experience to harness the new approach and to perform dose-effect analysis more easily and accurately. This could boost research across many different disciplines that examine the effects of chemicals on cells.

As machine learning research in the field of cardiovascular imaging continues to grow, obtaining reliable model performance estimates is critical to develop reliable baselines and compare different algorithms. While the machine learning community has generally accepted methods such as k-fold stratified cross-validation (CV) to be more rigorous than single split validation, the standard research practice in medical fields is the use of single split validation techniques. This is especially concerning given the relatively small sample sizes of datasets used for cardiovascular imaging. We aim to examine how train-test split variation impacts the stability of machine learning (ML) model performance estimates in several validation techniques on two real-world cardiovascular imaging datasets: stratified split-sample validation (70/30 and 50/50 train-test splits), tenfold stratified CV, 10 × repeated tenfold stratified CV, bootstrapping (500 × repeated), and leave one out (LOO) validation. We demonstrate that split validation methods lead to the highest range in AUC and statistically significant differences in ROC curves, unlike the other aforementioned approaches. When building predictive models on relatively small data sets as is often the case in medical imaging, split-sample validation techniques can produce instability in performance estimates with variations in range over 0.15 in the AUC values, and thus any of the alternate validation methods are recommended.

We show that a number of apparently disparate problems, involving distribution approximations in the presence of discontinuities, are actually closely related. One class of such problems involves developing bootstrap approximations to the distribution of a sample mean when the sample includes both ordinal and continuous data. Another class involves smoothing a lattice distribution so as to overcome rounding errors in the normal approximation. A third includes kernel methods for smoothing distribution estimates when constructing confidence bands. Each problem in these classes may be modelled in terms of sampling from a mixture of a continuous and a lattice distribution. We quantify the proportion of the continuous component that is sufficient to smooth away difficulties caused by the lattice part. The proportion is surprisingly small ? it is only a little larger than n_1 logn, where ? denotes sample size. Therefore, very few continuous variables are required in order to render a continuity correction unnecessary. The implications of this result in the problem of sampling both ordinal and continuous data are discussed, and numerical aspects are described through a simulation study. The result is also used to characterise bandwidths that are appropriate for smoothing distribution estimators in the confidence band problem. In this setting an empirical method for bandwidth choice is suggested, and a particularly simple derivation of Edgeworth expansions is given.

The machine learning method, now widely used for predicting well performance from unconventional reservoirs in the industry, generally needs large data sets for model development and training. The large data sets, however, are not always available, especially for newly developed unconventional plays. The objective of this work is to develop an innovative machine learning method for predicting well performance in unconventional reservoirs with a relatively small data set. For a small training data set, the corresponding machine learning model can significantly suffer from so-called overfitting meaning that the model can match the training data but has poor predictivity. To overcome this, our new method averages predictions from multiple models that are developed with the same model input, but different initial guesses of model parameters that are unknowns in a machine learning algorithm and determined in the model training. The averaged results are used for the final model prediction. Unlike traditional ensemble learning methods, each prediction in the new method uses all the input data rather than its subset. We mathematically prove that the averaged prediction provides less model uncertainty and under certain conditions the optimum prediction. It is also demonstrated that the method practically minimizes the overfitting and gives relatively unique prediction. The usefulness of the method is further confirmed by its successful application to the data set collected from less than 100 wells in an unconventional reservoir. Sensitivity results with the trained machine learning model show that the model results are consistent with the domain knowledge regarding the production from the reservoir.

Machine learning algorithms are occupying a larger space in medical and urology applications. However, typical medical physicians are not trained on these technologies and do not master the possibilities offered by these tools, to imagine their applications in the medical field. This manuscript is indented to be a guide in the use of machine learning in different urology applications, and to demystify the available machine learning and artificial intelligence algorithms. This manuscript reviews some of their applications and potential applications to the medical and urology field. Multiple works are published on the use of machine learning in urology, with performance demonstrated to be noninferior to human experts on multiple occasions. However, the major part of the machine learning publications in urology applications are concentrated on diagnosis and/or prognosis. Advanced machine learning algorithms based on agentic artificial intelligence, able to perform decisions and causality-based treatment optimization, are rarely put to use in urology. The democratization of advanced machine learning technologies in the medical fields can accelerate the adoption of these techniques, and potentially improve the patient care through relevant suggestive decision making. This work aims to demystify the machine learning tools for medical applications, facilitate decision making and adoption of the correct tools for the correct applications, and places a roadmap for the future of machine learning in the enhancement of patient care in urology.

Full text Figures and data Side by side Abstract Editor's evaluation Introduction Materials and methods Results Discussion Data availability References Decision letter Author response Article and author information Metrics Abstract Background: Oxygen uptake (VO2) is one of the most important measures of fitness and critical vital sign. Cardiopulmonary exercise testing (CPET) is a valuable method of assessing fitness in sport and clinical settings. There is a lack of large studies on athletic populations to predict VO2max using somatic or submaximal CPET variables. Thus, this study aimed to: (1) derive prediction models for maximal VO2 (VO2max) based on submaximal exercise variables at anaerobic threshold (AT) or respiratory compensation point (RCP) or only somatic and (2) internally validate provided equations. Methods: Four thousand four hundred twenty-four male endurance athletes (EA) underwent maximal symptom-limited CPET on a treadmill (n=3330) or cycle ergometer (n=1094). The cohort was randomly divided between: variables selection (nrunners = 1998; ncyclist = 656), model building (nrunners = 666; ncyclist = 219), and validation (nrunners = 666; ncyclist = 219). Random forest was used to select the most significant variables. Models were derived and internally validated with multiple linear regression. Results: Runners were 36.24±8.45 years; BMI = 23.94 ± 2.43 kg·m−2; VO2max=53.81±6.67 mL·min−1·kg−1. Cyclists were 37.33±9.13 years; BMI = 24.34 ± 2.63 kg·m−2; VO2max=51.74±7.99 mL·min−1·kg−1. VO2 at AT and RCP were the most contributing variables to exercise equations. Body mass and body fat had the highest impact on the somatic equation. Model performance for VO2max based on variables at AT was R2=0.81, at RCP was R2=0.91, at AT and RCP was R2=0.91 and for somatic-only was R2=0.43. Conclusions: Derived prediction models were highly accurate and fairly replicable. Formulae allow for precise estimation of VO2max based on submaximal exercise performance or somatic variables. Presented models are applicable for sport and clinical settling. They are a valuable supplementary method for fitness practitioners to adjust individualised training recommendations. Funding: No external funding was received for this work. Editor's evaluation The authors have established new formulas to predict maximum oxygen uptake for cyclists and runners based on submaximal exercise testing and anthropometric characteristics. This is an important study with a large and comprehensive dataset, which may be helpful for many exercise labs. The work is convincing, using appropriate and validated methodology in line with the current state-of-the-art, as shown by references to common exercise books. https://doi.org/10.7554/eLife.86291.sa0 Decision letter Reviews on Sciety eLife's review process Introduction The oxygen uptake (VO2) is considered an important metric in assessing cardiorespiratory fitness, health status, or endurance performance potential (Guazzi et al., 2012). With the application of standardised procedures and interpretation protocols, during graded exercise tests (GXT), the (maximal oxygen uptake) VO2max can be established (Bentley et al., 2007). GXT is the most widely used assessment to examine the dynamic relationship between exercise and integrated physiological systems (Albouaini et al., 2007; Bentley et al., 2007). The information from GXT during cardiopulmonary exercise testing (CPET) can be applied across the spectrum of sport performance, occupational safety screening, research, and clinical diagnostics (Guazzi et al., 2017). VO2 max is often used as a boundary between severe and extreme intensity domains and by definition requires maximal effort from the tested subject (Gaesser and Poole, 1996). However, it is not always recommended or possible to undertake a test to exhaustion (Guazzi et al., 2012). For the athletes, the proximity of competition or injury history can allow submaximal testing, but not testing to exhaustion (Sassi et al., 2006). Testing that requires maximal effort may be disruptive to the training process or interfere with race performance (Coutts et al., 2007; Lamberts et al., 2011). Due to practical constraints, tests to exhaustion or peak-power-output tests are often performed only two or three times a year (Coutts et al., 2007). However, VO2 values are widely used in sport science and the decision-making process (Mann et al., 2013). VO2 is widely considered one of the major endurance performance determinants (Joyner and Coyle, 2008). Using VO2max to guide the selection process, prescribing training intensity, assessing training adaptations, or predicting race times is a common practice in high-performance sports (Bassett and Howley, 2000; Bentley et al., 2007; Hawley and Noakes, 1992; Noakes et al., 1990). VO2max is also one of the critical vital signs coordinating the function of the cardiovascular, respiratory, and muscular systems, it is an indicator of overall body health status (Kaminsky et al., 2017). Quantifying VO2max provides additional input regarding clinical decision-making, risk stratification, evaluation of therapy, and physical activity guidelines (Guazzi et al., 2012). For patients undertaking a test to exhaustion is rarely needed or possible due to health restraints or cardiac risk (Guazzi et al., 2016). For many years researchers have studied indirect methods of estimating VO2max(Sartor et al., 2013). Protocols such as the Astrand-Ryhming Test, Six-Minute Walk Test, or YMCA Step Test have been established and validated (Astrand and Ryhming, 1954; Beutner et al., 2015; Carey, 2022; Jalili et al., 2018). Moreover, estimation of the VO2 and heart rate (HR) values below the ventilatory threshold can be based on cardiorespiratory kinetics assessment using randomised changes in the work rate known as a pseudo-random binary sequences testing (Hoffmann et al., 2022). However, with the development of technology, the accessibility of laboratory testing and mobile testing improved (Montoye et al., 2020; Pritchard et al., 2021). Therefore, new opportunities to develop more precise yet simple and accessible methods and models to assess VO2max occur (Jurov et al., 2023). This appears to be especially important considering the low prediction accuracy of most of the VO2max formulae that were validated in our previous study (Wiecha et al., 2023). Recently, we have been observing the development of prediction methods with the usage of machine learning (ML) and artificial intelligence (AI) (Ashfaq et al., 2022). Both ML and AI are used in sport science as forecasting and decision-making support tools (Abut and Akay, 2015; Bobowik and Wiszomirska, 2022; Chmait and Westerbeek, 2021; Hammes et al., 2022; Rossi et al., 2021). There is growing evidence that VO2max prediction based on ML models, especially support vector ML and artificial neural network models, exhibits more robust and accurate results compared to MLR only (Abut and Akay, 2015; Ashfaq et al., 2022). Therefore, in this research, with the support of ML, we look for algorithms and prediction patterns that allow us to use values obtained during submaximal CPET and somatic measurements to estimate maximal VO2max values in male runners and cyclists. We stipulate that prediction models allow for accurate calculation of VO2max based on somatic or submaximal CPET variables. Materials and methods We have applied the development and validation of the prediction TRIPOD guidelines to conduct the study (see Supplementary Material 1TRIPOD Checklist for Prediction Model Development and Validation) (Collins et al., 2015). The study is based on retrospective data analysis from the CPET registry collected from 2013 to 2021 at the medical clinic (Sportslab, Warsaw, Poland). All CPET have been performed at the individual request of participants, as a part of regular training monitoring or performance assessment. Ethical approval Request a detailed protocol The Institutional Review Board of the Bioethical Committee at the Medical University of Warsaw (AKBE/32/2021) has approved the study protocol. The regulations of the Declaration of Helsinki were met during all parts of the study. Each study participant delivered written consent to undergo CPET and participate in the study. Derivation cohort Request a detailed protocol We selected the cohort with the use of rigorous exclusion/inclusion criteria. Due to the insufficient number of women in our database and the number of potential variables in the regression models for adequate power, we had to limit ourselves to conduct analysis in the male population only (Martens and Logan, 2021). Out of 6439 healthy, adult male cyclists and long-distance runners that undergone CPET, 4423 met the criteria as further: (1) age ≥18 years, (2) declared regular cycling or running training for ≥3 months, (3) had no extreme outliers ≤ or ≥±3 standard deviations (SD) from mean for all of the testing variables (beyond ≥±3 SD in VO2max), (4) lack of any injury, medical condition, or addiction in medical history that may affect exercise capacity, (5) not taking any medications with a modifying effect on exercise capacity, (6) maximum exertion achieved during CPET. We defined the maximum exertion in CPET as the fulfilment of the minimum six of the following criteria: (1) respiratory exchange ratio (RER) ≥1.10, (2) present VO2 plateau (growth <100 mL·min–1 in VO2 despite increased running speed or cycling power), (3) respiratory frequency (fR) ≥45 breaths·min–1, (4) declared subjective exertion intensity during CPET ≥18 in the Borg scale (Borg, 1970), (5) blood lactate concentration [La-]b ≥8 mmol·L–1, (6) growth in speed/power ≥10% of respiratory compensation point (RCP) values after exceeding the RCP, (7) peak heart rate (HRpeak) ≥15 beats·min–1 below predicted maximal heart rate (HRmax) (Lach et al., 2021). Participants’ selection procedure has been shown in Figure 1. Figure 1 Download asset Open asset Flowchart of the preliminary inclusion and exclusion process. Abbreviations: EA, endurance athlete; CPET, cardiopulmonary exercise testing; SD, standard deviation; TE, treadmill; RER, respiratory exchange ratio; VO2, oxygen uptake (mL·min−1·kg−1); [La−]b, lactate concentration (mmol·L−1); fR, breathing frequency (breaths·min−1); RCP, respiratory compensation point; HRpeak, peak heart rate (beats·min−1); HRmax, maximal heart rate (bpm). At both stages of the selection, some participants met several (>1) exclusion criteria. Somatic measurements and CPET protocols Request a detailed protocol Body mass was measured with a body composition (BC) analyser (Tanita, MC 718, Japan) with the multifrequency of 5 kHz/50 kHz/250 kHz via the bioimpedance analysis and normal testing mode. The participants’ skin was cleaned with alcohol before placing the electrodes on the skin. Prior to the test, the participants received instructions to refrain from exercising for 2 hr, consume a light meal rich in carbohydrates 2–3 hr beforehand, and maintain hydration by drinking isotonic beverages. Additionally, they were advised to abstain from medications, caffeine, and cigarettes on the day of the test. Running CPET (TE) was performed on a mechanical treadmill (h/p/Cosmos Quasar, Germany). Cycling CPET (CE) was performed on Cyclus-2 (RBM elektronik-automation GmbH, Leipzig, Germany). Hans Rudolph V2 mask (Hans Rudolph, Inc, Shawnee, KS, USA), breath-by-breath method with Cosmed Quark CPET gas exchange analysing device (Cosmed Srl, Rome, Italy), and Quark PFT Suite to Omnia 1.6 software were utilised. The gas analyser device was regularly calibrated with the reference gas (16% O2; 5% CO2) in accordance with the manufacturer’s instructions (Airgas USA, LLC, Plumsteadville, PA, USA). From 2013 to 2021, three Cosmed Quark CPET units were used. HR was measured with the Cosmed torso belt (Cosmed srl, Rome, Italy). [La-]b was measured via enzymatic-amperometric electrochemical technique with Super GL2 analyser (Müller Gerätebau GmbH, Freital, Germany). The [La-]b analyser was regularly calibrated before each measurement series. The 40 m2 indoor, air-conditioned laboratory with 20–22°C temperature and 40–60% humidity, and 100 m ASL provided the same conditions for all BC and CPET. Each CPET began with a 5 min personalised warm-up (walk or easy jog with ‘conversational’ intensity for running, easy pedalling with ‘conversational’ intensity for cycling). Then after the preparation (about 5 min), the continuous progressive step test was conducted. Due to the population diversity (training status), the running test speed started from 7 to 12 km·hr–1 with a 1% treadmill incline. The choice of initial starting speed was determined by the interview and sports results achieved. For example, those running less than 60 min at a distance of 10 km started the test at 7 km/hr, while those running 10 km for less than 35 min started the test at an initial speed of 12 km/hr. The pace increased by 1 km·hr–1 every 2 min with no change in incline. The cycling test began at 60–150 W, depending on the athletes training status. The power increased by 20–30 W every 2 min. It was recommended to maintain a constant cadence of 80–90 (repetition·min–1) during the test. The tests were terminated due to exhaustion: volitional inability to continue the activity or/and VO2 and HR plateau with increasing load or/and observed disturbance of coordination in running or/and inability to maintain the set cadence. Due to the graded protocol used, the cycling power and running speed values have been calculated as a function of time to better reflect the actual level for the test moment being determined (Kuipers et al., 1985). Before the test, after every step, and 3 min after the termination of the effort technician took a 20 µL blood sample from a fingertip. Samples were collected during the test without interrupting the effort. The samples were taken from the initial puncture. The first blood drop was collected into the swab and the second blood drop was drawn for further analysis into the capillary. VO2max was recorded as the highest value (15 s intervals) before the termination of the test. HRmax was recorded as the highest value obtained at the end of the test, without averaging. The anaerobic threshold (AT) was established with the following criteria: (1) common start of VE/VO2 and VE/VCO2 curves, (2) end-tidal partial pressure of oxygen raised constantly with the end-tidal partial pressure of carbon dioxide (Beaver et al., 1986). The was established with the following criteria: (1) PetCO2 must decrease after reaching maximal amount, (2) the presence of fast nonlinear growth in VE (second deflection), (3) the VE/VCO2 ratio achieved minimum and started to rise, and (4) a nonlinear increase in VCO2 versus VO2 (lack of linearity) (Beaver et al., 1986). The [La-]b was estimated for AT and RCP in relation to power or speed (Wiecha et al., 2022). Data analysis Request a detailed protocol Our comprehensive ML approach enables the evaluation of each formula by preliminary variables precision (at the stage of selection), then accuracy (during the model’s building) and recall (in internal validation). Individual CPET results were saved into the Excel file (Microsoft Corporation, Redmond, WA, USA) and a custom-made script was used to generate the database in Excel (Python programming). Further, mean, SD, and 95% confidence intervals (CI) were calculated. The normality of the distribution of the data was examined using the Shapiro-Wilk test and intergroup differences were calculated using the Student’s t-test for independent variables. Three-step variable selection procedures based on random forests were applied using the R package VSURF in RStudio software (R Core Team, Vienna, Austria; version 3.6.4) (Genuer et al., 2016). For each level of measurement (AT, RCP) and their combination (AT+RCP), significant variables were identified separately. The first step was dedicated to eliminate irrelevant variables from the dataset. Second step aimed to select all variables related to the response for interpretation purposes. The third step refined the selection by eliminating redundancy in the set of variables selected by the second step, for prediction purposes (Genuer et al., 2017). Each time for variables selection, the anthropometric variables as in Tables 1–2 and the CPET parameters given in Tables 3–4 from a specific level of measurement (AT; RCP) and their combinations were visible. Table 1 Basic anthropometric characteristics for runners. Variable (unit)Derivation group n=1998Testing group n=666Validation group n=666MeanCISDMeanCISDMeanCISDAge (years)36.235.6–36.98.4535.935.5–36.38.0535.534.9–36.28.14Height (cm)180.0179.6–180.56.04179.4179.1–179.76.13179.7179.2–180.26.61BM (kg)77.777.0–78.49.3577.777.3–78.19.2977.977.1–78.610.1BMI (kg·m–2)23.923.8–24.12.4324.124.0–24.22.4124.123.9–24.32.56BF (%)15.415.1–15.74.5515.515.3–15.74.5215.415.1–15.84.55FM (kg)12.211.9–12.64.6812.312.1–12.54.6512.311.9–12.74.92FFM (kg)65.565.0–66.06.4365.465.1–65.76.3165.665.1–66.16.86 BM, body mass; BMI, body mass index; BF, body fat; FM, fat mass; FFM, fat-free mass; CI, 95% confidence interval; SD, standard deviation. Table 2 Basic anthropometric characteristics for cyclists. Variable (unit)Derivation group n=656Testing group n=219Validation group n=219MeanCISDMeanCISDMeanCISDAge (years)37.336.6–38.09.1337.135.9–38.49.5037.636.5–38.88.46Height (cm)179.9179.4–180.46.27180.1179.2–181.06.96180.2179.4–181.06.13BM (kg)78.878.1–79.69.8079.177.7–80.510.479.878.4–81.310.9BMI (kg·m–2)24.324.1–24.62.6324.424.0–24.72.8024.624.2–25.02.96BF (%)16.415.7–17.14.9916.115.7–16.54.8116.215.5–16.84.87FM (kg)13.312.6–14.15.6613.012.6–13.45.2713.312.5–14.05.85FFM (kg)65.864.9–66.66.2565.865.4–66.36.0666.665.7–67.46.58 BM, body mass; BMI, body mass index; BF, body fat; FM, fat mass; FFM, fat-free mass; CI, 95% confidence interval; SD, standard deviation. Table 3 Cardiopulmonary exercise testing (CPET) characteristics for runners. Variable (unit)Derivation group n=1998Testing group n=666Validation group n=666MeanCISDMeanCISDMeanCISDrVO2AT (mL·min–1·kg–1)38.438.1–38.85.0138.538.3–38.74.8838.137.7–38.55.16RERAT0.870.86–0.870.040.870.86–0.870.040.870.86–0.870.04HRAT (beats·min–1)151.5150.8–152.310.3151.0150.6–151.510.8152.0151.2–152.810.8VEAT (L·min–1)79.178.1–80.012.278.377.8–78.912.077.276.3–78.212.0SPEEDAT (km·h–1)11.010.9–11.11.4511.011.0–11.11.3610.910.8–11.01.42LAAT (mmol·L–1)2.082.02–2.140.631.801.76–1.830.622.352.27–2.420.72rVO2RCP (mL·min–1·kg–1)47.547.0–48.05.8847.747.4–48.06.1547.346.8–47.86.16RERRCP1.001.00–1.000.041.001.00–1.000.041.001.00–1.000.03HRRCP (beats·min–1)173.4172.7–174.19.21173.2172.8–173.69.30174.3173.5–175.09.50VERCP (L·min–1)114.7113.5–116.015.9113.9113.1–114.616.7112.7111.4–114.016.2SPEEDRCP (km·h–1)14.013.9–14.11.7714.114.0–14.11.7013.913.8–14.11.75LARCP (mmol·L–1)4.724.63–4.821.044.404.34–4.451.044.814.69–4.931.14rVO2max (mL·min–1·kg–1)53.853.3–54.36.6754.354.0–54.66.9553.853.3–54.37.09 CI, 95% confidence interval; SD, standard deviation; rVO2AT, oxygen uptake at anaerobic threshold relative to body mass; RERAT, respiratory exchange ratio at anaerobic threshold; HRAT, heart rate at anaerobic threshold; VEAT, pulmonary ventilation at anaerobic threshold; SPEEDAT, velocity at anaerobic threshold; LAAT, blood lactate concentration at anaerobic threshold; rVO2RCP, oxygen uptake at respiratory compensation point relative to body mass; RERRCP, respiratory exchange ratio at respiratory compensation point; HRRCP, heart rate at respiratory compensation point; VERCP, pulmonary ventilation at respiratory compensation point; SPEEDRCP, velocity at respiratory compensation point; LARCP, blood lactate concentration at respiratory compensation point; rVO2max, maximal oxygen uptake relative to body mass. Table 4 Cardiopulmonary exercise testing (CPET) characteristics for cyclists. Variable (unit)Derivation group n=656Testing group n=219Validation group n=219MeanCISDMeanCISDMeanCISDrVO2AT (mL·min–1·kg–1)33.032.5–33.45.8433.232.4–33.95.6833.732.9–34.55.89RERAT0.870.87–0.870.040.870.87–0.880.040.870.87–0.880.04HRAT CI, 95% confidence interval; SD, standard deviation; rVO2AT, oxygen uptake at anaerobic threshold relative to body mass; RERAT, respiratory exchange ratio at anaerobic threshold; HRAT, heart rate at anaerobic threshold; VEAT, pulmonary ventilation at anaerobic threshold; power at anaerobic threshold relative to body mass; LAAT, blood lactate concentration at anaerobic threshold; rVO2RCP, oxygen uptake at respiratory compensation point relative to body mass; RERRCP, respiratory exchange ratio at respiratory compensation point; HRRCP, heart rate at respiratory compensation point; VERCP, pulmonary ventilation at respiratory compensation point; LARCP, blood lactate concentration at respiratory compensation point; power at respiratory compensation point relative to body mass; rVO2max, maximal oxygen uptake relative to body mass. selection variables were in the further only selected parameters were into multiple linear regression The data for MLR model building were randomly into that is testing, validation and of the a only significant were in the Derived are by the of mean and mean analysis was used to the model’s precision and accuracy during validation and tests to the fulfilment of MLR test the of in MLR test assessment between and test of Each model was examined the and any have not been 2 package in RStudio (R Core Team, Vienna, Austria; version version for and software version were used in was considered as the Results Somatic measurements and CPET results data of the runners models for testing, and validation are in Table while cyclists are in Table The runners of and for testing, and validation the cyclists and differences between of runners and cyclists were in BMI and between testing in all between validation only in CPET results for runners models are in Table 3 and for cyclists in Table Runners in the cohort achieved relative to body mass VO2max of in testing group and in validation group cyclists mean was and for testing, and validation to body mass oxygen uptake at anaerobic threshold in runners for ± ± and ± of in testing, and validation it was ± ± and ± of rVO2max, relative to body mass oxygen uptake at respiratory compensation point in runners for ± ± and ± of for testing, and validation while in cyclists for ± ± and ± of rVO2max, There were no significant differences in values between testing, and validation the runners and cyclists between runners and cyclists results were all significant Prediction models based on AT and RCP Full of MLR prediction models for cyclists are in Table for runners in Table The models prediction performance is as with and for cyclists from for somatic parameters to for RCP equations. For runners from for to for AT and equations. for cyclists models was the for RCP and the highest for For from for AT and to for equation. observed for cyclists was the for RCP in the validation group and the highest for while in runners the for AT and and the highest for The performance of prediction is in Figure Figure 2 Download asset Open asset of prediction for Abbreviations: maximal oxygen anaerobic threshold; RCP, respiratory compensation point; All values are in performance for running while the performance for cycling equations. performance of the prediction model for for for AT and for somatic-only equation. Table 5 VO2max prediction for cyclists. linear regression group group = = = = based on anaerobic threshold; RCP, based on respiratory compensation point; based on somatic variables mean mean maximal oxygen uptake relative to body mass rVO2AT, oxygen uptake at anaerobic threshold relative to body mass power at anaerobic threshold relative to body mass rVO2RCP, oxygen uptake at respiratory compensation point relative to body mass VERCP, pulmonary ventilation at respiratory compensation point BF, body fat BM, body mass Table VO2max prediction for runners. linear regression group group = = = = based on anaerobic threshold; RCP, based on respiratory compensation point; based on somatic variables mean mean maximal oxygen uptake relative to body mass rVO2AT, oxygen uptake at anaerobic threshold relative to body mass SPEEDAT, velocity at anaerobic threshold FFM, fat mass VEAT, pulmonary ventilation at anaerobic threshold HRAT, heart rate at anaerobic threshold BF, body fat rVO2RCP, oxygen uptake at respiratory compensation point relative to body mass SPEEDRCP, velocity at respiratory compensation point Models validation of each model for cyclists is in Table while for runners in Table the performance of our prediction was to that observed in the

BackgroundBabies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1–2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings.MethodsThis study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed.ResultsOverall model estimated GA had MAE of 5.2 days (95% CI 4.6–6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6–6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31–94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0–99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5–23.7; p = 0.002).ConclusionsMachine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.

The subject of the research is the approach to the possibility of using data science methods in the field of health care for integrated data processing and analysis in order to optimize economic and specialized processes The purpose of writing this article is to address issues related to the specifics of the use of Data Science methods in the field of health care on the basis of comprehensive information obtained from various sources. Methodology. The research methodology is system-structural and comparative analyzes (to study the application of BI-systems in the process of working with large data sets); monograph (the study of various software solutions in the market of business intelligence); economic analysis (when assessing the possibility of using business intelligence systems to strengthen the competitive position of companies). The scientific novelty the main sources of data on key processes in the medical field. Examples of innovative methods of collecting information in the field of health care, which are becoming widespread in the context of digitalization, are presented. The main sources of data in the field of health care used in Data Science are revealed. The specifics of the application of machine learning methods in the field of health care in the conditions of increasing competition between market participants and increasing demand for relevant products from the population are presented. Conclusions. The intensification of the integration of Data Science in the medical field is due to the increase of digitized data (statistics, textual informa- tion, visualizations, etc.). Through the use of machine learning methods, doctors and other health professionals have new opportunities to improve the efficiency of the health care system as a whole. Key words: Data science, efficiency, information, machine learning, medicine, Python, healthcare.

In conventional distributed machine learning methods, distributed support vector machines (SVM) algorithms are trained over pre-configured intranet/internet environments to find out an optimal classifier. These methods are very complicated and costly for large datasets. Hence, we propose a method that is referred as the Cloud SVM training mechanism (CloudSVM) in a cloud computing environment with MapReduce technique for distributed machine learning applications. Accordingly, (i) SVM algorithm is trained in distributed cloud storage servers that work concurrently; (ii) merge all support vectors in every trained cloud node; and (iii) iterate these two steps until the SVM converges to the optimal classifier function. Single computer is incapable to train SVM algorithm with large scale data sets. The results of this study are important for training of large scale data sets for machine learning applications. We provided that iterative training of splitted data set in cloud computing environment using SVM will converge to a global optimal classifier in finite iteration size.

Commentary: Machine learning and cardiac surgery risk prediction

The advent of modern genotyping technologies has revolutionized genomic selection in animal breeding. Large marker datasets have shown several drawbacks for traditional genomic prediction methods in terms of flexibility, accuracy, and computational power. Recently, the application of machine learning models in animal breeding has gained a lot of interest due to their tremendous flexibility and their ability to capture patterns in large noisy datasets. Here, we present a general overview of a handful of machine learning algorithms and their application in genomic prediction to provide a meta-picture of their performance in genomic estimated breeding values estimation, genotype imputation, and feature selection. Finally, we discuss a potential adoption of machine learning models in genomic prediction in developing countries. The results of the reviewed studies showed that machine learning models have indeed performed well in fitting large noisy data sets and modeling minor nonadditive effects in some of the studies. However, sometimes conventional methods outperformed machine learning models, which confirms that there's no universal method for genomic prediction. In summary, machine learning models have great potential for extracting patterns from single nucleotide polymorphism datasets. Nonetheless, the level of their adoption in animal breeding is still low due to data limitations, complex genetic interactions, a lack of standardization and reproducibility, and the lack of interpretability of machine learning models when trained with biological data. Consequently, there is no remarkable outperformance of machine learning methods compared to traditional methods in genomic prediction. Therefore, more research should be conducted to discover new insights that could enhance livestock breeding programs.

VENTRICULAR-ARTERIAL DECOUPLING IS ASSOCIATED WITH IN-HOSPITAL ADVERSE EVENTS IN NORMOTENSIVE PULMONARY EMNBOLISM

BackgroundThere is currently a lack of model for predicting the occurrence of venous thromboembolism (VTE) in patients with lung cancer. Machine learning (ML) techniques are being increasingly adapted for use in the medical field because of their capabilities of intelligent analysis and scalability. This study aimed to develop and validate ML models to predict the incidence of VTE among lung cancer patients.MethodsData of lung cancer patients from a Grade 3A cancer hospital in China with and without VTE were included. Patient characteristics and clinical predictors related to VTE were collected. The primary endpoint was the diagnosis of VTE during index hospitalization. We calculated and compared the area under the receiver operating characteristic curve (AUROC) using the selected best-performed model (Random Forest model) through multiple model comparison, as well as investigated feature contributions during the training process with both permutation importance scores and the impurity-based feature importance scores in random forest model.ResultsIn total, 3,398 patients were included in our study, 125 of whom experienced VTE during their hospital stay. The ROC curve and precision–recall curve (PRC) for Random Forest Model showed an AUROC of 0.91 (95% CI: 0.893–0.926) and an AUPRC of 0.43 (95% CI: 0.363–0.500). For the simplified model, five most relevant features were selected: Karnofsky Performance Status (KPS), a history of VTE, recombinant human endostatin, EGFR-TKI, and platelet count. We re-trained a random forest classifier with results of the AUROC of 0.87 (95% CI: 0.802–0.917) and AUPRC of 0.30 (95% CI: 0.265–0.358), respectively.ConclusionAccording to the study results, there was no conspicuous decrease in the model’s performance when use fewer features to predict, we concluded that our simplified model would be more applicable in real-life clinical settings. The developed model using ML algorithms in our study has the potential to improve the early detection and prediction of the incidence of VTE in patients with lung cancer.