While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation compared to single-hit (SH) in lower-risk myelodysplastic syndrome (MDS), data are conflicting in ...both higher-risk MDS and acute myeloid leukemia (AML). We conducted an indepth analysis utilizing data from 10 US academic institutions to study differences in molecular characteristics and outcomes of SH (n= 139) versus MH (n= 243) TP53MTAML. Complex cytogenetics (CG) were more common in MH compared to SH TP53MT AML (p <0.001); whereas ASXL1 (p= <0.001), RAS (p<0.001), splicing factor (p= 0.003), IDH1/2 (p= 0.001), FLT3 ITD (p= <0.001) and NPM1 (p= 0.005) mutations significantly clustered with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between SH and MH (event free survival EFS: 3.0 vs 2.20 months, p= 0.22/ overall survival OS: 8.50 vs 7.53 months, respectively, p= 0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation (allo-HCT) as a time-dependent covariate were associated with superior EFS (HR; 0.44, 95% CI: 0.19-1.01, p= 0.05/ HR; 0.34, 95% CI: 0.18-0.62, p<0.001) and OS (HR; 0.24, 95% CI: 0.08-0.71, p= 0.01/ HR; 0.28, 95% CI: 0.16-0.47, p<0.001). While complex CG (HR; 1.56, 95% CI: 1.01-2.40, p= 0.04) retained unfavorable significance for OS. Our analysis suggests that unlike in MDS, multihit TP53MT is less relevant in independently predicting outcomes in patients with AML.
The purpose of this study is to develop non-exercise (N-Ex) VO2max prediction models by using support vector regression (SVR) and multilayer feed forward neural networks (MFFNN). VO2max values of 100 ...subjects (50 males and 50 females) are measured using a maximal graded exercise test. The variables; gender, age, body mass index (BMI), perceived functional ability (PFA) to walk, jog or run given distances and current physical activity rating (PA-R) are used to build two N-Ex prediction models. Using 10-fold cross validation on the dataset, standard error of estimates (SEE) and multiple correlation coefficients (R) of both models are calculated. The MFFNN-based model yields lower SEE (3.23mlkg−1min−1) whereas the SVR-based model yields higher R (0.93). Compared with the results of the other N-Ex prediction models in literature that are developed using multiple linear regression analysis, the reported values of SEE and R in this study are considerably more accurate. Therefore, the results suggest that SVR-based and MFFNN-based N-Ex prediction models can be valid predictors of VO2max for heterogeneous samples.
This study sought to develop a regression model to predict maximal oxygen uptake (VO
2max
) based on submaximal treadmill exercise (EX) and non-exercise (N-EX) data involving 116 participants, ages ...18-65 years. The EX data included the participants' self-selected treadmill speed (at a level grade) when exercise heart rate first reached at least 70% of predicted maximum heart rate (HR
max
; 220 - age) by the end of any one of three 4-min consecutive stages involving walking (3.0-4.0 mph; Stage 1), jogging (4.1-6.0 mph; Stage 2), and running (> 6.0 mph; Stage 3). The N-EX data included various demographic (age, gender), biometric (body mass), and questionnaire (participants' perceived functional ability PFA to walk, jog, or run given distances, and their self-reported level of physical activity PA-R) information. All participants (n = 100) who completed the study requirements and successfully achieved a maximal level of exertion during a graded exercise test (GXT) to assess VO
2max
(mean ± SD; 41.39 ± 9.15 ml · kg
−1
· min
−1
) were included in the data analysis. Stepwise regression was used to generate the following prediction equation (R = .94, SEE = 3.09 ml · kg
−1
· min
−1
): VO
2max
(ml · kg
−1
· min
−1
) = 30.04 + (6.37 × gender; females = 0, males = 1) - (0.243 × age) - (0.122 × body mass) + (3.263 × ending self-selected treadmill speed; mph) + (0.391 × PFA) + (0.669 × PA-R). Each of the predictor variables were statistically significant (p < .001) and cross-validation procedures using PRESS (predicted residual sum of squares) statistics revealed minimal shrinkage (R
p
= .92 and SEE
p
= 3.29 ml · kg
−1
· min
−1
). In summary, this submaximal treadmill test and accompanying regression model yields relatively accurate VO
2max
estimates in healthy men and women (ages 18-65 years) using both EX and N-EX data.
