In some clinical applications in oncology randomized, double armed, and double-blind trials are not possible. In case of device applications, double-blinded conditions are nonrealistic, and with many times the randomi...In some clinical applications in oncology randomized, double armed, and double-blind trials are not possible. In case of device applications, double-blinded conditions are nonrealistic, and with many times the randomization also has complications due to the high-line treatments where the reference cohort is not available;the active “arm” has mainly palliative initiative. Sometimes highly personalized therapies block the collection of the homogeneous group and limit its double-arm randomization. Our objective is to discuss the situations of the single arm evaluation and to give methods for the mining of information from this to increase the level of evidence of the measured dataset. The basic idea of the data-separation is the appropriate parameterization of the non-parametric Kaplan-Meier survival pattern by the poly-Weibull fit.展开更多
The Gompertz model is the long-time well-known mathematical model of exponential expression among mortality models in the literature that are used to describe mortality and survival data of a population. The death rat...The Gompertz model is the long-time well-known mathematical model of exponential expression among mortality models in the literature that are used to describe mortality and survival data of a population. The death rate of the “probacent” model developed by the author based on animal experiments, clinical applications and mathematical reasoning was applied to predict age-specific death rates in the US elderly population, 2001, and to express a relationship among dose rate, duration of exposure and mortality probability in total body irradiation in humans. The results of both studies revealed a remarkable agreement between “probacent”-formula-predicted and published-reported values of death rates in the US elderly population or mortality probabilities in total body irradiation in humans (p - value > 0.995 in χ2 test in each study). In this study, both the Gompertz and “probacent” models are applied to the Sacher’s comprehensive experimental data on survival times of mice daily exposed to various doses of total body irradiation until death occurs with an assumption that each of both models is applicable to the data. The purpose of this study is to construct general formulas expressing relationship between dose rate and survival time in total body irradiation in mice. In addition, it is attempted to test which model better fits the reported data. The results of the comparative study revealed that the “probacent” model not only fit the Sacher’s reported data but also remarkably better fit the reported data than the Gompertz model. The “probacent” model might be hopefully helpful in research in human tolerance to low dose rates for long durations of exposure in total body irradiation, and further in research in a variety of biomedical phenomena.展开更多
On the basis of experimental observations on animals, applications to clinical data on patients and theoretical statistical reasoning, the author developed a com-puter-assisted general mathematical model of the ‘prob...On the basis of experimental observations on animals, applications to clinical data on patients and theoretical statistical reasoning, the author developed a com-puter-assisted general mathematical model of the ‘probacent’-probability equation, Equation (1) and death rate (mortality probability) equation, Equation (2) derivable from Equation (1) that may be applica-ble as a general approximation method to make use-ful predictions of probable outcomes in a variety of biomedical phenomena [1-4]. Equations (1) and (2) contain a constant, γ and c, respectively. In the pre-vious studies, the author used the least maximum- difference principle to determine these constants that were expected to best fit reported data, minimizing the deviation. In this study, the author uses the method of computer-assisted least sum of squares to determine the constants, γ and c in constructing the ‘probacent’-related formulas best fitting the NCHS- reported data on survival probabilities and death rates in the US total adult population for 2001. The results of this study reveal that the method of com-puter-assisted mathematical analysis with the least sum of squares seems to be simple, more accurate, convenient and preferable than the previously used least maximum-difference principle, and better fit-ting the NCHS-reported data on survival probabili-ties and death rates in the US total adult population. The computer program of curved regression for the ‘probacent’-probability and death rate equations may be helpful in research in biomedicine.展开更多
BACKGROUND Lutetium has been shown to be an important potential innovation in pre-treated metastatic castration-resistant prostate cancer.Two clinical trials have evaluated lutetium thus far(therap and vision with 99 ...BACKGROUND Lutetium has been shown to be an important potential innovation in pre-treated metastatic castration-resistant prostate cancer.Two clinical trials have evaluated lutetium thus far(therap and vision with 99 and 385 patients,respectively),but their results are discordant.AIM To synthetize the available evidence on the effectiveness of lutetium in pre-treated metastatic castration-resistant prostate cancer;and to test the application of a new artificial intelligence technique that synthetizes effectiveness based on reconstructed patient-level data.METHODS We employed a new artificial intelligence method(shiny method)to pool the survival data of these two trials and evaluate to what extent the lutetium cohorts differed from one another.The shiny technique employs an original reconstruction of individual patient data from the Kaplan-Meier curves.The progression-free survival graphs of the two lutetium cohorts were analyzed and compared.RESULTS The hazard ratio estimated was in favor of the vision trial;the difference was statistically significant(P<0.001).These results indicate that further studies on lutetium are needed because the survival data of the two trials published thus far are conflicting.CONCLUSION Our study confirms the feasibility of reconstructing patient-level data from survival graphs in order to generate a survival statistics.展开更多
Juvenile survival is a key life-history influence on population dynamics and adaptive evolution.We analyzed the effects of individual chara-cteristics,early environment,and maternal investment on juvenile survival in ...Juvenile survival is a key life-history influence on population dynamics and adaptive evolution.We analyzed the effects of individual chara-cteristics,early environment,and maternal investment on juvenile survival in a large solitary hibernating rodent-yellow ground squirrel Spermophilus fulvus using Cox mixed-effects models.Only 48%of weaned pups survived to dispersal and 17%survived to hibernation.Early life expectancy was primarily determined by individual characteristics and,to a lesser extent,by the early environment.The strongest and pos-itive predictor of juvenile survival was body mass which crucially affected mortality immediately after weaning.Males suffered higher mortality than females after the onset of dispersal;however,the overall difference between sexes was partly masked by high rates of mortality in the first days after emergence in both sexes.Later emerged juveniles had lower life expectancy than the earliest pups.The overall effect of local juvenile density was positive.Prolonged lactation did not enhance juvenile survival:Pups nursed longer survived shorter than the young nursed for a shorter period.Our findings support the hypothesis that females of S.fulvus cannot effectively regulate maternal expenditures to mitigate the effects of unfavorable conditions on their offspring.The strategy to deal with seasonal time constraints on life history in female S.fulvus suggests an early termination of maternal care at the cost of juvenile quality and survival.This female reproductive strategy corresponds to a"fast-solitary"life of folivorous desert-dwelling S.fulvus and other solitary ground squirrels with prolonged hibernation.展开更多
文摘In some clinical applications in oncology randomized, double armed, and double-blind trials are not possible. In case of device applications, double-blinded conditions are nonrealistic, and with many times the randomization also has complications due to the high-line treatments where the reference cohort is not available;the active “arm” has mainly palliative initiative. Sometimes highly personalized therapies block the collection of the homogeneous group and limit its double-arm randomization. Our objective is to discuss the situations of the single arm evaluation and to give methods for the mining of information from this to increase the level of evidence of the measured dataset. The basic idea of the data-separation is the appropriate parameterization of the non-parametric Kaplan-Meier survival pattern by the poly-Weibull fit.
文摘The Gompertz model is the long-time well-known mathematical model of exponential expression among mortality models in the literature that are used to describe mortality and survival data of a population. The death rate of the “probacent” model developed by the author based on animal experiments, clinical applications and mathematical reasoning was applied to predict age-specific death rates in the US elderly population, 2001, and to express a relationship among dose rate, duration of exposure and mortality probability in total body irradiation in humans. The results of both studies revealed a remarkable agreement between “probacent”-formula-predicted and published-reported values of death rates in the US elderly population or mortality probabilities in total body irradiation in humans (p - value > 0.995 in χ2 test in each study). In this study, both the Gompertz and “probacent” models are applied to the Sacher’s comprehensive experimental data on survival times of mice daily exposed to various doses of total body irradiation until death occurs with an assumption that each of both models is applicable to the data. The purpose of this study is to construct general formulas expressing relationship between dose rate and survival time in total body irradiation in mice. In addition, it is attempted to test which model better fits the reported data. The results of the comparative study revealed that the “probacent” model not only fit the Sacher’s reported data but also remarkably better fit the reported data than the Gompertz model. The “probacent” model might be hopefully helpful in research in human tolerance to low dose rates for long durations of exposure in total body irradiation, and further in research in a variety of biomedical phenomena.
文摘On the basis of experimental observations on animals, applications to clinical data on patients and theoretical statistical reasoning, the author developed a com-puter-assisted general mathematical model of the ‘probacent’-probability equation, Equation (1) and death rate (mortality probability) equation, Equation (2) derivable from Equation (1) that may be applica-ble as a general approximation method to make use-ful predictions of probable outcomes in a variety of biomedical phenomena [1-4]. Equations (1) and (2) contain a constant, γ and c, respectively. In the pre-vious studies, the author used the least maximum- difference principle to determine these constants that were expected to best fit reported data, minimizing the deviation. In this study, the author uses the method of computer-assisted least sum of squares to determine the constants, γ and c in constructing the ‘probacent’-related formulas best fitting the NCHS- reported data on survival probabilities and death rates in the US total adult population for 2001. The results of this study reveal that the method of com-puter-assisted mathematical analysis with the least sum of squares seems to be simple, more accurate, convenient and preferable than the previously used least maximum-difference principle, and better fit-ting the NCHS-reported data on survival probabili-ties and death rates in the US total adult population. The computer program of curved regression for the ‘probacent’-probability and death rate equations may be helpful in research in biomedicine.
文摘BACKGROUND Lutetium has been shown to be an important potential innovation in pre-treated metastatic castration-resistant prostate cancer.Two clinical trials have evaluated lutetium thus far(therap and vision with 99 and 385 patients,respectively),but their results are discordant.AIM To synthetize the available evidence on the effectiveness of lutetium in pre-treated metastatic castration-resistant prostate cancer;and to test the application of a new artificial intelligence technique that synthetizes effectiveness based on reconstructed patient-level data.METHODS We employed a new artificial intelligence method(shiny method)to pool the survival data of these two trials and evaluate to what extent the lutetium cohorts differed from one another.The shiny technique employs an original reconstruction of individual patient data from the Kaplan-Meier curves.The progression-free survival graphs of the two lutetium cohorts were analyzed and compared.RESULTS The hazard ratio estimated was in favor of the vision trial;the difference was statistically significant(P<0.001).These results indicate that further studies on lutetium are needed because the survival data of the two trials published thus far are conflicting.CONCLUSION Our study confirms the feasibility of reconstructing patient-level data from survival graphs in order to generate a survival statistics.
基金supported by the Russian Science Foundation,project number 22-24-00610,https://rscf.ru/project/22-24-00610/.
文摘Juvenile survival is a key life-history influence on population dynamics and adaptive evolution.We analyzed the effects of individual chara-cteristics,early environment,and maternal investment on juvenile survival in a large solitary hibernating rodent-yellow ground squirrel Spermophilus fulvus using Cox mixed-effects models.Only 48%of weaned pups survived to dispersal and 17%survived to hibernation.Early life expectancy was primarily determined by individual characteristics and,to a lesser extent,by the early environment.The strongest and pos-itive predictor of juvenile survival was body mass which crucially affected mortality immediately after weaning.Males suffered higher mortality than females after the onset of dispersal;however,the overall difference between sexes was partly masked by high rates of mortality in the first days after emergence in both sexes.Later emerged juveniles had lower life expectancy than the earliest pups.The overall effect of local juvenile density was positive.Prolonged lactation did not enhance juvenile survival:Pups nursed longer survived shorter than the young nursed for a shorter period.Our findings support the hypothesis that females of S.fulvus cannot effectively regulate maternal expenditures to mitigate the effects of unfavorable conditions on their offspring.The strategy to deal with seasonal time constraints on life history in female S.fulvus suggests an early termination of maternal care at the cost of juvenile quality and survival.This female reproductive strategy corresponds to a"fast-solitary"life of folivorous desert-dwelling S.fulvus and other solitary ground squirrels with prolonged hibernation.
