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α decay and proton emission were combined using symbolic regression to improve the accuracy of predicting their respective half-lives using two theoretical formulations: (1) adjustable parameters for the universal decay law and universal decay law for proton emission are obtained by regressions with fully-constrained symbolic regressions. (2) New theoretical formulas for calculating the half-life of proton emission and α decay are obtained using unconstrained symbolic regressions combined with nuclear data. Our computational analysis indicates that fully-constrained symbolic regressions and unconstrained symbolic regressions are reliable for specific and general nuclei, respectively, in terms of replicating experimental results, and are sufficiently robust to produce accurate half-life predictions. Unlike other machine learning methods that generate complex and opaque results, our approach integrates physics and machine learning to create interpretable formulas that provide intuitive parametric outcomes and transparent and dependable inferences of half-lives, even in areas with limited experimental data. The test results show that the equation yields accurate results, and can be easily applied to future α decay and proton emission studies. [ABSTRACT FROM AUTHOR]

FITEVT is a FORTRAN program designed to analyze recorded arrival times of nuclear-decay events affected by dead-time. The primary goal of the program is precise and accurate determination of half-lives. Its method involves imposition of a known sufficiently long extending dead-time to the recorded event sequence, so that the original dead-time effects are completely obliterated and the remaining live-times of the survived events are known exactly. Upon completion of the analysis, the arrival-time spectrum and the live-time spectrum are predicted and compared to those constructed from the survived events. Program title: FITEVT Licensing provisions: MIT CPC Library link to program files: https://doi.org/10.17632/scg6p9jxjk.1 Programming language: FORTRAN (using double precision) Nature of problem: Accurate determination of the ideal event rate from the observed event rate in a nuclear decay can be a challenging task due to the inevitable presence of detection system's dead-time, whose nature and extent are typically unknown. Consequently, the results of nuclear half-life measurements may depend on the method used to correct for event losses due to dead-time. Therefore, there is a need for an exact method of data analysis and the means to apply it in order to ensure reproducibility, accuracy and optimized precision of the results. Solution method: FITEVT performs arrival-time analysis of the recorded events, in which a known, sufficiently large extending dead-time is imposed by means of software, so that in the resulting set of survived events the original dead-time effects are completely replaced by the effects of the imposed dead-time. As a result, the dead-time following each survived event and the remaining live-time preceding each surviving event are known exactly. This allows for application of the maximum-likelihood method of estimation, in which the half-lives as well as the other parameters of the ideal-decay-rate function can be accurately determined. Additional comments including restrictions and unusual features: In its original form the program can handle contributions from a constant event rate (i.e. , a typical background) plus up to 4 different exponentially-decaying event rates. One of these 4 contributions is allowed to be negative, so that the program can be applied to the general case involving a single two-component decay chain. The employed method of analysis produces accurate results even when the product of the ideal event rate (ρ) and the extending dead-time parameter (τ e) is as large as 51.2 [1]. Example used in the present paper involves simulated events having initial rate of 10 5 s − 1 , to which extending dead-time of 64 μs is imposed. Data analysis is based on maximum-likelihood principle, in which minimization of the deviance involves calculations in double precision and determination of its derivatives is based on analytical expressions. This is done in order to optimize precision and accuracy of the results as well as the program execution time. With the provided input data and a typical contemporary laptop computer, the program execution typically lasts about 5 minutes. Reducing the imposed dead-time to zero increases the number of survived events approximately by a factor of 6, but the program execution time increases by about a factor of 3. [1] V. Horvat, J.C. Hardy, Nucl. Instrum. Methods Phys. Res., Sect. A 713 (2013) 19. [ABSTRACT FROM AUTHOR]

Introduction: Pilots who use an impairing medication to treat a medical condition are required to wait an appropriate amount of time after completing the treatment before returning to duty. However, toxicology findings from fatal aviation accidents indicate not all pilots wait a sufficient period of time. Methods used today do not take into consideration the time required for the drug to reach subtherapeutic concentrations. Methods: An equation was developed based on the therapeutic range and the maximum expected half-life of the medication to objectively calculate a safe return-to-duty time for pilots. The new equation assumes the treating physician will not dose the patient beyond the upper therapeutic range of the medication and the person taking the medication has the maximum half-life reported in the literature. The equation N = ln(0.5*Cmin/Cmax)/ln(0.5) was developed to determine the number of half-lives (n) required to reach one-half of Cmin where Cmin = lower therapeutic concentration and Cmax = upper therapeutic concentration. Anonymous subjects were recruited under an approved IRB protocol. Blood and plasma were collected at approximately Cmax (2-3 h) and again after waiting approximately another 5 h. Toxicological analysis was performed on the specimens collected. Results: One subject taking a 25-mg dose had a 0.033 ug · ml-1 blood concentration after waiting 8 h, well above the 0.025 ug · ml-1 reported as impairing concentration. The new equation estimated a mean wait time for the 18 medications composed of 4 half-lives. Discussion: The new CAMI equation takes into consideration safety without grossly over estimating pilot wait times. [ABSTRACT FROM AUTHOR]

Abstract: It generally is difficult, if not impossible, to fully understand and interpret nonlinear time series models by considering the estimated values of the model parameters only. To shed light on the characteristics and implications of a nonlinear model it can then be useful to consider the effects of shocks on the future patterns of the time series variable. Most interest in such impulse response analysis has concentrated on measuring the persistence of shocks, or the magnitude of their (ultimate) effect. A framework is developed and implemented that is useful for measuring the rate at which this final effect is attained, or the rate of absorption of shocks. It is shown that the absorption rate can be used to examine whether the propagation of different types of shocks, such as positive and negative shocks or large and small shocks follows different patterns. The nonlinear floor-and-ceiling model for US output growth is used to illustrate the various concepts. The presence of substantial asymmetries in both persistence and absorption of shocks is documented, with interesting differences arising across magnitudes of shocks and across regimes in the model. Furthermore, it appears that asymmetry became much less pronounced due to a large decline in output volatility in the 1980s. [Copyright &y& Elsevier]

Abstract: The half-life is defined as the number of periods required for the impulse response to a unit shock to a time series to dissipate by half. It is widely used as a measure of persistence, especially in international economics to quantify the degree of mean-reversion of the deviation from an international parity condition. Several studies have proposed bias-corrected point and interval estimation methods. However, they have found that the confidence intervals are rather uninformative with their upper bound being either extremely large or infinite. This is largely due to the distribution of the half-life estimator being heavily skewed and multi-modal. A bias-corrected bootstrap procedure for the estimation of half-life is proposed, adopting the highest density region (HDR) approach to point and interval estimation. The Monte Carlo simulation results reveal that the bias-corrected bootstrap HDR method provides an accurate point estimator, as well as tight confidence intervals with superior coverage properties to those of its alternatives. As an application, the proposed method is employed for half-life estimation of the real exchange rates of 17 industrialized countries. The results indicate much faster rates of mean-reversion than those reported in previous studies. [Copyright &y& Elsevier]

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3 S )-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7 H -benzo[7]annulene-2-carboxylic acid ( 43d ), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.