Variable Duration Research Articles

Different Methods to Estimate the Phase of Neural Rhythms Agree But Only During Times of Low Uncertainty.

Rhythms are a common feature of brain activity. Across different types of rhythms, the phase has been proposed to have functional consequences, thus requiring its accurate specification from noisy data. Phase is conventionally specified using techniques that presume a frequency band-limited rhythm. However, in practice, observed brain rhythms are typically nonsinusoidal and amplitude modulated. How these features impact methods to estimate phase remains unclear. To address this, we consider three phase estimation methods, each with different underlying assumptions about the rhythm. We apply these methods to rhythms simulated with different generative mechanisms and demonstrate inconsistency in phase estimates across the different methods. We propose two improvements to the practice of phase estimation: (1) estimating confidence in the phase estimate, and (2) examining the consistency of phase estimates between two (or more) methods.

Growth of high carrier mobility 2-Dimensional hexagonal Bi2Te3-xSex nanoplatelets and its thermoelectric performance studies

Morphologically controlled growth of selenium-doped 2-Dimensional (2D) Bi2Te3-xSex nanoplatelets have been optimized by solvothermal synthesis using polyvinyl-pyrro-lidone (PVP) surfactant from the pre-optimized growth conditions of 2D-Bi2Te3 hexagonal nanoplatelet. An optimization was carried out using the Se-doping of x = 0.3 under variable growth durations of 4 h, 8 h, and 12 h. X-ray powder diffraction studies confirmed the complete crystallization with a pure phase of 2D-Bi2Te3-xSex at an extended duration of 12 h synthesis. Crystallization with defined hexagonal morphology was confirmed by FESEM analysis. Selenium doping into the 2D-Bi2Te3-xSex lattice from x = 0.1 to x = 0.4 indicates a step-by-step shift in the 2θ value of the (015) predominant peak towards higher 2θ values. Raman analysis revealed the alteration of the appearance of A1u2 to A1g2 upon the lattice inclusion of “Se” in the place of “Te”. Hall measurements on the consolidated pellet of 2D-Bi2Te3-xSex resulted in the highest electron mobility of 1675 cm2V−1s−1 with carrier concentration of 2.9 × 1018 cm−3 for Se-doping x = 0.2. Thermal conductivity analysis in comparison with the total thermal conductivity and the calculated electronic thermal conductivity revealed the lowest lattice thermal conductivity of 0.17 Wm−1K−1 for the Se-doping x = 0.2 after the correction for structural anisotropy factor (f). The highest thermoelectric figure of merit of 0.74 was achieved in this course of work.

THU214 Exploratory Study Of The Association Of Genetic Factors With Recovery Of Hypothalamic-Pituitary-Adrenal Axis In Cushing Disease

Abstract Disclosure: M.H. Nguyen: None. W. Zhang: None. N. Pankratz: None. J. Lane: None. P. Chittiboina: None. F.R. Faucz: None. A. Liu: None. J.L. Mills: None. C.A. Stratakis: None. C. Tatsi: None. Successful treatment of endogenous Cushing syndrome (CS) is often followed by a period of adrenal insufficiency of variable duration. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis may range from 6 months to more than 2 years. Previous studies have investigated potential clinical and biochemical factors involved in this process with variable results. We performed an exploratory study on genetic factors potentially involved in HPA axis recovery in patients with Cushing disease (CD). Ninety (90) patients with CD, who were treated with transsphenoidal surgery (TSS), had initial remission, and a follow up of at least 3 months postoperatively, were included in the study. Recovery of the HPA axis was defined as morning cortisol level or peak cortisol during a standard dose (250 mcg) IV corticotropin stimulation test of >18mcg/dL. Genetic data was obtained by whole exome sequencing (WES). Variants 1) in genes potentially involved in the HPA axis, 2) rare in the general population and 3) predicted as possibly or probably damaging in silico, were selected from WES. Statistical analysis was performed for each variant or for each gene (calculating all variants present in the same gene) using a Cox proportional hazard model. Correction for multiple comparisons was assessed with the false discovery rate (FDR) method.We identified 97 variants in 47 genes of interest that met the above criteria. Although five variants showed a trend toward association with shorter duration of postsurgical adrenal insufficiency (AI), no significant association was noted after correction for multiple comparisons. Furthermore, each variant was present in only one patient. At the gene-level, the BAG1 gene showed significant correlation with shorter postsurgical duration of AI (Hazard ratio: 28.7, 95% Confidence Interval: 5.4-151.1, FDR q-value=0.004), but both patients with a BAG1 variant later experienced recurrent disease, which could suggest an independent predictor of shorter recovery time. When we excluded patients with recurrence, no significant association was reported on the gene-level. In this exploratory study, we did not identify a significant genetic modifier of HPA recovery time. Other factors, clinical or surgical, may play a more important role in the recovery process or larger cohort studies may be required. Presentation: Thursday, June 15, 2023

The Association between Sleep and Bone Mineral Density: Cross-Sectional Study Using Health Check-up Data in a Local Hospital in Japan.

This study aimed to investigate the association between daily sleep duration of <7 hours and lower bone mineral density (BMD) using data from annual health check-ups conducted in Japan between 2020 and 2022. Multivariate regression models were used, where BMD was the objective variable and daily sleep duration (<5 hours, 5 to <7 hours, 7 to <9 hours [reference], ≥9 hours) was the exposure variable adjusted for age, body mass index, physical activity, smoking status, and alcohol intake for men and women and further adjusted for menopausal status for women. The association between insomnia and BMD was also investigated. BMD was determined using calcaneal quantitative ultrasound and expressed as a percentage of the young adult mean (%YAM). In total, 896 men and 821 women were included. Median age was 54 years (interquartile range [IQR]: 46 to 64) for men and 55 years (IQR: 46 to 64) for women). Median BMD for men and women was 79%YAM (IQR: 71 to 89) and 75%YAM (IQR: 68 to 84), respectively. Approximately 80% of men and women slept <7 hours daily. Multivariate regression showed no association between sleep duration and BMD in men. However, women who slept 5 to <7 hours daily had significantly higher BMD by 3.9% compared with those who slept 7 to<9 hours (p = 0.004). No association between insomnia and BMD was found. Overall, a daily sleep duration of <7 hours was not independently associated with lower BMD compared to those who slept 7 to <9 hours in men and women. However, as there is evidence of both shorter and longer sleep durations being associated with an increased risk of adverse events, including cardiovascular events, our result needs to be interpreted with caution. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Local Cost-Effectiveness of Nasopharyngeal Carcinoma Screening Strategies in Southern China: Secondary Analysis of the PRO-NPC-001 Cluster-Randomized Trial

Population-based screening for endemic nasopharyngeal carcinoma (NPC) detects most cases at an early stage. In a cluster-randomized trial conducted in Guangdong, a combination of Epstein-Barr Virus (EBV) anti-VCA/EBNA1 IgA serology and endoscopy reduced NPC mortality. We conducted a secondary analysis of this trial in conjunction with local incidence and cost data, hypothesizing that screening would be cost-effective in this region. We estimated population-level NPC mortality reduction, resource utilization, and cost-effectiveness of 12 unique screening strategies in six populations in Guangdong/Guangxi using a previously-validated time-inhomogeneous decision-analytic cohort model. These 12 strategies evaluated combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and head/neck MRI. Incidence data, screening costs, and healthcare costs were obtained from local cancer registries, laboratories conducting ELISA/PCR, and the Guangdong provincial healthcare system. We evaluated variable screening ages, sexes, intervals, and durations to identify optimal screening approaches from the perspective of the healthcare system in southern China. An incremental cost-effectiveness ratio (ICER) willingness-to-pay threshold of 1.50 times the per-capita GDP was considered cost-effective in southern China. For the base strategy screening 50-year-old men and women using only serology and endoscopy, the average cost per screened subject for a single round of screening over a five-year cycle was ¥175.69. The addition of MRI improved sensitivity (76% vs. 62%) and approximately doubled screening costs. Triage with NP PCR was cost-neutral when used in conjunction with MRI and reduced endoscopy/MRI utilization by 37% with a 3-4% reduction in screening sensitivity. Among 50-year-old men and women, screening was cost-effective in all populations provided that medium-risk subjects were not referred for endoscopy/MRI (ICER/GDP 0.62-0.83). The use of NP PCR without MRI (ICER/GDP 0.83) was dominated by the base strategy (ICER/GDP 0.62) due to higher costs and NPC mortality. After a single five-year screening cycle, screening reduced population NPC mortality by 14% with serology + endoscopy and 21% with serology + endoscopy + MRI. Introduction of MRI with or without NP PCR could be cost-effective in all populations. For MRI-based strategies, the most efficient use of resources was deferral of endoscopy unless MRI was abnormal (ICER/GDP 0.67). Overall, the best-performing strategies balanced NPC mortality, screening costs, and MRI utilization. EBV serology-based screening for endemic NPC is likely to be cost-effective among adult men and women in Guangdong and Guangxi. Referring medium-risk subjects for endoscopy/MRI should be avoided, and NP PCR should be used to triage individuals for MRI rather than endoscopy. These data may aid the design of population-based screening programs in this region.

Starting and Specialisation Ages of Elite Athletes across Olympic Sports: An International Cross-sectional Study

Talent development models are the frameworks that guide sports stakeholders in developing potential athletes, within which early specialisation and diversification remain contradictory strategies. This paper presents new insights into the starting and specialisation ages of world-class athletes in various Olympic sports. A total of 2,838 athletes from 13 nations and 44 Olympic sports were included in this study. The results show that world-class athletes started with their current sport at the age of 10.6 (±5.3) and decided to focus on this sport at the age of 15.6 (±5.0), with obvious variations in these ages across different sports. The study showed a moderate relationship between athletes’ starting and specialisation ages (r = 0.639), which demonstrates the variable duration of the multiple sport sampling period. This period, during which athletes pursue a variety of sports, lasts 4.9 years on average. There is a high degree of variation among different athletes in starting and specialisation ages, even within the same sport. All sports in the study can be classified into five categories based on a combination of their starting ages (early/intermediate/late) and specialisation ages (early/intermediate/late). The Developmental Model of Sports Participation provides the age guidelines for the categories. The five categories contain (I) early specialisation sports, (II) intermediate starting and specialisation sports, (III) late specialisation sports, (IV) late starting sports, and (V) late starting and late specialisation sports. The study concludes by proposing that there is a need for sport-specific talent development models with increased attention to each sport’s starting age, sampling period, and specialisation age.

Starting and Specialisation Ages of Elite Athletes across Olympic Sports: An International Cross-sectional Study

Talent development models are the frameworks that guide sports stakeholders in developing potential athletes, within which early specialisation and diversification remain contradictory strategies. This paper presents new insights into the starting and specialisation ages of world-class athletes in various Olympic sports. A total of 2,838 athletes from 13 nations and 44 Olympic sports were included in this study. The results show that world-class athletes started with their current sport at the age of 10.6 (±5.3) and decided to focus on this sport at the age of 15.6 (±5.0), with obvious variations in these ages across different sports. The study showed a moderate relationship between athletes’ starting and specialisation ages (r = 0.639), which demonstrates the variable duration of the multiple sport sampling period. This period, during which athletes pursue a variety of sports, lasts 4.9 years on average. There is a high degree of variation among different athletes in starting and specialisation ages, even within the same sport. All sports in the study can be classified into five categories based on a combination of their starting ages (early/intermediate/late) and specialisation ages (early/intermediate/late). The Developmental Model of Sports Participation provides the age guidelines for the categories. The five categories contain (I) early specialisation sports, (II) intermediate starting and specialisation sports, (III) late specialisation sports, (IV) late starting sports, and (V) late starting and late specialisation sports. The study concludes by proposing that there is a need for sport-specific talent development models with increased attention to each sport’s starting age, sampling period, and specialisation age.

Patterns of sedentary behaviour in adults with acute insomnia derived from actigraphy data.

Sleep disorders, such as insomnia, have been associated with extended periods of inactive, sedentary behaviour. Many factors contribute to insomnia, including stress, irregular sleep patterns, mental health issues, inadequate sleeping schedules, diseases, neurological disorders and prescription medications. Identification of the patterns of sedentary time and its duration in adults with acute insomnia and healthy controls to determine the statistically significant sedentary bouts; comparison of the sedentary behaviour patterns in acute insomnia adults with healthy controls. We investigate the daytime actigraphy data and identify temporal patterns of inactivity among adults with acute insomnia and healthy adults. Seven days of actigraphy data were utilised to calculate sedentary time and bouts of variable duration based on a threshold of activity counts (<100 counts per minute). Statistical analysis was applied to investigate sedentary bouts and total sedentary time during weekdays and weekend. A logistic regression model has been used to determine the significance of sedentary bouts. We found that individuals with acute insomnia accumulate a significant amount of their sedentary time in medium (6-30 minutes and 31-60 minutes) and longer (more than 60 minutes) duration bouts in comparison to healthy adults. Furthermore, a low p value for total sedentary time (2.54 ⋅ 10-4) association with acute insomnia supports the finding that acute insomnia individuals are significantly more engaged in sedentary activities compared to healthy controls. Also, as shown by the weekend vs weekday analysis, the physical and sedentary activity patterns of acute insomnia adults demonstrate higher variability during the weekdays in comparison to the weekend. The results of the present study demonstrate that adults with acute insomnia spend more time in low-intensity daily physical activities compared to healthy adults.

C/C soft-hard mixed preform multi-units compression compaction viscoelastic rebound technique and optimization

To address the issue of non-uniform fiber volume fraction between layers in the compression compaction process of C/C soft-hard mixed preforms, a multi-unit variable duration cyclic compression compaction process based on the inter-laminar fiber compression viscoelastic deformation behavior is proposed. This process aims to gradually eliminate the rebound characteristics of inter-laminar fibers and reduce the error of inter-laminar fiber volume fraction. The mapping relationships between the number of units, holding duration, and compaction times with the rebound height of inter-laminar fibers are established using data fitting. The compression compaction process is determined using the Box Behnken response surface design method, and digital devices are utilized for preform compaction experiments. The micro-morphology of the preform is observed using an optical microscope, and the density of inter-laminar fibers before and after process optimization is compared. Experimental results indicate that when the number of units is 3, the holding duration is 57 s, and the compaction times is 2, the fiber volume fraction of the soft-hard mixed preform is 42.90%, which is 12.16% higher than before process optimization, and the error of inter-laminar fiber volume fraction is less than 6.5%.

Complications following cardiac pacemaker insertions

Context: Permanent pacemaker insertion is a recognised mode of therapy for cardiac arrhythmias. The procedure is carried our regularly at the Cardiac Catheterization laboratory of Madras Medical Mission India.&#x0D; Aims: This study reviewed the associated morbidity and complications of cardiac pacemaker insertions carried out over fifteen years. &#x0D; Settings and Design: This study was carried out in the Cardiac Electrophysiology department, of the Institute of Cardiovascular diseases, Madras Medical Mission, India. The study was retrospective. &#x0D; Material and methods: Data was collected when previously paced patients presented for cardiac interrogation between January to July of 2013. The patients had undergone implantation over the preceding fifteen years. 501 consecutive cases were chosen for analysis.The data obtained was analysed using SPSS statistical software version 15.&#x0D; Results: The 501 patients had been on pacemaker for variable durations. They comprised 321 males and 180 females. A variety of complications were observed in 33 (6.58%) patients but there was no procedure-related mortality. &#x0D; Conclusions: Pacemakers were generally well tolerated. Majority of patients were asymptomatic and the rate of complications is 6.58%.

Daily stream temperature predictions for free-flowing streams in the Pacific Northwest, USA

Supporting sustainable lotic ecosystems and thermal habitats requires estimates of stream temperature that are high in scope and resolution across space and time. We combined and enhanced elements of existing stream temperature models to produce a new statistical model to address this need. Contrasting with previous models that estimated coarser metrics such as monthly or seasonal stream temperature or focused on individual watersheds, we modeled daily stream temperature across the entire calendar year for a broad geographic region. This model reflects mechanistic processes using publicly available climate and landscape covariates in a Generalized Additive Model framework. We allowed covariates to interact while accounting for nonlinear relationships between temporal and spatial covariates to better capture seasonal patterns. To represent variation in sensitivity to climate, we used a moving average of antecedent air temperatures over a variable duration linked to area-standardized streamflow. The moving average window size was longer for reaches having snow-dominated hydrology, especially at higher flows, whereas window size was relatively constant and low for reaches having rain-dominated hydrology. Our model’s ability to capture the temporally-variable impact of snowmelt improved its capacity to predict stream temperature across diverse geography for multiple years. We fit the model to stream temperatures from 1993–2013 and predicted daily stream temperatures for ~261,200 free-flowing stream reaches across the Pacific Northwest USA from 1990–2021. Our daily model fit well (RMSE = 1.76; MAE = 1.32°C). Cross-validation suggested that the model produced useful predictions at unsampled locations across diverse landscapes and climate conditions. These stream temperature predictions will be useful to natural resource practitioners for effective conservation planning in lotic ecosystems and for managing species such as Pacific salmon. Our approach is straightforward and can be adapted to new spatial regions, time periods, or scenarios such as the anticipated decline in snowmelt with climate change.

Impact of androgen receptor alterations on cell-free DNA genomic profiling on survival outcomes in metastatic castration-resistant prostate cancer.

Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.

Duration of intermittent hypoxia impacts metabolic outcomes and severity of murine NAFLD.

Obstructive sleep apnea (OSA) is associated with metabolic dysfunction, including progression of nonalcoholic fatty liver disease (NAFLD). Chronic intermittent hypoxia (IH) as a model of OSA worsens hepatic steatosis and fibrosis in rodents with diet induced obesity. However, IH also causes weight loss, thus complicating attempts to co-model OSA and NAFLD. We sought to determine the effect of various durations of IH exposure on metabolic and liver-related outcomes in a murine NAFLD model. We hypothesized that longer IH duration would worsen the NAFLD phenotype. Male C57BL/6J mice (n = 32) were fed a high trans-fat diet for 24 weeks, to induce NAFLD with severe steatohepatitis. Mice were exposed to an IH profile modeling severe OSA, for variable durations (0, 6, 12, or 18 weeks). Intraperitoneal glucose tolerance test was measured at baseline and at six-week intervals. Liver triglycerides, collagen and other markers of NAFLD were measured at sacrifice. Mice exposed to IH for 12 weeks gained less weight (p = 0.023), and had lower liver weight (p = 0.008) relative to room air controls. These effects were not observed in the other IH groups. IH of longer duration transiently worsened glucose tolerance, but this effect was not seen in the groups exposed to shorter durations of IH. IH exposure for 12 or 18 weeks exacerbated liver fibrosis, with the largest increase in hepatic collagen observed in mice exposed to IH for 12 weeks. Duration of IH significantly impacts clinically relevant outcomes in a NAFLD model, including body weight, fasting glucose, glucose tolerance, and liver fibrosis.

Deposition, Diagenesis, and Geochemistry of Upper Cretaceous Carbonates (Sarvak Formation) in the Zagros Basin and the Persian Gulf, Iran

Upper Cretaceous carbonate rocks of the Sarvak Formation are among the most important hydrocarbon reservoirs of the Middle East. This paper summarizes the depositional history, diagenetic alteration, and geochemistry of this formation in south and southwest Iran. The combined effects of tectonic activities and the paleoclimate had remarkable control over the depositional–diagenetic evolution of this formation. Large changes in facies types, their frequency, and thickness were recorded across the study area and attributed to the tectonic activities. The complex diagenetic history of this formation includes minor marine, intensive meteoric, and burial diagenesis. Two pronounced paleoexposure events were recorded at the Cenomanian–Turonian boundary (CT-ES) and the middle Turonian (mT-ES), which are associated with remarkable changes in facies and diagenetic characteristics and special geochemical trends. Elemental (Mg, Fe, Rb, Mn, Sr), isotopic (carbon, oxygen), and 87Sr/86Sr ratios provide useful tools for delineating the paleoexposure surfaces, their associated diagenetic alterations, and chemo-sequence stratigraphic interpretation. Variable exposure durations resulted in immature to over-matured karstified profiles below the CT-ES and mT-ES, respectively. Meteorically dissolved rudist-dominated facies provided the best reservoir zone of the Sarvak Fm. in the regressive systems tract of the Cenomanian sequence, just below the CT-ES. Microporous and dolomitized mud-dominated facies formed the second important reservoir intervals, especially within the transgressive systems tracts. The results of this study revealed that the reservoir characteristics of the Sarvak Fm. were considerably controlled by paleoexposure events and, therefore, it can be considered as a typical paleokarst hydrocarbon reservoir in Iran.

Severe Neuroinvasive West Nile Virus in Association With Anti-CD20 Monotherapy for Multiple Sclerosis.

The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). This is a case series study. In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ2 p < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.

Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org.

The MTXPK.org webtool was launched in December 2019 and was developed to facilitate model-informed supportive care and optimal use of glucarpidase following the administration of high-dose methotrexate (HDMTX). One limitation identified during the original development of the MTXPK.org tool was the perceived generalizability because the modeled population comprised solely of Nordic pediatric patients receiving 24-h infusions for the treatment of acute lymphoblastic leukemia. The goal of our study is to describe the pharmacokinetics of HDMTX from a diverse patient population (e.g., races, ethnicity, indications for methotrexate, and variable infusion durations) and identify meaningful factors that account for methotrexate variability and improve the model's performance. To do this, retrospectively analyzed pharmacokinetic and toxicity data from pediatric and adolescent young adult patients who were receiving HDMTX (>0.5 g/m2 ) for the treatment of a cancer diagnosis from three pediatric medical centers. We performed population pharmacokinetic modeling referencing the original MTXPK.org NONMEM model (includes body surface area and serum creatinine as covariates) on 1668 patients, 7506 administrations of HDMTX, and 30,250 concentrations. Our results support the parameterizations of short infusion duration (<8 h) and the presence of Down syndrome on methotrexate clearance, the parameterization of severe hypoalbuminemia (<2.5 g/dL) on the intercompartmental clearance (Q2 and Q3), and the parameterization of pleural effusion on the volume of distribution (V1 and V2). These novel parameterizations will increase the generalizability of the MTXPK.org model once they are added to the webtool.

FairLight: Fairness-Aware Autonomous Traffic Signal Control With Hierarchical Action Space

Although Reinforcement Learning (RL) approaches are promising in autonomous Traffic Signal Control (TSC), they often suffer from the unfairness problem that causes extremely long waiting time at intersections for partial vehicles. This is mainly because traditional RL methods focus on optimizing the overall traffic performance, while the fairness of individual vehicles is neglected. To address this problem, we propose a novel RL-based method named FairLight for the fair and efficient control of traffic with variable phase duration. Inspired by the concept of User Satisfaction Index (USI) proposed in the transportation field, we introduce a fairness index in the design of key RL elements, which specially considers the travel quality (e.g., fairness). Based on our proposed hierarchical action space method, FairLight can accurately allocate the duration of traffic lights for selected phases. Experimental results obtained from various well-known traffic benchmarks show that, compared with state-of-the-art RL-based TSC methods, FairLight can not only achieve better fairness performance, but also improve the control quality from the perspectives of the average travel time of vehicles and RL convergence speed.

The Integrated Problem of Construction Project Scheduling and Multiskilled Staff Assignment with Learning Effect

Effective multiskill resource scheduling requires comprehensive workforce assignments. Drawing on the multiskill project scheduling problem perspective, this study investigates the integrated problem of project scheduling and multiskilled staffing based on a more realistic perspective that human skill level is dynamic and has a variable activity duration caused by the learning effect. An integer linear programming model is innovatively constructed to solve the problem directly. Moreover, an adapted tabu search algorithm with six resource-oriented priority strategies is designed to solve large-scale problems efficiently. Based on a realistic construction project case and numerical instances, comprehensive computational experiments are conducted to validate the proposed algorithm. The findings reveal the impact of different resource strategies on project duration and personal skill growth, particularly through the optimization of project scheduling according to the dynamic scenarios. The research extends conventional project scheduling knowledge and its methods by solving complex scheduling problems for improved project objectives and employee value. In practice, the model and the algorithm can be integrated into the project management information system for strategizing a plan of project scheduling and staff assignment proactively.

A Novel PWM Signal-Generation Strategy for Pockels Cell Drivers

A Pockels cell driver (PCD) can be viewed as a high-voltage pulse width generator for controlling the bi-refringence effect of electro-optical crystals. The main features of a PCD include a high repetition rate, fast on and off switching, variable pulse duration, and a true square pulse shape. The most commonly used PCD has a narrow pulse width tuning range, typically within a few microseconds. In this paper, we propose a PCD based on a novel pulse width modulation (PWM) signal-generation strategy that can continuously adjust its pulse width with a minimum step size of 10 ns and no restriction on the maximum width. Therefore, it is easily compatible with both “On-type” and “Off-type” applications of the electro-optic crystal quarter-wave voltage. The experimental results show that the rising and falling times of the proposed PCD are approximately 7.3 ns and 7.8 ns, respectively, with a maximum repetition rate of 1 MHz and a maximum voltage of approximately 2.0 kV. Finally, the functionality of the PCD is demonstrated in a home-built slab laser.

The effect of warm ischemia and donor ejection fraction on 30-day mortality after donation after circulatory death heart transplantation: A national database analysis

Donation after circulatory death (DCD) donor hearts recovered using the direct procurement and perfusion method experience variable durations of warm ischemia at the time of procurement (WIP). We used the Organ Procurement and Transplantation Network database to assess the effect of WIP on 30-day mortality after DCD heart transplantation. The analysis evaluated outcomes in 237 recipients of DCD heart transplantation, demonstrating an optimal WIP cut point of <36minutes. Multivariable logistic regression modeling identified donor left ventricular ejection fraction (LVEF) <60% as an independent predictor of 30-day mortality. The area under the receiver operating characteristic curve for predicting 30-day mortality based on WIP ≥36minutes and donor LVEF <60% was 0.90. Based on these findings, we do not recommend proceeding with DCD heart transplantation for patients with WIP ≥36minutes, particularly in donors with LVEF <60%.