Variable Time Research Articles

Adherence and Persistence Among Risdiplam-Treated Individuals with Spinal Muscular Atrophy: A Retrospective Claims Analysis.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions and/or mutations in the survival of motor neuron1 (SMN1) gene. Risdiplam, the first and only oral SMN2 pre-mRNA splicing modifier, is US Food and Drug Administration-approved for the treatment of pediatric and adult patients with SMA. For patients with SMA, long-term adherence to and persistence with an SMA treatment may be important for achieving maximum clinical benefits. However, real-world evidence on patient adherence to and persistence with risdiplam is limited. This retrospective study examined real-worldadherence and persistence with risdiplamfrom a specialty pharmacy in patients with SMA over a 12-month period. Adherence was estimated by using proportion of days covered (PDC) and was calculated over variable (time between first and last fill) and fixed (time from first fill to study period end) intervals. Persistence was defined as no gap in supply ≥ 90days. Patients were included if the time between the index date and study observation period was ≥ 12months, if they initiated risdiplam between August 2020 and September 2022, received ≥ 2 risdiplam fills, and had an SMA diagnosis associated with a risdiplam fill. Subgroup analyses of risdiplam adherence and persistence were performed by age and primary payer type. The proportion of patients (N = 1636) adherent at 12months based on variable and fixed interval PDC was 93% and 79%, respectively. Adherence was high among patients on commercial insurance, Medicaid, or Medicare (range 86-96%). Mean persistence was 330.4days. The highest proportion of patients who were persistent were on Medicaid (81%). These findings demonstrate that patient adherence to and persistence with risdiplam treatment were high, including across all subgroups tested.

Time of the Day Variability in Pit-Building Behavior of Antlion Larvae

Pit-building behavior in antlion larvae is a unique trait that ensures survival, growth, and metamorphosis. In the present study, we examined the 24-hour rhythm in the pit-building behavior of 16 antlion larvae collected from the PRSU campus, Raipur. We kept each larva individually in a plastic drinking cup in the laboratory. We observed the pit-building behavior of antlion larvae by monitoring two variables, i.e., the time lag for the initiation of pit reconstruction (TLIPR) and total time for pit construction (TTPC) after its demolition over three consecutive days, at four time points each day. We employed single Cosinor Rhythmometry to compute the characteristics of 24-hour rhythm in TLIPR and TTPC. We found a statistically significant 24-hour rhythm in both variables. We found the peaks of TLIPR between 14.32 h and 17.15 h, irrespective of days. Further, the factor 'time of the day' produced a statistically significant effect on the TLIPR and the maximum and minimum values were found at 14.00 h and 02.00 h, respectively. This implies that antlion larvae took time during the afternoon to initiate pit construction. This phenomenon was reversed during nighttime. TTPC exhibited a statistically significant 24-hour rhythm on day 3 and at the group level. We concluded that antlion larvae exhibit a 24-hour rhythm in pit-building behavior and are nocturnal as they initiate pit construction quickly at night.

255 Anchor Talk: Consider intrinsic factors that regulate homeostasis to optimize sustainability of mineral supplements for swine

Abstract Decades of research has focused on methodologies to improve the efficiency of mineral use while assuring sufficient intake to meet animal well-being and production needs. A primary focus of these efforts is P, as P is the third most expensive category of nutrients supplemented in swine diets. Bioavailability of P is more variable than other nutrients in feed ingredients commonly fed to swine. Due to complexities involved in assessments of P bioavailability efforts shifted to defining P digestibilities for each ingredient. Efforts to refine P digestibilities, based on intake and fecal excretion, even with corrections for endogenous losses, have failed to provide a constant coefficient for feed ingredients that can be included in diet formulations, as the digestibility estimates vary with animal age, production phases and inclusion of enzymes such as phytase. An under-appreciated contribution to inaccuracies of digestible P relates to intrinsic regulation of Ca and P homeostasis by the animal. Regulation of Ca and P homeostasis by PTH and 1,25(OH)2D3, must now include a third mineralotropic hormone, FGF23. Applying insights for intrinsic roles of FGF23 will allow more efficient use of nutrients, especially P and vitamin D. FGF23 regulates activation of vitamin D and controls renal P excretion. Over-supplementation of P signals osteocytes (bone cells embedded in a mineralized matrix) to release intact FGF23 which targets the kidney to block reabsorption of P for maintenance of soft tissue homeostasis, resulting in an inefficient use of dietary P. Intact FGF23 also inhibits hydroxylation of 25-OH D3 to form 1,25(OH)2D3. These endocrine pathways illustrate major roles provided by kidneys and bone to allow adaptation to variable Ca and P inputs, thus maintaining homeostasis. Recent efforts to assess P requirements of sows during gestation and lactation illustrate the sensitivity of using renal excretion of Ca and P to assess requirements. Based on 24-h collections, urine Ca:P ratios > 1.5 were consistent with deficient P intake, ratios from 0.5 to 1.5 reflected P adequacy, and ratios < 0.5 indicated excessive P intake. As a practical method, spot urine samples collected at variable times throughout the day reliably predicted Ca:P ratios in 24-h urine collections. Thus, a simplified approach using Ca to P ratio in spot urine samples can be used to assess P intake adequacy. This practical approach can be applied in commercial sow herd to allow herd-based assessment of P status. In conclusion, within herd assessments, based on urine Ca:P ratios, can be used to determine if P supplements are deficient, adequate, and excessive. As such, significant progress can be made to provide a balance between the need to adequately meet animal need with efforts to minimize negative environmental impacts from over-supplementation of P.

Hydroelectric dam impacts shorten and delay the reproductive periods of female leaf-nosed bats in Western Amazonia

Abstract The life cycles of bats are constrained by availability of resources such as food and shelter. Disruptions limiting otherwise naturally regulated access to these resources ultimately affect the fitness of bat populations and may eventually lead to local extinctions. We sampled bats before and after an Amazonian mega-dam water filling and retrieved data on their reproductive phenology, testing if and how sex ratio, seasonal abundance, and reproductive patterns respond to impacts of the newly operating hydroelectric dam. We analyzed data from 3,298 bat captures of 49 species. Females outnumbered males, previously and after the dam implementation, and we observed seasonal variations in the abundance of bats, which was lower after the implementation of the dam for most species. All species had at least 1 reproductive peak of pregnancy and/or lactation beginning at a variable time across seasons. Most species and functional ensembles were reproductively bimodal, with exceptions being the polymodal Artibeus obscurus and unimodal Phylostomus elongatus. Operations of the hydroelectric dam affected the abundance of both sexes equally, and effects were stronger in the rainy season, altering the timing of reproduction for females, delaying and shortening pregnancy and lactation. These changes expressed in female reproductive activity may be related to the shortfall of resources because of loss of irreplaceable vegetation caused by the dam filling. As we cannot predict the roles of variation of reproductive patterns observed after the filling in the long run we reinforce the importance of long-term, continuous monitoring and management to safeguard the reestablishment of reproductive patterns of females in order to repopulate and keep bat populations healthy in remaining areas along following dam construction.

Virtual inertia control to active support of the variable-speed wind turbine in variable frequency limit time

Constraining the virtual inertia of variable-speed wind turbines within the variable frequency limit time will be the key to improving the wind power’s reliability in actively supporting the system frequency. First, this paper analyzes the controllable characteristics and evaluation methods of the virtual inertia of the wind turbine. Second, it quantifies the variable frequency limit time of the grid with high-proportion wind power and considers the wind turbine speed and power margin to restrict the virtual inertia of the wind turbine during the period of frequency drop or increase to provide reliable inertia support to ensure the safety of the system frequency. On this basis, the inertia demand under the frequency safety of the system was analyzed, and the virtual inertia control strategy of the variable-speed wind turbine in the variable frequency limit time was proposed using the speed tracking performance of the wind turbine. Finally, the grid with a high-proportion wind power simulation system is built to verify that the variable-speed wind turbine can reliably satisfy the inertia demand of system frequency modulation under the proposed control strategy and significantly improve its active support performance to the power grid.

Unilateral laser ventriculocordectomy results in increased arytenoid stability in horses with severe left sided recurrent laryngeal neuropathy.

There is no objective information reporting the effect of unilateral laser ventriculocordectomy (VeC) on arytenoid abduction or stability. To evaluate arytenoid stability and abduction in horses with severe recurrent laryngeal neuropathy (RLN) before and after unilateral laser VeC. Prospective cohort. Eight horses with grade C or D exercising laryngeal function that underwent unilateral laser VeC were included. Exercising endoscopy was performed before and ≥6 weeks after left-sided laser VeC. Arytenoid stability at maximal exercise was calculated by measuring the left-to-right quotient angle ratio (LRQ) of the corniculate processes at the points of maximal arytenoid abduction (expiration) and maximal arytenoid collapse (inspiration). For each horse, means of measurements obtained for four breaths pre- and post-operatively were used for statistical analysis. The difference in LRQ between inspiration and expiration was lower post-operatively (median 0.039; interquartile range [IQR] 0.032-0.047) compared with pre-operatively (median 0.158; IQR 0.083-0.249; p = 0.01) confirming the left arytenoid was more stable following unilateral laser VeC. The degree of improvement was significantly greater for grade D horses compared with grade C horses (p = 0.04). The LRQ measured on maximal abduction was also lower post-operatively (median 0.467; IQR 0.444-0.506) compared with pre-operatively (median 0.578; IQR 0.554-0.655; p = 0.02) indicating the left arytenoid was less abducted following surgery. The sample size was small, no racehorses were included and post-operative assessment was conducted at a variable time after surgery. Unilateral laser VeC in grade C and D RLN-affected horses results in slightly reduced left arytenoid abduction but increased arytenoid stability.

Fate of synthetic chemicals in the agronomic insect pest Spodoptera littoralis: experimental feeding-contact assay and toxicokinetic model.

Insecticides prevent or reduce insect crop damage, maintaining crop quality and quantity. Physiological traits, such as an insect's feeding behavior, influence the way insecticides are absorbed and processed in the body (toxicokinetics), which can be exploited to improve species selectivity. To fully understand the uptake of insecticides, it is essential to study their total uptake and toxicokinetics independent of their toxic effects on insects. We studied the toxicokinetics (TK) of insecticidally inactive test compounds incorporating agro-like structural motifs in larvae of the Egyptian cotton leafworm (Spodoptera littoralis,Lepidoptera),and their distribution across all biological matrices, using laboratory experiments and modeling. We measured Spodoptera larval behavior and temporal changes of whole-body concentrations of test compounds during feeding on treated soybean leaf disks and throughout a subsequent depuration period. Differences in the distribution of the total quantities of compounds were found between the biological matrices leaf, larva, and feces. Rate constants for uptake and elimination of test compounds were derived by calibrating a toxicokinetic model to the whole-body concentrations. Uptake and elimination rate constants depended on the physicochemical properties of the test compounds. Increasing hydrophobicity increased the bioaccumulation potential of test compounds. Incomplete quantities in larval matrices indicated that some compounds may undergo biotransformation. As fecal excretion was a major elimination pathway, the variable time of release and number of feces pellets led to a high variability in the body burden. We provide quantitative models to predict the toxicokinetics and bioaccumulation potential of inactive insecticide analogs (parent compounds) in Spodoptera.

Mode Selection Model Based on Travel Time and Price of Goods with Regression Analysis Model

Padang City Market is one of the shopping centres in Padang City, which is located in the West Padang District. The shopping centre presents a place for people to buy kitchen supplies or basic daily needs. This makes the area quite attractive for community travel. This research was conducted on 400 respondents who visited Padang City Market. In this study, the choice of mode is represented by the Y variable and is categorized into private vehicles, public transportation, rental vehicles, walking, and others. The travel time variable represents X1. The variable price of goods represents X2. This study aims to assess the level of correlation between the choice of mode (Y) on the variable travel time (X1) and the variable price of goods (X2). Furthermore, the mode selection (Y) was modeled based on the variables X1 and X2 using linear regression analysis with SPSS tools. The results of the analysis show a strong relationship between the Y variable and the X1 and X2 variables. The best linear regression model produced is Y = 0,010 + 0,76X1 + 0,029X2 with a value of R = 0,437. This means that the closer the travel time is and the lower the price of goods, the more the intensity of motorcycle mode selection to Pasar Raya Padang increases.

Evaluating middle to late Holocene climate variability from δ18O of aquatic invertebrate remains in southwestern Greenland

Holocene paleotemperature records from ice-free margins of Greenland suggest spatiotemporal heterogeneity in the timing of key climate transitions following retreat of the Greenland Ice Sheet. However, the paucity of high-resolution climate records from this region limits our understanding of the timing, spatial variation, and drivers of Holocene climate variability. Here, we present a middle to late Holocene climate reconstruction based on δ18O of aquatic invertebrate (chironomid and cladoceran) remains and sediment geochemistry from lake sediments to elucidate millennial to submillennial-scale drivers of climate in southwestern Greenland. We establish that our site, Arrowhead Lake, is a through-flowing basin with an integrated signal of annual meteoric water with no evidence of significant evaporative enrichment. Core sediment geochemistry captures the transition from minerogenic-dominated to organic-rich sediments ∼8 cal ka BP. Chitin-based δ18O measurements of both chironomid head capsules and ephippia exhibit similar temporal variability through the record, broadly decreasing from 8.2 cal ka BP to present, concurrent with decreasing summer insolation and regional Neoglacial cooling. A simplified assumption that temperature is the sole driver of changes in isotopes of precipitation yields an estimated average temperature change from the middle to late Holocene at Arrowhead Lake of 2.1–3.0 °C, comparable to existing estimates of middle to late Holocene temperature decline in western Greenland. Depleted δ18O values after 3.3 cal ka BP correspond to the onset of Neoglacial cooling and independent evidence for a slowdown of the West Greenland Current, and suggests that both temperature and sea-ice variability were important controls on isotopic variability at this site. Highly depleted isotopic values at 8.2 cal ka BP followed by high isotopic variability in the early part of the middle Holocene suggests that our record may capture regional 8.2 ka cooling. This new isotope record provides insight into climate influences during the middle and late Holocene along the western Greenland margin that are important for understanding how ongoing melt of the Greenland Ice Sheet and amplified warming in the Arctic may impact the climate system.

Transfer learning integrating similarity analysis for short-term and long-term building energy consumption prediction

Currently, building energy consumption prediction models are usually based on a large amount of historical operational data in high demands of building operating hours and monitoring systems. However, many buildings may lack operational data due to relatively limited monitoring systems, causing the failure to use data-driven methods to characterize the energy profile. In this context, transfer learning is a promising method to establish the knowledge transfer between many high-quality building operation datasets and a small amount of target building data, and to help predict energy consumption in the target building. This paper studies the possibility of employing transfer learning to achieve both short and long-term building energy consumption prediction. Firstly, a similarity analysis method, based on variable modal decomposition and dynamic time warping, is proposed for identifying the source buildings with the most similar energy features to the target building. Then, transfer learning for long-term prediction air-conditioning energy consumption is developed with weather parameters generated by the Morphing method as inputs. For the short-term single-step prediction, the proposed model CV-RMSE improves 81.3% (AEC) and 77.4% (EEC), respectively, compared to the prediction model that does not implement the transfer learning strategy and directly uses the target BEC data. As for the short-term multi-step prediction, the proposed model CV-RMSE improves 62.0% (AEC) and 65.5% (EEC), respectively. For the long-term prediction, the average CV-RMSE for the whole year is 6.62% and 11.15% for the proposed and directly target domain-based model, respectively. The proposed method explores the practicality of transfer learning in building energy forecasting, contributing to the use of existing building operation data for energy management at different timespan.

Characterisation of the observed diurnal cycle of precipitation over the Maritime Continent

AbstractThis study investigates the temporal and spatial complexities of the mean diurnal cycle (DC) of precipitation over the Maritime Continent during the wet season using the Integrated Multi‐satellite Retrievals for GPM (IMERG) data product and highlights systematic inaccuracies of amplitude and phase representation using the first diurnal harmonic (FDH). The first‐order nature of the DC of precipitation is already well documented, typically featuring heavy precipitation over near‐coastal land areas in the late afternoon and evening followed by maximum precipitation overnight over the surrounding seas, with offshore propagation evident in places. The DC is often described concisely in terms of an amplitude and phase based on the FDH parameters, however the omission of higher‐order components of variability results in the FDH parameters being poor indicators of the magnitude and peak time of diurnal variability in many locations. This study improves the accuracy of the amplitude and phase parameters by characterising the DC using two novel waveforms—a skew‐permitting waveform and a spike‐permitting waveform—which are constructed to characterise single‐peak cycles with rapid transitions more accurately. Key characterisation improvements include correction of a phase lag (averaging approximately 1 h) over near‐coastal land areas and capture of the short‐lasting but extreme peak in precipitation rate over Java which increases the amplitude by the order of 20%. The new skew parameter shows that locations close to coastlines experience rapid intensification and gradual weakening of diurnal precipitation, while there is a tendency toward gradual intensification and rapid weakening far inland and offshore. The new spike parameter shows that near‐coastal land experiences a brief and precisely timed peak in precipitation, whereas diurnal activity over inland locations is longer‐lasting and less precisely timed, and waters surrounding Java experience a precisely timed suppression of precipitation. Other potential applications of the novel waveforms used in this study are discussed.

Salience Interest Option: Temporal abstraction with salience interest functions

Reinforcement Learning (RL) is a significant machine learning subfield that emphasizes learning actions based on environment to obtain optimal behavior policy. RL agents can make decisions at variable time scales in the form of temporal abstractions, also known as options. The issue of discovering options has seen a considerable research effort. Most notably, the Interest Option Critic (IOC) algorithm first extends the initial set to the interest function, providing a method for learning options specialized to certain state space regions. This approach offers a specific attention mechanism for action selection. Unfortunately, this method still suffers from the classic issues of poor data efficiency and lack of flexibility in RL when learning options end-to-end through backpropagation. This paper proposes a new approach called Salience Interest Option Critic (SIOC), which chooses subsets of existing initiation sets for RL. Specifically, these subsets are not learned by backpropagation, which is slow and tends to overfit, but through particle filters. This approach enables the rapid and flexible identification of critical subsets using only reward feedback. We conducted experiments in discrete and continuous domains, and our proposed method demonstrate higher efficiency and flexibility than other methods. The generated options are more valuable within a single task and exhibited greater interpretability and reusability in multi-task learning scenarios.

Operational Definitions of Poly-Victimization: A Scoping Review.

Throughout the last two decades, research on poly-victimization (PV) has evolved from examinations of a core set of past-year victimization types in youth samples to investigations of a broad range of victimization types experienced during variable time intervals in diverse samples of varying ages. As the concept of PV expands, greater clarity regarding the definition and measurement of PV is needed to advance understanding of its risk and protective factors as well as its associated outcomes. This scoping review aimed to (a) identify approaches used to operationally define and measure PV across studies and (b) synthesize empirical findings concerning risk factors and outcomes associated with PV. A systematic search of peer-reviewed research published before 2022 across 12 databases yielded 98 studies that met inclusion criteria. Study characteristics including the research design, sample type, victimization timeframe, operational definition(s) of PV, measurement of PV, analytic methods, and key findings were synthesized across studies. Findings indicated that the majority of reviewed studies were cross-sectional investigations that utilized categorical measures of lifetime PV in samples of youth. Results also demonstrated that PV is robustly associated with a broad range of predictors, including mental health symptoms and diagnoses as well as family- and community-level factors. PV is also associated with numerous adverse outcomes including depression, anxiety, suicidality, substance use, and delinquency across diverse study types and populations. Future research that examines the conditional effects of PV is needed to identify subgroups of individuals at higher risk of adverse outcomes following PV and modifiable targets for interventions.

Delay analysis of ring resonator-based beam-forming network in z-domain

During the next generation of wireless cellular networks, the millimeter-wave (mm-wave) spectrum will bring new opportunities for exceptionally high data transfer speeds and extensive network connectivity. Millimeter waves, on the other hand, are subject to a significant loss of propagation, which is the most significant impediment. A beneficial solution to this difficulty, which can be overcome, is to use a beam-forming system that consists of many antennas. The purpose of this study is to provide a concept for an integrated photonic beam-forming system that utilises multiple ring resonators for a 1 × 4 phase array antenna operating in the Ka-Band frequency range. The waveguide technology is the foundation for a signal that operates at 28 GHz. It is through the use of the optical ring resonator that the actual time delay line may accomplish its goal. The suggested method can be imDuring the next generation of wireless cellular networks, the millimeter-wave (mm-wave) spectrum will bring new opportunities for exceptionally high data transfer speeds and extensive network connectivity. Millimeter waves, on the other hand, are subject to a significant loss of propagation, which is the most significant impediment. A beneficial solution to this difficulty, which can be overcome, is to use a beam-forming system that consists of many antennas. The purpose of this study is to provide a concept for an integrated photonic beam-forming system that utilises multiple ring resonators for a 1 × 4 phase array antenna operating in the Ka-Band frequency range. The waveguide technology is the foundation for a signal that operates at 28 GHz. It is through the use of the optical ring resonator that the actual time delay line may accomplish its goal. The suggested method can be implemented as a variable true time delay (TTD) line to change the radiation angle of phase array antennas (PAA). The main lobe radiated by the PAA can be directed squint-free between the angles from −28° to +28°. The mathematical analysis and design of the beam producing the structure are presented. Following that, delays of 650 ps, 350 ps, and 250 ps could be produced with coupling coefficients of κ = 0.5 , κ = 0.7, and κ = 0.9 , respectively, and the associated phase shifts were 0.469π, 0.146π, and 0.387π.plemented as a variable true time delay (TTD) line to change the radiation angle of phase array antennas (PAA). The main lobe radiated by the PAA can be directed squint-free between the angles from −28° to +28°. The mathematical analysis and design of the beam producing the structure are presented. Following that, delays of 650 ps, 350 ps, and 250 ps could be produced with coupling coefficients of κ = 0.5 , κ = 0.7, and κ = 0.9 , respectively, and the associated phase shifts were 0.469π, 0.146π, and 0.387π.

Heat Transfer Analysis of Memory-Dependent Derivative in Biological Tissue Subjected to a Moving Heat Source

Abstract A new bioheat transfer equation is developed by introducing the memory-dependent derivative into dual-phase lag model. The heat transfer process of memory-dependent derivative in biological tissue under a moving heat source is studied. Besides, thermal conductivity is usually no longer constant at high temperature. The nonlinear temperature governing equation with considering variable thermal conductivity is formulated and the solutions are obtained by the methods of Kirchhoff and Laplace transformations. The influences of heat source velocity, variable thermal conductivity, relaxation time, and kernel function on the variation of temperature are analyzed.

Study on the microstructure, optical performance, and electromagnetic shielding effectiveness of Al-Ag thin films for variable annealing time

Herein, the magnetron co-sputtering method is employed to fabricate 9 nm 5 mol% Al-Ag thin films, and subsequently annealing treatment is performed. The effect of the annealing time on the structure, optical, and electromagnetic (EM) shielding performance of them is thoroughly studied. It is observed that by subjecting the films to the appropriate annealing time, the Ag granules undergo a transformation into a planar growth structure and make the integrated performance of Al-Ag thin film more exceptional. Compared with other annealing time, when it is 5 min, the obtained Al-Ag thin films display the homogenous and smooth surface morphology. Moreover, it exhibits excellent optical properties with the highest transmittance value of 89.6% at 550 nm, and meanwhile the shielding effectiveness reaches a peak value of 28.7 dB. These characteristics render the Al-Ag thin films highly practical and valuable for EM shielding windows with high transmittance.

An investigation shell and tube heat exchanger for cooling system: A case study of biodiesel plants using lauric acid

Shell and Tube Heat Exchanger (STHE) is a commonly used type of heat exchanger in various industries due to its cost-effectiveness and ease of maintenance. Continuous washing and maintenance of STHE play an important role in influencing both the quality and quantity of production from biodiesel plants. In this particular investigation, the STHE serves as a cooling medium for biodiesel production, with cooling water circulating on the tube side and biodiesel flowing on the shell side. This study focuses on removing silica crust buildup caused by cooling water in the Shell and Tube Heat Exchanger. Furthermore, a Clean-in-Place machine and a 10 % citric acid solution with variable washing times of 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were used for the cleaning process. The results indicate a significant 250 % increase in the volumetric flow rate of the cooling tower along with an increase in the overall Heat Transfer Coefficient after 10 h of washing. Further analysis at the hours mark showed consistent results, suggesting a steady state. Beyond this point, no additional temperature decrease was observed, with temperature stabilizing at 32 °C. The results of the Scanning Electron Microscope analysis show that the crust formed in the STHE comes from silica found in cooling water.

A fast fluid–solid coupled heat transfer algorithm based on dividing the development stages of the flow field

In this study, a fast numerical method for solving the forced convection conjugate heat transfer problem was developed. The method first proposes a new dimensionless number (Fs) that represents the degree of influence of convection on the temperature field in the flow field. It delineates the stage of development of the flow field by monitoring the change in Fs to determine the moment when the flow field suspends updating and improve the computational efficiency of the transient temperature field. The accuracy of the algorithm is verified by taking the fluid–solid conjugate heat transfer under forced convection conditions as an example, which can accurately capture the changes of the flow field for a given monitoring step number of 100, and classify the flow field into E3, E4 and E5 development stages according to the judgment criteria. The results show that the higher development stages correspond to smaller levels of root mean square error (RMSE) of monitoring point temperatures within 3600 s of physical simulation time, and stages E3, E4, and E5 can reach the levels of E-2, E-3, and E-4, which are 3.4, 3.3, and 3.1 times faster than the traditional coupled calculations, respectively. The algorithm is still applicable at variable time steps, but it will require a higher number of determinations compared to a fixed step. The initial error of the quasi-steady algorithm can be reduced from the E-1 level to E-4 by choosing a higher stage of development. Finally the algorithm is tested under a variety of conditions by varying the inlet temperature and flow rate and is found to be robust to both device warming and cooling.

Highly variable timing renders immunotherapy efficacy and toxicity impractical biomarkers of one another in clinical practice.

A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI. Using two-sided Fisher exact and Cochran-Armitage tests, we determined the relative timing of initial efficacy assessment and irAE occurrence in a cohort of 155 ICI-treated patients (median age 68 years, 40% women). Initial efficacy assessment was performed a median of 50 days [interquartile range (IQR) 39-59 days] after ICI initiation; median time to any irAE was 77 days (IQR 28-145 days) after ICI initiation. Median time to first irAE was 42 days (IQR 20-88 days). Overall, 58% of any irAE and 47% of first irAE occurred after initial efficacy assessment. For clinically significant (grade ≥2) irAE, 60% of any and 53% of first occurred after initial efficacy assessment. The likelihood of any future irAE did not differ according to response (45% for complete or partial response vs. 47% for other cases; P=1). In landmark analyses controlling for clinical and toxicity follow-up, patients demonstrating greater tumor shrinkage at initial efficacy assessment were more likely to develop future grade ≥2 (P=0.05) and multi-organ (P=0.02) irAE. In contrast to that seen with chemotherapy and molecularly targeted therapies, the temporal relationship between ICI efficacy and toxicity is complex and bidirectional. In practice, neither parameter can be routinely relied on as a clinical biomarker to predict the other.

Can ESG Stocks Be a Safe Haven during Global Crises? Evidence from the COVID-19 Pandemic and the Russia-Ukraine War with Time-Frequency Wavelet Analysis

In times of intense economic variability and social turbulence worldwide, this paper aims to examine the existence of transient correlations and interdependencies between the most important MSCI ESG indices worldwide and the most important commodities’ index, economic uncertainty, natural gas, gold, and VIX, in a geographical and social context during two recent crises: the COVID-19 pandemic and the energy crisis due to the Ukrainian war. Using daily data from 3 January 2020 and extending until 23 August 2022, this study applies a wavelet coherence approach to analyze time series co-movements, in order to emphasize all possible combinations’ correlations and achieve more accurate outcomes at any given time and frequency band simultaneously and spontaneously. The results show robust coherence between different geographical areas, time, and frequency bands, indicating both positive and negative correlations with most of the combined ESG indices and other economic indicators. The study suggests that stock indices of leading ESG companies in North America and Europe constitute a safe investment haven during major upheavals and crises, providing a way for investors to manage risk and generate positive returns while contributing to economic sustainability.