Lag Time Research Articles

Method for analyzing urban waterlogging mechanisms based on a 1D-2D water environment dynamic bidirectional coupling model

Urban waterlogging is a significant global issue. To achieve precisely control urban waterlogging and enhance our understanding of its causes, a novel study method was introduced. This method is based on a dynamic bidirectional coupling model that combines 1D-2D hydrodynamic and water quality simulations. The waterlogging phenomenon in densely populated metropolitan areas of Changzhi city, China, was studied. This study focused on investigating the process involved in waterlogging formation, particularly overflow at nodes induced by the design of the topological structure of the pipe network, constraints on the capacity of the underground drainage system, and the surface runoff accumulation. The complex interplay among these elements and their possible influences on waterlogging formation were clarified. The results indicated notable spatial and temporal variation in the waterlogging formation process in densely populated urban areas. Node overflow in the drainage system emerged as the key influencing factor in the waterlogging formation process, accounting for up to 71% of the total water accumulation at the peak time. The peak lag time of waterlogging during events with short return periods was primarily determined by the rainfall peak moment. In contrast, the peak time of waterlogging during events with long return periods was influenced by the rainfall peak moment, drainage capacity and topological structure of the pipe network. Notably, the access of inflow from both upstream and downstream segments of the pipe network drainage system significantly impacted the peak time of waterlogging, with upstream water potentially delaying the peak time substantially. This study not only provides new insights into urban waterlogging mechanisms but also provides practical guidance for optimizing urban drainage systems, urban planning, and disaster risk management.

Development of single layer osmotic controlled release tablet for low soluble drug: Single Core Osmotic Pump (SCOP)

A novel Single Core Osmotic Pump (SCOP) pill has been created to administer high doses of the low solubility medication Rifaximin using osmosis. The formulations were evaluated using six comparative parameters: Q24 (total release after 24 hours), Q12 (total release after 12 hours), TL (lag time), RSQzero12 (R square of the zero-order equation for drug release in 12 hours), RR12 (in vitro release rate for 12 hours), and T80% (time required to deliver 80% of the drug). The drug release profile from osmotic devices shows that the choice of polymer and its concentration in the core formulation can significantly impact the release of the drug. Augmenting the osmogent quantity to an optimal level resulted in a substantial enhancement of Q12 and a notable improvement in the zero-order release pattern of rifaximin. In order to improve the bioavailability of the core formulation, an additive called citric acid was included. Citric acid has several properties that contribute to this enhancement, such as increased solubility of the active ingredient, the creation of a difference in osmotic pressure, regulation of the flow of the active ingredient, and making the composition containing the active ingredient more water-loving. Consequently, TL and T80% experienced a decline, whereas Q12 and RR12 saw a rise. The concentration of PEG 4000 in the semipermeable membrane of the SCOP was found to have a significant impact on TL, T80%, Q12, Q24, and RR12. Specifically, increasing the concentration of PEG 4000 led to a decrease in TL and T80%, while increasing Q12, Q24, and RR12. The optimal aperture diameter for achieving a zero-order release pattern was found to be 850 μm. This study also demonstrated that optimizing the thickness of SPM is crucial for achieving zero order kinetics. The invented SCOP technology has the potential to create a single layer osmotic controlled release tablet of a water insoluble medication with a high dosage.

Drought Monitoring and Prediction in Agriculture: Employing Earth Observation Data, Climate Scenarios and Data Driven Methods; a Case Study: Mango Orchard in Tamale, Ghana

The study focused on the prediction of the Temperature Vegetation Dryness Index (TVDI), an agricultural drought index, for a Mango orchard in Tamale, Ghana. It investigated the temporal relationship between the meteorological drought index, Standardized Precipitation Index (SPI), and TVDI. The SPI was calculated based on utilizing precipitation data from the World Meteorological Organization (WMO) database (2010–2022) and CMIP6 projected precipitation data (2023–2050) from 35 climate models representing various Shared Socioeconomic Pathway (SSP) climate change scenarios. Concurrently, TVDI was derived from Landsat 8/9 satellite imagery, validated using thermal data obtained from unmanned aerial vehicle (UAV) surveys. A comprehensive cross-correlation analysis between TVDI and SPI was conducted to identify lag times between these indices. Building on this temporal relationship, the TVDI was modeled as a function of SPI, with varying lag times as inputs to the Wavelet-Adaptive Neuro-Fuzzy Inference System (Wavelet-ANFIS). This innovative approach facilitated robust predictions of TVDI as an agricultural drought index, specifically relying on SPI as a predictor of meteorological drought occurrences for the years 2023–2050. The research outcome provides practical insights into the dynamic nature of drought conditions in the Tamale mango orchard region. The results indicate significant water stress projected for different time frames: 186 months for SSP126, 183 months for SSP245, and 179 months for both SSP370 and SSP585. This corresponds to a range of 55–57% of the projected months. These insights are crucial for formulating proactive and sustainable strategies for agricultural practices. For instance, implementing supplemental irrigation systems or crop adaptations can be effective measures. The anticipated outcomes contribute to a nuanced understanding of drought impacts, facilitating informed decision-making for agricultural planning and resource allocation.

#1552 The role of osteocytes in bone remodeling: comparison between biopsies from patients with osteitis fibrosa and mixed uremic osteodystrophy disease

Abstract Background and Aims Osteocytes represent about 95% of bone cells. They are located in mineralized bone tissue and connect with each other, with osteoblasts, osteoclasts, blood vessels and bone marrow cells. These cells express several proteins that regulate phosphorus-calcium metabolism and bone remodeling. Disorders of mineral metabolism resulting from chronic kidney disease – mineral bone disorder (CKD-MBD) alter tissue function leading to histological changes known as renal osteodystrophy (ROD). ROD is classified: in high turnover – osteitis fibrosa (OF) and mixed uremic osteodystrophy (MUO) and low turnover – adynamic bone disease and osteomalacia. The participation of osteocytes proteins in ROD pathogenesis is not fully explained. The aim of this study was to evaluate the expression of osteocytic proteins in bone biopsies from patients with OF and MUO and analyze clinical, biochemical and bone histomorphometric results. Method We evaluated patients with CKD on hemodialysis, who underwent bone biopsy to elucidate the diagnosis of ROD. Static and dynamic parameters by histomorphometry, including quantification of osteocytes, and the expression of proteins by immunohistochemistry (Sclerostin; Nuclear factor Kappa B ligand – RANKL; Osteoprotegerin – OPG; Dickkopf-related protein 1 - DKK1; Fibroblast growth factor 23 - FGF23; Dentin matrix protein 1 - DMP1; Matrix extracellular phosphoglycoprotein – MEPE; Phosphate regulatory gene with homologies to endopeptidases on the X chromosome – PHEX; podoplanin - E11; and CD44). Results We included 47 patients (24 with OF and 23 with MUO). Table 1 describes the results from the comparison between both groups. Patients with MUO were older and had lower serum P levels compared to patients with OF. Histomorphometric results showed that the structural parameter trabecular number was greater in patients with OF. The formation parameters, as osteoid volume, thickness and surface were greater in patients with MUO. Regarding mineralization, these patients also have lower bone formation rate, and mineralizing surface and a longer mineralization lag time. The expression of osteocytic proteins in both groups showed that DMP-1 was approximately 50% lower, near to statistical significance (p = 0.07) and RANKL was 23% lower in patients with MUO. In Table 2 are described the association found between proteins and histomorphometric parameters. The majority of the proteins involved in bone remodeling are negatively associated with histomorphometric parameters. Conclusion The clinical symptoms of CKD-BMD in patients with OF and MD are similar, and, except for serum P levels, other biochemical parameters did not contribute to differentiate Of and MUO. Bone biopsy, despite being an invasive procedure, revealed differences between the two pathologies, which could better guide clinical treatment, such as, vitamin D supplementation and VD analogs in patients with MUO who present an increase in osteoid parameters, which could improve bone mineralization. Regarding the expression of proteins in osteocytes, we found few differences between the two groups. However, several associations were observed between the expression of these proteins and structural, formation, reabsorption and mineralization parameters in high turnover bone disease.

Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy.

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication.

Zolpidem is a widely prescribed hypnotic Z-drug used to treat short-term insomnia. However, a growing number of individuals intentionally overdose on these drugs. This study aimed to develop a predictive tool for physicians to assess patients with zolpidem overdose. A population pharmacokinetic (PK) model was established using digitized data obtained from twenty-three healthy volunteers after a single oral administration of zolpidem. Based on the final PK model, a web application was developed using open-source R packages such as rxode2, nonmem2rx, and shiny. The final model was a one-compartment model with first-order absorption and elimination with PK parameters, including clearance (CL, 16.9 L/h), absorption rate constant (Ka, 5.41 h-1), volume of distribution (Vd, 61.7 L), and lag time (ALAG, 0.394 h). Using the established population PK model in the current study, we developed a web application that enables users to simulate plasma zolpidem concentrations and visualize their profiles. This user-friendly web application may provide essential clinical information to physicians, ultimately helping in the management of patients with zolpidem intoxication.

A Model-Informed Drug Development Approach to Design a Phase 3 Trial of Teverelix Drug Product in Advanced Prostate Cancer Patients with Increased Cardiovascular Risk.

Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach. Data from 9 phase 2 studies (229 patients) was utilized to develop a population pharmacokinetic (PK) model that described the concentration profile accommodating both IM and SC routes of administration. A 2-compartment model with sequential first-order absorption (slow and fast) and lag times best described the PK profiles of teverelix following SC and IM administration. An indirect response model with inhibition of production rate was fit to describe testosterone (T) concentrations based on physiological relevance. The final population PK-pharmacodynamic model was used to conduct simulations of various candidate dosing regimens to select the optimal dosing regimen to achieve clinical castration (T<0.5ng/mL by day 28) and to sustain clinical castration for 26 weeks. Model simulation showed that a loading dose of 360mg SC and 180mg IM with a maintenance dose of 360mg SC 6-weekly (Q6W) starting at day 28 can achieve a ≥95% castration rate up to 52 weeks. This dose regimen was selected for phase 3 clinical development, which includes cardiovascular safety assessment in comparison to a GnRH agonist.

Activity-driven chromatin organization during interphase: Compaction, segregation, and entanglement suppression

In mammalian cells, the cohesin protein complex is believed to translocate along chromatin during interphase to form dynamic loops through a process called active loop extrusion. Chromosome conformation capture and imaging experiments have suggested that chromatin adopts a compact structure with limited interpenetration between chromosomes and between chromosomal sections. We developed a theory demonstrating that active loop extrusion causes the apparent fractal dimension of chromatin to cross-over between two and four at contour lengths on the order of 30 kilo-base pairs. The anomalously high fractal dimension [Formula: see text] is due to the inability of extruded loops to fully relax during active extrusion. Compaction on longer contour length scales extends within topologically associated domains (TADs), facilitating gene regulation by distal elements. Extrusion-induced compaction segregates TADs such that overlaps between TADs are reduced to less than 35% and increases the entanglement strand of chromatin by up to a factor of 50 to several Mega-base pairs. Furthermore, active loop extrusion couples cohesin motion to chromatin conformations formed by previously extruding cohesins and causes the mean square displacement of chromatin loci during lag times ([Formula: see text]) longer than tens of minutes to be proportional to [Formula: see text]. We validate our results with hybrid molecular dynamics-Monte Carlo simulations and show that our theory is consistent with experimental data. This work provides a theoretical basis for the compact organization of interphase chromatin, explaining the physical reason for TAD segregation and suppression of chromatin entanglements which contribute to efficient gene regulation.

Analysis of Spatial Differentiation of NDVI and Climate Factors on the Upper Limit of Montane Deciduous Broad-Leaved Forests in the East Monsoon Region of China

The vertical transition zone of mountain vegetation is characterized by high species diversity, and the width of the transition zone may serve as an indirect indicator of climate change. However, research into the differential characteristics of vegetation response to climate changes at the boundary of vertical transition zones has been limited. This study employs MODIS and climate data spanning 2001 to 2018 to investigate spatiotemporal trends in precipitation (PRE), temperature (TMP), radiation (RAD), and Normalized Difference Vegetation Index (NDVI) across nine montane deciduous broad-leaved forests in the eastern monsoon region of China. It explores the time-lag and -accumulation effects of climatic variables on NDVI, quantifying their relative contributions to both its short-term and interannual variations. Results show that, notably, with the Qinling-Daba Mountains as a demarcation, northern regions exhibit significant increases in RAD (0.874–2.047 W m−2/a), whereas southern regions demonstrate notable rises in TMP (0.59–0.73 °C/10a). Areas of lower annual PRE correspond to the most rapid increases in annual average NDVI (5.045 × 10−3/a). NDVI’s lag time and cumulative duration responses to TMP are the shortest (0 and 2~4 periods), while its correlation with RAD is the strongest (0.815–0.975), generally decreasing from higher to lower latitudes. TMP significantly affects NDVI variations, impacting both short-term and interannual trends, with PRE driving short-term fluctuations and RAD dictating long-term shifts. This research provides critical data and a theoretical framework that enhances our understanding of how regional vegetation’s vertical zonation responds to climate change, thereby making a substantial contribution to the study of mountain vegetation’s diverse adaptability to climatic variations.

Design and Evaluation of Gastro-Retentive Floating Tablets of Ibandronic acid

The objective of this study is Preparation and evaluation of gastro-retentive floating tablets of Ibandronic acid by direct compression method polymers or combination. In this study, Ibandronic acid, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastro retentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDDs are an approach to prolong gastric residence time, there by targeting site-specific drug release in the upper GIT for local or systemic effect. GRDF tablets of Ibandronic acid (200 mg) were characterized with the effects of Carbopol 934P, HPMC 4KM and Na-CMC at various ratios on swelling, floating, physical integrity. A prolonged dissolution profile of Ibandronic acid GRDF tablets developed in this study was observed for its thickness, friability, hardness, drug content and in-vitro drug release. Formulated Floating tablets of Ibandronic acid gave satisfactory results for various physicochemical parameters like hardness, friability, thickness, weight variation and content uniformity. Sodium bicarbonate has predominant effect on the buoyancy lag time, while HPMC K4M has predominant effect on total floating time and drug release. From the study it is evident that a promising controlled release floating tablets of Ibandronic acid can be developed to increase gastric residence time and thereby increasing its bioavailability. Both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug. Keywords: Gastro retention, Ibandronic acid, floating tablet, Carbopol, GRDF, GRFT.

Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers.

Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM). Twenty-four healthy Caucasian volunteers were enrolled in a bioequivalence study, each receiving a test and a reference tablet of 600mg of rifampicin separated by a wash-out period of at least 9days. Monolix version 2023R1 was used for NLMEM. Monte Carlo simulations (MCS) were performed to visualize the relationship of body size descriptors to the exposure to rifampicin. A one-compartment model with nonlinear (Michaelis-Menten) elimination and zero-order absorption kinetics with a lag time best described the data. The covariate model including fat-free mass (FFM) on volume of distribution (V/F) and on maximum elimination rate (Vmax/F) lowered the objective function value (OFV) by 56.4. The second-best covariate model of sex on V/F and Vmax/F and BW on V/F reduced the OFV by 51.2. The decrease in unexplained inter-individual variability on Vmax/F in both covariate models was similar. For a given dose, MCS showed lower exposure to rifampicin with higher FFM and accordingly in males compared to females with the same BW and body height. Our results indicate that beyond BW, body composition as reflected by FFM could also be relevant for optimized dosing of rifampicin. This assumption needs to be studied further in patients treated with rifampicin.

Natural lipopeptide surfactin inhibits insulin aggregation and prevents amyloid-induced cytotoxicity and inflammation

Despite the centennial of the pioneering discovery of insulin, challenges regarding insulin aggregation at the site of repeated injection, as well as during industrial production, storage, and transportation, have cast a gloom over this remarkable success story. Aggregation substantially impacts the quality, potency, and effectiveness of insulin formulation, decreasing bioavailability, intensifying the risk of immunogenicity, and endangering patient health. Herein, the suitability of Bacillus-derived amphiphilic biosurfactant surfactin was demonstrated to evade temperature-induced fibrillation of insulin. Fluorometric assessment employing thioflavin-T and intrinsic tyrosine fluorescence indicated the dose-dependent reduction in insulin unfolding and subsequent formation of fibrils. Decreased thioflavin fluorescence at the plateau stage and about a 79% increase in fibrillation lag time was observed for samples containing an equimolar ratio of insulin to surfactin. Circular dichroism analysis further indicated about a 30% increase in α-helix content in samples containing an equimolar ratio of insulin and surfactin, as compared to controls. The findings were further bolstered by dynamic light scattering, electron microscopic analysis, and native polyacrylamide gel electrophoresis. Molecular docking and simulation studies did not indicate any structural destabilization of insulin with surfactin, having major interactions at the hydrophobic and potential amyloidogenic regions of insulin B-chain: B12-B19 (VEALYLVC) and B23-B27 (GFFYT) through hydrophobic and hydrogen bonds. Notably, an almost 22% increase in cell viability was observed for cells incubated with aggregated insulin containing equimolar concentrations of SFN. Surfactin also subdued insulin amyloid-induced upregulation of the pro-inflammatory genes. Thus, surfactin may be contemplated as an additive in biopharmaceutical formulations to imbue stability and may also be evaluated as anti-amyloid therapeutics for other pathological proteinopathies.

Responses to phytoplankton community succession and expression of key functional genes in plateau lakes under 17β-estradiol interference

Steroid estrogens (SEs) have garnered global attention because of their potential hazards to human health and aquatic organisms at low concentrations (ng/L). The ecosystems of plateau freshwater lakes are fragile, the water lag time is long, and pollutants easily accumulate, making them more vulnerable to the impact of SEs. However, the knowledge of the impact of SEs on the growth and decomposition of phytoplankton communities in plateau lakes and the eutrophication process is limited. This study investigated the effects and mechanisms of SEs exposure on dominant algal communities and the expression of typical algal functional genes in Erhai Lake using indoor simulations and molecular biological methods. The results showed that phytoplankton were sensitive to 17β-estradiol (E2β) pollution, with a concentration of 50, and 100 ng/L E2β exposure promoting the growth of cyanophyta and chlorophyta in the short term; this poses an ecological risk of inducing algal blooms. E2β of 1000 ng/L exposure led to cross-effects of estrogenic effects and toxicity, with most phytoplankton being inhibited. However, small filamentous cyanobacteria and diatoms exhibited greater tolerance; Melosira sp. even exhibited "low inhibition, high promotion" behavior. Exposure to E2β reduced the Shannon-Wiener diversity index (H'), Pielou index (J), and the number of dominant algal species (S) in phytoplankton communities, leading to instability in community succession. E2β of 50 ng/L enhanced the expression levels of relevant functional genes, such as ftsH, psaB, atpB, and prx, related to Microcystis aeruginosa. E2β of 50 ng/L and 5 mg/L can promote the transcription of Microcystis toxins (MC) related genes (mcyA), leading to more MC production by algal cells.

Using Polymers as Crystal Inhibitors to Prevent the Crystallization of the Rotigotine Patch.

This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/w). SEM and XRD analysis revealed that the Soluplus and Soluplus-TPGS groups with a high concentration (80%, w/w) of ROT could be stored at room temperature for at least 90 days without crystallization. Moreover, the crystallization nucleation time and growth rate were utilized to assess the ability of Poloxamer 188, Soluplus, and TPGS to hinder the formation of ROT crystals and slow down its crystallization rate. Molecular docking results elucidated the intermolecular forces between ROT and different polymers, revealing their mechanisms for crystal inhibition. The ROT-Soluplus-TPGS combination exhibited the lowest binding free energy (-5.3 kcal/mol), indicating the highest binding stability, thereby effectively reducing crystal precipitation. In vitro skin permeation studies demonstrated that ROT patches containing crystal inhibitors exhibited promising transdermal effects. With increasing ROT concentration, the cumulative drug permeation substantially increased, while the lag time was notably reduced. This study offers novel insights for the development of ROT patches.

Impacts of free nitrous acid on stabilizing food waste and sewage sludge for anaerobic digestion

This work investigated the effectiveness of free nitrous acid (FNA) in enhancing organic waste solubilization to improve biogas production in anaerobic digestion (AD). The results indicated that FNA pretreatment can enhance soluble organic content and control H2S odor in tested organic wastes, including food waste, sewage sludge, and their combination. However, a significant decrease (>50 %) in FNA concentration was found in the reactors, possibly due to denitrifier-driven NO2– consumption. Biochemical methane potential (BMP) tests showed a 25 ± 8 % enhancement in CH4 production in the reactors fed with mixed substrate pretreated with 2.9 mg FNA-N/L. However, the presence of NO2– (325.6–2368.0 mg N/L) in some BMP reactors, due to carryover from FNA pretreatment, adversely affected CH4 production (>55 %) and prolonged lag time (>4.2 times). These findings are valuable for researchers and practitioners in waste management, offering insights for implementing FNA pretreatment to enhance the biodegradability of organic wastes in AD.

Sensitivity of a Process for Heating Thin Metal Film Described by the Dual-Phase Lag Equation with Temperature-Dependent Thermophysical Parameters to Perturbations of Lag Times

In the paper, an equation with two delay times (dual-phase lag Equation (DPLE)) in a version that takes into account the dependence of thermophysical parameters (volumetric specific heat and thermal conductivity) on temperature is considered. In particular, an analysis of the sensitivity of transient temperature field in relation to disturbances in delay times (the relaxation and thermalization times) is performed. The sensitivity model concerns the process of heating an ultrathin metal layer with a laser beam. First, the equation with two delay times in the case of temperature-dependent thermophysical parameters is presented. Next, the sensitivity equations with respect to delay times are derived using the direct method. The algorithms for solving the basic and sensitivity tasks are also briefly presented. At the stage of computations, an authorial program based on the implicit scheme of a finite-difference method is developed. In the final part of the paper, examples of numerical solutions (for layers made from gold and nickel) are presented. The research conducted here shows that disturbances in the temperature field are clearly visible and depend, on the one hand, on the thermophysical parameters of the material, and on the other hand, on the intensity of heating with an external heat source.

Catchment-Scale Hydrologic Effectiveness of Residential Rain Gardens: A Case Study in Columbia, Maryland, USA

To mitigate the adverse impacts of urban stormwater on streams, watershed managers are increasingly using low-impact development and green infrastructure (LID-GI) stormwater control measures, such as rain gardens—vegetated depressional areas that collect and infiltrate runoff from rooftops and driveways. Their catchment-scale performance, however, can vary widely, and few studies have investigated the cumulative performance of residential rain gardens for event runoff control in intermediate-sized (i.e., 1–10 km2) suburban catchments. We modeled three years of continuous rainfall-runoff from a 3.1 km2 catchment in Columbia, MD, USA, using the Storm Water Management Model (SWMM). Various extents of rain garden implementation at residential houses were simulated (i.e., 25%, 50%, 75%, and 100% coverage) to determine the effects on peak flow, runoff volume, and lag time. On average, treating 100% of residential rooftops in the catchment reduced peak flows by 14.3%, reduced runoff volumes by 11.4%, and increased lag times by 3.2% for the 223 rainfall events during the simulation period. Peak flow reductions were greater for smaller storm events (p &lt; 0.01). Our results show that residential rain gardens can significantly improve the runoff response of suburban catchments, and that they represent an effective and relatively low-cost option for urban watershed management and restoration.

Social and spatial disparities in individuals’ mobility response time to COVID-19: A big data analysis incorporating changepoint detection and accelerated failure time models

Although an increasing number of studies have investigated the lag time between the outbreak of COVID-19 and behavior change, few have accurately measured response times to the epidemic at the individual scale as well as their social and spatial heterogeneities. Using a large-scale, long time series dataset of individual-level mobile phone trajectories from Shenzhen, China, we compared six changepoint detection (CPD) algorithms in terms of their performance in detecting true changepoints (CPs) in time series data of individuals’ daily travel distances. We found that the kernel-based CPD method outperformed other algorithms. We thus adopted this method to calculate Shenzhen residents’ mobility response times to the outbreak of COVID-19 and further used an accelerated failure time (AFT) model to explore factors affecting response times. The results suggest that the average and median mobility response times to the outbreak in Shenzhen were 4.64 days and 4 days, respectively. Males and the elderly responded more slowly to the outbreak, while responses were faster among residents in neighborhoods with a higher percentage of highly educated, married, or employed individuals; with better regional accessibility to the city center, railway stations, or the airport; and with higher residential density. These findings can assist policymakers in determining the policy timeline and re-assessing the effectiveness and equity impact of mobility restriction policies and designing more responsive policies varying by social groups and built environment features, helping build socially-resilient neighborhoods in the post-COVID era.

Depression and Time to Knee Arthroplasty Among Adults Who Have Knee Osteoarthritis

BackgroundDepression is common in osteoarthritis (OA) and is associated with poor outcomes following total knee arthroplasty (TKA). Depression can increase pain sensitivity and may be related to an increased likelihood of TKA. MethodsNationally distributed electronic health record data from 2010 to 2018 were used to identify eligible patients (n = 9,466) who had knee OA and were 45 to 80 years of age. Cox proportional hazard models were computed to estimate the association between depression and incident TKA for all patients and by age group (45 to 54, 55 to 64, and 65 to 80 years of age). Confounding was controlled using entropy balancing. Sensitivity analyses determined if the association between depression and TKA differed when depression occurred in the 12 months occurring 90, 60, 30, and 0 days lag time before TKA. ResultsThe mean age of the sample was 63 (range, 45 to 80), 64.0% were women, 83.3% were White race, and approximately 50% resided in the Midwest. There was no association between depression and incident TKA (hazard ratio = 0.97; confidence interval = 0.81 to 1.16]). Results did not differ in age-stratified analyses. Sensitivity analyses revealed a higher percentage of TKA among depressed versus nondepressed patients (24.2 versus 21.6%; P = .028) when the patient’s depression diagnosis was established in the 12 months with no lag time before TKA. ConclusionsPatients who have knee OA and comorbid depression, compared to those who have only knee OA, do not have an increased likelihood of TKA. The multifactorial, complex decision to obtain TKA does not appear to be influenced by depression, but depression is a common comorbidity.