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Although failures and other experiences can capture attention and motivate organizations to learn and improve, this knowledge is not always retained over time, leaving some organizations dangerously prone to repeat the same mistakes repeatedly. We adapt theory on the attention-based view—and specifically on attentional engagement and vigilance—to shed new light on this process. While prior research has examined how competing events may draw attention away, our theory leads us to consider the circumstances that will motivate employees to maintain attention on learning from failure that has already occurred. Our framework examines the conditions that preserve attention to past failures by increasing the perception that related issues exist elsewhere, serving as continuing reminders of or cues about the failure when attention begins to drift away. We find support for related hypotheses involving a failure's complexity, the firm's culpability, and the ongoing use of routines related to those involved in the failure. Our findings contribute to the attention-based view by developing theory about attentional engagement and vigilance and by emphasizing the conditions that can keep attention focused on, rather drawn away from, past failure. We also contribute to efforts to examine knowledge depreciation and forgetting in more depth in organizational learning theory. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity-related cardiometabolic disease in Samoa is among the highest globally. While physical activity is a modifiable risk factor for obesity-related disease, little is known about physical activity levels among adult Samoans. Using wrist-worn accelerometer-based devices, this study aimed to characterize physical activity among Samoan adults. Methods: Samoan adults (n = 385; 55% female, mean [SD] age 52 [10] y) wore Actigraph GT3X+ devices for 7 to 10 days. General linear models were used to examine mean daily minutes of sedentary time, light physical activity, and moderate to vigorous physical activity by various participant characteristics. Results: Time spent in moderate to vigorous physical activity did not differ statistically between men (88 [5] min; 95% confidence interval [CI], 80–97) and women (78 [4] min; 95% CI, 70–86; P =.08). Women, however, spent more time than men in light physical activity: 380 (7) minutes (95% CI, 367–393) versus 344 (7) minutes (95% CI, 329–358; P <.001). While there were no differences in physical activity by census region, education, or occupation among women, men in urban areas spent significantly less time in moderate to vigorous physical activity than those in peri-urban and rural areas (P =.015). Women with class II/III obesity spent more time in sedentary activities than those with healthy weight or overweight/class I obesity (P =.048). Conclusions: This study characterizes physical activity among Samoan adults and highlights variation by sex, urbanicity, and weight status. In providing initial device-measured estimates of physical activity in Samoa, this analysis establishes a baseline from which the success of future attempts to intervene on physical activity may be assessed. [ABSTRACT FROM AUTHOR]

Myristica swamps are one of the world's unique freshwater ecosystems. In recent years there has been an increase in reports about their distribution along the Western Ghats. In this paper, we present a new distribution record for Myristica swamps in the northern part of the Western Ghats in Maharashtra. The Myristica swamp is located within the Bhalandeshwar Sacred Grove of Kumbral Bagwadi, Dodamarg Maharastra, India. This forms the second report from the state of Maharastra. Frequent field visits were made to study and document the floral assemblage and biodiversity in the swamp from November 2023 to January 2024. The swamp is dominated by Myristica magnifica Bedd. and is part of a sacred grove protected by villagers due to religious beliefs. The second discovery of a Myristica swamp with a gap of just six years points out to the potential existence of more swamps in the region. Therefore, systematic surveys are needed to document undocumented swamps in various areas. [ABSTRACT FROM AUTHOR]

Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box–Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained ex vivo release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. In vivo pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (Cmax = 16.77 µg/g, tmax = 30 min) after intranasal administration compared to intravenous administration (Cmax = 2.53 µg/g, tmax = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain via olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders. [ABSTRACT FROM AUTHOR]

Bacteriophages have been explored as indicators of the presence of human viruses in water. F+ coliphages are of particular interest due to their abundance in wastewater and some groups surviving the treatment process. This study assessed the prevalence of F+ coliphages and FRNA bacteriophage (FRNAPH) groups in the wastewaters of Mumbai city and explored its correlation with the presence of SARS-CoV-2. Wastewater samples (raw = 63, treated = 99) collected from three wastewater treatment plants (WWTPs) were assessed for F+ coliphages, FRNAPH groups and SARS-CoV-2. Of the 63 raw wastewater samples, 92% were positive for F+ coliphages and FRNAPH, while SARS-CoV-2 was detected in 76% of samples; FRNAPH GI RNA was the most prevalent (96.82%) followed by FRNAPH GII (77.77%), FRNAPH GIII (36.50%), and FRNAPH GIV (4.76%). A significant correlation was observed between the occurrence of SARS-CoV-2 and F+ coliphages, FRNAPH GII and FRNAPH GIII RNA copies and also between F+ coliphages and FRNAPH GII and GIII. These observations suggest that F+ coliphages, FRNAPH GII and GIII can be explored further as indicators of SARS-CoV-2 in wastewaters. Also, F+ coliphage detection may be a cost-effective and practical approach for monitoring virus elimination during wastewater treatment. [ABSTRACT FROM AUTHOR]

A pulsar's pulse profile gets broadened at low frequencies due to dispersion along the line of sight or due to multipath propagation. The dynamic nature of the interstellar medium makes both of these effects time-dependent and introduces slowly varying time delays in the measured times-of-arrival similar to those introduced by passing gravitational waves. In this article, we present an improved method to correct for such delays by obtaining unbiased dispersion measure (DM) measurements by using low-frequency estimates of the scattering parameters. We evaluate this method by comparing the obtained DM estimates with those, where scatter-broadening is ignored using simulated data. A bias is seen in the estimated DMs for simulated data with pulse-broadening with a larger variability for a data set with a variable frequency scaling index, |$\alpha$|⁠ , as compared to that assuming a Kolmogorov turbulence. Application of the proposed method removes this bias robustly for data with band averaged signal-to-noise ratio larger than 100. We report the measurements of the scatter-broadening time and |$\alpha$| from analysis of PSR J1643 |$-$| 1224, observed with upgraded Giant Metrewave Radio Telescope as part of the Indian Pulsar Timing Array experiment. These scattering parameters were found to vary with epoch and |$\alpha$| was different from that expected for Kolmogorov turbulence. Finally, we present the DM time-series after application of this technique to PSR J1643 |$-$| 1224. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of prophylactic mesh placement in reducing the incidence of parastomal hernias following colostomy, ileostomy, and ileal conduit formation. Methods: A systematic review identified relevant studies evaluating parastomal hernia incidence with prophylactic mesh use during stoma formation. Pairwise meta-analysis and network meta-analysis using Bayesian modeling were performed. Results: 25 studies, consisting of 16 randomized control trials (RCT), 6 follow up studies, and 3 retrospective cohort studies, were included. Prophylactic mesh led to significantly fewer parastomal hernias beyond 6 months follow-up (OR 0.43, 95% CI 0.33–0.58). Hernias were reduced with mesh for both ileal conduits and colostomies. When analyzing hazard ratios (HRs), only 6 studies were included, and a statistically significant difference was observed among both randomized controlled trials (RCTs) (HR 0.75 [0.53, 0.92], p = 0.01) and non-RCTs (HR 0.57 [0.36, 0.92], p = 0.02). Network meta-analysis found the retromuscular approach with mesh had the lowest hernia rate. Regression was non-significant for variations between study types. Conclusion: This meta-analysis demonstrated prophylactic mesh placement during ostomy creation significantly reduced parastomal hernia risk, more prominently beyond 6 months, consistently across randomized trials and observational studies for urologic and gastrointestinal ostomies. The retromuscular technique was most effective. [ABSTRACT FROM AUTHOR]

Three new hybrid polyoxometalates (POMs) based on transition metals, namely, copper metal with γ-[Mo8O26]4− polyoxometalates [Cu(DMF)4(Mo8O26)·2C3H8NO]·1.8 DMF (1), cobalt metal with hexamolybdate [Co(DMSO)6][Mo6O19] (2), and nickel metal with hexamolybdate [Ni(DMSO)6][Mo6O19] (3), were developed. These materials were characterised by applying both analytical and spectroscopic techniques (IR, TGA, and CHNO elemental analysis), and structural elucidation was performed using single-crystal X-ray diffraction studies. Among these hybrid POMs, octamolybdate with copper was used for the catalytic production of benzimidazoles. The incorporation of [Cu(DMF)4] between two octamolybdates results in the transformation of POMs into a useful catalyst, which effectively catalyses the oxidative cross-coupling of anilines, benzyl alcohol, and sodium azide to produce benzimidazole. This catalytic reaction occurs in the presence of tert-butyl hydroperoxide (TBHP) at a moderate temperature. Benzimidazole and its derivatives are highly preferred owing to their wide-ranging biological activities and clinical applications. These compounds are exceptionally effective in terms of their selectivity ratio and inhibitory activity. The catalytic reaction presented herein is a one-pot procedure that includes a series of reactions, such as C–H functionalization, condensation, ortho selective amination, and cyclization. [ABSTRACT FROM AUTHOR]

Background: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways. Methods: The authors analyzed whole genome sequencing data from the Trans‐Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers. Results: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03–1.64; p =.02) but not colorectal (p =.77) or lung cancer (p =.32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced‐stage (p =.01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41–6.62; p <.001) and without adjustment (HR, 2.50; 95% CI, 1.32–4.72; p =.004) for advanced‐stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98–2.41; p =.06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06–1.83; p =.01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11–4.3; p =.02) with mCA >5%. Conclusions: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification. In the Women's Health Initiative Trans‐Omics for Precision Medicine study, participants with clonal hematopoiesis of indeterminate potential (CHIP) had higher breast cancer incidence and a higher colorectal cancer mortality than women without CHIP. The presence of autosomal mosaic chromosomal alterations with >5% cell fraction was associated with higher incidence of breast cancer but no other cancers. [ABSTRACT FROM AUTHOR]

Purpose: Physical activity research among patients with metastatic breast cancer (MBC) is limited. This study examined the feasibility and potential benefits of Fit2ThriveMB, a tailored mHealth intervention. Methods: Insufficiently active individuals with MBC (n = 49) were randomized 1:1 to Fit2ThriveMB (Fit2ThriveMB app, Fitbit, and weekly coaching calls) or Healthy Lifestyle attention control (Cancer.Net app and weekly calls) for 12 weeks. Fit2ThriveMB aimed to increase daily steps via an algorithm tailored to daily symptom rating and step goal attainment. The primary outcome was feasibility defined as ≥ 80% completion rate. Secondary feasibility metrics included meeting daily step goal and wearing the Fitbit ≥ 70% of study days, fidelity, adherence to intervention features and safety. Secondary outcomes included physical activity, sedentary time, patient reported outcomes (PROs), health-related quality of life (QOL) and social cognitive theory constructs. A subsample (n = 25) completed functional performance tests via video conferencing. Results: The completion rate was 98% (n = 1 died). No related adverse events were reported. Fit2ThriveMB participants (n = 24) wore the Fitbit 92.7%, met their step goal 53.1%, set a step goal 84.6% and used the app 94.1% of 84 study days. Intent-to-treat analyses indicated trends toward improvements in activity, QOL, and some PROs, social cognitive theory constructs, and functional performance tests favoring the Fit2ThriveMB group. Significant effects favoring Fit2ThriveMB were observed for self-efficacy and goal-setting. However, some PROs and functional performance improvements favored the control group (p-values > 0.05). Conclusions: Fit2ThriveMB is feasible and safe for patients with MBC and warrants further evaluation in randomized controlled trials with larger sample sizes. Registration Clinicaltrials.gov NCT04129346, https://clinicaltrials.gov/ct2/show/NCT04129346 [ABSTRACT FROM AUTHOR]

Minimally invasive procedures for endovascular interventions involve manual navigation of a guidewire. Endovascular interventions encompassing highly tortuous vessels would benefit from guidewires which exhibit higher dexterity. This paper introduces a version of the COAST (COaxially Aligned STeerable) guidewire system capable of exhibiting higher dexterity. The system presented in this paper consists of three coaxially aligned tubes with a tendon to actuate the middle tube. Furthermore, it is possible to independently rotate the middle tube with respect to the outer tube. This variation enables the guidewire to achieve curvature in different planes while avoiding rotation of the entire structure. We also present the simulated stability of the guidewire with different outer tube geometries and experimentally validate the model. Experimental analysis and modeling of the kinematic behavior of the system is presented. A model to calculate the curvature vs. tendon stroke relationship for the optimal notch geometry is presented with an average RMSE of 0.16 mm. A control strategy addressing the snapping instabilities to ensure reliable operation is discussed. A custom phantom vessel and an aortic arch phantom model were used to demonstrate the ability of the system to safely navigate through tortuous pathways without exhibiting these elastic instabilities. [ABSTRACT FROM AUTHOR]

Objective: There is a rising effort for hospital emergency departments (EDs) to offer and expand substance use disorder (SUD) services. This state-wide evaluation studies SUD services offered along the continuum of implementation across Kentucky's EDs to inform future state efforts to build ED bridge programs. Methods: We conducted a mixed-methods study using an online survey of all Kentucky Emergency Department Directors between January and May of 2023. We created a hospital-level dataset which we used to summarize quantitative questions and thematically analyze open-ended responses. Results: Our sample included 85 unique respondents (89% of all eligible Kentucky hospitals). Nine (11%) had active bridge programs to initiate opioid use disorder patients on buprenorphine. Respondents reported that the most challenging SUD-related services for EDs to implement were buprenorphine induction for opioid use disorder treatment (n = 36, 42%), referrals to community-based providers (n = 34, 40%), and providing social work services (n = 25, 29%). Respondents noted that the implementation and improvement of screening protocols were needed to better identify patients with SUD, expressed concerns about care continuity, and explicitly conveyed the need and desire for additional supports to provide SUD care. Conclusions: The landscape of Kentucky's ED SUD supports shows several hospitals that offer services along the continuum of SUD care, and highlights the importance of technical assistance and financial resources to ensure the continuum is broadly available. Kentucky's experience speaks to broader national challenges in supporting SUD in EDs – specifically the need for financial resources, buy-in and education, and creating referral relationships to ensure care continuity. [ABSTRACT FROM AUTHOR]

This study investigates the spheroidization of titanium Ti-6Al-4V powder particles using numerical models developed in Abaqus and OpenFOAM. Spherical particles are crucial in powder-based additive manufacturing due to their superior flowability, packing density, and mechanical properties, enhancing printing precision and the quality of final products. While conventional techniques such as gas atomization and plasma spheroidization have been extensively researched, the potential of laser spheroidization remains underexplored. To address this gap, detailed numerical analyses of laser spheroidization were conducted, modeling heat transfer from the laser to powder particles using a transient uncoupled heat transfer method with latent heat considerations, while particle deformation was simulated with a phase-fraction-based interface-capturing approach integrated with Navier-Stokes equations. The results, validated against analytical models, indicate that particles within the 20–80 μm range experience optimal spheroidization within a 0.005-second residence time under laser heating, with particles smaller than 30 μm reaching evaporation temperatures of 5,000°C, while larger particles reshape without evaporating under a typical heat flux of 94 MW/m2 (1.8 kW laser power). This study demonstrates that laser spheroidization of Ti-6Al-4V powder can potentially increase powder yield by 10%, offering higher power density and shorter melting times compared to plasma spheroidization, thus presenting a more efficient alternative for achieving spherical particles of specific sizes. [ABSTRACT FROM AUTHOR]

Introduction: Receptor activity-modifying proteins (RAMPs) are known to modulate the pharmacology and function of several G-protein-coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R). However, the precise effects of different RAMPs on PTH1R signalling and trafficking remain poorly understood. This study investigated the impact of RAMP2 and RAMP3 on PTH1R function using a range of PTH and PTH-related protein (PTHrP)-derived ligands. Methods: We employed FRET imaging to assess PTH1R interactions with RAMPs. Cell surface expression of PTH1R was evaluated in the presence of RAMPs. PTH1R-mediated cAMP accumulation, β-arrestin recruitment, and calcium signalling were measured in response to various ligands. Antibody-capture scintillation proximity assays were used to examine G-protein activation patterns. Results: PTH1R preferentially interacted with RAMP2 and, to a lesser extent, RAMP3, but not with RAMP1. RAMP3 co-expression reduced cell surface expression of PTH1R. RAMP2 significantly enhanced PTH1R-mediated signalling responses to PTH (1-34), PTHrP (1-34), PTH (1-84), and PTH (1-17) analogue ZP2307, while RAMP3 co-expression attenuated or abolished these responses. Full-length PTHrP analogues exhibited lower potency and efficacy than PTHrP (1-34) in activating PTH1R. RAMP2 increased the potency and/or efficacy of these analogues, whereas RAMP3 reduced these responses. RAMP2 differentially modulated G-protein activation by PTH1R in a ligand-dependent manner, with PTH (1-34) and PTHrP (1-34) inducing distinct patterns of G-protein subtype activation. Discussion: These findings highlight the complex role of RAMPs in regulating PTH1R signalling and trafficking, revealing differential effects of RAMP2 and RAMP3 on receptor function. The data suggest that targeting the PTH1R/RAMP2 complex may be a promising strategy for developing novel bone anabolic therapies by leveraging biased agonism and functional selectivity. Further research using physiologically relevant models is needed to elucidate the therapeutic potential of this approach. [ABSTRACT FROM AUTHOR]

Background: In-vivo CRISPR Cas genome editing is a complex therapy involving lipid nanoparticle (LNP), messenger RNA (mRNA), and single guide RNA (sgRNA). This novel modality requires prior modeling to predict dose-exposure-response relationships due to limited information on sgRNA and mRNA biodistribution. This work presents a QSP model to characterize, predict, and translate the Pharmacokinetics/Pharmacodynamics (PK/PD) of CRISPR therapies from preclinical species (mouse, non-human primate (NHP)) to humans using two case studies: transthyretin amyloidosis and LDL-cholesterol reduction. Methods: PK/PD data were sourced from literature. The QSP model incorporates mechanisms post-IV injection: 1) LNP binding to opsonins in liver vasculature; 2) Phagocytosis into the Mononuclear Phagocytotic System (MPS); 3) LNP internalization via endocytosis and LDL receptor-mediated endocytosis in the liver; 4) Cellular internalization and transgene product release; 5) mRNA and sgRNA disposition via exocytosis and clathrin-mediated endocytosis; 6) Renal elimination of LNP and sgRNA; 7) Exonuclease degradation of sgRNA and mRNA; 8) mRNA translation into Cas9 and RNP complex formation for gene editing. Monte-Carlo simulations were performed for 1000 subjects and showed a reduction in serum TTR. Results: The rate of internalization in interstitial layer was 0.039 1/h in NHP and 0.007 1/h in humans. The rate of exocytosis was 6.84 1/h in mouse, 2690 1/h in NHP, and 775 1/h in humans. Pharmacodynamics were modeled using an indirect response model, estimating first-order degradation rate (0.493 1/d) and TTR reduction parameters in NHP. Discussion: The QSP model effectively characterized biodistribution and dose-exposure relationships, aiding the development of these novel therapies. The utility of platform QSP model can be paramount in facilitating the discovery and development of these novel agents. [ABSTRACT FROM AUTHOR]

Background: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology. Objective: The purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation. Methods: We used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed. Results: We identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways. Conclusion: MiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients. Trial registration: LOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840]. [ABSTRACT FROM AUTHOR]

Summary: Persistent albuminuria (PA) is common in sickle cell anaemia (SCA). With the association of chronic kidney disease (CKD) with increased mortality, biomarkers that predict its development or progression are needed. We evaluated the association of select biomarkers with PA in adults with SCA using Kruskal–Wallis rank‐sum test and logistic regression models, with adjustment for multiple testing. Of 280 subjects, 100 (35.7%) had PA. Median plasma levels of soluble vascular cell adhesion molecule‐1 (VCAM‐1) (1176.3 vs. 953.4 ng/mL, false discovery rate [FDR] q‐value <0.003), thrombin–antithrombin complex (5.5 vs. 4.7 ng/mL, FDR q‐value = 0.04), and urinary angiotensinogen (AGT) (12.2 vs. 5.3 ng/mg, FDR q‐value <0.003), urinary nephrin (30.6 vs. 27.2 ng/mg, FDR q‐value = 0.04), and urinary kidney injury molecule‐1 (KIM‐1) (0.8 vs. 0.5 ng/mg, FDR q‐value <0.003), normalized to urine creatinine, were significantly higher in subjects with PA. In multivariable analysis, only urinary AGT (odds ratio = 1.058, FDR q‐value <0.0001) remained a significant predictor of PA. In addition, soluble VCAM‐1 (FDR q‐value <0.0001), D‐dimer (FDR q‐value <0.0001), urinary AGT (FDR q‐value <0.0001), KIM‐1 (FDR q‐value <0.0001), and nephrin (FDR q‐value <0.0001) were significantly associated with urine albumin–creatinine ratio in multivariable analyses. Longitudinal studies to evaluate the predictive capacity of biomarkers for the development and progression of CKD in SCA are warranted. [ABSTRACT FROM AUTHOR]

Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities. [ABSTRACT FROM AUTHOR]

Background: Earlier research on internet addiction (IA) in the adult population in India has concentrated on isolated prevalence surveys conducted nationwide. A systematic grasp of pooled prevalence necessitates a meta-level evaluation of all prior literature. This study aims to investigate the prevalence of IA and its correlates among adults in India. Methods: We searched EBSCOhost, PubMed, PsycInfo, PsycArticles, and ProQuest for the studies published from 1990 to 2022 and included studies using Young's Internet Addiction Test criteria (age range 18–40 years). The authors obtained a total of 358 non-duplicate records after a thorough search, and they found 10 pertinent epidemiological studies involving 12,286 adults. Results: The pooled prevalence for mild, moderate, severe, and any level of IA was 36.33% (95% confidence interval [CI]: 30.72%–42.13%), 18.04% (95% CI: 13.49%–23.08%), 0.88% (95% CI:0.50%–1.36%), and 58.34% (95% CI:49.34%–67.07%), respectively. The review of correlates suggested psychosocial factors like male gender, single-parent families, co-morbidities like depression, stress, anxiety, interpersonal issues, andmediating factors like loneliness. Conclusions: Based on the synthesis of findings, this review underlines the common factors of IA and emphasizes the significance of psycho-social factors in IA; thus, to promote healthy use of technology and to manage IA, a multi-modal psychotherapeutic intervention module for mental health practitioners needs to be developed in line with this review. [ABSTRACT FROM AUTHOR]

Introduction: Non Carious Cervical Lesions (NCCLs) represent a prevalent dental condition characterised by the erosion of tooth structure at the cementoenamel junction without the involvement of dental caries. These lesions pose significant challenges due to their aesthetic impact, potential for dentinal hypersensitivity, plaque accumulation, pulpal complications and compromised structural integrity of the teeth. Tooth preparation traditionally uses diamond abrasive points and tungsten carbide burs for micromechanical adhesion. Newer methods, like ultrasonic tips, offer a more conservative approach, but limited research has compared their effects on bond strength, particularly in cervical cavity restorations with nanohybrid composites. Aim: To compare the surface roughness of cervical cavity preparations utilising diamond abrasive points and ultrasonic tips, and to evaluate the shear bond strength of restorations with composite resin. Materials and Methods: The present in-vitro comparative study was conducted in the Department of Conservative Dentistry and Endodontics, Guru Nanak Institute of Dental Sciences and Research, Panihati, Kolkata, West Bengal, India, from October 2023 to December 2023. The study included 52 freshly extracted maxillary 1st premolar teeth extracted for orthodontic reasons. These teeth were divided into two groups: Group-I (n=26) underwent surface preparation using a diamond abrasive point (No. 835-012, Piranha, SS White, USA), while Group-II (n=26) was prepared using an ultrasonic tip (Woodpecker G 20, Guilin Woodpecker, China). Teeth were cleaned, disinfected and stored in 0.1% thymol solution before being prepared with diamond abrasive points or ultrasonic tips, following which the specimens were restored using nanohybrid composite material (Solare X, GC Corporation, Japan). Surface roughness was assessed using a digital profilometer before the restoration, and the shear bond strength of repaired specimens was measured with a Universal Testing Machine. Statistical analysis was performed using GraphPad Prism, with independent samples t-tests applied to compare results between groups, and a significance level set at 5%. Results: Group-I exhibited greater surface roughness (6.33±2.18 μm) compared to Group-II (4.91±1.57 μm). Group-I also showed higher shear bond strength (62±13 MPa) than Group-II (59.3±19.9 MPa), though this variation was not statistically significant (p-value=0.56). Conclusion: Within the present study's limitations, diamond abrasive points created significantly greater surface roughness compared to ultrasonic tips. However, no statistically significant variations have been observed in shear bond strength among the two methods, suggesting that ultrasonic tips may be considered as an alternative to diamond abrasive points in clinical settings, avoiding their drawbacks while achieving adequate restoration retention. [ABSTRACT FROM AUTHOR]

Background: The Levodopa Equivalent Daily Dosage (LEDD) calculation algorithms help in capturing and harmonization of Parkinson's Disease (PD) therapies. Analyzing these updates is essential for validating their effectiveness. Objective: To assess updated LEDD conversion factors in capturing the newer therapies in PD and therapy modules in different geographical cohorts. Methods: Data were sourced from 10 Centers from 6 countries representing 2 different continents. The study compared the LEDD conversion factors proposed by Tomlinson et al and Jost et al, alongside investigating demographic disparities. Results: The analysis involved 2943 subjects; 87% (n = 2577) met the UK Brain Bank criteria for PD. The LEDD differed significantly across methodologies (Tomlinson vs. Jost, 598 mg vs 610 mg, P < 0.0001). Geographical disparities highlighted variations in PD onset age (P < 0.0001). Jost and Tomlinson's calculations demonstrated consistency within but significant differences across countries (P < 0.0001).Age at onset revealed statistically significant differences in LEDD requirements (P < 0.0001), which were particularly higher in 21–50 years (718 mg vs 566 mg). This subgroup also demonstrated increased usage of non‐Levodopa therapies (P < 0.0001). Men exhibited higher total LEDD (P = 0.001). 34% reported dyskinesia, associated with higher LEDD (756 mg, P < 0.0001). Surgically treated patients also had higher LEDD (P < 0.0001) and a significant difference between Jost and Tomlinson dosages (761 mg vs716mg) reflecting the incorporation of newer therapeutic molecules. Conclusion: This analysis delineates the importance of updated LEDD algorithms and intricacies in the landscape of PD treatment, underscored by geographical, age‐related, and gender‐specific variations, in real‐life management scenarios. [ABSTRACT FROM AUTHOR]

Objective Racially minoritized youth with T1D are made vulnerable to disproportionately adverse health outcomes compared to White peers due to enduring systems of oppression. Thus, understanding modifiable psychosocial factors associated with diabetes-related outcomes in racially minoritized youth may help to buffer deleterious effects of racism. One factor meriting exploration is racial-ethnic identity. There is currently limited research on measures fit to assess ethnic identity in youth with chronic illnesses. This study's purpose is to examine the factor structure, reliability, and validity of the revised Multigroup Ethnic Identity Measure (MEIM-R) in a racially- and income-diverse sample of youth with T1D across sociodemographic and illness-related proxies for one's positionality in oppressive systems. Method As part of a larger study examining resilience, 142 youth with T1D ages 12–18 (M age  =  14.66, SD age = 1.62, 55.6% Black/African-American, 44.4% White) completed the MEIM-R and various psychosocial measures. HbA1c levels and illness duration were extracted from medical records and caregivers reported income information. Confirmatory factor analyses compared the structural validity of competing MEIM-R models, and uniform and non-uniform differential item functioning (DIF) was explored across sociodemographic and illness-related factors. Results While a bifactor structure was supported, the MEIM-R was found to exhibit DIF by race and gender on multiple MEIM-R items and did not demonstrate linear bivariate relations with other psychosocial factors. Conclusions Since different MEIM-R item response patterns were observed across racial/ethnic and gender groups, caution is warranted in using this measure in racially and gender diverse youth with T1D. [ABSTRACT FROM AUTHOR]

This paper studies the impact of nonstrategic seller-induced delays on the buyer's willingness to pay in price negotiations. Price negotiations are often characterized by either the buyer or the seller introducing delays and interruptions. In the bargaining literature, time delays are considered costly and could lower the consumer's incentives to engage in bargaining and also reduce the available surplus if the buyer and the seller engage in bargaining. In this paper, we explore the possibility that unanticipated delays from the seller can change the consumer's willingness to pay (WTP) for the product. In a set of laboratory experiments, we find evidence that, relative to fixed pricing, bargaining can result in an increase in WTP and, consequently, in purchase likelihood. In particular, we find that the increase in WTP exists only when the seller delays the response in an unanticipated manner. Based on the recovered distributions of WTP, we find that the increase in profits under bargaining because of the increase in WTP can be sizable as compared with the gains from pure price discrimination. The results provide evidence that a seller can potentially benefit from manipulating response time but only when such manipulation is not anticipated by the consumer. We provide preliminary evidence of the underlying mechanisms and discuss the implications of these findings for researchers as well as practitioners. History: K. Sudhir served as the senior editor. Supplemental Material: The web appendix and data files are available at https://doi.org/10.1287/mksc.2021.0296. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a global issue and can lead to cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B surface antigen (HBsAg) is an important marker of HBV infection and HBsAg quantification could be a useful tool in clinical practice. This systematic literature review aimed to explore the association between HBsAg titres and long‐term disease outcomes and evaluate the relationship between HBsAg titres, or changes in HBsAg titres, and clinical and treatment characteristics in patients with chronic HBV infection. Structured searches were performed in MEDLINE and Embase (January 2000 to 31 March 2023). Eighty‐two studies were included, comprising 51% retrospective cohort studies, mostly conducted in Asia (85%). HBsAg levels were shown to predict the long‐term development of cirrhosis and HCC in patients who were untreated prior to and during follow‐up; however, these data were inconclusive in mixed and treated populations. HBsAg titres were significantly associated with various virological markers including serum HBV DNA, HBcrAg, HBeAg, HBV RNA levels, intrahepatic covalently closed circular DNA (cccDNA) and intrahepatic HBsAg expression. HBsAg titres generally declined over time; this decline was more pronounced in early (HBeAg‐positive) than later disease phases (HBeAg‐negative). Higher decline in HBsAg levels was consistently associated with subsequent HBsAg seroclearance and a greater decline in total intrahepatic HBV DNA and cccDNA levels. In conclusion, this review showed that HBsAg levels and rates of decline could inform assessment, management and prediction of outcomes in chronic HBV infection. Further studies in broader, more diverse populations and treated patients are needed. [ABSTRACT FROM AUTHOR]

Several technologies are implemented for serving industrial information and controlling the process in which the increased complexity and allied fault failed to achieve a reliable transmission to activate the timely network. These data must be transferred from one node to another node without any fault or delay in their nodes. To resolve this problem, an algorithm named SAOA is proposed to communicate the messages from various services without any delay in their nodes. IoT with mobile sink node is simulated in the network based on the MoO4RPL objective and the phases involved in this strategy are topology, route discovery, communication, and route maintenance phase. The topology network is generated for network topology and the rank is computed based on the energy, trust, delay, fault tolerance, and link quality in the multi-objective route discovery phase. In the communication phase, the optimal route is selected using proposed SAOA with fitness function factors. At last, the route maintenance phase is performed, and the proposed SAOA has achieved a minimum distance of 53.807 m, maximum energy of 0.415 J, maximum link quality of 2.163, and maximum trust of 0.701, respectively. In the future, another algorithm is implemented in IoT applications with minimum modifications to evaluate the various metric values. [ABSTRACT FROM AUTHOR]

Unmeasured confounding is often raised as a source of potential bias during the design of nonrandomized studies, but quantifying such concerns is challenging. We developed a simulation-based approach to assess the potential impact of unmeasured confounding during the study design stage. The approach involved generation of hypothetical individual-level cohorts using realistic parameters, including a binary treatment (prevalence 25%), a time-to-event outcome (incidence 5%), 13 measured covariates, a binary unmeasured confounder (u 1; 10%), and a binary measured "proxy" variable (p 1) correlated with u 1. Strengths of unmeasured confounding and correlations between u 1 and p 1 were varied in simulation scenarios. Treatment effects were estimated with (1) no adjustment, (2) adjustment for measured confounders (level 1), and (3) adjustment for measured confounders and their proxy (level 2). We computed absolute standardized mean differences in u 1 and p 1 and relative bias with each level of adjustment. Across all scenarios, level 2 adjustment led to improvement in the balance of u 1, but this improvement was highly dependent on the correlation between u 1 and p 1. Level 2 adjustments also had lower relative bias than level 1 adjustments (in strong u 1 scenarios: relative bias of 9.2%, 12.2%, and 13.5% at correlations of 0.7, 0.5, and 0.3, respectively, vs 16.4%, 15.8%, and 15.0% for level 1). An approach using simulated individual-level data is useful to explicitly convey the potential for bias due to unmeasured confounding while designing nonrandomized studies, and can be helpful in informing design choices. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Least absolute shrinkage and selection operator (LASSO) regression is widely used for large-scale propensity score (PS) estimation in health-care database studies. In these settings, previous work has shown that undersmoothing (overfitting) LASSO PS models can improve confounding control, but it can also cause problems of nonoverlap in covariate distributions. It remains unclear how to select the degree of undersmoothing when fitting large-scale LASSO PS models to improve confounding control while avoiding issues that can result from reduced covariate overlap. Here, we used simulations to evaluate the performance of using collaborative-controlled targeted learning to data-adaptively select the degree of undersmoothing when fitting large-scale PS models within both singly and doubly robust frameworks to reduce bias in causal estimators. Simulations showed that collaborative learning can data-adaptively select the degree of undersmoothing to reduce bias in estimated treatment effects. Results further showed that when fitting undersmoothed LASSO PS models, the use of cross-fitting was important for avoiding nonoverlap in covariate distributions and reducing bias in causal estimates. [ABSTRACT FROM AUTHOR]

The paranasal sinuses are a group of hollow spaces within the human skull, surrounding the nose. They are lined with an epithelium that contains mucus-producing cells and tiny hairlike active appendages called cilia. The cilia beat constantly to sweep mucus out of the sinus into the nasal cavity, thus maintaining a clean mucus layer within the sinuses. This process, called mucociliary clearance, is essential for a healthy nasal environment and disruption in mucus clearance leads to diseases such as chronic rhinosinusitis, specifically in the maxillary sinuses, which are the largest of the paranasal sinuses. We present here a continuum mathematical model of mucociliary clearance inside the human maxillary sinus. Using a combination of analysis and computations, we study the flow of a thin fluid film inside a fluid-producing cavity lined with an active surface: fluid is continuously produced by a wall-normal flux in the cavity and then is swept out, against gravity, due to an effective tangential flow induced by the cilia. We show that a steady layer of mucus develops over the cavity surface only when the rate of ciliary clearance exceeds a threshold, which itself depends on the rate of mucus production. We then use a scaling analysis, which highlights the competition between gravitational retention and cilia-driven drainage of mucus, to rationalise our computational results. We discuss the biological relevance of our findings, noting that measurements of mucus production and clearance rates in healthy sinuses fall within our predicted regime of steady-state mucus layer development. [ABSTRACT FROM AUTHOR]

Purpose: The investigation aims to improve Nd: YAG laser technology for precision cutting of carbon fiber reinforcing polymers (CFRPs), specifically those containing newly created resin (NDR) from the polyethylene and polyurea group, is the goal of the study. The focus is on showing how Nd: YAG lasers may be used to precisely cut CFRP with NDR materials, emphasizing how useful they are for creating intricate and long-lasting components. Design/methodology/approach: The study employs a systematic approach that includes complicated factorial designs, Taguchi L27 orthogonal array trials, Gray relational analysis (GRA) and machine learning predictions. The effects of laser cutting factors on CFRP with NDR geometry are investigated experimentally, with the goal of optimizing the cutting process for greater quality and efficiency. The approach employs data-driven decision-making with GRA, which improves cut quality and manufacturing efficiency while producing high-quality CFRP composites. Integration of machine learning models into the optimization process significantly boosts the precision and cost-effectiveness of laser cutting operations for CFRP materials. Findings: The work uses Taguchi L27 orthogonal array trials for systematically explore the effects of specified parameters on CFRP cutting. The cutting process is then optimized using GRA, which identifies influential elements and determines the ideal parameter combination. In this paper, initially machining parameters are established at level L3P3C3A2, and the optimal machining parameters are determined to be at levels L3P2C3A3 and L3P2C1A2, based on predictions and experimental results. Furthermore, the study uses machine learning prediction models to continuously update and optimize kerf parameters, resulting in high-quality cuts at a lower cost. Overall, the study presents a holistic method to optimize CFRP cutting processes employing sophisticated techniques such as GRA and machine learning, resulting in better quality and efficiency in manufacturing operations. Originality/value: The novel concept is in precisely measuring the kerf width and deviation in CFRP samples of NDR using sophisticated imaging techniques like SEM, which improves analysis and precision. The newly produced resin from the polyethylene and polyurea group with carbon fiber offers a more precise and comprehensive understanding of the material's behavior under different cutting settings, which makes it novel for kerf width and kerf deviation in their studies. To optimize laser cutting settings in real time while considering laser machining conditions, the study incorporates material insights into machine learning models. [ABSTRACT FROM AUTHOR]

Solid organ transplantation (SOT) is the gold standard of therapy for individuals with end‐organ dysfunction. Improved survival outcomes after SOT can help adolescent and young adult (AYA) recipients lead long and healthy life. However, successful SOT during adolescence and young adulthood is often complicated by the innate developmental challenges of this age group. The psychosocial tasks of adolescence include identity development, autonomous decision‐making, establishing social networks, educational and vocational preparation, and navigating romantic relationships. These goals may be amplified or delayed for pediatric SOT recipients. Adolescence is also marked by rapid physical changes in linear growth and the development of secondary sexual characteristics. Yet AYA may experience physical and pubertal delays related to transplantation, as well as exaggerated body image dissatisfaction due to medication side effects. Strict adherence to medication and post‐transplant regimens may interfere with adolescents' desire for normalcy and fitting in with peers. Healthcare providers should be aware that AYA value education and self‐empowerment in transplant care. Transplant success needs to be defined by both medical and psychosocial outcomes, particularly when it relates to the vulnerable AYA population. Fortunately, investment from the patient, family, and care team can aid in transplant recovery and success. This article will identify the developmental challenges faced by AYA undergoing solid organ transplantation as well as strategies to engage positive outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To assess artificial intelligence (AI) ability to evaluate intraprostatic prostate cancer (PCa) on prostate‐specific membrane antigen positron emission tomography (PSMA PET) scans prior to active treatment (radiotherapy or prostatectomy). Materials and Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42023438706). A search was performed on Medline, Embase, Web of Science, and Engineering Village with the following terms: 'artificial intelligence', 'prostate cancer', and 'PSMA PET'. All articles published up to February 2024 were considered. Studies were included if patients underwent PSMA PET scan to evaluate intraprostatic lesions prior to active treatment. The two authors independently evaluated titles, abstracts, and full text. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used. Results: Our search yield 948 articles, of which 14 were eligible for inclusion. Eight studies met the primary endpoint of differentiating high‐grade PCa. Differentiating between International Society of Urological Pathology (ISUP) Grade Group (GG) ≥3 PCa had an accuracy between 0.671 to 0.992, sensitivity of 0.91, specificity of 0.35. Differentiating ISUP GG ≥4 PCa had an accuracy between 0.83 and 0.88, sensitivity was 0.89, specificity was 0.87. AI could identify non‐PSMA‐avid lesions with an accuracy of 0.87, specificity of 0.85, and specificity of 0.89. Three studies demonstrated ability of AI to detect extraprostatic extensions with an area under curve between 0.70 and 0.77. Lastly, AI can automate segmentation of intraprostatic lesion and measurement of gross tumour volume. Conclusion: Although the current state of AI differentiating high‐grade PCa is promising, it remains experimental and not ready for routine clinical application. Benefits of using AI to assess intraprostatic lesions on PSMA PET scans include: local staging, identifying otherwise radiologically occult lesions, standardisation and expedite reporting of PSMA PET scans. Larger, prospective, multicentre studies are needed. [ABSTRACT FROM AUTHOR]

Background: There are increasing reports of the misuse of prescription psychostimulants for cognitive enhancement together with recreational cannabis. This raises a concern that chronic use of cannabis high in Δ9-THC may alter the sensitivity to amphetamines. In this exploratory study we hypothesized chronic exposure to Δ9-THC through vaporized cannabis would diminish the central nervous system (CNS) activity of Adderall. Methods: To address this issue we exposed male and female mice to inhaled vaporized cannabis (10.3% Δ9-THC) or placebo for 30 min each day for ten consecutive days. After 24 h, mice were imaged fully awake for changes in BOLD signal following an IP injection of Adderall (60 µg) during the scanning session. After a 2-week washout, without any cannabis or placebo exposure, mice were again imaged and challenged with Adderall during the scanning session. The data were registered to a mouse 3D MRI atlas with 134 brain regions providing sitespecific increases and decreases in global brain activity. Results: Mice exposed to cannabis when compared to placebo showed a decrease in brain activation to Adderall. The blunted Adderall response was characterized by a decrease in positive BOLD signal and increase in negative BOLD. The prefrontal cortex, accumbens, ventral pallidum, caudate/putamen, and thalamus were most affected. After a 2-week wash out there were no significant differences between the cannabis and placebo groups when challenged with Adderall. Summary: This exploratory study shows that short, daily exposures to inhaled cannabis, something equivalent to recreational use, affects the sensitivity to the psychostimulant Adderall. The reduced Adderall effect on brain activity, particularly circuitry associated with dopaminergic signaling raises concerns about escalation in psychostimulant use. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to investigate the determinants of capital expenditures (CAPEX) in the theme park industry, particularly following the financial stresses induced by the COVID-19 pandemic. CAPEX drivers are poorly understood due to the idiosyncratic nature of this industry, which is dominated by a few large players. It also aims to identify the variables influencing both the growth and maintenance components of CAPEX among U.S. theme park operators. Design/methodology/approach: The paper uses contingency theory to analyze both financial and nonfinancial data from U.S. theme park operators between 2009 and 2021. The paper also uses partial least squares structural equation modeling to manage issues of multicollinearity and to ensure robustness in the findings. Findings: The analysis identifies several key determinants of CAPEX. Resources and the presence of competing theme parks in proximity to an operator's parks positively affect CAPEX. Conversely, higher leverage, dividend payouts, intellectual property (IP) dominance and population density in areas with their active parks correlate with reduced CAPEX. The paper also notes distinct trends in maintenance versus growth CAPEX post-COVID-19, with maintenance CAPEX increasing as operators invest in existing assets while growth CAPEX trending downwards. Research limitations/implications: The study's scope is confined to U.S.-based theme park operators, limiting the generalizability of the findings internationally. Moreover, data limitations restrict the sample size due to the consolidation of the industry players, potentially affecting the statistical power of the analysis. Practical implications: This research offers significant insights for theme park operators, industry analysts and policymakers. Understanding the factors influencing CAPEX can aid operators in strategic planning and investment decisions, especially in a post-pandemic economic environment where efficient capital allocation will be crucial for recovery and growth. A major contribution of this research is the development of a new measure for IP dominance, which allows theme park operators to quantify the impact of IP on their investment strategies. Originality/value: This study contributes uniquely by incorporating both financial and nonfinancial determinants in analyzing CAPEX within the theme park industry, a sector significantly impacted by the pandemic. It introduces novel metrics for assessing the impact of IP on CAPEX and differentiates between the factors driving maintenance and growth expenditures. The findings enrich the existing literature on hospitality management and provide actionable insights that could guide the strategic financial decisions of theme park operators. [ABSTRACT FROM AUTHOR]

To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 µg/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage. [ABSTRACT FROM AUTHOR]