University of California, Irvine

Background While the acute exposure to electronic cigarette (E-cig) vapor has been associated with an increase in blood pressure, the chronic effect of E-cig vapor on blood pressure compared to standard cigarette smoke has not been extensively studied. We determined the effect of E-cig exposure on blood pressure and other measures of cardiac function in both young and old rats. Methods Young Sprague Dawley rats (6 weeks old, both sexes) were randomly exposed to air (n = 34), E-cig with nicotine (E-cig Nic+; n = 30), E-cig without nicotine (E-cig Nic-; n = 28) or standard cigarette smoke (n = 27). Old Fischer 344 rats (25 months old, both sexes) were randomized into 2 groups: (1) 26 rats in the purified air (negative control) group and (2) 17 rats in the electronic cigarette vapor plus nicotine group (E-cig Nic+). After 12 weeks of exposure, hemodynamics were determined by Millar catheter, echocardiography, and thermodilution catheter, a few days after their last exposure. Results In young rats, cigarette smoke was associated with higher systolic, diastolic and mean blood pressures and peak LV systolic pressure, compared to air or E-cig Nic + or E-cig Nic- groups. Neither fractional shortening nor cardiac output differed among the groups. Absolute value for dp/dt min, a measure of diastolic LV function, was lowest in the E-cig Nic- group. Tau, a measure of LV relaxation was worse in this group as well. In old rats, E-cig vaping did not change heart rate, blood pressure, and cardiac function. However, E-cig Nic + exposure was associated with a greater heart weight/BW and LV weight/BW compared to air exposure in old rats. Conclusions Chronic exposure to E-cig vaping did not cause an increase in blood pressure or heart rate, nor did it change cardiac function compared to air in young rats after 12 weeks of exposure, while standard cigarette smoking was associated with an increase in blood pressure. E-cig vaping was associated with a greater heart weight/BW and LV weight/BW compared to air exposure in old rats, suggested that older animals might be more vulnerable to E-cig stimulus than younger ones.

Amid the rapidly evolving digital age, caregivers are adapting their parenting strategies to effectively navigate and co-exist within this new landscape. Each chapter in this section on parenting in the digital age focuses on distinct facets and/or ages related to this overarching theme, with a collective goal of supporting a comprehensive understanding of this critical subject. The first chapter by Reich et al. provides an overview of definitions as well as various research approaches and methodologies focused on parenting and media. Following this, three chapters target specific developmental periods: early childhood (age 0–5; Hirsh-Pasek et al.), middle childhood (age 6–11; Bickham et al.), and adolescence (age 12–18; Wisniewski et al.). McDaniel et al.’s chapter reviews research on the role of digital technology in parent–child interactions, while the final chapter by Browne and colleagues describes how digital media can synergistically affect family interactions among all members (e.g., parents, siblings, etc.). Each chapter in this section shares current understandings, needs for future research, and practical strategies for families. Together, these chapters provide a multifaceted view of the extant research on parenting in the digital age and highlight key considerations for contemporary families.

Background In the last 30 years, consolidation of healthcare systems in the United States has accelerated through mergers and acquisitions. We completed a systematic literature review on integration to determine if its reputation for enhancing the value of healthcare by reducing price and cost/spending and improving overall quality of care is justified. Methods A systematic review of the literature was completed for articles published in the United States from 1990-2024. Primary inclusion criteria were horizontal integration (joining two or more hospitals) (HI) and vertical integration (merging of physicians and hospitals) (VI) and reporting on at least one measure of value (price, cost/spending, or quality) Results Neither HI nor VI has resulted in consistent and significant improvements in price, cost/spending, or quality associated with healthcare delivery. We screened 1297 articles and identified 37 that met inclusion criteria. Results from any form of integration were mixed. Thirteen of 14 studies (93%) about price reported price increases. Thirteen of 16 studies (81%) about cost/spending showed cost increases or no change. Twenty of 26 studies (77%) about quality showed reductions or no change from integration (HI, VI or both). Conclusions Our review suggests that evidence is lacking to support the theory that integration is an effective strategy for improving the value of healthcare delivery. This finding represents an opportunity for healthcare leaders, including surgeons, to better define value in their efforts to improve quality while balancing the financial stability of the healthcare industry with a focus on benefiting the patient.

Objectives Balloon sinuplasty (BSP) and functional endoscopic sinus surgery (FESS) have undergone changes in utilization over time. This study investigates national trends in BSP and FESS and postoperative outcomes over the last decade as well as the impact of Corona Virus Disease 2019 (COVID‐19) on these trends. Methods The TriNetX database was queried for patients undergoing either FESS or BSP from 1/1/2011 to 5/4/2024. Data were collected on patient demographics, diagnoses, and postoperative outcomes. Results A total of 1738 patients underwent BSP and 90,311 underwent FESS. A greater proportion of FESS patients had diabetes (p = 0.001), hypertension (p < 0.001), and chronic pulmonary disease, p = 0.001) compared to BSP whereas a similar proportion of patients for both cohorts had a history of ischemic heart disease (p = 0.73). Body mass index was higher for patients undergoing FESS (28.6 ± 6.5) compared to BSP (28.1 ± 6.578; p = 0.02). Overall postoperative complications were similar between BSP and FESS (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.58–1.09) with similar rates of epistaxis (OR = 0.77, 95% CI = 0.53–1.12) and cerebrospinal fluid (CSF) leak (OR = 0.14, 95% CI = 0.01–2.25). Overall revision rate was higher for FESS (OR = 0.34, 95% CI = 0.21–0.57). Thirty‐day readmission (OR = 0.44, 95% CI = 0.29–0.66) and Emergency Department visits (OR = 0.51, 95% CI = 0.28–0.92) were less common in patients who received BSP. Surgical volume consistently increased over time for both cohorts but at a more rapid pace for BSP (425.64%) compared to FESS (274.19%) and a dramatic decrease in volume by 44.85% and 22.28%, respectively, at the onset of COVID‐19. Conclusion Overall, BSP and FESS surgical volume have steadily increased over time with a drastic reduction following the COVID‐19 pandemic. BSP and FESS carry different complication profiles emphasizing the importance of patient selection and preoperative counseling. Level of Evidence Level 4.

Oligometastatic disease is an increasingly recognized intermediate tumor state between locally confined and widely metastatic cancer. Oligometastatic gastrointestinal (GI) malignancies represent a heterogeneous spectrum of disease, and treatment strategies are tailored to each patient and are impacted by multiple factors. Recent advances in systemic therapies, imaging techniques, and local treatment modalities have revolutionized cancer treatment and present new opportunities to improve outcomes in patients with a limited burden of metastatic disease. However, there is currently a lack of consensus and robust literature to guide patient selection and treatment strategies, including the optimal role and timing of local therapies as adjuncts to standard-of-care systemic therapy. The intent of this review is to comprehensively discuss the role of local therapies in the modern management of oligometastatic GI malignancies.

Background Strong evidence for therapeutic drug monitoring exists for olanzapine and clozapine, however, olanzapine therapeutic drug monitoring is often underutilized. Evidence for pharmacogenomic-guided dosing of antipsychotics is not as robust, especially for cytochrome P450 1A2 metabolized agents such as olanzapine and clozapine. Herein, we present a case involving a patient suspected of having poor CYP1A2 metabolism. Therapeutic drug monitoring of olanzapine was employed to guide the titration of clozapine following olanzapine failure. Despite pursuing pharmacogenetic testing, no meaningful results were obtained due to the omission of CYP1A2 variants associated with poor metabolism. Case presentation A 32-year-old Caucasian male with schizoaffective disorder-bipolar type, ADHD, and autism spectrum disorder presented with extrapyramidal symptoms due to antipsychotic polypharmacy, resulting in multiple falls. He experienced a partial response to olanzapine 40 mg, thus his dose was increased to 50 mg. Sampling an olanzapine trough revealed a supratherapeutic level of 152 ng/mL. Given his history of EPS and other reported adverse effects from antipsychotics, including clozapine, pharmacogenomic testing was pursued. The patient cross-tapered to clozapine slowly, with the knowledge that the patient would likely exhibit elevated levels of olanzapine. Clozapine was efficacious and tolerated well. As expected, the patient exhibited higher clozapine trough concentrations for someone of his age, ethnicity, and gender. Pharmacogenomic testing yielded no relevant findings relating to olanzapine or clozapine metabolism. Conclusion This case highlights the utility of TDM over pharmacogenetic testing for patients on these medications with a suspected alteration in CYP1A2 metabolism. therapeutic drug monitoring emerges as a more practical approach with stronger evidence for its use, particularly in cases of suspected reduced CYP1A2 activity, where suballeles resulting in decreased enzyme function are not readily detectable on standard commercial pharmacogenomic panels.

This study investigated barriers to assessing community health services, and utilization of primary healthcare (PHC) services in Bwari Area Council, Abuja FCT, Nigeria, focusing on identifying barriers and assessing community satisfaction. A cross-sectional quantitative approach was employed over six months, involving 404 participants selected through a multistage sampling technique. Structured survey questionnaires were utilized to collect data on demographics, healthcare utilization, and barriers to PHC. The study revealed diverse demographic characteristics, with a predominant level of satisfaction among 213 (52.87%) participants. Proximity, 128 (31.68%), and cost of services, 103(25.50%) emerged as primary motivators for utilizing healthcare services. Noteworthy barriers include long waiting times, 230(56.93%), inadequate healthcare facilities 206(50.99%), and stigma associated with healthcare-seeking 183 (45.30%). The findings highlight the significance of addressing these barriers to enhance accessibility and satisfaction with community healthcare services. Recommendations include strategies to reduce waiting times, improve infrastructure, conduct awareness campaigns, and explore measures to reduce the cost of services, contributing to the broader goal of fostering equitable healthcare access and enhancing community well-being. The study makes a valuable contribution to the understanding of PHC utilization patterns, satisfaction levels, and barriers, offering insights for policymakers, healthcare providers, and researchers working towards enhancing community health services.

Background Recurrence of sinonasal squamous cell carcinoma (SNSCC) follows an aggressive course, and early detection is paramount. This study identifies the parameters of different surveillance modalities. Methods We conducted a retrospective study of 105 SNSCC patients at three academic institutions from November 2009 to July 2024. Patient records were reviewed for demographics, tumor characteristics, endoscopy, CT, PET/CT, and MRI findings. Multivariable analyses were performed in RStudio. Results Mean time to recurrence was 12.1 months (SD 13.9 months). Patients with higher Charlson Comorbidity Index ( p = 0.041), endoscopic surgical approach ( p = 0.015), and suspicious surveillance findings ( p = 0.029) had higher rates of recurrence. Endoscopy showed a sensitivity of 18.5% and specificity of 99.2%, with a positive predictive value (PPV) of 45.5% and negative predictive value (NPV) of 97.0%. CT had a sensitivity of 75.0% and specificity of 100.0%, with a PPV of 100.0% and NPV of 97.6%. PET/CT demonstrated a sensitivity of 95.2% and specificity of 90.8%, with a PPV of 64.5% and NPV of 97.6%. MRI showed a sensitivity of 72.4% and specificity of 97.1%, with a PPV of 65.6% and NPV of 97.9%. The median time from the last normal surveillance to recurrence was 2.07 months for endoscopy, 8.61 months for CT, 8.15 months for PET/CT, and 6.49 months for MRI. Conclusions The high specificity and NPV of endoscopy, alongside the high sensitivity of PET/CT, support a multimodal approach for surveillance. Given the mean onset of SNSCC recurrence at 12.1 months, surveillance beyond the National Comprehensive Cancer Network's asymptomatic 6‐month guideline is warranted, and follow‐up should be tailored to patient‐specific risk factors.

Cell-cell communication (CCC) occurs across different biological scales, ranging from interactions between large groups of cells to interactions between individual cells, forming a hierarchical structure. Globally, CCC may exist between clusters or only subgroups of a cluster with varying size, while locally, a group of cells as sender or receiver may exhibit distinct signaling properties. Current existing methods infer CCC from single-cell RNA-seq or Spatial Transcriptomics only between predefined cell groups, neglecting the existing hierarchical structure within CCC that are determined by signaling molecules, in particular, ligands and receptors. Here, we develop CrossChat, a novel computational framework designed to infer and analyze the hierarchical cell-cell communication structures using two complementary approaches: a global hierarchical structure using a multi-resolution clustering method, and multiple local hierarchical structures using a tree detection method. This framework provides a comprehensive approach to understand the hierarchical relationships within CCC that govern complex tissue functions. By applying our method to two nonspatial scRNA-seq datasets sampled from COVID-19 patients and mouse embryonic skin, and two spatial transcriptomics datasets generated from Stereo-seq of mouse embryo and 10x Visium of mouse wounded skin, we showcase CrossChat’s functionalities for analyzing both global and local hierarchical structures within cell-cell communication.

Ventricular catheterization with a pressure-volume (PV) catheter is the gold-standard method for assessing in vivo cardiac function in animal studies, providing valuable ‘load-independent’ indices of systolic and diastolic heart performance. PV studies are commonly performed to elucidate mechanistic insights into cardiovascular disease using surgical and genetically engineered rat and mouse models, but there is considerable heterogeneity in how these studies are performed. Wide variation in protocol design, volume calibration, anesthesia, manipulation of cardiac loading conditions and how load-independent indices of cardiac function are derived, as well as in data analysis and reporting, is constraining reliability and reproducibility in the field. The purpose of this manuscript is to combine our collective expertise in performing open- and closed-chest left and right ventricle PV studies in rodents to provide consensus guidelines on how to perform, analyze and interpret these studies using either conductance or admittance PV catheters. We first review recent methodological reporting in rodent PV studies in this journal, and discuss important details required to improve reproducibility within and across PV studies. We then recommend steps to obtain high-quality PV data, from volume calibration to choice of anesthetic agent and acquiring load-independent indices of both systolic and diastolic function. We also consider between- and within-animal variation and recommend how to perform data analysis and visualization. We hope that this consensus paper guides those performing PV studies in rodents and helps align the field with best practices in surgical/analytical methodologies and reporting, facilitating better reliability and reproducibility in the PV field.

Background Academic productivity is believed to be correlated with years of experience and departmental rank, yet there is a paucity of granular academic data between rhinology faculty regarding departmental rank and industry engagement, and how these relate to experience. Objective To examine the interrelationships between experience, department rank and reputation, funding, industry engagement, and academic output of rhinology faculty. Methods Demographics, academic metrics (publications, citations, h‐index, National Institutes of Health [NIH] funding), program rankings, and industry compensation for academic U.S. rhinologists through June 2022 were collected and compared between academic rank and years of experience. Results A cohort of 278 rhinologists were included. Full professors had greater academic metrics (all p < 0.001) and industry compensation (all p < 0.05) than associate professors, assistant professors, and private practice rhinologists. Full professors were also more likely to receive NIH funding than other groups (p < 0.001). Years of experience and industry compensation positively correlated with each other and with academic metrics (all p < 0.001) with significant jumps between the 5th–9th and 10th–14th years of practice (p < 0.001). However, early career (≤8 years) rhinologists published more articles per year than later career (>8 years) rhinologists (p < 0.001). Rhinologists at Doximity top 10 and 25 residency programs by reputation and research output and top 50 U.S. News and World Report departments had significantly greater academic metrics and NIH funding compared to those who were not (p < 0.001). Top 10 and 25 reputations was associated with increased industry compensation (p = 0.024). Conclusions Although early career rhinologists published more frequently, ascending professorial rank, years of experience, and affiliation with top‐ranked departments were associated with total academic productivity. Industry engagement was linked to reputation and years of experience.

Monte Carlo methods have been widely adopted in physics-based rendering. A key property of a Monte Carlo estimator is its variance, which dictates the convergence rate of the estimator. In this paper, we devise a mathematical formulation for derivatives of rendering variance with respect to not only scene parameters (e.g., surface roughness) but also sampling probabilities. Based on this formulation, we introduce unbiased Monte Carlo estimators for those derivatives. Our theory and algorithm enable variance-aware inverse rendering which alters a virtual scene and/or an estimator in an optimal way to offer a good balance between bias and variance. We evaluate our technique using several synthetic examples.

Background Adult trauma centers, including combined pediatric/adult centers (CPACs), see high volumes of penetrating trauma. Few studies have compared outcomes of adolescents presenting with gunshot wounds (GSWSs) at CPACs vs. pediatric only hospitals (POHs). This study aimed to compare injury patterns, complications, and mortality for adolescents sustaining GSWs presenting to CPACs vs POHs, hypothesizing decreased associated risk of complications and mortality at CPACs. Study Design The 2017-2021 Trauma Quality Improvement Program database was queried for adolescents (aged 12-17) with isolated GSWs. Patients transferred or with brain injury were excluded. CPACs included centers with adult and pediatric ACS-verification while POHs only had pediatric ACS-verification. Multivariable logistic regression analysis was performed to identify risk factors associated with in-hospital complications and mortality, controlling for age, injury severity score (ISS), vitals, surgery, and blood transfusions. Results Of 3,064 adolescents presenting with GSWs, 1,512 (49.3%) presented to CPACs. When compared to POH, CPAC patients were slightly older (median, 16 vs. 15 years old, p<0.001) had increased ISS (median: 9 vs. 4, p<0.001), and injuries to the spine (9.3% vs. 5.7%, p<0.001), heart (2.3% vs. 0.7%, p<0.001), lung (19.1% vs. 10.6%, p<0.001), liver (8.5% vs. 4.8%, p<0.001), and spleen (3.2% vs. 1.5%, p=0.002). CPAC adolescents also had increased rates of emergent operations (31.9% vs. 23.5%, p<0.001). However, on multivariable analysis, CPAC adolescents had a similar associated risk of in-hospital complications (OR 0.91, CI 0.59-1.41, p=0.68) and mortality (OR 0.76, CI 0.40-1.48, p=0.42). Conclusions Adolescent GSW patients had similar associated risk of mortality and complications when comparing POHs to CPACs. This suggests that adolescents with GSWs receive similar care at both CPACs and POHs. Additional research is warranted to corroborate these findings.

Background A possible explanation for the continued risk of asthma exacerbations while utilizing current asthma guideline‐based management is the failure to consider small airway dysfunction (SAD) and eosinophilic airway inflammation in assuming asthma‐controlled status. Objective To construct a practical algorithm that potentially identifies additional risks of not well‐controlled (NWC) asthma and exacerbations beyond guideline criteria with oscillometry and fractional exhaled nitric oxide (FENO) determination. Methods This was a retrospective, posthoc analysis of 183 children, ages 4–18 years, with moderate‐to‐severe asthma, characterized by demographic factors, National Health Lung and Blood Institute (NHLBI) determined asthma‐controlled status, therapy step, and lung function status. Impulse oscillometry (IOS) and FENO were performed before spirometry. Abnormal lung function values were determined for spirometry, SAD, and FENO based on established thresholds. Statistical analysis included a decision tree and Venn diagram. Results For 53 patients with guideline‐based NWC, 15 (28.3%) had an FEV1 ≤ 80% predicted. An additional 30 patients (56.6%) had abnormal SAD and/or FENO with a preserved FEV1. Of 130 patients, well‐controlled (WC) by guidelines 76 (58.5%) exhibited SAD and/or abnormal FENO. Conclusions These data demonstrate that over 50% of WC patients with moderate‐to‐severe asthma, with few symptoms and preserved FEV1, had SAD and/or abnormal FENO levels, suggesting the potential of early phenotype‐specific therapy to prevent risk of future exacerbations.

The design of optimization algorithms has long been a matter of art, and it calls for systematic development of methods in which algorithms can be analyzed, designed, and benchmarked with regard to their key attributes such as efficiency, complexity, and robustness. This paper answers to this need by providing a frequency-domain framework for algorithm analysis and synthesis, with a particular emphasis on distributed optimization problems. We propose a general class of gradient-based distributed algorithms that can be viewed as interconnected dynamical systems consisting of a linear time-invariant subsystem and a Lur'e-type nonlinear component, thereby enabling analysis and synthesis of such algorithms from a robust control perspective via the usage of the circle criterion and the Zames–Falb theorem. By linking the convergence of an algorithm with the absolute stability of a corresponding Lur'e system, optimization of the algorithmic convergence rate is recast as a Nevanlinna–Pick interpolation problem akin to an $\mathcal {H}_{\infty }$ optimal control problem. Solutions to such interpolation problems lead to a variety of gradient-based algorithms with optimal and suboptimal convergence rates, and algorithmic complexity judiciously controlled.

Aircraft navigation without global navigation satellite system (GNSS) signals is considered. To this end, a high sensitivity receiver design is presented that could exploit terrestrial cellular signals of opportunity. The receiver operates on downlink orthogonal frequency division multiplexing (OFDM) signals transmitted by long-term evolution (LTE) eNodeBs. Two challenges encountered on high altitude aircraft are addressed: weak signal power and insufficiently accurate initial Doppler estimation. A so-called ultimate reference signal is proposed, which exploits all available LTE resources transmitted by eNodeB's multiple antenna ports. A time-domain-based receiver design is presented to extract carrier phase observables without the need to reconstruct the received OFDM frame. The proposed approach is shown to significantly improve the receiver's sensitivity, amplifying the received power by nearly 21 dB, while also improving the carrier phase estimation accuracy. To evaluate the efficacy of the proposed receiver, experimental results are presented of an aircraft flying over two regions in California, USA: (i) Region A: Edwards Air Force Base (rural) and (ii) Region B: Palmdale (semi-urban). For three aircraft maneuvers (climbing teardrop, descending teardrop, and grid), the results were consistent: more than 100 eNodeBs were trackable, some of which more than 100 km away, at altitudes as high as about 11,000 ft with carrier-to-noise ratio over 40 dB-Hz. Upon fusing the carrier phase observables with altimeter data via an extended Kalman filter, a sustained accurate navigation solution was achieved. Over trajectories of 43.6 km and 56.8 km in regions A and B, traversed in 455 s and 601 s, a three-dimensional position root mean-squared error (RMSE) of 6.8 m and 8.2 was achieved by exploiting an average of about 22 and 11 eNodeBs, respectively

Macromodeling is a crucial technique to enhance a circuit design. Machine learning and neural networks have been recognized as useful techniques to perform macromodeling. In this paper, we have shown that using neural networks to perform macromodeling is feasible. We have presented different neural network methods for modeling the transient response of a low-noise amplifier (LNA) circuit. LSTM-based method has proven to have a superior performance against multilayer perceptron (MLP) and simple recurrent neural network (RNN). Finally, we have proposed a Siamese-LSTM-based neural network (S-LSTM) that can model the LNA circuit with a range of input amplitudes. We have also shown that our proposed S-LSTM model can model the transient response on a power amplifier circuit.