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This paper identifies the aspects of living environment elements (PM2.5, PM10, Noise) throughout Seoul and the urban planning characteristics that affect them by utilizing the big data of the S-Dot sensor in Seoul, which has recently become a hot topic. In other words, it proposes a big data-based research methodology and research direction to confirm the relationship between urban characteristics and environmental sectors that directly affect citizens. The temporal range is from 2020 to 2022, which is the available range of time series data for S-Dot sensors, and the spatial range is throughout Seoul by 500m*500m GRID. First of all, as part of analyzing specific living environment patterns, simple trends through EDA are identified, and cluster analysis is conducted based on the trends. After that, in order to derive specific urban planning characteristics of each cluster, basic statistical analysis such as ANOA and OLS, and MNL analysis were conducted to confirm more specific characteristics. As a result of this study, cluster patterns of PM2.5, PM10, noise and urban planning characteristics that affect them are identified, and there are areas with relatively high or low long-term living environment values compared to other regions. The results of this study are believed to be a reference for urban planning management measures for vulnerable areas of living environment, and it is expected to be an exploratory study that can provide directions to studies related to data in various fields related to environmental data in the future.

Regional air quality over East Asia, including South Korea, has been a center of public attention recently because of a few episodes in which very high particulate matter (PM) concentrations have been observed. Predicting PM variation with lead time of a few hours up to days is one of the key areas that the governments are working on because it can benefit from early warning system to short-term mitigation effort. In this study, the influence of synoptic weather conditions on regional air quality was investigated with the occurrence frequencies of PM episodes as a function of various synoptic weather patterns during winter and spring. (1) During winter, dry moderate (DM) types occur frequently alongside high PM cases (24-h mean PM10 concentration > ). The composite weather map showed a weak northwesterly wind field as a potential cause. On the contrary, it is interesting to note that dry polar (DP) types can be associated with low PM cases (24-h mean PM10 concentration < ) as well as high PM depending on near-surface wind speed. (2) Furthermore, during spring, DM and dry tropical (DT) types were found to be highly correlated with high (much higher) PM concentrations, likely because of the enhanced static stability in the lower troposphere. It should be noted that PM concentration depends on the lower atmospheric stability. The close relationship between synoptic weather patterns and PM concentration suggests that synoptic weather can play an important role in regional air quality.

In the present study, carbon nanofibers containing multi-walled carbon nanotubes (MWCNTs) were fabricated using electrospinning and used as an electrode for structural supercapacitors. Electrospun polyacrylonitrile (PAN) nanofibers were converted to carbon nanofibers with stabilization and carbonization processes assisted by thermal treatment. The surface area of the electrospun carbon nanofiber electrodes was further increased several thousand times using an activation process. Multifunctional supercapacitors were fabricated using electrospun carbon nanofibers and a vacuum resin infusion technique. The specific capacitance was dramatically improved due to the decreased equivalent series resistance and increased surface area of the nanofiber electrodes. Moreover, the carbon nanofiber electrodes helped increase interlaminar fracture toughness of structural supercapacitors because it acted like ‘Velcro’ between the fabric interfaces. This work is a ‘proof-of-concept’ for a simple and effective method to produce an electrode for structural supercapacitors based on the electrospinning technique.

Comprehensive understanding of gene-diet interactions is necessary to establish proper dietary guidelines to prevent and manage general and abdominal obesity. We investigated the role of genetic variants and their interactions with general and abdominal obesity-associated nutrients using a largescale genome-wide association study of Korean adults.A total of 50,808 participants from a Korean genome and epidemiology study were included. Dietary intake was assessed using a food frequency questionnaire. Obesity was defined as a body mass index ≥25 kg/mAmong the individuals consuming fat (%) above DRI, carriers of Ca binding protein 39 (CAB39)- rs6722579 minor allele (A) have a higher risk of AO than those not carrying the SNP (odds ration [OR] = 3.73, p-value = 2.05e-07; interaction p-value = 1.80e-07). Among the individuals consuming vitamin C above DRI, carriers of carboxypeptidase Q (CPQ)- rs59465035 minor allele (T) have a lower risk of AO than those without that SNP (OR = 0.89, p-value = 1.44e-08; interaction p-value = 9.50e-06). The genetic association with obesity was stronger among individuals with a genetic variant rs4130113 near GHR gene region in those consume folate above DRI and with a genetic variant rs5760920 near CRYBB2 gene region in those consume vitamin B2 above DRI.Our study results suggested that interactions of specific polymorphisms at loci and certain nutrients may influence obesity and abdominal obesity.

Community involvement and citizenship have been crucial drivers in energy transitions worldwide. To deepen our understanding of the energy transition and to further promote energy citizenship, we leverage Bourdieu’s concept of cultural capital to shed light on the inequities in community-centered energy transition processes. More specifically, this study demonstrates that cultural capital is an important indicator of an individual’s willingness to participate in renewable energy-related behavior and social movements. Using survey data in the Netherlands as a case study, it finds that depending on the type of energy citizenship, i.e., material participation (investments) or communicative participation (protest), different types of cultural capital are in play. The results of this study imply that a nuanced approach towards both concepts, namely energy citizenship and cultural capital, is needed. The scholarly and practical implications of this study are discussed, and the study concludes with pathways for more comprehensive community engagement.

Purpose The role that corporations play in environmental and social sustainability has become increasingly important due to their size and embeddedness in our everyday lives. This study aims to examine the relationship between corporate social responsibility (CSR) and corporate interlocks for the Fortune 500 companies. Design/methodology/approach To collect data, various sources were used including data web scraped from US Securities and Exchange Commission, Bloomberg ESG, ASSET4, Carbon Disclosure Project and data from each companies’ websites. To measure CSR, this paper uses an original United Nations Sustainable Development Goals (SDG) index, and to measure corporate interlocks, it uses the Bonacich centrality score and has a sample of 401 companies. To account for missing data, Bayesian multiple imputation was used. For the final analysis, linear regression analysis was conducted, for which all the assumptions are met. Findings The findings show that for most SDGs, corporate interlocks is an important predictor, but not for all SDGs. In other words, they indicate that corporate centrality remains to be an important variable in most aspects of CSR, but a more nuanced approach is required. Originality/value This paper uses the SDGs to provide a granular perspective of CSR, which is stronger and more methodologically rigorous compared to the existing metrics of CSR. Consequently, it provides an original insight into the corporate interlocks literature, which has not been empirically researched using granular CSR data.

Treprostinil is a prostacyclin approved for the treatment of pulmonary arterial hypertension. Commercial data sets indicate that approximately 20–25% of patients are prescribed a higher dose than the maximum recommended dosage of nine breaths per treatment session (bps) (54 μg), four times a day (QID) and numerous studies have demonstrated the safety of doses >9 bps QID. This phase 4, retrospective analysis of specialty pharmacy records assessed the effects of inhaled treprostinil at doses >9 bps QID. Patients receiving inhaled treprostinil between September 2009 and June 2018 were included, and a random sampling of 5000 patients was selected for further analysis. Subjects were grouped based on the highest dose reached for ≥2 months within a rolling six-month window and were followed for up to three years. Of the total of 5000 patients analyzed, 28.5% received >9 bps QID. Survival rates were significantly higher in the >9 bps QID dosing group for years one, two, and three ( P 9 bps (17.5 months) compared to doses ≤9 bps (9.5 moths; P 9 bps at years 1, 2, and 3 ( P 9 bps QID had a higher rate of survival and drug persistence over a three-year period, suggesting that higher doses may provide clinically relevant benefits while remaining tolerable.

One dimension of the emerging politics of connected and automated vehicles (CAVs) is the development of public concerns over their societal implications and associated policy issues. This study uses original survey data from the United States to contribute to the anticipation of future policy and political issues for CAVs. Several studies have surveyed the public regarding CAVs; however, there are few studies that highlight the multidimensional public concerns that CAVs will most likely bring. The study breaks down the concept of “public” by showing that the demographic variables of gender, age, race, ethnicity, income, location (rural, suburban, urban), and political ideology (conservative, moderate, liberal) are significantly associated with three of the most salient public concerns to date (safety, privacy, and data security). Furthermore, the effects of demographic variables also vary across the type of policy issue. For example, women tend to be more concerned about safety than their male counterparts, and Hispanics (Latinx) tend to be more concerned about privacy than non-Hispanics. The research shows how the social scientific analysis of the “politics” of CAVs will require attention to the variegated connections between different types of public concern and different demographic variables.

In many clinical trials, patient outcomes are often binary-valued which are measured asynchronously over time across various dose levels. To account for autocorrelation among such longitudinally observed outcomes, a first-order Markov model for binary data is developed. Moreover, to account for the asynchronously observed time points, nonhomogeneous models for the transition probabilities are proposed. The transition probabilities are modeled using B-spline basis functions after suitable transformations. Additionally, if the underlying dose-response curve is assumed to be non-decreasing, our model allows for the estimation of any underlying non-decreasing curve based on suitably constructed prior distributions. We also extended our model to the mixed effect model to incorporate individual-specific random effects. Numerical comparisons with traditional models are provided based on simulated data sets, and also practical applications are illustrated using real data sets.

Background Direct-to-consumer (DTC) genetic testing provides genetic risk to consumers and motivates consumers to take care of their own customized health care. In 2018, we developed and provided a DTC genetic testing service (GENESTART™) in collaboration with Herbalife Korea Co. Ltd. Methods The analyzed dataset consisted of the body fat percentage (BFP), body mass index (BMI), 31 genetic polymorphism genotypes, and responses to 19 questionnaire items of 24,447 individuals. The genetic main effects for BFP and BMI were examined by linear regression analysis, and the interaction effects were examined using a generalized linear model that controlled age and sex as covariates. In the case of BFP, the sample average was 31.47% overall, 24.76% for men, and 32.79% for women, showing that men had an average BFP that was 8 percentage points lower than that of women. The average BMI was 25.38 overall, 26.45 for men, and 25.17 for women, showing that men had an average BMI of 1.2 kg/m2 higher than that of women. Results The FTO and MC4R genes, well-known obesity markers, showed a significant correlation with both phenotypes, and the BDNF gene, which is related to stress obesity, showed a highly significant association with BMI but only a weak association with BFP. Among the remaining genes, TRIB1, ABCA1, MYL2, G6PC, GCKR, GLIS3, CYP17A1, HECTD4, and NT5C2 genes showed significant associations with the obesity-related phenotypes. In this study, we found four interaction results for BFP (ABO and fruits, CYP1A2 and sugary foods, FTO and muscle exercise, MC4R and vitamins) and five interactions for BMI (MC4R and proteins, CSK and fruits, MC4R and calcium, DGKB and calcium, CSK and water). Conclusions This study is expected to enable the provision of personalized and accurate solutions for BFP and BMI management to customers who have undergone genetic testing.

Introduction Aggressive natural killer cell leukemia (ANKL) is a rare hematologic malignancy characterized by the EBV-driven proliferation of mature natural killer cells. It mostly frequently affects younger adults and has a fulminant course with a median overall survival of 2 months. Challenges in managing this disease include an aggressive clinical course, hematologic complications, limited clinical evidence, and a lack of consensus on therapeutic strategies. Areas covered Here, authors reviewed the key aspects of the epidemiology and current understandings of the molecular pathogenesis of ANKL. The available clinical evidence and proposed diagnostic and therapeutic algorithms in treating ANKL are discussed. Currently, the only potential cure is induction therapy with L-asparaginase-based combined chemotherapy regimens, followed by allogeneic hematologic stem transplant. However, options are extremely limited in the relapsed/refractory setting. Recently, international efforts have been made to understand the aberrant molecular pathways of ANKL and identify potential drug targets for this disease; PD-1 inhibitors, EBV-specific cytotoxic lymphocyte therapy, BCL-2 inhibitors, and JAK2 inhibitors in combination with other agents have been shown to have promising potential in treating this aggressive disease. Expert opinion When clinical trials are not available, a personalized approach using next-generation sequencing results should be encouraged in the relapse/refractory setting.

Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses. In this study, 750 older adults with mild cognitive impairment and Alzheimer’s disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion. The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions. Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities.

The potential use of gelatin materials in the liquid composite molding manufacturing (LCM) process was investigated, with specific focus on the reinforcement deformation phenomenon. The adoptability of gelatin as a binder in a composite material with glass fiber for application in the LCM process was evaluated by analyzing the permeability and microscopic structure of the gelatin-coated glass fiber. To assess the tow deformation, the permeability of the non-crimped unidirectional glass fiber mat was evaluated at different flow rates that could be applied in the LCM process. Hysteresis of the permeability was observed as the flow rate increased and decreased, indicative of tow deformation. The permeability of the gelatin-treated glass fiber mat exhibited a relatively smaller variation than that of the untreated glass fiber at the same flow rate. Tow deformation in the untreated and gelatin-treated non-crimped glass fiber mats at different flow rates was evaluated by microscopic analysis and quantified using the tow thickness index. Relatively smaller variations in the permeability and minimal changes in the tow thickness of the gelatin-treated glass fiber mat were observed via microscopic analysis, indicating that gelatin effectively maintained the binding structure of the glass fiber mat.

Introduction: Metastatic breast cancer (MBC) is the 2nd leading cause of cancer-related deaths in American women. While improvements in local and systemic therapies have significantly improved survival, 43,250 MBC patients are expected to succumb to their disease in the United States in 2022 alone. Triple-negative breast cancer (TNBC) represents 15% of all breast cancer and is defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is the most aggressive subtype of breast cancer, known for its early relapse rate, chemo-resistance, and reduced survival. TNBC is also nearly twice as common in African American (AA) than in White women. In this study, we aim to ascertain the cancer disparity in a large cohort of Black/AA TNBC patients compared to their White counterparts in Hampton Roads, Virginia, as well as to the national SEER database. Methods: A retrospective chart review and survival study of 554 TNBC patients who received standard of care (SOC) treatment at Sentara-EVMS-VOA was performed. Kaplan-Meier survival curves were generated. Statistical analyses were conducted to determine if any clinicopathologic parameters, chemotherapy regimens, insurance, or socioeconomic status could be used to predict patient survival and risk stratify Black/AA and White TNBC patients in this Sentara cohort. Results: According to the national SEER TNBC database, 5-year survival rates for Black/AA and Whites are reported as 71.65% and 78.98%, respectively, compared to 70.33% and 75.53% within our local TNBC cohort. The Kaplan-Meier curve, which stratified our TNBC patients by race, predicted significant reduction in breast cancer-specific survival among Black/AA patients as compared to their White counterparts at all TNBC stages, especially in advanced and metastatic settings. This disparity is notably pronounced at stages II and III, as the Black/AA survival curves trend below that of the White TNBC patients for years following surgical intervention. A higher percentage of Black/AA patients were uninsured or under Medicaid coverage and did not receive standard AC-T regimens, particularly for TNBC patients with stage II disease, likely contributing to a reduced 5-year survival in the Black/AA TNBC cohort. We detected racial disparity in prescription of monotherapy or combination chemotherapy that might have also linked to reduced survival in the Black/AA patients from the Sentara catchment areas. Conclusion: Low socioeconomic status is a major impediment for access to health care. Multipronged combination chemotherapy regimens are critical in treating high-risk and high-grade TNBC patients. Therefore, it is imperative that Medicaid coverage includes AC-T regimens to improve TNBC survival, especially in our Black/AA patients in Hampton Roads, Virginia. Citation Format: Taylor N. Drake, Brandon Euker, Angela M. Tang-Tan, Caroline Dasom Lee, Emily L. Breeding, Janet S. Winston, Billur Samli, Rick J. Jansen, Michael Danso, Mary L. Guye, Richard A. Hoefer, Amy H. Tang. Stratifying high-risk patients, quantifying therapy efficacy, and detecting treatment/racial disparity in triple-negative breast cancer (TNBC) at Sentara-EVMS-VOA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1961.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and disproportionately affects BRCA1 mutation carriers and young black women. Black/African American (AA) patients with TNBC have the highest mortality rate and the shortest survival of any racial/ethnic group in the United States. TNBC challenges our ability to personalize effective therapy. Neoadjuvant chemotherapy (NACT) is the standard-of-care (SOC) to treat T2 or LN+ TNBC. The addition of immune checkpoint blockade (ICB) has revolutionized treatment for these high-risk patients. Pembrolizumab plus chemotherapy is the new SOC for neoadjuvant systemic therapy (NST) in TNBC. Pathologic complete response (pCR) is a reliable indicator that correlates with improved long-term survival. However, clinical uncertainties remain in those who have an incomplete pathologic response (pIR) since many similarly treated TNBC patients with identical stage and comparable residual cancer burden (RCB) demonstrate disparate clinical outcomes. Current methods fall short in predicting tumor recurrence and treatment resistance in the clinic. Supported by ample evidence in developmental, evolutionary, and cancer biology, we proposed that EGFR-K-RAS-SIAH pathway activation is a major driving force in TNBC and that its most downstream gatekeeper, SIAH, is a tumor-specific, therapy-responsive, and prognostic biomarker for patient risk stratification in TNBC. The persistent high expression of SIAH in residual tumors after neoadjuvant therapy reflects EGFR/K-RAS pathway activation (ON) and resistance to treatment. The loss of expression of SIAH in residual tumors reflects EGFR/K-RAS pathway inactivation (OFF) and response to treatment (i.e. treatment efficacy). Here we propose to establish the power of SIAH as a prognostic biomarker to differentiate high-risk from low-risk tumors and predict “real-time” therapy response, in both pre- and post-neoadjuvant (NACT/NST) setting. Breast cancer mortality rates in Hampton Roads Virginia and Richmond Virginia are among the worst in the U.S. and demonstrate a major cancer health disparity. Black patients in our region have a 60-70% higher mortality rate than white patients according to CDC/SEER databases. Using a large cohort of 525 racially diverse TNBC patients (246 black and 279 white patients) at Sentara Cancer Network, we conducted Kaplan-Meier survival analyses and detected a major racial disparity, with significantly lower survival among the Black/AA TNBC cohort, compared to national databases. We will expand this TNBC disparity study by using 2 large racially-diverse cohorts of 981 TNBC patients (459 Black and 493 white patients) from the Sentara Cancer Network and VCU Massey Cancer Center to analyze the prognosis of SIAH expression. By focusing on this tumor-driving EGFR-K-RAS-SIAH pathway, we aim to delineate the underlying molecular basis of treatment resistance and racial disparity in high-risk TNBC. Citation Format: Amy H. Tang, Richard A. Hoefer, Dasom Lee, Emily L. Breeding, Mary L. Guye, Janet S. Winston, Billur Samli, Jennifer Koblinski, Valentina Robila, Michael O. Idowu, Rick J. Jansen, Harry D. Bear. Early detection of cancer disparity and treatment resistance in TNBC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5531.

CD19 targeted chimeric antigen receptor-modified T-cell therapy (CAR-T) leads to B cell aplasia and low serum immunoglobulin levels. Long-lived CD19-negative plasma cells may persist through the therapy and generate antibodies. There is a paucity of data describing how CAR-T impacts the persistence of antibodies against vaccine-related antigens and the degree to which CAR-T recipients may respond to vaccines. We characterized the effect of CAR-T on pneumococcal immunoglobulin G (IgG) titers and determine whether pneumococcal conjugate vaccine (PCV13) administered after CAR-T develops long-term humoral protection against pneumococcus. A retrospective chart review was performed to identify CAR-T recipients who had serum pneumococcal IgG titers drawn before (baseline) or at days 90, 180, 270, 360, or 540 after CAR-T. We then determined whether they received PCV13 vaccination at these timepoints. IgG concentration ≥1.3 μg/mL was considered protective for that serotype, and patients with ≥6/11 tested vaccine-specific serotypes meeting this threshold were deemed to have humoral protection against pneumococcus. Absolute pneumococcal IgG titers and the proportion of patients with humoral protection, stratified by serotype, and vaccination status were compared by paired nonparametric t-tests. Absolute counts for lymphocyte, CD4 T-cell, and CD19 cell and total IgG level, along with the rate of invasive pneumococcal infections, were measured at these timepoints. A total of 148 CAR-T recipients with pneumococcal IgG titers measured for at least one of the defined time points were identified. At baseline, 25% (19/76) patients with evaluable pneumococcal IgG titers met the definition of humoral protection. Among 44 patients with paired pneumococcal IgG titers at baseline and day 90, absolute IgG titers of all serotypes decreased (geometric mean = 0.41 and 0.32 µg/mL, respectively; P.001). Thirteen patients were vaccinated following the titer blood draw at day 90 and had paired pneumococcal IgG titers at day 90 and day 180. Absolute IgG titers of all vaccine specific serotypes in these vaccinated patients decreased from day 90 to day 180 (geometric mean = 0.36 and 0.29 µg/mL, respectively; P = .03). The proportion of patients meeting the criteria of humoral protection remained the same at day 180 despite vaccination at day 90. The results were similar among 8 patients vaccinated at day 180, as well as 7 patients consecutively vaccinated at day 90 and day 180 with corresponding pneumococcal IgG titers. When all vaccine-specific pneumococcal IgG titers were pooled together by timepoint regardless of vaccination status, the proportion of patients with humoral protection decreased until day 540. Some patients developed humoral protection after vaccination at day 360, maintained seroprotective IgG titers from baseline, or developed protection after receiving intravenous immunoglobulin treatment secondary to recurrent infections. Our study demonstrated that few large B-cell lymphoma patients had humoral protection against pneumococcus at baseline, and existing IgG titers decreased after CAR-T. PCV13 vaccination at day 90 or day 180 after CAR-T did not increase humoral protection against pneumococcus. Only at day 540 was there evidence of humoral protection against pneumococcus in a modest proportion of patients. Clinical trials are needed to determine the optimal timing of vaccination, before or after CAR-T, to develop protective immunity against Staphylococcus pneumoniae infections.

Recent Internet-of-Things or Wireless Sensor Network devices are often operated with energy harvesters. As there are no energy storages in those devices, power is not consistently provided to the devices at all times. In such transiently powered systems, in order to keep the system reliable without losing any execution contexts, non-volatile memories (NVMs) are typically used for swift backup/restoration of execution contexts. In this article, we perform a real-time schedulability analysis of the transiently powered processors with NVMs. We first quantitatively characterize the charging and discharging behaviors of the energy harvester and extract the compute capability of the system in time interval domain. Then, based on Real-Time Calculus, we determine whether the given multi-task workload is schedulable or not with respect to the earliest deadline first (EDF) or fixed-priority (FP) scheduling policies. In addition, we study how the choice of the threshold voltage parameter affects the schedulability, then propose a feasible threshold selection algorithm to enhance schedulability. We verify the effectiveness of the proposed technique with extensive simulations. Compared to the naive selection method, the proposed technique always shows improvements in schedulability in various workloads.

During the braking process, frictional heat generated between a disc and a pad can lead to high temperatures. The location of friction blocks on the brake pad can lead directly to differences in friction contact time and friction speed at each point on the brake disc surface, this can lead to non-uniform temperature distribution on the brake disc surface. In this paper, the optimum design for friction blocks on a brake pad is investigated using the design of experiments (DOE) of Taguchi approach and response surface method (RSM) with an aim to minimize the deviation in the rate of friction heating in each area along the radial direction of brake disc. 18 design variables on 2 levels are adjusted. A table of orthogonal arrays, L32 (218), is used. Finite element analysis (FEA) is performed to analyze the mean squared error (MSE) values in the temperature deviations from frictional heat, the disc’s thermo-mechanical characteristics are taken into account. Analysis of variance (ANOVA) is carried out using the data gathered from the DOE stage, we find 7 significant factors among the design variables. A meta-model using RSM is proposed for reduction of temperature deviations over the brake disc. An optimized brake pad is analyzed in terms of the temperature and thermal stress imparted on the brake disc, this optimized pad is then compared with the original pad. The maximum temperatures of the optimized pad and original pad were 399.8 °C and 480.6 °C, respectively. The thermal stress of the optimized pad and original pad were 640.4 MPa and 721.4 MPa, respectively. In the optimized model, the size of the hot band on the disc is larger than that from the original model, so the thermal stress distribution on the disc is smaller. Finally, the optimized pad was found to give significant performance benefits with a 16.8 % decrease in maximum temperature and 11.2 % decrease in thermal stress.

OBJECTIVE To determine internal medicine (IM) residents' knowledge of, attitudes towards, and barriers to prescribing buprenorphine for opioid use disorder (OUD). METHODS We conducted a cross-sectional study of IM residents across all 35 Accreditation Council for Graduate Medical Education (ACGME) accredited Florida IM residency programs. We used an online survey to collect information about resident demographics, substance use curriculums, career interests, content knowledge about diagnosing and managing OUD, and attitudes about and barriers to prescribing buprenorphine for OUD. We used Chi-square test to explore differences in interest in prescribing buprenorphine. We created a composite knowledge score and investigated distribution of knowledge among characteristics via Mann-Whitney U test. RESULTS There were 161 participants (response rate 16.0%, n = 1008) across 35 programs Seventy-seven percent of residents provided care for patients with OUD more than once per month. Seventy-four percent report no buprenorphine prescribing training. Higher knowledge scores, interest in primary care, being an intern, and caring for patients with OUD more than monthly were associated with interest in obtaining a buprenorphine waiver (P

Herein, the rheological properties of 2,2,6,6-tetramethylpiperidin-1-oxyl radical-oxidized cellulose nanofiber (TOCNF) suspensions individualized using high-intensity ultrasonication were investigated. The surface charge density of the nanofibers and sonication time were 0.659–1.24 mmol/g and 30–600 s, respectively. With increased surface charge density, the minimum time required for disintegration decreased due to the repulsive force between oxidized nanofibers. Additionally, increased sonication time enhanced the TOCNF nanofibrillation, thereby forming networks between the nanofibers. Further disintegrating TOCNF increased shear viscosity and yield stress of TOCNF suspensions. Based on the crowding factor theory, the relationship between the average fiber width and sonication time was found at various surface charge densities. Ultrasonication was considered as an energy saving and precisely controllable nanofibrillation method. This research shows the change of fiber shapes during the nanofibrillation process, and suggests an estimation of disintegration degree by the relationship between the rheological properties and TOCNF morphology.

Polyamide-6 (PA6)/silica (SiO2) composites with different sizes and concentrations of SiO2 nanoparticles were prepared via in situ anionic ring opening polymerization. An electron probe microanalyzer was used for visual examination to analyze the distribution of SiO2 nanoparticles in PA6/SiO2 composites. In addition, the thermal behavior of PA6/SiO2 composites was evaluated using thermogravimetric analysis and differential scanning calorimetry. As a result, the SiO2 nanoparticles were found to be well dispersed in the ϵ-caprolactam monomer with a watery viscosity. The sizes and the concentrations of the nanoparticles could affect both the polymerization and the crystallization behaviors of the composites.

We demonstrated the effect of a mixture containing fermented Achyranthes japonica Nakai (FS) in the context of a monosodium iodoacetate (MIA)-induced osteoarthritis animal model. The mineralization...

골관절염은 통증을 동반한 만성질환으로 염증성 cytokines, 금속단백분해효소, 단백질가수분해효소 등이 복합적으로 관여한다. 골관절염의 주요 치료 목표는 관절 운동유지 및 통증감소이며 치료 약물로는 주로 비스테로이드성 항염제를 처방하고 있으나, 이러한 약물은 장기 복용 시 부작용이 따른다는 보고가 있어 장기간 복용이 가능한 건강기능식품 개발이 활발히 일어나고 있다. 본 연구에서는 관절염에 효능이 알려진 우슬, 두충, 당귀를 소재로 선정하였고 그중 우슬을 Lactobacillus plantarum으로 발효시켰으며, 이를 복합물로 사용하여 연골세포의 항염증 효능을 확인하고자 연구를 진행하였다. Primary 한 연골 세포에 발효우슬, 두충, 당귀 복합물을 처리한 후 NF-κB와 COX-2 유전자 발현, 염증성 cytokine의 활성 및 유전자 발현, MMPs 유전자 발현, 연골 형성 인자의 유전자 발현 등을 측정하였다. 그 결과 발효우슬, 두충, 당귀 복합물 처리 시 MMP 발현(MMP-3, MMP-13)을 감소시키고 aggrecan 및 collagen type Ⅱ의 발현은 증가시켜 연골 보호 효과에 대한 활성을 확인하였으며, 염증 반응에 관하여 NF-κB 활성 및 염증성 cytokines 의 발현을 억제시켜 항염증 효과에도 영향을 미친 것을 확인하였다. 따라서 발효우슬, 두충, 당귀 추출 복합물이 연골세포에서 항염증 효과를 가진 천연 기능성 식품의 개발에 있어 기초자료로 활용될 수 있을 것으로 기대할 수 있다.

Although there is great media attention to connected and automated vehicles (CAVs) and strong public interest in the technology, it is still under development. Their deployment to the broader public will require new regulations and road traffic rules that are also under development, and there is not yet a globally harmonized approach. This paper reviews the main safety and liability issues for CAVs with a focus on the rules developed for on-road testing to date in Australia, the United States, and Germany. It also reviews government policies from Victoria, Australia, and California, the United States, and it provides an appendix on European Union (E.U.) regulations. After a review of similarities and differences regarding safety and liability provisions, the study suggests how the current provisions can be brought together toward a globally harmonized approach to safety issues that builds on best practices in the three countries.

Objective Long-acting injectable (LAI) antipsychotics, such as paliperidone palmitate (PP), are known to improve treatment adherence in patients with schizophrenia, which can lead to reductions in relapse and hospitalization rates. However, relatively few studies have demonstrated the economic impact of LAIs, especially in Asian populations. Methods We conducted a claim-based mirror-image study to explore changes in healthcare utilization and associated costs, among 1,272 South Korean patients with schizophrenia (ICD-10-CM code F20), between the 1-year periods before and after the initiation of PP treatment. Results Patients accessed outpatient services more frequently after versus before starting PP treatment, with the number of prescription days increasing by 133.45 (p ＜ 0.0001) and the associated costs increasing by USD 1,497.15 (p ＜ 0.0001). The number of admission days was reduced by 11.33 after starting PP treatment (p ＜ 0.0001) and the associated costs were reduced by USD 1,220.75 (p ＜ 0.0001). However, admission cost savings were different according to patients' oral drug compliance. The daily dosages for benztropine, procyclidine, and propranolol decreased, showing that there were fewer side-effects after PP-treatment (p ＜ 0.0001). Conclusion Although the high acquisition cost of PP has been regarded as an obstacle to its clinical use, our results imply that the high prescription costs for PP may be counterbalanced by the reduced admission costs associated with its use. Economic outcomes for patients treated with LAIs should be investigated further to help healthcare decision-makers and providers to determine the value of LAIs relative to other treatment medications.

Background: The non-saponin fraction of Korean Red Ginseng has been reported to have many biological activities. However, the effect of this fraction on anti-diabetic activity has not been elucidated in detail. In this study, we investigated the effects of KGC05P0, a non-saponin fraction of Korean Red Ginseng, on anti-diabetic activity in vitro and in vivo. Methods: We measured the inhibition of commercially obtained α-glucosidase and α-amylase activities in vitro and measured the glucose uptake and transport rate in Caco-2 cells. C57BL/6J mice and C57BLKS/Jdb/db (diabetic) mice were fed diets with or without KGC05P0 for eight weeks. To perform the experiments, the groups were divided as follows: normal control (C57BL/6J mice), db/db control (C57BLKS/Jdb/db mice), positive control (inulin 400 mg/kg b.w.), low (KGC05P0 100 mg/kg b.w.), medium (KGC05P0 200 mg/kg b.w.), and high (KGC05P0 400 mg/kg b.w.). Results: KGC05P0 inhibited α-glucosidase and α-amylase activities in vitro, and decreased glucose uptake and transport rate in Caco-2 cells. In addition, KGC05P0 regulated fasting glucose level, glucose tolerance, insulin, HbA1c, carbonyl contents, and proinflammatory cytokines in blood from diabetic mice and significantly reduced urinary glucose excretion levels. Moreover, we found that KGC05P0 regulated glucose production by down-regulation of the PI3K/AKT pathway, which inhibited gluconeogenesis. Conclusion: Our study thereby demonstrated that KGC05P0 exerted anti-diabetic effects through inhibition of glucose absorption and the PI3K/AKT pathway in in vitro and in vivo models of diabetes. Our results suggest that KGC05P0 could be developed as a complementary food to help prevent T2DM and its complications. Keywords: Diabetes mellitus, Korean Red Ginseng, Non-saponin fraction, Glucose regulation

CPX-351 was approved by the FDA in 2017 as frontline induction chemotherapy for patients aged ≥18 years with newly diagnosed acute myeloid leukemia (AML) which includes myelodysplasia-related changes (AML-MRC) and therapy-related acute myeloid leukemia (t-AML). The efficacy of CPX-351 among younger patients (aged60 years) is currently unclear, as the large, randomized phase 3 study that led to approval of CPX-351 only included patients between the ages of 60 and 75 years.We performed a retrospective study of clinical and molecular data from adult patients with newly diagnosed AML-MRC or t-AML treated with CPX-351. Patients were divided into 2 cohorts: aged 60 years (cohort A) and aged ≥60 years (cohort B). We compared overall response rate (ORR) and median overall survival (mOS) between the cohorts.Of 169 evaluable patients, 21.3% were in cohort A and 78.7% were in cohort B. ORR of the entire cohort was 53.3%; ORR of cohort A was 47.2% compared with 54.9% for cohort B (P = .46). Overall, 54.4% of responding patients proceeded to allogenic stem cell transplant (allo-SCT), including 52.9% of patients in cohort A and 54.8% in cohort B (P = 1.00). At a median follow-up of 24 months, mOS of the entire cohort was 16 months and was similar between cohorts A and B (18 vs. 15 months, respectively; P = .29).CPX-351 resulted in similar response rates and survival outcomes among both younger and older adult patients with newly diagnosed AML-MRC or t-AML.

The Japanese sea lion (Z. japonicus) has been regarded as an extinct species since the last report on Dokdo in 1951. Not much ecological information on the Z. japonicus on Dokdo (hereafter Dokdo sea lion) is currently available. Using a discrete time stage-structured population model, we reconstructed the Dokdo sea lion population to explore the effect of human hunting pressure on them. This study provides the first estimate for the Dokdo sea lion population from 1900 to 1951. The reconstructed capture numbers of the Dokdo sea lion and the parameters estimated in this study were well matched with the recorded numbers and ecological parameters reported previously for the Californian sea lion. Based on the reconstructed population, their number rapidly declined after hunting started and it took less than 10 years for a 70% decline of the initial population, which would be considered to be an extinction risk. Since some caveats exist in this study, some caution about our results is necessary. However, this study demonstrates how rapidly human over-hunting can cause the extermination of a large local population. This study will be helpful to raise people’s awareness about endangered marine animals such as local finless porpoises in Korea.

IntroductionWe have demonstrated that intensive cognitive training can produce sustained improvements in cognitive performance in adolescents. Few studies, however, have investigated the neural basis of these training effects, leaving the underlying mechanism of cognitive plasticity during this period unexplained.MethodsIn this study, we trained 51 typically developing adolescents on cognitive control tasks and examined how their intrinsic brain networks changed by applying graph theoretical analysis. We hypothesized that the training would accelerate the process of network integration, which is a key feature of network development throughout adolescence.ResultsWe found that the cognitive control training enhanced the integration of functional networks, particularly the cross-network integration of the cingulo-opercular network. Moreover, the analysis of additional data from older adolescents revealed that the cingulo-opercular network was more integrated with other networks in older adolescents than in young adolescents.DiscussionThese findings are consistent with the hypothesis that cognitive control training may speed up network development, such that brain networks exhibit more mature patterns after training.

Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces the covariate balance between the RCT and OS, therefore improving the trial-based estimator's generalizability. Exploiting semiparametric efficiency theory, we propose a doubly robust augmented calibration weighting estimator that achieves the efficiency bound derived under the identification assumptions. A nonparametric sieve method is provided as an alternative to the parametric approach, which enables the robust approximation of the nuisance functions and data-adaptive selection of outcome predictors for calibration. We establish asymptotic results and confirm the finite sample performances of the proposed estimators by simulation experiments and an application on the estimation of the treatment effect of adjuvant chemotherapy for early-stage non-small cell lung patients after surgery. This article is protected by copyright. All rights reserved.

Graphene oxide (GO) and multiwalled carbon nanotubes with silver particles (MWNT-Ag) of different concentrations were used as nanofillers to prepare poly(lactic acid) (PLA) nanoparticle films through the solvent casting method. In this study, the effects of nanoparticles on the crystallization behavior, relationships between the dispersion and electrical properties, and hydrolytic degradation behaviors were investigated for the PLA/MWNT-Ag and PLA/rGO films. Differential scanning calorimetry was used to evaluate the crystallization behaviors of the PLA/MWNT-Ag and PLA/reduced GO (rGO) films. Electron probe microanalysis was performed to characterize the dispersion of MWNT-Ag, and X-ray diffraction and Raman spectroscopy were used to determine the degree of dispersion of rGO in the PLA matrix. The results showed that nanoparticles enhanced the crystallization kinetics of PLA as well as the hydrolytic degradation rate. From the measurement of electrical properties, the electrical conductivity of PLA/MWNT-Ag 1.0 wt% was much higher than that of the pure PLA and PLA/rGO films, showing that MANT and Ag nanoparticles contribute greatly to enhancing the electrical conductivity of the PLA/MWNT-Ag films.

Given the growing frequency, severity, and salience of social mobilization and community action on energy and climate issues, in this study we systematically explore the configurations of types of infrastructure, actors, tactics, and outcomes of recent opposition to energy transitions across seven carbon-intensive regions in Asia, Europe, and North America. Based on both a literature review and an original dataset of 130 case studies spanning the past decade, we track opposition to a wide range of energy infrastructure in these regions, including low-carbon options such as renewable energy and nuclear power; provide network analyses of the actors and coalitions involved in such events; and develop a typology and frequency analysis of tactics (such as litigation or protest), and outcomes (such as remuneration, policy change, concessions, or labor protections). We show that the politics of energy transitions in carbon-intensive regions varies significantly from country to country and across types of energy, and we discuss how the configurations of infrastructure, actors, tactics, and outcomes can be explained by differences in national institutions and their responses to global or supranational pressures. By bringing both a sociotechnical and comparative perspective to the global analysis of social movements and energy transitions, we suggest how goals of energy transition are refracted through national and subnational institutions and through local mobilizations both in support of and opposed to those transitions.

Real-world dosing and titration of parenteral (subcutaneous, SC; intravenous, IV) prostacyclin, a mainstay of pulmonary arterial hypertension (PAH) treatment, is not always consistent with prescribing information or randomized trials and has yet to be adequately characterized. The current study describes real-world outpatient dosing and titration patterns over time, in PAH patients initiated on SC or IV treprostinil. A longitudinal, cross-sectional analysis of medication shipment records from US specialty pharmacy services between 2009 and 2018 was conducted to determine dosing and titration patterns of SC or IV treprostinil in the outpatient setting beginning with the patient's first shipment. The sample for analysis included shipment records for 2647 patients (IV = 1040, SC = 1607). Although more patients were started on SC treprostinil than IV, median initial outpatient IV treprostinil dose (11 ng/kg/min at month on therapy one [MOT1]) was consistently and statistically significantly higher than initial outpatient SC dose (7.5 ng/kg/min at MOT1

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This article concerns evaluating treatment effects on survival outcomes for a target population and considers a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root- n n consistency and efficiency, the so-called rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show that it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small cell lung cancer.

With the growth of commercial and recreational use of unmanned aerial vehicles (UAVs, or drones), there is increasing attention to the need for regulation. A systematic review is conducted using a multiple comparative perspective: across three political jurisdictions (the United States, the European Union, and Japan) and across two areas of societal implication and policy (i.e., privacy and safety), with additional comparisons drawn from regulations for related cyber-physical systems. The multiple comparative analysis conducted in this paper shows that safety is a much more salient concern than privacy. Moreover, safety is focused on technical features of the UAVs, registration and certification, and differentiation by use case. Privacy regulations tend to follow broader digital privacy guidelines. Although there are some privacy rules that are UAV-specific, many of them do not yet directly address privacy challenges that are specific for UAVs. Additional comparisons with safety and privacy policies for automated vehicles and the smart grid reveal areas of potential development for harmonization and policy guidance. The study concludes with ten recommendations for future policy development.