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Introduction: Axial spondyloarthritis (axSpA) is a chronic rheumatic disease affecting the spine and sacroiliac joints, encompassing both ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) patients. Patient quality of life (QoL) is assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) (disease-specific measure) and the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) (disease-specific measure). Both ASQoL and ASAS HI have similar parameters and scoring ranges, however, their performance relative to each other is unknown. We conducted a cross-walk analysis of the ASAS HI to the ASQoL in AS and nr-axSpA patients. Methods: A cross-sectional survey using the Adelphi axSpA Disease Specific Programme™, conducted with rheumatologists and their consulting AS and nr-axSpA patients in the United States, was undertaken between Jun and Aug 2018. Rheumatologists provided confirmed diagnoses of AS and nr-axSpA alongside patients' demographic and clinical characteristics. Patients reported quality-of-life measures using the validated ASAS HI and ASQoL questionnaires. Model performance was assessed by comparing root-mean squared error (RMSE) from tenfold cross-validation to determine the best mapping from ASAS HI to ASQoL, and vice versa. RMSE was calculated overall, and for lower, middle and upper thirds of the predicted scale. Results: Data from 283 AS and 274 nr-axSpA patients were analyzed. Predicting ASAS HI using ASQoL values, the best model was non-parametric local linear regression, with overall RMSE of 1.851. Predicting ASQoL using ASAS HI values, the best model also used non-parametric local-linear regression, with overall RMSE of 2.254. In predicting ASAS HI and ASQoL, models performed better in predicting lower values in the predicted scale (RMSE 1.597, 1.871, 2.871 across thirds for ASAS HI; and 1.719, 2.577, 3.140 for ASQoL). Conclusions: Results present a scoring algorithm for cross-walking the ASAS HI to the ASQoL and vice versa, with the approach enabling comparisons to be made across studies. [ABSTRACT FROM AUTHOR]

Abstract Climate change impacts all water sources, including high quality groundwater that supplies agricultural irrigation in many regions of the United States. This study assessed groundwater level changes in the U.S. Mid-Atlantic region with a focus on cultivated areas. Trends of groundwater level were estimated using linear regression, and examined for shallow, medium, and deep depths across physiographic regions of Mid-Atlantic. A hotspot analysis was conducted to identify spatial clusters of wells with rising or declining groundwater levels. In addition, differences in the percentage of cultivated area with declining groundwater between cultivated land categories was examined at the county level. From 2002–2016, the Mid-Atlantic region had an overall decline in groundwater level (0.06 m/yr, 95% CI: 0.03, 0.09) although groundwater changes varied by physiographic regions. The Coastal Plain physiographic region was dominated by declining groundwater wells (48%) and had the most significant groundwater level declines (0.23 m/yr, 95% CI: 0.19, 0.26). Significant groundwater level rises were detected in Southern Virginia adjacent to the Chesapeake Bay (0.92 m/yr on average), which could be due to the cessation of groundwater withdrawal from one of the region's largest groundwater users. In the Mid-Atlantic region, shallow groundwater was found to have slight rising trends (0.08 m, p < 0.05) while deeper groundwater showed distinctive declining trends (1.36 m, p < 0.05) between 2002 and 2016. There were significantly more cultivated areas with declining groundwater levels (88% vs. 35%, p < 0.05) in counties with high percentages of cropland (> 50%) compared to areas covered by less cropland. As climate and human pressures increase, it will be critical to identify and evaluate alternative water sources, such as reclaimed water, to sustain agricultural production and protect groundwater resources. Highlights • U.S. Mid-Atlantic region had overall groundwater decline from 2002 to 2016 (0.06 m/yr). • Coastal Plain physiographic region had highest declining groundwater trends (48%). • Coastal Plain region had most significant groundwater level declines (0.23 m/yr). • Shallow groundwater slightly rose (0.08 m), deep groundwater declined (1.36 m). • Counties with high-density cropland had most areas with groundwater decline (88%). [ABSTRACT FROM AUTHOR]

This paper proposes a new model to identify if and how much the educational attainment gap between blacks and whites is due to the difference in their neighborhoods. In this model, individuals belong to two unobserved types: the endogenous type, which may move in response to the neighborhood effect on their education; or the exogenous type, which may move for reasons unrelated to education. The Heckman sample selection model becomes a special case of the current model in which the probability of one type of individuals is zero. Although we cannot find any significant neighborhood effect in the usual Heckman sample selection model, we do find heterogeneous effects in our two-type model. In particular, there is a substantial neighborhood effect for the movers who belong to the endogenous type. No significant effects exist for other groups. We also find that the endogenous type has more education and moves more often than the exogenous type. On average, we find that the neighborhood variable, the percentage of high school graduates in the neighborhood, accounts for about 28.96% of the education gap between blacks and whites. [ABSTRACT FROM AUTHOR]

Abstract: The paper investigates the linkages between customer service, customer satisfaction, and firm performance in the US airline industry. In particular, the moderating effects of market concentration and firm dominance on the service–satisfaction–performance relationship are examined. Our major finding is that market concentration dampens the relationship between customer satisfaction and airline profitability. Although the same moderating relationship was not found for market power, these results, combined, indicate that airlines can increase profits in concentrated markets without providing for the same, concomitant increases in customer satisfaction as airlines operating in more competitive markets. From a public policy perspective, our results point to the importance of regulators monitoring airline actions, such as mergers and alliances, that serve to increase the concentration of markets, but may result in lower levels of customer satisfaction. [Copyright &y& Elsevier]

Abstract: Carbon taxes have largely been discussed as individual country measures (even if taken simultaneously) aimed to reduce carbon emissions, slow global warning, and internalizing the externalities associated with carbon generating activities, such as power generation. There has however been little emphasis on the incentives for subgroups of countries to jointly peruse carbon taxes. Yet for large importers of oil such as the US, the EU and China, their incentive is clearly to act together and have their taxes partly or wholly borne by oil exporters given this incentives. This paper discusses the potential for joint OECD (or non-OPEC) carbon taxes to reduce OPEC''s monopoly rent and provide benefits to non-OPEC countries provided jointly agreed trigger strategies are adhered to enforce mutual cooperation. To this end, we develop a multi-region general equilibrium structure with an endogenously determined oil supply by OPEC in which both emissions and energy prices are endogenously determined. Our results suggest that jointly enacted carbon taxes by the US, the EU and China can be heavily borne by oil exporters; they reduce the welfare of OPEC and increase the welfare of non-OPEC countries. These carbon taxes reduce global emissions, but the effect is small. [Copyright &y& Elsevier]

The People's Republic of China can become an important and influential player in the world through its overseas investments in developing countries. This article examines and compares the determinants of Chinese and American direct investment around the world. The cross-sectional analysis is adopted for the years 2005 and 2006. Basic and improved Sala-i-Martin extreme bound analyses are applied in searching for robust determinants. The results suggest that distance, infrastructure facilities, and energy reserves are important factors in attracting investment from China and the United States. Institutional factors are not robust determinants of China's outward direct investment, suggesting that Chinese investors do not pay enough attention to institutional risks in making investments. [ABSTRACT FROM AUTHOR]

An interview is presented with the Chinese virologist Jin Dong-Yan of the University of Hong Kong, discussing his experiences working in several different national research systems. Questions address topics such as his work in the United States, Hong Kong, and mainland China; the tenure and recruitment policies of the University of Hong Kong; and changes occurring in the Chinese research system.

Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects., (© 2022. The Author(s).)

Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC 50 ) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC 50 1.13-2.01 μM). Bexarotene demonstrated the highest Cmax:EC 50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: (1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules <1 cm in diameter., Materials and Methods: In the present study, 1000 thyroid nodules in 894 consecutive patients with final diagnoses were included; these thyroid nodules were investigated via FNA biopsies in our hospital. The ultrasound (US) features of the thyroid nodules were reviewed and stratified according to the categories defined by the ACR TIRADS and ATA guidelines., Results: Compared with the ACR TIRADS guidelines, the ATA guidelines had a higher sensitivity (93.4% (P < 0.001)) and a larger negative predictive value (NPV) (85.3% (P= 0.034)). Compared with the ATA guidelines, the ACR TIRADS guidelines had a higher specificity (66.0% (P < 0.001)), a greater PPV (73.6% (P= 0.001)), and greater accuracy (75.5% (P= 0.017)). Compared with the ATA guidelines, the ACR TIRADS guidelines resulted in significantly fewer unnecessary FNA biopsies (P= 0.007)., Conclusions: This study suggests that both the ACR TIRADS and ATA guidelines have unique strengths with regard to their diagnostic performance. In terms of reducing the number of FNA biopsies, the ACR TIRADS guidelines were superior to the ATA guidelines.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC 50 of 1.3 ± 0.3 µM and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity.

Purpose: The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation., Materials and Methods: Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men., Results: Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group., Conclusions: The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: The 4Kscore Test is a prebiopsy blood test that incorporates four prostate protein biomarkers along with patient clinical information to determine a man's risk for high-grade, aggressive (Gleason ≥7) prostate cancer. However, some men likely to benefit from the test may be seen in primary care settings where the digital rectal examination (DRE) information is not always obtained. In this study, we assessed the clinical validity of the 4Kscore Test when the DRE information was not included in the algorithm., Methods: The Prospective 4Kscore Validation Study enrolled 1012 men scheduled for prostate biopsy across 26 urology practices in the United States. The 4Kscore was calculated for each patient with and without DRE information. The primary outcome was Gleason ≥7 prostate cancer on prostate biopsy. The contribution of DRE to the predictive accuracy of the test was evaluated by area under the receiver operating curve (AUC-ROC), risk calibration and clinical consequences., Results: High-grade, aggressive prostate cancer was found in 231 (23%) of the 1012 patients. Both versions of the 4Kscore Test, with and without DRE, showed excellent discrimination (AUC=0.821 with DRE and AUC=0.818 without DRE input) and excellent calibration. No clinically significant difference was found between the two versions of the 4Kscore., Conclusions: The 4Kscore Test algorithm, whether DRE findings are available or not, performs well in predicting a man's risk of high-grade, aggressive prostate cancer. Patients who are suspected of having aggressive prostate cancer can safely have their risk better defined by 4Kscore even if a DRE has not been performed recently., (© 2017 John Wiley & Sons Ltd.)

Objectives: The purpose of this study was to assess the health literacy levels of Hispanic college students., Methods: Participants were students at a major Hispanic-serving university in the southwestern United States. The design was cross-sectional, and data were collected using the Newest Vital Sign in English. Analyses included frequencies and descriptive statistics, simple and multiple logistic regression, and χ(2)/Fisher exact tests., Results: A total of 331 students participated. The overall Newest Vital Sign mean score was 5.1 (standard deviation 1.18); more than 90% (n = 299) obtained a score equivalent to an "always adequate literacy." A lower percentage than that found by a national survey scored at the "below adequate literacy" level. Language spoken at home was the only covariate that significantly affected test scores (P = 0.01)., Conclusions: The overall health literacy level of the participants was higher than the general Hispanic adult population. Investing in the education of Hispanics may help to address disparities in health literacy.

Background: Many epidemiological studies have found a positive association between periodontal disease (PD) and risk of chronic obstructive pulmonary disease (COPD), but this association is varied and even contradictory among studies. We performed a meta-analysis to ascertain the relationship between PD and COPD., Methods: PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD. Data from the studies selected were extracted and analyzed independently by two authors. The meta-analysis was performed using the Comprehensive Meta-Analysis software., Results: Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional) involving 3,988 COPD patients were yielded. Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001), with sensitivity analysis showing that the result was robust. Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association. Publication bias was detected., Conclusions: Based on current evidence, PD is a significant and independent risk factor of COPD. However, whether a causal relationships exists remains unclear. Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression.

Background: Fenofibrate significantly reduces circulating triglyceride (TG) concentrations, particularly in individuals with elevated levels. The purpose of the current study was to determine whether fenofibrate treatment reduces markers of oxidative stress, oxidized low density lipoprotein (ox-LDL) and 8-isoprostane (8-isoP), in a manner similar to TG where those with the highest levels show the greatest reductions., Materials/methods: The concentrations of TG, 8-isoP, and ox-LDL were measured in plasma before and after 3 weeks of fenofibrate treatment (160 mg/d) in a sub-cohort (n=187) of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study., Results: Data were divided into tertiles as determined by pre-treatment values of the respective target. Fenofibrate treatment resulted in significant reductions in TG concentrations by 24.2% (p<0.0001), 41.9% (p < 0.0001), and 46.6% (p < 0.0001) in tertiles 1, 2, and 3, respectively. Significant reductions were also observed in ox-LDL of 7.2% (p=0.0096), 8.5% (p = 0.0019) and 12.1% (p < 0.0001) in tertiles 1, 2, and 3, respectively. Finally, fenofibrate treatment resulted in a 32.7% increase (p=0.0201) in 8-isoP levels in tertile 1, but a significant decrease of 34.4% (p < 0.0001) in tertile 3., Conclusions: This study is the largest to date to demonstrate that fenofibrate reduces oxidative stress and the first to show a suppressive effect on 8-isoP levels in individuals with a high oxidative burden following short term (3 wk) drug therapy. Those with the highest baseline levels of ox-LDL and 8-isoP showed the greatest reductions following fenofibrate treatment. Given the role of oxidative stress in atherosclerosis and coronary heart disease, our observations may partially explain the efficacy of fenofibrate in reducing cardiovascular events in select patients., (Published by Elsevier Ireland Ltd.)