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We present a novel approach for iodide sensing based on the heavy-atom effect to quench the green fluorescent emission of organosilicon nanoparticles (OSiNPs). The fluorescence of OSiNPs was significantly quenched (up to 97.4% quenching efficiency) in the presence of iodide ions (I-) through oxidation by hydrogen peroxide. Therefore, OSiNPs can serve as a fluorescent probe to detect I- with high selectivity and sensitivity. The highly selective response is attributed to the hydrophilic surface enabling good dispersion in aqueous solutions and the lipophilic core allowing the generated liposoluble I2 to approach and quench the fluorescence of OSiNPs. The linear working range for I- was from 0 to 50 µM, with a detection limit of 0.1 µM. We successfully applied this nanosensor to determine iodine content in edible salt. Furthermore, the fluorescent OSiNPs can be utilized for the determination of total antioxidant capacity (TAC). Antioxidants reduce I2 to I-, and the extent of quenching by the remaining I2 on the OSiNPs indicates the TAC level. The responses to ascorbic acid, pyrogallic acid, and glutathione were investigated, and the detection limit for ascorbic acid was as low as 0.03 µM. It was applied to the determination of TAC in ascorbic acid tablets and fruit juices, indicating the potential application of the OSiNP-based I2 sensing technique in the field of food analysis.
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Antioxidantes , Corantes Fluorescentes , Iodetos , Limite de Detecção , Nanopartículas , Iodetos/análise , Iodetos/química , Nanopartículas/química , Antioxidantes/análise , Antioxidantes/química , Corantes Fluorescentes/química , Compostos de Organossilício/química , Espectrometria de Fluorescência/métodos , Ácido Ascórbico/análise , Sucos de Frutas e Vegetais/análiseRESUMO
BACKGROUND: Medication misuse or overuse is significantly associated with poor health outcomes. Information regarding the knowledge, cultural beliefs, and behavior about medication safety in the general population is important. AIM: To conduct a survey on medication habits and explored the potential factors impacting medication safety. METHODS: The current survey included adults from 18 districts and counties in Harbin, China. A questionnaire on medication safety was designed based on knowledge, cultural beliefs, and behavior. Both univariate and multivariate analyses were used to explore the factors that impacted medication safety. RESULTS: A total of 394 respondents completed the questionnaires on medication safety. The mean scores for knowledge, cultural beliefs, and behavior about medication safety were 59.41 ± 19.33, 40.66 ± 9.24, and 60.97 ± 13.69, respectively. The medication knowledge score was affected by age (P = 0.044), education (P < 0.001), and working status (P = 0.015). Moreover, the cultural beliefs score was significantly affected by education (P < 0.001). Finally, education (P = 0.003) and working status (P = 0.011) significantly affected the behavior score. CONCLUSION: The knowledge, cultural beliefs, and behavior about medication safety among the general population was moderate. Health education should be provisioned for the elderly, individuals with a low education level, and the unemployed to improve medication safety in Harbin, China.
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Low-carbon city pilot policy (LCCP) is an innovative initiative for promoting low-carbon transformation and green development in China, which is of great practical significance for realizing China's vision of "double carbon" on schedule. In this study, LCCP implementation is treated as a "quasi-natural experiment," and the spatial difference-in-differences approach is used to quantitatively examine the carbon reduction effects and impact mechanisms of LCCP using panel data of 283 cities in China from 2006 to 2017. The results show that since 2011, LCCP has significantly reduced the carbon intensity of the pilot cities by 0.13%, resulting from the effects of urban environmental governance, industrial structure optimization, and urban innovation level improvement. Meanwhile, there is a significant spatial spillover effect which results in a 0.9% reduction in carbon intensity of neighboring cities. The spatial spillover range of the reduction effect is about 500 km, which decays with distance. Moreover, the carbon reduction effect of the policy is spatially and temporally heterogeneous, and the reduction effect is more significant for resource-based cities, and different for resource-based cities in different development stages. The above findings provide useful policy insights for constructing low-carbon cities under China's "dual carbon goals" and help to realize the win-win path of green development and carbon reduction transition.
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Conservação dos Recursos Naturais , Política Ambiental , Cidades , China , Carbono , Políticas , Desenvolvimento EconômicoRESUMO
In the current work, the influence of high-pressure homogenization (HPH) (200, 250, and 300 MPa) on pH, Brix, turbidity, viscosity, particle size distribution (PSD), zeta potential, color, polyphenol oxidase (PPO), peroxidase (POD), polyphenol profile and bioaccessibility of total phenolic compounds was studied. The results show no change in the apple juice's pH, TSS and density. In contrast, other physiochemical properties of apple juice treated with HPH were significantly changed. Besides total phenolic content (15% degradation) in the HPH-treated apple juice at 300 MPa, the PPO and POD activities were reduced by a maximum of 70 and 35%, respectively. Furthermore, among different digestion stages, various values corresponding to PSD and zeta potential were recorded; the total phenolic content was gradually reduced from the mouth to the intestine stage. The polyphenol bioaccessibility of HPH-treated apple juice was 17% higher compared to the untreated apple juice.
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Land intensive use is important for sustainable land use while carbon emission is a constraint to achieve carbon neutrality; they are closely related and committed to sustainable socioeconomic development. The spatial interactions and complex mechanisms between them make it difficult to clarify their relationship precisely. This paper combines the spatial Durbin model and mediating effect model to describe the effects of urban land intensive use (ULIU) on carbon emissions (CEs) for 30 provinces in China during 1995-2018. An inverse U-shaped relationship between ULIU and CEs is proved while considering the spatial interaction. All the provincial observed values of ULIU are less than the inflection point of the curve, which means that the improvement of the ULIU will cause more CEs. Meanwhile, ULIU has multi-indirect effects on CEs, with urbanization and industrial structure upgrading playing mediating roles in the mechanism. The spatial spillover effects of CEs per unit area on the neighboring provinces are negative, indicating that the interregional influence cannot be ignored. These findings have theoretical and practical significance as they reveal the multi-effects of ULIU on CEs. To realize carbon emission reduction effectively, more attention should be paid to improving the intensity of the urban land and strengthening the regional cooperation.
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Carbono , Urbanização , Carbono/análise , China , Indústrias , Dióxido de Carbono/análise , Desenvolvimento EconômicoRESUMO
Introduction: Systemic nutrition and immune inflammation are the key factors in cancer development and metastasis. This study aimed to compare and assess four nutritional status and immune indicators: prognostic nutritional index (PNI), nutritional risk index (NRI), neutrophil-to-lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII) as prognostic indicators for patients with thymic epithelial tumors. Materials: We retrospectively reviewed 154 patients who underwent thymic epithelial tumor resection at our hospital between 2004 and 2015. The optimal cutoff value for each nutritional and immune index was obtained using the X-tile software. Kaplan-Meier curves and Cox proportional hazards models were used for survival analysis. Results: Univariate analysis showed that PNI, NRI, NLR, SII, albumin (ALB), the albumin/globulin ratio (A/G), WHO stage, T stage, and drinking history were associated with the overall survival (OS) of patients (P < 0.05). The NRI, NLR, A/G, ALB, T stage, and WHO stage were significant independent prognostic factors of OS in multivariate analysis (P < 0.05). Finally, we constructed a coNRI-NLR model to predict OS and recurrence-free survival (RFS). Conclusions: This study suggests that the preoperative NRI, NLR, and coNRI-NLR model may be important prognostic factors for patients with thymic epithelial tumors who undergo surgical resection.
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The increasingly serious problem of consumers returning goods on e-commerce platforms has brought high costs to the Internet economy, carbon pollution to the environment, and waste of social resources. E-commerce platforms can provide useful information to assist consumers to make rational decisions, but they are often filled with useless, repetitive, and even false excessive information, which will lead to information overload and impulsive decision-making of consumers. Most of the previous literature focuses on reverse logistics, return policy, and consumer behavior tendency, etc. From the perspective of consumers' perception of information displayed on e-commerce platforms, there are few research endeavors on the formation mechanism of perceived information overload on consumers' return intention. Taking perceived information overload as an independent variable and consumers' perceived environmental effectiveness as a moderation variable, this study constructs a chain mediation model that affects consumers' online return intention. Based on the analysis of the mediating effects of impulsive buying behavior and cognitive dissonance, this study explored the moderating mechanism of consumers' perceived environmental effectiveness on the chain mediation model. The results show that perceived information overload has a positive influence on online return intention through impulsive buying behavior, and perceived information overload has a positive influence on online return intention through cognitive dissonance. Perceived information overload also positively affects cognitive dissonance through impulsive buying behavior and thus has a significant positive chain mediating effect on consumers' online return intention. More importantly, this research shows that consumers' perceived environmental effectiveness can significantly moderate the chain mediation path by reducing the positive effect of the cognitive dissonance on online return intention. On this basis, this study put forward the corresponding managerial implications from the perspectives of consumers and e-commerce platforms.
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Comércio , Comportamento do Consumidor , Custos e Análise de Custo , IntençãoRESUMO
For assessing the carotenoid bioaccessibility during in vitro digestion, obtaining the micelle fraction that can diffuse through the mucin layer according to the particle size is an important step. However, the accuracy of the various approaches to obtaining the right fraction of micelles described in literature has not been investigated. In many studies the reported bioaccessible fraction might therefore be over- or underestimating the real bioaccessibility. The present study aimed to fill this gap and give approaches to get accurate data on the bioaccessible fraction from samples with different properties. Results illustrated that optimizing the centrifugal speed and duration of the digesta are essential in obtaining the micelle fraction. Different digesta have different optimum centrifugal parameters to obtain the bioaccessible fraction. 6,000 rpm and 40 min was selected as the optimum centrifugal parameter for combined juice (CJ). 6,000 rpm and 60 min was the optimum centrifugal parameter for CJ with oil, and CJ with emulsion using non-ionic emulsifier. 8,000 rpm and 20 min was the optimum centrifugal parameter for CJ with emulsion using ionic emulsifier. Polygalacturonanase (PG)-digested systems required higher centrifugal speed (10,000 rpm) compared with CJ-based systems (6,000 rpm or 8,000 rpm). A prediction model to determine the optimal centrifugation speed/time from the properties of the intestinal digesta was developed. Sample preparation conditions strongly affect carotenoid bioaccessibility assessment from juices during in vitro digestion. Based on these results, it is highly recommended to perform an optimized preparation procedure for bioaccessible fraction prior to carotenoid bioaccessibility analysis.
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Carotenoides , Micelas , Disponibilidade Biológica , Carotenoides/metabolismo , Digestão , Tamanho da PartículaRESUMO
Benzophenone (BP) derivatives (BPs) ultraviolet filters are used in industrial and commercial products and have been reported to be toxic. Studies have investigated the ecological risks but not the human exposure risks of BPs. Residues of 10 BPs (BP, BP-1, BP-2, BP-3, BP-8, 2-OHBP, 4-OHBP, 4-MBP, M2BB, and PBZ) were measured in 110 commercial samples of saltwater fish (SF) and freshwater fish (FF) from Taiwan. The estimated daily intakes (EDIs) and noncarcinogenic risks (as hazard quotients [HQs] and hazard indices [HIs]) were predicted for eight age groups by using Monte Carlo simulation, and sensitivity analysis was conducted to determine the factors influencing risks. The carcinogenic risk of exposure to BP was estimated using lifetime cancer risk (LTCR). The results revealed that seven BPs (BP, BP-3, 2-OHBP, 4-OHBP, 4-MBP, PBZ, and M2BB) were ubiquitous in the fish samples. The mean sums of the content of these seven BPs in FF and SF were 46.4 ng/g and 25.0 ng/g, respectively. Infants (age 0-3 years) exhibited the highest HI of BPs (1.6E-2) and LTCR of BP (2.8E-7) among all age groups. The HQs and HIs of all BPs were less than 1 and the LTCR for BP was lower than the acceptable range (10-4 to10-6) in all age groups, suggesting that BPs intake through fish consumption is not a health concern for Taiwanese people. The results of the sensitivity analysis demonstrated that the amount of SF consumed and 2-OHBP levels exerted the greatest effect on risk. Considering the relatively higher risk of fish consumption and concerns that ultraviolet filters are endocrine disruptors, the potential health risks of BPs intake for infants deserves further attention.
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Benzofenonas , Disruptores Endócrinos , Animais , Benzofenonas/análise , Pré-Escolar , Peixes , Água Doce , Humanos , Lactente , Recém-Nascido , Medição de RiscoRESUMO
In this paper, a mathematical model is formulated to study the transmission dynamics of the novel coronavirus infection under the effect of treatment. The compartmental model is firstly formulated using a system of nonlinear ordinary differential equations. Then, with the help of Caputo operator, the model is reformulated in order to obtain deeper insights into disease dynamics. The basic mathematical features of the time fractional model are rigorously presented. The nonlinear least square procedure is implemented in order to parameterize the model using COVID-19 cumulative cases in Saudi Arabia for the selected time period. The important threshold parameter called the basic reproduction number is evaluated based on the estimated parameters and is found R 0 ≈ 1.60 . The fractional Lyapunov approach is used to prove the global stability of the model around the disease free equilibrium point. Moreover, the model in Caputo sense is solved numerically via an efficient numerical scheme known as the fractional Adamas-Bashforth-Molten approach. Finally, the model is simulated to present the graphical impact of memory index and various intervention strategies such as social-distancing, disinfection of the virus from environment and treatment rate on the pandemic peaks. This study emphasizes the important role of various scenarios in these intervention strategies in curtailing the burden of COVID-19.
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Mitochondrial DNA (mtDNA) is highly polymorphic and encodes 13 proteins which are critical to the production of ATP via oxidative phosphorylation. As mtDNA is maternally inherited and undergoes negligible recombination, acquired mutations have subdivided the human population into several discrete haplogroups. Mitochondrial haplogroup has been found to significantly alter mitochondrial function and impact susceptibility to adverse drug reactions. Despite these findings, there are currently limited models to assess the effect of mtDNA variation upon susceptibility to adverse drug reactions. Platelets offer a potential personalised model of this variation, as their anucleate nature offers a source of mtDNA without interference from the nuclear genome. This study, therefore, aimed to determine the effect of mtDNA variation upon mitochondrial function and drug-induced mitochondrial dysfunction in a platelet model. The mtDNA haplogroup of 383 healthy volunteers was determined using next-generation mtDNA sequencing (Illumina MiSeq). Subsequently, 30 of these volunteers from mitochondrial haplogroups H, J, T and U were recalled to donate fresh, whole blood from which platelets were isolated. Platelet mitochondrial function was tested at basal state and upon treatment with compounds associated with both mitochondrial dysfunction and adverse drug reactions, flutamide, 2-hydroxyflutamide and tolcapone (10-250 µM) using extracellular flux analysis. This study has demonstrated that freshly-isolated platelets are a practical, primary cell model, which is amenable to the study of drug-induced mitochondrial dysfunction. Specifically, platelets from donors of haplogroup J have been found to have increased susceptibility to the inhibition of complex I-driven respiration by 2-hydroxyflutamide. At a time when individual susceptibility to adverse drug reactions is not fully understood, this study provides evidence that inter-individual variation in mitochondrial genotype could be a factor in determining sensitivity to mitochondrial toxicants associated with costly adverse drug reactions.
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Plaquetas/efeitos dos fármacos , DNA Mitocondrial/efeitos dos fármacos , Flutamida/análogos & derivados , Tolcapona/toxicidade , Adolescente , Adulto , DNA Mitocondrial/genética , Feminino , Flutamida/toxicidade , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Depression is a widespread and persistent psychiatric disease. Due to various side effects and no curative treatments of conventional antidepressant drugs, botanical medicines have attracted considerable attention as a complementary and alternative approach. The pathogenesis of depression is quite complicated and unclear. Metabolomics is a promising new technique for the discovery of novel biomarkers for exploring the potential mechanisms of diverse diseases and assessing the therapeutic effects of drugs. In this article, we systematically reviewed the study of botanical medicine for the treatment of depression using metabolomics over a period from 2010 to 2019. Additionally, we summarized the potential biomarkers and metabolic pathways associated with herbal medicine treatment for depression. Through a comprehensive evaluation of herbal medicine as novel antidepressants and understanding of their pharmacomechanisms, a new perspective on expanding the application of botanical medicines for the treatment of depression is provided.
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Medicamentos de Ervas Chinesas , Plantas Medicinais , Depressão/tratamento farmacológico , Medicina Herbária , Humanos , Metabolômica , Compostos Fitoquímicos/farmacologiaRESUMO
Objective: We aim to investigate how a specialization differentiation strategy impacts a physician's online economic rewards and the market conditions under which a specialization differentiation strategy has stronger effects. Methods: The study was performed using data from the health care system of the People's Republic of China. We used physician-based secondary data (data that were collected by someone other than the researcher) in an econometric analysis of transactions obtained from an e-consultation website (haodf.com) for four clinical specialties (pediatrics, endocrinology, gynecology, and oncology) from 2008 to 2015. Patient economics are not considered in this study. A total of 1,153 physicians were included in the analysis. Results: The specialization differentiation strategy has a significant positive impact on the physician's online income (ß = 0.009, p < 0.001) and service price (ß = 0.003, p < 0.001). Moreover, specialization will improve a physician's competitive advantage in terms of income (ß = 0.129, p < 0.001) and service price (ß = 0.024, p < 0.01) when market competition is more intense.Conclusions: Physicians whose expertise is different from that of the majority have higher online incomes and service prices, and this impact will be stronger when market competition is more intense. Our study indicates that e-consultations may accelerate the specialization trend observed in the health care industry because the online market favors more-specialized physicians, and competition in the online market is stronger than in the off-line market. The e-consultation impact may be positive for some complicated diseases but less positive or even negative for chronic diseases, and therefore, policy-makers should be cautious about unintended consequences.
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Renda , Médicos , Especialização , Telemedicina , China , Humanos , Médicos/economia , Encaminhamento e Consulta , Especialização/economia , Telemedicina/economiaRESUMO
BACKGROUND: Currently, reliable approaches for accurate assessment of lymph node metastases (LNM), which is an important indication of preoperative chemoradiotherapy (CRT), are not available for clinically node-negative rectal cancer patients. This study aims to identify clinical factors associated with LNM and to establish a nomogram for LNM prediction in clinically node-negative rectal cancer patients. METHODS: The least absolute shrinkage and selection operator (LASSO) aggression and multivariate logistic regression analyses were applied to identify clinical factors associated with LNM. A nomogram was established to predict the probability of LNM in clinically node-negative rectal cancer patients based on the multivariate logistic regression model. RESULTS: Six potential risk factors were selected on the basis of LASSO aggression analysis, and five of them were identified as independent risk factors for LNM based on multivariate analysis, including MRI-reported tumor location, clinical T classification, MRI-reported tumor diameter, white blood cell count (WBC), and preoperative elevated tumor markers. A nomogram consisting of the five clinical factors was established and showed good discrimination. Decision curve analysis demonstrated that the established nomogram was reliable and accurate for LNM prediction in clinically node-negative rectal cancer patients. CONCLUSIONS: A nomogram based on five clinical factors, including MRI-reported tumor location, clinical T classification, MRI-reported tumor diameter, WBC, and preoperative elevated tumor markers, are useful for assessing LNM in clinically node-negative rectal cancer patients, which is important for preoperative CRT regimens.
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China's Belt and Road Initiative (BRI) is an unprecedented global development program that involves nearly half of the world's countries [1]. It not only will have economic and political influences, but also may generate multiple environmental challenges and is a focus of considerable academic and public concerns [2-6]. The Chinese government expects BRI to be a sustainable development, paying equal attention to economic development and environmental conservation [7]. However, BRI's high expenditure on infrastructure construction, by accelerating trade and transportation, is likely to promote alien species invasions [5], one of the primary anthropogenic threats to global biodiversity [8]. BRI countries may have different susceptibilities to invasive species due to different financial and response capacities [9]. Moreover, these countries overlap 27 of 35 recognized global biodiversity hotspots [10]. Identifying those areas with high-invasion risks, and species with high invasive potentials within BRI countries, is therefore of vital importance for the sustainable implementation of the BRI, and the development of early, economical, and effective biosecurity strategies [11]. In response, we present here a comprehensive study to evaluate invasion risks by alien vertebrates within BRI. We identified a total of 14 invasion hotspots, the majority of which fall along the six proposed BRI economic corridors, with the proportion of grid cells in invasion hotspots 1.6 times higher than other regions. Based on our results, we recommend the initiation of a project targeting early prevention, strict surveillance, rapid response, and effective control of alien species in BRI countries to ensure that this development is sustainable.
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Biodiversidade , Desenvolvimento Econômico , Espécies Introduzidas/estatística & dados numéricos , Vertebrados , Animais , China , Meios de TransporteRESUMO
What causes an older adult to fall? Could the same factor lead to a recurring fall? The purposes of this study sought to address these questions by developing a causal-based assessment method for detection of the initial biomechanical cause of fall, and investigating the causation of 97 falls (out of 195 community dwelling older adults who participated in this study) based on this method. The unrecoverable limb collapse, or unrecoverable instability, along with its point of no return was defined, and the assessment method was established. Both the novel and the second slips of 97 participants who experienced laboratory induced slip related falls were assessed. The results showed that these older adults had more limb collapse (59.8%) initiated falls than instability (40.2%; and 32.0% of which from anteroposterior instability while only 8.2% from mediolateral instability) initiated falls. Interestingly, the majority (86.4%) of those 22 repeated fallers fell twice because of the same cause. These findings shed light on the vulnerability and the causation of recurring falls, which is one of the most challenging healthcare issues that an active but aging population is facing.
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Acidentes por Quedas , Extremidade Inferior/fisiologia , Equilíbrio Postural , Caminhada/fisiologia , Idoso , Feminino , Humanos , MasculinoRESUMO
In this study, we investigate and validate a novel approach to assess and remove additive noise for optical coherence tomography (OCT) imaging. Our method first generates a map of additive noise for the OCT image through Doppler variation analysis. We then remove the additive noise from the real and imaginary parts of the complex OCT signal through pixelwise Wiener filtering. Our results show that the method described in this manuscript improves the sensitivity of OCT imaging and preserves the spatial resolution without the need to modify the imaging apparatus and data acquisition protocol.
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We demonstrated the capability of quantitative optical coherence elastography (qOCE) for robust assessment of material stiffness under different boundary conditions using the reaction force and displacement field established in the sample.
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The distribution, sources, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) were investigated in surface sediments from the Haihe River. Total PAH concentrations varied from 171.4 to 9511.2 ng g-1 with an average of 2125.4 ng g-1, suggesting serious pollution of the Haihe River in comparison with other reported rivers worldwide. PAH contaminants differed significantly among 17 sampling locations with high values occurring in industrial areas and densely populated areas. The composition of PAHs was characterized by high abundance of 4-ring and 5-ring PAHs, and benzo[a]anthracene, chrysene, and benzo[a]pyrene were the predominant components. Molecular diagnostic ratios have confirmed that PAHs in Haihe River sediments resulted from mixed sources, primarily including various combustion processes. Ecological risk assessment using the Sediments Quality Guidelines indicated that PAHs in sediments could cause certain negative effects on aquatic organisms in most survey regions.
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Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Animais , Organismos Aquáticos , China , Monitoramento Ambiental , Sedimentos Geológicos , Medição de Risco , RiosRESUMO
BACKGROUND: Many markets have traditionally been dominated by a few best-selling products, and this is also the case for the health care industry. However, we do not know whether the market will be more or less concentrated when health care services are delivered online (known as E-consultation), nor do we know how to reduce the concentration of the E-consultation market. OBJECTIVE: The aim of this study was to investigate the concentration of the E-consultation market and how to reduce its concentration through information disclosure mechanisms (online reputation and self-representation). METHODS: We employed a secondary data econometric analysis using transaction data obtained from an E-consultation Website (haodf.com) for three diseases (infantile pneumonia, diabetes, and pancreatic cancer) from 2008 to 2015. We included 2439 doctors in the analysis. RESULTS: The E-consultation market largely follows the 20/80 principle, namely that approximately 80% of orders are fulfilled by nearly 20% of doctors. This is much higher than the offline health care market. Meanwhile, the market served by doctors with strong online reputations (beta=0.207, P<.001) or strong online self-representation (beta=0.386, P<.001) is less concentrated. CONCLUSIONS: When health care services are delivered online, the market will be more concentrated (known as the "Superstar" effect), indicating poor service efficiency for society as a whole. To reduce market concentration, E-consultation websites should provide important design elements such as ratings of doctors (user feedback), articles contributed by doctors, and free consultation services (online representation). A possible and important way to reduce the market concentration of the E-consultation market is to accumulate enough highly rated or highly self-represented doctors.