Project description:In the era of innovation dividends, whether investors, as the main participants in the capital market, can tolerate enterprise innovation activities is the key to whether the capital market can help enterprises innovate. This paper takes the listed companies of Shanghai and Shenzhen A-shares in China that disclosed quantitative performance forecasts from 2016 to 2021 as samples, obtains the market reaction of performance forecasts through the event study method and uses them as proxy variables of investors' short-term performance expectations, and uses multiple regression analysis to explore the impact of corporate R&D on investors' short-term performance expectations. The results are as follows: (1) corporate R&D investment significantly reduces investors' short-term performance expectations (that is, investors have a significant tolerance effect on enterprises with higher R&D investment); (2) the increase in the shareholding ratio of institutional investors weakens the tolerance effect; and (3) with the implementation of China's innovation-driven strategy, the tolerance effect of its capital market on enterprise R&D gradually increases, especially for high-tech companies, but has a low tolerance effect on state-owned companies' R&D risk. The results show that investors in China's capital market are not completely rational in their response to corporate R&D, and investors are willing to bear more short-term performance losses for high R&D investment, which is consistent with prospect theory.
Project description:Coastlines are the boundary between the ocean and land and are an important line feature in spatial data. Coastlines must be adapted via map generalization when they are stored in multi-scale spatial databases. This article presents a new method of coastline generalization that considers the buffer consistency from the original coastline to the generalized coastlines. This method uses the geographical distance field to identify the feature points and bends that influence the buffer consistency from the original coastline to the generalized coastline, and the process is also used to simplify the bends and maintain the concave and convex characteristics in the generalization. This method is compared to the bend-simplification method, and the results indicate that the proposed method can preserve the shape characteristics of coastlines. Moreover, the seaward buffer boundaries from the original coastline to the generalized coastline are consistent when the distance is greater than the tolerance of the coastline generalization.
Project description:ObjectivesProfessional paediatrics associations play an important role in promoting the highest standard of care for women and children. Education and guidelines must be made in the best interests of patients. Given the importance of breastfeeding for the health, development and survival of infants, children and mothers, paediatric associations have a particular responsibility to avoid conflicts of interest with companies that manufacture breast-milk substitutes (BMSs). The objective of this study was to investigate the extent to which national and regional paediatric associations are sponsored by BMS companies.MethodsData were collected on national paediatric associations based on online searches of websites and Facebook pages. Sites were examined for evidence of financial sponsorship by the BMS industry, including funding of journals, newsletters or other publications, conferences and events, scholarships, fellowship, grants and awards. Payment for services, such as exhibitor space at conferences or events and paid advertisements in publications, was also noted.ResultsOverall, 68 (60%) of the 114 paediatric associations with a website or Facebook account documented receiving financial support from BMS companies. Sponsorship, particularly of conferences or other events, was the most common type of financial support. The prevalence of conference sponsorship is highest in Europe and the Americas, where about half of the associations have BMS company-sponsored conferences. Thirty-one associations (27%) indicated that they received funding from BMS companies as payment for advertisements or exhibitor space. Only 18 associations (16%) have conflict of interest policies, guidelines, or criteria posted online.ConclusionDespite the well-documented importance of breastfeeding and the widespread recognition that commercial influences can shape the behaviours of healthcare professionals, national and regional paediatric associations commonly accept funding from companies that manufacture and distribute BMS. Paediatric associations should function without the influence of commercial interests.
Project description:BackgroundCancer is a disease of genome alterations that arise through the acquisition of multiple somatic DNA sequence mutations. Some of these mutations can be critical for the development of a tumor and can be useful to characterize tumor types or predict outcome.DescriptionWe have constructed an integrated biological information system termed the Roche Cancer Genome Database (RCGDB) combining different human mutation databases already publicly available. This data is further extended by hand-curated information from publications.The current version of the RCGDB provides a user-friendly graphical interface that gives access to the data in different ways: (1) Single interactive search by genes, samples, cell lines, diseases, as well as pathways, (2) batch searches for genes and cell lines, (3) customized searches for regularly occurring requests, and (4) an advanced query interface enabling the user to query for samples and mutations by various filter criteria.ConclusionThe interfaces of the presented database enable the user to search and view mutations in an intuitive and straight-forward manner. The database is freely accessible at http://rcgdb.bioinf.uni-sb.de/MutomeWeb/.
Project description:Importance:Understanding the profitability of pharmaceutical companies is essential to formulating evidence-based policies to reduce drug costs while maintaining the industry's ability to innovate and provide essential medicines. Objective:To compare the profitability of large pharmaceutical companies with other large companies. Design, Setting, and Participants:This cross-sectional study compared the annual profits of 35 large pharmaceutical companies with 357 companies in the S&P 500 Index from 2000 to 2018 using information from annual financial reports. A statistically significant differential profit margin favoring pharmaceutical companies was evidence of greater profitability. Exposures:Large pharmaceutical vs nonpharmaceutical companies. Main Outcomes and Measures:The main outcomes were revenue and 3 measures of annual profit: gross profit (revenue minus the cost of goods sold); earnings before interest, taxes, depreciation, and amortization (EBITDA; pretax profit from core business activities); and net income, also referred to as earnings (difference between all revenues and expenses). Profit measures are described as cumulative for all companies from 2000 to 2018 or annual profit as a fraction of revenue (margin). Results:From 2000 to 2018, 35 large pharmaceutical companies reported cumulative revenue of $11.5 trillion, gross profit of $8.6 trillion, EBITDA of $3.7 trillion, and net income of $1.9 trillion, while 357 S&P 500 companies reported cumulative revenue of $130.5 trillion, gross profit of $42.1 trillion, EBITDA of $22.8 trillion, and net income of $9.4 trillion. In bivariable regression models, the median annual profit margins of pharmaceutical companies were significantly greater than those of S&P 500 companies (gross profit margin: 76.5% vs 37.4%; difference, 39.1% [95% CI, 32.5%-45.7%]; P < .001; EBITDA margin: 29.4% vs 19%; difference, 10.4% [95% CI, 7.1%-13.7%]; P < .001; net income margin: 13.8% vs 7.7%; difference, 6.1% [95% CI, 2.5%-9.7%]; P < .001). The differences were smaller in regression models controlling for company size and year and when considering only companies reporting research and development expense (gross profit margin: difference, 30.5% [95% CI, 20.9%-40.1%]; P < .001; EBITDA margin: difference, 9.2% [95% CI, 5.2%-13.2%]; P < .001; net income margin: difference, 3.6% [95% CI, 0.011%-7.2%]; P = .05). Conclusions and Relevance:From 2000 to 2018, the profitability of large pharmaceutical companies was significantly greater than other large, public companies, but the difference was less pronounced when considering company size, year, or research and development expense. Data on the profitability of large pharmaceutical companies may be relevant to formulating evidence-based policies to make medicines more affordable.
Project description:As an RNA virus, hepatitis C virus (HCV) is able to rapidly acquire drug resistance, and for this reason the design of effective anti-HCV drugs is a real challenge. The HCV subgenomic replicon-containing cells are widely used for experimental studies of the HCV genome replication mechanisms, for drug testing in vitro and in studies of HCV drug resistance. The NS3/4A protease is essential for virus replication and, therefore, it is one of the most attractive targets for developing specific antiviral agents against HCV. We have developed a stochastic model of subgenomic HCV replicon replication, in which the emergence and selection of drug resistant mutant viral RNAs in replicon cells is taken into account. Incorporation into the model of key NS3 protease mutations leading to resistance to BILN-2061 (A156T, D168V, R155Q), VX-950 (A156S, A156T, T54A) and SCH 503034 (A156T, A156S, T54A) inhibitors allows us to describe the long term dynamics of the viral RNA suppression for various inhibitor concentrations. We theoretically showed that the observable difference between the viral RNA kinetics for different inhibitor concentrations can be explained by differences in the replication rate and inhibitor sensitivity of the mutant RNAs. The pre-existing mutants of the NS3 protease contribute more significantly to appearance of new resistant mutants during treatment with inhibitors than wild-type replicon. The model can be used to interpret the results of anti-HCV drug testing on replicon systems, as well as to estimate the efficacy of potential drugs and predict optimal schemes of their usage.
Project description:AimsThe aims of the present study were to compare the pharmacokinetics of oseltamivir and its active antiviral metabolite oseltamivir carboxylate in obese and non-obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and oseltamivir carboxylate.MethodsThe population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese [body mass index (BMI) ≥30 kg m(-2) ) and 12 non-obese (BMI <30 kg m(-2) ) Thai adult volunteers receiving a standard dose of 75 mg and a double dose of 150 mg in a randomized sequence. Concentration-time data were collected and analysed using nonlinear mixed-effects modelling.ResultsThe pharmacokinetics of oseltamivir and oseltamivir carboxylate were described simultaneously by first-order absorption, with a one-compartment disposition model for oseltamivir, followed by a metabolism compartment and a one-compartment disposition model for oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance {3.84% increase for each 10 ml min(-1) increase in creatinine clearance [95% confidence interval (CI) 0.178%, 8.02%]}. Obese individuals had an approximately 25% (95% CI 24%, 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI 19%, 23%) and 10% higher oseltamivir carboxylate clearance (95% CI 9%, 11%) compared with non-obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate.ConclusionsThe results confirmed that a dose adjustment for oseltamivir in obese individuals is not necessary on the basis of its pharmacokinetics.
Project description:This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.