Identifying and Managing Technical Risks in the Process of Innovative Drugs Development in China

Objective To identify technical risks in the process of innovative drug development,and to provide reference for technical risk management so as to reduce the uncertainties and improve the efficiency of research and development.Methods The initial risk index was investigated by literature research.Then,the Likert scale was used to design a questionnaire,and the experts’opinion was used to analyze the risk factors affecting the different stages of the development of innovative drugs in China.Results and Conclusion Based on the analysis of questionnaire,31 risk indicators of five key stages in the development of innovative drugs from drug discovery to marketing authorization were established.The key risk indicators constructed in this study can provide reference for technology-related risk management in the process of innovative drug development.

Analytic Hierarchy Process for Technological Risks in the Process of Innovative Drug Development in China

Objective To identify the critical risks in the process of innovative drug research and development,and to provide reference for improving the efficiency of innovative drug development and risk control in China.Methods Expert investigation and analytic hierarchy process were used to determine the weights of different risks.Results and Conclusion The research and analysis results showed that the risks at different stages of development had different effects on the success rate of drug development,among which the risk at the drug discovery stage influenced the most.In the drug discovery stage,inappropriate target selection had the greatest impact on the success rate of drug development.The lack of appropriate cell tissue or animal models had the greatest impact on the success rate of drug development from the discovery of a compound to the application for clinical trials.The difference in changes between nonclinical and clinical studies had the greatest impact on the success rate of drug development from early clinical studies to pivotal clinical studies.Incorrect dose selection had the greatest impact on the success rate of drug development from pivotal clinical studies to marketing authorization applications.The biggest impact from the marketing authorization application to the approval stage was inadequate communication with regulators.After investigating the weight of risk factors in the process of innovative drug development based on scientific methods,a new perspective for the risk control of new drug development and improving the research and development efficiency is provided.

Health risk assessment of trace metal(loid)s in agricultural soils based on Monte Carlo simulation coupled with positive matrix factorization model in Chongqing, southwest China

This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed the source apportionment and assessed the health risk of TMs in agricultural soils by using positive matrix factorization(PMF) model and health risk assessment(HRA) model based on Monte Carlo simulation. Meanwhile, we combined PMF and HRA models to explore the health risks of TMs in agricultural soils by different pollution sources to determine the priority control factors. Results showed that the average contents of cadmium(Cd), arsenic (As), lead(Pb), chromium(Cr), copper(Cu), nickel(Ni), and zinc(Zn) in the soil were found to be 0.26, 5.93, 27.14, 61.32, 23.81, 32.45, and 78.65 mg/kg, respectively. Spatial analysis and source apportionment analysis revealed that urban and industrial sources, agricultural sources, and natural sources accounted for 33.0%, 27.7%, and 39.3% of TM accumulation in the soil, respectively. In the HRA model based on Monte Carlo simulation, noncarcinogenic risks were deemed negligible(hazard index <1), the carcinogenic risks were at acceptable level(10^(-6)<total carcinogenic risk ≤ 10^(-4)), with higher risks observed for children compared to adults. The relationship between TMs, their sources, and health risks indicated that urban and industrial sources were primarily associated with As, contributing to 75.1% of carcinogenic risks and 55.7% of non-carcinogenic risks, making them the primary control factors. Meanwhile, agricultural sources were primarily linked to Cd and Pb, contributing to 13.1% of carcinogenic risks and 21.8% of non-carcinogenic risks, designating them as secondary control factors.

The measure and decision of technical risk in the development of naval vessels

The risks in development of navy vessels were explored, The resources of technical risk in the design and development of vessels were mentioned, It was pointed that technical risk dominated the other risk components. Based on the writers＇ understanding and experience from risk analysis and risk ,nanagement to the development of a navy vessel, four measure indexes of technical risk were presented. The decision criteria and the rules corresponding to the indexes were estahlished by the statistic information,

Application of Feature, Event, and Process Methods to Leakage Scenario Development for Offshore CO_(2) Geological Storage

Offshore carbon dioxide(CO_(2)) geological storage(OCGS) represents a significant strategy for addressing climate change by curtailing greenhouse gas emissions. Nonetheless, the risk of CO_(2) leakage poses a substantial concern associated with this technology. This study introduces an innovative approach for establishing OCGS leakage scenarios, involving four pivotal stages, namely, interactive matrix establishment, risk matrix evaluation, cause–effect analysis, and scenario development, which has been implemented in the Pearl River Estuary Basin in China. The initial phase encompassed the establishment of an interaction matrix for OCGS systems based on features, events, and processes. Subsequent risk matrix evaluation and cause–effect analysis identified key system components, specifically CO_(2) injection and faults/features. Building upon this analysis, two leakage risk scenarios were successfully developed, accompanied by the corresponding mitigation measures. In addition, this study introduces the application of scenario development to risk assessment, including scenario numerical simulation and quantitative assessment. Overall, this research positively contributes to the sustainable development and safe operation of OCGS projects and holds potential for further refinement and broader application to diverse geographical environments and project requirements. This comprehensive study provides valuable insights into the establishment of OCGS leakage scenarios and demonstrates their practical application to risk assessment, laying the foundation for promoting the sustainable development and safe operation of ocean CO_(2) geological storage projects while proposing possibilities for future improvements and broader applications to different contexts.

Comprehensive Risk Assessment of Sea Level Rise and Tropical Cyclones in Dongzhaigang Mangroves,China

Mangroves play a pivotal role in tropical and subtropical coastal ecosystem,yet they are highly vulnerable to the effects of climate change,particularly the accelerated global sea level rise(SLR)and stronger tropical cyclones(TCs).However,there is a lack of research addressing future simultaneous combined impacts of the slow-onset of SLR and rapid-onset of TCs on China's mangroves.In order to develop a comprehensive risk assessment method considering the superimposed effects of these two factors and analyze risk for mangroves in Dongzhaigang,Hainan Island,China,we used observational and climate model data to assess the risks to mangroves under low,intermediate,and very high greenhouse gas(GHG)emission scenarios(such as SSP1-2.6,SSP2-4.5,and SSP5-8.5)in 2030,2050,and 2100,and compiled a risk assessment scheme for mangroves in Dongzhaigang,China.The results showed that the combined risks from SLR and TCs will continue to rise;however,SLRs will increase in intensity,and TCs will decrease.The comprehensive risk of the Dongzhaigang mangroves posed by climate change will remain low under SSP1-2.6 and SSP2-4.5 scenarios by 2030,but it will increase substantially by 2100.While under SSP5-8.5 scenario,the risks to mangroves in Dongzhaigang are projected to increase considerably by 2050,and approximately 68.8%of mangroves will be at very high risk by 2100.The risk to the Dongzhaigang mangroves is not only influenced by the hazards but also closely linked to their exposure and vulnerability.We therefore propose climate resilience developmental responses for mangroves to address the effects of climate change.This study for the combined impact of TCs and SLR on mangroves in Dongzhaigang,China can enrich the method system of mangrove risk assessment and provide references for scientific management.

Competing Risk Model for Time to Development of Tuberculosis among Adults on Combination Antiretroviral Treatment

The purpose of this study was to identify factors affecting the time to development of tuberculosis in the presence of competing risks. In this case death before developing tuberculosis was deemed a competing risk because it altered the occurrence of the outcome of interest being time to development of tuberculosis from baseline. We used data from a randomized longitudinal clinical trial study called the “Tshepo” study. The “Tshepo” study was a 3-year randomized clinical study following 650 ART-naïve adults (69.4% female) from Botswana who initiated first-line NNRTI-based ART. Participants were assigned in equal proportions (in an open-label, unblinded fashion) to one of 6 initial treatment arms and one of two adherence arms using permuted block randomization. Randomization was stratified by CD4+ cell count (less than 200 cells/mm3, 201 - 350 cells/mm3) and by whether the participants had an adherence assistant. Classical methods such as the Kaplan-Meier method and standard Cox proportional hazards regression were used to analyze survival data ignoring the competing event(s) which may have been inappropriate in the presence of competing risks. The idea was to use competing risk models to investigate how different treatment regimens affect the time to the development of TB and compare the results to those obtained using the classical survival analysis model which does not account for competing risks. Amongst 38 patients who died 15.8% of them developed tuberculosis whilst 84.2% of those who died did not develop the outcome of interest. The hazard ratio of treatment C was 1.069 implying that the risk of developing TB in patients taking treatment C is about 6.9% higher compared to those taking treatment A having adjusted for baseline age, baseline BMI, baseline CD4, Hemoglobin and gender. Similarly, after accounting for competing risks the hazard ratio for treatment C was about 1.89 implying that the risk of developing TB amongst those taking treatment C was about 89% higher as compared to those taking treatment A. From the obtained results it was thus concluded that the standard Cox model of time to event data in the presence of competing risks underestimated the hazard ratios hence when dealing with data with multiple failure events it is important to account for competing events.

Equipment Development Risk Evaluation Based on Fuzzy Comprehensive Evaluation

The equipment development risk evaluation refers to evaluating the equipment risks in the equipment development phase based on risk analysis,risk score calculation,and risk level identification.The results could lead the direction of future work.The risk management in equipment development phase was studied.The risk management model in equipment development phases was established on the base of basic theories in risk management and some interrelated risk management models in other fields.The application of the established model was illuminated by an instance.

Research on strategic risk identification method of equipment system development based on system dynamics

Strategic management of equipment system develop-ment must attach importance to effective strategic risk manage-ment.Aiming at the identification of strategic risk of equipment system development,firstly,the source of strategic risk of equip-ment system development is analyzed and classified.Based on this,a causal loop diagram of strategic risk of equipment sys-tem development based on system dynamics is established.The system dynamics analysis software Vensim PLE is used to carry out the risk influencing factors analysis,risk consequences ana-lysis,risk feedback loop identification and corresponding pre-control measures,and achieves a good risk identification effect.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

HV Process Model of Software Development

Software Development Life Cycle (SDLC) is one of the major ingredients for the development of efficient software systems within a time frame and low-cost involvement. From the literature, it is evident that there are various kinds of process models that are used by the software industries for the development of small, medium and long-term software projects, but many of them do not cover risk management. It is quite obvious that the improper selection of the software development process model leads to failure of the software products as it is time bound activity. In the present work, a new software development process model is proposed which covers the risks at any stage of the development of the software product. The model is named a Hemant-Vipin (HV) process model and may be helpful for the software industries for development of the efficient software products and timely delivery at the end of the client. The efficiency of the HV process model is observed by considering various kinds of factors like requirement clarity, user feedback, change agility, predictability, risk identification, practical implementation, customer satisfaction, incremental development, use of ready-made components, quick design, resource organization and many more and found through a case study that the presented approach covers many of parameters in comparison of the existing process models. .

Epidemiological Aspects of Obesity, Overweight and Cardiovascular Risk Factors at Associes in Semi-Urban Areas (Case of Sébikotane)

Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

Surgical and non-surgical risk factors affecting the insufficiency of ileocolic anastomosis after first-time surgery in Crohn’s disease patients

BACKGROUND Crohn's disease(CD)often necessitates surgical intervention,particularly when it manifests in the terminal ileum and ileocecal valve.Despite undergoing radical surgery,a subset of patients experiences recurrent inflammation at the anasto-motic site,necessitating further medical attention.AIM To investigate the risk factors associated with anastomotic insufficiency following ileocecal resection in CD patients.METHODS This study enrolled 77 patients who underwent open ileocolic resection with pri-mary stapled anastomosis.Patients were stratified into two groups:Group I co-mprised individuals without anastomotic insufficiency,while Group II included patients exhibiting advanced anastomotic destruction observed endoscopically or those requiring additional surgery during the follow-up period.Surgical and non-surgical factors potentially influencing anastomotic failure were evaluated in both cohorts.RESULTS Anastomotic insufficiency was detected in 12 patients(15.6%),with a mean time interval of 30 months between the initial surgery and recurrence.The predomi-nant reasons for re-intervention included stenosis and excessive perianastomotic lesions.Factors associated with a heightened risk of anastomotic failure encompassed prolonged postoperative obstruction,anastomotic bleeding,and clinically confirmed micro-leakage.Additionally,patients in Group II exhibited preoperative malnutrition and early recurrence of symptoms related to CD.CONCLUSION Successful surgical outcomes hinge on the attainment of a fully functional anastomosis,optimal metabolic status,and clinical remission of the underlying disease.Vigilant endoscopic surveillance following primary resection facilitates the timely identification of anastomotic failure,thereby enabling noninvasive interventions.

Risk factors for acute kidney injury following coronary artery bypass graft surgery in a Chinese population and development of a prediction model

BACKGROUND Acute kidney injury(AKI)after coronary artery bypass graft(CABG)surgery is associated with significant morbidity and mortality.This retrospective study aimed to establish a risk score for postoperative AKI in a Chinese population.METHODS A total of 1138 patients undergoing CABG were collected from September 2018 to May 2020 and divided into a derivation and validation cohort.AKI was defined according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Multivariable logistic regression analysis was used to determine the independent predictors of AKI,and the predictive ability of the model was determined using a receiver operating characteristic(ROC)curve.RESULTS The incidence of cardiac surgery–associated acute kidney injury(CSA-AKI)was 24.17%,and 0.53%of AKI patients required dialysis(AKI-D).Among the derivation cohort,multivariable logistic regression showed that age≥70 years,body mass index(BMI)≥25 kg/m2,estimated glomerular filtration rate(eGFR)≤60 mL/min per 1.73 m2,ejection fraction(EF)≤45%,use of statins,red blood cell transfusion,use of adrenaline,intra-aortic balloon pump(IABP)implantation,postoperative low cardiac output syndrome(LCOS)and reoperation for bleeding were independent predictors.The predictive model was scored from 0 to32 points with three risk categories.The AKI frequencies were as follows:0-8 points(15.9%),9-17 points(36.5%)and≥18 points(90.4%).The area under of the ROC curve was 0.730(95%CI:0.691-0.768)in the derivation cohort.The predictive index had good discrimination in the validation cohort,with an area under the curve of 0.735(95%CI:0.655-0.815).The model was well calibrated according to the Hosmer-Lemeshow test(P=0.372).CONCLUSION The performance of the prediction model was valid and accurate in predicting KDIGO-AKI after CABG surgery in Chinese patients,and could improve the early prognosis and clinical interventions.

Human Rights and Development:China's Contributions Based on a Larger Concept of Human Rights

The Western liberal view of global governance can no longer effectively address the challenges facing the world today or respond to the demands of developing countries in the fields of human rights and development.Meanwhile,the United Nations human rights and development agenda also has its limitations.Against such a backdrop,China's path of human rights development has avoided the trap of human rights confrontation and the clash of civilizations.It has set an example of complementarity and positive interaction between human rights and development by unifying collective human rights with individual human rights and integrating the universality and particularity of human rights.Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,delivered a speech at the 37th group study session of the Political Bureau of the CPC Central Committee on China's Path of Human Rights Development.This elevated China's human rights development to a new historical height.Practice has proved that China's concept and path of human rights in the new era have not only effectively promoted the development of its human rights cause,but also contributed Chinese wisdom to the global cause of human rights and development with a larger concept of human rights.Under the framework of the concept of building a community with a shared future for mankind,the Belt and Road Initiative,and the Global Development Initiative,China has contributed to enhancing the discourse power of developing countries in human rights and building a fairer,more just,more reasonable and more inclusive system for global human rights governance.

Distribution, Mobility, and Health Risks Assessment of Trace Metals in River Sediments from Intense Agricultural Activity Areas in West Africa

The economy of West African countries is mainly based on agriculture. However, the trace metal(loid)s contamination status in rivers is relatively unknown in the region. In this work, 45 surface sediments collected from the Bandama, Comoé, and Bia Rivers in south and south eastern Côte d’Ivoire (West Africa), were analyzed for total metal concentrations and chemical speciation. The results showed that the river sediments were considerably contaminated by Cd and moderately contaminated by As, Cu, Pb, and Zn. Significant spatial variations were observed among the stations but not between the rivers. Metals Cd and Cu were likely to cause more ecological risks. The speciation analysis unravelled that the metal(loid)s partitioned mainly in the residual fraction, with the potential mobile fraction varying from 14% to 28%. The study calls for establishment of strict policies relative to the application of fertilizers and agrochemicals and mining activities to protect the environment and human health risks.

Pioneering a New Realm of Human Rights Civilization in the Chinese Path to Modernization——An Overview of the Symposium on“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”

On October 14,2023,a symposium themed“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”was held in Changchun,Jilin Province,China.More than fifty experts,scholars,and researchers from national institutions and universities engaged in discussions and exchanges on human rights on the Chinese path to modernization,including the path,practice,knowledge systems,and civilization forms of human rights.This symposium played a significant role in advancing the construction of the disciplinary system,academic system,and discourse system of human rights in China.

Financial Risk Evaluation System in the Context of Great Intelligence Movement Cloud: A Hierarchical Analysis Approach

This paper examines the financial risk evaluation system in the context of the“Great Intelligence Movement Cloud”and employs the hierarchical analysis method as the primary research tool.With the rapid advancement of“Great Intelligence Movement Cloud”technology,enterprise financial risks have expanded from the offline domain to the information domain,encompassing a broader scope and more diverse channels.The traditional approach to risk identification,relying solely on single financial indicators,no longer meets current demands.Therefore,it is essential to integrate a non-financial early warning indicator system and adopt a combination of quantitative and qualitative analysis methods.Hierarchical analysis enables the decomposition of complex problems into multiple components and organizes them into a hierarchical structure based on their relationships,facilitating a more accurate assessment of financial risk.This study seeks to establish a comprehensive financial risk evaluation system suited to the“Great Intelligence Movement Cloud”context,offering enterprises more precise risk assessments to better address financial risks and achieve steady development.

The Market Development of Children’s Go Training and the Difficulty and Countermeasure Analysis of Go Training

The children’s Go training market is experiencing vigorous growth but also faces several challenges.As the importance of Go in cultural education increases,the market expands,with growing demand and involvement from training and educational institutions.However,the market encounters difficulties such as a shortage of high-quality Go coaches,uniformity in training content and methods,and high training costs.To address these issues,measures can be taken to strengthen the team of Go coaches,diversify training content and methods,and optimize the training cost structure,thereby promoting the healthy development of the children’s Go training market.

Research on Financial Risk Management in the S Water Conservancy Project and Its Implications for Similar Projects

As a vital infrastructure initiative with significant impacts on national development and public welfare,water conservancy projects play an essential role in advancing agricultural development and mitigating losses caused by flooding.However,these projects often require substantial investments and extended construction periods,leading to the inevitable emergence of various financial risks during implementation.This paper aims to explore the current challenges in financial risk management of the S water conservancy project,offering practical management strategies and solutions to address these financial difficulties.Through a detailed assessment and analysis of the S water conservancy project,the study seeks to provide valuable references and insights for similar projects to better manage financial risks,ensuring their smooth progression and successful completion.The proposed control measures are designed not only to effectively mitigate the financial risks specific to the S water conservancy project but also to offer actionable lessons for other similar projects.By promoting and applying these measures,the overall financial management capabilities of the industry can be enhanced,providing robust support for the sustainable development of water conservancy projects.