Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Deep learning approaches to recover the plasma current density profile from the safety factor based on Grad–Shafranov solutions across multiple tokamaks

Many magnetohydrodynamic stability analyses require generation of a set of equilibria with a fixed safety factor q-profile while varying other plasma parameters.A neural network(NN)-based approach is investigated that facilitates such a process.Both multilayer perceptron(MLP)-based NN and convolutional neural network(CNN)models are trained to map the q-profile to the plasma current density J-profile,and vice versa,while satisfying the Grad–Shafranov radial force balance constraint.When the initial target models are trained,using a database of semianalytically constructed numerical equilibria,an initial CNN with one convolutional layer is found to perform better than an initial MLP model.In particular,a trained initial CNN model can also predict the q-or J-profile for experimental tokamak equilibria.The performance of both initial target models is further improved by fine-tuning the training database,i.e.by adding realistic experimental equilibria with Gaussian noise.The fine-tuned target models,referred to as fine-tuned MLP and fine-tuned CNN,well reproduce the target q-or J-profile across multiple tokamak devices.As an important application,these NN-based equilibrium profile convertors can be utilized to provide a good initial guess for iterative equilibrium solvers,where the desired input quantity is the safety factor instead of the plasma current density.

Spatiotemporal Characteristics of Typical Ecosystem Services and Their Spatial Responses to Driving Factors in Ecologically Fragile Areas in Upper Yellow River,China

The identification of dominant driving factors for different ecosystem services(ESs)is crucial for ecological conservation and sustainable development.However,the spatial heterogeneity of the dominant driving factors affecting various ESs has not been adequately elucidated,particularly in ecologically fragile regions.This study employed the integrated valuation of ESs and trade-offs(InVEST)model to evaluate four ESs,namely,water yield(WY),soil conservation(SC),habitat quality(HQ),and carbon storage(CS),and then to identify the dominant driving factors of spatiotemporal differentiation of ES and further to characterize the spatial heterogeneity characteristics of the dominant driving factors in the eco-fragile areas of the upper Yellow River,China from 2000 to 2020.The results demonstrated that WY exhibited northeast-high and northwest-low patterns in the upper Yellow River region,while high values of SC and CS were distributed in central forested areas and a high value of HQ was distributed in vast grassland areas.The CS,WY,and SC exhibited decreasing trends over time.The most critical factors affecting WY,SC,HQ,and CS were the actual evapotranspiration,precipitation,slope,and normalized difference vegetation index,respectively.In addition,the effects of different factors on various ESs exhibited spatial heterogeneity.These results could provide spatial decision support for eco-protection and rehabilitation in ecologically fragile areas.

Survey on the Demand for Elderly Care Services of Community Residents in Beijing and Analysis of Influencing Factors

Objective: To investigate the current situation of the demand for geriatric care services of community residents in Beijing and analyze the influencing factors to provide a reference basis for meeting the demand for diversified and professional geriatric care services. Methods: A self-made questionnaire was used to randomly survey 1558 elderly individuals at community health service centers in 8 urban districts where elderly care centers were planned to be built. The influencing factors of the different characteristics of elderly care service needs from three aspects were analyzed using a dichotomous logistic regression model: predisposing, enabling, and, need factors. Results: 69.7% of the elderly required home care services, 22.8% wanted to get care services at elderly care centers, 15.9% wanted to get care services at nursing homes, 12.3% required community care services, and 7.4% didn’t know where to access care services. 68.5% of the elderly required care services for disabilities/semi-disabilities, 58.0% for dementia, 54.7% for common diseases, 34.9% for rehabilitation training, 33.0% for plumbing care, and 7.5% for hospice care. At the same time, there were urban- rural differences in the demand for elderly care services, with suburban elderly having a higher demand for care services than those living in urban areas (P < 0.05). The elderly’s demand for care services was mainly related to age, place of residence, and gender in the causative factors, mode of residence and physical condition among able factors, and mode of care services and care needs among need factors (P < 0.05). Conclusion: The demand for elderly care services was differentiated by factors including place of residence, age, and gender. It is crucial to accurately match the demand for elderly care services, innovate the mode of elderly care services, and improve the service quality to improve the elderly health service system.

A study on the health service demands and influence factors among elderly people based on a community survey in Western China

Objective:To investigate the health service demands and to analyze influencing factors among elderly people based on a community survey in Guilin,China.Methods:A random sampling was used to investigate 366 elderly people in a community using a Health-Care-Needs questionnaire,which was designed by The Western Nursing Alliance research team in China.This survey was used to understand the basic situation,financial condition,health condition,self-care abilities,pension plan,and care services demands of the elderly residing at home.Additionally,this article analyzed the influencing factors contributing to the obtained results.Results:The top 3 nursing needs were security needs(1.61±0.45 points),health education needs(1.54±0.57 points),and respect and self-development needs(1.13±0.64 points).Logistic multifactor regression analysis showed that gender,monthly income,lack of exercise,activities of daily living(ADL)scores,methods of medical payment,and pension plan were independent factors affecting elderly nursing needs.Conclusions:The home-based health services supply for elders did not meet their needs.Therefore,a comprehensive approach considering multifactors such as gender,income,exercise,self-care ability,medical expense payments,and supporting preferences should be considered to address the complex needs of health care.

Response of Ecosystem Service Value Based on Land Use Changes and Analysis of its Driving Factors in Typical Hilly Region with Red Soil

The contribution rate of ecosystem service value variation was used to analyze the effects of land use changes on the changes of ecosystem service value in Xingguo County during 1996-2005.Grey integrated correlation was employed to explore the contribution level of the indicators such as total population,urbanization level,proportion of primary industry and investment of social fixed assets on ecosystem service value,and the correlation analysis was also carried out.The results showed that the ecosystem service value in Xingguo County during 1996-2005 mainly was woodland,and the decrease of woodland area was the major reason for the sustained reduction of ecosystem service value.With the further increase of market demand and the incentives of local government,the garden area rapidly increased during 2001-2005,and the influence degree of garden towards the changes of ecosystem service value was only second to woodland,ranking No.2.Four socio-economic indicators had different correlation degree with ecosystem service value during the different research periods.Total population,urbanization level and proportion of primary industry had high correlation degree with ecosystem service value,whereas the influence degree of various socio-economic indicators on ecosystem service value was equal with each other day by day.Urbanization level,investment of social fixed assets and total population had significant negative correlation with ecosystem service value,while the proportion of primary industry had positive correlation with ecosystem service value.

Influence Factors for Safety Full Heading of Machine-transplanted Rice Seedlings in Cool-warm Rice Area

[Objective] This study was conducted to discuss influence factors for safety full heading of machine-transplanted rice seedlings in cool-warm rice area. [Method] Effects of variety, seedling age and nitrogen fertilizer dosage and strategy of machine-transplanted seedlings on safety full heading of machine-transplanted seedlings were investigated. [Result] During mechanized rice production in coolwarm rice area, mid-early-maturing cold-resistant varieties with growth periods no longer than 180 d could selected, and seedling age could controlled within 30-35 d; and the total amount of pure nitrogen should be less than 300 kg/hm^2, and the proportion of nitrogen fertilizer applied in later stages should be properly reduced. [Conclusion] Under this condition, safety full heading of rice is ensured, and the target yield is realized.

Impact of Improving Design Factor over 0.72 on the Safety and Reliability of Gas Pipelines and Feasibility Justification

Many years experience of the operation of high stress (>72% specified minimum yield strength, SMYS) gas pipelines and statistical analysis results of pipeline incidents showed that the operating pipelines at stress levels over 72% SMYS have not presented problems in USA and Canada, and design factor does not control incidents or the safety of pipelines. Enhancing pipeline safety management level is most important for decreasing incident rate. The application history of higher design factors in the U.S and Canada was reviewed. And the effect of higher factors to the critical flaw size, puncture resistance, change of reliability with time, risk level and the arrest toughness requirements of pipeline were analyzed here. The comparison of pipeline failure rates and risk levels between two design factors (0.72 and 0.8) has shown that a change in design factor from 0.72 to 0.8 would bring little effect on failure rates and risk levels. On the basis of the analysis result, the application feasibility of design factor of 0.8 in China was discussed and the related suggestions were proposed. When an operator wishes to apply design factor 0.8 to gas pipeline, the following process is recommended: stress level of line pipe hydro test should be up to 100% SMYS, reliability and risk assessment at the design feasibility or conceptual stage should be conducted, Charpy impact energy should meet the need of pipeline crack arrest; and establish and execute risk based integrity management plan. The technology of pipeline steel metallurgy, line pipe fabrication and pipeline construction, and line pipe quality control level in China achieved tremendous progresses, and line pipe product standards and property indexes have come up to international advanced level. Furthermore, pipeline safety management has improved greatly in China. Consequently, the research for the feasibility of application of design factor of 0.8 in China has fundamental basis.

Comprehensive safety factor of roof in goaf underdeep high stress

The safety factor of roof under deep high stress is a quantitative index for evaluating roof stability.Based on the failure mode of surrounding rock of stope roof,the mechanics model of goaf roof is constructed,and the internal force of roof is deduced by the theory of hingeless arch.The calculation method of roof safety factor(K)under the environment of deep mining is proposed in view of compression failure and shear failure of roof.The calculation formulas of shear safety factor(K1),compression safety factor(K2)and comprehensive safety factor(K)of roof are given.The influence of stope span and roof thickness on roof stability is considered in this paper.The results show that when the roof thickness remains constant,the roof safety factor decreases with the increasing of the stope span;when the stope span remains constant,the roof safety factor increases with the increasing of the roof thickness.The deep mining example shows that when the stope span is 30 m and the roof thickness is 10 m,the roof comprehensive safety factor is 1.12,which indicates the roof is in a stable state.

Factors Influencing the Emergency Medical Service Response Time for Cardiovascular Disease in Guangzhou, China

While emergency medical service (EMS) response time (ERT) is a major factor associated with the survival of patients with cardiovascular disease (CVD), relatively few studies have explored the factors associated with ERT. This study aimed to assess the current status of ERT and to identify the factors affecting ERT in patients with CVD in China. Between January 1, 2011 and December 31, 2015, EMS responses to CVD incidents in Guangzhou, China, were examined. The primary outcome was ERT, defined as the time from receipt of an emergency call to the arrival of paramedics on the scene. Factors associated with ERT were evaluated by multivariable logistic regression. A total of 44 383 CVD incidents were analysed. The median ERT was 12.58 min (interquartile range=9.98-15.67). Among the risk factors, distance (OR=13.73, 95% CI=11.76- 16.04), level of hospital (OR=1.57, 95% CI=1.40-1.75), and site of the incident (OR=1.53, 95% CI=1.38-1.69) were the top three significant factors affecting the ERT. Our results suggest that greater attention should be given to factors affecting the ERT. It is essential to make continuous efforts to promote the development of effective interventions to reduce the response time.

Addressing Human Factors in Burnout and the Delivery of Healthcare: Quality & Safety Imperative of the Quadruple Aim

Human factors in the delivery of service are considered in many occupations of high impact on others such as airline industry and nuclear power industry, but not sufficiently in healthcare delivery. A common administrative framework of healthcare involves focus upon costs, quality and patient satisfaction (The Triple Aim). Many industries which support healthcare and healthcare administrators do not have firsthand knowledge of the complexities in delivering care. As a result, the experience and human factors of providing care are often overlooked at high level decision-making unless incorporated into the healthcare delivery framework, proposed as the fourth aim of The Quadruple Aim framework. Research is pointing to consequent negative effects on quality, safety, joy, meaning and sustainability of healthcare practice. High acute occupational stress and chronic occupational stress can cause direct and indirect effects on safety and quality of care. The biological, psychological and social consequences of burnout from excessive acute and chronic occupational stress are more of a threat to healthcare than commonly acknowledged. Patient safety, quality of care and clinician well-being are inextricably linked. This report will describe the process of transition from The Triple Aim to The Quadruple Aim administrative framework of healthcare delivery at the University of Rochester Medical Center. Developing the fourth aim of improving the experience of providing care, had high acceptability and aligned with other health system goals of optimization of safety, quality, and performance by applying a human factors/ergonomic (HFE) framework that considers human capabilities and human limitations. The goal of HFE is to fit the healthcare system to the human instead of the human to the healthcare system. Concepts include removal of extraneous cognitive load, using clinician neural resource (brain power) optimally for highest order decision making in patient care. An integrative model of patient safety and clinician wellbeing is a product of this effort.

Three-dimensional stability of landslides based on local safety factor

Unlike the limit equilibrium method(LEM), with which only the global safety factor of the landslide can be calculated, a local safety factor(LSF) method is proposed to evaluate the stability of different sections of a landslide in this paper. Based on three-dimensional(3D) numerical simulation results, the local safety factor is defined as the ratio of the shear strength of the soil at an element on the slip zone to the shear stress parallel to the sliding direction at that element. The global safety factor of the landslide is defined as the weighted average of all local safety factors based on the area of the slip surface. Some example analyses show that the results computed by the LSF method agree well with those calculated by the General Limit Equilibrium(GLE) method in two-dimensional(2D) models and the distribution of the LSF in the 3D slip zone is consistent with that indicated by the observed deformation pattern of an actual landslide in China.

Factor of safety of strain-softening slopes

Stability analysis of strain-softening slopes is carried out using the shear strength reduction method and Mohr-Coulomb model with degrading cohesion and friction angle.The e ffect of strain-softening behavior on the slope factor of safety is investigated by performing a series of analyses for various slope geometries and strength properties.Stability charts and equations are developed to estimate the factor of safety of strain-softe ning slopes from the results of traditional stability analysis based on perfectly-plastic behavior.Two example applications including an open pit mine in weak rock and clay shale slope with daylighting bedding planes are presented.The results of limit equilibrium analysis and shear strength reduction method with perfectly-plastic models were in close agreement.Using perfectly-plastic models with peak strength properties led to overly optimistic results while adopting residual strength properties gave excessively conservative outcomes.The shear strength reduction method with a strain-softening model gave realistic factors of safety while accounting for the process of strength degradation.

The Need and Its Influence Factors for Community-based Rehabilitation Services for Disabled Persons in One District in Beijing

Purpose To explore the needs for basic community-based rehabilitation services for disabled persons in Xuanwu District, Beijing, China, and to identify factors which influence disabled persons to accept rehabilitation services. Method One hundred and eight disabled persons were selected by systematic sampling and simple random sampling to assess their needs for community-based rehabilitation services. Results Of the interviewees, 57A% needed the community-based rehabilitation services, but only 13.9% took advantage of it. The main factors influencing the interviewees to accept these services were cost （P〈0.05）, knowledge about rehabilitation medicine （P〈0.05）; and the belief in the therapeutic benefit of the community-based rehabilitation service （P〈0.05）. Conclusion A considerable gap exists between the supply of community-based rehabilitation services in Beijing and the needs for these services by disabled residents underscoring the need for improved availability, and for additional research.

An Evaluation of the Effects of Human Factors on Pilotage Operations Safety

In recent years,marine pilotage accidents occurring on a worldwide basis as a result of human error have not been ceased to transpire,despite advances in technology and a significant set of international conventions,regulations,and recommendations to reduce them.This paper aims to investigate the effect of human factors on the safety of maritime pilotage operations.The human factors that affect the operators who are performing ships’berthing operations have also been examined in detail.In this study,in order to determine the causes of human-related errors occurred in maritime pilotage accidents,a comprehensive literature review is carried out,and a considerable number of real past case examples and an analysis of the maritime accident investigation reports regarding pilotage operations events that occurred between 1995 and 2015 have been reviewed.To validate the identified humanrelated risk factors(HCFs)and explore other contributory factors,survey questionnaires and semi-structured interviews with domain experts have been conducted.A structural hierarchy diagram for the identified risk factors(HCFs)has been developed and validated through experienced experts belonging to the maritime sector.A questionnaire for pair-wise comparison is carried out and analysed using the analytic hierarchy process(AHP)approach to evaluate the weight and rank the importance of the identified human causal factors.The findings of this study will benefit the maritime industry,by identifying a new database on causal factors that are contributing to the occurrence of maritime pilotage disasters.The database can be used as a stand-alone reference or help implement effective risk reduction strategies to reduce the human error,that might occur during pilotage operations.

The stability safety factor calibration based on the reliability index

When the bridge structure stability safety factor of the first type is 4, the research that whether the structure reliability index will reach target reliability index under the more-likely-to-happen collapse situation of the second type is necessary. The stability calculations of the first and the second type are made respectively for single layer and single span rigid frame bridge. Based on the critical load obtained from the stability calculation of the first type, the stability safety factor of the first type is taken as 4, and the first order reliability method is used to program and calculate the reliability index. Then, the load effect under the stability reliability index cal- culation of the first type and the critical load of the second type are employed to calculate the reliability index of the second type. The evaluation of structure stability safety factor is discussed according to reliability index. Based on the discussion above, parameter analysis of the stable critical loads of two types is made, and the in- fluence of critical load change on reliability index is researched. The result shows that stability analysis should identify collapse state; when the stability safety factor of the first type is 4, but the structure has the collapse of the second type, the reliability index cannot be ensured to reach the target reliability index under certain condi- tions.

Factors Affecting Patient Satisfaction with Community Health Service under the Gatekeeper System:A Cross-sectional Study in Nanjing,China

The gatekeeper policy has been implemented for approximately ten years on a pilot population in China. It is necessary to assess the satisfaction of patients utilizing community health service（CHS） under the gatekeeper system. Our study showed that the cognition of gatekeeper policy was associated with four dimensions including doctor‐patient relationships, information and support, organization of care, and accessibility（P 〈 0.001）. One or more factors such as gender and self‐perceived health scores also affected their satisfaction. General practitioners must be prepared to focus on these aspects of information and support, organization of care, and accessibility as indicators of potential opportunities for improvement. Additionally, policymakers can improve patients＇ satisfaction with CHS by strengthening their awareness of the gatekeeper policy.

Optimizing slope safety factor prediction via stacking using sparrow search algorithm for multi-layer machine learning regression models

The safety factor is a crucial quantitative index for evaluating slope stability.However,the traditional calculation methods suffer from unreasonable assumptions,complex soil composition,and inadequate consideration of the influencing factors,leading to large errors in their calculations.Therefore,a stacking ensemble learning model(stacking-SSAOP)based on multi-layer regression algorithm fusion and optimized by the sparrow search algorithm is proposed for predicting the slope safety factor.In this method,the density,cohesion,friction angle,slope angle,slope height,and pore pressure ratio are selected as characteristic parameters from the 210 sets of established slope sample data.Random Forest,Extra Trees,AdaBoost,Bagging,and Support Vector regression are used as the base model(inner loop)to construct the first-level regression algorithm layer,and XGBoost is used as the meta-model(outer loop)to construct the second-level regression algorithm layer and complete the construction of the stacked learning model for improving the model prediction accuracy.The sparrow search algorithm is used to optimize the hyperparameters of the above six regression models and correct the over-and underfitting problems of the single regression model to further improve the prediction accuracy.The mean square error(MSE)of the predicted and true values and the fitting of the data are compared and analyzed.The MSE of the stacking-SSAOP model was found to be smaller than that of the single regression model(MSE=0.03917).Therefore,the former has a higher prediction accuracy and better data fitting.This study innovatively applies the sparrow search algorithm to predict the slope safety factor,showcasing its advantages over traditional methods.Additionally,our proposed stacking-SSAOP model integrates multiple regression algorithms to enhance prediction accuracy.This model not only refines the prediction accuracy of the slope safety factor but also offers a fresh approach to handling the intricate soil composition and other influencing factors,making it a precise and reliable method for slope stability evaluation.This research holds importance for the modernization and digitalization of slope safety assessments.

Promoting Clinician Well-Being and Patient Safety Using Human Factors Science: Reducing Unnecessary Occupational Stress

Our healthcare delivery system has accumulated complexity of payment, regulation systems, expectations and requirements. Often these are not designed to align with clinical thinking process flow of patient care. As a result, clinicians are utilizing enormous mental (cognitive) resource to comply with these complexities, over and above the baseline mental effort required to give good care to the patient. Recent studies suggest a significant number of physicians, advanced practice providers and nurses no longer want to stay in healthcare due to difficult work expectations and conditions that have become unreasonable. Technology has benefitted healthcare delivery, but also is a conduit of many expectations that have been grafted upon clinician workloads, exceeding the resources provided to accomplish them. Cognitive load is a measure of mental effort and is divided into Intrinsic, Germane and Extraneous Cognitive Load. Extraneous Cognitive Load (ECL) is what is not necessary and can be removed by better design. High cognitive load is associated with increased risk of both medical error and clinician burnout. Chronic high level occupational stress occurs from dealing with this job/resource imbalance and is showing serious personal health impact upon clinicians and the quality of the work they can provide for patients. Since organizational systems have become more complex, leadership methods, clinician wellbeing and patient safety efforts need to adjust to adapt and succeed. Safety efforts have tended to predominantly follow methods of a few decades ago with predominant focus upon how things go wrong (Safety I) but are now being encouraged to include more of the study of how things go right (Safety II). Human Factors/Ergonomics (HFE) science has been used in many industries to preserve worker wellbeing and improve system performance. Patient safety is a product of good system performance. HFE science helps inform mechanisms behind Safety I and II approach. HFE concepts augment existing burnout and safety interventions by providing a conceptual roadmap to follow that can inform how to improve the multiple human/technology, human/system, and human/work environment interfaces that comprise healthcare delivery. Healthcare leaders, by their influence over culture, resource allocation, and implementation of requirements and workflows are uniquely poised to be effective mitigators of the conditions leading to clinician burnout and latent medical error. Basic knowledge of HFE science is a strategic advantage to leaders and individuals tasked with achieving quality of care, controlling costs, and improving the experiences of receiving and providing care.

High-Risk Rural Road Safety Study and Determining the Crash-Reduction Factors for High-Risk Rural-Road Usage

More than 32,000 motorists are killed on U.S. roads and streets annually, and approximately 54% of the accidents occur on rural roads. In an attempt to address and reduce these fatalities, the current transportation act, the Safe, Accountable, Flexible, Efficient Transportation Equality Act: A Legacy for Users (SAFETY-LU), elevated the Highway Safety Improvement Program (HSIP) to a core program and included a $90,000,000 High-Risk Rural Road Program (HRRRP) to address and significantly reduce traffic fatalities and incapacitating injuries on rural major or minor collectors, and/or rural local roads. While there were many challenges to properly implement the HRRRP in counties, this study provided important information that was needed to identify the predominant crash types on HRRRP-eligible roads and compiled a list of countermeasures for the predominant crash types that were identified on Kansas’ high-risk rural roads. For the gathered countermeasures, crash reduction factors (CRFs) were also provided from the literature review, and their values were validated by conducting interviews with Kansas county engineers/officials. This study provided valuable information for the county engineers and local government officials while they worked on improving the safety of high-risk rural roads using HRRRP funds.