A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve cli...A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.展开更多
As the Web of Data grows, the number of available SPARQL endpoints increases. SPARQL endpoints conceptually represent RPC-style, coarse-grained data access mechanisms. Nevertheless, through the potential interlinking ...As the Web of Data grows, the number of available SPARQL endpoints increases. SPARQL endpoints conceptually represent RPC-style, coarse-grained data access mechanisms. Nevertheless, through the potential interlinking of the contained entities, SPARQL endpoints should be able to over distinct advantages over plain Web APIs. To our knowledge, to date, there has been no study conducted that gauges the impact of the link on SPARQL query execution, especially in a federated set-up. In this paper, we investigate how the existence and types of typed links influences the execution characteristics of different SPARQL federation frameworks. In order to measure the query performance, we propose a combined cost model based on a statistic analysis of the query performance metrics that involves parameters such as type of link, the data catalogues and cache, number of links, and number of distinct subjects. As result, we show that number of distinct subject and number of links have significant impact on Federation over SPARQL Endpoints performance whereas type of link does not have significantly influence in federation query performance.展开更多
Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube＇s endpoints and then ...Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube＇s endpoints and then fix any geometric errors correspondingly. However, the traditional tube inspection method is time-consuming and complex operations. Therefore, a new measurement method for a tube＇s endpoints based on machine vision is proposed. First, reflected light on tube＇s surface can be removed by using photometric linearization. Then, based on the optimization model for the tube＇s endpoint measurements and the principle of stereo matching, the global coordinates and the relative distance of the tube＇s endpoint are obtained. To confirm the feasibility, ll tubes are processed to remove the reflected light and then the endpoint＇s positions of tubes are measured. The experiment results show that the measurement repeatability accuracy is 0.167 mm, and the absolute accuracy is 0.328 ram. The measurement takes less than 1 min. The proposed method based on machine vision can measure the tube＇s endpoints without any surface treatment or any tools and can realize on line measurement.展开更多
OBJECTIVE: To evaluate the risk of ischemic stroke endpoints by establishing risk assessment models that combine Traditional Chinese Medicine(TCM)and modern medicine indicators.METHODS/DESIGN: The proposed study is a ...OBJECTIVE: To evaluate the risk of ischemic stroke endpoints by establishing risk assessment models that combine Traditional Chinese Medicine(TCM)and modern medicine indicators.METHODS/DESIGN: The proposed study is a registry-based participant survey conducted in seven hospitals nationwide in China. After obtaining informed consent, 3000 patients diagnosed with ischemic stroke will be recruited. One-year follow-ups will be performed on-site in hospitals and by telephone to track endpoint events. Comparative analysis of the prevalence of endpoint events and other TCM or modern medicine features in different groups will be conducted using frequency analysis and χ2tests, and the results will be expressed as composition ratios. Comparative analysis of quantitative scores and related patterns or symptoms will be conducted using a rank-sum test. Correlation analysis of endpoint events and TCM or modern medicine factors will be performed using a multivariate Cox proportional hazard model.DISCUSSION: Previous reports have described modern medicine indicator-based risk assessment models for ischemic stroke endpoint events, but no such studies have included TCM features. Our new risk assessment model combines TCM and modern medicine indicators and thus has the potential to facilitate early warning, early intervention, and early control of ischemic stroke endpoint events.展开更多
In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is...In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.展开更多
In the design of chemical processes,such as catalytic cracking of bitumen and heavy oil,the knowledge of phase behavior at the critical endpoint is essential.Based on the PR equation of state,the algorithm developed b...In the design of chemical processes,such as catalytic cracking of bitumen and heavy oil,the knowledge of phase behavior at the critical endpoint is essential.Based on the PR equation of state,the algorithm developed by Heidemann and Khalil for calculating critical properties was used to compute critical points.An algorithm for determining the equilibrium phase of the critical point using the tangent plane criterion was developed,and was used to calculate the critical endpoints of different mixtures,including non-polar,polar and associating systems.The critical endpoint,representing the type of the phase behavior,was employed to fit the interaction parameter of mixtures in critical state at high pressure.Lines of critical endpoints for ternary mixtures were also determined with the algorithm.展开更多
Cervical spinal cord injury （SCI） results in partial to full paralysis of the upper and lower extrem- ities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in...Cervical spinal cord injury （SCI） results in partial to full paralysis of the upper and lower extrem- ities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control （e.g., upper extremity motor score, motor level change） show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement.展开更多
Due to ethical and logistical concerns it is common for data monitoring committees to periodically monitor accruing clinical trial data to assess the safety, and possibly efficacy, of a new experimental treatment. Whe...Due to ethical and logistical concerns it is common for data monitoring committees to periodically monitor accruing clinical trial data to assess the safety, and possibly efficacy, of a new experimental treatment. When formalized, monitoring is typically implemented using group sequential methods. In some cases regulatory agencies have required that primary trial analyses should be based solely on the judgment of an independent review committee (IRC). The IRC assessments can produce difficulties for trial monitoring given the time lag typically associated with receiving assessments from the IRC. This results in a missing data problem wherein a surrogate measure of response may provide useful information for interim decisions and future monitoring strategies. In this paper, we present statistical tools that are helpful for monitoring a group sequential clinical trial with missing IRC data. We illustrate the proposed methodology in the case of binary endpoints under various missingness mechanisms including missing completely at random assessments and when missingness depends on the IRC’s measurement.展开更多
The present work considers the endpoint in the abstract metric space. It firstly introduces the metric space of partially ordered groups and the metric space of partially ordered modules, respectively;and defines the ...The present work considers the endpoint in the abstract metric space. It firstly introduces the metric space of partially ordered groups and the metric space of partially ordered modules, respectively;and defines the convergence of sequences and the multi-valued weak contractions, etc., on the introduced space. And then, with the methods of functional analysis and abstract algebra, it successively establishes an endpoint theorem for the metric space of partially ordered groups and an endpoint theorem for the metric space of partially ordered modules. The contributions of this article extend the theory of cone metric space constructed by Huang and Zhang (2007) and some recent results on the fixed point and endpoint theory, such as the endpoint theorem given by Amini-Harandi (2010).展开更多
Objectives To explore the optimization method of vaccine clinical trial design based on immunological surrogate endpoint to improve the quality and efficiency of vaccine clinical research and development.Methods As to...Objectives To explore the optimization method of vaccine clinical trial design based on immunological surrogate endpoint to improve the quality and efficiency of vaccine clinical research and development.Methods As to the problems in the vaccine clinical research in China,the relevant guidelines and literatures of FDA and WHO were used to analyze and summarize the methods of optimizing the design of vaccine clinical trials.Results and Conclusion The adaptive design guidelines are established to guide clinical trial design,encourage the development and application of immunological surrogate endpoints,establish qualification process for drug development tools and information disclosure procedures to improve vaccine development efficiency.展开更多
The successful completion of practice-changing clinical trials is hampered by multiple potential challenges including regulatory procedures,patient recruitment,safety concerns,and cost(1).Study duration is a primary f...The successful completion of practice-changing clinical trials is hampered by multiple potential challenges including regulatory procedures,patient recruitment,safety concerns,and cost(1).Study duration is a primary factor in clinical trial feasibility and several approaches have been employed to mitigate its impact.Overall survival(OS)has long been the predominant primary endpoint in cancer clinical trials due to its objectivity,clarity,patient benefit,and role in regulatory approval for new therapies.展开更多
Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by ...Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.展开更多
BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vesse...BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vessels treated with successful anatomical PCI in patients from PANDA Ⅲ trial were retrospectively measured for postPCI QFR.The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs,composite of target vessel-related cardiac death,target vessel-related myocardial infarction,and ischemia-driven target vessel revascularization).Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs,and all vessels were stratified by this optimal cutoff value.Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.RESULTS Among 428 CTO vessels treated with PCI,353 vessels (82.5%) were analyzable for post-PCI QFR.31 VOCEs (8.7%) occurred at 2 years.Mean value of post-PCI QFR was 0.92±0.13.Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91.The incidence of 2-year VOCEs in the vessel with post-PCI QFR<0.91 (n=91) was significantly higher compared with the vessels with post-PCI QFR≥0.91 (n=262)(22.0%vs.4.2%,HR=4.98,95%CI:2.32–10.70).CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO.Achieving functionally optimal PCI results (post-PCI QFR value≥0.91) tends to get better prognosis for patients with CTO lesions.展开更多
＂Living with cancer＂ and symptom control are the features and advantages of integrative medicine in advanced non-small cell lung cancer （NSCLC） treatment. However, with the current concept of response evaluation c...＂Living with cancer＂ and symptom control are the features and advantages of integrative medicine in advanced non-small cell lung cancer （NSCLC） treatment. However, with the current concept of response evaluation criteria by the WHO and RECIST, it is difficult to exhibit the above characteristics. Clinical benefit （CB） is designed as an endpoint recently widely understood and accepted in oncology clinical trials. With the review of its definition and development, we suggest CB to be used as an endpoint in advanced NSCLC treatment with integrative medicine. CB should encompass two connotations： one is improved quality of life and symptom control and the other is disease control rate （DCR）, including complete response （CR）, partial response （PR）, and stable disease （SD）. We need to design randomized controlled trials （RCT） to investigate the interrelationship of CB rate and survival to provide high-grade evidence proving that advanced lung cancer patients could really benefit from integrative medicine treatment.展开更多
Celiac disease is a lifelong disorder for which there is currently only one known,effective treatment:a gluten-free diet.New treatment approaches have recently emerged;several drugs are in Phase 2 trials and results a...Celiac disease is a lifelong disorder for which there is currently only one known,effective treatment:a gluten-free diet.New treatment approaches have recently emerged;several drugs are in Phase 2 trials and results appear promising;however,discussion around regulatory endpoints is in its infancy.We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints,such as patient-reported outcomes,histology,serology,gene expression analysis and other tests.We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials,with a particular emphasis on current thinking in regulatory agencies.We conclude our paper with recommendations and a glossary of regulatory terms,to enable readers who are less familiar with regulatory language to take maximum advantage of this review.展开更多
Objective:A conventional endpoint for locally advanced cervical cancer(LACC)clinical trials is overall survival(OS)with five years of follow-up.The primary hypothesis was that progression-free survival(PFS)with three ...Objective:A conventional endpoint for locally advanced cervical cancer(LACC)clinical trials is overall survival(OS)with five years of follow-up.The primary hypothesis was that progression-free survival(PFS)with three years of follow-up(PFS36)would be an appropriate primary surrogate endpoint.Materials and methods:The primary hypothesis,which was developed from our data,was further investigated using phase III randomized controlled trials and then externally validated using retrospective studies up to 2023.Correlation analysis at the treatment-arm level was performed between 2-,3-,4-,and 5-year PFS rates and 5-year OS.Results:A total of 613 patients with histologically confirmed cervical cancer who underwent radiotherapy or chemoradiation at our institute between January 2010 and December 2013 were eligible.The recurrence rates for years 1 through 5 were 12.9%,7.3%,3%,2.3%,and 1.8%,respectively.Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%.However,patients who achieved PFS36 had a 5-year OS rate of 98.2%.Further data were extracted from 26 randomized phase III trials on LACC.The trials included 55 arms,with a pooled sample size of 7,281 patients.Trial-level surrogacy results revealed that PFS36(r2,0.732)was associated with 5-year OS.The correlation between PFS36 and OS was externally validated using independent retrospective data.Conclusion:A significant positive correlation was found between PFS36 and OS at 5 years of follow-up both within patients and across trials.These results suggest that PFS36 is an appropriate endpoint for LACC clinical trials of radiotherapy-based regimens.展开更多
The endpoint carbon content in the converter is critical for the quality of steel products,and accurately predicting this parameter is an effective way to reduce alloy consumption and improve smelting efficiency.Howev...The endpoint carbon content in the converter is critical for the quality of steel products,and accurately predicting this parameter is an effective way to reduce alloy consumption and improve smelting efficiency.However,most scholars currently focus on modifying methods to enhance model accuracy,while overlooking the extent to which input parameters influence accuracy.To address this issue,in this study,a prediction model for the endpoint carbon content in the converter was developed using factor analysis(FA)and support vector machine(SVM)optimized by improved particle swarm optimization(IPSO).Analysis of the factors influencing the endpoint carbon content during the converter smelting process led to the identification of 21 input parameters.Subsequently,FA was used to reduce the dimensionality of the data and applied to the prediction model.The results demonstrate that the performance of the FA-IPSO-SVM model surpasses several existing methods,such as twin support vector regression and support vector machine.The model achieves hit rates of 89.59%,96.21%,and 98.74%within error ranges of±0.01%,±0.015%,and±0.02%,respectively.Finally,based on the prediction results obtained by sequentially removing input parameters,the parameters were classified into high influence(5%-7%),medium influence(2%-5%),and low influence(0-2%)categories according to their varying degrees of impact on prediction accuracy.This classi-fication provides a reference for selecting input parameters in future prediction models for endpoint carbon content.展开更多
lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an u...lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an unparalleled speed.Theavailability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates,which is crucial to control COVID-19 pandemic.Several phase 3 efficacy trials of COVID-19 vaccine candidates are underway,which provide opportunities for the determination of COVID-19 correlates of protection.In this paper,we review currentknowledge for existence of COVD-19 correlates of protection,methods for assessment of immune correlates of protection andissues related to COVID-19 correlates of protection.展开更多
Ultrahigh-dose-rate radiotherapy(FLASH-RT)is a revolutionary radiotherapy technology that can spare normal tissues without compromising tumor control.Although qualitative experimental results have been reported,quanti...Ultrahigh-dose-rate radiotherapy(FLASH-RT)is a revolutionary radiotherapy technology that can spare normal tissues without compromising tumor control.Although qualitative experimental results have been reported,quantitative and systematic analysis of data is necessary.Particularly,the FLASH effect response model to the dose or dose rate is still unclear.This study investigated the relationships between the FLASH effect and experimental parameters,such as dose,dose rate,and other factors by analyzing published in vivo experimental data from animal models.The data were modeled based on logistic regression analysis using the sigmoid function.The model was evaluated using prediction accuracy,receiver operating characteristic(ROC)curve,and area under the ROC curve.Results showed that the FLASH effect was closely related to the dose,mean dose rate,tissue type,and corresponding biological endpoints.The dose rate corresponding to a 50% probability of triggering cognitive protection in the brain was 45 Gy s^(-1).The dose rate corresponding to a 50% probability of triggering intestinal crypt survival and regeneration was 140 Gy s^(-1).For the skin toxicity effect,the dose corresponding to a 50% probability of triggering the FLASH effect was 24 Gy.This study helps to characterize the conditions underlying the FLASH effect and provides important information for optimizing experiments.展开更多
Conventional dentistry or periodontal research often ignores the human component in favor of clinical outcomes and biological causes.Clinical research is driven by the statistical significance of outcome parameters ra...Conventional dentistry or periodontal research often ignores the human component in favor of clinical outcomes and biological causes.Clinical research is driven by the statistical significance of outcome parameters rather than the satisfaction level of the patient.In this context,patient-centric periodontal research(PCPR)is an approach that considers the patient´s feedback concerning their functional status,experience,clinical outcomes,and accessibility to their treatments.It is argued that data self-reported by the patient might have low reliability owing to the confounding effect of their personal belief,cultural background,and social and economic factors.However,literature has shown that the incorporation of“patient-centric outcome”components considerably enhances the validity and applicability of research findings.Variations in the results of different studies might be due to the use of different and non-standardized assessment tools.To overcome this problem,this editorial enlists various reliable tools available in the literature.In conclusion,we advocate that the focus of researchers should shift from mere periodontal research to PCPR so that the results can be effectively applied in clinical settings and the therapeutic strategy can also change from mere periodontal therapy to patient-centric periodontal therapy.展开更多
文摘A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.
文摘As the Web of Data grows, the number of available SPARQL endpoints increases. SPARQL endpoints conceptually represent RPC-style, coarse-grained data access mechanisms. Nevertheless, through the potential interlinking of the contained entities, SPARQL endpoints should be able to over distinct advantages over plain Web APIs. To our knowledge, to date, there has been no study conducted that gauges the impact of the link on SPARQL query execution, especially in a federated set-up. In this paper, we investigate how the existence and types of typed links influences the execution characteristics of different SPARQL federation frameworks. In order to measure the query performance, we propose a combined cost model based on a statistic analysis of the query performance metrics that involves parameters such as type of link, the data catalogues and cache, number of links, and number of distinct subjects. As result, we show that number of distinct subject and number of links have significant impact on Federation over SPARQL Endpoints performance whereas type of link does not have significantly influence in federation query performance.
基金Supported by National Natural Science Foundation of China(Grant No51305031)
文摘Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube＇s endpoints and then fix any geometric errors correspondingly. However, the traditional tube inspection method is time-consuming and complex operations. Therefore, a new measurement method for a tube＇s endpoints based on machine vision is proposed. First, reflected light on tube＇s surface can be removed by using photometric linearization. Then, based on the optimization model for the tube＇s endpoint measurements and the principle of stereo matching, the global coordinates and the relative distance of the tube＇s endpoint are obtained. To confirm the feasibility, ll tubes are processed to remove the reflected light and then the endpoint＇s positions of tubes are measured. The experiment results show that the measurement repeatability accuracy is 0.167 mm, and the absolute accuracy is 0.328 ram. The measurement takes less than 1 min. The proposed method based on machine vision can measure the tube＇s endpoints without any surface treatment or any tools and can realize on line measurement.
基金Supported by Special Research Project by the State Administration of Traditional Chinese Medicine:Traditional Chinese Medicine Health Management Based Risk Assessment System Development and Demonstration for Recurrence of Ischemic Stroke(No.201507003-8)
文摘OBJECTIVE: To evaluate the risk of ischemic stroke endpoints by establishing risk assessment models that combine Traditional Chinese Medicine(TCM)and modern medicine indicators.METHODS/DESIGN: The proposed study is a registry-based participant survey conducted in seven hospitals nationwide in China. After obtaining informed consent, 3000 patients diagnosed with ischemic stroke will be recruited. One-year follow-ups will be performed on-site in hospitals and by telephone to track endpoint events. Comparative analysis of the prevalence of endpoint events and other TCM or modern medicine features in different groups will be conducted using frequency analysis and χ2tests, and the results will be expressed as composition ratios. Comparative analysis of quantitative scores and related patterns or symptoms will be conducted using a rank-sum test. Correlation analysis of endpoint events and TCM or modern medicine factors will be performed using a multivariate Cox proportional hazard model.DISCUSSION: Previous reports have described modern medicine indicator-based risk assessment models for ischemic stroke endpoint events, but no such studies have included TCM features. Our new risk assessment model combines TCM and modern medicine indicators and thus has the potential to facilitate early warning, early intervention, and early control of ischemic stroke endpoint events.
文摘In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.
文摘In the design of chemical processes,such as catalytic cracking of bitumen and heavy oil,the knowledge of phase behavior at the critical endpoint is essential.Based on the PR equation of state,the algorithm developed by Heidemann and Khalil for calculating critical properties was used to compute critical points.An algorithm for determining the equilibrium phase of the critical point using the tangent plane criterion was developed,and was used to calculate the critical endpoints of different mixtures,including non-polar,polar and associating systems.The critical endpoint,representing the type of the phase behavior,was employed to fit the interaction parameter of mixtures in critical state at high pressure.Lines of critical endpoints for ternary mixtures were also determined with the algorithm.
文摘Cervical spinal cord injury （SCI） results in partial to full paralysis of the upper and lower extrem- ities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control （e.g., upper extremity motor score, motor level change） show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement.
文摘Due to ethical and logistical concerns it is common for data monitoring committees to periodically monitor accruing clinical trial data to assess the safety, and possibly efficacy, of a new experimental treatment. When formalized, monitoring is typically implemented using group sequential methods. In some cases regulatory agencies have required that primary trial analyses should be based solely on the judgment of an independent review committee (IRC). The IRC assessments can produce difficulties for trial monitoring given the time lag typically associated with receiving assessments from the IRC. This results in a missing data problem wherein a surrogate measure of response may provide useful information for interim decisions and future monitoring strategies. In this paper, we present statistical tools that are helpful for monitoring a group sequential clinical trial with missing IRC data. We illustrate the proposed methodology in the case of binary endpoints under various missingness mechanisms including missing completely at random assessments and when missingness depends on the IRC’s measurement.
文摘The present work considers the endpoint in the abstract metric space. It firstly introduces the metric space of partially ordered groups and the metric space of partially ordered modules, respectively;and defines the convergence of sequences and the multi-valued weak contractions, etc., on the introduced space. And then, with the methods of functional analysis and abstract algebra, it successively establishes an endpoint theorem for the metric space of partially ordered groups and an endpoint theorem for the metric space of partially ordered modules. The contributions of this article extend the theory of cone metric space constructed by Huang and Zhang (2007) and some recent results on the fixed point and endpoint theory, such as the endpoint theorem given by Amini-Harandi (2010).
文摘Objectives To explore the optimization method of vaccine clinical trial design based on immunological surrogate endpoint to improve the quality and efficiency of vaccine clinical research and development.Methods As to the problems in the vaccine clinical research in China,the relevant guidelines and literatures of FDA and WHO were used to analyze and summarize the methods of optimizing the design of vaccine clinical trials.Results and Conclusion The adaptive design guidelines are established to guide clinical trial design,encourage the development and application of immunological surrogate endpoints,establish qualification process for drug development tools and information disclosure procedures to improve vaccine development efficiency.
文摘The successful completion of practice-changing clinical trials is hampered by multiple potential challenges including regulatory procedures,patient recruitment,safety concerns,and cost(1).Study duration is a primary factor in clinical trial feasibility and several approaches have been employed to mitigate its impact.Overall survival(OS)has long been the predominant primary endpoint in cancer clinical trials due to its objectivity,clarity,patient benefit,and role in regulatory approval for new therapies.
文摘Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.
基金supported by the CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-008)the National High Level Hospital Clinical Research Funding(No.2023-GSP-GG-2&No.2023-GSP-QN-34&No.2023-GSPRC-05).
文摘BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vessels treated with successful anatomical PCI in patients from PANDA Ⅲ trial were retrospectively measured for postPCI QFR.The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs,composite of target vessel-related cardiac death,target vessel-related myocardial infarction,and ischemia-driven target vessel revascularization).Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs,and all vessels were stratified by this optimal cutoff value.Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.RESULTS Among 428 CTO vessels treated with PCI,353 vessels (82.5%) were analyzable for post-PCI QFR.31 VOCEs (8.7%) occurred at 2 years.Mean value of post-PCI QFR was 0.92±0.13.Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91.The incidence of 2-year VOCEs in the vessel with post-PCI QFR<0.91 (n=91) was significantly higher compared with the vessels with post-PCI QFR≥0.91 (n=262)(22.0%vs.4.2%,HR=4.98,95%CI:2.32–10.70).CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO.Achieving functionally optimal PCI results (post-PCI QFR value≥0.91) tends to get better prognosis for patients with CTO lesions.
文摘＂Living with cancer＂ and symptom control are the features and advantages of integrative medicine in advanced non-small cell lung cancer （NSCLC） treatment. However, with the current concept of response evaluation criteria by the WHO and RECIST, it is difficult to exhibit the above characteristics. Clinical benefit （CB） is designed as an endpoint recently widely understood and accepted in oncology clinical trials. With the review of its definition and development, we suggest CB to be used as an endpoint in advanced NSCLC treatment with integrative medicine. CB should encompass two connotations： one is improved quality of life and symptom control and the other is disease control rate （DCR）, including complete response （CR）, partial response （PR）, and stable disease （SD）. We need to design randomized controlled trials （RCT） to investigate the interrelationship of CB rate and survival to provide high-grade evidence proving that advanced lung cancer patients could really benefit from integrative medicine treatment.
文摘Celiac disease is a lifelong disorder for which there is currently only one known,effective treatment:a gluten-free diet.New treatment approaches have recently emerged;several drugs are in Phase 2 trials and results appear promising;however,discussion around regulatory endpoints is in its infancy.We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints,such as patient-reported outcomes,histology,serology,gene expression analysis and other tests.We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials,with a particular emphasis on current thinking in regulatory agencies.We conclude our paper with recommendations and a glossary of regulatory terms,to enable readers who are less familiar with regulatory language to take maximum advantage of this review.
基金funded by the CAMS Innovation Fund for Medical Sciences(CIFMS)(grant number:2024-I2M-C&T-B-071)the Beijing Hope Run Special Fund of Cancer Foundation of China(grant number:LC2018B04).
文摘Objective:A conventional endpoint for locally advanced cervical cancer(LACC)clinical trials is overall survival(OS)with five years of follow-up.The primary hypothesis was that progression-free survival(PFS)with three years of follow-up(PFS36)would be an appropriate primary surrogate endpoint.Materials and methods:The primary hypothesis,which was developed from our data,was further investigated using phase III randomized controlled trials and then externally validated using retrospective studies up to 2023.Correlation analysis at the treatment-arm level was performed between 2-,3-,4-,and 5-year PFS rates and 5-year OS.Results:A total of 613 patients with histologically confirmed cervical cancer who underwent radiotherapy or chemoradiation at our institute between January 2010 and December 2013 were eligible.The recurrence rates for years 1 through 5 were 12.9%,7.3%,3%,2.3%,and 1.8%,respectively.Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%.However,patients who achieved PFS36 had a 5-year OS rate of 98.2%.Further data were extracted from 26 randomized phase III trials on LACC.The trials included 55 arms,with a pooled sample size of 7,281 patients.Trial-level surrogacy results revealed that PFS36(r2,0.732)was associated with 5-year OS.The correlation between PFS36 and OS was externally validated using independent retrospective data.Conclusion:A significant positive correlation was found between PFS36 and OS at 5 years of follow-up both within patients and across trials.These results suggest that PFS36 is an appropriate endpoint for LACC clinical trials of radiotherapy-based regimens.
基金financially supported by the National Natural Science Foundation of China(No.52174297).
文摘The endpoint carbon content in the converter is critical for the quality of steel products,and accurately predicting this parameter is an effective way to reduce alloy consumption and improve smelting efficiency.However,most scholars currently focus on modifying methods to enhance model accuracy,while overlooking the extent to which input parameters influence accuracy.To address this issue,in this study,a prediction model for the endpoint carbon content in the converter was developed using factor analysis(FA)and support vector machine(SVM)optimized by improved particle swarm optimization(IPSO).Analysis of the factors influencing the endpoint carbon content during the converter smelting process led to the identification of 21 input parameters.Subsequently,FA was used to reduce the dimensionality of the data and applied to the prediction model.The results demonstrate that the performance of the FA-IPSO-SVM model surpasses several existing methods,such as twin support vector regression and support vector machine.The model achieves hit rates of 89.59%,96.21%,and 98.74%within error ranges of±0.01%,±0.015%,and±0.02%,respectively.Finally,based on the prediction results obtained by sequentially removing input parameters,the parameters were classified into high influence(5%-7%),medium influence(2%-5%),and low influence(0-2%)categories according to their varying degrees of impact on prediction accuracy.This classi-fication provides a reference for selecting input parameters in future prediction models for endpoint carbon content.
基金supported by Jiangsu Province Special Funds for Key Research&Developm ent(2060499).
文摘lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an unparalleled speed.Theavailability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates,which is crucial to control COVID-19 pandemic.Several phase 3 efficacy trials of COVID-19 vaccine candidates are underway,which provide opportunities for the determination of COVID-19 correlates of protection.In this paper,we review currentknowledge for existence of COVD-19 correlates of protection,methods for assessment of immune correlates of protection andissues related to COVID-19 correlates of protection.
基金supported by the National Key R&D Program of China(No.2022YFC2402300)National Natural Science Foundation of China(No.12075330)。
文摘Ultrahigh-dose-rate radiotherapy(FLASH-RT)is a revolutionary radiotherapy technology that can spare normal tissues without compromising tumor control.Although qualitative experimental results have been reported,quantitative and systematic analysis of data is necessary.Particularly,the FLASH effect response model to the dose or dose rate is still unclear.This study investigated the relationships between the FLASH effect and experimental parameters,such as dose,dose rate,and other factors by analyzing published in vivo experimental data from animal models.The data were modeled based on logistic regression analysis using the sigmoid function.The model was evaluated using prediction accuracy,receiver operating characteristic(ROC)curve,and area under the ROC curve.Results showed that the FLASH effect was closely related to the dose,mean dose rate,tissue type,and corresponding biological endpoints.The dose rate corresponding to a 50% probability of triggering cognitive protection in the brain was 45 Gy s^(-1).The dose rate corresponding to a 50% probability of triggering intestinal crypt survival and regeneration was 140 Gy s^(-1).For the skin toxicity effect,the dose corresponding to a 50% probability of triggering the FLASH effect was 24 Gy.This study helps to characterize the conditions underlying the FLASH effect and provides important information for optimizing experiments.
文摘Conventional dentistry or periodontal research often ignores the human component in favor of clinical outcomes and biological causes.Clinical research is driven by the statistical significance of outcome parameters rather than the satisfaction level of the patient.In this context,patient-centric periodontal research(PCPR)is an approach that considers the patient´s feedback concerning their functional status,experience,clinical outcomes,and accessibility to their treatments.It is argued that data self-reported by the patient might have low reliability owing to the confounding effect of their personal belief,cultural background,and social and economic factors.However,literature has shown that the incorporation of“patient-centric outcome”components considerably enhances the validity and applicability of research findings.Variations in the results of different studies might be due to the use of different and non-standardized assessment tools.To overcome this problem,this editorial enlists various reliable tools available in the literature.In conclusion,we advocate that the focus of researchers should shift from mere periodontal research to PCPR so that the results can be effectively applied in clinical settings and the therapeutic strategy can also change from mere periodontal therapy to patient-centric periodontal therapy.
