BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there ar...BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.展开更多
In contrast to the traditional Western approach to macro-fiscal management,China’s proactive fiscal policy is founded on a people-centered development philosophy and,with distinctive Chinese characteristics,is a sign...In contrast to the traditional Western approach to macro-fiscal management,China’s proactive fiscal policy is founded on a people-centered development philosophy and,with distinctive Chinese characteristics,is a significant policy innovation of macroeconomic management in the Chinese modernization.Although there are notable distinctions between the Western“Keynesian”and the“nonKeynesian”schools of thought,both of these approaches’core policy goals and methodological roots are the same,composing the traditional Western macro-fiscal approach.This approach faces increasing real dilemmas.China’s proactive fiscal policy,however,places greater emphasis on future potential growth rates in addition to equilibrium between supply and demand,achieving a fiscal policy transformation with a new approach.In this paper we argue that with such a new approach,China should reconsider the nature and reasonable level of the fiscal deficit,the function and risk assessment criteria of government debt,the scope and effects of reductions in taxes and fees,its approach and focus of demand management,and the costs and resulting efficiencies of policies in order to develop a new fiscal policy paradigm that is more in line with its stated goals.展开更多
Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) a...Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.展开更多
This paper introduces Certis, a powerful framework that addresses the challenges of cloud asset tracking, management, and threat detection in modern cybersecurity landscapes. It enhances asset identification and anoma...This paper introduces Certis, a powerful framework that addresses the challenges of cloud asset tracking, management, and threat detection in modern cybersecurity landscapes. It enhances asset identification and anomaly detection through SSL certificate parsing, cloud service provider integration, and advanced fingerprinting techniques like JARM at the application layer. Current work will focus on cross-layer malicious behavior identification to further enhance its capabilities, including minimizing false positives through AI-based learning techniques. Certis promises to offer a powerful solution for organizations seeking proactive cybersecurity defenses in the face of evolving threats.展开更多
As cyber threats keep changing and business environments adapt, a comprehensive approach to disaster recovery involves more than just defensive measures. This research delves deep into the strategies required to respo...As cyber threats keep changing and business environments adapt, a comprehensive approach to disaster recovery involves more than just defensive measures. This research delves deep into the strategies required to respond to threats and anticipate and mitigate them proactively. Beginning with understanding the critical need for a layered defense and the intricacies of the attacker’s journey, the research offers insights into specialized defense techniques, emphasizing the importance of timely and strategic responses during incidents. Risk management is brought to the forefront, underscoring businesses’ need to adopt mature risk assessment practices and understand the potential risk impact areas. Additionally, the value of threat intelligence is explored, shedding light on the importance of active engagement within sharing communities and the vigilant observation of adversary motivations. “Beyond Defense: Proactive Approaches to Disaster Recovery and Threat Intelligence in Modern Enterprises” is a comprehensive guide for organizations aiming to fortify their cybersecurity posture, marrying best practices in proactive and reactive measures in the ever-challenging digital realm.展开更多
Although it is becoming increasingly popular for organizations to offer programs of mind–body practices to their employees to improve their physical and mental health,the effects that after-work sessions of mind–bod...Although it is becoming increasingly popular for organizations to offer programs of mind–body practices to their employees to improve their physical and mental health,the effects that after-work sessions of mind–body prac-tices have on employees’work behavior remain unclear.Using the model of proactive motivation and experience sampling,this study explored the relationship between employees’mind–body practices after work and their proactive behavior in the workplace on the following day.A multilevel path analysis of data from 82 employees over seven consecutive workdays showed that employees’mind–body practices after work had a positive effect on their proactive behavior in the workplace on the following day.The relationship was mediated by next-day high-activated positive affect and problem-solving confidence.Furthermore,job control positively moderated the rela-tionship between high-activated positive affect and proactive behavior but not that between problem-solving con-fidence and proactive behavior.We discuss the theoretical and practical implications of thesefindings,and propose future research directions.展开更多
A major challenge for the future wireless network is to design the self-organizing architecture.The reactive self-organizing model of traditional networks needs to be transformed into an active self-organizing network...A major challenge for the future wireless network is to design the self-organizing architecture.The reactive self-organizing model of traditional networks needs to be transformed into an active self-organizing network.Due to the user mobility and the coverage of small cells,the network load often becomes unbalanced,resulting in poor network performance.Mobility management has become an important issue to ensure seamless communication when users move between cells,and proactive mobility management is one of the important functions of the active Self-Organizing Network(SON).This paper proposes a proactive mobility management framework for active SON,which transforms the original reactive load balancing into a forward-aware and proactive load balancing.The proposed framework firstly uses the BART model to predict the users’temporal and spatial mobility based on a weekly cycle and then formulate the MLB optimization problem based on the soft load.Two solutions are proposed to solve the above MLB problem.The simulation results show that the proposed method can better optimize the network performance and realize intelligent mobile management for the future network.展开更多
Scientific workflows have gained the emerging attention in sophisti-cated large-scale scientific problem-solving environments.The pay-per-use model of cloud,its scalability and dynamic deployment enables it suited for ex...Scientific workflows have gained the emerging attention in sophisti-cated large-scale scientific problem-solving environments.The pay-per-use model of cloud,its scalability and dynamic deployment enables it suited for executing scientific workflow applications.Since the cloud is not a utopian environment,failures are inevitable that may result in experiencingfluctuations in the delivered performance.Though a single task failure occurs in workflow based applications,due to its task dependency nature,the reliability of the overall system will be affected drastically.Hence rather than reactive fault-tolerant approaches,proactive measures are vital in scientific workflows.This work puts forth an attempt to con-centrate on the exploration issue of structuring a nature inspired metaheuristics-Intelligent Water Drops Algorithm(IWDA)combined with an efficient machine learning approach-Support Vector Regression(SVR)for task failure prognostica-tion which facilitates proactive fault-tolerance in the scheduling of scientific workflow applications.The failure prediction models in this study have been implemented through SVR-based machine learning approaches and the precision accuracy of prediction is optimized by IWDA and several performance metrics were evaluated on various benchmark workflows.The experimental results prove that the proposed proactive fault-tolerant approach performs better compared with the other existing techniques.展开更多
During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to me...During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.展开更多
This review explores entrepreneurial orientation and innovation ecosystems in the industrial sector of the Central Region, Kampala, Uganda, through an analysis of ten scholarly articles. The study contextualizes the r...This review explores entrepreneurial orientation and innovation ecosystems in the industrial sector of the Central Region, Kampala, Uganda, through an analysis of ten scholarly articles. The study contextualizes the research within the regional landscape and establishes a theoretical framework through a focused literature review. Key findings highlight the intersection of entrepreneurial activities and innovation dynamics, emphasizing the region’s unique contributions to the broader field. Discussions on discrepancies and unexplored territories within the articles offer insights into limitations and research gaps. The manuscript concludes by identifying future research avenues, providing a roadmap for ongoing inquiry into the entrepreneurial and innovative dimensions of the Central Region’s industrial sector. This synthesis underscores the importance of cultivating an entrepreneurial mindset and collaborative innovation strategies for sustainable industrial development in the region.展开更多
基金Supported by the National Natural Science Foundation of China,No.82020108031,No.81973398,and No.82104290Guangdong Provincial Key Laboratory of Construction Foundation,No.2020B1212060034Guangdong Basic and Applied Basic Research Foundation,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
文摘In contrast to the traditional Western approach to macro-fiscal management,China’s proactive fiscal policy is founded on a people-centered development philosophy and,with distinctive Chinese characteristics,is a significant policy innovation of macroeconomic management in the Chinese modernization.Although there are notable distinctions between the Western“Keynesian”and the“nonKeynesian”schools of thought,both of these approaches’core policy goals and methodological roots are the same,composing the traditional Western macro-fiscal approach.This approach faces increasing real dilemmas.China’s proactive fiscal policy,however,places greater emphasis on future potential growth rates in addition to equilibrium between supply and demand,achieving a fiscal policy transformation with a new approach.In this paper we argue that with such a new approach,China should reconsider the nature and reasonable level of the fiscal deficit,the function and risk assessment criteria of government debt,the scope and effects of reductions in taxes and fees,its approach and focus of demand management,and the costs and resulting efficiencies of policies in order to develop a new fiscal policy paradigm that is more in line with its stated goals.
文摘Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.
文摘This paper introduces Certis, a powerful framework that addresses the challenges of cloud asset tracking, management, and threat detection in modern cybersecurity landscapes. It enhances asset identification and anomaly detection through SSL certificate parsing, cloud service provider integration, and advanced fingerprinting techniques like JARM at the application layer. Current work will focus on cross-layer malicious behavior identification to further enhance its capabilities, including minimizing false positives through AI-based learning techniques. Certis promises to offer a powerful solution for organizations seeking proactive cybersecurity defenses in the face of evolving threats.
文摘As cyber threats keep changing and business environments adapt, a comprehensive approach to disaster recovery involves more than just defensive measures. This research delves deep into the strategies required to respond to threats and anticipate and mitigate them proactively. Beginning with understanding the critical need for a layered defense and the intricacies of the attacker’s journey, the research offers insights into specialized defense techniques, emphasizing the importance of timely and strategic responses during incidents. Risk management is brought to the forefront, underscoring businesses’ need to adopt mature risk assessment practices and understand the potential risk impact areas. Additionally, the value of threat intelligence is explored, shedding light on the importance of active engagement within sharing communities and the vigilant observation of adversary motivations. “Beyond Defense: Proactive Approaches to Disaster Recovery and Threat Intelligence in Modern Enterprises” is a comprehensive guide for organizations aiming to fortify their cybersecurity posture, marrying best practices in proactive and reactive measures in the ever-challenging digital realm.
基金supported by the Natural Science Foundation of Hubei Province(2021CFB297)the Natural Science Foundation of Guangdong Province(2022A1515010563).
文摘Although it is becoming increasingly popular for organizations to offer programs of mind–body practices to their employees to improve their physical and mental health,the effects that after-work sessions of mind–body prac-tices have on employees’work behavior remain unclear.Using the model of proactive motivation and experience sampling,this study explored the relationship between employees’mind–body practices after work and their proactive behavior in the workplace on the following day.A multilevel path analysis of data from 82 employees over seven consecutive workdays showed that employees’mind–body practices after work had a positive effect on their proactive behavior in the workplace on the following day.The relationship was mediated by next-day high-activated positive affect and problem-solving confidence.Furthermore,job control positively moderated the rela-tionship between high-activated positive affect and proactive behavior but not that between problem-solving con-fidence and proactive behavior.We discuss the theoretical and practical implications of thesefindings,and propose future research directions.
基金supported in part by the Guangdong Basic and Applied Basic Research Foundation under grant 2020A1515110269.
文摘A major challenge for the future wireless network is to design the self-organizing architecture.The reactive self-organizing model of traditional networks needs to be transformed into an active self-organizing network.Due to the user mobility and the coverage of small cells,the network load often becomes unbalanced,resulting in poor network performance.Mobility management has become an important issue to ensure seamless communication when users move between cells,and proactive mobility management is one of the important functions of the active Self-Organizing Network(SON).This paper proposes a proactive mobility management framework for active SON,which transforms the original reactive load balancing into a forward-aware and proactive load balancing.The proposed framework firstly uses the BART model to predict the users’temporal and spatial mobility based on a weekly cycle and then formulate the MLB optimization problem based on the soft load.Two solutions are proposed to solve the above MLB problem.The simulation results show that the proposed method can better optimize the network performance and realize intelligent mobile management for the future network.
文摘Scientific workflows have gained the emerging attention in sophisti-cated large-scale scientific problem-solving environments.The pay-per-use model of cloud,its scalability and dynamic deployment enables it suited for executing scientific workflow applications.Since the cloud is not a utopian environment,failures are inevitable that may result in experiencingfluctuations in the delivered performance.Though a single task failure occurs in workflow based applications,due to its task dependency nature,the reliability of the overall system will be affected drastically.Hence rather than reactive fault-tolerant approaches,proactive measures are vital in scientific workflows.This work puts forth an attempt to con-centrate on the exploration issue of structuring a nature inspired metaheuristics-Intelligent Water Drops Algorithm(IWDA)combined with an efficient machine learning approach-Support Vector Regression(SVR)for task failure prognostica-tion which facilitates proactive fault-tolerance in the scheduling of scientific workflow applications.The failure prediction models in this study have been implemented through SVR-based machine learning approaches and the precision accuracy of prediction is optimized by IWDA and several performance metrics were evaluated on various benchmark workflows.The experimental results prove that the proposed proactive fault-tolerant approach performs better compared with the other existing techniques.
文摘During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.
文摘This review explores entrepreneurial orientation and innovation ecosystems in the industrial sector of the Central Region, Kampala, Uganda, through an analysis of ten scholarly articles. The study contextualizes the research within the regional landscape and establishes a theoretical framework through a focused literature review. Key findings highlight the intersection of entrepreneurial activities and innovation dynamics, emphasizing the region’s unique contributions to the broader field. Discussions on discrepancies and unexplored territories within the articles offer insights into limitations and research gaps. The manuscript concludes by identifying future research avenues, providing a roadmap for ongoing inquiry into the entrepreneurial and innovative dimensions of the Central Region’s industrial sector. This synthesis underscores the importance of cultivating an entrepreneurial mindset and collaborative innovation strategies for sustainable industrial development in the region.