AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent fou...AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.展开更多
TheRussia-Ukrainecrisiswas araremilitary crisis between European powers after the end of the Cold War,which led to confrontation between Western countries and Russia.Such a crisis also triggered the extensive involvem...TheRussia-Ukrainecrisiswas araremilitary crisis between European powers after the end of the Cold War,which led to confrontation between Western countries and Russia.Such a crisis also triggered the extensive involvement of nonstate actors,such as international capital giants,small and micro technology enterprises,emerging international platforms,and multinational corporations.Nonstate actors play an important role in international politics.Benefiting from the development of globalization and the accelerated evolution of the digital age,nonstate actors have exerted a significant influence on the international pattern by intervening in the competition between countries,participating in the process of global governance,and influencing the thoughts of science and technology.These actors have become an important variable affecting the world.The rising role of nonstate actors has many implications for China to expand its strength and safeguard national interests and security.展开更多
This paper investigates survivability escalation strategies in multi layers transport networks such as ATM/SDH/WDM networks, and presents oriented failures and oriented traffic escalation mechanisms. Furthermore, W...This paper investigates survivability escalation strategies in multi layers transport networks such as ATM/SDH/WDM networks, and presents oriented failures and oriented traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi layer networks, such as WDM based ATM networks or WDM based SDH networks.展开更多
Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤...Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.展开更多
Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patien...Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.展开更多
Objective: Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer (NSCLC). Due to absence of phase I trial in China, we conducted this study to define the maximum-to...Objective: Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer (NSCLC). Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose (MTD) of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC. Methods: Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m2, bid, on days d5-d 18, and docetaxe130 mg/m2 on days 1 and 8, respectively. The regimen was repeated every 21 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared. Results: Eighteen patients received 67 cycles at capecitabine of level I (1250 mg/m2, divided into 625 mg/m2, bid) and level II (1500 mg/m2, 750 mg/m2, bid). The most common toxicities were neutropenia, hand and feet syndrome, fatigue and nausea. Eight DLTs occurred in 5 patients in the whole group, including 1 DLT in dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD. Cunclusion: MTD of our phase I trial was capecitabine of 1250 mg/m2/d combined with docetaxel of 30 mg/m2/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial.展开更多
Objective:To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy(ADT)in high-risk prostate cancer in three radiotherapy dose groups.Methods:Between 1998 a...Objective:To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy(ADT)in high-risk prostate cancer in three radiotherapy dose groups.Methods:Between 1998 and 2013,patients with high-risk prostate cancer underwent threedimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy,72 Gy,or 78 Gy with ADT.Prostate-specific antigen(PSA)relapse was defined using the Phoenix definition.PSA relapse-free survival(PRFS)was evaluated in each radiotherapy dose group.Moreover,high-risk patients were divided into H-1(patients with multiple high-risk factors)and H-2(patients with a single high-risk factor)as risk subgroups.Results:Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study.The median duration of ADT was 10.1 months.Age,Gleason score,T stage,and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses.The 4-year PRFS rates in Group-66 Gy,Group-72 Gy and Group-78 Gy were 72.7%,81.6%and 90.3%,respectively.PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS,while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose.Conclusion:Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS.PRFS for patients in the H-1 subgroup was poor,but dose escalation in those patients was beneficial,while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS.展开更多
There have been a lot of research exertions and studies to improve the safety of critical infrastructures using the Security Operations Center (SOC). As part of efforts, the purpose of this research is to propose a fr...There have been a lot of research exertions and studies to improve the safety of critical infrastructures using the Security Operations Center (SOC). As part of efforts, the purpose of this research is to propose a framework to automate the SOC’s performance of triage, containment and escalation. The research leveraged on qualitative desk review to collect data for analysis, deduced strengths and weaknesses for the current SOC implementations and used that as a basis for proposing the framework. In view of the constant evolution of SOC operations and capabilities coupled with the huge volumes of data collected for analysis, an efficient framework for SOC operations is proposed. The qualitative analysis is used to deduce strengths and weaknesses for the current SOC implementations as a premise for proposing the framework. It consists of eight interactive stages that further leverage on a proposed algorithm for baselining, remediation and escalation. The result of this research is a proposed framework that serves as a unique contribution to enhancing the SOC’s ability to automatically perform triage, containment and escalation. Supplementary to similar and earlier work reviewed, the framework is proposed as the way forward to automatically enable SOC setups with the capacity to efficiently perform triage of security threats, vulnerabilities and incidents, effectively contain identified breaches and appropriately escalate for prompt and accurate solutions.展开更多
BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of respons...BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.展开更多
Xi Jinping,General Secretary of the Communist Party of China(CPC)Central Committee,has creatively put forward a holistic approach to national security,making a major breakthrough beyond the traditional national securi...Xi Jinping,General Secretary of the Communist Party of China(CPC)Central Committee,has creatively put forward a holistic approach to national security,making a major breakthrough beyond the traditional national security concepts and providing the world with a new one characterized by universality and inclusivity.This thesis uses a holistic approach to national security to analyze the ongoing Russia-Ukraine crisis:its underlying causes,latest developments,tactics deployed,and potential implications.The outbreak of the Russia-Ukraine crisis highlights the antagonism between different national security paths of the US,Russia,and Ukraine.Moreover,the crisis has proven the correctness of the path of national security with Chinese characteristics and the importance of pursuing peaceful development.The process of the Russia-Ukraine crisis has foregrounded the necessity and scientificity of balancing development and security-that is,a higher level of national security provides a guarantee and support for high-quality development,which in turn improves its competence and efficiency.Typified by intertwined traditional and non-traditional security issues,the form of the RussiaUkraine crisis has indicated that,to safeguard national security,China must coordinate a full spectrum of security issues,be prepared for worst-case scenarios,and remain keenly alert to potential dangers.Efforts must be made to strengthen a well-coordinated,interconnected,and multi-pronged approach.The consequences of the Russia-Ukraine crisis shed light on the complexity of the international security environment wheredisorder prevails,and underscore the importance of paying equal attention to our security and that shared by the world.China must continue to encourage all other countries to pursue peaceful development,actively respond to the legitimate security concerns of the international community,and promote a new type of international security framework that features mutually beneficial cooperation under the vision of a community with a shared future for humanity.展开更多
As a convenient passenger transit facility between floors with different heights, escalators have been extensively used in shopping malls, metro stations, airport terminals, etc. Compared with other vertical transit f...As a convenient passenger transit facility between floors with different heights, escalators have been extensively used in shopping malls, metro stations, airport terminals, etc. Compared with other vertical transit facilities including stairs and elevators, escalators usually have large transit capacity. It is expected to reduce pedestrian traveling time and thus improve the quality of pedestrian’s experiences especially in jamming conditions. However, it is noticed that pedestrians may present different movement patterns, e.g., queuing on each step of the escalator, walking on the left-side and meanwhile standing on the right-side of the escalator. These different patterns affect the actual escalator traffic volume and finally the passenger spatiotemporal distribution in different built environments. Thus, in the present study, a microscopic cellular automaton(CA) simulation model considering pedestrian movement behavior on escalators is built. Simulations are performed considering different pedestrian movement speeds, queuing modes, and segregation on escalators with different escalator speeds.The actual escalator capacities under different pedestrian movement patterns are investigated. It is found that walking on escalators will not always benefit escalator transit volume improvement, especially in jamming conditions.展开更多
In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing(MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hosp...In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing(MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis(UC) and Crohn's disease(CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.展开更多
Dengue virus infection is more and more acknowledged as one of the world’s major escalating problems. Dengue is prevalent in most tropical and subtropical countries. To solve this problem, pharmacists need to underst...Dengue virus infection is more and more acknowledged as one of the world’s major escalating problems. Dengue is prevalent in most tropical and subtropical countries. To solve this problem, pharmacists need to understand the epidemiology, risk factors, clinical spectrum, diagnosis, management, prevention, and novel avenues of dengue.展开更多
“China will fight to the end if the United States continues to escalate trade frictions,”the Ministry of Commerce(MOC)said recently.China will not give ground on issues of principle during bilateral economic and tra...“China will fight to the end if the United States continues to escalate trade frictions,”the Ministry of Commerce(MOC)said recently.China will not give ground on issues of principle during bilateral economic and trade talks,which are clearly stated in a white paper on bilateral trade consultations issued earlier this month,MOC spokesperson Gao Feng said.In response to the new threat of tarrifs by the United States,Gao said China is firmly against US unilateralism and bullying.展开更多
Objective:Escalator signage could be playing a vital role to alert users for safe use of escalators.This study aimed to evaluate the availability,standardization,and content of safety information on escalator signage ...Objective:Escalator signage could be playing a vital role to alert users for safe use of escalators.This study aimed to evaluate the availability,standardization,and content of safety information on escalator signage in the shopping malls.Methods:An observational study was conducted from November 2017 to February 2018 to assess the availability,standardization of safety information among the signage inside the shopping mall,and the content of safety information for public safety in Malaysia.A checklist was developed by adapting escalator safety guidelines from seven countries and regions including Malaysia.Data collctors identified from the selected states were required to capture three photographs at different angles of the escalator signage for each ascending and descending directions at each entrance of the mall.Descriptive analysis was performed;each criterion was presented in frequency and percentage.Results:A total of 268 escalators from 84 shopping malls in 9 states of Malaysia were assessed.Two operating escalators were not equipped with signage.More than one-ifth(23.0%)of the signage was not standardized within the mall.The majority of safety information was displayed in the form of a pictogram,a minority of signage displayed information in both pictogram and text format:"children must hold hand"(12.7%)and"be careful of long clothing"(10.8%),respectively.Nevertheless,"toddlers should be carried"(8.6%)and"take extra care with rubber shoes/tied shoes/laces"(30.2%)were found absent in most of the signage.Conclusion:Escalator signage was present in almost all of the escalators observed.However,non-standardization of the signage of escalators should warrant the attention of relevant authorities to revise the safety guideline s and improve the quality of escalator.展开更多
Escalation of commitment has been linked to losses in information systems (IS) projects. Understanding the nature and the rationality of escalation allows the firm to promote optimal project management practices. Th...Escalation of commitment has been linked to losses in information systems (IS) projects. Understanding the nature and the rationality of escalation allows the firm to promote optimal project management practices. This study takes an inter-disciplinary approach and draws on research from economics and management to create a model of irrational escalation and a model of rational escalation. The forces that contribute to irrational escalation include the responsibility of the same manager for both the project selection and project continuation decisions that create proneness to self-justification, the potential for negative framing of decision options due to large sunk costs, the proximity of project completion and the presence of organizational inertia. Identifying these irrational escalation factors helps design appropriate de-escalation techniques. The rational escalation model draws on the real option theory and the bandit process theory to identify conditions when project continuation is justified by the value of information and the value of flexibility that the firm receives from continuing the project.展开更多
A new method for quantity configuration of escalator linear profile in SAP system is proposed. This method is to create the calculation formula of the assembly length of escalator linear profile according to the chara...A new method for quantity configuration of escalator linear profile in SAP system is proposed. This method is to create the calculation formula of the assembly length of escalator linear profile according to the characteristic value of escalator, the requirements of assembly process and the technical specification of packaging and transportation,and then optimize the configuration method in SAP system. It avoids the waste caused by the SAP system configuration of 6 m long profile that needs to be cut to the actual length,which reduce the scrap rate of escalator assembly profiles. It provides an example to reduce manufacturing cost by improving the configuration in SAP system without change of assembly process.展开更多
Escalator is a vehicle related to people's daily life closely while it incurs safety problems frequently.Therefore,developing a new methodology for escalator safety assessment is very important.In this paper,the r...Escalator is a vehicle related to people's daily life closely while it incurs safety problems frequently.Therefore,developing a new methodology for escalator safety assessment is very important.In this paper,the related suitable risk analysis models for the escalator overturned accident were proposed on different risk management stages.Firstly,field of the escalator was surveyed and information was collected to identify the danger sources.Secondly,a safety assessment process was done for escalator risk evaluation.Then the dangerous levels were devised based on the LEC evaluation method.According to the results,targeted management measures suggestions and effective safety strategy were proposed finally to solve the escalator overturned problems.The practice has proven that the safety assessment method in this paper is convenient,efficient and effective,which helps to improve the elevators safety level in China and supports the government management.展开更多
文摘AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.
文摘TheRussia-Ukrainecrisiswas araremilitary crisis between European powers after the end of the Cold War,which led to confrontation between Western countries and Russia.Such a crisis also triggered the extensive involvement of nonstate actors,such as international capital giants,small and micro technology enterprises,emerging international platforms,and multinational corporations.Nonstate actors play an important role in international politics.Benefiting from the development of globalization and the accelerated evolution of the digital age,nonstate actors have exerted a significant influence on the international pattern by intervening in the competition between countries,participating in the process of global governance,and influencing the thoughts of science and technology.These actors have become an important variable affecting the world.The rising role of nonstate actors has many implications for China to expand its strength and safeguard national interests and security.
文摘This paper investigates survivability escalation strategies in multi layers transport networks such as ATM/SDH/WDM networks, and presents oriented failures and oriented traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi layer networks, such as WDM based ATM networks or WDM based SDH networks.
文摘Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.
文摘Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.
基金Supported by a grant of Science and Technology Department of Hebei Province,China(No.072761711)
文摘Objective: Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer (NSCLC). Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose (MTD) of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC. Methods: Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m2, bid, on days d5-d 18, and docetaxe130 mg/m2 on days 1 and 8, respectively. The regimen was repeated every 21 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared. Results: Eighteen patients received 67 cycles at capecitabine of level I (1250 mg/m2, divided into 625 mg/m2, bid) and level II (1500 mg/m2, 750 mg/m2, bid). The most common toxicities were neutropenia, hand and feet syndrome, fatigue and nausea. Eight DLTs occurred in 5 patients in the whole group, including 1 DLT in dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD. Cunclusion: MTD of our phase I trial was capecitabine of 1250 mg/m2/d combined with docetaxel of 30 mg/m2/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial.
基金This work was supported in part by the Research and Development Fund of the National Cancer Center and by the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development(AMED)(26-A-18 and 26-A-28).
文摘Objective:To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy(ADT)in high-risk prostate cancer in three radiotherapy dose groups.Methods:Between 1998 and 2013,patients with high-risk prostate cancer underwent threedimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy,72 Gy,or 78 Gy with ADT.Prostate-specific antigen(PSA)relapse was defined using the Phoenix definition.PSA relapse-free survival(PRFS)was evaluated in each radiotherapy dose group.Moreover,high-risk patients were divided into H-1(patients with multiple high-risk factors)and H-2(patients with a single high-risk factor)as risk subgroups.Results:Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study.The median duration of ADT was 10.1 months.Age,Gleason score,T stage,and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses.The 4-year PRFS rates in Group-66 Gy,Group-72 Gy and Group-78 Gy were 72.7%,81.6%and 90.3%,respectively.PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS,while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose.Conclusion:Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS.PRFS for patients in the H-1 subgroup was poor,but dose escalation in those patients was beneficial,while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS.
文摘There have been a lot of research exertions and studies to improve the safety of critical infrastructures using the Security Operations Center (SOC). As part of efforts, the purpose of this research is to propose a framework to automate the SOC’s performance of triage, containment and escalation. The research leveraged on qualitative desk review to collect data for analysis, deduced strengths and weaknesses for the current SOC implementations and used that as a basis for proposing the framework. In view of the constant evolution of SOC operations and capabilities coupled with the huge volumes of data collected for analysis, an efficient framework for SOC operations is proposed. The qualitative analysis is used to deduce strengths and weaknesses for the current SOC implementations as a premise for proposing the framework. It consists of eight interactive stages that further leverage on a proposed algorithm for baselining, remediation and escalation. The result of this research is a proposed framework that serves as a unique contribution to enhancing the SOC’s ability to automatically perform triage, containment and escalation. Supplementary to similar and earlier work reviewed, the framework is proposed as the way forward to automatically enable SOC setups with the capacity to efficiently perform triage of security threats, vulnerabilities and incidents, effectively contain identified breaches and appropriately escalate for prompt and accurate solutions.
文摘BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.
文摘Xi Jinping,General Secretary of the Communist Party of China(CPC)Central Committee,has creatively put forward a holistic approach to national security,making a major breakthrough beyond the traditional national security concepts and providing the world with a new one characterized by universality and inclusivity.This thesis uses a holistic approach to national security to analyze the ongoing Russia-Ukraine crisis:its underlying causes,latest developments,tactics deployed,and potential implications.The outbreak of the Russia-Ukraine crisis highlights the antagonism between different national security paths of the US,Russia,and Ukraine.Moreover,the crisis has proven the correctness of the path of national security with Chinese characteristics and the importance of pursuing peaceful development.The process of the Russia-Ukraine crisis has foregrounded the necessity and scientificity of balancing development and security-that is,a higher level of national security provides a guarantee and support for high-quality development,which in turn improves its competence and efficiency.Typified by intertwined traditional and non-traditional security issues,the form of the RussiaUkraine crisis has indicated that,to safeguard national security,China must coordinate a full spectrum of security issues,be prepared for worst-case scenarios,and remain keenly alert to potential dangers.Efforts must be made to strengthen a well-coordinated,interconnected,and multi-pronged approach.The consequences of the Russia-Ukraine crisis shed light on the complexity of the international security environment wheredisorder prevails,and underscore the importance of paying equal attention to our security and that shared by the world.China must continue to encourage all other countries to pursue peaceful development,actively respond to the legitimate security concerns of the international community,and promote a new type of international security framework that features mutually beneficial cooperation under the vision of a community with a shared future for humanity.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.71473207 and 71871189)the Research Grant Council of the Hong Kong Administrative Region,China(Grant No.CityU118909)the Open Fund of Beijing Engineering and Technology Research Center of Rail Transit Line Safety and Disaster Prevention(Grant No.RRC201701)
文摘As a convenient passenger transit facility between floors with different heights, escalators have been extensively used in shopping malls, metro stations, airport terminals, etc. Compared with other vertical transit facilities including stairs and elevators, escalators usually have large transit capacity. It is expected to reduce pedestrian traveling time and thus improve the quality of pedestrian’s experiences especially in jamming conditions. However, it is noticed that pedestrians may present different movement patterns, e.g., queuing on each step of the escalator, walking on the left-side and meanwhile standing on the right-side of the escalator. These different patterns affect the actual escalator traffic volume and finally the passenger spatiotemporal distribution in different built environments. Thus, in the present study, a microscopic cellular automaton(CA) simulation model considering pedestrian movement behavior on escalators is built. Simulations are performed considering different pedestrian movement speeds, queuing modes, and segregation on escalators with different escalator speeds.The actual escalator capacities under different pedestrian movement patterns are investigated. It is found that walking on escalators will not always benefit escalator transit volume improvement, especially in jamming conditions.
文摘In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing(MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis(UC) and Crohn's disease(CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.
文摘Dengue virus infection is more and more acknowledged as one of the world’s major escalating problems. Dengue is prevalent in most tropical and subtropical countries. To solve this problem, pharmacists need to understand the epidemiology, risk factors, clinical spectrum, diagnosis, management, prevention, and novel avenues of dengue.
文摘“China will fight to the end if the United States continues to escalate trade frictions,”the Ministry of Commerce(MOC)said recently.China will not give ground on issues of principle during bilateral economic and trade talks,which are clearly stated in a white paper on bilateral trade consultations issued earlier this month,MOC spokesperson Gao Feng said.In response to the new threat of tarrifs by the United States,Gao said China is firmly against US unilateralism and bullying.
文摘Objective:Escalator signage could be playing a vital role to alert users for safe use of escalators.This study aimed to evaluate the availability,standardization,and content of safety information on escalator signage in the shopping malls.Methods:An observational study was conducted from November 2017 to February 2018 to assess the availability,standardization of safety information among the signage inside the shopping mall,and the content of safety information for public safety in Malaysia.A checklist was developed by adapting escalator safety guidelines from seven countries and regions including Malaysia.Data collctors identified from the selected states were required to capture three photographs at different angles of the escalator signage for each ascending and descending directions at each entrance of the mall.Descriptive analysis was performed;each criterion was presented in frequency and percentage.Results:A total of 268 escalators from 84 shopping malls in 9 states of Malaysia were assessed.Two operating escalators were not equipped with signage.More than one-ifth(23.0%)of the signage was not standardized within the mall.The majority of safety information was displayed in the form of a pictogram,a minority of signage displayed information in both pictogram and text format:"children must hold hand"(12.7%)and"be careful of long clothing"(10.8%),respectively.Nevertheless,"toddlers should be carried"(8.6%)and"take extra care with rubber shoes/tied shoes/laces"(30.2%)were found absent in most of the signage.Conclusion:Escalator signage was present in almost all of the escalators observed.However,non-standardization of the signage of escalators should warrant the attention of relevant authorities to revise the safety guideline s and improve the quality of escalator.
文摘Escalation of commitment has been linked to losses in information systems (IS) projects. Understanding the nature and the rationality of escalation allows the firm to promote optimal project management practices. This study takes an inter-disciplinary approach and draws on research from economics and management to create a model of irrational escalation and a model of rational escalation. The forces that contribute to irrational escalation include the responsibility of the same manager for both the project selection and project continuation decisions that create proneness to self-justification, the potential for negative framing of decision options due to large sunk costs, the proximity of project completion and the presence of organizational inertia. Identifying these irrational escalation factors helps design appropriate de-escalation techniques. The rational escalation model draws on the real option theory and the bandit process theory to identify conditions when project continuation is justified by the value of information and the value of flexibility that the firm receives from continuing the project.
文摘A new method for quantity configuration of escalator linear profile in SAP system is proposed. This method is to create the calculation formula of the assembly length of escalator linear profile according to the characteristic value of escalator, the requirements of assembly process and the technical specification of packaging and transportation,and then optimize the configuration method in SAP system. It avoids the waste caused by the SAP system configuration of 6 m long profile that needs to be cut to the actual length,which reduce the scrap rate of escalator assembly profiles. It provides an example to reduce manufacturing cost by improving the configuration in SAP system without change of assembly process.
文摘Escalator is a vehicle related to people's daily life closely while it incurs safety problems frequently.Therefore,developing a new methodology for escalator safety assessment is very important.In this paper,the related suitable risk analysis models for the escalator overturned accident were proposed on different risk management stages.Firstly,field of the escalator was surveyed and information was collected to identify the danger sources.Secondly,a safety assessment process was done for escalator risk evaluation.Then the dangerous levels were devised based on the LEC evaluation method.According to the results,targeted management measures suggestions and effective safety strategy were proposed finally to solve the escalator overturned problems.The practice has proven that the safety assessment method in this paper is convenient,efficient and effective,which helps to improve the elevators safety level in China and supports the government management.