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
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
AIM:To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.METHODS:This was a retrospective review of patients receiving infliximab therapy for Crohn’s disease(CD)...AIM:To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.METHODS:This was a retrospective review of patients receiving infliximab therapy for Crohn’s disease(CD)at two outpatient gastroenterology clinics during July2009 to October 2010.All patients included in the study were biologic agent na?ve and had moderate to severe CD(Harvey Bradshaw index>8).Patients were divided into groups based on length of time between diagnosis to therapy initiation and concurrent immunosuppressant therapy.Kaplan-Meier survival analysis was used to compare the time to dose escalation for the four groups.RESULTS:There were 68 patients,51% female and 49% male,with an average age at diagnosis of 24.7±11.9 years.The average age at infliximab initiation was 34.8±14.8 years.Of the 68 patients,19%initiated inflixiamb within 2 years of diagnosis,and 51%had concurrent immunosuppressant therapy at the time of therapy initiation.Fifty percent of patients required dose escalation and the median time from therapy initiation to dose escalation was 10 mo(interquartile range:5.3-14.8).There was a statistically significant higher probability of requiring dose esclataion in patients who initiated biologic therapy within 2 years of diagnosis,without concurrent immunosuppressant therapy(P<0.01).CONCLUSION:Those who receive infliximab within 2years of CD diagnosis require more intense immunosuppressant therapy than those who received infliximab later.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
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
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
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:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug ...Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.展开更多
Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patien...Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patients treated with definitive chemoradiotherapy and pre-therapeutic ^(18)FFDG PET/CT were included in this study.Retrospectively,a threshold of 50%of SUVmax was used to define the high FDG uptake region of the GTV(GTVPET).Three intensity-modulated radiation therapy(IMRT)plans were generated,delivering three dose levels to three different planning target volumes(PTVs).50.4 Gy delivered to PTV50.4 was defined on computed tomography(CT)as Plan50.4,63 Gy was delivered to PTV63 was defined as GTV plus a uniform margin of 0.5 cm as Plan63,and 70 Gy delivered to PTV70 was defined as GTVPET plus a 0.5 cm margin as Plan70.A dosimetric comparison was performed based on normal tissue complication probability(NTCP)for the lung and heart.Results:Clinically acceptable dose escalation failed for 2 of 10 patients in Plan63 due to heart dose constraints.One patient failed heart dose constraint for Plan70.Two patients failed spinal cord constraint for Plan63.Three patients failed lung dose constraints for both Plan63 and Plan70,two of which were even not suitable for Plan50.4 for the same reason.NTCP modeling for lung showed increased risk for Plan63 and Plan70 compared to Plan50.4.The difference between Plan63 and Plan70 was insignificant.NTCP modeling for heart showed an increased risk from 6.38%of Plan50.4 to 8.88%of Plan70(P=0.009)or 9.79%of Plan63(P=0.007).The risk of heart mortality was significantly higher for Plan63 than Plan70(P=0.047).Conclusions:Selective boosting of sub-volumes based on ^(18)F-FDG PET/CT is feasible way with a modest increase in the risk of cardiac and lung toxicities.展开更多
We review the evidence for predation of shelly benthic prey over 125 million years of earth history in the James Ross Basin,Antarctica(~65°S).Although poor in the Early Cretaceous lower parts of the sequence,whic...We review the evidence for predation of shelly benthic prey over 125 million years of earth history in the James Ross Basin,Antarctica(~65°S).Although poor in the Early Cretaceous lower parts of the sequence,which represent essentially deeper water facies,evidence for both potential crushers and drillers becomes more apparent in the Santonian–Campanian Santa Marta Formation,and by the Maastrichtian López de Bertodano Formation there is an extensive fossil record of drill holes attributable to naticid gastropods,and some evidence of crushing by decapods crustaceans and possibly other taxa too.This continues at a similar level of intensity across the K/Pg boundary into the Danian Sobral Formation,but is less well constrained in the latest Paleocene–Early Eocene.The most extensive record of predation occurs in the Middle Eocene section of the La Meseta Formation on Seymour Island which also records the highest levels of benthic diversity within the entire basin.This key section is providing some important new evidence to suggest that the rate of acceleration of benthic predation intensity through the Late Mesozoic–Early Cenozoic in the polar regions may be similar to that seen in lower latitude regions.Predator–prey interaction was a key factor in the evolution of polar marine faunas too.展开更多
Constant escalations in the number of diabetics worldwide and the failure of conventional therapy to restore normoglycemia without adverse effects,in spite of tremendous strides in modern medicine,calls for naturopath...Constant escalations in the number of diabetics worldwide and the failure of conventional therapy to restore normoglycemia without adverse effects,in spite of tremendous strides in modern medicine,calls for naturopathy and alternative medicine.Because diabetes is multi-factorial and has secondary complications,prevention of hyperglycemia is the central dogma for its management.To date,no oral hypoglycemic exists which can achieve tight glycemic control without side effects.Dietary adjuncts,lifestyle interventions and a resurgence of interest in phyto-therapy have consequently gained ground.Natural hypoglycemics have attracted attention due to ease of incorporation in everyday diet,affordability,less adverse effects,and long term safety.Ethno botanical literature reports more than 800 anti-diabetic plants species.Eucalyptus is well represented in the Aboriginal Pharmacopoeias for its various pharmacological activities.Its hot aqueous decoction has been used as a hypoglycemic in various regions of world.This editorial attempts to summarize the data on the hypoglycemic potential of the different eucalyptus species,highlight the value of its natural biomolecules for the prophylaxis and treatment of type2 diabetes,describe their mechanistic actions,shed light on the posology and safety aspects of eucalyptusand assess its applicability as a reinforcement to currently used therapy.展开更多
Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTO...Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%);26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.展开更多
BACKGROUND Chronic total occlusion(CTO) is found in 18-31% of patients who undergo coronary angiography. Successful recanalization of CTOs is associated with reduced recurrent angina pectoris rates and increased long-...BACKGROUND Chronic total occlusion(CTO) is found in 18-31% of patients who undergo coronary angiography. Successful recanalization of CTOs is associated with reduced recurrent angina pectoris rates and increased long-term survival.Although the success rate of CTO percutaneous coronary intervention(CTO-PCI)has improved, CTO-PCI remains technically challenging. The Fielder XT guidewire was designed for CTO lesions. To validate whether the use of the guidewire increases the success rate, we compared the results of CTO-PCI with or without the guidewire. We hypothesized that the use of Fielder XT guidewire can increase the success rate of CTO-PCI.AIM To investigate whether the use of Fielder XT guidewire increases the final procedural success of CTO-PCI via the anterograde approach.METHODS Between January 2013 and December 2015, a retrospective study was conducted on 1230 consecutive patients with CTO who received PCI via the anterograde approach at the General Hospital of Northern Theater Command. The patients were divided into an XT Group(n = 686) and a no-XT Group(n = 544) depending on whether Fielder XT guidewire was used. Both groups were compared for clinical parameters, lesion-related characteristics, procedural outcomes and inhospital complications. The data were statistically analyzed using Pearson's χ~2 test for categorical variables, and Students' t test was used to compare the quantitative data. Significant independent factors and a risk ratio with 95%confidence interval(CI) were assessed by multivariate logistic regression analysis.RESULTS In total, 1230 patients were recruited; 75.4% of the patients were male, and 55.8%of the patients were in the XT group. The overall success rate was 83.9%, with87.8% in the XT group. Based on multivariate logistic regression analysis, factors positively associated with procedural success were the use of Fielder XT guidewire(P = 0.005, 95%CI: 1.172-2.380) and systolic blood pressure(P = 0.011,95%CI: 1.003-1.022), while factors negatively associated with procedural success were blunt stump(P = 0.013, 95%CI: 1.341-11.862), male sex(P = 0.016, 95%CI:0.363-0.902), New York Heart Association(NYHA) class(P = 0.035, 95%CI: 0.553-0.979), contrast amount(P = 0.018, 95%CI: 0.983-0.998) and occlusion time(P =0.009, 95%CI: 0.994-0.999). No significant differences were found between the XT group and the no-XT group with respect to clinical parameters, lesion-related characteristics, coronary artery rupture [3(0.4%) vs 8(1.5%), P = 0.056], inhospital death [2(0.3%) vs 6(1.1%), P = 0.079] or in-hospital target lesion revascularization [3(0.4%) vs 7(1.3%), P < 0.099]. However, there were significant differences between the groups with respect to success rate [602(87.8%) vs 430(79.0%), P < 0.001], procedure time [(74 ± 23) vs(83 ± 21), P < 0.001], stent length[(32.0 ± 15.8) vs(37.3 ± 17.6), P < 0.001], contrast amount [(148 ± 46) vs(166 ± 43),P < 0.001], post-PCI myocardial infarction [43(6.3%) vs 59(10.8%), P = 0.004],major adverse cardiovascular event [44(6.4%) vs 57(10.7%), P = 0.007], side branch loss [31(4.5%) vs 44(8.1%), P = 0.009], contrast-induced nephropathy [29(4.2%) vs 40(7.4%), P = 0.018] and no reflow [8(1.2%) vs 14(2.9%), P = 0.034].CONCLUSION The use of Fielder XT guidewire shortens the Procedure and increases the success rate of CTO-PCI, and is also associated with reduced complication rates.展开更多
Patients with inflammatory bowel diseases (IBD) represent heterogeneous groups with different characteristics and different clinical course. A great deal of effort is made to discover proxies for more severe disease n...Patients with inflammatory bowel diseases (IBD) represent heterogeneous groups with different characteristics and different clinical course. A great deal of effort is made to discover proxies for more severe disease needing more intense treatment and early intervention to gain the maximum therapeutic benefit. Endoscopy remains an invaluable method in assessment of patients with IBD. Pseudopolyps are often encountered during endoscopy and, although they are a well described entity, their presence is of unclear importance. In one of our recent studies and in conjunction with one study with a large cohort of patients with IBD and pseudopolyps, patients with pseudopolyps were found to face a higher inflammatory burden in terms of receiving more intense biological treatment. This letter comes as a comment and proposition regarding the concept of reevaluation of pseudopolyps as a promising marker in IBD scores.展开更多
After a reivew of basic concepts in multiple criteria optimization, the paper presents a characterization of noncooperative equilibria in multiple criteria games in normal form either by weighted sums or by. order-con...After a reivew of basic concepts in multiple criteria optimization, the paper presents a characterization of noncooperative equilibria in multiple criteria games in normal form either by weighted sums or by. order-consistent achievement scalarizing functions, for convex and nonconvex cases. Possible applications of multiple criteria games and such characterizations of their equilibria are indicated. The analysis of multiple criteria games might be especially useful when studying reasons of possible conflict escalation processes and ways of preventing them.展开更多
For high risk prostate cancer, the treatment volumes and even dose levels are still a controversial issue. The aim of this study is to evaluate the dosemetric parameters and acute toxicity of dose-escalated whole pelv...For high risk prostate cancer, the treatment volumes and even dose levels are still a controversial issue. The aim of this study is to evaluate the dosemetric parameters and acute toxicity of dose-escalated whole pelvis (WP) Intensity Modulated Radiation Therapy (IMRT) and volumetric modulated arc therapy (VMAT) prostate boost following neoadjuvant and concomitant with androgen deprivation therapy in high-risk prostate cancer patients. This analysis included 73 high-risk prostate cancer patients treated with WP-IMRT followed by boost to the prostate by VMAT to total dose of 80 Gy;between January 2014 and October 2016. Androgen deprivation therapy (ADT) was given for all patients before and during radiation therapy. Drawing the dose volume histograms (DVHs) was done for planning target volumes (PTVs), including Prostate PTV & nodal PTV, and organs at risk including rectum, bladder, femoral heads, and bowel bag for the plans. Acute radiation toxicities were reported during the radiation course and the following 3 months. The DVH analysis showed good coverage of PTVs and organs at risk doses were acceptable. No recorded acute Grade ≥ 3 toxicity. Acute grade 1 toxicity for Gastrointestinal (GI) and Genitourinary (GU) were 65% and 35% respectively, while Grade 2 toxicity was 30% for both. The Proctitis and frequency were the commonest acute toxicity and were maximal during the 5th week of radiation therapy. Dose escalation in two phases utilizing Simultaneous integrated boost (SIB) combined with ADT in high risk prostate cancer patient is feasible and associated with acceptable acute GI and GU toxicity.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
This paper focuses on the distribution of passenger flow in Huoying Station,Line 13 of Beijing subway system.The transformation measures taken by Line 13 since operation are firstly summarized.Then the authors elabora...This paper focuses on the distribution of passenger flow in Huoying Station,Line 13 of Beijing subway system.The transformation measures taken by Line 13 since operation are firstly summarized.Then the authors elaborate the facilities and equipment of this station,especially the node layout and passenger flow field.An optimization scheme is proposed to rapidly distribute the passenger flow in Huoying Station by adjusting the operation time of the escalator in the direction of Xizhimen.The authors adopt Queuing theory and Anylogic simulation software to simulate the original and the optimized schemes of Huoying Station to distribute the passenger flow.The results of the simulation indicate that the optimized scheme could effectively alleviate the traffic congestion in the hall of Huoying Station,and the pedestrian density in other places of the hall is lowered;passengers could move freely in the hall and no new congestion points would form.The rationality of the scheme is thus proved.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AIM:To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.METHODS:This was a retrospective review of patients receiving infliximab therapy for Crohn’s disease(CD)at two outpatient gastroenterology clinics during July2009 to October 2010.All patients included in the study were biologic agent na?ve and had moderate to severe CD(Harvey Bradshaw index>8).Patients were divided into groups based on length of time between diagnosis to therapy initiation and concurrent immunosuppressant therapy.Kaplan-Meier survival analysis was used to compare the time to dose escalation for the four groups.RESULTS:There were 68 patients,51% female and 49% male,with an average age at diagnosis of 24.7±11.9 years.The average age at infliximab initiation was 34.8±14.8 years.Of the 68 patients,19%initiated inflixiamb within 2 years of diagnosis,and 51%had concurrent immunosuppressant therapy at the time of therapy initiation.Fifty percent of patients required dose escalation and the median time from therapy initiation to dose escalation was 10 mo(interquartile range:5.3-14.8).There was a statistically significant higher probability of requiring dose esclataion in patients who initiated biologic therapy within 2 years of diagnosis,without concurrent immunosuppressant therapy(P<0.01).CONCLUSION:Those who receive infliximab within 2years of CD diagnosis require more intense immunosuppressant therapy than those who received infliximab later.
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.
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.
基金This study was supported by the Natural Science Foundation of Guangdong Province(2020A1515010105)Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province(U1601224).
文摘Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
文摘Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patients treated with definitive chemoradiotherapy and pre-therapeutic ^(18)FFDG PET/CT were included in this study.Retrospectively,a threshold of 50%of SUVmax was used to define the high FDG uptake region of the GTV(GTVPET).Three intensity-modulated radiation therapy(IMRT)plans were generated,delivering three dose levels to three different planning target volumes(PTVs).50.4 Gy delivered to PTV50.4 was defined on computed tomography(CT)as Plan50.4,63 Gy was delivered to PTV63 was defined as GTV plus a uniform margin of 0.5 cm as Plan63,and 70 Gy delivered to PTV70 was defined as GTVPET plus a 0.5 cm margin as Plan70.A dosimetric comparison was performed based on normal tissue complication probability(NTCP)for the lung and heart.Results:Clinically acceptable dose escalation failed for 2 of 10 patients in Plan63 due to heart dose constraints.One patient failed heart dose constraint for Plan70.Two patients failed spinal cord constraint for Plan63.Three patients failed lung dose constraints for both Plan63 and Plan70,two of which were even not suitable for Plan50.4 for the same reason.NTCP modeling for lung showed increased risk for Plan63 and Plan70 compared to Plan50.4.The difference between Plan63 and Plan70 was insignificant.NTCP modeling for heart showed an increased risk from 6.38%of Plan50.4 to 8.88%of Plan70(P=0.009)or 9.79%of Plan63(P=0.007).The risk of heart mortality was significantly higher for Plan63 than Plan70(P=0.047).Conclusions:Selective boosting of sub-volumes based on ^(18)F-FDG PET/CT is feasible way with a modest increase in the risk of cardiac and lung toxicities.
基金the NERC grant NE/I005803/1 and various colleagues who have been worked in the field to collect the many samples on which our studies are based
文摘We review the evidence for predation of shelly benthic prey over 125 million years of earth history in the James Ross Basin,Antarctica(~65°S).Although poor in the Early Cretaceous lower parts of the sequence,which represent essentially deeper water facies,evidence for both potential crushers and drillers becomes more apparent in the Santonian–Campanian Santa Marta Formation,and by the Maastrichtian López de Bertodano Formation there is an extensive fossil record of drill holes attributable to naticid gastropods,and some evidence of crushing by decapods crustaceans and possibly other taxa too.This continues at a similar level of intensity across the K/Pg boundary into the Danian Sobral Formation,but is less well constrained in the latest Paleocene–Early Eocene.The most extensive record of predation occurs in the Middle Eocene section of the La Meseta Formation on Seymour Island which also records the highest levels of benthic diversity within the entire basin.This key section is providing some important new evidence to suggest that the rate of acceleration of benthic predation intensity through the Late Mesozoic–Early Cenozoic in the polar regions may be similar to that seen in lower latitude regions.Predator–prey interaction was a key factor in the evolution of polar marine faunas too.
文摘Constant escalations in the number of diabetics worldwide and the failure of conventional therapy to restore normoglycemia without adverse effects,in spite of tremendous strides in modern medicine,calls for naturopathy and alternative medicine.Because diabetes is multi-factorial and has secondary complications,prevention of hyperglycemia is the central dogma for its management.To date,no oral hypoglycemic exists which can achieve tight glycemic control without side effects.Dietary adjuncts,lifestyle interventions and a resurgence of interest in phyto-therapy have consequently gained ground.Natural hypoglycemics have attracted attention due to ease of incorporation in everyday diet,affordability,less adverse effects,and long term safety.Ethno botanical literature reports more than 800 anti-diabetic plants species.Eucalyptus is well represented in the Aboriginal Pharmacopoeias for its various pharmacological activities.Its hot aqueous decoction has been used as a hypoglycemic in various regions of world.This editorial attempts to summarize the data on the hypoglycemic potential of the different eucalyptus species,highlight the value of its natural biomolecules for the prophylaxis and treatment of type2 diabetes,describe their mechanistic actions,shed light on the posology and safety aspects of eucalyptusand assess its applicability as a reinforcement to currently used therapy.
文摘Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%);26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.
基金Supported by the National Natural Science Foundation of China,No.81570464 and No.81770271Special Fund for the Cultivation of College Students’ Science and Technology Innovation in 2018,No.pdjha0095Municipal Planning Projects of Scientific Technology of Guangzhou,No.201804020083
文摘BACKGROUND Chronic total occlusion(CTO) is found in 18-31% of patients who undergo coronary angiography. Successful recanalization of CTOs is associated with reduced recurrent angina pectoris rates and increased long-term survival.Although the success rate of CTO percutaneous coronary intervention(CTO-PCI)has improved, CTO-PCI remains technically challenging. The Fielder XT guidewire was designed for CTO lesions. To validate whether the use of the guidewire increases the success rate, we compared the results of CTO-PCI with or without the guidewire. We hypothesized that the use of Fielder XT guidewire can increase the success rate of CTO-PCI.AIM To investigate whether the use of Fielder XT guidewire increases the final procedural success of CTO-PCI via the anterograde approach.METHODS Between January 2013 and December 2015, a retrospective study was conducted on 1230 consecutive patients with CTO who received PCI via the anterograde approach at the General Hospital of Northern Theater Command. The patients were divided into an XT Group(n = 686) and a no-XT Group(n = 544) depending on whether Fielder XT guidewire was used. Both groups were compared for clinical parameters, lesion-related characteristics, procedural outcomes and inhospital complications. The data were statistically analyzed using Pearson's χ~2 test for categorical variables, and Students' t test was used to compare the quantitative data. Significant independent factors and a risk ratio with 95%confidence interval(CI) were assessed by multivariate logistic regression analysis.RESULTS In total, 1230 patients were recruited; 75.4% of the patients were male, and 55.8%of the patients were in the XT group. The overall success rate was 83.9%, with87.8% in the XT group. Based on multivariate logistic regression analysis, factors positively associated with procedural success were the use of Fielder XT guidewire(P = 0.005, 95%CI: 1.172-2.380) and systolic blood pressure(P = 0.011,95%CI: 1.003-1.022), while factors negatively associated with procedural success were blunt stump(P = 0.013, 95%CI: 1.341-11.862), male sex(P = 0.016, 95%CI:0.363-0.902), New York Heart Association(NYHA) class(P = 0.035, 95%CI: 0.553-0.979), contrast amount(P = 0.018, 95%CI: 0.983-0.998) and occlusion time(P =0.009, 95%CI: 0.994-0.999). No significant differences were found between the XT group and the no-XT group with respect to clinical parameters, lesion-related characteristics, coronary artery rupture [3(0.4%) vs 8(1.5%), P = 0.056], inhospital death [2(0.3%) vs 6(1.1%), P = 0.079] or in-hospital target lesion revascularization [3(0.4%) vs 7(1.3%), P < 0.099]. However, there were significant differences between the groups with respect to success rate [602(87.8%) vs 430(79.0%), P < 0.001], procedure time [(74 ± 23) vs(83 ± 21), P < 0.001], stent length[(32.0 ± 15.8) vs(37.3 ± 17.6), P < 0.001], contrast amount [(148 ± 46) vs(166 ± 43),P < 0.001], post-PCI myocardial infarction [43(6.3%) vs 59(10.8%), P = 0.004],major adverse cardiovascular event [44(6.4%) vs 57(10.7%), P = 0.007], side branch loss [31(4.5%) vs 44(8.1%), P = 0.009], contrast-induced nephropathy [29(4.2%) vs 40(7.4%), P = 0.018] and no reflow [8(1.2%) vs 14(2.9%), P = 0.034].CONCLUSION The use of Fielder XT guidewire shortens the Procedure and increases the success rate of CTO-PCI, and is also associated with reduced complication rates.
文摘Patients with inflammatory bowel diseases (IBD) represent heterogeneous groups with different characteristics and different clinical course. A great deal of effort is made to discover proxies for more severe disease needing more intense treatment and early intervention to gain the maximum therapeutic benefit. Endoscopy remains an invaluable method in assessment of patients with IBD. Pseudopolyps are often encountered during endoscopy and, although they are a well described entity, their presence is of unclear importance. In one of our recent studies and in conjunction with one study with a large cohort of patients with IBD and pseudopolyps, patients with pseudopolyps were found to face a higher inflammatory burden in terms of receiving more intense biological treatment. This letter comes as a comment and proposition regarding the concept of reevaluation of pseudopolyps as a promising marker in IBD scores.
文摘After a reivew of basic concepts in multiple criteria optimization, the paper presents a characterization of noncooperative equilibria in multiple criteria games in normal form either by weighted sums or by. order-consistent achievement scalarizing functions, for convex and nonconvex cases. Possible applications of multiple criteria games and such characterizations of their equilibria are indicated. The analysis of multiple criteria games might be especially useful when studying reasons of possible conflict escalation processes and ways of preventing them.
文摘For high risk prostate cancer, the treatment volumes and even dose levels are still a controversial issue. The aim of this study is to evaluate the dosemetric parameters and acute toxicity of dose-escalated whole pelvis (WP) Intensity Modulated Radiation Therapy (IMRT) and volumetric modulated arc therapy (VMAT) prostate boost following neoadjuvant and concomitant with androgen deprivation therapy in high-risk prostate cancer patients. This analysis included 73 high-risk prostate cancer patients treated with WP-IMRT followed by boost to the prostate by VMAT to total dose of 80 Gy;between January 2014 and October 2016. Androgen deprivation therapy (ADT) was given for all patients before and during radiation therapy. Drawing the dose volume histograms (DVHs) was done for planning target volumes (PTVs), including Prostate PTV & nodal PTV, and organs at risk including rectum, bladder, femoral heads, and bowel bag for the plans. Acute radiation toxicities were reported during the radiation course and the following 3 months. The DVH analysis showed good coverage of PTVs and organs at risk doses were acceptable. No recorded acute Grade ≥ 3 toxicity. Acute grade 1 toxicity for Gastrointestinal (GI) and Genitourinary (GU) were 65% and 35% respectively, while Grade 2 toxicity was 30% for both. The Proctitis and frequency were the commonest acute toxicity and were maximal during the 5th week of radiation therapy. Dose escalation in two phases utilizing Simultaneous integrated boost (SIB) combined with ADT in high risk prostate cancer patient is feasible and associated with acceptable acute GI and GU toxicity.
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.
基金This research is supported by Beijing Municipal Natural Science Foundation(9204023)Ministry of Education“Tiancheng Huizhi”Innovation and Education Promotion Foundation(2018A01012).
文摘This paper focuses on the distribution of passenger flow in Huoying Station,Line 13 of Beijing subway system.The transformation measures taken by Line 13 since operation are firstly summarized.Then the authors elaborate the facilities and equipment of this station,especially the node layout and passenger flow field.An optimization scheme is proposed to rapidly distribute the passenger flow in Huoying Station by adjusting the operation time of the escalator in the direction of Xizhimen.The authors adopt Queuing theory and Anylogic simulation software to simulate the original and the optimized schemes of Huoying Station to distribute the passenger flow.The results of the simulation indicate that the optimized scheme could effectively alleviate the traffic congestion in the hall of Huoying Station,and the pedestrian density in other places of the hall is lowered;passengers could move freely in the hall and no new congestion points would form.The rationality of the scheme is thus proved.
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.