Selective Catalyst Reduction(SCR)Urea Dosing System(UDS)directly affects the system accuracy and the dynamic response performance of a vehicle.However,the UDS dynamic response is hard to keep up with the changes o...Selective Catalyst Reduction(SCR)Urea Dosing System(UDS)directly affects the system accuracy and the dynamic response performance of a vehicle.However,the UDS dynamic response is hard to keep up with the changes of the engine's operating conditions.That will lead to low NO_χconversion efficiency or NH_3 slip.In order to optimize the injection accuracy and the response speed of the UDS in dynamic conditions,an advanced control strategy based on an air-assisted volumetric UDS is presented.It covers the methods of flow compensation and switching working conditions.The strategy is authenticated on an UDS and tested in different dynamic conditions.The result shows that the control strategy discussed results in higher dynamic accuracy and faster dynamic response speed of UDS.The inject deviation range is improved from being between-8%and 10%to-4%and 2%and became more stable than before,and the dynamic response time was shortened from 200 ms to 150 ms.The ETC cycle result shows that after using the new strategy the NH_3 emission is reduced by 60%,and the NO_χemission remains almost unchanged.The trade-off between NO_χconversion efficiency and NH_3 slip is mitigated.The studied flow compensation and switching working conditions can improve the dynamic performance of the UDS significantly and make the UDS dynamic response keep up with the changes of the engine's operating conditions quickly.展开更多
In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients....In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.展开更多
The principle and working process of Vacuum Resin Shot Dosing Equipment(VRSDE) are analyzed and the characteristics of IP1612-220PLC (Programmable Logical Controller) areintroduced briefly at first. Then the authors d...The principle and working process of Vacuum Resin Shot Dosing Equipment(VRSDE) are analyzed and the characteristics of IP1612-220PLC (Programmable Logical Controller) areintroduced briefly at first. Then the authors discuss the flow of program, the assignment of PLCI/O ports, the wiring diagram, and the ladder logic program of the PLC control system of VRSDE indetail. Some application issues of the system are accounted for in addition. Finally, according tothe information acquired from users, the authors draw the conclusion: this system owns a highreliability and a-vailability and greatly improves the automatic degree of VRDE.展开更多
On the basis of the analysis of faults and their causes of vacuum resin shot dosing equipment, the fuzzy model of fault diagnosis for the equipment is constructed, and the fuzzy relationship matrix, the symptom fuzzy ...On the basis of the analysis of faults and their causes of vacuum resin shot dosing equipment, the fuzzy model of fault diagnosis for the equipment is constructed, and the fuzzy relationship matrix, the symptom fuzzy vector, the fuzzy compound arithmetic operator, and the diagnosis principle of the model are determined. Then the fault auto-diagnosis system for the equipment is designed , and the functions for real-time monitoring its operation condition and for fault auto diagosis are realized. Finally, the experiments of fault auto-diagnosis are conducted in practical production and the veracity of the system is verified.展开更多
BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors ...BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.展开更多
Background: The 2020 consensus guidelines recommend AUC guided dosing as the preferred monitoring method for vancomycin. AUC based dosing has shown to reduce incidence of acute kidney injury (AKI), utilize lower daily...Background: The 2020 consensus guidelines recommend AUC guided dosing as the preferred monitoring method for vancomycin. AUC based dosing has shown to reduce incidence of acute kidney injury (AKI), utilize lower daily doses in obese patients, and maintain efficacy. Several institutions have adjusted their protocols to utilize AUC guided dosing. However, there are limited studies comparing the clinical outcomes of AUC versus trough monitoring. Methods: This was a retrospective, observational, single centered study. The primary outcome was to evaluate the clinical success of AUC dosing versus trough based dosing of vancomycin for MRSA infections using a composite outcome of afebrile post treatment ( Results: Forty-seven patients were included in this study, 17 in the AUC group and 30 in the trough group. The primary composite outcome showed a significant benefit of AUC dosing (p = 0.04). The composite component culture clearance showed the largest improvement for the AUC group when compared with the trough group (p = 0.03). More patients achieved therapeutic target attainment and reached the target sooner (3 days versus 4 days, p = 0.2) in the AUC group. Over the study course, 94.1% of patients in the AUC group were considered therapeutic compared to 63.8% in the trough group (p = 0.03). Vancomycin levels were collected less frequently in the AUC group (3 versus 4, p = 0.2). Conclusion: The outcomes of this study may suggest AUC guided dosing as a beneficial alternative to trough based dosing. AUC based dosing may improve clinical success which can be further explored in larger prospective clinical trials.展开更多
Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxid...Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.展开更多
Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid no...Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.展开更多
Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging...Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its sub-variants.This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies.Here,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its sub-variants.Cryo-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S protein.The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex.Furthermore,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus particles.Compared to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro.The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.展开更多
Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be improved....Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be improved.This phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL.Expected objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months.No dose-limiting events were observed,RP2D of chidamide was 30 mg twice a week.Twenty-nine patients were enrolled in phase 2.In the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,respectively.The most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)patients.Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role.STAT3 mutation shows an unfavorable prognosis.Although outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time.It is a promising therapeutic option for this population.展开更多
The safety and efficacy of COVID-19 vaccines in the elderly,a high-risk group for severe COVID-19 infection,have not been fully understood.To clarify these issues,this prospective study followed up 157 elderly and 73 ...The safety and efficacy of COVID-19 vaccines in the elderly,a high-risk group for severe COVID-19 infection,have not been fully understood.To clarify these issues,this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety,immunogenicity,and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001.The results showed that this vaccination protocol was safe and tolerable in the elderly.After administering two doses of the BBIBP-CorV,the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals.After the ZF2001 booster dose,the antibody-positive rates in the elderly were comparable to those in the young;however,the antibody titers remained lower.Gender,age,and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals.The pseudovirus neutralization assay showed that,compared with those after receiving two doses of BBIBP-CorV priming,some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster.Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms.The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young.Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.展开更多
Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID eff...Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was proposed.The digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional area.Each of these three parts was separately modeled.Using the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using VHDL-AMS.In the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area models.Furthermore,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital IC.TID experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose point.This confirms the practicality and accuracy of the proposed modeling method.The TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.展开更多
X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.Howev...X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.展开更多
Fetal and Maternal Atomic Bomb Survivor Dosimetry Using the J45 Pregnant Female Phantom Series:Considerations of the Kneeling and Lying Posture with Comparisons to the DS02 System Sean J.Domal1,Camilo M.Correa-Alfonso...Fetal and Maternal Atomic Bomb Survivor Dosimetry Using the J45 Pregnant Female Phantom Series:Considerations of the Kneeling and Lying Posture with Comparisons to the DS02 System Sean J.Domal1,Camilo M.Correa-Alfonso1,Colin J.Paulbeck2,Keith T.Griffin3,4,Tatsuhiko Sato5,Sachiyo Funamoto6,Harry M.Cullings6,Stephen D.Egbert7,Akira Endo8,Nolan E.Hertel4,Choonsik Lee3,Wesley E.Bolch9(1.Medical Physics Program,College of Medicine,University of Florida,Gainesville,FL;2.Department of Radiology,Johns Hopkins University,Baltimore,MD;3.National Cancer Institute,National Institutes of Health,Rockville,MD;4.George W.Woodruff School of Mechanical Eng.,Georgia Institute of Technology,Atlanta,GA;5.Nuclear Science and Engineering Center,Japan Atomic Energy Agency,Tokaimura,Japan;6.Department of Statistics,Radiation Effects Research Foundation,Hiroshima,Japan;7.Consultant,San Diego,CA;8.Nuclear Science Research Institute,Japan Atomic Energy Agency,Tokaimura,Japan;9.J.Crayton Pruitt Family Department of Biomedical Eng.,University of Florida,Gainesville,FL USA)Abstract:Organ dosimetry data of the atomic bomb survivors and the resulting cancer risk models derived from these data are currently assessed within the DS02 dosimetry system developed through the Joint US-Japan Dosimetry Working Group.In DS02,the anatomical survivor models are limited to three hermaphroditic stylized phantoms—an adult(55 kg),a child(19.8 kg),and an infant(9.7 kg)—that were originally designed for the preceding DS86 dosimetry system.As such,organ doses needed for assessment of in-utero cancer risks to the fetus have continued to rely upon the use of the uterine wall in the adult non-pregnant stylized phantom as the dose surrogate for all fetal organs regardless of gestational age.展开更多
The rise in breast cancer diagnoses among Chinese women has necessitated the use of X-ray breast screening,which carries a radiation risk.This study aimed to provide a dosimetry protocol for the Chinese female populat...The rise in breast cancer diagnoses among Chinese women has necessitated the use of X-ray breast screening,which carries a radiation risk.This study aimed to provide a dosimetry protocol for the Chinese female population to replace the traditional standard that utilizes simplified breast models,for the accurate estimation of the mean glandular dose of a patient undergoing digital breast tomosynthesis(DBT).The first set of detailed Chinese female breast models and representative breast parameters was constructed.Considering backscatter radiation and computational efficiency,we improved the combination of these models and the Chinese reference adult female whole-body voxel phantom.Image acquisition for four commercial DBT systems that are widely employed in China was simulated using the Monte Carlo method to obtain the normalized glandular dose coefficients of DBT(D_(gN)^(DBT))and the glandular depth dose(D_(g)^(dep)(z))for different breast characteristics and X-ray spectra.We calculated a series of D_(gN)^(DBT) values for breasts with different percentage mass glandularities(5%,25%,50%,75%,and 100%)and compressed breast thicknesses(2,3,4,5,6,and 7 cm)at various tube potentials(25,28,30,32,35,and 49 kV)and target/filter combinations(W/Rh,W/Al,Mo/Mo,Rh/Rh,and Rh/Ag).The parameter dependence of the breast characteristics and beam conditions on D_(gN)^(DBT) in detailed breast models was investigated.The D_(gN)^(DBT) results were 14.6-51.0%lower than those of the traditional dosimetry standard in China.The difference in D_(gN)^(DBT) was mainly due to a decrease in the depth of the main energy deposition area caused by the glandular distribution along the depth direction.The results obtained in this study may be used to improve breast dosimetry in China and provide more detailed information on risk assessment during DBT.展开更多
BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resi...BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.展开更多
Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with s...Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with sickle cell disease frequently experience painful episodes necessitating hospitalization, and their hemoglobin levels are typically lower than those of the general population. There are different treatment options available to manage complications, such as transfusing blood, hydroxyurea, and strong anti-pains. However, with all these treatments, patients still commonly experience pain crises and suffer from organ damage. Hydroxyurea, the sole approved medication for sickle cell anemia in developed and developing countries, is widely used in children despite being primarily indicated for adults. Multiple studies have demonstrated the efficacy of hydroxyurea in inducing HbF production in young children with SCD. Elevated HbF levels have been associated with improved clinical outcomes, including a reduction in vaso-occlusive crises, acute chest syndrome, and the need for blood transfusions. Furthermore, increased HbF levels have been shown to ameliorate disease-related organ damage, such as pulmonary hypertension and sickle cell retinopathy. The response to hydroxyurea treatment in young children with SCD is variable. Some patients achieve substantial increases in HbF levels and experience significant clinical benefits, while others may have a more modest response. Factors influencing the response include baseline HbF levels, genetic modifiers, treatment adherence, and dose optimization. Safety is a crucial consideration when using hydroxyurea in young children. Studies have shown that hydroxyurea is generally well-tolerated, with the most common adverse effects being myelosuppression, gastrointestinal symptoms, and dermatological manifestations. However,long-term effects and potential risks, such as renal dysfunction and reproductive impacts, require further investigation. The effectiveness of hydroxyurea in young children with SCD has been demonstrated in various clinical trials and observational studies. These studies have shown a significant reduction in disease-related complications and improved quality of life. However, optimal dosing, treatment duration, and long-term outcomes are still areas of ongoing research. This review focuses on recent studies investigating the benefits, effectiveness, responses, and safety of hydroxyurea in pediatric individuals diagnosed with sickle cell disease.展开更多
BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of th...BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.展开更多
Timer error as well as its convention is very important for dose accuracy during irradiation. This paper determines the timer error of irradiators at Secondary Standard Dosimetry Laboratory (SSDL) in Nigeria. The irra...Timer error as well as its convention is very important for dose accuracy during irradiation. This paper determines the timer error of irradiators at Secondary Standard Dosimetry Laboratory (SSDL) in Nigeria. The irradiators are Cs-137 OB6 irradiator and X-ray irradiators at the Protection level SSDL;and Co-60 irradiator at the Therapy Level SSDL. PTW UNIDOS electrometer and LS01 Ionization chamber were used at the Protection Level to obtain doses for both Cs-137 OB6 and X-ray irradiators while an IBA farmer type ionization chamber and an IBA DOSE 1 electrometer were used at the Protection Level SSDL. Single/multiple exposure method and graphical method were used in the determination of the timer error for the three irradiators. The timer error obtained for Cs-137 OB6 irradiator was 0.48 ± 0.01 s, the timer error for the X-ray irradiator was 0.09 ± 0.01 s while the timer error obtained for GammaBeam X200 was 1.21 ± 0.04 s. It was observed that the timer error is not affected by source to detector distance. It was also observed that the timer error of Co-60 Gamma X200 irradiator is increasing with the age of the machine. Source to detector distance and field size do not contribute towards the timer error of the irradiators. The timer error of the Co-60 Gamma X200 irradiator (the only irradiator among the irradiators with a pneumatic system) increases with the age of the irradiator.展开更多
The risk of radiation-induced second cancer and the late tissue loss due to Off-field doses in radiotherapy remain a serious concern. Monte Carlo (MC) simulation is currently one of the most accurate methods for calcu...The risk of radiation-induced second cancer and the late tissue loss due to Off-field doses in radiotherapy remain a serious concern. Monte Carlo (MC) simulation is currently one of the most accurate methods for calculating these doses. MC simulation model based on the Particle Simulation Tool (TOPAS) has been developed to simulate the off-field dose of an Elekta Synergy linear accelerator (Linac) emitting 6 MV photons. Measurements were taken in a water phantom using an ionization chamber to validate this model. The Percentage Depth Dose (PDD) at the depth of 0.0, 5.0, 10.0 and 15.0 cm from the beam axis for a 10 × 10 cm2 field size was measured and simulated. Off-field dose profiles at the depth of 1.5 (dmax), 5.0 and 10.0 cm for field sizes of 5 × 5, 10 × 10, 15 × 15, and 20 × 20 cm2 respectively were measured and simulated. Comparison of measured and simulated off-field dose values showed a good agreement. The average gamma passing rate of the PDDs and profiles curves for off-field doses were 87.5% and 98.11% respectively. The local dose difference based on the PDD curve between the measured and simulated was less than 6.0 % for all locations. For all field size considered in this study, the average difference between profile curves for off-field dose measured and simulated was 9.1%. PDDs and Profiles curves for off-field dose simulation uncertainties were less than 2.0% and 1.0% respectively. TOPAS-MC simulation model developed is a good representation of our 6 MV Linac Elekta Synergy for assessing off-field dose, which would be the primary cause of some secondary cancers.展开更多
基金Supported by National Hi-tech Research and Development Program of China(863 Program,Grant No.2012AA111708)
文摘Selective Catalyst Reduction(SCR)Urea Dosing System(UDS)directly affects the system accuracy and the dynamic response performance of a vehicle.However,the UDS dynamic response is hard to keep up with the changes of the engine's operating conditions.That will lead to low NO_χconversion efficiency or NH_3 slip.In order to optimize the injection accuracy and the response speed of the UDS in dynamic conditions,an advanced control strategy based on an air-assisted volumetric UDS is presented.It covers the methods of flow compensation and switching working conditions.The strategy is authenticated on an UDS and tested in different dynamic conditions.The result shows that the control strategy discussed results in higher dynamic accuracy and faster dynamic response speed of UDS.The inject deviation range is improved from being between-8%and 10%to-4%and 2%and became more stable than before,and the dynamic response time was shortened from 200 ms to 150 ms.The ETC cycle result shows that after using the new strategy the NH_3 emission is reduced by 60%,and the NO_χemission remains almost unchanged.The trade-off between NO_χconversion efficiency and NH_3 slip is mitigated.The studied flow compensation and switching working conditions can improve the dynamic performance of the UDS significantly and make the UDS dynamic response keep up with the changes of the engine's operating conditions quickly.
文摘In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.
文摘The principle and working process of Vacuum Resin Shot Dosing Equipment(VRSDE) are analyzed and the characteristics of IP1612-220PLC (Programmable Logical Controller) areintroduced briefly at first. Then the authors discuss the flow of program, the assignment of PLCI/O ports, the wiring diagram, and the ladder logic program of the PLC control system of VRSDE indetail. Some application issues of the system are accounted for in addition. Finally, according tothe information acquired from users, the authors draw the conclusion: this system owns a highreliability and a-vailability and greatly improves the automatic degree of VRDE.
文摘On the basis of the analysis of faults and their causes of vacuum resin shot dosing equipment, the fuzzy model of fault diagnosis for the equipment is constructed, and the fuzzy relationship matrix, the symptom fuzzy vector, the fuzzy compound arithmetic operator, and the diagnosis principle of the model are determined. Then the fault auto-diagnosis system for the equipment is designed , and the functions for real-time monitoring its operation condition and for fault auto diagosis are realized. Finally, the experiments of fault auto-diagnosis are conducted in practical production and the veracity of the system is verified.
基金Supported by Veloxis Pharmaceuticals,Inc.1001 Winstead Drive Suite 310,Cary,NC 27513.
文摘BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.
文摘Background: The 2020 consensus guidelines recommend AUC guided dosing as the preferred monitoring method for vancomycin. AUC based dosing has shown to reduce incidence of acute kidney injury (AKI), utilize lower daily doses in obese patients, and maintain efficacy. Several institutions have adjusted their protocols to utilize AUC guided dosing. However, there are limited studies comparing the clinical outcomes of AUC versus trough monitoring. Methods: This was a retrospective, observational, single centered study. The primary outcome was to evaluate the clinical success of AUC dosing versus trough based dosing of vancomycin for MRSA infections using a composite outcome of afebrile post treatment ( Results: Forty-seven patients were included in this study, 17 in the AUC group and 30 in the trough group. The primary composite outcome showed a significant benefit of AUC dosing (p = 0.04). The composite component culture clearance showed the largest improvement for the AUC group when compared with the trough group (p = 0.03). More patients achieved therapeutic target attainment and reached the target sooner (3 days versus 4 days, p = 0.2) in the AUC group. Over the study course, 94.1% of patients in the AUC group were considered therapeutic compared to 63.8% in the trough group (p = 0.03). Vancomycin levels were collected less frequently in the AUC group (3 versus 4, p = 0.2). Conclusion: The outcomes of this study may suggest AUC guided dosing as a beneficial alternative to trough based dosing. AUC based dosing may improve clinical success which can be further explored in larger prospective clinical trials.
基金supported by Guangzhou Science and Technology Planning Project(2023A04J0131)Special fund for scientific innovation strategyconstruction of high level Academy of Agriculture Science(R2020PY-JG009,R2022PY-QY007,202106TD)+2 种基金China Agriculture Research System-CARS-35the Project of Swine Innovation Team in Guangdong Modern Agricultural Research System(2022KJ126)Special Fund for Rural Revitalization Strategy of Guangdong(2023TS-3),China。
文摘Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.
基金The College Students’ Innovative Entrepreneurial Training Plan Program [202110594024]Science and Technology Plan Projects of Liuzhou [2022CAC0299]
文摘Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.
基金supported by the National Key R&D Program of China(2022YFC2303403)the National Science Fund for Distinguished Young Scholars(82225021)supported by the Young Scientists in Basic Research(YSBR-010).
文摘Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its sub-variants.This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies.Here,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its sub-variants.Cryo-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S protein.The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex.Furthermore,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus particles.Compared to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro.The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.
基金supported by the National Natural Science Foundation of China(grant numbers 82170188 and 81970176)Guangdong Basic and Applied Basic Research Foundation(grant number 2021A1515110012).
文摘Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be improved.This phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL.Expected objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months.No dose-limiting events were observed,RP2D of chidamide was 30 mg twice a week.Twenty-nine patients were enrolled in phase 2.In the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,respectively.The most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)patients.Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role.STAT3 mutation shows an unfavorable prognosis.Although outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time.It is a promising therapeutic option for this population.
基金supported by Guangzhou Laboratory,Grant Award Number:EKPG21-30-4.
文摘The safety and efficacy of COVID-19 vaccines in the elderly,a high-risk group for severe COVID-19 infection,have not been fully understood.To clarify these issues,this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety,immunogenicity,and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001.The results showed that this vaccination protocol was safe and tolerable in the elderly.After administering two doses of the BBIBP-CorV,the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals.After the ZF2001 booster dose,the antibody-positive rates in the elderly were comparable to those in the young;however,the antibody titers remained lower.Gender,age,and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals.The pseudovirus neutralization assay showed that,compared with those after receiving two doses of BBIBP-CorV priming,some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster.Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms.The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young.Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.
基金This work was supported by the special fund of the State Key Laboratory of Intense Pulsed Radiation Simulation and Effect(No.SKLIPR2011).
文摘Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was proposed.The digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional area.Each of these three parts was separately modeled.Using the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using VHDL-AMS.In the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area models.Furthermore,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital IC.TID experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose point.This confirms the practicality and accuracy of the proposed modeling method.The TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.
基金funded by the National Natural Science Foundation of China (Nos.81771972,52171243,and 52371256)the National Key Research and Development Program of China (No.2017YFC0107405).
文摘X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.
文摘Fetal and Maternal Atomic Bomb Survivor Dosimetry Using the J45 Pregnant Female Phantom Series:Considerations of the Kneeling and Lying Posture with Comparisons to the DS02 System Sean J.Domal1,Camilo M.Correa-Alfonso1,Colin J.Paulbeck2,Keith T.Griffin3,4,Tatsuhiko Sato5,Sachiyo Funamoto6,Harry M.Cullings6,Stephen D.Egbert7,Akira Endo8,Nolan E.Hertel4,Choonsik Lee3,Wesley E.Bolch9(1.Medical Physics Program,College of Medicine,University of Florida,Gainesville,FL;2.Department of Radiology,Johns Hopkins University,Baltimore,MD;3.National Cancer Institute,National Institutes of Health,Rockville,MD;4.George W.Woodruff School of Mechanical Eng.,Georgia Institute of Technology,Atlanta,GA;5.Nuclear Science and Engineering Center,Japan Atomic Energy Agency,Tokaimura,Japan;6.Department of Statistics,Radiation Effects Research Foundation,Hiroshima,Japan;7.Consultant,San Diego,CA;8.Nuclear Science Research Institute,Japan Atomic Energy Agency,Tokaimura,Japan;9.J.Crayton Pruitt Family Department of Biomedical Eng.,University of Florida,Gainesville,FL USA)Abstract:Organ dosimetry data of the atomic bomb survivors and the resulting cancer risk models derived from these data are currently assessed within the DS02 dosimetry system developed through the Joint US-Japan Dosimetry Working Group.In DS02,the anatomical survivor models are limited to three hermaphroditic stylized phantoms—an adult(55 kg),a child(19.8 kg),and an infant(9.7 kg)—that were originally designed for the preceding DS86 dosimetry system.As such,organ doses needed for assessment of in-utero cancer risks to the fetus have continued to rely upon the use of the uterine wall in the adult non-pregnant stylized phantom as the dose surrogate for all fetal organs regardless of gestational age.
基金supported by the National Natural Science Foundation of China(Nos.U2167209 and 12175114)the National Key R&D Program of China(No.2021YFF0603600).
文摘The rise in breast cancer diagnoses among Chinese women has necessitated the use of X-ray breast screening,which carries a radiation risk.This study aimed to provide a dosimetry protocol for the Chinese female population to replace the traditional standard that utilizes simplified breast models,for the accurate estimation of the mean glandular dose of a patient undergoing digital breast tomosynthesis(DBT).The first set of detailed Chinese female breast models and representative breast parameters was constructed.Considering backscatter radiation and computational efficiency,we improved the combination of these models and the Chinese reference adult female whole-body voxel phantom.Image acquisition for four commercial DBT systems that are widely employed in China was simulated using the Monte Carlo method to obtain the normalized glandular dose coefficients of DBT(D_(gN)^(DBT))and the glandular depth dose(D_(g)^(dep)(z))for different breast characteristics and X-ray spectra.We calculated a series of D_(gN)^(DBT) values for breasts with different percentage mass glandularities(5%,25%,50%,75%,and 100%)and compressed breast thicknesses(2,3,4,5,6,and 7 cm)at various tube potentials(25,28,30,32,35,and 49 kV)and target/filter combinations(W/Rh,W/Al,Mo/Mo,Rh/Rh,and Rh/Ag).The parameter dependence of the breast characteristics and beam conditions on D_(gN)^(DBT) in detailed breast models was investigated.The D_(gN)^(DBT) results were 14.6-51.0%lower than those of the traditional dosimetry standard in China.The difference in D_(gN)^(DBT) was mainly due to a decrease in the depth of the main energy deposition area caused by the glandular distribution along the depth direction.The results obtained in this study may be used to improve breast dosimetry in China and provide more detailed information on risk assessment during DBT.
文摘BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.
文摘Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with sickle cell disease frequently experience painful episodes necessitating hospitalization, and their hemoglobin levels are typically lower than those of the general population. There are different treatment options available to manage complications, such as transfusing blood, hydroxyurea, and strong anti-pains. However, with all these treatments, patients still commonly experience pain crises and suffer from organ damage. Hydroxyurea, the sole approved medication for sickle cell anemia in developed and developing countries, is widely used in children despite being primarily indicated for adults. Multiple studies have demonstrated the efficacy of hydroxyurea in inducing HbF production in young children with SCD. Elevated HbF levels have been associated with improved clinical outcomes, including a reduction in vaso-occlusive crises, acute chest syndrome, and the need for blood transfusions. Furthermore, increased HbF levels have been shown to ameliorate disease-related organ damage, such as pulmonary hypertension and sickle cell retinopathy. The response to hydroxyurea treatment in young children with SCD is variable. Some patients achieve substantial increases in HbF levels and experience significant clinical benefits, while others may have a more modest response. Factors influencing the response include baseline HbF levels, genetic modifiers, treatment adherence, and dose optimization. Safety is a crucial consideration when using hydroxyurea in young children. Studies have shown that hydroxyurea is generally well-tolerated, with the most common adverse effects being myelosuppression, gastrointestinal symptoms, and dermatological manifestations. However,long-term effects and potential risks, such as renal dysfunction and reproductive impacts, require further investigation. The effectiveness of hydroxyurea in young children with SCD has been demonstrated in various clinical trials and observational studies. These studies have shown a significant reduction in disease-related complications and improved quality of life. However, optimal dosing, treatment duration, and long-term outcomes are still areas of ongoing research. This review focuses on recent studies investigating the benefits, effectiveness, responses, and safety of hydroxyurea in pediatric individuals diagnosed with sickle cell disease.
文摘BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.
文摘Timer error as well as its convention is very important for dose accuracy during irradiation. This paper determines the timer error of irradiators at Secondary Standard Dosimetry Laboratory (SSDL) in Nigeria. The irradiators are Cs-137 OB6 irradiator and X-ray irradiators at the Protection level SSDL;and Co-60 irradiator at the Therapy Level SSDL. PTW UNIDOS electrometer and LS01 Ionization chamber were used at the Protection Level to obtain doses for both Cs-137 OB6 and X-ray irradiators while an IBA farmer type ionization chamber and an IBA DOSE 1 electrometer were used at the Protection Level SSDL. Single/multiple exposure method and graphical method were used in the determination of the timer error for the three irradiators. The timer error obtained for Cs-137 OB6 irradiator was 0.48 ± 0.01 s, the timer error for the X-ray irradiator was 0.09 ± 0.01 s while the timer error obtained for GammaBeam X200 was 1.21 ± 0.04 s. It was observed that the timer error is not affected by source to detector distance. It was also observed that the timer error of Co-60 Gamma X200 irradiator is increasing with the age of the machine. Source to detector distance and field size do not contribute towards the timer error of the irradiators. The timer error of the Co-60 Gamma X200 irradiator (the only irradiator among the irradiators with a pneumatic system) increases with the age of the irradiator.
文摘The risk of radiation-induced second cancer and the late tissue loss due to Off-field doses in radiotherapy remain a serious concern. Monte Carlo (MC) simulation is currently one of the most accurate methods for calculating these doses. MC simulation model based on the Particle Simulation Tool (TOPAS) has been developed to simulate the off-field dose of an Elekta Synergy linear accelerator (Linac) emitting 6 MV photons. Measurements were taken in a water phantom using an ionization chamber to validate this model. The Percentage Depth Dose (PDD) at the depth of 0.0, 5.0, 10.0 and 15.0 cm from the beam axis for a 10 × 10 cm2 field size was measured and simulated. Off-field dose profiles at the depth of 1.5 (dmax), 5.0 and 10.0 cm for field sizes of 5 × 5, 10 × 10, 15 × 15, and 20 × 20 cm2 respectively were measured and simulated. Comparison of measured and simulated off-field dose values showed a good agreement. The average gamma passing rate of the PDDs and profiles curves for off-field doses were 87.5% and 98.11% respectively. The local dose difference based on the PDD curve between the measured and simulated was less than 6.0 % for all locations. For all field size considered in this study, the average difference between profile curves for off-field dose measured and simulated was 9.1%. PDDs and Profiles curves for off-field dose simulation uncertainties were less than 2.0% and 1.0% respectively. TOPAS-MC simulation model developed is a good representation of our 6 MV Linac Elekta Synergy for assessing off-field dose, which would be the primary cause of some secondary cancers.