Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendati...Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.展开更多
The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg)...The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.展开更多
The pattern dependence in synergistic effects was studied in a 0.18 μm static random access memory（SRAM） circuit.Experiments were performed under two SEU test environments：3 Me V protons and heavy ions.Measured re...The pattern dependence in synergistic effects was studied in a 0.18 μm static random access memory（SRAM） circuit.Experiments were performed under two SEU test environments：3 Me V protons and heavy ions.Measured results show different trends.In heavy ion SEU test,the degradation in the peripheral circuitry also existed because the measured SEU cross section decreased regardless of the patterns written to the SRAM array.TCAD simulation was performed.TIDinduced degradation in n MOSFETs mainly induced the imprint effect in the SRAM cell,which is consistent with the measured results under the proton environment,but cannot explain the phenomena observed under heavy ion environment.A possible explanation could be the contribution from the radiation-induced GIDL in pMOSFETs.展开更多
Purpose: To quantitatively evaluate four different Proton SFUD PBS initial planning strategies for lung mobile tumor. Methods and Materials: A virtual lung patient’s four-dimensional computed tomography (4DCT) was ge...Purpose: To quantitatively evaluate four different Proton SFUD PBS initial planning strategies for lung mobile tumor. Methods and Materials: A virtual lung patient’s four-dimensional computed tomography (4DCT) was generated in this study. To avoid the uncertainties from target delineation and imaging artifacts, a sphere with diameter of 3 cm representing a rigid mobile target (GTV) was inserted into the right side of the lung. The target motion is set in superior-inferior (SI) direction from ?5 mm to 5 mm. Four SFUD planning strategies were used based on: 1) Maximum-In-tensity-Projection Image (MIP-CT);2) CT_average with ITV overridden to muscle density (CTavg_muscle);3) CT_average with ITV overridden to tumor density (CTavg_tumor);4) CT_average without any override density (CTavg_only). Dose distributions were recalculated on each individual phase and accumulated together to assess the “actual” treatment. To estimate the impact of proton range uncertainties, +/?3.5% CT calibration curve was applied to the 4DCT phase images. Results: Comparing initial plan to the dose accumulation: MIP-CT based GTV D98 degraded 2.42 Gy (60.10 Gy vs 57.68 Gy). Heart D1 increased 6.19 Gy (1.88 Gy vs 8.07 Gy);CTavg_tumor based GTV D98 degraded 0.34 Gy (60.07 Gy vs 59.73 Gy). Heart D1 increased 2.24 Gy (3.74 Gy vs 5.98 Gy);CTavg_muscle based initial GTV D98 degraded 0.31 Gy (60.4 Gy vs 60.19 Gy). Heart D1 increased 3.44 Gy (4.38 Gy vs 7.82 Gy);CTavg_only based Initial GTV D98 degraded 6.63 Gy (60.11 Gy vs 53.48 Gy). Heart D1 increased 0.30 Gy (2.69 Gy vs 2.96 Gy);in the presence of ±3.5% range uncertainties, CTavg_tumor based plan’s accumulated GTV D98 degraded to 57.99 Gy (+3.5%) 59.38 Gy (?3.5%), and CTavg_muscle based plan’s accumulated GTV D98 degraded to 59.37 Gy (+3.5%) 59.37 Gy (?3.5%). Conclusion: This study shows that CTavg_Tumor and CTavg_Muscle based planning strategies provide the most robust GTV coverage. However, clinicians need to be aware that the actual dose to OARs at distal end of target may increase. The study also indicates that the current SFUD PBS planning strategy might not be sufficient to compensate the CT calibration uncertainty.展开更多
Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of si...Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.Methods An open-label,non-randomized,single and multiple dose clinical trial was conducted.In single dose study,12 subjects took 200 mg antofloxacin hydrochloride.In multiple dose study,12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7.HPLC was used to assay the serum and urinary concentrations of antofloxacin.Results In single dose study,the maximum concentration of drug in serum （Cmax）,the time to reach Cmax （Tmax）,and the area under the serum concentration-time curve （AUC （O-∞）） of antofloxacin were （1.89±0.65） mg/L,（1.29±0.26） hours,39.1%.In multiple dose study,blood concentration of antofloxiacin achieved stable state on day 2 after dosing.The minimum concentration drug in serum （Cmin）,AUCss,mean concentration of drug in serum （Cav）,and degree offluctuation （DF） were （0.73±0.18） mg/L, （47.59±7.85） mg·h^-1·L^-1, （1.98±0.33） mg/L, and 1.74±0.60, respectively. On day 7 after dosing, Tmax ,Cmax and AUC （0-∞） was （1.14±0.50） hours, （2.52±0.38） mg/L, and （48.77±8.44） mg·h^-1·L^-1, respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.Conclusions The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.展开更多
Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid de...Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs.Methods:We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(EPR)effect.This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system.The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo.Results:The accumulation of Nano(cetuximab)within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration,which was contrary to the biodistribution of native cetuximab.Nano(cetuximab)accumulated in tumor tissues via the EPR effect and released cetuximab.The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect,which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab,Nano(cetuximab)showed an effective tumor suppressive effect for 3 weeks.Conclusions:The nanocapsule-based delivery system efficiently delivered tAbs to tum or tissues and released them to boost the EPR effect,which facilitated further tumor accumulation of the tAbs.This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs,and stimulated new ideas for antibody-based tumor therapy.展开更多
In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid ...In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.展开更多
The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was...The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was designed to perform a 6-year field experiment to unveil the rice yield with time due to various biochar application strategies.Moreover,an alternative strategy of the Annual Low dose biochar application(AL,8×35%=2.8 t ha^(−1))was also conducted to make a comparison with the High Single dose(HS,22.5 t ha^(−1)),and annual Rice Straw(RS,8 t ha^(−1))amendment to investigate the effects on annual rice yield attributes and soil nutrient concentrations.Results showed that the rice yield in AL with a lower biochar application exceeded that of HS significantly(p<0.05)in the 6th experimental year.The rice yield increased by 14.3%in RS,10.9%in AL,and 4.2%in HS.The unexpectedly higher rice yield in AL than HS resulted from enhanced soil total carbon(TC),pH,and available Ca.However,compared to AL,liable carbon fraction increased by 33.7%in HS,while refractory carbon fraction dropped by 22.3%.Likewise,biochar characterization showed that more oxygen functional groups existed in HS than in AL.Decreasing inert organic carbon pools due to the constant degradation of the aromatic part of biochar in HS led to a lower soil TC than AL,even with a higher amount of biochar application.Likewise,the annual depletion lowered the soil pH and available Ca declination in HS.Based on the obtained results,this study suggested AL as a promising strategy to enhance rice productivity,soil nutrient enrichment,and carbon sequestration in the paddy ecosystem.展开更多
文摘Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.
文摘The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.
基金Project supported by the National Natural Science Foundation of China(Grant No.U1532261)
文摘The pattern dependence in synergistic effects was studied in a 0.18 μm static random access memory（SRAM） circuit.Experiments were performed under two SEU test environments：3 Me V protons and heavy ions.Measured results show different trends.In heavy ion SEU test,the degradation in the peripheral circuitry also existed because the measured SEU cross section decreased regardless of the patterns written to the SRAM array.TCAD simulation was performed.TIDinduced degradation in n MOSFETs mainly induced the imprint effect in the SRAM cell,which is consistent with the measured results under the proton environment,but cannot explain the phenomena observed under heavy ion environment.A possible explanation could be the contribution from the radiation-induced GIDL in pMOSFETs.
文摘Purpose: To quantitatively evaluate four different Proton SFUD PBS initial planning strategies for lung mobile tumor. Methods and Materials: A virtual lung patient’s four-dimensional computed tomography (4DCT) was generated in this study. To avoid the uncertainties from target delineation and imaging artifacts, a sphere with diameter of 3 cm representing a rigid mobile target (GTV) was inserted into the right side of the lung. The target motion is set in superior-inferior (SI) direction from ?5 mm to 5 mm. Four SFUD planning strategies were used based on: 1) Maximum-In-tensity-Projection Image (MIP-CT);2) CT_average with ITV overridden to muscle density (CTavg_muscle);3) CT_average with ITV overridden to tumor density (CTavg_tumor);4) CT_average without any override density (CTavg_only). Dose distributions were recalculated on each individual phase and accumulated together to assess the “actual” treatment. To estimate the impact of proton range uncertainties, +/?3.5% CT calibration curve was applied to the 4DCT phase images. Results: Comparing initial plan to the dose accumulation: MIP-CT based GTV D98 degraded 2.42 Gy (60.10 Gy vs 57.68 Gy). Heart D1 increased 6.19 Gy (1.88 Gy vs 8.07 Gy);CTavg_tumor based GTV D98 degraded 0.34 Gy (60.07 Gy vs 59.73 Gy). Heart D1 increased 2.24 Gy (3.74 Gy vs 5.98 Gy);CTavg_muscle based initial GTV D98 degraded 0.31 Gy (60.4 Gy vs 60.19 Gy). Heart D1 increased 3.44 Gy (4.38 Gy vs 7.82 Gy);CTavg_only based Initial GTV D98 degraded 6.63 Gy (60.11 Gy vs 53.48 Gy). Heart D1 increased 0.30 Gy (2.69 Gy vs 2.96 Gy);in the presence of ±3.5% range uncertainties, CTavg_tumor based plan’s accumulated GTV D98 degraded to 57.99 Gy (+3.5%) 59.38 Gy (?3.5%), and CTavg_muscle based plan’s accumulated GTV D98 degraded to 59.37 Gy (+3.5%) 59.37 Gy (?3.5%). Conclusion: This study shows that CTavg_Tumor and CTavg_Muscle based planning strategies provide the most robust GTV coverage. However, clinicians need to be aware that the actual dose to OARs at distal end of target may increase. The study also indicates that the current SFUD PBS planning strategy might not be sufficient to compensate the CT calibration uncertainty.
文摘Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.Methods An open-label,non-randomized,single and multiple dose clinical trial was conducted.In single dose study,12 subjects took 200 mg antofloxacin hydrochloride.In multiple dose study,12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7.HPLC was used to assay the serum and urinary concentrations of antofloxacin.Results In single dose study,the maximum concentration of drug in serum （Cmax）,the time to reach Cmax （Tmax）,and the area under the serum concentration-time curve （AUC （O-∞）） of antofloxacin were （1.89±0.65） mg/L,（1.29±0.26） hours,39.1%.In multiple dose study,blood concentration of antofloxiacin achieved stable state on day 2 after dosing.The minimum concentration drug in serum （Cmin）,AUCss,mean concentration of drug in serum （Cav）,and degree offluctuation （DF） were （0.73±0.18） mg/L, （47.59±7.85） mg·h^-1·L^-1, （1.98±0.33） mg/L, and 1.74±0.60, respectively. On day 7 after dosing, Tmax ,Cmax and AUC （0-∞） was （1.14±0.50） hours, （2.52±0.38） mg/L, and （48.77±8.44） mg·h^-1·L^-1, respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.Conclusions The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.
基金the National Key Research and Development Program(Grant Nos.2016YFC0902502 and 2018YFA0209700)the National Natural Science Foundation of China(Grant Nos.81772667 and 51773151)the Special Construction Innovation Funded Project for Community in Beijing,Tianjin and Hebei of China(Grant No.18247792D).
文摘Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs.Methods:We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(EPR)effect.This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system.The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo.Results:The accumulation of Nano(cetuximab)within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration,which was contrary to the biodistribution of native cetuximab.Nano(cetuximab)accumulated in tumor tissues via the EPR effect and released cetuximab.The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect,which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab,Nano(cetuximab)showed an effective tumor suppressive effect for 3 weeks.Conclusions:The nanocapsule-based delivery system efficiently delivered tAbs to tum or tissues and released them to boost the EPR effect,which facilitated further tumor accumulation of the tAbs.This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs,and stimulated new ideas for antibody-based tumor therapy.
文摘In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.
基金National Natural Science Foundation of China[grant numbers 42077032 and 41571241]National Key Technology Research and Development Program of the Ministry of Science and Technology of China[grant number 2015BAC02B01]+1 种基金We gratefully acknowledge the financial support from the China Scholarship Council[grant number 202106320251]Doctoral Rising Star Program of Zhejiang University.
文摘The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was designed to perform a 6-year field experiment to unveil the rice yield with time due to various biochar application strategies.Moreover,an alternative strategy of the Annual Low dose biochar application(AL,8×35%=2.8 t ha^(−1))was also conducted to make a comparison with the High Single dose(HS,22.5 t ha^(−1)),and annual Rice Straw(RS,8 t ha^(−1))amendment to investigate the effects on annual rice yield attributes and soil nutrient concentrations.Results showed that the rice yield in AL with a lower biochar application exceeded that of HS significantly(p<0.05)in the 6th experimental year.The rice yield increased by 14.3%in RS,10.9%in AL,and 4.2%in HS.The unexpectedly higher rice yield in AL than HS resulted from enhanced soil total carbon(TC),pH,and available Ca.However,compared to AL,liable carbon fraction increased by 33.7%in HS,while refractory carbon fraction dropped by 22.3%.Likewise,biochar characterization showed that more oxygen functional groups existed in HS than in AL.Decreasing inert organic carbon pools due to the constant degradation of the aromatic part of biochar in HS led to a lower soil TC than AL,even with a higher amount of biochar application.Likewise,the annual depletion lowered the soil pH and available Ca declination in HS.Based on the obtained results,this study suggested AL as a promising strategy to enhance rice productivity,soil nutrient enrichment,and carbon sequestration in the paddy ecosystem.
