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1.
Polyplex micelles formed with plasmid DNA (pDNA) and poly(ethylene glycol) (PEG)-block-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] exhibit effective endosomal escaping properties based on di-protonation of diamine side chains with decreasing pH, which improves their transfection efficiency and thus are promising candidates for local in vivo gene transfer. Here, PEG-PAsp(DET) polyplex micelles were further improved as in vivo systemic vectors by introduction of cholesterol (Chole) into the ω-terminus of PEG-PAsp(DET) to obtain PEG-PAsp(DET)-Chole. Introduction of the cholesterol resulted in enhanced association of block copolymers with pDNA, which led to increased stability in proteinous medium and also in the blood stream after systemic injection compared to PEG-PAsp(DET) micelles. The synergistic effect between enhanced polymer association with pDNA and increased micelle stability of PEG-PAsp(DET)-Chole polyplex micelles led to high in vitro gene transfer even at relatively low concentrations, due to efficient cellular uptake and effective endosomal escape of block copolymers and pDNA. Finally, PEG-PAsp(DET)-Chole micelles achieved significant suppression of tumor growth following intravenous injection into mice bearing a subcutaneous pancreatic tumor using therapeutic pDNA encoding an anti-angiogenic protein. These results suggest that PEG-PAsp(DET)-Chole micelles can be effective systemic gene vectors for treatment of solid tumors.  相似文献   

2.
BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. METHODS: Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. RESULTS: Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS: One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.  相似文献   

3.
Clinically relevant intensity modulated proton therapy (IMPT) treatment plans were measured in a newly developed anthropomorphic phantom (i) to assess plan accuracy in the presence of high heterogeneity and (ii) to measure plan robustness in the case of treatment uncertainties (range and spatial). The new phantom consists of five different tissue substitute materials simulating different tissue types and was cut into sagittal planes so as to facilitate the verification of co-planar proton fields. GafChromic films were positioned in the different planes of the phantom, and 3D-IMPT and distal edge tracking (DET) plans were delivered to a volume simulating a skull base chordoma. In addition, treatments planned on CTs of the phantom with HU units modified were delivered to simulate systematic range uncertainties (range-error treatments). Finally, plans were delivered with the phantom rotated to simulate spatial errors. Results show excellent agreement between the calculated and the measured dose distribution: >99% and 98% of points with a gamma value <1 (3%/3 mm) for the 3D-IMPT and the DET plan, respectively. For both range and spatial errors, the 3D-IMPT plan was more robust than the DET plan. Both plans were more robust to range than to the spatial uncertainties. Finally, for range error treatments, measured distributions were compared to a model for predicting delivery errors in the treatment planning system. Good agreement has been found between the model and the measurements for both types of IMPT plan.  相似文献   

4.
BACKGROUND: Single embryo transfer (SET) is the sole strategy with which to reduce the incidence of twins following assisted reproductive technology (ART), but SET may increase the number of ART cycles needed per live-born child. Its cost-effectiveness compared with double embryo transfer (DET) is therefore unknown. METHODS: A decision-analytic model comparing SET with DET was developed. Estimates were obtained from literature, national pregnancy registers and local hospital records. A sensitivity analysis was performed, using pregnancy rates from four published studies. The outcome measure was the cost per child born, calculated from IVF procedure-related, pregnancy-related and neonatal care costs. Neonatal mortality and long-term morbidity costs were not taken into account. RESULTS: Independently of the pregnancy rates used, the SET cost per child born was in all instances the same as with DET, varying from EURO= 9520 (SET) versus EURO= 9511 (DET) to EURO= 12254 (SET) versus EURO= 12934 (DET). CONCLUSIONS: More ART cycles are required to obtain the same numbers of children born following SET compared with DET. Because SET allows the avoidance of twins and thus diminishes pregnancy-related and neonatal care costs, there is no difference in the cost per child born between SET and DET. The real advantage of SET is the avoidance of the very high long-term costs resulting from the increased morbidity of twins after birth.  相似文献   

5.
BACKGROUND: With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer (SET) and one cycle with double embryo transfer (DET) after IVF and calculated the cost-effectiveness of both strategies. Methods: A randomized controlled trial was performed in 107 women, aged <35 years, in their first IVF cycle, with at least one good quality embryo. They were randomized to the SET (n = 54) or DET (n = 53) group using a computer-generated random block number table, stratified for primary or secondary infertility. RESULTS: The cumulative live birth rates per woman randomized of two consecutive cycles of SET [41%; 95% confidence interval (CI) 27-54] versus one cycle of DET (36%; 95% CI 23-49) were comparable, whereas the multiple pregnancy rate was significantly higher: 37% (95% CI 15-59) in the DET and 0% in the in the SET group (P = 0.002). Combining the medical costs of the IVF treatments (where 1.5 more SET cycles were required to achieve each live birth) and of pregnancies up to 6 weeks after delivery, the total medical costs of DET per live birth were 13,680 and 13,438 for SET. CONCLUSIONS: Two cycles with SET were equally effective as one cycle with DET, and the medical costs per live birth up to 6 weeks after delivery were the same. However, if lifetime costs for severe handicaps are included, more than 7000 per live birth will be saved after implementing SET. Because of the high probability of multiple pregnancies in this group of IVF patients, only SET should be performed.  相似文献   

6.
BACKGROUND: Transfer of several embryos after IVF results in a high multiple birth rate associated with increased morbidity and high costs for the neonatal care. In a previous randomized trial we demonstrated that a single embryo transfer (SET) strategy, including one fresh single embryo transfer and, if no live birth, one additional frozen-thawed SET, resulted in a live-birth rate that was not substantially lower than after double embryo transfer (DET) but markedly reduced the multiple birth rate. METHODS: We compared costs for maternal health care and productivity losses and paediatric costs for the SET and DET strategies. In addition, maternal and paediatric outcomes between the two groups were compared. RESULTS: The SET strategy resulted in lower average total costs from treatment until 6 months after delivery. There were a few more deliveries with at least one live-born child in the DET group. The incremental cost per extra delivery in the DET alternative was high, 71 940. The rates of prematurely born and low birthweight children were significantly lower with the SET strategy. There were also markedly fewer maternal and paediatric complications in the SET group. CONCLUSIONS: The SET strategy is superior to the DET strategy, when number of deliveries with at least one live-born child, incremental cost-effectiveness ratio and maternal and paediatric complications are taken into consideration. The findings do not support continuing transfers of two embryos in this group of patients.  相似文献   

7.
BACKGROUND: We analysed the difference in maternal, neonatal and total costs after single (SET) versus double day 3 embryo transfer (DET). METHODS: We performed a two-centre prospective study of women in their first IVF/ICSI cycle choosing between SET or DET. Infertility treatment data were gathered from a database; maternal and neonatal outcome data from a case report form (CRF); health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills. SET was performed in 206/367 (56.1%) and DET in 161/367 (43.9%) women. RESULTS: In all, 367 transfers yielded 186 positive pregnancy tests, 148 ongoing pregnancies and 136 live deliveries (50.7, 40.3 and 37.1% per embryo transfer) of which 15 (11.0%) were twins. Live birth rate was 37.4% for SET, 36.6% for DET. Intention-to-treat analysis showed differences for: duration of pregnancy (SET: 39.0 +/- 1.4 versus DET: 38.3 +/- 2.2 weeks; P = 0.055), percentage prematurity (8.5 versus 23.8%; P = 0.033), percentage of neonates hospitalized (5.7 versus 17.9%; P = 0.121) and duration of neonatal hospitalization (6.3 +/- 2.2 versus 10.3 +/- 10.1 days; P = 0.01). Total cost after DET was higher (SET: 4700 +/- 3239 versus DET: 8613 +/- 10 105; P = 0.105), due to significantly higher neonatal costs (451 +/- 957 versus 3453 +/- 8154; P < 0.001) and not to differences in maternal costs (4250 +/- 2882 versus 5160 +/- 4106; P = 0.152). CONCLUSIONS: This prospective health economic study shows that transfer of a single top quality embryo is equally effective as, but substantially cheaper than, double embryo transfer in women <38 years of age in their first IVF/ICSI cycle.  相似文献   

8.
BACKGROUND: Single-embryo transfer (SET) has proven efficient in reducing multiple pregnancy rates after assisted reproduction technologies (ART). This study compares outcome of singletons after SET and double-embryo transfer (DET). METHODS: We studied 404 SET and 431 DET patients, who delivered a singleton child of >500 g after fresh embryo transfer in a first, second or third cycle. Preterm birth and low birthweight incidences and gestational age and birthweight were compared between both groups. Adjustments were made for maternal age, parity, cycle rank number, treatment indication, ART method, embryo characteristics and sex of the child. RESULTS: Singletons born after DET have a significantly lower birthweight than that after SET (3204.3 +/-617.5 g versus 3324.6+/-509.7 g , P<0.01). Also preterm birth (<37 weeks) [odds ratio (OR) 1.77, 95% confidence interval (CI) 1.06-2.94] and low birthweight (<2500 g) (OR 3.38, 95% CI 1.86-6.12) are significantly more common in DET singletons. CONCLUSIONS: Singleton birth after SET is advantageous compared with DET. This sheds new light on the reasons why singleton births following ART do worse than spontaneously conceived singletons in IVF programs, where double- or multiple-embryo transfer is standard.  相似文献   

9.
The effects of calculational uncertainties on 3D and distal edge tracking (DET) intensity modulated proton therapy (IMPT) treatment plans have been investigated. Dose calculation uncertainties have been assessed by comparing analytical and Monte Carlo dose calculations, and potential range uncertainties by recalculating plans with all CT values modified by +/-3%. Analysis of the volume of PTV agreeing to within +/-3% between the two calculations shows that the 3D approach provides significantly improved agreement (87.1 versus 80.3% of points for the 3D and DET approaches, respectively). For the DET approach, doses in the CTV have also been found to globally change by 5% as a result of 3% changes in CT value. When varying the intra-field gradients of the plans a similar trend is seen, but with the more complex plans also being found to be more sensitive to both uncertainties. In conclusion, the DET approach has been found to be relatively sensitive to the calculational errors investigated here. In contrast, the 3D approach appears to be quite robust, unless strong internal gradients are present. Nevertheless, the routine use of uncertainty analysis is advised when assessing all forms of IMPT plans.  相似文献   

10.
Multiple pregnancies lead to complications and induce high costs. The most successful way to decrease multiple pregnancies in IVF is to transfer only one embryo, which might reduce the efficacy of treatment. The objective of this review is to determine which embryo-transfer policy is most cost-effective: elective single-embryo transfer (eSET) or double-embryo transfer (DET). Several databases were searched for (cost* or econ*) and (single embryo* or double embryo* or one embryo* or two embryo* or elect* embryo or multip* embryo*). On the basis of five exclusion criteria, titles and abstracts were screened by two individual reviewers. The remaining papers were read for further selection, and data were extracted from the selected studies. A total of 496 titles were identified through the searches and resulted in the selection of one observational study and three randomized studies. Study characteristics, total costs and probability of live births were extracted. Besides this, cost-effectiveness and incremental cost-effectiveness were derived. It can be concluded that DET is the most expensive strategy. DET is also most effective if performed in one fresh cycle. eSET is only preferred from a cost-effectiveness point of view when performed in good prognosis patients and when frozen/thawed cycles are included. If frozen/thawed cycles are excluded, the choice between eSET and DET depends on how much society is willing to pay for one extra successful pregnancy.  相似文献   

11.
The authors present a comparative study of intensity modulated proton therapy (IMPT) treatment planning employing algorithms of three-dimensional (3D) modulation, and 2.5-dimensional (2.5D) modulation, and intensity modulated distal edge tracking (DET) [A. Lomax, Phys. Med. Biol. 44, 185-205 (1999)] applied to the treatment of head-and-neck cancer radiotherapy. These three approaches were also compared with 6 MV photon intensity modulated radiation therapy (IMRT). All algorithms were implemented in the University of Florida Optimized Radiation Therapy system using a finite sized pencil beam dose model and a convex fluence map optimization model. The 3D IMPT and the DET algorithms showed considerable advantages over the photon IMRT in terms of dose conformity and sparing of organs at risk when the beam number was not constrained. The 2.5D algorithm did not show an advantage over the photon IMRT except in the dose reduction to the distant healthy tissues, which is inherent in proton beam delivery. The influences of proton beam number and pencil beam size on the IMPT plan quality were also studied. Out of 24 cases studied, three cases could be adequately planned with one beam and 12 cases could be adequately planned with two beams, but the dose uniformity was often marginally acceptable. Adding one or two more beams in each case dramatically improved the dose uniformity. The finite pencil beam size had more influence on the plan quality of the 2.5D and DET algorithms than that of the 3D IMPT. To obtain a satisfactory plan quality, a 0.5 cm pencil beam size was required for the 3D IMPT and a 0.3 cm size was required for the 2.5D and the DET algorithms. Delivery of the IMPT plans produced in this study would require a proton beam spot scanning technique that has yet to be developed clinically.  相似文献   

12.
BACKGROUND Embryologists currently face a challenge when counselling patients regarding the stage and the number of embryos to transfer when no top-quality embryos (TQE) are available. METHODS The aim of this study was to evaluate the efficacy of single blastocyst transfer (SBT) in comparison with the transfer of two cleavage-stage embryos in women under 36 years old. A total of 450 women under 36 years undergoing their first or second IVF treatment who had no TQE on Day 2 were included in this prospective study. Couples were assigned to either a SBT or a double cleavage-stage embryo transfer (DET). The clinical end-points monitored were rates of implantation, delivery and multiple deliveries. RESULTS The rate of transfer was significantly lower for couples assigned to the SBT group compared with the DET group (88 versus 100%, respectively, P < 0.001) while the delivery rate per oocyte retrieval was similar in both groups (26.7%). By contrast, the rate of multiple deliveries was significantly lower in the SBT group compared with the DET group (3.3 versus 23.3%, respectively, P < 0.01). Blastocyst cryopreservation was twice as high in the SBT group compared with the DET group (39 versus 18%, respectively, P < 0.001). CONCLUSIONS These findings show the value of extended embryo culture for couples without TQE. In such situations, delaying embryo transfer in order to select a single blastocyst with the highest potential for implantation can reduce the number of multiple pregnancies. Furthermore, our results demonstrate that extended culture allows blastocyst cryopreservation from embryos not available for Day 2 cryopreservation.  相似文献   

13.
IVF/ICSI twin pregnancies: risks and prevention   总被引:2,自引:0,他引:2  
Since the 1970s, the national twin birth rates have been increasing worldwide. Apart from the increasing childbearing age, the main cause is the use of assisted reproductive technologies (ART). To explore the overall consequences of dual embryo transfer (DET), the literature has been reviewed systematically regarding short- and long-term outcomes of IVF/ICSI twin pregnancies i.e. pregnancy complications, maternal risks, obstetric outcome and long-term morbidity including neurological sequelae, cognitive development and family implications. Another consequence of DET is vanishing twins, which seems to be a possible cause of adverse outcome in IVF singletons. The sparse literature on vanishing twins in IVF pregnancies and the influence on the surviving co-twin were also addressed. Finally, to determine the effects of implementing elective single embryo transfer (eSET), trials concerning eSET versus DET were analysed. In the light of the steadily increasing twin birth rates and the findings in this overview, where IVF/ICSI twins carry adverse outcome, it should be emphasized that the major obstacle in IVF remains the high twin birth rate. Furthermore vanishing twins account for another hazard of DET. These problems can be resolved by implementing eSET, diminishing the twin birth rate without affecting the overall goal of achieving a healthy infant.  相似文献   

14.
AIMS--To detect intestinal microsporidiosis in paraffin wax embedded biopsy specimens using a fluorescence technique incorporating optical brighteners. METHODS--Eight HIV infected patients with confirmed intestinal microsporidiosis (six with Enterocytozoon bieneusi, one with Encephalitozoon intestinalis and one with Encephalitozoon cuniculi infection) and 10 without infection were studied. Tissue sections of paraffin wax embedded duodenal biopsy specimens were stained with 1% Uvitex 2B, coded and analysed independently by two investigators. RESULTS--In all eight cases with confirmed intestinal microsporidian infection, spores could be detected easily in tissue sections using the fluorescence technique. Spores or other elements consistent with microsporidiosis were not found in the 10 patients without infection. CONCLUSION--Staining of tissue sections from paraffin wax embedded intestinal biopsy specimens with stains incorporating Uvitex 2B is a rapid and easy technique for the diagnosis of intestinal microsporidiosis.  相似文献   

15.
Simple tools for studying the effects of inter-fraction and inter-field motions on intensity modulated proton therapy (IMPT) plans have been developed, and have been applied to both 3D and distal edge tracking (DET) IMPT plans. For the inter-fraction motion, we have investigated the effects of misaligned density heterogeneities, whereas for the inter-field motion analysis, the effects of field misalignment on the plans have been assessed. Inter-fraction motion problems have been analysed using density differentiated error (DDE) distributions, which specifically show the additional problems resulting from misaligned density heterogeneities for proton plans. Likewise, for inter-field motion, we present methods for calculating motion differentiated error (MDE) distributions. DDE and MDE analysis of all plans demonstrate that the 3D approach is generally more robust to both inter-fraction and inter-field motions than the DET approach, but that strong in-field dose gradients can also adversely affect a plan's robustness. An important additional conclusion is that, for certain IMPT plans, even inter-fraction errors cannot necessarily be compensated for by the use of a simple PTV margins, implying that more sophisticated tools need to be developed for uncertainty management and assessment for IMPT treatments at the treatment planning level.  相似文献   

16.
During the last several years, legged locomotive mechanism has been considered as one of the main self-propelling mechanisms for future endoscopic microrobots due to its superior propulsion efficiency of an endoscopic microrobot inside the intestinal track. Nevertheless, its clinical application has been largely limited since the legged locomotive mechanism utilizes an end effector which has a sharp tip to generate sufficient traction by physically penetrating and interlocking with the intestinal tissue. This can cause excessive physical tissue damage or even complete perforation of the intestinal wall that can lead to abdominal inflammation. Hence, in this work two types of new end effectors, penetration-limited end effector (PLEE) and bi-material structured end effector (BMEE) were specially designed to acquire high medical safety as well as effective traction generation performance. The microscopic end effector specimens were fabricated with micro-wire electric discharge machining process. Traction generation performance of the end effectors was evaluated by direct measurement of resistance forces during contact-sliding tests using a custom-built contact-sliding tester. The safety of the end effector design was evaluated by examination of microscopic intestinal tissue damage using a scanning electron microscope (SEM). Physical damage characteristics of the intestinal tissue and related contact physics of the end effectors were discussed. From the results, the end effectors were evaluated with respect to their prospects in future medical applications as safe end effectors as well as micro-surgical tools.  相似文献   

17.
背景:小肠黏膜下层既具有良好的生物相容性和降解性,又富含多种生长因子,能明显促进细胞的黏附、增殖及分化,在国外已被广泛应用于骨与软骨、血管、皮肤、膀胱、平滑肌及胰岛等组织的修复,且已表现出良好的组织工程化细胞支架性能。 目的:探讨兔骨髓间充质干细胞经体外诱导成成骨细胞与猪小肠黏膜下层复合构建组织工程骨膜的可行性。 方法:采用贴壁筛选法分离2周龄健康新西兰大白兔骨髓间充质干细胞,并进行体外扩增培养、诱导分化及鉴定。将经成骨诱导分化的骨髓间充质干细胞与猪小肠黏膜下层复合构建组织工程骨膜,观察细胞在生物材料上的附着、生长、增殖情况。 结果与结论:接种5 d后,细胞散在附着于小肠黏膜下层材料上,细胞形态呈圆形,细胞之间无连接;10 d后细胞之间形成桥粒连接,成骨细胞伸出突起,与小肠黏膜下层贴附;15 d后细胞增殖,分泌基质,在小肠黏膜下层表面形成多层细胞组成的复层膜样结构。表明将骨髓间充质干细胞诱导成成骨细胞后与猪小肠黏膜下层复合可构建组织工程骨膜,有可能成为理想的组织工程支架材料。  相似文献   

18.
Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.  相似文献   

19.
Today, inverse treatment planning for intensity modulated proton therapy (IMPT) usually employs a constant relative biological effectiveness (RBE). In this paper, the potential clinical relevance of RBE variations for scanning techniques in IMPT is investigated, and a new strategy to include the RBE into the inverse planning process is presented. Three-dimensional RBE distributions are calculated based on a phenomenological model that describes the RBE as a function of dose, linear energy transfer (LET) and tissue type in the framework of the linear-quadratic model. This RBE model is integrated into the optimization loop of inverse planning by using a modified version of the standard quadratic objective function, where the physical dose is replaced by the biological effect. This system for "biological optimization" was implemented into a research version of the inverse planning software KonRad and allows the direct optimization of the product of RBE and physical dose. Several treatment plans for a prostate case are presented, which compare the biological with the conventional physical dose optimization for IMPT scanning techniques, in particular distal edge tracking (DET) and the full three-dimensional (3D) modulation of beam spots. Mainly due to their different LET distributions, the RBE effects for these two techniques are quite different: while the RBE distribution was more or less homogeneous in the planning target volume (PTV) for 3D modulation, considerable RBE variations within the PTV were observed for DET. These unfavorable effects could be compensated for by employing the new biological objective function, which led to a more homogeneous distribution of the product of RBE and physical dose in the PTV. The computation time increased by a factor of 2 compared to the optimization of the physical dose. In conclusion, the proposed method allows the simultaneous multifield optimization of the biological effect in a reasonable time, and is therefore well suited for studying the influence of a variable RBE in IMPT as well as for minimizing potentially adverse effects.  相似文献   

20.
于阳  赵顺 《中国组织工程研究》2012,16(36):6810-6814
背景:干细胞移植后可迁移至受损肠道参与损伤组织修复和功能重建,并可恢复肠道正常的免疫功能。 目的:综述不同来源干细胞移植治疗炎症性肠病的研究进展。 方法:应用计算机检索1990/2008 PubMed数据库相关文章,检索词为“stem cells,tissue engineering,biliary complications,intestinal disease,human intestinal tract”,并限定文章语言种类为English。同时计算机检索1990/2008万方数据库相关文章,检索词为“干细胞,组织工程,肠道疾病,人工肠道”,并限定文章语言种类为中文。最终纳入符合标准的文献24篇。 结果与结论:目前炎症性肠病的治疗在于控制活动性炎症和调节免疫紊乱,包括抗炎药物、激素、免疫抑制剂、生物治疗等多种治疗手段,但无一具有长期疗效且不良反应颇多,而近年来干细胞再生、营养、免疫调节等方面的研究给肠性疾病相关治疗带来了新希望,其多向分化潜能、免疫调节作用、营养作用使干细胞移植有望成为肠道疾病治疗的有效途径,干细胞和组织工程在肠道的研究有十分广阔的应用前景。  相似文献   

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