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151.
It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low‐dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low‐dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. 相似文献
152.
Paul M. O Neill Paul A. Stocks Sunil Sabbani Natalie L. Roberts Richard K. Amewu Emma R. Shore Ghaith Aljayyoussi I?igo Angulo-Barturén María Belén Santiago Ferrer Bazaga María Santos Martínez Brice Campo Raman Sharma Susan A. Charman Eileen Ryan Gong Chen David M. Shackleford Stephen A. Ward 《Bioorganic & medicinal chemistry》2018,26(11):2996-3005
A series of aryl carboxamide and benzylamino dispiro 1,2,4,5-tetraoxane analogues have been designed and synthesized in a short synthetic sequence from readily available starting materials. From this series of endoperoxides, molecules with in vitro IC50s versus Plasmodium falciparum (3D7) as low as 0.84?nM were identified. Based on an assessment of blood stability and in vitro microsomal stability, N205 (10a) was selected for rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models. The results indicate that the 4-benzylamino derivatives have excellent profiles with a representative of this series, N205, an excellent starting point for further lead optimization studies. 相似文献
153.
Annamaria Didona Valentina Lancellotta Claudio Zucchetti Bianca Moira Panizza Alessandro Frattegiani Martina Iacco Anna Concetta Di Pilato Simonetta Saldi Cynthia Aristei 《Reports of Practical Oncology and Radiotherapy》2018,23(3):175-182
Background
Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer.Methods and materials
Step and shoot IMRT (SS-IMRT), CDR-VMAT and VDR-VMAT plans were created for 15 HN cancer patients and were generated by Pinnacle3 TPS (v 9.8) using 6 MV photon energy. Three PTVs were defined to receive respectively prescribed doses of 66 Gy, 60 Gy and 54 Gy, in 30 fractions. Organs at risk (OARs) included the mandible, spinal cord, brain stem, parotids, salivary glands, esophagus, larynx and thyroid. SS-IMRT plans were based on 7 co-planar beams at fixed gantry angles. CDR-VMAT and VDR-VMAT plans, generated by the SmartArc module, used a 2-arc technique: one clockwise from 182° to 178° and the other one anti-clockwise from 178° to 182°. Comparison parameters included dose distribution to PTVs (Dmean, D2%, D50%, D95%, D98% and Homogeneity Index), maximum or mean doses to OARs, specific dose-volume data, the monitor units and treatment delivery times.Results
Compared with SS-IMRT, CDR-VMAT significantly reduced the maximum doses to PTV1 and PTV2 and significantly improved all PTV3 parameters, except D98% and D95%. It significantly spared parotid and submandibular glands and was associated with a lower Dmean to the larynx. Compared with VDR-VMAT, CDR-VMAT was linked to a significantly better Dmean, to the PTV3 but results were worse for the parotids, left submandibular gland, esophagus and mandible. Furthermore, the Dmean to the larynx was also worse. Compared with SS-IMRT and VDR-VMAT, CDR-VMAT was associated with higher average monitor unit values and significantly shorter average delivery times.Conclusions
CDR-VMAT appeared to be a valid option in Radiation Therapy Centers that lack a dedicated linear accelerator for volumetric arc therapy with variable dose-rates and gantry velocities, and are unwilling or unable to sanction major expenditure at present but want to adopt volumetric techniques. 相似文献154.
Hediye Acun-Bucht Ebru Tuncay Emin Darendeliler Gönül Kemikler 《Reports of Practical Oncology and Radiotherapy》2018,23(4):242-250
Aim
This study aims at examining absolute dose verification of step-and-shoot intensity modulated radiation treatment (IMRT) of prostate and brain patients by use of ion chambers of two different volumes and thermoluminescent detectors (TLD).Background
The volume of the ion chamber (IC) is very important for absolute dose verification of IMRT plans since the IC has a volume average effect. With TLD detectors absolute dose verification can be done measuring the dose of multiple points simultaneously.Materials and methods
Ion chambers FC65-P of volume 0.65 cc and semiflex of volume 0.125 cc as well as TLDs were used to measure the central axis absolute dose of IMRT quality assurance (QA) plans. The results were compared with doses calculated by a treatment planning system (TPS). The absolute doses of off axis points located 2 cm and 4 cm away from the isocenter were measured with TLDs.Results
The measurements of the 0.125 cc ion chamber were found to be closer to TPS calculations compared to the 0.65 cc ion chamber, for both patient groups. For both groups the root mean square (RMS) differences between doses of the TPS and the TLD detectors are within 3.0% for the central axis and points 2 cm away from the isocenter of each axis. Larger deviations were found at the field edges, which have steep dose gradient.Conclusions
The 0.125 cc ion chamber measures the absolute dose of the isocenter more accurately compared to the 0.65 cc chamber. TLDs have good accuracy (within 3.0%) for absolute dose measurements of in-field points. 相似文献155.
Aim
In this study, at different fields, energies and gantry angles, treatment couch and rails dose absorption ratio and treatment couch effect on surface and build-up region doses were examined.Background
It is assumed that radiation attenuation is minimal because the carbon fiber couches have low density and it is not generally accounted for during treatment planning. Consequently, it leads to a major dosimetric mistake.Materials and methods
Solid water phantom was used for relative dose measurement. The measurements were done using a Farmer ion chamber with 0.6 cc volume and a parallel plane ion chamber starting from surface with 1 mm depth intervals at 10 × 10 cm2 field, SSD 100 cm. Measurements were taken for situations where the beams intersect the couch and couch rails.Results
Dose absorption ratio of carbon fiber couch obtained at gantry angle of 180° was 1.52%, 0.69%, 0.33% and 0.25% at different field sizes for 6 MV. For 15 MV, this ratio was 0.95%, 0.27%, 0.20% and 0.05%. The absorption ratio is between 3.4% and 1.22% when the beams intersect with couch rails. The couch effect increased surface dose from 14% to 70% for 6 MV and from 11.34% to 53.03% for 15 MV.Conclusions
The results showed that the carbon fiber couch increased surface dose during posterior irradiation. Therefore, the skin-sparing effect of the high energy beams was decreased. If the effect of couch is not considered, it may cause significant differences at dose which reaches the patient and may cause tissue problems such as erythema. 相似文献156.
Chao Fang Katie K. Lee Raymond Nietupski Robert H. Bates Raquel Fernandez-Menendez Eva Maria Lopez-Roman Laura Guijarro-Lopez Yunxing Yin Zuozhong Peng James E. Gomez Stewart Fisher David Barros-Aguirre Brian K. Hubbard Michael H. Serrano-Wu Deborah T. Hung 《Bioorganic & medicinal chemistry letters》2018,28(22):3529-3533
Previous work established a coumarin scaffold as a starting point for inhibition of Mycobacterium tuberculosis (Mtb) FadD32 enzymatic activity. After further profiling of the coumarin inhibitor 4 revealed chemical instability, we discovered that a quinoline ring circumvented this instability and had the advantage of offering additional substitution vectors to further optimize. Ensuing SAR studies gave rise to quinoline-2-carboxamides with potent anti-tubercular activity. Further optimization of ADME/PK properties culminated in 21b that exhibited compelling in vivo efficacy in a mouse model of Mtb infection. 相似文献
157.
PurposeTo compare, via Monte Carlo simulations, homogeneous and non-homogenous breast models adopted for mean glandular dose (MGD) estimates in mammography vs. patient specific digital breast phantoms.MethodsWe developed a GEANT4 Monte Carlo code simulating four homogenous cylindrical breast models featured as follows: (1) semi-cylindrical section enveloped in a 5-mm adipose layer; (2) semi-elliptical section with a 4-mm thick skin; (3) semi-cylindrical section with a 1.45-mm skin layer; (4) semi-cylindrical section in a 1.45-mm skin layer and 2-mm subcutaneous adipose layer. Twenty patient specific digital breast phantoms produced from a dedicated CT scanner were assumed as reference in the comparison. We simulated two spectra produced from two anode/filter combinations. An additional digital breast phantom was produced via BreastSimulator software.ResultsWith reference to the results for patient-specific breast phantoms and for W/Al spectra, models #1 and #3 showed higher MGD values by about 1% (ranges [–33%; +28%] and [−31%; +30%], respectively), while for model #4 it was 2% lower (range [−34%; +26%]) and for model #2 –11% (range [−39%; +14%]), on average. On the other hand, for W/Rh spectra, models #1 and #4 showed lower MGD values by 2% and 1%, while for model #2 and #3 it was 14% and 8% lower, respectively (ranges [−43%; +13%] and [−41%; +21%]). The simulation with the digital breast phantom produced with BreastSimulator showed a MGD overestimation of +33%.ConclusionsThe homogeneous breast models led to maximum MGD underestimation and overestimation of 43% and 28%, respectively, when compared to patient specific breast phantoms derived from clinical CT scans. 相似文献
158.
目的:探讨高剂量生长抑素、奥美拉唑联合止血芳酸治疗急性上消化道出血合并凝血功能障碍患者的临床效果及安全性。方法:选择我院2014年1月~2017年12月收治的92例急性上消化出血合并凝血功能障碍的患者,并按随机数表法将其分为对照组和研究组。对照组予以常规剂量生长抑素、奥美拉唑联合止血芳酸治疗,研究组予以高剂量生长抑素治疗,其余奥美拉唑及止血芳酸用法同对照组。治疗后,比较两组的临床疗效、止血情况、住院时间,治疗前后血常规指标、凝血功能的变化及并发症的发生情况。结果:治疗后,研究组总有效率明显高于对照组[91.30%vs.74.42%](P0.05),而平均止血时间、再止血率及住院时间均明显短于对照组(P0.05);两组白细胞计数(WBC)、部分活化凝血酶原时间(APTT)及凝血酶原时间(PT)均较治疗前明显下降,血红蛋白(Hb)、红细胞计数(RBC)、红细胞压积(Hct)及血小板计数(PLT)均较治疗前明显上升,且研究组以上指标变化较对照组更明显(P0.05)。两组并发症的发生率比较差异均无统计学意义(P0.05)。结论:高剂量生长抑素、奥美拉唑联合止血芳酸治疗急性上消化道出血合并凝血功能障碍的效果明显优于常规剂量生长抑素、奥美拉唑联合止血芳酸治疗,其能够更有效缩短止血时间,避免再出血,且未增加药物不良反应,安全性高。 相似文献
159.
目的:探讨能谱CT优化胃肿瘤扫描辐射剂量对肾上腺嗜铬细胞瘤的诊断价值。方法:采用回顾性、抽样、随机研究方法选择2012年9月到2017年2月在我院诊治的肾上腺嗜铬细胞瘤患者59例作为研究对象,所有患者都给予常规CT扫描与能谱CT优化胃肿瘤扫描,记录和比较辐射剂量与图像质量。结果:所有病例包膜均完整,边缘清楚,肿瘤内见单发或多发低密度区,肿瘤实质区呈不均匀显著强化。常规CT与能谱CT的图像质量主观评分分别为3.89±0.45分和4.54±0.34分;常规CT与能谱CT图像的胃肿瘤CT值分别为31.94±6.39HU和35.29±5.19HU,对比都有显著差异(P0.05)。能谱CT图像的膀胱和皮下脂肪图像噪声值都显著低于常规CT图像,对比差异都有统计学意义(P0.05);能谱CT扫描的CTDIvol和DLP分别为12.39±3.48mGy和624.10±39.19mGy.cm,都显著低于常规CT扫描的14.09±4.13mGy和653.92±56.29mGy.cm(P0.05)。结论:能谱CT优化胃肿瘤扫描在肾上腺嗜铬细胞瘤诊断中的应用能有效减少辐射剂量与图像噪声,提高图像CT值与主观质量,临床应用价值更高。 相似文献
160.
以达峰时为时间单位,探讨了血管外给药-房室模型残余面积的估计问题,研究结果表明,当采样时间持续为达峰时的6倍左右,或最后采样的血药浓度小于峰浓度的20%,可保证残余面积不超过总面积的20%. 相似文献