BACKGROUND & AIMS: :Cupriavidus necator JMP134(pJP4) harbors a catabolic plasmid, pJP4, which confers the ability to grow on chloroaromatic compounds. Repeated growth on 3-chlorobenzoate (3-CB) results in selection of a recombinant strain, which degrades 3-CB better but no longer grows on 2,4-dichlorophenoxyacetate (2,4-D). We have previously proposed that this phenotype is due to a double homologous recombination event between inverted repeats of the multicopies of this plasmid within the cell. One recombinant form of this plasmid (pJP4-F3) explains this phenotype, since it harbors two copies of the chlorocatechol degradation tfd gene clusters, which are essential to grow on 3-CB, but has lost the tfdA gene, encoding the first step in degradation of 2,4-D. The other recombinant plasmid (pJP4-FM) should harbor two copies of the tfdA gene but no copies of the tfd gene clusters. A molecular analysis using a multiplex PCR approach to distinguish the wild-type plasmid pJP4 from its two recombinant forms, was carried out. Expected PCR products confirming this recombination model were found and sequenced. Few recombinant plasmid forms in cultures grown in several carbon sources were detected. Kinetic studies indicated that cells containing the recombinant plasmid pJP4-FM were not selectable by sole carbon source growth pressure, whereas those cells harboring recombinant plasmid pJP4-F3 were selected upon growth on 3-CB. After 12 days of repeated growth on 3-CB, the complete plasmid population in C. necator JMP134 apparently corresponds to this form. However, wild-type plasmid forms could be recovered after growing this culture on 2,4-D, indicating that different plasmid forms can be found in C. necator JMP134 at the population level.

背景与目标： ：Cupriavidus necator JMP134（pJP4）带有分解代谢质粒pJP4，可赋予其在氯代芳香族化合物上生长的能力。在3-氯苯甲酸酯（3-CB）上重复生长导致选择了重组菌株，该菌株可更好地降解3-CB，但不再在2,4-二氯苯氧基乙酸酯（2,4-D）上生长。我们先前已经提出，该表型是由于该质粒在细胞内多拷贝的反向重复之间的双重同源重组事件引起的。该质粒的一种重组形式（pJP4-F3）解释了此表型，因为它具有两个副本的氯邻苯二酚降解tfd基因簇，这对于在3-CB上生长是必不可少的，但已经丢失了tfdA基因，编码了第一步。 2，4-D的降解。另一个重组质粒（pJP4-FM）应该包含tfdA基因的两个副本，但不包含tfd基因簇的副本。使用多重PCR方法进行了分子分析，以将野生型质粒pJP4与它的两种重组形式区分开。找到并证实了确认该重组模型的预期PCR产物。在几种碳源中培养的培养物中几乎没有检测到重组质粒形式。动力学研究表明，含有重组质粒pJP4-FM的细胞不能通过唯一的碳源生长压力进行选择，而带有重组质粒pJP4-F3的细胞则是在3-CB上生长时选择的。在3-CB上重复生长12天后，C。necator JMP134中的完整质粒群体显然对应于这种形式。但是，在2,4-D上培养此培养物后，可以回收野生型质粒形式，表明在种群水平上，在C. necator JMP134中可以找到不同的质粒形式。

BACKGROUND & AIMS: :The yeast S. cerevisiae is a central model organism in eukaryotic cell studies and a major component in many food and biotechnological industrial processes. However, the wide knowledge regarding genetics and molecular biology of S. cerevisiae is based on an extremely narrow range of strains. Studies of natural populations of S. cerevisiae, not associated with human activities or industrial fermentation environments, are very few. We isolated a panel of S. cerevisiae strains from a natural microsite, "Evolution Canyon" at Mount Carmel, Israel, and studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed high allelic diversity and variation in ploidy level across the panel, from diploids to tetraploids, confirmed by flow cytometry. No significant differences were found in the level of microsatellite variation between strains derived from the major localities or microniches, whereas strains of different ploidy showed low similarity in allele content. Maximum genetic diversity was observed among diploids and minimum among triploids. Phylogenetic analysis revealed clonal, rather than sexual, structure of the triploid and tetraploid subpopulations. Viability tests in tetrad analysis also suggest that clonal reproduction may predominate in the polyploid subpopulations.

背景与目标： ：酿酒酵母是真核细胞研究中的中心模型生物，在许多食品和生物技术工业过程中都是主要成分。但是，关于酿酒酵母的遗传学和分子生物学的广泛知识是基于非常狭窄的菌株。与人类活动或工业发酵环境无关的酿酒酵母自然种群研究很少。我们从以色列卡梅尔山的天然微型站点“进化峡谷”中分离出一组酿酒酵母菌株，并研究了它们的基因组生物多样性。对19个微卫星基因座的分析显示，从二倍体到四倍体，整个等位基因组中的高等位基因多样性和倍性水平存在差异，这已通过流式细胞仪进行了确认。在来自主要地区或微生态位的菌株之间，微卫星变异水平没有发现显着差异，而具有不同倍性的菌株在等位基因含量上的相似性很低。在二倍体中观察到最大的遗传多样性，在三倍体中观察到最小的遗传多样性。系统发育分析显示三倍体和四倍体亚群的克隆结构，而不是有性结构。四元分析中的生存力测试还表明，在多倍体亚群中克隆繁殖可能占主导地位。

BACKGROUND & AIMS: BACKGROUND:Little is known about the impact of the recent varicella vaccine shortage. To assess the temporal trend in varicella vaccine administration before 18 and 24 months of age in a community cohort of children prior to, during and after the recent varicella vaccine shortage. And to compare the temporal trends in varicella vaccinations to trends of an older, more widely accepted vaccine, the MMR. METHODS:Community population-based birth cohorts were identified who were eligible for the varicella vaccination before, during and after the 2001 to 2002 varicella vaccine shortage. Only children (84% of all) who remained in the community through their second birthday were included. For each child in the cohort, the medical records and immunization registry records from both medical facilities in the county were reviewed to identify the dates and sites for all varicella immunizations given. In addition to varicella immunizations, the dates of all MMR vaccinations were recorded. Additional data abstracted included the child's birth date, gender and dates of any recognized cases of chickenpox up through age 24 months. RESULTS:Of the 2,512 children in the birth cohorts, 50.8% were boys. In the three cohorts combined, 81.1% of the boys and 79.3% of the girls (p = 0.30) received the varicella vaccine by age 24 months. The pre-shortage community rate of varicella immunization was 79.7% by 24 months of age. During the varicella vaccine shortage, the rate of varicella immunization by 24 months fell to 77.2%. Only 6 additional children received a "catch-up" immunization by 36 months of age. In the post shortage period the community 24-month immunization rate rebounded to a level higher than the pre-shortage rate 84.0%. During the almost three years of observation, the MMR immunization rate by age 24 months was constant (87%). CONCLUSION:The varicella shortage was associated with an immediate drop in the 24-month varicella immunizations rate but rebounded quickly to above pre-shortage rates. In this community the only long term impact of the varicella vaccine shortage may be on the small number of children who still had not received catch-up varicella immunizations by 36 months of age.

背景与目标： 背景：对最近水痘疫苗短缺的影响知之甚少。在最近的水痘疫苗短缺之前，期间和之后，评估社区队列中儿童在18和24个月大之前接种水痘疫苗的时间趋势。并将水痘疫苗接种的时间趋势与较旧的，被更广泛接受的疫苗MMR的趋势进行比较。
方法：确定2001年至2002年水痘疫苗短缺之前，之中和之后有水痘疫苗接种资格的以社区人群为基础的出生队列。仅包括直到第二个生日仍留在社区中的儿童（占总数的84％）。对于该队列中的每个孩子，都检查了县内两个医疗机构的病历和免疫登记记录，以确定所有水痘疫苗接种的日期和地点。除水痘疫苗接种外，还记录了所有MMR疫苗接种的日期。提取的其他数据包括孩子的出生日期，性别以及直至24个月的任何公认的水痘病例的日期。
结果：在出生队列的2,512名儿童中，男孩占50.8％。在这三个队列中，到24个月大时，有81.1％的男孩和79.3％的女孩（p = 0.30）接受了水痘疫苗。到24个月大时，水痘疫苗的短缺前社区接种率为79.7％。在水痘疫苗短缺期间，水痘疫苗的免疫率在24个月内下降到77.2％。到36个月大时，仅再有6名儿童接受了“追赶”免疫。在短缺后时期，社区24个月的免疫接种率反弹到高于短缺前84.0％的水平。在将近三年的观察中，到24个月大时的MMR免疫率是恒定的（87％）。
结论：水痘短缺与24个月水痘疫苗接种率立即下降有关，但迅速反弹至短缺前水平。在这个社区中，水痘疫苗短缺的唯一长期影响可能是对仍在36个月大时仍未接受追赶水痘免疫接种的少数儿童。

BACKGROUND & AIMS: OBJECTIVE:To identify reasons why rural general practitioners (GPs) treat a large proportion of patients with a primary psychiatric diagnosis in general beds of their local hospitals, and the barriers encountered when providing this treatment. DESIGN:A postal questionnaire was developed and distributed to a sample of rural GPs, asking about the treatment of patients with an acute mental illness in their local hospital. RESULTS:The majority of GPs agreed that they treat the acutely mentally ill in general beds of their local hospital due to lack of availability of, and inability to gain access to, mental health beds in the larger centres; and also to enable ongoing family involvement and continuity of care. Distance factors were identified as least significant. Barriers to providing care to this group of patients included a perceived lack of support by consultant psychiatrists, confidentiality issues, lack of community mental health workers to provide assistance, aggression levels of patients, inappropriate local hospital setting, and lack of confidence of GPs and general hospital nursing staff. CONCLUSION:Addressing these barriers is necessary if rural Australians are to receive a quality of care that is equal to that received by those located in metropolitan Australia. Continuing research in this area is crucial.

背景与目标： 目的：查明农村全科医生（GPs）在其当地医院的普通病床中治疗大部分患有原发性精神病诊断的患者的原因，以及提供这种治疗时遇到的障碍。
设计：开发了一份邮政调查表，并将其分发给农村全科医生的样本，询问在当地医院治疗患有急性精神疾病的患者的情况。
结果：大多数全科医生都同意，由于在较大的中心缺乏精神病床，并且无法获得精神病床，他们在当地医院的普通病床中治疗严重的精神疾病；并使家庭不断参与并获得连续护理。距离因素被确定为最不重要的。向此类患者提供护理的障碍包括：咨询精神病医生缺乏支持，机密性问题，缺乏社区精神卫生工作者提供援助，患者的攻击性，当地医院的环境不适当以及全科医生和普通医生的信心不足医院护理人员。
结论：如果要使澳大利亚农村人口获得与澳大利亚大都市居民相同的医疗质量，则必须解决这些障碍。在这一领域的持续研究至关重要。

BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

背景与目标： ：在本项初步研究中，对希腊北部农村地区服务水平低下的346名妇女进行了基于宫颈癌阴道自我采样方法的HPV筛查的可行性的测试。这些妇女提供了自己收集的宫颈阴道样本以及研究问卷。在进行分子测试后，使用cobas®HPV测试，将Roche®，HPV阳性女性进行阴道镜检查，并在发现异常后进行活检和治疗。参与率为100％。定期进行巴氏试验检查的报道为17.1％。在hrHPV测试中，有11.9％呈阳性，阴道镜检查/活检显示有2例CIN3病例。不遵守是没有参加会议的最普遍原因。大多数妇女在自我抽样中报告没有困难和不舒服（分别为77.6％和82.4％）。他们将选择自采样而不是临床医生采样（86.2％），并且如果可以使用自采样，他们将更定期地进行自我测试（92.3％）。总之，对于基于HPV的筛查，自我抽样是可行的并且被广泛接受，并且可以扩大服务不足地区的人口覆盖率，有助于成功进行预防。

BACKGROUND & AIMS: :The possible combined effects of caffeine and exercise on blood pressure (BP) regulation were examined in 34 healthy, normotensive (BP less than 135/85 mm Hg) young men (mean age 27 +/- 3 years) in a placebo-controlled, double-blind crossover design. Each subject performed submaximal and symptom-limited maximal supine bicycle exercise 1 hour apart after ingestion of placebo or caffeine (3.3 mg/kg). Heart rate, BP, cardiac output and peripheral vascular resistance were compared for placebo and caffeine days. Postdrug baseline showed that caffeine increased systolic and diastolic BP and peripheral vascular resistance (p less than 0.001 for each) and decreased heart rate (p less than 0.01) but did not change stroke volume or cardiac output. BP and vascular resistance effects of caffeine remained during submaximal exercise resulting in an additive increase in BP while negative chronotropic effects of caffeine disappeared. At maximal exercise substantially more subjects (15 on caffeine vs 7 on placebo, p less than 0.02) had systolic BP greater than or equal to 230 mm Hg and/or greater than or equal to 100 mm Hg for diastolic BP. Plasma norepinephrine levels were not significantly different across days, but epinephrine was higher at maximal exercise and cortisol was increased post-drug and throughout maximal exercise on caffeine days. Data indicate that caffeine increases BP additively during submaximal exercise and may cause excessive BP responses at maximal exercise for some individuals. The pressor effects of caffeine appear to be due to increasing vascular resistance rather than cardiac output.

背景与目标： ：在安慰剂对照的34名健康，血压正常（血压低于135/85 mm Hg的年轻人）（平均年龄27 /-3岁）中，研究了咖啡因和运动对血压（BP）调节的可能联合作用，双盲交叉设计。服用安慰剂或咖啡因（3.3 mg / kg）后，每位受试者间隔1小时进行次最大和症状受限的最大仰卧自行车运动。比较安慰剂和咖啡因天的心率，血压，心输出量和外周血管阻力。药物后基线显示，咖啡因可增加收缩压和舒张压以及周围血管阻力（每个P值均小于0.001）和降低心率（P值均小于0.01），但并未改变中风量或心输出量。在次最大运动量下，咖啡因的血压和血管阻力作用仍然存在，从而导致血压增加，而咖啡因的负变时效作用消失了。在最大程度的运动中，更多的受试者（咖啡因为15，安慰剂为7，p小于0.02）的收缩压大于或等于230 mm Hg和/或舒张压大于或等于100 mm Hg。血浆去甲肾上腺素水平在各天之间无显着差异，但在最大运动量时，肾上腺素较高，而在咖啡因日后和整个最大运动量中，皮质醇增加。数据表明，咖啡因在次最大运动量时会增加BP，并且可能对某些个体在最大运动量时导致过度的BP反应。咖啡因的升压作用似乎是由于血管阻力增加而非心输出量增加所致。

BACKGROUND & AIMS: INTRODUCTION:Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS:BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS:Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION:Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

背景与目标： 简介：乳腺癌（BC）治疗后的疲劳很普遍，但了解甚少。我们根据放疗（局部或局部），激素治疗（HT）和化学疗法（CT）的程度，检查了放疗（RT）后第一年的疲劳水平。还探讨了合并症的影响。此外，我们将一般人群（GenPop）数据的患者的疲劳水平进行了比较。
材料与方法：招募了在挪威特隆赫姆的圣奥拉夫斯医院接受手术后放疗的BC患者（n = 250）。疲劳通过EORTC QLQ-C30疲劳分量表进行测量，范围为0至100，RT前（基线），RT后以及3、6和12个月。在基线记录临床和治疗相关因素。 GenPop数据可从以前的调查中获得（n = 652）。应用线性混合模型和协方差分析。
结果：依从性从87％到98％不等。基线时，BC患者的疲劳平均值（SD）为26.8（23.4）。在放疗期间该水平升高（平均变化8.3，95％CI 5.5-11.1），但此后下降，并且在随后的时间点与治疗前水平无显着差异。在年龄校正的分析中，局部RT比局部RT引起的整体疲劳更多（平均差异6.6，95％CI 1.2-12.0），但在校正CT和HT时，关联性减弱并且没有统计学意义。 CT和HT观察到相似的模式。 CT的疲劳过程明显不同（p <0.001，相互作用测试）。在基线时，有CT的患者的疲劳水平高于没有CT的患者，但是在随后的时间点，相似的水平也很明显，表明CT的暂时不良反应。与其他因素无关，合并症与疲劳程度增加显着相关（平均差异8.1，95％CI 2.2-14.1）。 BC患者没有比GenPop明显疲劳，除了RT结束后立即缓解，然后才出现在没有合并症的患者中（平均35.9 vs. 25.8，p <0.001）。
结论：合并症似乎是比癌症治疗更为重要的疲劳程度决定因素。

BACKGROUND & AIMS: :The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

背景与目标： ：铁缺乏性贫血（IDA）和骨质疏松症之间的因果关系尚未建立。因此，当前的纵向研究通过分析全国范围内大量的基于人群的样本，确定了IDA作为骨质疏松症危险因素的作用。在1998年至2012年的1,000,000个随机样本中进行抽样。台湾国家健康保险研究数据库比较了IDA患者（病例组（n = 35,751））和无IDA患者（对照组（n = 178,755））。年龄小于20岁且在IDA诊断之前已存在骨质疏松症的患者被排除在外。每名IDA患者的年龄和性别均与5名没有IDA的患者相匹配。通过血液测试结果和X射线骨密度测定进一步证实了IDA和骨质疏松的诊断（使用ICD-9CM编码），以确保诊断的准确性。与没有IDA的患者相比，IDA患者的骨质疏松症发生率更高（2.27％对1.32％，p <0.001）。 Cox比例风险分析显示，骨质疏松症的风险明显高于对照组（风险比（HR）= 1.74； 95％CI = 1.61-1.88），并且在调整协变量后（调整后HR = 1.81； 95％CI = 1.67-1.97）。与没有IDA的个体相比，接受静脉铁素治疗的IDA患骨质疏松症的风险更高（校正后的HR = 2.21； 95％CI = 1.85-2.63）。相反，接受输血的IDA患者的骨质疏松风险降低（校正后的HR = 1.47； 95％CI = 1.20-1.80）。作为预测因素，先前的IDA是骨质疏松症发展的重要且独立的危险因素。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population. METHODS:Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and gastrointestinal stromal tumors) as a single agent or in combination with chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM®. RESULTS:The PKs of olaratumab were best described by a two-compartment PK model with linear clearance (CL). Patient body weight was found to have a significant effect on both CL and central volume of distribution (V 1), whereas tumor size significantly affected CL. A small subset of patients developed treatment-emergent anti-drug antibodies (TE-ADAs); however, TE-ADAs did not have any effect on CL or PK time course of olaratumab. There was no difference in the PKs of olaratumab between patients who received olaratumab as a single agent or in combination with chemotherapy. CONCLUSION:The PKs of olaratumab were best described by a model with linear disposition. Patient body weight and tumor size were found to be significant covariates. The PKs of olaratumab were not affected by immunogenicity or chemotherapeutic agents.

背景与目标： 背景与目的：Olaratumab是一种重组人单克隆抗体，可与血小板衍生的生长因子受体-α（PDGFRα）结合。在一项随机的II期研究中，奥拉单抗加阿霉素达到了无进展生存的预定主要终点，与晚期或转移性软组织肉瘤（STS）患者相比，阿霉素的总生存率有了显着提高。在这项研究中，我们表征了olaratumab在癌症患者人群中的药代动力学（PKs）。
方法：奥拉单抗在四项II期研究（非小细胞肺癌，多形性胶质母细胞瘤，STS和胃肠道间质瘤患者）中以15或20 mg / kg的浓度进行了单药或联合化疗的测试。进行PK采样以测量olaratumab血清水平。使用NONMEM®通过非线性混合效应建模技术分析PK数据。
结果：用具有线性清除率（CL）的两室PK模型可以最好地描述olaratumab的PK。发现患者体重对CL和中心分布体积（V 1）均具有显着影响，而肿瘤大小显着影响CL。一小部分患者发展了治疗性抗药物抗体（TE-ADAs）；但是，TE-ADAs对olaratumab的CL或PK时间进程没有任何影响。在单药或联合化疗的情况下，接受olaratumab治疗的患者中olaratumab的PKs没有差异。
结论：用线性处置模型可以最好地描述olaratumab的PKs。发现患者体重和肿瘤大小是显着的协变量。 Olaratumab的PKs不受免疫原性或化学治疗剂的影响。