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Accurate ionization chamber measurements of the absorbed dose to water require the correction of incomplete collection of charges created within the chamber volume. According to current dosimetry protocols such as the TRS-398 or the DIN 6800-2, incomplete charge collection is accounted for by the correction factor ks, which can be determined numerically or experimentally. The method proposed by Burns & McEwen (Phys. Med. Biol., 1998) was used in this study to determine the coefficients γ and δ used for the calculation of the correction factor ks of three ionization chambers, the SNC 125c, the SNC 600c and the SNC 350p (all Sun Nuclear Corp., Melbourne, Florida) for an absorbed dose to water range of 0.2 mGy to 1.6 mGy per pulse in pulsed photon beams. The shift of the effective point of measurement from the reference point Δz and the correction factor kr were determined for the SNC 350p according to the draft DIN 6800-2:2019-07.  相似文献   
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Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Patients and Methods

We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.

Results

Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.

Conclusions

FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.  相似文献   
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Paediatric palliative care and neurodisability are two relatively new, evolving paediatric sub-specialities that have increasing relevance in the current paediatric landscape. For many people palliative care has been synonymous with end of life care, but in paediatrics it encompasses much more and is for all children with life-threatening or life-limiting conditions, from the point of diagnosis. This breadth of focus is demonstrated well through the interface between paediatric palliative care and paediatric neurodisability. In this article we explore this unique interface through the three domains of complex symptom management, advanced care planning and end of life care. We describe the practicalities involved in all three areas and highlight the importance of early referral and the process of “dual” or “parallel” planning. We cover in more depth the specific management of the symptoms: dystonia/abnormalities of muscle tone, seizures, pain, agitation, secretions, respiratory failure, and gut failure.  相似文献   
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ABSTRACT

Purpose

New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates.  相似文献   
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LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel 18O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H218O in the presence of the enzyme, generating singly- and doubly-18O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.  相似文献   
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目的了解7~14岁学龄期儿童前房深度发育情况。探索其与屈光度数间的关系。方法收集2012年6月至2014年6月眼科门诊7~14岁儿童为研究对象,共计521例(1042只眼)。采用IOLMaster人工晶状体生物测量仪测量各屈光参数,同时测量身高、体重。散瞳后验光测得静态屈光度。分析前房深度发育情况及不同屈光状态的学龄期儿童前房深度发育情况。结果(1)随着年龄的增长,7~14岁学龄期的儿童前房深度随之增长,差异具有统计学意义(P<0.01)。同一年龄段儿童的左右眼之间的均值相近,且生长发育趋势相近(均P>0.05)。(2)随着年龄的增长,男女的前房深度均逐渐增大,同一年龄段男性前房深度大于女性前房深度(均P<0.01)。(3)儿童前房深度与身高正相关(P<0.01)。(4)前房深度随近视度数增高而增大,低度近视组与中度近视组及高度近视组差异有统计学意义(P<0.05)。结论学龄期儿童的前房深度的发育受到身高、性别及屈光度数的影响,与身高呈正相关,同一年龄段,男性前房深度大于女性。双眼前房深度发育同步。低中度近视的儿童前房深度增大。  相似文献   
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Platinum (Pt) levels were determined in various tissues and body fluids obtained from a patient who died 181 days after cisplatin overdosing. The symptoms of cisplatin overdose, however, might have almost disappeared by day 40, and the patient’s death was ascribed to the recurrence of malignant lymphoma. Determination of Pt derived from cisplatin was performed by electrospray ionization mass spectrometry (ESI-MS) using silver (Ag) as internal standard. Pt and Ag complexed with diethyldithiocarbamate (DDC) in wetashed blood, and tissue solutions were extracted into isoamyl alcohol, and then acidified with oxalic acid. By injecting an aliquot of the isoamyl alcohol layer into a mass spectrometer in the direct flow injection mode, the quantitation was performed using the signals of Pt(DDC)3 + and Ag(DDC)2 + at m/z 639 and 403, respectively. The Pt levels ranged from 25ng/ml in blood to 2050ng/g wet weight in the liver of the patient, indicating that Pt remained at high levels in tissues, even after a period as long as 181 days after cisplatin overdosing.  相似文献   
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