Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.     

Precision of dual-photon absorptiometry

Summary Precision of dual-photon absorptiometry (DPA) measurements was determined in a lumbar spine phantom and in humans. Approximately half of the measurements were made before and half after a¹⁵³gadolinium source change. The phantom was measured with different amounts of acrylic, which simulates human soft tissue, in order to evaluate the influence of body thickness on bone mineral density (BMD). Results of scans analyzed with two software versions from Lunar Radiation Corp., the widely used 08B and a prototype 08C, are compared. DPA with a cold source significantly overestimated BMD in the phantom in the presence of large amounts (more than 25 cm) of soft tissue equivalent with version 08B but not with the newer version 08C. Similiarly, in nine subjects, there was a significant decrease in spine BMD after a source change when scans were analyzed with version 08B (mean difference 0.026 g/cm²,P=0.002) but not with 08C (0.01 g/cm²,P=0.234). No systematic effect of source change on femoral BMD measurements was observed. The SD of the mean difference of two measurements of the nine subjects was 0.019 g/cm² (1.6% of the mean value) for the spine with software version 08B and 0.024 g/cm² (2.0%) with version 08C, 0.03 g/cm² (3.3%) for the femur neck, 0.03 g/cm² (4.0%) for the greater trochanter, and 0.04 g/cm² (4.9%) for Ward's triangle region of the proximal femur. The spine phanton was scanned on two other commercial bone densitometers in order to assess inter-instrument variation. Phantom measurements of L2-4 BMD made on two Lunar Radiation Corp model DP3 scanners which differed by 2% were 10 and 12% higher than those with a Norland Corp. model 2600 scanner.     

QCT骨密度测量的质量控制及意义

目的目前国内对QCT骨密度测量的质量控制研究较少，本文介绍了QCT骨密度测量的准确度、精密度试验方法和意义。方法使用东芝CT机自带体模和软件为测量工具，测量四川大学华西骨质疏松研究中心等研制的QCT骨体模（称四川体模）的骨密度值。四川体模固定于15cm深的水浴中模拟人体腰椎，东芝体模置于水浴容器与扫描床面之间，按照人腰椎QCT骨密度测量相同的条件和方法进行操作，每日1次对测量体模连续测量25日，计算SD和CV，分别以25次测量125d25次测量／1d基线作3m的shewhart图。结果测量四川体模从小到大三管骨密度分别的准确度误差为-60．4％、-39．1％和-13．6％，其分别的校正系数为2．69、1．64、1．15，相关系数为0．9966，回归方程Y=35．6＋0．958X（X为测量骨密度，Y为校正后骨密度）。本型QCT机骨密度测量的25次／1d及25次，25d精密度误差分别为1．25～5．54％和1．98～7．87％。25次125d的精密度误差要大于25次，d，显示机器一日内精密度误差变化小，随时间延长其变化增大。以25次125d的结果为基线绘制的shewhart图优于25次/d。结论一切QCT骨密度测量都应进行质量控制，准确度必须予以校正，精密度试验应在此基础上进行。这样结果才真实、科学、可靠并具有可比性。     

Influence of Bone Quality on Precision of Calcaneal Ultrasonometry

This study was designed to determine the changes in precision of the ultrasound parameters speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) as a function of bone quality. The instrument used in this investigation was the LUNAR Achilles. Of the 608 female patients who had paired measurements with repositioning, 200 had t scores ≥−1 and 408 had t scores ≤−2.5, thus rendering a normal and a grossly abnormal group for comparison of precision results. It was found that the median precision error (CV%) for BUA was 1.99% for normal bone and 1.44% for abnormal bone (P= 0.02). No significant difference was obtained between median precision errors in normal and abnormal bone for the parameters SOS and SI, which were 0.23% and 0.19%, and 2.15% and 2.02%, respectively. In the interquartile range, the mean precision errors for SOS and BUA were significantly different in normal and abnormal bone: SOS was 0.25% and 0.21%, respectively, and BUA was 2.31% and 1.85%, respectively. No significant change was registered for SI. Precision error appears to decrease slightly at lower values for calcaneal variables. Received: 21 August 1996 / Accepted: 5 March 1997     

ABX MICROS 60-OT型血细胞分析仪的性能评价

目的　评价ABXMICROS 60 -OT(以下简称ABX -60 )血细胞分析仪的分析性能 ,推广临床应用。　方法　用EDTA -K2静脉抗凝血标本连续测定和每天随机插入常规标本测定及稀释法分别测定ABX -60的精密度 ,携带污染率和线性性能 ,并与COULTERJT -IR结果进行比较。　结果　ABX -60的批内和批间精密度的变异系数均 <5 ,病人标本测定携带污染率均≤ 0 4% ,对白细胞、红细胞、血红蛋白、血小板测定结果与COULTERJT -IR比较有良好的相关性。　结论　ABX -60是一种较为理想的中档血细胞分析仪 ,适合中心型单位使用。     

Three-dimensional recording of the human face with a 3D laser scanner.

Three-dimensional recording of the surface of the human body or of certain anatomical areas has gained an ever increasing importance in recent years. When recording living surfaces, such as the human face, not only has a varying degree of surface complexity to be accounted for, but also a variety of other factors, such as motion artefacts. It is of importance to establish standards for the recording procedure, which will optimise results and allow for better comparison and validation. In the study presented here, the faces of five male test persons were scanned in different experimental settings using non-contact 3D digitisers, type Minolta Vivid 910). Among others, the influence of the number of scanners used, the angle of recording, the head position of the test person, the impact of the examiner and of examination time on accuracy and precision of the virtual face models generated from the scanner data with specialised software were investigated. Computed data derived from the virtual models were compared to corresponding reference measurements carried out manually between defined landmarks on the test persons' faces. We describe experimental conditions that were of benefit in optimising the quality of scanner recording and the reliability of three-dimensional surface imaging. However, almost 50% of distances between landmarks derived from the virtual models deviated more than 2mm from the reference of manual measurements on the volunteers' faces.     

Reach to grasp: the natural response to perturbation of object size

This study assessed the reach to grasp movement and its adaptive response to a perturbation of object size. In blocked trials, subjects (n = 12) were instructed to reach 35 cm to grasp and lift a small- (0.7 cm) or large-diameter (8 cm) cylinder. Under an unconstrained condition (condition 1), no instructions as to the type of grasp to adopt were given. Subjects thus naturally used a precision grip (PG) for the small cylinder and whole hand prehension (WHP) for the large cylinder. Under condition 2, subjects were instructed to utilize a PG for grasps of both the large and small cylinders. For condition 3, the instruction was to use WHP irrespective of object size. Kinematic organization was determined with analysis of the recordings of active markers placed on the wrist, thumb, and three fingers. For condition 1 the results showed a temporal arrangement of both components (transport and manipulation) which differed from that of conditions 2 and 3. In perturbed trials, illumination shifted from the small to large cylinder or vice versa. With condition 1, subjects automatically switched from one grasp to another with no or little increase of movement duration. This was generally achieved by an earlier temporal setting of peak wrist deceleration. For conditions 2 and 3, where a change of aperture was required, movement duration was prolonged without adaptation of earlier transport component parameters. It is concluded that the adaptive responses to a change of distal patterning also affect the organization of the proximal component. Assessment of grasps constrained by instructions may lead to interpretations of central control of the reach to grasp movement which differ from those obtained by assessing more natural prehensile patterns.     

A comparison of prehension force control in young and elderly individuals

Age-related changes were investigated in the control of precision grip force during the lifting and holding of objects with slippery (silk) and nonslippery (sandpaper) surface textures. Two groups of active elderly adults comprising individuals aged 69–79 years (n = 10), and 80–93 years (n = 10) together with a group of young adults aged 18–32 years (n = 10) participated in the study. Each subject lifted a free weight (3N) during which time gripping and lifting forces were monitored. The elderly subjects, especially the individuals in the 81–93 year group, had a larger number of fluctuations in the grip force rate curve and longer force application time than the younger subjects during lifting. The effect of prior experience with one surface on the following different surface was more pronounced in the younger subjects than the elderly subjects. These results suggest a decline in programmed force production capacity with increased age. The fingers of the elderly subjects were more slippery and they exhibited a greater safety margin of the grip force while holding the object than the younger adults. The overall results demonstrated that precision grip force control capacity declines with advancing age. It is suggested that this decline is due mainly to age-related changes in skin properties, and cutaneous sensibility functions, and in part to central nervous system function.