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Temperature and pH-dependent stability of fentanyl analogs: Degradation pathways and potential biomarkers 芬太尼类似物随温度和 pH 值变化的稳定性:降解途径和潜在生物标记物
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-12 DOI: 10.1111/1556-4029.15578
Madison Schackmuth BS, Sarah Kerrigan PhD

The collection, storage, and transport of samples prior to and during analysis is of utmost importance, especially for highly potent analogs that may not be present in high concentrations and are susceptible to pH or thermally mediated degradation. An accelerated stability study was performed on 17 fentanyl analogs (fentalogs) over a wide range of pH (2–10) and temperature (20–60°C) conditions over 24 h. Dilute aqueous systems were used to investigate temperature and pH-dependent kinetics using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Liquid chromatography-quadrupole/time-of-flight-mass spectrometry (LC-Q/TOF–MS) was used for structural elucidation of degradants. With the exception of remifentanil, all fentalogs evaluated were stable at pH 6 or lower. Fentalogs were generally unstable in strongly alkaline environments and at elevated temperatures. Remifentanil was the least stable drug and N-dealkylated fentalogs were the most stable. Fentanyl degraded to acetylfentanyl, norfentanyl, fentanyl N-oxide, and 1-phenethylpyridinium salt (1-PEP). A total of 26 unique breakdown products were observed for 15 of the fentanyl derivatives studied. Common degradation pathways involved N-dealkylation, oxidation of the piperidine nitrogen, and β-elimination of N-phenylpropanamide followed by oxidation/dehydration of the piperidine ring. Ester and amide hydrolysis, demethylation at the propanamide, and O-demethylation were observed for selected fentalogs only. The potential for analyte loss should be considered during the pre-analytical phase (i.e., shipping and transport) where environmental conditions may not be controlled, as well as during the analysis itself.

分析前和分析过程中的样品收集、储存和运输至关重要,尤其是对于可能存在浓度不高且易受 pH 值或热介导降解影响的强效类似物。研究人员对 17 种芬太尼类似物(fentalogs)进行了加速稳定性研究,研究在广泛的 pH 值(2-10)和温度(20-60°C)条件下持续 24 小时。液相色谱-四极杆/飞行时间质谱(LC-Q/TOF-MS)用于降解剂的结构鉴定。除瑞芬太尼外,所有接受评估的芬太尼类药物在 pH 值为 6 或更低的条件下都很稳定。在强碱性环境和高温条件下,芬太尼一般都不稳定。瑞芬太尼是最不稳定的药物,而 N-脱烷基芬太尼则是最稳定的药物。芬太尼降解为乙酰芬太尼、诺芬太尼、芬太尼 N-氧化物和 1-苯乙基吡啶鎓盐(1-PEP)。在所研究的 15 种芬太尼衍生物中,共观察到 26 种独特的分解产物。常见的降解途径包括 N-脱烷基化、哌啶氮的氧化和 N-苯基丙酰胺的β-消除,然后是哌啶环的氧化/脱水。仅在某些芬太尼类化合物中观察到酯和酰胺水解、丙酰胺脱甲基和 O-脱甲基现象。在分析前阶段(即装运和运输),环境条件可能无法控制,在分析过程中也应考虑分析物流失的可能性。
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引用次数: 0
Osteon shape variation in the femoral diaphysis: A geometric-morphometric approach on human cortical bone microstructure in an elderly sample 股骨干骺端的骨形态变化:老年样本人体皮质骨微观结构的几何形态计量学方法。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-11 DOI: 10.1111/1556-4029.15584
Luisa Leiss MSc, Tshegofatso Ramphaleng PhD, Nicholas Bacci PhD, Tobias M. R. Houlton PhD, Julieta G. García-Donas PhD

Geometric morphometrics (GMM) have been applied to understand morphological variation in biological structures. However, research studying cortical bone through geometric histomorphometrics (GHMM) is scarce. This research aims to develop a landmark-based GHMM protocol to depict osteonal shape variation in the femoral diaphysis, exploring the role of age and biomechanics in bone microstructure. Proximal, midshaft, and distal anatomical segments from the femoral diaphysis of six individuals were assessed, with 864 secondary intact osteons from eight periosteal sampling areas being manually landmarked. Observer error was tested using Procrustes ANOVA. Average osteonal shape and anatomical segment-specific variation were explored using principal component analysis. Osteon shape differences between segments were examined using canonical variate analysis (CVA). Sex differences were assessed through Procrustes ANOVA and discriminant function analysis (DFA). The impact of osteonal size on osteonal shape was investigated. High repeatability and reproducibility in osteon shape landmarking were reported. The average osteon shape captured was an elliptical structure, with PC1 reflecting more circular osteons. Significant differences in osteon shape were observed between proximal and distal segments according to CVA. Osteon shape differed between males and females, with DFA showing 52% cross-validation accuracies. No effect of size on shape was reported. Osteonal shape variation observed in this study might be explained by the elderly nature of the sample as well as biomechanical and physiological mechanisms playing different roles along the femoral diaphysis. Although a larger sample is needed to corroborate these findings, this study contributes to the best of our knowledge on human microanatomy, proposing a novel GHMM approach.

几何形态计量学(GMM)已被用于了解生物结构的形态变化。然而,通过几何组织形态计量学(GHMM)研究皮质骨的研究却很少。本研究旨在开发一种基于地标的 GHMM 方案,以描述股骨头干骺端的骨形态变化,探索年龄和生物力学在骨微结构中的作用。研究人员评估了六个人股骨干骺端的近端、中轴和远端解剖节段,并对八个骨膜取样区的 864 个次要完整骨块进行了人工地标测量。观察者误差采用 Procrustes 方差分析进行检验。采用主成分分析法探讨了平均骨块形状和解剖节段特异性变化。采用典型变量分析法(CVA)检验不同节段之间的骨形态差异。性别差异通过 Procrustes ANOVA 和判别函数分析(DFA)进行评估。还研究了骨质大小对骨质形状的影响。据报道,骨小梁形状标记的重复性和再现性都很高。捕获的骨小梁平均形状为椭圆形结构,PC1反映了更多的圆形骨小梁。根据 CVA 的不同,近端和远端节段的骨块形状存在显著差异。骨块形状在男性和女性之间存在差异,DFA 的交叉验证准确率为 52%。没有关于大小对形状的影响的报道。本研究中观察到的骨质形状差异可能是由于样本为老年人,以及生物力学和生理机制在股骨干骺端发挥了不同的作用。虽然需要更多的样本来证实这些发现,但这项研究为我们了解人类显微解剖学做出了最大贡献,并提出了一种新颖的 GHMM 方法。
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引用次数: 0
Phytocannabinoid profile and potency of cannabis resin (hashish) of northwest Himalayas of India 印度喜马拉雅山西北部大麻树脂(印度大麻脂)的植物大麻素特征和功效。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-11 DOI: 10.1111/1556-4029.15583
Jyotsnessh Chauhan MSc, Binaya Kumar Bastia MD, Kanchan Kohli PhD, Babulal Chaudhary MD, Gaurav Chikara MD, Annie Gupta PhD, Ankit Kumar MD

Cannabis is one of the most consumed illicit drugs and the potency of cannabis products is of note due to health-related concerns. Hand-rubbed hashish is the ancient technique of extracting psychoactive resin from cannabis plants and is practiced in the Indian Himalayas. This study establishes the cannabinoid profile and potency of hand-rubbed hashish collected from 20 regions of the northwest Himalayas. Fifty-eight hashish samples were analyzed using a validated high-performance liquid chromatography-diode array detection (HPLC-DAD) method. Ten cannabinoids were quantified including acidic (THCA & CBDA), and neutral compounds (CBDV, THCV, CBD, CBG, CBN, Δ9-THC, Δ8-THC, and CBC). The mean concentration (w/w%) of Δ9-THC is 26%; THCA is 15% and THCTotal is 40% is observed in the studied hashish samples. The majority (70%) of the hashish samples were categorized in chemotype I with the THC:CBD:CBN ratio of 91:3:4, and the remaining 30% were categorized under chemotype II with the ratio of 76:15:8. Diverse qualities of hashish are produced in the studied regions as per the seed, plant selection, and skills of manual rubbing, which results in potency variations. The average difference between the least and highest potent hand-rubbed hashish of a region is 27 w/w% (THCTotal). The other studied non-psychoactive cannabinoids have a mean w/w% of <5%, followed by 6% of CBDA. It is concluded that the cultivated and wild cannabis fields in the northwest Himalayas belong to the drug-type cannabis subspecies. Hand-rubbed hashish holds traditional significance and impacts the current policies of legislation.

大麻是消耗量最大的非法药物之一,由于健康方面的原因,大麻产品的功效值得关注。手搓印度大麻是一种从大麻植物中提取精神活性树脂的古老技术,在印度喜马拉雅山地区盛行。本研究确定了从喜马拉雅山西北部 20 个地区采集的手搓印度大麻的大麻素特征和效力。采用经过验证的高效液相色谱-二极管阵列检测法(HPLC-DAD)分析了 58 份印度大麻样本。对十种大麻素进行了量化,包括酸性(THCA 和 CBDA)和中性化合物(CBDA、THCV、CBD、CBG、CBN、Δ9-THC、Δ8-THC 和 CBC)。在所研究的印度大麻样本中,Δ9-四氢大麻酚的平均浓度(w/w%)为 26%,四氢大麻酚为 15%,四氢大麻总酚为 40%。大部分(70%)印度大麻样本属于化学类型 I,四氢大麻酚:CBD:CBN 的比例为 91:3:4,其余 30% 属于化学类型 II,比例为 76:15:8。根据种子、植物选择和手工揉搓技巧的不同,所研究地区生产的印度大麻品质各异,这导致了大麻效力的差异。一个地区手工揉搓的印度大麻药效最低和最高的平均差异为 27 w/w% (THCTotal)。所研究的其他非精神活性大麻素的平均重量百分比为
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引用次数: 0
Letter to the editor—Answering the call for a scientific consensus regarding the application of retrograde extrapolation to determine blood alcohol content in DUI cases 致编辑的信--回应就应用逆推法确定酒驾案件中血液酒精含量达成科学共识的呼吁。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-11 DOI: 10.1111/1556-4029.15582
Marc A. LeBeau PhD, F-ABFT, Jennifer F. Limoges MS
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引用次数: 0
Pollen identification of three notorious illicit drug plants and its potential applications in forensic practice 三种臭名昭著的非法毒品植物的花粉鉴定及其在法医实践中的潜在应用。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-10 DOI: 10.1111/1556-4029.15581
Yi-Ming Wu, Li-Li Lu PhD, Gan Xie PhD, David Kay Ferguson PhD, Hong-Ling Guo PhD, Yu-Fei Wang PhD, Jin-Feng Li PhD

Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations.

罂粟、古柯和大麻是三种臭名昭著的非法毒品的原料。长期以来,毒枭们通过各种方式和渠道种植和走私这些毒品,并不断寻找新的贩运方式,导致全球缉毒工作难度不断增加。在本文中,我们针对这些重要的毒品植物提出了一种创新的花粉识别系统,为筛查和检测毒品提供了工具,有助于缉毒执法。利用这些细小颗粒产量大、抗衰老能力强的特点,我们认为该工具可应用于以下场景:检测和动态监控毒品种植活动;确定嫌疑人是否去过毒品植物种植地;确定该地点是否种植过毒品植物和/或参与过毒品生产。未来,结合显微镜自动图像采集技术和智能图像识别技术,该花粉识别系统有望用于筛查三种臭名昭著的非法毒品植物,从而提高毒品相关犯罪的侦查效率。
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引用次数: 0
Analysis of the privacy-performance tradeoff of reference testing in Forensic Investigative Genetic Genealogy 法医调查基因谱系中参考测试的隐私与性能权衡分析。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-08 DOI: 10.1111/1556-4029.15579
Yuchen Hu MS, Lawrence M. Wein PhD

During an investigation using Forensic Investigative Genetic Genealogy, which is a novel approach for solving violent crimes and identifying human remains, reference testing—when law enforcement requests a DNA sample from a person in a partially constructed family tree—is sometimes used when an investigation has stalled. Because the people considered for a reference test have not opted in to allow law enforcement to use their DNA profile in this way, reference testing is viewed by many as an invasion of privacy and by some as unethical. We generalize an existing mathematical optimization model of the genealogy process by incorporating the option of reference testing. Using simulated versions of 17 DNA Doe Project cases, we find that reference testing can solve cases more quickly (although many reference tests are required to substantially hasten the investigative process), but only rarely (<1%) solves cases that cannot otherwise be solved. Through a mixture of mathematical and computational analysis, we find that the most desirable people to test are at the bottom of a path descending from an ancestral couple that is most likely to be related to the target. We also characterize the rare cases where reference testing is necessary for solving the case: when there is only one descending path from an ancestral couple, which precludes the possibility of identifying an intersection (e.g., marriage) between two descendants of two different ancestral couples.

法医调查遗传系谱是解决暴力犯罪和鉴定遗骸的一种新方法,在使用这种方法进行调查的过程中,有时会在调查陷入僵局时使用参考检测--即执法部门要求从部分构建的家谱中的某个人身上提取 DNA 样本。由于被考虑进行参考检测的人并没有选择允许执法部门以这种方式使用他们的 DNA 资料,因此许多人认为参考检测侵犯了隐私,有些人则认为参考检测不道德。我们对现有的家谱流程数学优化模型进行了归纳,将参考检测选项纳入其中。利用 17 个 DNA 无名氏项目案例的模拟版本,我们发现参考检测可以更快地解决案件(尽管需要进行多次参考检测才能大大加快调查进程),但只在极少数情况下(例如,在一些案件中,参考检测可以更快地解决案件)才会使用。
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引用次数: 0
The impacts of thermocouple insulation failure on the accuracy of temperature measurement data in forensic fire-death scenarios—Part I: Physical disintegration 热电偶绝缘失效对火灾死亡法证场景中温度测量数据准确性的影响--第一部分:物理分解。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-04 DOI: 10.1111/1556-4029.15576
David Silveira MS, Ashley Kendell PhD, Beth Shook PhD

Thermocouples are utilized to monitor a wide range of temperatures in industrial applications. They are also used in both fire and forensic science research to measure temperatures of fires and of materials exposed to fire. Taking accurate temperature measurements during forensic fire-death scenarios is very difficult due to direct fire exposure to thermocouples, shrinkage and destruction of tissues, and movements from pyre collapse and pugilistic posturing of human donors. This two-part study investigates the impacts on the accuracy of temperature data if the selected thermocouples are unable to withstand fire exposure. Part I (this article) provides an overview of thermocouple theory along with evidence of the physical deterioration that occurs when glass fiber-insulated thermocouple wires are overheated by exposure to fire-level temperatures in a muffle furnace. This study verified that insulation overheating causes embrittlement and disintegration, which can cause the indicated temperature to reflect a new location of measurement located far away from the original measuring junction at the thermocouple tip. Part II will discuss the measurement errors that occurred due to low electrical resistance of insulation when three different thermocouple models were passed through fire-level temperatures to measure an ice bath at a constant temperature of 0°C.

热电偶可用于监测工业应用中的各种温度。热电偶还用于火灾和法医科学研究,测量火灾和暴露于火中的材料的温度。由于热电偶直接暴露在火中、组织收缩和破坏、火堆坍塌造成的移动以及人体捐献者的姿势,在法医火灾死亡场景中进行精确的温度测量非常困难。本研究由两部分组成,调查如果所选热电偶无法承受火灾暴露,对温度数据准确性的影响。第一部分(本文)概述了热电偶理论,并提供了玻璃纤维绝缘热电偶丝在马弗炉中暴露于火级温度而过热时发生物理劣化的证据。这项研究证实,绝缘层过热会导致脆化和解体,从而使指示温度反映出远离热电偶顶端原始测量结点的新测量位置。第二部分将讨论三种不同型号的热电偶在测量恒温 0°C 的冰浴时,由于绝缘电阻低而产生的测量误差。
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引用次数: 0
The impacts of thermocouple insulation failure on the accuracy of temperature measurement data in forensic fire-death scenarios—Part II: Low electrical resistance and contamination 热电偶绝缘失效对火灾死亡法证场景中温度测量数据准确性的影响--第二部分:低电阻和污染。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-04 DOI: 10.1111/1556-4029.15577
David Silveira MS, Ashley Kendell PhD, Beth Shook PhD

Part II of this two-part article investigates the impact of thermocouple insulation failure on temperature measurement data in forensic fire-death scenarios. Two different models of glass fiber-insulated thermocouple wires (GG-K-24-SLE and HH-K-24 from Omega Engineering) were passed through a ceramic kiln at temperatures up to 1093°C to measure an ice bath at a constant 0°C. In a separate experiment, the same two models of thermocouple wire plus a BLMI-XL-K-18U-120 mineral-insulated metal-sheathed thermocouple probe were passed through a wood pallet fire to measure an ice bath. In the ceramic kiln, the effect on measurement errors was determined for short vs. long exposure lengths and clean insulation vs. insulation contaminated with pork fat. Glass fiber-insulated thermocouple wires showed severe failure in both experiments, with errors ranging from −270°C to almost 2200°C. The metal-sheathed probe showed no evidence of insulation failure and continued to accurately measure the ice bath temperature within expected margins of error around 0°C. This study highlights how exposure of inadequate thermocouples to fire-level temperatures produces severe errors in temperature data. Consequently, it will not be possible to use this data to draw any accurate conclusions about the effects of fire exposure to human donors or animal proxies.

本文由两部分组成,第二部分研究了在法医火灾死亡场景中热电偶绝缘失效对温度测量数据的影响。将两种不同型号的玻璃纤维绝缘热电偶丝(欧米茄工程公司的 GG-K-24-SLE 和 HH-K-24)穿过温度高达 1093°C 的陶瓷窑,测量恒定在 0°C 的冰浴。在另一项实验中,将同样的两种型号的热电偶线和 BLMI-XL-K-18U-120 矿物绝缘金属铠装热电偶探头穿过木托盘火,测量冰浴。在陶瓷窑中,确定了短暴露时间与长暴露时间、清洁隔热材料与受猪肉脂肪污染的隔热材料对测量误差的影响。玻璃纤维绝缘热电偶丝在两次实验中都出现了严重故障,误差范围从 -270°C 到接近 2200°C。而金属护套探头则没有出现绝缘失效的迹象,并能在 0°C 左右的预期误差范围内继续准确测量冰浴温度。这项研究强调了不适当的热电偶暴露在火级温度下会产生严重的温度数据误差。因此,无法利用这些数据就火灾对人体捐献者或动物替代品的影响得出任何准确的结论。
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引用次数: 0
Correction to: Accuracy of comparisons conducted by forensic firearms examiners 更正:法医枪支检验员进行比较的准确性。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-03 DOI: 10.1111/1556-4029.15580

Monson KL, Smith ES, Peters EM. Accuracy of comparisons conducted by forensic firearms examiners. J Forensic Sci. 2023;68(1):86–100. https://doi.org/10.1111/1556-4029.15152

This communication corrects two inadvertent errors. The denominator of Equation 2 (page 89 of the publication) contains an extra value (848), although the stated result (2.92%) is correct. The corrected equation is:

The first paragraph on page 91 of the publication, which refers to Figure 5, is also revised as follows:

Examples of comparisons that resulted in false-positive errors are provided in Figures 3 (bullets), 4 (cartridge cases), and 5 (bullets). An example of a comparison that resulted in a false-negative error is provided in Figure 6 (cartridge cases). In addition to exemplifying erroneous conclusions, Figures 3–6 illustrate the difficulty level of many of the comparisons in this study.

We apologize for any convenience resulting from these oversights.

Monson KL, Smith ES, Peters EM.法医枪支检验员进行比较的准确性。J Forensic Sci. 2023;68(1):86-100。https://doi.org/10.1111/1556-4029.15152This 通讯更正了两个无心之过。等式 2 的分母(出版物第 89 页)包含一个额外值(848),尽管所述结果(2.92%)是正确的。更正后的等式为:出版物第 91 页第一段提及图 5,现修改如下:图 3(子弹)、图 4(弹壳)和图 5(子弹)提供了导致假阳性错误的比较示例。图 6(弹壳)提供了导致假阴性错误的比较示例。除了举例说明错误结论外,图 3-6 还说明了本研究中许多比较的难度。
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引用次数: 0
Selective postmortem arterial angiography of head and neck using digital x-ray or computed tomography: A practical and rapid method to identify vascular injuries 使用数字 X 光或计算机断层扫描对头颈部进行选择性死后动脉造影:识别血管损伤的实用快速方法。
IF 1.5 4区 医学 Q2 MEDICINE, LEGAL Pub Date : 2024-07-01 DOI: 10.1111/1556-4029.15568
Zabiullah Ali MD, Nikki Mourtzinos DO, MHS

Identification of vascular injuries is crucial for complete postmortem evaluation and understanding of trauma deaths by the Medical Examiner. Some vascular injuries are difficult to evaluate due to challenging anatomic locations, especially in the head and neck. Documenting injuries of the facial and vertebral arteries is challenging and necessitates time-consuming dissections that can create artifacts and disfigurement. In busy medical examiner offices with a significant number of traumatic injuries, finding a creative solution to employ reliable postmortem angiography is desirable. At the Office of the Chief Medical Examiner for the State of Maryland (OCME), we created and effectively implemented a selective angiography procedure using traditional indwelling Foley catheters and water-soluble barium swallow contrast to evaluate arterial injuries using either digital radiography or computed tomography imaging modalities. This technique and imaging interpretation can be performed by a medical examiner or forensic pathology fellow after basic technical training and basic radiology training. This study outlines the technique, methods, and utilization of the procedure and describes the findings of six deaths due to vascular lesions from different injury mechanisms and disease processes and describes the ease of implementation on a broader scale in busy Medical Examiner's offices.

血管损伤的鉴定对于法医对创伤死亡进行完整的尸检评估和理解至关重要。由于解剖位置具有挑战性,有些血管损伤很难评估,尤其是在头部和颈部。记录面部和椎动脉的损伤具有挑战性,必须进行耗时的解剖,否则会造成假象和毁容。繁忙的法医办公室需要处理大量的外伤,因此需要找到一种创造性的解决方案来采用可靠的死后血管造影术。在马里兰州首席法医办公室(OCME),我们创建并有效实施了一种选择性血管造影程序,使用传统的留置 Foley 导管和水溶性吞钡造影剂,利用数字射线或计算机断层扫描成像模式评估动脉损伤。经过基本技术培训和基本放射学培训后,法医或法医病理学研究员即可进行这项技术和成像解读。本研究概述了该程序的技术、方法和使用情况,描述了六例因不同损伤机制和疾病过程导致的血管病变而死亡的调查结果,并说明了在繁忙的法医办公室更广泛地实施该程序的难易程度。
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引用次数: 0
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Journal of forensic sciences
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