Chemical Attribution of the Homemade Explosive ETN - Part II: Isotope Ratio Mass Spectrometry Analysis of ETN and Its Precursors

In this follow-up study the collaboration between two research groups from the USA and the Netherlands was continued to expand the framework of chemical attribution for the homemade explosive erythritol tetranitrate (ETN). Isotope ratio mass spectrometry (IRMS) analysis was performed to predict possible links between ETN samples and its precursors. Carbon, nitrogen, hydrogen and oxygen isotope ratios were determined for a wide variety of precursor sources and for ETN samples that were prepared with selected precursors. The stability of isotope ratios of ETN has been demonstrated for melt-cast samples and two-year old samples, which enables sample comparison of ETN in forensic casework independent of age and appearance. Erythritol and nitric acid (or nitrate salt) are the exclusive donor of carbon and nitrogen atoms in ETN, respectively, and robust linear relationships between precursor and the end-product were observed for these isotopes. This allowed for defining isotopic enrichment ranges for carbon and nitrogen that support the hypothesis that a given erythritol or nitrate precursor was used to synthesize a specific ETN batch. The hydrogen and oxygen atoms in ETN do not originate from one exclusive donor material, making linkage prediction more difficult. However, the large negative enrichments observed for both isotopes do provide powerful information to exclude suspected precursor materials as donor of ETN. Additionally, combing the isotopic data of all elements results in a higher discrimination power for ETN samples and its precursor materials. Combining the findings of our previously reported LC–MS analysis of ETN with this IRMS study is expected to increase the robustness of the forensic comparison even further. The partially nitrated impurities can provide insight on the synthesis conditions while the isotope data contain information on the raw materials used for the production of ETN

PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols

IntroductionPCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection.MethodsHundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA.ResultsInformative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score >6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479).ConclusionsInformative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined

Structural Remodeling in Atrial Fibrillation : A small pilot study in hypertensive and non-hypertensive patients with atrial fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Structural cardiac remodeling seems to play a key role in the onset of AF. Hypertension is strongly associated with structural remodeling and is suspected to be a major risk factor in the development of structural remodeling, resulting in AF. Therefore, we investigated the effect of hypertension on structural cardiac remodeling measured by clinical, echocardiographic and electrocardographic parameters in patients with paroxysmal or persistent AF. Method: In this retrospective observational study, eighty-nine patients with paroxysmal or persistent AF, treated with either endocardial or epicardial pulmonary vein isolation (PVI) were investigated. The patients treated with endocardial PVI were included if they were diagnosed with hypertension. All patients treated with epicardial PVI had lone AF. Endocardial PVI was performed as described by Pappone using radiofrequency current. Epicardial PVI was performed by minimal invasive video-assisted thoracoscopic surgery (VATS), 15 patients were treated using high-intensity focused ultrasound (HIFU) and 19 patients were treated using radiofrequency current. Clinical, echocardiographic and electrocardiographic characteristics were measured before PVI occurred (baseline), after one year of follow-up the measures were done again. Primary endpoint was the degree of structural cardiac remodeling, measured by left atrial (LA) volume (ml/m2), LA volume was considered normal if < 29 ml/m2. Secondary endpoint was AF recurrence with one year after initial PVI. Results: Mean age was 53.7 ± 11.2 years, 60 patients (69.0%) were male, 67 patients (77.0%) had paroxysmal AF, the remaining patients had persistent AF. 55 patients (63.2%) had hypertension and were treated with endocardial PVI, 32 patients (36.8%) had lone AF and were treated with epicardial PVI. Hypertensive patients had larger LA volumes compared to non-hypertensive patients, respectively 29.1 ± 10.9 ml/m2 and 23.5 ± 4.9 ml/m2. In 52 patients (60.5%) AF recurred within one year after the initial PVI. 38 of them (73.1%) were treated endocardial PVI, the remaining patients with AF recurrence were treated with epicardial PVI. Conclusion: LA volumes of hypertensive AF patients were larger than LA volumes of non-hypertensive AF patients. Hypertension, left ventricular ejection fraction and persistent AF were independently associated with LA volume < 29 ml/m2. In addition, AF recurrence after PVI occurred more often in patients treated with endocardial PVI compared to patients treated with epicardial PVI. Duration of AF was independently associated with AF recurrence within one year after initial PVI.