Multi-residue enantioselective determination of emerging drug contaminants in seawater by solid phase extraction and liquid chromatography-tandem mass spectrometry.

This study proposes a new multi-residue enantioselective method for the determination of emerging drug contaminants in sea water by solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). To achieve satisfactory enantiomeric separation with a vancomycin stationary phase it was essential to limit sodium chloride in extracted samples to [less than] 1 µg injection-1. This was achieved through a straightforward SPE method using a 50 mL water wash volume and analyte elution in acetonitrile. A Chiral-V enantioselective column (150 x 2.1mm; 2.7µm particle size) operated in polar ionic mode enabled simultaneous drug separations in 30 minutes. Analytes with enantioresolution E$ were the stimulants amphetamine and methamphetamine, the beta-agonist salbutamol, the beta-blockers propranolol, sotalol and acebutolol, the anti-depressants fluoxetine, venlafaxine, desmethylvenlafaxine and citalopram, and the antihistamine chlorpheniramine. Method quantitation limits were [less than] 10 ng L-1 and method trueness was 80-110% for most analytes. The method was applied to samples from the Forth and Clyde estuaries, Scotland. Chiral drugs were present at concentrations in the range 4-159 ng L-1 and several were in non-racemic form (enantiomeric fraction G 0.50) demonstrating enantiomer enrichment. This emphasises the need for further enantiospecific drug exposure and effect studies in the marine environment

Left ventricular outcomes following multivessel PCI vs. infarct artery-only PCI in patients with acute STEMI: the Glasgow PRAMI CMR sub-study

No abstract available

Drones and Digital Photogrammetry: From Classifications to Continuums for Monitoring River Habitat and Hydromorphology

Recently, we have gained the opportunity to obtain very high-resolution imagery and topographic data of rivers using drones and novel digital photogrammetric processing techniques. The high-resolution outputs from this method are unprecedented, and provide the opportunity to move beyond river habitat classification systems, and work directly with spatially explicit continuums of data. Traditionally, classification systems have formed the backbone of physical river habitat monitoring for their ease of use, rapidity, cost efficiency, and direct comparability. Yet such classifications fail to characterize the detailed heterogeneity of habitat, especially those features which are small or marginal. Drones and digital photogrammetry now provide an alternative approach for monitoring river habitat and hydromorphology, which we review here using two case studies. First, we demonstrate the classification of river habitat using drone imagery acquired in 2012 of a 120 m section of the San Pedro River in Chile, which was at the technological limits of what could be achieved at that time. Second, we review how continuums of data can be acquired, using drone imagery acquired in 2016 from the River Teme in Herefordshire, England. We investigate the precision and accuracy of these data continuums, highlight key current challenges, and review current best practices of data collection, processing, and management. We encourage further quantitative testing and field applications. If current difficulties can be overcome, these continuums of geomorphic and hydraulic information hold great potential for providing new opportunities for understanding river systems to the benefit of both river science and management

Semi-quantitative mass spectrometry in AML cells identifies new non-genomic targets of the EZH2 methyltransferase

Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-transretinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML

DOE Environmental Management Programs in New Mexico: Environmental and Economic Impacts

In August 2001 Nuclear Watch of New Mexico (NWNM) was funded by the Citizens’ Monitoring and Technical Assessment (MTA) Fund to conduct an “Assessment of the Environmental and Economic Impacts of Department of Energy Environmental Management Programs in New Mexico.” New Mexico is home to two of the three nuclear weapons laboratories in the United States, Los Alamos and Sandia National Laboratories. New Mexico also hosts the Waste Isolation Pilot Plant, the world’s only deep geological disposal site for radioactive transuranic wastes (which are primarily plutonium contaminated wastes resulting from bomb research and production). These three sites were the focus of NWNM’s project. In May 2002, the New Mexico Environment Department (NMED) issued under its Resource and Recovery Act (RCRA) authority a draft “Corrective Action Order” against Los Alamos National Laboratory (LANL). This Order mandates the investigation and compilation by the lab of comprehensive environmental information categorized by different lab Technical Areas, watersheds and groundwater. The bulk of our project on LANL environmental issues turned to analyzing and commenting on the draft Corrective Action Order. Subsequently Bernd Franke and Jay Coghlan collaboratively provided NMED with 19 pages of technical comments, which we believe had a salutary effect in strengthening the November 2002 Final Order. It is our hope that the LANL Order will lead, in time, to State-mandated cleanup. Unfortunately, to date implementation of the Order has been stayed under the threat of DOE lawsuits against NMED. The purpose of our Waste Isolation Pilot Plant (WIPP) project to was to look closely at the Department of Energy’s (DOE’s) anticipated remote-handled transuranic (RH-TRU) waste program as it pertains to WIPP. [RH-TRU wastes are those too hot for humans to handle.] However, because of the consistently changing nature of the DOE’s environmental management program and because of the interlocking nature of those changes, our WIPP project took on a broader scope. Not only did NWNM analyze and comment on the proposed addition of RH-TRU waste disposal, but also analyzed and commented on 22 other proposed additions or changes to WIPP. We believe that we have played a significant role in helping to ensure that the State WIPP RCRA permit remains strong and that the DOE’s requested modifications are not just perfunctorily approved by the NMED. This research was completed money allocated during Round 2 of the Citizens’ Monitoring and Technical Assessment Fund (MTA Fund). Clark University was named conservator of these works. If you have any questions or concerns please contact us at [email protected]://commons.clarku.edu/nuclearwatch/1000/thumbnail.jp

Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction

<b>Background:</b> The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.<p></p> <b>Methods and Results:</b> The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.<p></p> <b>Conclusion:</b> Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.<p></p&gt

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

Objective: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar

Comparative significance of invasive measures of microvascular injury in acute myocardial infarction

Background: The resistive reserve ratio (RRR) expresses the ratio between basal and hyperemic microvascular resistance. RRR measures the vasodilatory capacity of the microcirculation. We compared RRR, index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) for predicting microvascular obstruction (MVO), myocardial hemorrhage, infarct size, and clinical outcomes, after ST-segment–elevation myocardial infarction. Methods: In the T-TIME trial (Trial of Low-Dose Adjunctive Alteplase During Primary PCI), 440 patients with acute ST-segment–elevation myocardial infarction from 11 UK hospitals were prospectively enrolled. In a subset of 144 patients, IMR, CFR, and RRR were measured post-primary percutaneous coronary intervention. MVO extent (% left ventricular mass) was determined by cardiovascular magnetic resonance imaging at 2 to 7 days. Infarct size was determined at 3 months. One-year major adverse cardiac events, heart failure hospitalizations, and all-cause death/heart failure hospitalizations were assessed. Results: In these 144 patients (mean age, 59±11 years, 80% male), median IMR was 29.5 (interquartile range: 17.0–55.0), CFR was 1.4 (1.1–2.0), and RRR was 1.7 (1.3–2.3). MVO occurred in 41% of patients. IMR>40 was multivariably associated with more MVO (coefficient, 0.53 [95% CI, 0.05–1.02]; P=0.031), myocardial hemorrhage presence (odds ratio [OR], 3.20 [95% CI, 1.25–8.24]; P=0.016), and infarct size (coefficient, 5.05 [95% CI, 0.84–9.26]; P=0.019), independently of CFR≤2.0, RRR≤1.7, myocardial perfusion grade≤1, and Thrombolysis in Myocardial Infarction frame count. RRR was multivariably associated with MVO extent (coefficient, −0.60 [95% CI, −0.97 to −0.23]; P=0.002), myocardial hemorrhage presence (OR, 0.34 [95% CI, 0.15–0.75]; P=0.008), and infarct size (coefficient, −3.41 [95% CI, −6.76 to −0.06]; P=0.046). IMR>40 was associated with heart failure hospitalization (OR, 5.34 [95% CI, 1.80–15.81] P=0.002), major adverse cardiac events (OR, 4.46 [95% CI, 1.70–11.70] P=0.002), and all-cause death/ heart failure hospitalization (OR, 4.08 [95% CI, 1.55–10.79] P=0.005). RRR was associated with heart failure hospitalization (OR, 0.44 [95% CI, 0.19–0.99] P=0.047). CFR was not associated with infarct characteristics or clinical outcomes. Conclusions: In acute ST-segment–elevationl infarction, IMR and RRR, but not CFR, were associated with MVO, myocardial hemorrhage, infarct size, and clinical outcomes