The effect of migrating dune forms on the flow field of an alluvial river

The bed of an alluvial river is highly susceptible to changes during the course of its existence. Besides variations of the large scale topography and plan form of the river, smaller scale dune forms can be observed. These recurring dune forms migrate on top of the large scale topography and can yield local yet important variations in the flow field. In order to study the effect of migrating dune forms on the flow characteristics and consequently the erosive capacity of an alluvial river, an experiment with mobile bed has been carried out in a laboratory flume representing a sharp meander bend. In this experiment, changes to an initially flat, slightly sloped river bed under a steady flow and sediment discharge were observed until a recurring pattern of migrating dune forms could be seen on top of the characteristic pool-bar topography of meander bends. Once the dune forms were established, an Acoustic Doppler Velocity Profiler (ADVP) was placed in several positions alongside the river bend and used to measure the flow depth and flow characteristics under the influence of the passing dunes. Several times during the experiment, the topography was mapped using laser altimetry on a grid of large spatial resolution in order to isolate the dune forms from the large scale topography and determine the dune characteristics and the dune celerity. In this paper the large scale topography and dune characteristics will be shown and the effect of the migrating dune forms on the flow field and the erosive capacity will be discussed in detail

A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700)

&lt;p&gt;A 30-year old man was found dead in his home after inhaling fumes of a powder burned on aluminum foil. Blood and urine were taken by the medical examiner during the external body examination and submitted to the laboratory for a comprehensive systematic toxicological analysis. A toxic fentanyl level of 10.9μg/L was measured in the subclavian blood. Police investigation revealed that the man searched the internet for information on new psychotropic substances, among others including U-47700. A powder found in the victims&#039; home was transferred to the laboratory for analysis, in which trace amounts of fentanyl (0.0035%, m/m) and U-47700 (0.0012%, m/m) were identified by gas chromatography mass spectrometry. U-47700 is an opioid analgesic drug, considered to have a potency of approximately 7.5 times that of morphine. A target analysis on U-47700 was performed using liquid-liquid extraction and ultra performance liquid chromatography tandem mass spectrometry operating in multiple reaction monitoring mode. The method validation was based on the Scientific Working Group of Forensic Toxicology document &#039;Standard Practices of Method Validation in Forensic Toxicology&#039;. In blood and urine the U-47700 concentration was 13.8 and 71.0μg/L, respectively. To the author&#039;s knowledge, this is the first case report of a fatal intoxication involving U-47700 abused as a new psychotropic substance.&lt;/p&gt;</p

Synthesis and in vivo evaluation of [123I]-3-I-CO: a potential SPECT tracer for the serotonin 5-HT2A receptor

The aim of this doctoral dissertation was the precursor synthesis, radiosynthesis and in vivo evaluation of [123I]-3-I-CO as a possible new tracer for imaging of the central serotonin 5-HT2A receptor with SPECT. [123I]-(4-fluorophenyl)[1-(3-iodophenethyl)piperidin-4-yl] methanone ([123I]-3-I-CO) demonstrates good affinity for the 5-HT2A receptor (Ki = 0.51 nM) and good selectivity ratios over other receptor types and was therefore selected as the ligand. First, the in vivo behaviour of a currently used 5-HT2A SPECT tracer, [123I]-R91150, was evaluated (chapter 3), and brain uptake of the tracer was assessed in rodents, as a standard for comparison. The influence of P-glycoprotein blocking (with cyclosporin A) on the biodistribution and brain uptake of [123I]-R91150 was also evaluated in rodents, and these results were compared with the data obtained from the normal biodistribution studies with [123I]-R91150. Also, the influence of P-glycoprotein blocking on pinhole μSPECT imaging with [123I]-R91150 in rodents was investigated. In NMRI mice, a dose-dependent influence of cyclosporin A on the brain uptake of [123I]-R91150 was observed, indicating that the increased brain uptake is the result of a decreased efflux of tracer out of the brain after blocking of the P-glycoprotein efflux transporter with cyclosporin A. Pre-treatment of Sprague-Dawley rats with cyclosporin A resulted in a drastically increased brain uptake of [123I]-R91150 (brain uptake increased seven-fold after Pglycoprotein blocking) and a vastly improved pinhole μSPECT imaging quality. From these results it can be concluded that [123I]-R91150 is a substrate for P-glycoprotein efflux in vivo, and that it’s brain efflux can be blocked by administration of cyclosporin A. Organic synthesis of the tributylstannyl precursor for the radiosynthesis of [123I]-3-I-CO was performed in adequate yield. An average yield of about 85 % was obtained in the radiosynthesis reaction. The radioligand was purified with semi-preparative HPLC, and radiochemical purities of > 95 % were obtained consistently. The radioligand was stable at room temperature until 48 h after synthesis. A logP value of 3.10 ± 0.10 was obtained for [123I]-3-I-CO (chapter 4). In vivo evaluation of [123I]-3-I-CO in NMRI mice revealed high initial brain uptake (6.26 ± 1.36 % ID/g tissue at 10 min post injection), but radioactivity concentrations in brain decreased rapidly over time. No radiolabelled metabolites were observed in blood or brain of NMRI mice. Brain uptake of [123I]-3-I-CO was also investigated in Sprague-Dawley rats (chapter 5): highest brain radioactivity concentrations were obtained in the occipital (0.942 ± 0.034 % ID/g tissue at 20 min post injection) and frontal cortex (0.674 ± 0.074 % ID/g tissue at 20 min post injection). Blood radioactivity concentrations were consistently low (a maximum value of 0.062 ± 0.014 % ID/g tissue was obtained at 20 min post injection). An average frontal cortex-to-cerebellum ratio of about 1.7 was obtained. In the Sprague-Dawley rat biodistribution studies, a rapid washout of radioactivity from the brain was observed. [123I]-3-I-CO was displaced from the 5-HT2A receptor by ketanserin: radioactivity concentration in the 5-HT2A rich areas of the brain decreased by 50 % after ketanserin displacement. Nevertheless, the residual radioactivity levels in cerebellum after ketanserin displacement remained high, especially compared to the results obtained with [123I]-R91150, and are probably caused by aspecific binding of the radioligand to brain tissues. No radiolabelled metabolites could be detected in the blood or brain of Sprague-Dawley rats. The influence of P-glycoprotein modulation with cyclosporin A on the brain uptake of [123I]-3-I-CO was also investigated. On average, a 67 % increase in [123I]-3-I-CO radioactivity concentration was observed throughout the brain after treatment of the animals with cyclosporin A. We can conclude from these results that [123I]-3-I-CO is at least a partial substrate for P-glycoprotein efflux, but the increase in brain radioactivity concentration after cyclosporin A treatment was not as large as the increase observed with [123I]-R91150 (chapter 3). Although cortical tissues could be visualized using pinhole μSPECT imaging with [123I]-3-ICO, aspecific binding of the radioligand was observed in the cerebellum, probably limiting its application as a serotonin 5-HT2A receptor tracer in humans. μSPECT imaging quality also did not improve after cyclosporin A pre-treatment of the animals. Although the initial rodent studies demonstrated promising brain uptake of the radioligand, it can be concluded that [123I]-3-I-CO probably has very limited potential as a 5-HT2A tracer for SPECT, due to high aspecific binding and rapid washout of the radioligand out of the brain. Also, compared to other clinically used brain tracers (for example [123I]-R91150), the specific ‘signal’ of [123I]-3-I-CO in brain is too limited for application as a tracer in brain receptor imaging studies

Identification and characterization of 4-chloromethamphetamine (4-CMA) in seized ecstacy : a risk to public health

A

Identification of a new tert -leucinate class synthetic cannabinoid in powder and 'spice-like' herbal incenses : methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA)

&lt;p&gt;A brown powder and different product packages of &quot;spice-like&quot; herbal incenses were analyzed using a systematic identification approach based on liquid chromatography with diode array detector (HPLC-PDA) and gas chromatography mass spectrometry (GC-MS) with computer based library search against spectral libraries. However, the most predominant compound in the methanolic sample solutions could not be identified. In order to elucidate the chemical structure, a more extensive analysis of the material was initiated using liquid chromatography mass spectrometry (LC-MS), electrospray high resolution mass spectrometry (ESI-HRMS) and (1)H, (13)C and (19)F nuclear magnetic resonance spectroscopy (NMR), which allowed the identification and characterization of the major compound as methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA). The goal of this study is to provide analytical information for the identification of this new tert-leucinate class synthetic cannabinoid by various analytical methods.&lt;/p&gt;</p

Medical emergencies related to ethanol and illicit drugs at an annual, nocturnal, indoor, electronic dance music event

Introduction: Medical problems are frequently encountered during electronic dance music (EDM) events. Problem: There are uncertainties about the frequencies and severity of intoxications with different types of recreational drugs: ethanol, "classical" illicit party drugs, and new psychoactive substances (NPS). Methods: Statistical data on the medical problems encountered during two editions of an indoor electronic dance event with around 30,000 attendants were retrieved from the Belgian Red Cross (Mechelen, Belgium) database. Data on drug use were prospectively collected from the patient (or a bystander), the clinical presentation, and/or toxicological screening. Results: In the on-site medical station, 487 patients were treated (265 in 2013 and 222 in 2014). The most frequent reasons were trauma (n = 171), headache (n = 36), gastro-intestinal problems (n = 44), and intoxication (n = 160). Sixty-nine patients were transferred to a hospital, including 53 with severe drug-related symptoms. Analysis of blood samples from 106 intoxicated patients detected ethanol in 91.5%, 3,4-methylenedioxymethamphetamine (MDMA) in 34.0%, cannabis in 30.2%, cocaine in 7.5%, amphetamine in 2.8%, and gamma-hydroxybutyric acid (GHB) in 0.9% of patients (alone or in combination). In only six of the MDMA-positive cases, MDMA was the sole substance found. In 2014, the neuroleptic drug clozapine was found in three cases and ketamine in one. Additional analyses for NPS were performed in 20 cases. Only in one agitated patient, the psychedelic phenethylamines 25B-NBOMe and 25C-NBOMe were found. Conclusions: At this particular event, recreational drug abuse necessitated on-site medical treatment in one out of 350 attendants and a hospital transfer in one out of 1,000. Ethanol remains the most frequently abused (legal) drug, yet classical illicit recreational drugs are also frequently (co-) ingested. The most worrying observation was high-risk poly-drug use, especially among MDMA users. Regarding NPS, the number of cases was low and the clinical presentations were rather mild. It should be stressed that these observations only apply to this particular event and cannot be generalized to other EDM events

Multicentre evaluation of the Boehringer Mannheim/Hitachi 917 analysis system

The new selective access analysis system BM/Hitachi 917 was evaluated in an international multicentre study, mainly according to the ECCLS protocol for the evaluation of analysers in clinical chemistry. Forty-three different analytes, covering 56 different methods enzymes, substrates, electrolytes, specific proteins, drugs and urine applications were tested in seven European clinical chemistry laboratories. Additionally, the practicability of the BM/ Hitachi 917 was tested according to a standardized questionnaire. Within-run CVs (median of 3 days) for enzymes, substrates and electrolytes were <2% except for creatine-kinase MB isoform and lipase at low concentration. For proteins, drugs and urine analytes the within-run CVs were < 4% except for digoxin and albumin in urine. Between-day median CVs were generally < 3% for enzymes, substrates and electrolytes, and < 6% for proteins, drugs and urine analytes, except for lipase, creatine kinase and MB isoform, D-dimer, glycosylated haemoglobin, rheumatoid factors, digoxin, digitoxin, theophylline and albumin in urine in some materials. Linearity was found according to the test specifications or better and there were no relevant effects seen in drift and carry-over testing. The interference results clearly show that also for the BM/Hitachi 917 interference exists sometimes, as could be expected because of the chemistries applied. It is a situation that can be found in equivalent analysers as well. The accuracy is acceptable regarding a 95–105% recovery in standard reference material, with the exception of the creatinine Jaffé method. Most of the 160 method comparisons showed acceptable agreement according to our criteria: enzymes, substrates, urine analytes deviation of slope ± 5%, electrolytes ± 3%, and proteins and drugs ± 10%. The assessment of practicability for 14 groups of attributes resulted in a grading of one–three scores better for the BM/Hitachi 917 than the present laboratory situation. In conclusion, the results of the study showed good analytical performance and confirmed the usefulness of the system as a consolidated workstation in medium-sized to large clinical chemistry laboratories

Physical complexity to model morphological changes at a natural channel bend

This study developed a two‐dimensional (2‐D) depth‐averaged model for morphological changes at natural bends by including a secondary flow correction. The model was tested in two laboratory‐scale events. A field study was further adopted to demonstrate the capability of the model in predicting bed deformation at natural bends. Further, a series of scenarios with different setups of sediment‐related parameters were tested to explore the possibility of a 2‐D model to simulate morphological changes at a natural bend, and to investigate how much physical complexity is needed for reliable modeling. The results suggest that a 2‐D depth‐averaged model can reconstruct the hydrodynamic and morphological features at a bend reasonably provided that the model addresses a secondary flow correction, and reasonably parameterize grain‐sizes within a channel in a pragmatic way. The factors, such as sediment transport formula and roughness height, have relatively less significance on the bed change pattern at a bend. The study reveals that the secondary flow effect and grain‐size parameterization should be given a first priority among other parameters when modeling bed deformation at a natural bend using a 2‐D model