Assessment of total uncertainty in cocaine and benzoylecgonine wastewater load measurements

To check the effectiveness of campaigns preventing drug abuse or indicating local effects of efforts against drug trafficking, it is beneficial to know consumed amounts of substances in a high spatial and temporal resolution. The analysis of drugs of abuse in wastewater (WW) has the potential to provide this information. In this study, the reliability of WW drug consumption estimates is assessed and a novel method presented to calculate the total uncertainty in observed WW cocaine (COC) and benzoylecgonine (BE) loads. Specifically, uncertainties resulting from discharge measurements, chemical analysis and the applied sampling scheme were addressed and three approaches presented. These consist of (i) a generic model-based procedure to investigate the influence of the sampling scheme on the uncertainty of observed or expected drug loads, (ii) a comparative analysis of two analytical methods (high performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry), including an extended cross-validation by influent profiling over several days, and (iii) monitoring COC and BE concentrations in WW of the largest Swiss sewage treatment plants. In addition, the COC and BE loads observed in the sewage treatment plant of the city of Berne were used to back-calculate the COC consumption. The estimated mean daily consumed amount was 107 ± 21 g of pure COC, corresponding to 321 g of street-grade COC.

Water isotopic ratios from a continuously melted ice core sample

A new technique for on-line high resolution isotopic analysis of liquid water, tailored for ice core studies is presented. We built an interface between a Wavelength Scanned Cavity Ring Down Spectrometer (WS-CRDS) purchased from Picarro Inc. and a Continuous Flow Analysis (CFA) system. The system offers the possibility to perform simultaneuous water isotopic analysis of δ18O and δD on a continuous stream of liquid water as generated from a continuously melted ice rod. Injection of sub μl amounts of liquid water is achieved by pumping sample through a fused silica capillary and instantaneously vaporizing it with 100% efficiency in a~home made oven at a temperature of 170 °C. A calibration procedure allows for proper reporting of the data on the VSMOW–SLAP scale. We apply the necessary corrections based on the assessed performance of the system regarding instrumental drifts and dependance on the water concentration in the optical cavity. The melt rates are monitored in order to assign a depth scale to the measured isotopic profiles. Application of spectral methods yields the combined uncertainty of the system at below 0.1‰ and 0.5‰ for δ18O and δD, respectively. This performance is comparable to that achieved with mass spectrometry. Dispersion of the sample in the transfer lines limits the temporal resolution of the technique. In this work we investigate and assess these dispersion effects. By using an optimal filtering method we show how the measured profiles can be corrected for the smoothing effects resulting from the sample dispersion. Considering the significant advantages the technique offers, i.e. simultaneuous measurement of δ18O and δD, potentially in combination with chemical components that are traditionally measured on CFA systems, notable reduction on analysis time and power consumption, we consider it as an alternative to traditional isotope ratio mass spectrometry with the possibility to be deployed for field ice core studies. We present data acquired in the field during the 2010 season as part of the NEEM deep ice core drilling project in North Greenland.

Enhancing BOLD response in the auditory system by neurophysiologically tuned fMRI sequence

Auditory neuroscience has not tapped fMRI's full potential because of acoustic scanner noise emitted by the gradient switches of conventional echoplanar fMRI sequences. The scanner noise is pulsed, and auditory cortex is particularly sensitive to pulsed sounds. Current fMRI approaches to avoid stimulus-noise interactions are temporally inefficient. Since the sustained BOLD response to pulsed sounds decreases with repetition rate and becomes minimal with unpulsed sounds, we developed an fMRI sequence emitting continuous rather than pulsed gradient sound by implementing a novel quasi-continuous gradient switch pattern. Compared to conventional fMRI, continuous-sound fMRI reduced auditory cortex BOLD baseline and increased BOLD amplitude with graded sound stimuli, short sound events, and sounds as complex as orchestra music with preserved temporal resolution. Response in subcortical auditory nuclei was enhanced, but not the response to light in visual cortex. Finally, tonotopic mapping using continuous-sound fMRI demonstrates that enhanced functional signal-to-noise in BOLD response translates into improved spatial separability of specific sound representations.

(18)F-Immuno-PET: Determination of Anti-CD66 Biodistribution in a Patient with High-Risk Leukemia

The monoclonal antibody anti-CD66 labeled with (99m)Tc is widely used as Scintimun((R)) granulocyte for bone marrow immunoscintigraphy. Further, recently performed clinical radioimmunotherapy studies with [(90)Y]Y-anti-CD66 proved to be suitable for the treatment of hematologic malignancies. Before radioimmunotherapy with [(90)Y]Y-anti-CD66, dosimetric estimations are required to minimize radiotoxicity and determine individual applicable activities. Planar imaging, using gamma-emitting radionuclides, is conventionally carried out to estimate the absorbed organ doses. In contrast, immuno-PET (positron emission tomography) enables the quantification of anti-CD66 accumulation and provides better spatial and temporal resolution. Therefore, in this study, a semiautomated radiosynthesis of [(18)F] F-anti-CD66 was developed, using the (18)F-acylation agent, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). As a proof of concept, an intraindividual comparison between PET and conventional scintigraphy, using (18)F- and (99m)Tc-labeled anti-CD66 in 1 patient with high-risk leukemia, is presented. Both labeled antibodies displayed a similar distribution pattern with high preferential uptake in bone marrow. Urinary excretion of [(18)F] F-anti-CD66 was increased and bone marrow uptake reduced, in comparison to [(99m)Tc]Tc-anti-CD66. Nevertheless, PET-based dosimetry with [(18)F] F-anti-CD66 could provide additional information to support conventional scintigraphy. Moreover, [(18)F]F-anti-CD66 is ideally suited for bone marrow imaging using PET.

Neurophysiology and neuroanatomy of reflexive and volitional saccades as revealed by lesion studies with neurological patients and transcranial magnetic stimulation (TMS)

This review discusses the neurophysiology and neuroanatomy of the cortical control of reflexive and volitional saccades in humans. The main focus is on classical lesion studies and studies using the interference method of transcranial magnetic stimulation (TMS). To understand the behavioural function of a region, it is essential to assess oculomotor deficits after a focal lesion using a variety of oculomotor paradigms, and to study the oculomotor consequences of the lesion in the chronic phase. Saccades are controlled by different cortical regions, which could be partially specialised in the triggering of a specific type of saccade. The division of saccades into reflexive visually guided saccades and intentional or volitional saccades corresponds to distinct regions of the neuronal network, which are involved in the control of such saccades. TMS allows to specifically interfere with the functioning of a region within an intact oculomotor network. TMS provides advantages in terms of temporal resolution, allowing to interfere with brain functioning in the order of milliseconds, thereby allowing to define the time course of saccade planning and execution. In the first part of the paper, we present an overview of the cortical structures important for saccade control, and discuss the pro's and con's of the different methodological approaches to study the cortical oculomotor network. In the second part, the functional network involved in reflexive and volitional saccades is presented. Finally, studies concerning recovery mechanisms after a lesion of the oculomotor cortex are discussed.

The cranial bone window model: studying angiogenesis of primary and secondary bone tumors by intravital microscopy

The successful treatment of primary and secondary bone tumors in a huge number of cases remains one of the major unsolved challenges in modern medicine. Malignant primary bone tumor growth predominantly occurs in younger people, whereas older people predominantly suffer from secondary bone tumors since up to 85% of the most frequently occurring malignant solid tumors, such as lung, mammary, and prostate carcinomas, metastasize into the bone. It is well known that a tumor's course may be altered by its surrounding tissue. For this reason, reported here is the protocol for the surgical preparation of a cranial bone window in mice as well as the method to implant tumors in this bone window for further investigations of angiogenesis and other microcirculatory parameters in orthotopically growing primary or secondary bone tumors using intravital microscopy. Intravital microscopy represents an internationally accepted and sophisticated experimental method to study angiogenesis, microcirculation, and many other parameters in a wide variety of neoplastic and nonneoplastic tissues. Since most physiologic and pathophysiologic processes are active and dynamic events, one of the major strengths of chronic animal models using intravital microscopy is the possibility of monitoring the regions of interest in vivo continuously up to several weeks with high spatial and temporal resolution. In addition, after the termination of experiments, tissue samples can be excised easily and further examined by various in vitro methods such as histology, immunohistochemistry, and molecular biology.

Aperistaltic effect of hyoscine N-butylbromide versus glucagon on the small bowel assessed by magnetic resonance imaging

The aim of this prospective study was to compare the intraindividual aperistaltic effect of 40 mg hyoscine N-butylbromide (HBB/Buscopan) with that of 1 mg glucagon on small bowel motility by using magnetic resonance imaging (MRI). Ten healthy volunteers underwent two separate 1.5-T MRI studies (HBB/glucagon) after a standardized oral preparation with an aqueous solution of Gd-DOTA and ispaghula (Metamucil). A 2D T1-w GRE sequence was acquired (TR 2.7 ms/TE 1.3 ms, temporal resolution 0.25 s) before and after intravenous (i.v.) drug administration and motility was followed over 1 h. On the resulting images the cross-sectional luminal diameters were assessed and plotted over time. Baseline motility frequency, onset of aperistalsis, duration of arrest, reappearance of motility and return to normal motility were analysed. Significant differences regarding reliability and duration of aperistalsis were observed. In the HBB group aperistalsis lasted a mean of 6.8 +/- 5.3 min compared with 18.3 +/- 7 min after glucagon (p < 0.0001). In 50% of cases HBB did not accomplish aperistalsis, whereas glucagon always succeeded (p = 0.05). There were no significant differences in terms of baseline and end frequencies for the onset of aperistalsis (22.2 +/- 37.5 s HBB/13.4 +/- 9.2 s glucagon, p = 0.1), nor for the return to normal motility. Arrest of small bowel motion is achieved more reliably and lasts significantly longer after i.v. administration of 1 mg glucagon compared with 40 mg HBB.

Comparison of climate field reconstruction techniques: Application to Europe

This paper presents a comparison of principal component (PC) regression and regularized expectation maximization (RegEM) to reconstruct European summer and winter surface air temperature over the past millennium. Reconstruction is performed within a surrogate climate using the National Center for Atmospheric Research (NCAR) Climate System Model (CSM) 1.4 and the climate model ECHO-G 4, assuming different white and red noise scenarios to define the distortion of pseudoproxy series. We show how sensitivity tests lead to valuable “a priori” information that provides a basis for improving real world proxy reconstructions. Our results emphasize the need to carefully test and evaluate reconstruction techniques with respect to the temporal resolution and the spatial scale they are applied to. Furthermore, we demonstrate that uncertainties inherent to the predictand and predictor data have to be more rigorously taken into account. The comparison of the two statistical techniques, in the specific experimental setting presented here, indicates that more skilful results are achieved with RegEM as low frequency variability is better preserved. We further detect seasonal differences in reconstruction skill for the continental scale, as e.g. the target temperature average is more adequately reconstructed for summer than for winter. For the specific predictor network given in this paper, both techniques underestimate the target temperature variations to an increasing extent as more noise is added to the signal, albeit RegEM less than with PC regression. We conclude that climate field reconstruction techniques can be improved and need to be further optimized in future applications.

Determining the long-term changes in biodiversity and provisioning services along a transect from Central Europe to the Mediterranean

Climate, land use and fire are strong determinants of plant diversity, potentially resulting in local extinctions, including rare endemic and economically valuable species. While climate and land use are decisive for vegetation composition and thus the species pool, fire disturbance can lead to landscape fragmentation, affecting the provisioning of important ecosystem services such as timber and raw natural resources. We use multi-proxy palaeoecological data with high taxonomic and temporal resolution across an environmental gradient to assess the long-term impact of major climate shifts, land use and fire disturbance on past vegetation openness and plant diversity (evenness and richness). Evenness of taxa is inferred by calculating the probability of interspecific encounter (PIE) of pollen and spores and species richness by palynological richness (PRI). To account for evenness distortions of PRI, we developed a new palaeodiversity measure, which is evenness-detrended palynological richness (DE-PRI). Reconstructed species richness increases from north to south regardless of time, mirroring the biodiversity increase across the gradient from temperate deciduous to subtropical evergreen vegetation. Climatic changes after the end of the last ice age contributed to biodiversity dynamics, usually by promoting species richness and evenness in response to warming. The data reveal that the promotion of diverse open-land ecosystems increased when human disturbance became determinant, while forests became less diverse. Our results imply that the today’s biodiversity has been shaped by anthropogenic forcing over the millennia. Future management strategies aiming at a successful conservation of biodiversity should therefore consider the millennia-lasting role of anthropogenic fire and human activities.

Evaluating watershed service availability under future management and climate change scenarios in the Pangani Basin

Watershed services are the benefits people obtain from the flow of water through a watershed. While demand for such services is increasing in most parts of the world, supply is getting more insecure due to human impacts on ecosystems such as climate or land use change. Population and water management authorities therefore require information on the potential availability of watershed services in the future and the trade-offs involved. In this study, the Soil and Water Assessment Tool (SWAT) is used to model watershed service availability for future management and climate change scenarios in the East African Pangani Basin. In order to quantify actual “benefits”, SWAT2005 was slightly modified, calibrated and configured at the required spatial and temporal resolution so that simulated water resources and processes could be characterized based on their valuation by stakeholders and their accessibility. The calibrated model was then used to evaluate three management and three climate scenarios. The results show that by the year 2025, not primarily the physical availability of water, but access to water resources and efficiency of use represent the greatest challenges. Water to cover basic human needs is available at least 95% of time but must be made accessible to the population through investments in distribution infrastructure. Concerning the trade-off between agricultural use and hydropower production, there is virtually no potential for an increase in hydropower even if it is given priority. Agriculture will necessarily expand spatially as a result of population growth, and can even benefit from higher irrigation water availability per area unit, given improved irrigation efficiency and enforced regulation to ensure equitable distribution of available water. The decline in services from natural terrestrial ecosystems (e.g. charcoal, food), due to the expansion of agriculture, increases the vulnerability of residents who depend on such services mostly in times of drought. The expected impacts of climate change may contribute to an increase or decrease in watershed service availability, but are only marginal and much lower than management impacts up to the year 2025.

Geomorphic coupling between hillslopes and channels in the Swiss Alps

The coupling relationships between hillslope and channel network are fundamental for the understanding of mountainous landscapes' evolution. Here, we applied dendrogeomorphic methods to identify the hillslope–channel relationship and the sediment transfer dynamics within an alpine catchment, at the highest possible resolution. The Schimbrig catchment is located in the central Swiss Alps and can be divided into two distinct geomorphic sectors. To the east, the Schimbrig earth flow is the largest sediment source of the basin, while to the west, the Rossloch channel network is affected by numerous shallow landslides responsible for the supply of sediment from hillslopes to channels. To understand the connectivity between hillslopes and channels and between sources and sink, trees were sampled along the main Rossloch stream, on the Schimbrig earth flow and on the Rossloch depositional area. Geomorphic observations and dendrogeomophic results indicate different mechanisms of sediment production, transfer and deposition between upper and lower segments of the channel network. In the source areas (upper part of the Rossloch channel system), sediment is delivered to the channel network through slow movements of the ground, typical of earth flow, shallow landslides and soil creep. Contrariwise, in the depositional area (lower part of the channel network), the mechanisms of sediment transfer are mainly due to torrential activity, floods and debris flows. Tree analysis allowed the reconstruction of periods of high activity during the last century for the entire catchment. The collected dataset presents a very high temporal resolution but we encountered some limitations in establishing the source-to-sink connectivity at the catchment-wide scale. Despite these uncertainties, for decennial timescales the results suggest a direct coupling between hillslopes and neighbouring channels in the Rossloch channel network, and a de-coupling between sediment sources and sink farther downstream, with connections possible only during extraordinary events.

Dilution of non-reactive tracers in variably saturated sandy structures

Based on a dye tracer experiment in a sand tank we addressed the problem of local dispersion of conservative tracers in the unsaturated zone. The sand bedding was designed to have a defined spatial heterogeneity with a strong anisotropy. We estimated the parameters that characterize the local dispersion and dilution from concentration maps of a high spatial and temporal resolution obtained by image analysis. The plume spreading and mixing behavior was quantified on the basis of the coefficient of variation of the concentration and of the dilution index. The heterogeneous structure modified the flow pattern depending on water saturation. The shape of the tracer plumes revealed the structural signature of the sand bedding at low saturation only. In this case pronounced preferential flow was observed. At higher flow rates the structure remained hidden by a spatially almost homogeneous behavior of the plumes. In this context, we mainly discuss the mechanism of re-distributing a finite mass of inert solutes over a large volume, due to macro- and micro-heterogeneities of the structure. (C) 2001 Elsevier Science Ltd. AU rights reserved.

Continuous Flow Analysis of labile iron in ice-cores

The important active and passive role of mineral dust aerosol in the climate and the global carbon cycle over the last glacial/interglacial cycles has been recognized. However, little data on the most important aeolian dust-derived biological micronutrient, iron (Fe), has so far been available from ice-cores from Greenland or Antarctica. Furthermore, Fe deposition reconstructions derived from the palaeoproxies particulate dust and calcium differ significantly from the Fe flux data available. The ability to measure high temporal resolution Fe data in polar ice-cores is crucial for the study of the timing and magnitude of relationships between geochemical events and biological responses in the open ocean. This work adapts an existing flow injection analysis (FIA) methodology for low-level trace Fe determinations with an existing glaciochemical analysis system, continuous flow analysis (CFA) of ice-cores. Fe-induced oxidation of N,N′-dimethyl-p-pheylenediamine (DPD) is used to quantify the biologically more important and easily leachable Fe fraction released in a controlled digestion step at pH ∼1.0. The developed method was successfully applied to the determination of labile Fe in ice-core samples collected from the Antarctic Byrd ice-core and the Greenland Ice-Core Project (GRIP) ice-core.

Northern Hemisphere temperature reconstruction during the last millennium using multiple annual proxies

Previous studies have either exclusively used annual tree-ring data or have combined tree-ring series with other, lower temporal resolution proxy series. Both approaches can lead to significant uncertainties, as tree-rings may underestimate the amplitude of past temperature variations, and the validity of non-annual records cannot be clearly assessed. In this study, we assembled 45 published Northern Hemisphere (NH) temperature proxy records covering the past millennium, each of which satisfied 3 essential criteria: the series must be of annual resolution, span at least a thousand years, and represent an explicit temperature signal. Suitable climate archives included ice cores, varved lake sediments, tree-rings and speleothems. We reconstructed the average annual land temperature series for the NH over the last millennium by applying 3 different reconstruction techniques: (1) principal components (PC) plus second-order autoregressive model (AR2), (2) composite plus scale (CPS) and (3) regularized errors-in-variables approach (EIV). Our reconstruction is in excellent agreement with 6 climate model simulations (including the first 5 models derived from the fifth phase of the Coupled Model Intercomparison Project (CMIP5) and an earth system model of intermediate complexity (LOVECLIM), showing similar temperatures at multi-decadal timescales; however, all simulations appear to underestimate the temperature during the Medieval Warm Period (MWP). A comparison with other NH reconstructions shows that our results are consistent with earlier studies. These results indicate that well-validated annual proxy series should be used to minimize proxy-based artifacts, and that these proxy series contain sufficient information to reconstruct the low-frequency climate variability over the past millennium.

State-of-the-art aortic imaging: part I - fundamentals and perspectives of CT and MRI

Over the last two decades, imaging of the aorta has undergone a clinically relevant change. As part of the change non-invasive imaging techniques have replaced invasive intra-arterial digital subtraction angiography as the former imaging gold standard for aortic diseases. Computed tomography (CT) and magnetic resonance imaging (MRI) constitute the backbone of pre- and postoperative aortic imaging because they allow for imaging of the entire aorta and its branches. The first part of this review article describes the imaging principles of CT and MRI with regard to aortic disease, shows how both technologies can be applied in every day clinical practice, offering exciting perspectives. Recent CT scanner generations deliver excellent image quality with a high spatial and temporal resolution. Technical developments have resulted in CT scan performed within a few seconds for the entire aorta. Therefore, CT angiography (CTA) is the imaging technology of choice for evaluating acute aortic syndromes, for diagnosis of most aortic pathologies, preoperative planning and postoperative follow-up after endovascular aortic repair. However, radiation dose and the risk of contrast induced nephropathy are major downsides of CTA. Optimisation of scan protocols and contrast media administration can help to reduce the required radiation dose and contrast media. MR angiography (MRA) is an excellent alternative to CTA for both diagnosis of aortic pathologies and postoperative follow-up. The lack of radiation is particularly beneficial for younger patients. A potential side effect of gadolinium contrast agents is nephrogenic systemic fibrosis (NSF). In patients with high risk of NSF unenhanced MRA can be performed with both ECG- and breath-gating techniques. Additionally, MRI provides the possibility to visualise and measure both dynamic and flow information.