Blood flow in the capillary bed

From arteries to veins, the blood has to go through the ‘capillary’ blood vessels. These blood vessels are so small that often their diameter is smaller than that of the red blood cells. Intimate interactions occur, therefore, between the blood cells and the blood vessels.

A general survey of recent works on capillary blood flow is given in this article. Some details are presented for two problems: the problem of deformation of the flexible red blood cells, their motion in the capillary blood vessels, and the pressure drop due to the red cell blood vessel interaction; and the problem of the flow of plasma ‘bolus’ between neighboring red cells.

The solution supplies many details about the microcirculation phenomenon. Taken together, a method is offered for the calculation of pressure drop in the capillary as a function of various physical parameters: the red cell volume per unit blood volume, (hematocrit), the ratio of the cell diameter to the blood vessel diameter, the ratio of the length of the blood vessel to its length, the volume of individual red cells, and a parameter relating the cell membrane elasticity, plasma viscosity and the cell velocity.     

A method for in situ monitoring of the isotope composition of tree xylem water using laser spectroscopy

Field studies analyzing the stable isotope composition of xylem water are providing important information on ecosystem water relations. However, the capacity of stable isotopes to characterize the functioning of plants in their environment has not been fully explored because of methodological constraints on the extent and resolution at which samples could be collected and analysed. Here, we introduce an in situ method offering the potential to continuously monitor the stable isotope composition of tree xylem water via its vapour phase using a commercial laser‐based isotope analyser and compact microporous probes installed into the xylem. Our technique enables efficient high‐frequency measurement with intervals of only a few minutes per sample while eliminating the need for costly and cumbersome destructive collection of plant material and laboratory‐based processing. We present field observations of xylem water hydrogen and oxygen isotope compositions obtained over several days including a labelled irrigation event and compare them against results from concurrent destructive sampling with cryogenic distillation and mass spectrometric analysis. The data demonstrate that temporal changes as well as spatial patterns of integration in xylem water isotope composition can be resolved through direct measurement. The new technique can therefore present a valuable tool to study the hydraulic architecture and water utilization of trees.     

USING ISOLATION BY DISTANCE AND EFFECTIVE DENSITY TO ESTIMATE DISPERSAL SCALES IN ANEMONEFISH

Robust estimates of dispersal are critical for understanding population dynamics and local adaptation, as well as for successful spatial management. Genetic isolation by distance patterns hold clues to dispersal, but understanding these patterns quantitatively has been complicated by uncertainty in effective density. In this study, we genotyped populations of a coral reef fish (Amphiprion clarkii) at 13 microsatellite loci to uncover fine‐scale isolation by distance patterns in two replicate transects. Temporal changes in allele frequencies between generations suggested that effective densities in these populations are 4–21 adults/km. A separate estimate from census densities suggested that effective densities may be as high as 82–178 adults/km. Applying these effective densities with isolation by distance theory suggested that larval dispersal kernels in A. clarkii had a spread near 11 km (4–27 km). These kernels predicted low fractions of self‐recruitment in continuous habitats, but the same kernels were consistent with previously reported, high self‐recruitment fractions (40–60%) when realistic levels of habitat patchiness were considered. Our results suggested that ecologically relevant larval dispersal can be estimated with widely available genetic methods when effective density is measured carefully through cohort sampling and ecological censuses, and that self‐recruitment studies should be interpreted in light of habitat patchiness.     

Activation of the MAPKs ERK1/2 by cell swelling in turbot hepatocytes

Background information. Activation of MAPKs (mitogen‐activated protein kinases), in particular ERK1/2 (extracellular‐signal‐regulated kinase 1/2), has been reported to take place in a large variety of cell types after hypo‐osmotic cell swelling. Depending on cell type, ERK1/2 phosphorylation can then serve or not the RVD (regulatory volume decrease) process. The present study investigates ERK1/2 activation after aniso‐osmotic stimulations in turbot hepatocytes and the potential link between phosphorylation of these proteins and RVD. Results. In turbot hepatocytes, Western‐blot analysis shows that a hypo‐osmotic shock from 320 to 240 mOsm·kg^?1 induced a rapid increase in ERK1/2 phosphorylation, whereas a hyper‐osmotic shock from 320 to 400 mOsm·kg^?1 induced no significant change in the phosphorylation of these proteins. The hypo‐osmotic‐induced ERK1/2 phosphorylation was significantly prevented when hypo‐osmotic shock was performed in the presence of the specific MEK (MAPK/ERK kinase) inhibitor PD98059 (100 μM). In these conditions, the RVD process was not altered, suggesting that ERK1/2 did not participate in this process in turbot hepatocytes. Moreover, the hypo‐osmotic‐induced activation of ERK1/2 was significantly prevented by breakdown of extracellular ATP by apyrase (10 units·ml^?1), by inhibition of purinergic P₂ receptors by suramin (100 μM) or by calcium depletion using EGTA (1 mM) and thapsigargin (1 μM). Conclusions. In turbot hepatocytes, hypo‐osmotic swelling but not hyper‐osmotic shrinkage induced the activation of ERK1/2. However, these proteins do not seem to be involved in the RVD process. Their hypo‐osmotic‐induced activation is partially due to cascades of signalling events triggered by the binding of released ATP on purinergic P₂ receptors and requires the presence of calcium.     

Testing and interpreting the shared space‐environment fraction in variation partitioning analyses of ecological data

Variation partitioning analyses combined with spatial predictors (Moran's eigenvector maps, MEM) are commonly used in ecology to test the fractions of species abundance variation purely explained by environment and space. However, while these pure fractions can be tested using a classical residuals permutation procedure, no specific method has been developed to test the shared space‐environment fraction (SSEF). Yet, the SSEF is expected to encompass a major driver of community assembly, that is, an induced spatial dependence effect (ISD; i.e. the reflection of a spatially structured habitat filter on a species distribution). A reliable test of this fraction is therefore crucial to properly test the presence of an ISD on ecological data. To bridge the gap, we propose to test the SSEF through spatially‐constrained null models: torus‐translations, and Moran spectral randomisations. We investigated the type I error rate and statistical power of our method based on two real environmental datasets and simulations of tree distributions. Ten types of tree distribution displaying contrasted aggregation properties were simulated, and their abundances were sampled in 153 regularly‐distributed 20 × 20 m quadrats. The SSEF was tested for 1000 simulated tree distributions either unrelated to the environment, or filtered by environmental variables displaying contrasting spatial structures. The method proposed provided a correct type I error rate (< 0.05). The statistical power was high (> 0.9) when abundances were filtered by an environmental variable structured at broad scale. However, the spatial resolution allowed by the sampling design limited the power of the method when using a fine‐scale filtering variable. This highlighted that an ISD can be properly detected providing that the spatial pattern of the filtering process is correctly captured by the sampling design of the study. An R function to apply the SSEF testing method is provided and detailed in a tutorial.     

Local discriminative spatial patterns for movement-related potentials-based EEG classification

A novel discriminant method, termed local discriminative spatial patterns (LDSP), is proposed for movement-related potentials (MRPs)-based single-trial electroencephalogram (EEG) classification. Different from conventional discriminative spatial patterns (DSP), LDSP explicitly considers local structure of EEG trials in the construction of scatter matrices in the Fisher-like criterion. The underlying manifold structure of two-dimensional spatio-temporal EEG signals contains more discriminative information. LDSP is an extension to DSP in the sense that DSP can be formulated as a special case of LDSP. By constructing an adjacency matrix, LDSP is calculated as a generalized eigenvalue problem, and so is computationally straightforward. Experiments on MRPs-based single-trial EEG classification show the effectiveness of the proposed LDSP method.     

A spatially explicit method for evaluating accuracy of species distribution models

Aim Models predicting the spatial distribution of animals are increasingly used in wildlife management and conservation planning. There is growing recognition that common methods of evaluating species distribution model (SDM) accuracy, as a global overall value of predictive ability, could be enhanced by spatially evaluating the model thereby identifying local areas of relative predictive strength and weakness. Current methods of spatial SDM model assessment focus on applying local measures of spatial autocorrelation to SDM residuals, which require quantitative model outputs. However, SDM outputs are often probabilistic (relative probability of species occurrence) or categorical (species present or absent). The goal of this paper was to develop a new method, using a conditional randomization technique, which can be applied to directly spatially evaluate probabilistic and categorical SDMs. Location Eastern slopes, Rocky Mountains, Alberta, Canada. Methods We used predictions from seasonal grizzly bear (Ursus arctos) resource selection functions (RSF) models to demonstrate our spatial evaluation technique. Local test statistics computed from bear telemetry locations were used to identify areas where bears were located more frequently than predicted. We evaluated the spatial pattern of model inaccuracies using a measure of spatial autocorrelation, local Moran’s I. Results We found the model to have non‐stationary patterns in accuracy, with clusters of inaccuracies located in central habitat areas. Model inaccuracies varied seasonally, with the summer model performing the best and the least error in areas with high RSF values. The landscape characteristics associated with model inaccuracies were examined, and possible factors contributing to RSF error were identified. Main conclusions The presented method complements existing spatial approaches to model error assessment as it can be used with probabilistic and categorical model output, which is typical for SDMs. We recommend that SDM accuracy assessments be done spatially and resulting accuracy maps included in model metadata.     

Detection of process-related changes in plant patterns at extended spatial scales during early dryland desertification

Arid and semiarid shrublands occupy extensive land areas over the world, are susceptible to desertification by anthropic use and can contribute to regional climate change. These prompt the interest to monitor and evaluate these lands adequately in order to detect early stages of degradation. Evaluation topics must refer to biology‐relevant characteristics of these systems, while simultaneously satisfying sampling consistency over extended landscape areas. We present an analysis of process‐relevant parameters related to changes in the spatial arrangement of the plant canopy of shrublands inferred from high‐resolution panchromatic aerial photos and Interferometric Synthetic Aperture Radar imagery. We obtained low‐altitude images systematically located along several gradients of land‐use intensity in a Patagonian Monte shrubland in Argentina. Images were digitized to spatial resolutions ranging from 0.09 to 0.72 m (pixel size) and the average values and an‐isotropic characteristics of the plant canopy patterns were quantified by means of a Fourier metric. We used radar‐derived imagery to overlay the panchromatic images on a digital elevation model in order to study the correspondence of potential runoff patterns and the spatial arrangement of plants. We related an‐isotropic features of the plant canopy images to the prevailing wind regime. Observed trends were further interpreted on the basis of a spatial‐explicit simulation model describing the dynamics of the main functional groups in the plant community. We conclude that early stages of anthropic‐driven dryland degradation in the Patagonian Monte can be characterized by the incipient un‐coupling of spatial vegetation patterns from those of runoff at a landscape scale, and a progressive coupling to the spatial pattern of the wind regime. The method and metrics we present can be used to quantify early desertification changes in other similar drylands at extended spatial scales.     

A viscoelastic model of blood capillary extension and regression: derivation, analysis, and simulation

This work studies a fundamental problem in blood capillary growth: how the cell proliferation or death induces the stress response and the capillary extension or regression. We develop a one-dimensional viscoelastic model of blood capillary extension/regression under nonlinear friction with surroundings, analyze its solution properties, and simulate various growth patterns in angiogenesis. The mathematical model treats the cell density as the growth pressure eliciting a viscoelastic response from the cells, which again induces extension or regression of the capillary. Nonlinear analysis captures two cases when the biologically meaningful solution exists: (1) the cell density decreases from root to tip, which may occur in vessel regression; (2) the cell density is time-independent and is of small variation along the capillary, which may occur in capillary extension without proliferation. The linear analysis with perturbation in cell density due to proliferation or death predicts the global biological solution exists provided the change in cell density is sufficiently slow in time. Examples with blow-ups are captured by numerical approximations and the global solutions are recovered by slow growth processes, which validate the linear analysis theory. Numerical simulations demonstrate this model can reproduce angiogenesis experiments under several biological conditions including blood vessel extension without proliferation and blood vessel regression.     

Automatic and label‐free identification of blood vessels in gliomas using the combination of multiphoton microscopy and image analysis

Currently, the targeted treatment of tumor based on the tumor microenvironment is newly developed. Blood vessels are the key parts in the tumor microenvironment, which is taken as a new visible target for tumor therapy. Multiphoton microscopy (MPM), based on the second harmonic generation and two‐photon excited fluorescence, is available to make the label‐free analysis on the blood vessels in human gliomas. MPM can reveal the vascular morphological characteristics in gliomas, including vascular malformation, intense vascular proliferation, perivascular collagen deposition, perivascular lymphocytes aggregation and microvascular proliferation. In addition, the image analysis algorithms were developed to automatically calculate the perivascular collagen content, vascular cavity area, lumen area, wall area and vessel number. Thus, the vascular morphology, the perivascular collagen deposition and intense vascular proliferation degree can be further quantitatively characterized. Compared with the pathological analysis, the combination of MPM and image analysis has potential advantages in making a quantitative and qualitative analyzing on vascular morphology in glioma microenvironment. As micro‐endoscope and two‐photon fiberscope are technologically improved, this combined method will be a useful imaging way to make the real‐time research on the targeting tumor microenvironment in gliomas.     

Impacts of tropospheric ozone and climate change on net primary productivity and net carbon exchange of China's forest ecosystems

Aim We investigated how ozone pollution and climate change/variability have interactively affected net primary productivity (NPP) and net carbon exchange (NCE) across China's forest ecosystem in the past half century. Location Continental China. Methods Using the dynamic land ecosystem model (DLEM) in conjunction with 10‐km‐resolution gridded historical data sets (tropospheric O₃ concentrations, climate variability/change, and other environmental factors such as land‐cover/land‐use change (LCLUC), increasing CO₂ and nitrogen deposition), we conducted nine simulation experiments to: (1) investigate the temporo‐spatial patterns of NPP and NCE in China's forest ecosystems from 1961–2005; and (2) quantify the effects of tropospheric O₃ pollution alone or in combination with climate variability and other environmental stresses on forests' NPP and NCE. Results China's forests acted as a carbon sink during 1961–2005 as a result of the combined effects of O₃, climate, CO₂, nitrogen deposition and LCLUC. However, simulated results indicated that elevated O₃ caused a 7.7% decrease in national carbon storage, with O₃‐induced reductions in NCE (Pg C year^?1) ranging from 0.4–43.1% among different forest types. Sensitivity experiments showed that climate change was the dominant factor in controlling changes in temporo‐spatial patterns of annual NPP. The combined negative effects of O₃ pollution and climate change on NPP and NCE could be largely offset by the positive fertilization effects of nitrogen deposition and CO₂. Main conclusions In the future, tropospheric O₃ should be taken into account in order to fully understand the variations of carbon sequestration capacity of forests and assess the vulnerability of forest ecosystems to climate change and air pollution. Reducing air pollution in China is likely to increase the resilience of forests to climate change. This paper offers the first estimate of how prevention of air pollution can help to increase forest productivity and carbon sequestration in China's forested ecosystems.     

Spatial patterns of neutral and functional genetic variations reveal patterns of local adaptation in raccoon (Procyon lotor) populations exposed to raccoon rabies

Local adaptation is necessary for population survival and depends on the interplay between responses to selective forces and demographic processes that introduce or retain adaptive and maladaptive attributes. Host–parasite systems are dynamic, varying in space and time, where both host and parasites must adapt to their ever‐changing environment in order to survive. We investigated patterns of local adaptation in raccoon populations with varying temporal exposure to the raccoon rabies virus (RRV). RRV infects approximately 85% of the population when epizootic and has been presumed to be completely lethal once contracted; however, disease challenge experiments and varying spatial patterns of RRV spread suggest some level of immunity may exist. We first assessed patterns of local adaptation in raccoon populations along the eastern seaboard of North America by contrasting spatial patterns of neutral (microsatellite loci) and functional, major histocompatibility complex (MHC) genetic diversity and structure. We explored variation of MHC allele frequencies in the light of temporal population exposure to RRV (0–60 years) and specific RRV strains in infected raccoons. Our results revealed high levels of MHC variation (66 DRB exon 2 alleles) and pronounced genetic structure relative to neutral microsatellite loci, indicative of local adaptation. We found a positive association linking MHC genetic diversity and temporal RRV exposure, but no association with susceptibility and resistance to RRV strains. These results have implications for landscape epidemiology studies seeking to predict the spread of RRV and present an example of how population demographics influence the degree to which populations adapt to local selective pressures.     

Automated quantification of superficial retinal capillaries and large vessels for diabetic retinopathy on optical coherence tomographic angiography

Optical coherence tomography angiography (OCTA) is a relatively new technique with capillary‐level resolution, which has shown great potential for the diagnosis of diabetic retinopathy (DR). A fully automatic algorithm for the quantitative measurement of microcirculatory changes in sight‐threatening DR is presented. The foveal avascular zone (FAZ) segmentation was improved with a graph‐theoretic method and the large vessels and capillaries were separately identified and analyzed. The method was evaluated in healthy and diabetic eyes with various stages of retinopathy. Results showed that, compared with the healthy group, the diabetic group showed a significantly larger large vessel density, but a significantly smaller capillary density (P < .001). Circularity of FAZ was significantly smaller while nonperfusion area was significantly larger in the diabetic group. The combined variable of all image metrics reached an area under the ROC of 0.853 (95% CI, 0.784‐0.923) for mild to moderate nonproliferative DR and 0.950 (95% CI, 0.922‐0.979) for proliferative DR. Microvascular and FAZ changes with various DR stages can be accurately delineated using the developed automatic program. Quantitative metrics on OCTA serve as potential biomarkers for the staging of DR.     

The circulatory dynamics of human red blood cell homeostasis: Oxy-deoxy and PIEZO1-triggered changes

The vital function of red blood cells (RBCs) is to mediate the transport of oxygen from lungs to tissues and of CO₂ from tissues to lungs. The gas exchanges occur during capillary transits within fractions of a second. Each oxygenation-deoxygenation and deoxygenation-reoxygenation transition on hemoglobin triggers sharp changes in RBC pH, leading to downstream changes in ion fluxes, membrane potential, and cell volume. The dynamics of these changes during the variable periods between capillary transits in vivo remains a mystery inaccessible to study by current methodologies, a knowledge gap on a fundamental physiological process that is the focus of the present study. The use of a computational model of human RBC homeostasis of tested accreditation enabled a detailed investigation of the expected RBC changes during intercapillary transits, with results advancing novel insights and predictions. The predicted rates of relative RBC volume change on oxygenation-deoxygenation (oxy-deoxy) and deoxygenation-reoxygenation transitions were about 1.5%/min and ?0.9%/min, respectively, far too slow to allow the cells to reach steady states in the intervals between capillary transits. The amplitude of the oxy-deoxy-reoxygenation volume fluctuations varied in proportion with the duration of the intercapillary transit intervals. Upon capillary entry, oxy-deoxy-induced changes occur concurrently with deformation-induced PIEZO1 channel activation, both processes affecting cell pH, membrane potential, and cell volume during intertransit periods. The model showed that the effects were strictly additive as expected from processes operating independently on the cell’s homeostatic fabric. Analysis of the mechanisms behind these predictions revealed, for the first time, the complex interactions between oxy-deoxy and ion transport processes that ensure the long-term homeostatic stability of RBCs for optimal gas transport in physiological conditions and how these may become altered in diseased states. Possible designs of microfluidic devices to test the model predictions are discussed.     

Capillary blood flow imaging within human finger cuticle using optical microangiography

We report non‐invasive 3D imaging of capillary blood flow within human finger cuticle by the use of Doppler optical microangiography (DOMAG) and ultra‐high sensitive optical microangiography (UHS‐OMAG) techniques. Wide velocity range DOMAG method is applied to provide red blood cell (RBC) axial velocity mapping in capillary loops with ranges of ±0.9 mm/s and ±0.3 mm/s. Additionally, UHS‐OMAG technique is engineered to acquire high resolution image of capillary morphology. The presented results are promising to facilitate clinical trials of treatment and diagnosis of various diseases such as diabetes, Raynaud's phenomenon, and connective tissue diseases by quantifying cutaneous blood flow changes within human finger cuticle. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Optimal Hematocrit: Theory, Regulation and Implications

SYNOPSIS. Hematocrit is likely to be optimized because of itsinfluences on oxygen transport. However, optimal hematocritmust also change because shear rates and blood vessel radiiwithin circulations change temporally. Blood vessel endotheliaregulate shear stress on their walls by changing their radius.Wall shear stress is dependent on shear rate and viscosity.Because there is regulation of vessel radius by the endotheliumit is hypothesized that hematocrit may be regulated near optimalby changes in plasma volume. The implication of such regulationis that changes in vascular volume (blood volume) would occurwith alterations in red blood cell mass. Data are presentedwhich indicate that regulation of optimal hematocrit normallyoccurs through changes in plasma volume. The regulation of optimalhematocrit has significant implications for processes that dependon oxygen transport (e.g., exercise) because of the effect ofblood volume on cardiac output.     

Role of shear forces and adhesion molecule distribution on P-selectin-mediated leukocyte rolling in postcapillary venules

Rolling on the venular endothelium is a critical step in the recruitment of leukocytes during the inflammatory response. P-selectin is a key mediator of leukocyte rolling, which is an early event in the inflammatory cascade; this rolling is likely to be directly regulated by both local fluid shear forces and P-selectin site densities in the microvasculature. However, neither the spatial pattern of P-selectin expression in postcapillary venules nor the effect of local expression patterns on rolling behavior in intact functional venules is known. We investigated the influence of local shear forces and the spatial distribution of endothelial P-selectin in intact blood perfused post capillary venules in anesthetized mice using intravital confocal microscopy, high temporal resolution particle tracking, and immunofluorescent labeling. We demonstrated a shear-dependent increase in average leukocyte rolling velocity that was attributable to a shear-dependent increase in the occurrence of transient leukocyte detachments from the endothelial surface: translational velocity during leukocyte contact with the vessel wall remained constant. P-selectin expression was not different in venules with characteristically different shear rates or diameters but varied significantly within individual venules. In postcapillary venules, regions of high P-selectin expression correlated with regions of slow leukocyte rolling. Thus the characteristically variable leukocyte rolling in vivo is a function of the spatial heterogeneity in P-selectin expression. The study shows how the local hydrodynamic forces and the nonuniform pattern of P-selectin expression affect the behavior of interacting leukocytes, providing direct evidence for the local variation of adhesion molecule expression as a mechanism for the regulation of leukocyte recruitment.     

NONSTATIONARY PATTERNS OF ISOLATION‐BY‐DISTANCE: INFERRING MEASURES OF LOCAL GENETIC DIFFERENTIATION WITH BAYESIAN KRIGING

Patterns of isolation‐by‐distance (IBD) arise when population differentiation increases with increasing geographic distances. Patterns of IBD are usually caused by local spatial dispersal, which explains why differences of allele frequencies between populations accumulate with distance. However, spatial variations of demographic parameters such as migration rate or population density can generate nonstationary patterns of IBD where the rate at which genetic differentiation accumulates varies across space. To characterize nonstationary patterns of IBD, we infer local genetic differentiation based on Bayesian kriging. Local genetic differentiation for a sampled population is defined as the average genetic differentiation between the sampled population and fictive neighboring populations. To avoid defining populations in advance, the method can also be applied at the scale of individuals making it relevant for landscape genetics. Inference of local genetic differentiation relies on a matrix of pairwise similarity or dissimilarity between populations or individuals such as matrices of between pairs of populations. Simulation studies show that maps of local genetic differentiation can reveal barriers to gene flow but also other patterns such as continuous variations of gene flow across habitat. The potential of the method is illustrated with two datasets: single nucleotide polymorphisms from human Swedish populations and dominant markers for alpine plant species.     

Monitoring for occupational exposure to 4,4′-methylenebis(2-chloroaniline) by gas chromatographic-mass spectrometric analysis of haemoglobin adducts, blood, plasma and urine

The feasibility of using plasma, blood and haemoglobin adducts for monitoring occupational exposure to the suspected human carcinogen 4,4′-methylenebis(2-chloroaniline) (MOCA) was investigated. A method utilising capillary gas chromatography-negative-ion chemical-ionisation mass spectrometry (GC-MS) for the determination of pentafluoropropionyl (PFP) derivatives of MOCA, released by alkaline hydrolysis from protein adducts and conjugates, was both sensitive and selective. When selected ion monitoring was used, sub-femtomole amounts of PFP-MOCA could be measured. The detection limit for haemoglobin adducts of MOCA was below 10 fmol/g Hb, well below the levels found for occupationally exposed individuals. Capillary GC with electron-capture detection also had the required sensitivity for the determination of MOCA in blood and urine of five individuals who were exposed to MOCA during the manufacture of polyurethane elastomers were determined by the GC-MS method. The MOCA concentrations for the various blood fractions and urine were within the following ranges: haemoglobin adducts, 0.73–43.3 pmol MOCA/g Hb; plasma alkaline hydrolysate, 0.05–22.0 nmol/l; whole blood, 0.13–17.4nmol/l; urine, 4.5–2390 nmol/l. Because the products of MOCA in the blood reflect metabolic activation of MOCA and integrate exposure over a period of weeks, the use of blood samples for monitoring exposure to MOCA offers advantages over the currently used urinary MOCA measurements.