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Hypotheses (1) The equilibrium size and characteristics of a radially wicked fluid on porous material such as paper is expected to be dependent on the fluid properties and therefore could serve as a diagnostic tool. (2) The change in wicked stain size between biological fluids is dependent on a change in solid-liquid surface interfacial energy due to protein adsorption. Experiments Sessile droplets of increasing volume of blood, its components, and model fluids were deposited onto paper and the equilibrium stain size after coming to a halt was recorded. The contact angle of fluid droplets on model cellulose surfaces was measured to quantify the effect that blood protein adsorption at the solid-liquid interface has on radially wicked equilibrium size. Finally the significance of droplet evaporation for the time scale of interest was analysed. Findings The final stain area of all fluids tested on paper scales remarkably linearly with droplet volume. Different fluids were compared and the gradient of this linear relation was measured. Model fluids varying in surface tension and viscosity all behave similarly and exhibit a constant gradient. Blood and its components produce smaller stains, demonstrated by lower gradients. The gradient is a function of protein concentration, thus the mechanism of this phenomenon was identified as protein adsorption at the cellulose-liquid interface. The slope of the area/volume relationship for droplets is an important quantitative mechanistic variable. [ABSTRACT FROM AUTHOR]

Hypothesis The process of dried blood spot sampling involves simultaneous spreading and penetration of blood into a porous filter paper with subsequent evaporation and drying. Spreading of small drops of blood, which is a non-Newtonian liquid, over a dry porous layer is investigated from both theoretical and experimental points of view. Experiments and theory A system of two differential equations is derived, which describes the time evolution of radii of both the drop base and the wetted region inside the porous medium. The system of equations does not include any fitting parameters. The predicted time evolutions of both radii are compared with experimental data published earlier. Findings For a given power law dependency of viscosity of blood with different hematocrit level, radii of both drop base and wetted region, and contact angle fell on three universal curves if appropriate scales are used with a plot of the dimensionless radii of the drop base and the wetted region inside the porous layer and dynamic contact angle on dimensionless time. The predicted theoretical relationships are three universal curves accounting satisfactorily for the experimental data. [ABSTRACT FROM AUTHOR]

Abstract: Since its inception over twenty years ago, the field of functional magnetic resonance imaging (fMRI) has grown in usage, sophistication, range of applications, and impact. After twenty years, it''s useful to briefly look back as well as forward — to size up just how far we have come and speculate just how far we may go. This is an introduction to the special issue of “Twenty years of fMRI: the science and the stories.” The one-hundred and three papers in this special issue highlight the major methodological developments and controversies of fMRI from a first person perspective over the past twenty years. The growth of this field is not just fascinating from a science and technology perspective, but also from a human perspective. Most who were fortunate enough to be part of this effort at the beginning, as well as those who jumped in along the way have their fair share of interesting stories consisting of top rate science as well as intense thought and effort, good or bad fortune, and some claim to a contribution. These stories are in the following papers, written by the current leaders in the field and the innovators throughout the twenty year history. The categories, designed to cover every aspect of the emergence and development of fMRI, include: pre-fMRI; the first BOLD brain activation results; developments in pulse sequences, imaging methods, and hardware for fMRI; methodological developments, issues, and mechanisms; new paradigm designs; education; and the future. Within this issue, we have a collage of overlapping, complementary, yet sometimes contradictory accounts of what happened during the breathtakingly diverse and intense development of this still growing field over the past twenty years. [Copyright &y& Elsevier]

Abstract: Angiogenesis, the growth of a network of blood vessels, is a crucial component of solid tumour growth, linking the relatively harmless avascular growth phase and the potentially fatal vascular growth phase. As a process, angiogenesis is a well-orchestrated sequence of events involving endothelial cell migration, proliferation; degradation of tissue; new capillary vessel (sprout) formation; loop formation (anastomosis) and, crucially, blood flow through the network. Once there is blood flow associated with the nascent network, the subsequent growth of the network evolves both temporally and spatially in response to the combined effects of angiogenic factors, migratory cues via the extracellular matrix and perfusion-related haemodynamic forces in a manner that may be described as both adaptive and dynamic. In this paper we present a mathematical model which simultaneously couples vessel growth with blood flow through the vessels—dynamic adaptive tumour-induced angiogenesis (DATIA). This new mathematical model presents a theoretical and computational investigation of the process and highlights a number of important new targets for therapeutic intervention. In contrast to earlier flow models, where the effects of perfusion (blood flow) were essentially evaluated a posteriori, i.e. after generating a hollow network, blood flow in the model described in this paper has a direct impact during capillary growth, with radial adaptations and network remodelling occurring as immediate consequences of primary anastomoses. Capillary network architectures resulting from the dynamically adaptive model are found to differ radically from those obtained using earlier models. The DATIA model is used to examine the effects of changing various physical and biological model parameters on the developing vascular architecture and the delivery of chemotherapeutic drugs to the tumour. Subsequent simulations of chemotherapeutic treatments under different parameter regimes lead to the identification of a number of new therapeutic targets for tumour management. [Copyright &y& Elsevier]

In vivo studies of hepatic carbohydrate metabolism in (genetically modified) conscious mice are hampered by limitations of blood and urine sample sizes. We developed and validated methods to quantify stable isotope dilution and incorporation in small blood and urine samples spotted onto filter paper. Blood glucose and urinary paracetamol–glucuronic acid were extracted from filter paper spots reproducibly and with high yield. Fractional isotopomer distributions of glucose and paracetamol–glucuronic acid when extracted from filter paper spots were almost identical to those isolated from the original body fluids. Rates of infusion of labeled compounds could be adjusted without perturbing hepatic glucose metabolism. This approach was used in mice to find the optimal metabolic condition for the study of hepatic carbohydrate metabolism. In fed mice, no isotopic steady state was observed during a 6-h label-infusion experiment. In 9-h-fasted mice, isotopic steady state was reached after 3 h of label infusion and important parameters in hepatic glucose metabolism could be calculated. The rate of de novo glucose-6-phosphate synthesis was 143 ± 17 μmol kg−1 min−1 and partitioning to plasma glucose was 79.0 ± 5.2%. In 24-h-fasted mice, abrupt changes were noticed in whole body and in hepatic glucose metabolism at the end of the experiment. [Copyright &y& Elsevier]

Objective D-lactic acid in the mammalian body is mainly of microbiological origin and is often located somewhere along the digestive tract. Surgical, extensive re-sectioning of the small bowel may be one of the risk factors for altered balance in the microbiological environment. Higher levels in the body may lead to D-lactate acidosis and neurotoxicity; consequently, the possibility of diagnosis of this condition is important. Several analytical procedures for D-lactate have been introduced, but it is absolutely mandatory to distinguish this metabolite from the much more abundant and naturally occurring stereoisomer L-lactate. If enzymatic analytical methods are used, it is consequently essential to eliminate the response from L-lactate and the ubiquitous enzyme L-lactate dehydrogenase (L-LDH) (and other oxido-reductases) which will interfere with the D-lactate determination heavily. Design and methods The present paper introduces an enzymatic-fluorometric method for determination of D-lactate in biological matrices, including blood plasma, serum and urine. Macro molecules, including enzymes, were initially precipitated by ethanol and the supernatant used for analyses. Several plasma samples were analysed with and without standard addition of both L- and D-lactate in order to validate the assay. Results and conclusions The procedure effectively eliminates enzyme activities that may interfere with the D-lactate quantification, resulting in the situation that L-lactate in the sample does not interfere with the determination. Intra- and inter-assay precision, accuracy and recovery of the analyte were investigated and everything suggests that this method will be acceptable for analytical as well as descriptive purposes. The analytical procedure is suitable for a semi-automated large scale set-up in the laboratory. [ABSTRACT FROM AUTHOR]

Wild ungulates may act as reservoirs of various vector borne pathogens that can infect humans and domestic animals. In the present study, blood samples from 196 red deer ( Cervus elaphus ) from Western Austria (Vorarlberg, Tyrol and Salzburg) were collected on filter paper and tested for Anaplasmataceae , Piroplasmida, Rickettsia and filarioid helminths using molecular tools. Babesia divergens was detected in ten (5.1%) and Anaplasma phagocytophilum in three (1.5%) of the 196 samples. Filarioid helminths, Rickettsia spp. and Theileria spp. were not detected. These findings indicate that red deer may serve as reservoirs of Babesia divergens and Anaplasma phagocytophilum in Western Austria. Further investigations are needed to assess the presence of these pathogens in ticks in this geographical region, and the significance of these pathogens in both animals and humans. [ABSTRACT FROM AUTHOR]

• PCF-based sensors have been investigated for biomedical applications. • Various novel PCF-based structures have been also investigated. • Various novel nanomaterials used with PCF have been tested. • Several diseases diagnosis can be also perform with PCF. • Sensing performance of PCF-based sensors are high. Nowadays, the usage of photonic crystal fibers (PCF) has become a very quick and prevalent innovation in sensor implementation. PCFs have unique features and capabilities due to their geometric design, which makes them ideal choice for sensing applications. In this study, various simulations of biomedical sensors are analyzed. A biosensor is a type of an analytical device that analyses a biological system using either chemical or biological components. By filling the solutions into PCF shows good results in diagnosing disease, malignancies, hemoglobin concentrations and antibodies. PCF type biosensors are widely used in biological research, clinical trials, medication development and other applications. This research proposes a survey for different shapes of PCFs in biomedical sensors. This research paper main objective is to describe the numerous applications of biomedical sensors like glucose, blood, protein, and DNA sensors. The sensitivity and confinement loss are compared using this different-shaped PCF with different background materials. [ABSTRACT FROM AUTHOR]

This paper proposes a novel method for measuring blood plasma and serum viscosity with a microcantilever-based MEMS sensor. MEMS cantilevers are made of electroplated nickel and actuated remotely with magnetic field using an electro-coil. Real-time monitoring of cantilever resonant frequency is performed remotely using diffraction gratings fabricated at the tip of the dynamic cantilevers. Only few nanometer cantilever deflection is sufficient due to interferometric sensitivity of the readout. The resonant frequency of the cantilever is tracked with a phase lock loop (PLL) control circuit. The viscosities of liquid samples are obtained through the measurement of the cantilever’s frequency change with respect to a reference measurement taken within a liquid of known viscosity. We performed measurements with glycerol solutions at different temperatures and validated the repeatability of the system by comparing with a reference commercial viscometer. Experimental results are compared with the theoretical predictions based on Sader’s theory and agreed reasonably well. Afterwards viscosities of different Fetal Bovine Serum and Bovine Serum Albumin mixtures are measured both at 23°C and 37°C, body temperature. Finally the viscosities of human blood plasma samples taken from healthy donors are measured. The proposed method is capable of measuring viscosities from 0.86cP to 3.02cP, which covers human blood plasma viscosity range, with a resolution better than 0.04cP. The sample volume requirement is less than 150μl and can be reduced significantly with optimized cartridge design. Both the actuation and sensing are carried out remotely, which allows for disposable sensor cartridges. [ABSTRACT FROM AUTHOR]

Abstract: Di-isononyl phthalate (DINP) is a high molecular weight general purpose plasticizer used principally in the manufacture of flexible polyvinyl chloride (PVC) articles. DINP metabolites can be measured in biological media such as blood and urine. However, measurement of a substance in the blood or urine does not by itself mean that the chemical causes or is associated with adverse health outcomes. This is particularly pertinent given the advances in modern analytical techniques whereby ever diminishing trace amounts of substances can be detected. Therefore, it is a scientific necessity that risk assessors understand the relationship of biomonitoring data to estimation of exposure so that appropriate comparisons can be made to the no observed adverse effects levels (NOAELs) or other points of departure from toxicological studies in animals. In this paper, estimates of daily DINP intake are calculated for various population segments based on urinary biomonitoring data and are compared to estimates of exposure based on indirect methods and to health-based exposure guidance values. In general, intake estimates converge on a mean of 1–2μg/kg/day regardless of source of exposure or population cluster; a value 2-orders of magnitude lower than health-based exposure guidance values, ranging from 120 to 290μg/kg/day, which have been established by regulatory authorities and other authoritative bodies as representing acceptable levels. [Copyright &y& Elsevier]

Abstract: Dried blood spot (DBS) methods are currently available for identification of a range of lysosomal storage disorders (LSDs). These disorders are generally characterized by a deficiency of activity of a lysosomal enzyme and by a broad spectrum of phenotypes. Diagnosis of LSD patients is often delayed, which is of particular concern as therapeutic outcomes (e.g. enzyme replacement therapy) are generally more favorable in early disease stages. Experts in the field of LSDs diagnostics and screening programs convened and reviewed experiences with the use of DBS methods, and discuss the diagnostic challenges, possible applications and quality programs in this paper. Given the easy sampling and shipping and stability of samples, DBS has evident advantages over other laboratory methods and can be particularly helpful in the early identification of affected LSD patients through neonatal screening, high-risk population screening or family screening. [Copyright &y& Elsevier]

Abstract: Blood progenitors arise from a pool of pluripotential cells (“hemangioblasts”) within the Drosophila embryonic mesoderm. The fact that the cardiogenic mesoderm consists of only a small number of highly stereotypically patterned cells that can be queried individually regarding their gene expression in normal and mutant embryos is one of the significant advantages that Drosophila offers to dissect the mechanism specifying the fate of these cells. We show in this paper that the expression of the Notch ligand Delta (Dl) reveals segmentally reiterated mesodermal clusters (“cardiogenic clusters”) that constitute the cardiogenic mesoderm. These clusters give rise to cardioblasts, blood progenitors and nephrocytes. Cardioblasts emerging from the cardiogenic clusters accumulate high levels of Dl, which is required to prevent more cells from adopting the cardioblast fate. In embryos lacking Dl function, all cells of the cardiogenic clusters become cardioblasts, and blood progenitors are lacking. Concomitant activation of the Mitogen Activated Protein Kinase (MAPK) pathway by Epidermal Growth Factor Receptor (EGFR) and Fibroblast Growth Factor Receptor (FGFR) is required for the specification and maintenance of the cardiogenic mesoderm; in addition, the spatially restricted localization of some of the FGFR ligands may be instrumental in controlling the spatial restriction of the Dl ligand to presumptive cardioblasts. [Copyright &y& Elsevier]

Abstract: In Korea, there have been a number of efforts to measure levels of exposure to environmental pollutants among the population. This paper focuses on investigating the distribution of, extent of, and factors influencing the blood levels of lead, cadmium, and mercury in the Korean population, working from data obtained from the Second Korean National Human Exposure and Bio-monitoring Examination. To that end, blood metal concentrations were analyzed from a total of 2369 participants who were 18 years of age and older. The geometric mean concentrations and their 95% confidence intervals of metals in blood were found to be lead, 1.72μg/dL (95% CI, 1.68–1.76); cadmium, 1.02μg/L (95% CI, 1.00–1.05); and mercury, 3.80μg/L (95% CI, 3.66–3.93). Regression analyses indicate that the levels of metals in the blood are mainly influenced by gender, age, and the education levels of the participants. Current smoking status is also found to be a significant factor for increasing both lead and cadmium levels. Although our study, as the first nationwide survey of exposure to environmental pollutants in Korea, has value on its own, it should be expanded and extended in order to provide information on environmental exposure pathways and to watch for changes in the level of exposure to environmental pollutants among the population. [Copyright &y& Elsevier]

Abstract: Quantitative structure property relationship (QSPR) models for the prediction of human blood:air partition coefficient (log K blood) of volatile organic compounds (VOCs) has been developed based on the linear heuristic method (HM) and non-linear radial basis function neural networks (RBFNNs). Molecular descriptors that are calculated from the structures alone were used to represent the characteristics of the compounds. HM was used both to pre-select the whole descriptor sets and to build the linear model. RBFNN was performed to obtain more accurate models. Both the linear and the non-linear models can give very satisfactory prediction results: the correlation coefficient R was 0.964 and 0.979, and the root-mean-square (RMS) error was 0.3303 and 0.2542 for the whole data set, respectively. The prediction result of the non-linear model is better than that obtained by the linear model. In addition, this paper provides an effective method for predicting log K blood from its structures and gives some insight into the structural features related to the solubility of VOCs in human blood. [Copyright &y& Elsevier]

Abstract: Epstein–Barr virus (EBV) is an important human pathogen that establishes a life-long persistent infection and for which no precise animal model exists. In this paper, we describe in detail an agent-based model and computer simulation of EBV infection. Agents representing EBV and sets of B and T lymphocytes move and interact on a three-dimensional grid approximating Waldeyer''s ring, together with abstract compartments for lymph and blood. The simulation allows us to explore the development and resolution of virtual infections in a manner not possible in actual human experiments. Specifically, we identify parameters capable of inducing clearance, persistent infection, or death. [Copyright &y& Elsevier]

The potential effects of proposed lead–zinc mining in an ecologically sensitive area were assessed by studying a nearby mining district that has been exploited for about 30yr under contemporary environmental regulations and with modern technology. Blood and liver samples representing fish of three species (largescale stoneroller, Campostoma oligolepis, n=91; longear sunfish, Lepomis megalotis, n=105; and northern hog sucker, Hypentelium nigricans, n=20) were collected from 16 sites representing a range of conditions relative to lead–zinc mining and ore beneficiation in southeastern Missouri. Samples were analyzed for lead, zinc, and cadmium, and for a suite of biomarkers (reported in a companion paper). A subset of the hog sucker (n=9) representing three sites were also analyzed for nickel and cobalt. Blood and liver lead concentrations were highly correlated (r=0. 84–0. 85, P<0. 01) in all three species and were significantly (ANOVA, P<0. 01) greater at sites <10km downstream of active lead–zinc mines and mills and in a historical lead–zinc mining area than at reference sites, including a site in the area proposed for new mining. Correlations between blood and liver cadmium concentrations were less evident than for lead but were nevertheless statistically significant (r=0. 26–0. 69, P <0. 01–0. 07). Although blood and liver cadmium concentrations were highest in all three species at sites near mines, within-site variability was greater and mining-related trends were less evident than for lead. Blood and liver zinc concentrations were significantly correlated only in stoneroller (r=0. 46, P<0. 01) and mining-related trends were not evident. Concentrations of cobalt and nickel in blood and liver were significantly higher (ANOVA, P<0. 01) at a site near an active mine than at a reference site and a site in the historical lead–zinc mining area. These findings confirm previous studies indicating that lead and other metals are released to streams from active lead–zinc mines and are available for uptake by aquatic organisms. [Copyright &y& Elsevier]

Abstract: Near-infrared spectroscopy (NIRS) is widely used to record activation-related blood oxygenation changes in human brain tissue. However, the changes in the NIRS signal upon increased flow are influenced not only by the hemoglobin and oxyhemoglobin concentrations but also by changes in light scattering by various brain constituents. This paper points out the large contribution of flow-dependent red blood cell (RBC) aggregation as a cause of this altered light scattering, a phenomenon which has not previously been considered in the theoretical analysis of NIRS signals. Here, we show that RBCs, which constitute a major chromophore in the tissue, not only absorb light at hemoglobin molecules but also scatter it strongly at the cell membranes of aggregated RBCs, and that the blood optical density per se changes greatly with the size of the plasma gap, which varies according to flow. When local blood flow increases by 50%, the amount of the optical attenuation due to RBC dispersion/disaggregation (the flow effect) can reach 90% of the NIRS signal change for venous blood. The reasons why the optical signal due to blood oxygenation alone can be amount to less than 10% of the total are because the near-infrared lies in the most unfavorable range in the hemoglobin absorption spectrum for determining blood oxygenation, while the flow effect in the NIR range is large. We conclude that reported activation-related changes in brain blood oxygenation, at least in the peripheral region around the activation focus, based on NIRS can be mainly ascribed to the flow effect arising from RBC dispersion/disaggregation with increased flow in the venous system. [Copyright &y& Elsevier]

Abstract: Blood and protein residue identification in archaeological research has been a controversial subject for the last 20years. This paper reports on the use of an improved protein radioimmunoassay (pRIA) technique in identifying protein residues. Results from the blind testing of the original and improved pRIA techniques in identifying bloodstains on experimental lithic artifacts are described and compared. We argue that the improved pRIA technique is highly sensitive and accurate for identifying protein residues to genus, and thus has excellent applications for archaeological research. [Copyright &y& Elsevier]

Abstract: Several prevalent and life-threatening agents enter the organism via the mucosa. In this case, a mucosal cellular immune response is essential for protection and is therefore considered the main objective of vaccination. The frequency of antigen-specific CD4+ and CD8+ T cells can be determined directly in human whole blood by a combination of surface marker and intracellular cytokine staining. Immune cells primed in the mucosal compartment also migrate through the blood and can be identified by expression of the gut-specific homing receptor α4β7. Simultaneously, these lymphocytes can be functionally characterized regarding their differentiation status by analysis of CD45RO and CD27 expression and effector functions by measuring intracellular perforin or granzyme B content. Thus, the technique described in the paper is a powerful tool for clinical monitoring of the total cellular immune response to complex antigens during infection or vaccination. [Copyright &y& Elsevier]

Abstract: This paper describes the optimisation of a screen-printing water-based carbon ink containing cobalt phthalocyanine (CoPC) and glucose oxidase (GOD) for the fabrication of a glucose biosensor. To optimise the performance of the biosensor, the loadings of the electrocatalyst (CoPC) and enzyme (GOD) were varied. It was found that the maximum linear range was achieved with a CoPC loading of 20% (m/m, relative to the mass of carbon) and a GOD loading of 628U per gram of carbon. In our studies we chose to employ chronoamperometry, as this technique is commonly used for commercial devices. The optimum operating applied potential was found to be +0.5V, following an incubation period of 60s. The optimum supporting electrolyte was found to be 0.05M phosphate buffer at pH 8.0, which resulted in a linear range of 0.2–5mM, the former represents the detection limit. The sensitivity was 1.12μAmM−1. The effect of temperature was also investigated, and it was found that 40°C gave optimal performance. The resulting amperometric biosensors were evaluated by measuring the glucose concentrations for 10 different human plasma samples containing endogenous glucose and also added glucose. The same samples were analysed by a standard spectrophotometric method, and the results obtained by the two different methods were compared. A good correlation coefficient (R 2 =0.95) and slope (0.98) were calculated from the experimental data, indicating that the new devices hold promise for biomedical studies. [Copyright &y& Elsevier]

Abstract: Widespread exposure to the volatile aromatic hydrocarbons, ortho-, meta-, and para-xylene occurs in many industries including the manufacture of plastics, pharmaceuticals, and synthetic fibers. This paper describes the development of a physiologically based toxicokinetic model using biomonitoring data to quantify the kinetics of ortho-, meta-, and para-xylenes. Serial blood concentrations of deuterium-labeled xylene isomers were obtained over 4 days after 37 controlled, 2h inhalation exposures to different concentrations of the isomers. Peak toxicant concentrations in blood occurred in all subjects at the termination of exposure. Systemic clearance averaged 116L/h±34L/h, 117L/h±23L/h, and 129L/h±33L/h for ortho-, para-, and meta-xylene, respectively. The half-life of each toxicant in the terminal phase (>90h post-exposure) was fit by the model, yielding values of 30.3±10.2h for para-xylene, 33.0±11.7 h for meta-xylene and 38.5±18.2h for ortho-xylene. Significant isomeric differences were found (p <0.05) for toxicant half-life, clearance and extrahepatic metabolism. Inter-individual variability seen in this study suggests that airborne concentration guidelines may not protect all workers. A Biological Exposure Index is preferred for this purpose since it is integrative and reflective of inter-individual kinetic variability. [Copyright &y& Elsevier]

Abstract: In MRI and fMRI, images or voxel measurement are complex valued or bivariate at each time point. Recently, (Rowe, D.B., Logan, B.R., 2004. A complex way to compute fMRI activation. NeuroImage 23 (3), 1078–1092) introduced an fMRI magnitude activation model that utilized both the real and imaginary data in each voxel. This model, following traditional beliefs, specified that the phase time course were fixed unknown quantities which may be estimated voxel-by-voxel. Subsequently, (Rowe, D.B., Logan, B.R., 2005. Complex fMRI analysis with unrestricted phase is equivalent to a magnitude-only model. NeuroImage 24 (2), 603–606) generalized the model to have no restrictions on the phase time course. They showed that this unrestricted phase model was mathematically equivalent to the usual magnitude-only data model including regression coefficients and voxel activation statistic but philosophically different due to it derivation from complex data. Recent findings by (Hoogenrad, F.G., Reichenbach, J.R., Haacke, E.M., Lai, S., Kuppusamy, K., Sprenger, M., 1998. In vivo measurement of changes in venous blood-oxygenation with high resolution functional MRI at .95 Tesla by measuring changes in susceptibility and velocity. Magn. Reson. Med. 39 (1), 97–107) and (Menon, R.S., 2002. Postacquisition suppression of large-vessel BOLD signals in high-resolution fMRI. Magn. Reson. Med. 47 (1), 1–9) indicate that the voxel phase time course may exhibit task related changes. In this paper, a general complex fMRI activation model is introduced that describes both the magnitude and phase in complex data which can be used to specifically characterize task related change in both. Hypotheses regarding task related magnitude and/or phase changes are evaluated using derived activation statistics. It was found that the Rowe–Logan complex constant phase model strongly biases against voxels with task related phase changes and that the current very general complex linear phase model can be cast to address several different hypotheses sensitive to different magnitude/phase changes. [Copyright &y& Elsevier]

In the present study, we determined the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Cyprus using two different procedures in two separate adult population groups: a semiquantitative fluorescence test on blood spotted on filter paper and a quantitative spectrophotometric test on liquid blood. The frequency of G6PD deficiency among healthy adult males was found to be 5.1% using the semiquantitative procedure and 6.4% using the quantitative procedure. Neither method was able to detect all the expected female heterozygotes (5.3% and 47.1% of the expected number, respectively). A total of 21 male hemizygotes, 1 female homozygote and 9 female heterozygotes that tested positive for G6PD deficiency were studied at the molecular level. All 32 chromosomes were genotyped and five different mutations were identified. The Mediterranean mutation in exon 6 (563C→T) (Ser188Phe) was found to be the most common variant in the Cypriot population, accounting for 52.6% of the deficient alleles. In the remaining chromosomes, four different mutations were identified: three known mutations, Kaiping 1388G→A (Arg463His), Chatham 1003G→A (Ala335Thr) and Acrokorinthos 463C→G (His155Asp), and one previously undescribed mutation in exon 3, 148C→T (Pro50Ser), which we called G6PD Kambos. We conclude that the frequency of G6PD deficiency in Cypriot males is 6.4%, and that this deficiency is the result of several different mutations. Although all the individuals carrying the Mediterranean variant can be detected using a semiquantitative screening method, a quantitative enzyme measurement is required to detect the G6PD variants with less severe enzyme deficiencies, while the most appropriate method for heterozygote detection is DNA analysis. [Copyright &y& Elsevier]

The complexity of Nucleic acid Amplification Technology (NAT11Also known as Nucleic acid Amplification Testing or Technology.), comprising sample preparation, amplification and detection methods, requires specific design considerations for both the laboratory and the procedures utilized in such testing. The purpose of this paper is to establish technical considerations for the performance of NAT. These include the collection, handling and assay of specimens and the design of laboratories to routinely and reliably detect low levels of nucleic acid sequences. The sensitivity of NAT due to the exponential amplification of nucleic acids makes contamination a major concern from specimen collection to sample detection. Therefore, laboratories need to be designed to prevent and control contamination through adequate equipment and appropriate workflow. These technical considerations should provide a basis for establishing a robust and reproducible NAT system. [Copyright &y& Elsevier]

The lacrimal urea content was found to be proportional to that of blood, which suggested its possible utilization in the monitoring of hemodialysis as a less invasive method. On the other hand, however, arginase activity was detected in tears, which may influence the urea content independently of blood urea concentration. The feasibility of using lacrimal urea measurement to replace blood urea measurement in the monitoring hemodialysis was also investigated.Blood and tear samples of 35 healthy persons and 43 renal patients undergoing hemodialysis were tested. Tear samples were collected on Schirmer paper strips. After elution the lacrimal urea content was measured by a colorimetric method. The determination of arginase activity was based on the release of urea and ornithine. The correlation between blood and lacrimal urea and arginase was studied by multivariate regression analysis. The lacrimal arginase isoenzyme pattern was investigated by native polyacrylamide gel electrophoresis and Western blotting. The effect of partially isoform-specific inhibitors was also studied.Blood urea levels in blood were significantly higher in the renal patients before dialysis than in the control patients (12·86±0·59 vs. 6·45±0·41 mm, p<0·0001). Blood sera arginase activity was very low. Lacrimal arginase activity was significantly higher in tears than in sera (p<0·0001 for each group). The tear/serum ratio of urea content was significantly different between controls and renal patients, particularly in postdialytic samples (1·89±0·07 vs. 3·49±0·31, p<0·0001). The correlation between lacrimal and blood sera urea was best in controls (r=0·89) and was better in predialytic (r=0·75) than in postdialytic (r=0·52) samples, depending on the level of arginase activity. In postdialytic samples a stronger correlation (r=0·77) between tear urea and arginase was observed. Both arginase isoforms were detected in tears, but the extrahepatic (arginase II) isoenzyme was present in higher concentration.In conclusion, the determination of lacrimal urea level as a possible less invasive replacement for blood urea determination could only be utilized in the monitoring of hemodialysis if lacrimal arginase is also measured. Blood urea levels can be correctly determined by using equations, which take into account arginase activity. The accuracy of these equations was checked on a new patient population. Both arginase isoenzymes were observed in lacrimal samples. [Copyright &y& Elsevier]