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In this paper, we focus on situations where documents serve to coordinate the work of a distributed collective engaged in common goal-directed activities. After defining the concept of semiotic products as resulting from symbolic communicational transactions, we present some coordination strategies which can be used to compensate for the spatio-socio-temporal distribution typical of these transactions. Among these strategies, it is proposed to study in detail the documentarisation strategy, which makes the material substrate mediating the transactions relatively durable and endows it with attributes making its further use possible. In our study of documentarisation processes, several novel concepts are introduced and used to describe Documents for Action (DofA), their characteristics and the conditions that should be respected for correctly annotating them. [ABSTRACT FROM AUTHOR]

We demonstrated a Diode Oscillator Fiber Amplification (DOFA) system in order to study the 63 P1 ↔53 D1 (1539 nm) transition line of a neutral ytterbium atom that is accessed by the stepwise excitation of the ground state. The frequency of the DOFA system was doubled by a MgO:PPLN crystal for the resonant excitation of the 61 S0 ↔63 P1 transition. The frequency of the second harmonic beam was stabilized to the 61 S0 ↔63 P1 transition of each isotope with the stability of about 2 MHz. We performed absorption spectroscopy on the 63 P1 ↔53 D1 (1539 nm) transition after the velocity selective excitation by the frequency-doubled beam. The isotope shifts in the 63 P1 ↔53 D1 (1539 nm) transition were directly measured for the first time. The relative isotope shifts from 174Yb were measured as −105.8 MHz and 109.7 MHz for 176Yb and 172Yb, respectively. [ABSTRACT FROM AUTHOR]

In this study, a multi-pass shaped roll drawing process was designed that applied four non-driven idle rolls to manufacture square-shaped profiles. Unlike other drawing processes, this process doesn't require an intermediate heat treatment between passes. The concept of average reduction was applied to design a pass schedule, and a method for designing the intermediate die shape was developed to ensure uniform deformation and limit strain deviation. The Geleji model was modified with a correction factor to predict the forming load, which can be ultimately used to confirm the process feasibility. The Taguchi method for experimental design was used to select the optimal process conditions to ensure dimensional accuracy. The derived conditions were used to fabricate dies and perform drawing experiments. The experimental results showed high dimensional accuracy and were consistent with the finite element (FE) analysis results. Thus, the proposed process can potentially be applied to various profiles in the future. [ABSTRACT FROM AUTHOR]

To efficiently learn new words, children use constraints such as mutual exclusivity (ME) to narrow the search for potential referents. The current study investigated the use of ME in toddlers with autism spectrum disorder (ASD) and neurotypical (NT) peers matched on nonverbal cognition. Thirty-two toddlers with ASD and 26 NT toddlers participated in a looking-while-listening task. Images of novel and familiar objects were presented along with a novel or familiar label. Overall, toddlers with ASD showed less efficient looking toward a novel referent when a novel label was presented compared to NT toddlers, controlling for age and familiar word knowledge. However, toddlers with ASD and higher language ability demonstrated more robust use of ME than those with lower language ability. [ABSTRACT FROM AUTHOR]

The main approaches to the incorporation of tritium and deuterium labels into various classes of biologically active compounds (lipids, nucleotides, amino acids, peptides, low molecular weight bioregulators, etc.) are summarized. The preparation of organic compounds labeled with hydrogen isotopes using various physicochemical methods is described. The effect of reaction conditions on the yield and content of hydrogen isotopes in labeled preparations is considered. Much attention is paid to the incorporation of deuterium and tritium through isotope exchange. Possible mechanisms for the incorporation of hydrogen isotopes and the distribution of the label in organic compounds associated with these processes are demonstrated. It was shown that irradiation of preparations, the use of intermediates, and other innovations can significantly improve the parameters of the desired labeled biologically active compounds. [ABSTRACT FROM AUTHOR]

In the case of the fuzzy correlation between variables of faults due to the complex monitoring information of diesel engines, neither Mahalanobis distance (MD) nor Euclidean distance (ED) can effectively diagnose by features, in this paper, a novel Adaptive Dynamic Weighted Hybrid Distance-Taguchi method (ADWHD-T) is presented to diagnose diesel engine faults. The method used Adaptive Dynamic Weighted Hybrid Distance (ADWHD) to fuse data of many sensors into the single system-level performance index. The ADWHD is an adaptive and dynamic weighting of MD and Standardized Euclidean distance (SED). The adaptive weights are adjusted according to the distance scale of MD and SED. The dynamic weight coefficients are calculated by the correlation coefficient of characteristic variables to consider the correlation and independence of characteristic variables. The diagnosis results are derived according to the optimized and adjusted fault threshold of ADWHD defined by 3σ method. In view of the dimension reduction optimization of characteristic variables, combining Taguchi method (T), ADWHD-T provides one systematic method for determining the key parameters of characteristic variables to solve the cost problem of multi-sensor analysis. Aiming at the real-time diagnosis, offline-online modeling and real-time fault diagnosis program based on ADWHD-T are designed. Quoting real-time data from diesel engine benches verifies the effectiveness of the scheme. Compared with MD and MD-T methods, ADWHD-T could promote diagnosis efficiency, enhance classification accuracy and expand its application range in fault diagnosis. [ABSTRACT FROM AUTHOR]

Humic substances (HS) are heterogeneous and polydisperse compounds formed in soils, sediments and waters during the decay and transformation of organic residues (the process called humification). The role of extracellular free-radical condensation reactions (secondary synthesis) in the formation of HS is a subject of debate. Here we have studied the formation of HS from a mixture of monomers under the dynamic conditions and at low substrate concentrations in the presence of laccase from the fungus Coprinus comatus F-2940. Laccase was immobilized on kaolinite modified with aluminum hydroxide. We have investigated some properties of the enzyme, reactivity of phenolic acids and amino acids in the presence of laccase. The optimum of 2.6-dimethoxyphenol (2.6-DMP) oxidation by free laccase was at pH 6.0. Upon immobilization, it shifted to the acidic region (pH 4.4), the thermal stability decreased, however the kinetic parameters of 2.6-DMP oxidation remained unchanged. In terms of reactivity (% of substrate conversion by free laccase) the individual phenolic acids formed a series: caffeic (72) > ferulic (53) > gallic = syringic (43) > protocatechuic (5.5) > vanillic = p-hydroxybenzoic (0). In the mixture of phenolic acids, gallic acid was most efficiently oxidized (50%), while the other acids were oxidized in comparable amounts (13–17%). The conversion of phenolic acids increased in the presence of lysine. When a mixture of gallic, protocatechuic, syringic, ferulic acids (0.01 mM each) and lysine (0.02 mM) was passed through a flow-through microcolumn, immobilized laccase effectively oxidized the phenolic acids, the reaction products bound to the mineral phase, staining it dark. According to high performance liquid chromatography, the molecular weights of compounds extracted from the mineral phase did not exceed 900 Da, thus fulvic acid-like substances were formed. Results of the study suggest an important role of free-radical heterophase reactions in the formation of the molecular composition of the liquid phase and organo-mineral complexes. [ABSTRACT FROM AUTHOR]

Objective: To reveal the anatomical relationships of the ethmoid roof on CT in pediatric case group. Methods: We measured the depth of olfactory fossa (DOF), the width of olfactory fossa (WOF), the angle between lateral lamella and cribriform plate (LLCPA), the width of the olfactory cleft (WOC), the length of lateral lamella (LLL), orbital roof fovea to ethmoidal distance (ORFED) and orbital roof to cribriform plate distance (ORCPD) and we determined Keros and LLCPA types from paranasal sinus CT of subjects under 16 years of age retrospectively. Results: The incidence of Keros type I was higher in females and Keros Type II in males. The ORCPD, DOF and LLL values were found to be higher in 13–16 years age group and WOF and LLCPA in 4–6 years age group. The prevalence of Keros type II was higher in the 13–16 age group, and Keros type I was higher in other age groups. LLCPA type A was the most frequent in all age groups and in both sexes. There was a positive correlation between age and ORCPD, DOF, LLL, and a negative correlation with ORFED, WOF, LLCPA. Olfactory fossa width and depth had a negative correlation. LLCPA had a positive correlation with WOF and a negative correlation with DOF. There was a positive correlation between LLCPA and LLL. DOF and LLL had a positive correlation too. Conclusions: Paranasal sinus CT provides useful information about frontal skull base anatomic relations before sinus surgery in pediatric cases. [ABSTRACT FROM AUTHOR]

The use reactivity of native (intravital) exometabolites excreted into cultural medium by actinomycetes, cyanobacteria and microalgae as a probable ecophysiological criterion for the selection of partners for artificial mixed cultures and associative pairs of microorganisms has been considered. [ABSTRACT FROM AUTHOR]

The transition from young carbon-importing sink leaves of higher plants to mature carbon-exporting source leaves is paralleled by a complete reversal of phloem function. While sink-leaf phloem mediates the influx of reduced carbon from older source leaves and the release of this imported carbon to the sink-leaf mesophyll, source-leaf phloem catalyzes the uptake of photoassimilates into companion cells (CCs) and sieve elements (SEs) and the net carbon export from the leaf. Phloem loading in source leaves with sucrose, the main or exclusive transport form for fixed carbon in most higher plants, is catalyzed by plasma membrane-localized sucrose transporters. Consistent with the described physiological switch from sink to source, the promoter of the Arabidopsis AtSUC2 gene is active only in source-leaf CCs of Arabidopsis or of transgenic tobacco ( Nicotiana tabacum). For the identification of regulatory elements involved in this companion cell-specific and source-specific gene expression, we performed detailed analyses of the AtSUC2 promoter by truncation and mutagenesis. A 126-bp promoter fragment was identified, which seems to contain these fragments and which drives AtSUC2-typical expression when combined with a 35S minimal promoter. Within this fragment, linker-scanning analyses revealed two cis-regulatory elements that were further characterized as putative binding sites for transcription factors of the DNA-binding-with-one-finger or the homeo-domain-leucine-zipper families. Similar or identical binding sites are found in other genes and in different plant species, suggesting an ancient regulatory mechanism for this important physiological switch. [ABSTRACT FROM AUTHOR]

Myxobacteria are Gram-negative soil microorganisms that prey on other microorganisms. Myxobacteria have significant potential for applications in biotechnology because of their extraordinary ability to produce natural products such as secondary metabolites. Myxobacteria also stand out as model organisms for the study of cell–cell interactions and multicellular development during their complex life cycle. Cellular morphogenesis during multicellular development in myxobacteria is very similar to that in the eukaryotic soil amoebae. Recent studies have started uncovering molecular mechanisms directing the myxobacterial life cycle. We describe recent studies on signal transduction and gene expression during multicellular development in the myxobacterium Myxococcus xanthus. We provide our current model for signal transduction pathways mediated by a two-component His–Asp phosphorelay system and a Ser/Thr kinase cascade. [ABSTRACT FROM AUTHOR]

This article presents a community learning model formulated by Engineers Without Borders Colombia with the aim of providing communities with tools to create sustainable productive solutions which have relevancy for members and for potential customers. The goal of this formulation is to promote learning processes that are guided by decisions made by community members to propose sustainable and replicable initiatives. The model applicability is evidenced through a case study devoted to strengthening community-led green businesses in the Guavio Province, Colombia by collecting lessons and conclusions. Ultimately, this collection will prove useful in replicating the learning model in other similar rural communities. [ABSTRACT FROM AUTHOR]

Cysteine cathepsins are proteolytic enzymes involved in protein degradation in lysosomes and endosomes. Cysteine cathepsins have been also found in the tumor microenvironment during carcinogenesis, where they are implicated in proliferation, invasion and metastasis of tumor cells through the degradation of extracellular matrix, suppression of cell–cell interactions, and promotion of angiogenesis. In this regard, cathepsins can have a diagnostic value and represent promising targets for antitumor drugs aimed at inhibition of these proteases. Moreover, cysteine cathepsins can be used as activators of novel targeted therapeutic agents. This review summarizes recent discovered roles of cysteine cathepsins in carcinogenesis and discusses new trends in cancer therapy and diagnostics using cysteine cathepsins as markers, targets, or activators. [ABSTRACT FROM AUTHOR]

Purpose: The ultrarapid delayed rectifier current (IKur) carried by Kv1.5 channels, which are solely expressed in the atrium, is a potential target for safer treatment of paroxysmal atrial fibrillation (PAF). XEN-D0103 is a nanomolar ion channel blocker that selectively inhibits potassium ion flux through the Kv1.5 ion channel. The efficacy of XEN-D0103 in reducing AF burden was assessed in patients with DDDRp permanent pacemakers (PPMs) and PAF.Methods: A double-blind, placebo-controlled, cross-over study was performed in patients with PAF and DDDRp PPMs with advanced atrial and ventricular Holters allowing beat-to-beat arrhythmia follow-up. All anti-arrhythmic drugs were withdrawn before randomised treatment. After baseline assessment, patients were randomly assigned to two treatment periods of placebo then XEN-D0103 50 mg bd, or XEN-D0103 50 mg bd then placebo.Results: Fifty-four patients were screened and 21 patients were eligible and included in the randomised trial. All 21 patients completed both treatment periods. The primary endpoint was change in AF burden assessed by PPM. There was no significant difference in AF burden on treatment with XEN-D0103 versus placebo. There was a reduction in the mean frequency of AF episodes (relative reduction 0.72, 95% CI 0.66 to 0.77; p < 0.0001). XEN-D0103 was safe and well tolerated, and there were no serious adverse events. XEN-D0103 did not have any apparent effect on heart rate compared to placebo.Conclusions: XEN-D0103 did not reduce AF burden in patients with PAF and dual chamber pacemakers providing beat-to-beat monitoring. XEN-D0103 was well tolerated and did not have any apparent effect on heart rate. Although single-ion channel blockade with XEN-D0103 did not affect AF in this study, there might be a potential for this agent to be used in combination with other atrially specific drugs in the treatment of AF.Eudract Trial Registration Number: 2013-004456-38. [ABSTRACT FROM AUTHOR]

Magnetic core-shell nanoparticles (mag-NPs) of type SiO2@Fe3O4 were covalently modified with the ionic liquid dimethyl octadecyl[3-(trimethoxysilyl propyl)]ammonium chloride. The NPs were characterized via FTIR and scanning electron microscopy and evaluated with respect to the extraction of the nonsteroidal anti-inflammatory drugs (NSAIDs) tolmetin, indometacin and naproxen from blood samples. Supercritical fluid extraction was used to eliminate matrix effects before extraction with the mag-NPs. The effects of pH value of sample solution, amount of adsorbent, times of adsorption and desorption, salt effect, type and volume of suitable solvent for desorption were optimized. Under optimum conditions, magnetic solid phase extraction (MSPE) resulted in limits of detection that range between 0.1 and 0.3 μg L. In case of supercritical fluid extraction along with magnetic solid phase extraction (SFE- MSPE), the LODs ranged from 0.2 to 0.3 mg kg. The analytical ranges for all of the NSAIDs varied within 0.2-15 mg kg and 0.1-250 μg L in the SFE-MSPE and MSPE methods, respectively. The relative standard deviations for the extraction of the NSAIDs from blood samples via SFE-MSPE are <10.2%. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

This study prepared $$\hbox {SiO}_\mathrm{x}\hbox {N}_\mathrm{y}$$ film by using plasma-enhanced chemical vapor deposition in organic light-emitting diode (OLED) encapsulation to prevent the invasion of moisture and oxygen for longer light-emitting lifetime of OLED components. It applied high density inductively coupled plasma for the coating of film on polyethersulfone, silicon and glass substrate, and discussed the relevance between process parameters and quality characteristics including coating uniformity, coating thickness and moisture permeation. This study used Taguchi method to plan the experiment and calculated the optimal parameters of each quality, used technique for order preference by similarity to ideal solution and grey relational analysis to determine the optimal parameter of all qualities. The back-propagation neural network was combined with Levenberg-Marquardt algorithm to construct the simulation and prediction system. Based on the quality optimization design, the single layer film's moisture permeation rate was 0.02 g/m $$^{2}$$ /day, the maximum coating thickness reached 420 nm, and the fastest rate was 21 nm/min, which was higher than the industrial standard specification (10 nm/min) by 110 %. [ABSTRACT FROM AUTHOR]

The dynamics of hemoglobin affinity to oxygen, Bohr effect value, and concentrations of sodium, potassium, calcium and magnesium were studied in the bream, Abramis brama, erythrocytes of the Rybinsk reservoir during an annual cycle. The studied parameters were most variable during the fish reproductive period. On the basis of the original studies, as well as of some published data concerning physiological-biochemical parameters, it is suggested that the state of spawning is comparable to the state of stress. The relation between the seasonal dynamics of hemoglobin functional properties and the parameters of ionic environment is revealed. [ABSTRACT FROM AUTHOR]

This paper explains the effect of turning parameters such as cutting speed, feed rate, depth of cut and cutting tool nose radius on surface roughness of hybrid metal matrix (Al-SiC-Fly ash) composite. Experiments have been conducted based on the orthogonal array L16(4) and surface roughness was tested on the composites turned by an high speed CNC centre lathe. Analysis of variance (ANOVA) was performed to predict the significant parameters and their contribution towards surface finish of the composite. A mathematical model was developed using non-linear regression analysis. Taguchi method and Genetic algorithm have been employed to optimize the turning parameters for optimum surface roughness of the composite. The optimum turning parametric conditions have been checked with the confirmation experiments. It has been noted that the optimum condition of genetic algorithm exhibited better results than the experimental results based on the orthogonal array and the optimum condition of Taguchi method. [ABSTRACT FROM AUTHOR]

The effects of the ionic liquids CMImCl and CMImCl as background electrolyte components on the migration parameters of amino acids under the conditions of capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) were found. It was established that the introduction of the above ionic liquids based on imidazole into a background electrolyte (phosphate buffer solution, pH 2.0) led to an increase in efficiency by a factor of 2-3 in the determination of tryptophan, tyrosine, and 3,4-dihydroxyphenylalanine under the conditions of CZE and in separation selectivity in the MEKC mode. The application of intracapillary concentration (field-amplified sample stacking) with the use of CMImCl as a background electrolyte constituent made it possible to concentrate tryptophan, tyrosine, and 3,4-dihydroxyphenylalanine by a factor of 10-14. The limits of detection of the amino acids were 30-55 ng/mL. It was found that the inclusion of CMImCl into the composition of the electrophoretic system makes it possible to determine glycine, which does not absorb in the UV of the region of the spectrum, under the conditions of indirect detection at 220 nm. A procedure was proposed for urine sample preparation for the electrophoretic determination of amino acids with the use of CMImNTf as an extractant. The degrees of amino acid recovery were 92-100%. [ABSTRACT FROM AUTHOR]

In this study, phosphate and chemical oxygen demand removals of medical waste sterilization plant wastewater were investigated and the Taguchi experimental method was used to determine optimum treatment conditions. In the scope of the study, four important factors influencing the phosphate and chemical oxygen demand removal namely initial pH, current density, initial wastewater concentration, and contact time were optimized. Results show that about 52 % of chemical oxygen demand removal has been obtained at optimum conditions. Also, phosphorus has been completely removed at optimum levels. In addition, analysis of variance shows that the biggest contribution ratio belongs to initial wastewater concentration on the electrocoagulation process efficiency. The contribution percentages of each factor in descending order are as follows: initial wastewater concentration (42.51 %) > pH (32.02 %) > current density (14.56 %) > contact time (6.64 %). [ABSTRACT FROM AUTHOR]

Continuous-wave single-frequency tunable 544- and 272-nm beams have been demonstrated by the second- and fourth-harmonic conversions of a 1088-nm fundamental beam from a diode-oscillator fiber-amplifier. The single-pass second-harmonic generation with a MgO-doped periodically poled stoichiometric LiTaO crystal and the external-cavity frequency-doubling technique with a bulk BBO crystal were employed to achieve an approximately 6-W 544-nm beam and a 1.5-W 272-nm beam, respectively. We characterized the second- and fourth-harmonic generations and discussed their applications to calcium spectroscopy. [ABSTRACT FROM AUTHOR]

The influence of the most important parameters on the service life of reinforced asphalt overlay with geogrid materials in bending mode was examined by employing the Taguchi method and analysis of variance techniques. The objectives of this experiment was to investigate the effects of grid stiffness, tensile strength, coating type, amount of tack coat, overlay thickness, crack width and stiffnesses of asphalt overlay and existing asphalt concrete on propagation of the reflection cracking. Results indicate that the stiffnesses of cracked layer and overlay are the main significant factors that can directly improve the service life of an overlay against the reflection cracking. Generally, glass grid is more effective in reinforced overlay than polyester grid. Effect of crack width of the existing layer is significant when its magnitude increases from 6 to 9 mm. [ABSTRACT FROM AUTHOR]

The article offers information on the role of ambient particulate matter (PM) components in health effects and discusses the respiratory and cardiovascular effects of metals in PM. Topics include Health Effects Institute (HEI) National Particle Component Toxicity (NPACT) Initiative, epidemiologic studies of the health effects of PM and the Multi-Ethnic Study of Atherosclerosis (MESA).

Taguchi method was applied to optimize cloud point extraction ( CPE) conditions for preconcentration and determination of trace amounts of copper by UV-Vis spectrophotometry. Briefly, the copper ions formed complexes with neocuproine in aqueous solution; then, Triton X-114 (0.15%, w/v) was added and phase separation occurred upon heating to 60°C. The copper complexes were preconcentrated into the small volume of the surfactant-rich phase; after centrifugation, the surfactant-rich phase was diluted with methanol and absorbance was measured at 455 nm. The main factors affecting the CPE were evaluated and optimized with Taguchi orthogonal array design ( OA). Under the optimum conditions, the calibration curve was linear in the range 2-500 μg/L ( r > 0.997). The limit of detection and preconcentration factor were 1.8 μg/L and 37.2, respectively. The applicability of the proposed method was successfully confirmed by preconcentration and determination of trace amounts of copper in water samples and satisfactory results were obtained. [ABSTRACT FROM AUTHOR]

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Liposomes reduce toxicity of their encapsulated APIs. They allow drugs to penetrate cell membranes, serve as containers for drug delivery, protect drugs from enzymatic degradation, provide prolonged action due to slow drug release, and protect drugs from the reticuloendothelial system. Liposomeencapsulated drugs break through the blood brain barrier. Liposomes can solubilize water-insoluble drugs [54, 55, 58, 76, 77, 82]. [ABSTRACT FROM AUTHOR]

An efficient approach to the study of deactivation pathways of chiral organocatalysts in asymmetric Michael reactions by modifying original catalysts with ionic-liquid fragments followed by the electrospray ionization mass spectrometry analysis of recovered catalyst samples has been proposed. [ABSTRACT FROM AUTHOR]

The significance of the adverse effects of information delays (IDs) on flexible manufacturing system (FMS) performance is getting increasing attention from manufacturing systems managers, planners, schedulers, Enterprise Resource Planning software developers, and researchers because of their potential to disrupt production schedules. In this paper, we examine the extent of the adverse impact that IDs have on FMS performance. The FMSs are assumed to operate in a 'review period' mode; i.e., the control decisions (e.g., sequencing and dispatching) are taken based on information monitored at predetermined intervals of time called 'review periods'. The performance deterioration occurs due to the obsolescence of system status information. Key empirical findings based on extensive simulation experiments are: (1) IDs significantly degrade FMS performance for due date-based measures ( mean tardiness and percent of jobs tardy); (2) IDs also degrade FMS performance for non-due date-based measures ( mean flowtime and average machine utilization), albeit to a less severe degree; (3) routing flexibility, often regarded as a significant factor to influence FMS performance, is superseded by status review information delay. [ABSTRACT FROM AUTHOR]

This work describes an application of an integrated approach using the Taguchi method (TM), neural network (NN) and genetic algorithm (GA) for optimizing the lap joint quality of aluminum pipe and flange in automotive industry. The proposed approach (Taguchi-Neural-Genetic approach) consists of two phases. In first phase, the TM was adopted to collect training data samples for the NN. In second phase, a NN with a Levenberg-Marquardt back-propagation (LMBP) algorithm was adopted to develop the relationship between factors and the response. Then, a GA based on a well-trained NN model was applied to determine the optimal factor settings. Experimental results illustrated the Taguchi-Neural-Genetic approach. [ABSTRACT FROM AUTHOR]

We report on a nanostructured self-doped polypyrrole (SPPy) film that was prepared by an electrochemical technique in an electrolyte containing fluorosulfonic acid as the sulfonation reagent. The film was applied as a new fiber material for solid-phase microextraction (SPME) of the pesticides lindane, heptachlor, aldrin, endosulfans I and II prior to their quantitation by GC with electron capture detection. The SPPy nanoparticles have a diameter of <100 nm. The introduction of covalently bound sulfo groups into the backbone of the polymer resulted in improved temperature resistance (~350 °C) and satisfactory extraction efficiency. The thermal stability of the SPPy fiber is superior to common polypyrrole fibers. Extraction was optimized by means of the Taguchi orthogonal array experimental design with an OA (4) matrix including extraction temperature, extraction time, salt concentration, stirring rate, and headspace volume. The method displays good repeatability (RSD < 6%) and linearity (in the range from 0.78 to 100 ng mL; with an R of >0.998. The detection limits are <0.23 ng mL. The method was successfully applied to the analysis of the pesticides in skimmed milk and fruit juice samples, and recoveries are from 84 ± 1 to 105 ± 1%. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Clobazam was initially developed in the early 1970s as a nonsedative anxiolytic agent, and is currently available as adjunctive therapy for epilepsy and anxiety disorders in more than 100 countries. In October 2011, clobazam (Onfi™; Lundbeck Inc., Deerfield, IL, USA) was approved by the US FDA for use as adjunctive therapy for the treatment of seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older. It is a longacting 1,5-benzodiazepine whose structure distinguishes it from the classic 1,4-benzodiazepines, such as diazepam, lorazepam and clonazepam. Clobazam is well absorbed, with peak concentrations occurring linearly 1-4 hours after administration. Both clobazam and its active metabolite, N-desmethylclobazam, are metabolized in the liver via the cytochrome P450 pathway. The mean halflife of N-desmethylclobazam (67.5 hours) is nearly double the mean half-life of clobazam (37.5 hours). Clobazam was synthesized with the anticipation that its distinct chemical structure would provide greater efficacy with fewer benzodiazepine-associated adverse effects. Frequently reported adverse effects of clobazam therapy include dizziness, sedation, drowsiness and ataxia. Evidence gathered from approximately 50 epilepsy clinical trials in adults and children indicated that the sedative effects observed with clobazam treatment were less severe than those reported with 1,4-benzodiazepines. In several studies of healthy volunteers and patients with anxiety, clobazam appeared to enhance participants' performance in cognitive tests, further distinguishing it from the 1,4-benzodiazepines. The anxiolytic and anticonvulsant effects of clobazam are associated with allosteric activation of the ligand-gated GABAA receptor. GABAA receptors are found extensively throughout the CNS, occurring synaptically and extrasynaptically. GABAA receptors are composed of five protein subunits, two copies of a single type of α subunit, two copies of one type of β subunit and a γ subunit. This arrangement results in a diverse assortment of receptor subtypes. As benzodiazepine pharmacology is influenced by differences in affinity for particular GABAA subtypes, characterizing the selectivity of different benzodiazepines is a promising avenue for establishing appropriate use of these agents in neurological disorders. Molecular techniques have significantly advanced since the inception of clobazam as a clinical agent, adding to the understanding of the GABAA receptor, its subunits and benzodiazepine pharmacology. Transgenic mouse models have been particularly useful in this regard. Comparative studies between transgenic and wild-type mice have further defined relationships between GABAA receptor composition and drug effects. From such studies, we have learned that sedating and amnesic effects are mediated by the GABAA α1 subunit,α2 receptors mediate anxiolytic effects, α subunits are involved with anticonvulsant activity, α5 may be implicated in learning and memory, and β3 subunit deficiency decreases GABA inhibition. Despite progress in determining the role of various subunits to specific benzodiazepine pharmacological actions, the precise mechanism of action of clobazam, and more importantly, how that mechanism of action translates into clinical consequences (i.e. efficacy, tolerability and safety) remain unknown. Testing clobazam and 1,4-benzodiazepines using a range of recombinant GABAA receptor subtypes would hopefully elucidate the subunits involved and strengthen our understanding of clobazam and its mechanism of action. [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring of tacrolimus is a major support to patient management and could help improve the outcome of lung transplant recipients, by minimizing the risk of rejections and infections. However, despite the wide use of tacrolimus as part of maintenance immunosuppressive regimens after lung transplantation, little is known about its pharmacokinetics in this population. Better knowledge of the pharmacokinetics of tacrolimus in lung transplant recipients, and the development of tools dedicated to its therapeutic drug monitoring, could thus help improve their outcome. Objectives: The aims of this study were (i) to characterize the population pharmacokinetics of tacrolimus in lung transplant recipients, including the influence of biological and pharmacogenetic covariates; and (ii) to develop a Bayesian estimator of the tacrolimus area under the blood concentration-time curve from time zero to 12 hours (AUC12) for its therapeutic drug monitoring in lung transplant recipients. Methods: A population pharmacokinetic model was developed by nonlinear mixed-effects modelling using NONMEM® version VI, from 182 tacrolimus full concentration-time profiles collected in 78 lung transplant recipients within the first year post-transplantation. Patient genotypes for the cytochrome P450 3A5 (CYP3A5) A6986G single nucleotide polymorphism (SNP) were characterized by TaqMan allelic discrimination. Patients were divided into an index dataset (n = 125 profiles) and a validation dataset (n = 57 profiles). A Bayesian estimator was derived from the final model using the index dataset, in order to determine the tacrolimus AUC12 on the basis of a limited number of samples. The predictive performance of the Bayesian estimator was evaluated in the validation dataset by comparing the estimated AUC12 with the trapezoidal AUC12. Results: Tacrolimus pharmacokinetics were described using a two-compartment model with Erlang absorption and first-order elimination. The model included cystic fibrosis (CF) and CYP3A5 polymorphism as covariates. The relative bioavailability in patients with CF was approximately 60% of the relative bioavailability observed in patients without CF, and the transfer rate constant between the transit compartments was 2-fold smaller in patients with CF than in those without CF (3.32 vs 7.06 h-1). The apparent clearance was 40% faster in CYP3A5 expressers than in non-expressers (24.5 vs 17.5 L/h). Good predictive performance was obtained with the Bayesian estimator developed using the final model and concentrations measured at 40 minutes and at 2 and 4 hours post-dose, as shown by the mean bias (1.1%, 95% CI -1.4, 3.7) and imprecision (9.8%) between the estimated and the trapezoidal AUC12. The bias was >20% in 1.8% of patients. Conclusion: Population pharmacokinetic analysis showed that lung transplant patients with CF displayed lower bioavailability and a smaller transfer rate constant between transit compartments than those without CF, while the apparent clearance was faster in CYP3A5 expressers than in non-expressers. The Bayesian estimator developed in this study provides an accurate prediction of tacrolimus exposure in lung transplant patients, with and without CF, throughout the first year post-transplantation. This tool may allow routine tacrolimus dose individualization and may be used to conduct clinical trials on therapeutic drug monitoring of tacrolimus after lung transplantation. [ABSTRACT FROM AUTHOR]

Vildagliptin is an orally active, potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor, shown to be effective and well tolerated in patients with type 2 diabetes mellitus (T2DM) as either monotherapy or in combination with other anti-diabetic agents. Vildagliptin possesses several desirable pharmacokinetic properties that contribute to its lower variability and low potential for drug interaction. Following oral administration, vildagliptin is rapidly and well absorbed with an absolute bioavailability of 85%. An approximately dose-proportional increase in exposure to vildagliptin over the dose range of 25-200 nag has been reported. Food does not have a clinically relevant impact on the pharmacokinetics of vildagliptin, and it can be taken without regard to food. Vildagliptin is minimally bound to plasma proteins (9.3%) and, on the basis of a volume of distribution of 71 L, it is considered to distribute extensively into extravascular spaces. Renal clearance of vildagliptin (13 L/h) accounts for 33% of the total body clearance after intravenous administration (41 L/h). The primary elimination pathway is hydrolysis by multiple tissues/organs. The DPP-4 enzyme contributes to the formation of the major hydrolysis metabolite, LAY 151 ; therefore, vildagliptin is also a substrate of DPP-4. Vildagliptin has a low potential for drug interactions, as cytochrome P450 (CYP) enzymes are minimally (<1.6%) involved in the overall metabolism. Clinical pharmacokinetic studies have reported the lack of drug interaction with several drugs (metformin, pioglitazone, glyburide, simvastatin, amlodipine, valsartan, ramipril, digoxin and warfarin) that are likely to be frequently co-administered to patients with T2DM. In particular, vildagliptin does not affect the pharmacokinetics of pioglitazone, glyburide, warfarin and simvastatin; therefore, it is not expected to affect the pharmacokinetics of a drug that is a substrate for CYP2C8, CYP2C9 or CYP3A4. In the elderly, vildagliptin exposure increases by approximately 30%, which is considered to be mostly attributable to compromised renal function in the elderly population and is not considered to be clinically relevant. Viidagliptin has been demonstrated to be efficacious, safe and well tolerated in elderly patients with T2DM without dose adjustment. In subjects with varying degrees of renal impairment, vildagliptin exposure increases by approximately 2-fold; however, the increase in the exposure does not correlate with the severity of renal impairment. The lack of a clear correlation between the increased exposure and the severity of renal impairment is considered to be attributable to the fact that the kidneys contribute to both the excretion and the hydrolysis metabolism of vildagliptin. Hepatic impairment, gender, body mass index (BMI) and ethnicity do not have an influence on the pharmacokinetics of vildagliptin. These findings suggest that vildagliptin can be used in a diverse patient population without dose adjustment. Oral administration of vildagliptin to patients with T2DM completely inhibits DPP-4 activity at a variety of doses. The onset of DPP-4 inhibition is rapid, and the duration of DPP-4 inhibition is dose dependent. Vildagliptin is a potent inhibitor of the DPP-4 enzyme, with a concentration required to achieve 50% DPP-4 inhibition (IC50) of 4.5 nmol/L in patients with T2DM. Similar potency of DPP-4 inhibition by vildagliptin has been reported in different ethnic groups, indicating that ethnicity does not affect the pharmacodynamics of vildagliptin. Vildagliptin significantly increases the active glucagon-like peptide 1 (GLP-1) levels by approximately 2- to 3-fold and glucose-dependent insulinotropic polypeptide (GIP) levels by approximately 5-fold, and significantly suppresses the postprandial glucagon levels in response to a meal or following an oral glucose tolerance test (OGTT) in patients with T2DM. Vildagliptin significantly reduces both fasting and postprandial glucose levels over the dose range of 50-100 mg daily (administered either once daily or twice daily), and there are no substantial additional benefits of doses greater than 50 mg twice daily. The primary clinical dosing regimen is 50 mg twice daily as monotherapy or in combination with metformin. Vildagliptin increases the insulin levels following an OGTT and an intravenous glucose tolerance test (IVGTT), and the stimulation of insulin secretion is glucose dependent. Vildagliptin has been shown to improve beta-cell function on the basis of pharmacodynamic modelling taking the reduced glucose levels into account. The improvement of beta-cell function by vildagliptin has been confirmed after chronic treatment with vildagliptin for up to 2 years. Reduction of the endogenous glucose production appears to contribute to the glucose-lowering effects. Unlike the GLP-1 receptor agonists, vildagliptin does not affect gastric emptying, and this is consistent with the favourable gastrointestinal safety profile. Vildagliptin improves the sensitivity of the alpha cell to glucose in patients with T2DM by enhancing the alpha-cell responsiveness to both suppressive effects of hyperglycaemia and stimulatory effects of hypoglycaemia. Consistently, a lower incidence of hypoglycaemic events with vildagliptin is reported when it is used as either monotherapy or in combination with other anti-diabetic agents, such as metformin or insulin, as compared with a sulphonylurea. Numerous long-term clinical trials of up to 2 years have demonstrated that vildagliptin 50 mg once daily or twice daily is effective, safe and well tolerated in patients with T2DM as either monotherapy or in combination with a variety of other anti-diabetic agents. [ABSTRACT FROM AUTHOR]

Rasagiline (Azilect®), a selective, irreversible, monoamine oxidase-B inhibitor, is available in the EU, the US and in several other countries worldwide, including Canada and Israel. It is indicated as monotherapy or as adjunctive therapy to levodopa for the treatment of idiopathic Parkinson's disease in adult patients with end-of-dose fluctuations in the EU and for the treatment of adult patients with the signs and symptoms of idiopathic Parkinson's disease in the US. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of rasagiline as monotherapy or as adjunctive therapy to levodopa in patients with Parkinson's disease. Oral rasagiline as monotherapy or as adjunctive therapy to levodopa was effective in the symptomatic treatment of adult patients with Parkinson's disease participating in double-blind, placebo-controlled, multinational studies. In patients with early Parkinson's disease, monotherapy with rasagiline 1 mg/day (recommended dosage) significantly slowed the rate of worsening (i.e. an increase in the Unified Parkinson's Disease Rating Scale [UPDRS] score) in the ADAGIO and TEMPO studies, with the results from the ADAGIO study for rasagiline 1 mg/day suggesting a slowing of clinical progression. However, at the higher dosage of 2 mg/day, rasagiline met the primary endpoint in the TEMPO study and the first, but not the second, of three hierarchical primary endpoints in the ADAGIO study. Compared with delayed-start rasagiline monotherapy, early initiation was associated with a slower long-term progression of the clinical signs and symptoms of Parkinson's disease in the TEMPO study. As adjunctive therapy to levodopa in the LARGO and PRESTO studies, rasagiline 0.5 and/or 1 mg/day significantly reduced the total daily 'off time (primary efficacy endpoint) and significantly improved the Clinical Global Impression score, the UPDRS activities of daily living subscale score during 'off time and the UPDRS motor subscale score during 'on' time compared with placebo in patients with advanced Parkinson's disease. Although rasagiline showed neuroprotective properties both in vitro and in vivo, identifying its potential to slow clinical progression in the clinical setting has been elusive to date and was not definitively demonstrated in the studies discussed in this article. Additional rasagiline studies specifically designed to assess the clinical progression of Parkinson's disease while addressing the potentially confounding factors of the delayed-start study design would therefore be of interest. As monotherapy or as adjunctive therapy to levodopa, rasagiline was generally well tolerated, with the frequency and nature of treatment-emergent adverse events generally similar across clinical studies and between rasagiline and placebo groups. Therapy with rasagiline appears to be associated with a low incidence of cognitive and behavioural adverse events. Thus, oral rasagiline as monotherapy or as adjunctive therapy to levodopa provides a useful option in the treatment of adult patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD. Objective: This study aimed to evaluate the onset of effect of single-dose formoterol 9 µg versus single-dose salmeterol 50 µg in patients with moderate COPD. Methods: In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 µg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 µg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5 mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV1 at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12% increase in FEV1 at 5 minutes post-dose. Results: 109 patients were randomized, and 108 completed the study. The increase in FEV1 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p=0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p<0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV1 5 minutes post-dose were 23.1%, 9.2% and 6.4% for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated. Conclusion: In COPD patients, formoterol 9 µg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 µg based on FEV1 at 5 minutes post-dose. [ABSTRACT FROM AUTHOR]

Chronic pain is a major healthcare issue in Europe and globally, and inadequate or undertreated pain significantly reduces the ability of many patients to participate in ordinary daily activities, adversely affects their employment status and contributes to a substantial rate of depression and anxiety in patients with chronic pain. There is a broad distinction of chronic pain into chronic non-cancer pain and chronic cancer pain, and important subgroups of these include patients with rheumatic and/or orthopaedic diseases, pain syndromes caused by cancer itself and caused by cancer treatment. Despite comprising the majority of non-cancer pain in Europe, chronic noncancer pain associated with rheumatic diseases and/or orthopaedic conditions is often inadequately managed. Although paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) play a continuing role in the treatment of chronic rheumatic diseases, accumulating evidence of potential toxicity with both traditional non-selective NSAIDs and selective cyclooxygenase 2 inhibitors has prompted a reassessment of their use. This has particular resonance for the elderly, who are more likely to have significant pain issues than younger patients and are at high risk of NSAID-related adverse events. The use of mild opioids, such as codeine and tramadol, and strong opioids, such as morphine, hydromorphone and oxycodone, may be appropriate where paracetamol and other non-opioid analgesics are ineffective in chronic non-cancer pain. Cancer pain, either related to the underlying disease or caused by cancer treatment, is also a common cause of chronic pain in the elderly. An understanding of individual needs is essential in providing adequate pain relief, which is a central goal of care in all patients with chronic pain. [ABSTRACT FROM AUTHOR]

Oral aripiprazole (Abilify®) is an atypical antipsychotic agent that is approved worldwide for use in adult patients with schizophrenia. It is a quinolinone deriv- ative that has a unique receptor binding profile as it exhibits both partial agonist activity at dopamine D2 receptors and serotonin 5-HT1A receptors and antagonist activity at 5-HT2A receptors. In several well designed, randomized, clinical trials of 4-6 weeks duration, aripiprazole provided symptomatic control for patients with acute, relapsing schizophrenia or schizoaffective disorder. Furthermore, following 26 weeks' treat- ment, the time to relapse was significantly longer for patients with chronic, stabilized schizophrenia receiving aripiprazole compared with those receiving placebo. Using a variety of efficacy outcomes, aripiprazole showed a mixed response when evaluated against other antipsychotic agents in randomized clinical trials. Longer-term data showed that improvements in remission rates and response rates favoured aripiprazole over haloperidol, although, the time to failure to maintain a response was not significantly different between the treatment arms. On the other hand, improvements in positive and negative symptom scores mostly favoured olanzapine over aripiprazole, although, the time to all-cause treatment discontinuation was not significantly different between the two treatments. Several open-label, switching trials showed that aripiprazole provided continued control of symptoms in patients with schizophrenia or schizoaffective disorder. Using a variety of efficacy outcomes or quality-of-life scores, longer- term treatment generally favoured patients switched to receive aripiprazole compared with standard-of-care oral antipsychotics. Aripiprazole was generally well tolerated in patients with schizophrenia. In particular, its use seems to be associated with a lower incidence of extrapyramidal symptoms than haloperidol and fewer weight-gain issues than olanzapine. Aripiprazole also showed a favourable cardiovascular tolerability profile and its use was associated with a reduced risk of metabolic syndrome than placebo or olan- zapine. As a consequence, aripiprazole may provide a more cost-effective treat- ment option compared with other atypical antipsychotics. In conclusion, oral aripiprazole provides an effective and well tolerated treatment alternative for the acute and long-term management of patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: For genetic polymorphisms known to alter drug effect or safety, regulatory authorities can tap into population genomic databases and other sources of allele and genotype distribution data to make a more informed decision about the anticipated impact of such variants on the main ethnic groups in a country's population.Objective: The aim of this short communication is to describe how the Singapore Health Sciences Authority (HSA) made use of allele and genotype distributions in the main ethnic groups in Singapore (Chinese, Malay, Indian) and population genetic tools to compare with North American Caucasians and Japanese.Methods: Published papers and publicly accessible genomic databases were searched up to August 2009 to obtain allele and genotype frequencies for UGT1A1*6 and *28, two common variants of UGT1A1, a gene that encodes for a key enzyme in the pathway of irinotecan metabolism. These variants are associated with greater risk of serious toxicity.Results: In Singapore, the combined prevalence of three high-risk genotypes, UGT1A1*6/*6, *6/*28 and *28/*28, is 9.7% in Chinese, 5.0% in Malays and 18.7% in Indians, compared with 11.5% in North American Caucasians and 8.1% in Japanese. Indians are at an elevated risk of irinotecan-induced neutropenia associated with UGT1A1*28 compared with Chinese and Japanese, and at an even higher risk compared with North American Caucasians. On the other hand, Chinese and Japanese are at an elevated risk of irinotecan-induced neutropenia associated with UGT1A1*6 relative to Indians in Singapore or North American Caucasians. Population genotype data were the basis for the HSA to request revision of the package insert from manufacturers of irinotecan products. Moreover, the data provided the impetus for the HSA to publicize the availability of UGT1A1 genetic testing at the National Cancer Centre.Conclusion: With the growing volume of genomic data and pharmacogenomic associations, a regulatory authority is now able to more readily utilize population genetic information and tools to supplement evaluations of drug products pertinent to the country's ethnic demography. [ABSTRACT FROM AUTHOR]

The salt tolerance of two representatives of genus Spirulina (Arthrospira) Spirulina platensis and Spirulina maxima has been investigated. They both are the wide-spread objects of photobiotechnology and it has been shown that the content of 5-15 % sea-water in medium has not caused the decreasing of biomass yield more than 15-20% as compared with control. The further decreasing of biomass was proportionate to sea-water content in medium. The investigation of reactivity of native (intravital) exometabolites secreted into cultural medium has showed that the sea-water content influence the oxidative activity (OA) of exometabolites and hour's rhythmics. [ABSTRACT FROM AUTHOR]

The diagnosis and management of four cases of dermatological disorders, most of which are related to the endocrine disorder of androgen excess, are presented. Combined oral contraceptives (COCs) may be useful when well-tolerated hormonal therapy and/or when contraception is required. A female patient with androgenetic alopecia or female pattern balding, without underlying hyperandrogenism, was treated with ethinylestradiol/chlormadinone acetate (EE/CMA) 0.03 mg/2 mg for 6 months and experienced stabilization of hair loss (case report I). A patient who had previously received a COC for an irregular menstrual pattern but again experienced irregular menses and also acne after stopping treatment was diagnosed with acne associated with polycystic ovary syndrome (PCOS) [case report 2]. After 6 month's treatment with EE/CMA 0.03 mg/2 mg, this patient had fewer acne lesions and became eumenorrheic. A third patient who had excess hair since childhood was diagnosed with idiopathic hirsutism (no underlying gynecological or endocrinological disorder was found) and was treated with EE/CMA 0.03 mg/2 mg (case report 3). Less hair growth was reported after 6 months' treatment. Case report 4 describes a patient who presented with oligomenorrhea and acne. She was diagnosed with PCOS with acne, seborrhea and mild hirsutism. Treatment with EE/CMA 0.03mg/2mg for 6 months resulted in improvements in her facial acne, seborrhea and hirsutism; she also became eumenorrheic. These four cases illustrate that EE/CMA may be a useful and well tolerated treatment option in the management of patients with dermatological disorders with or without hyperandrogenization. [ABSTRACT FROM AUTHOR]

Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed- model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athiete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly mod- erate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5mmoL/kg/BM (-0.3g/kgIBM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of l.SmmoL/kgIBM (-0.5gIkgJBM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5mmoL/kgIBM (-0.3glkg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (± 1 .1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ± 1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bi- carbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and am- monium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5 glkg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration. [ABSTRACT FROM AUTHOR]