A. S. T. M. viscosity index tables, based on and amplified from A. S. T. M. tentative method for calculating viscosity index (D 567-40 T)

"Acknowledgment is hereby given to E.W. Dean and G. H. B. Davis for the development of the viscosity index scale (Journal of Industrial and engineering chemistry, vol. 32, p. 102 (1940)) and to the Standard oil development co., for the compilation of these tables."

The transform likelihood ratio method for rare event simulation with heavy tails

We present a novel method, called the transform likelihood ratio (TLR) method, for estimation of rare event probabilities with heavy-tailed distributions. Via a simple transformation ( change of variables) technique the TLR method reduces the original rare event probability estimation with heavy tail distributions to an equivalent one with light tail distributions. Once this transformation has been established we estimate the rare event probability via importance sampling, using the classical exponential change of measure or the standard likelihood ratio change of measure. In the latter case the importance sampling distribution is chosen from the same parametric family as the transformed distribution. We estimate the optimal parameter vector of the importance sampling distribution using the cross-entropy method. We prove the polynomial complexity of the TLR method for certain heavy-tailed models and demonstrate numerically its high efficiency for various heavy-tailed models previously thought to be intractable. We also show that the TLR method can be viewed as a universal tool in the sense that not only it provides a unified view for heavy-tailed simulation but also can be efficiently used in simulation with light-tailed distributions. We present extensive simulation results which support the efficiency of the TLR method.

A simple practical method for bulk and rapid extraction of free-living nematodes from marine and estuarine sediments

A simple, rapid method is described for the extraction of large numbers of free-living nematodes from estuarine sediments. This method does not physically or chemically alter or damage the nematodes, but instead relies on their downward movement through a filtering layer of double ply tissue paper and into aerated water-filled trays. Seven trials each with 10 trays kept at 25degreesC for an initial period of 24 h yielded 3985 live nematodes l(-1) (+/-511.5 standard deviation) of estuarine sediment, free of sediment and with minimal debris. Time effects were statistically significantly different, with the same 10 trays yielding another 1259 nematodes l(-1) (+/-413.4) when kept for a second period of 24 h at the same temperature. Temperature effects were also significant, and 7 trials each with 10 trays kept for 24 h at 20-21degreesC, produced a lower yield of 2160 nematodes l(-1) (+/-532.7) of sediment. The method is expected to be of use in nematode extractions from both estuarine and marine sediments.

A PCR method for the identification of methicillin-resistant Staphylococcus aureus (MRSA) from screening swabs

Aim: The aim of this study was to assess the discriminatory power and potential turn around time ( TAT) of a PCR-based method for the detection of methicillin-resistant Staphylococcus aureus (MRSA) from screening swabs. Methods: Screening swabs were examined using the current laboratory protocol of direct culture on mannitol salt agar supplemented with oxacillin (MSAO-direct). The PCR method involved pre-incubation in broth for 4 hours followed by a multiplex PCR with primers directed to mecA and nuc genes of MRSA. The reference standard was determined by pre-incubation in broth for 4 hours followed by culture on MSAO (MSAO-broth). Results: A total of 256 swabs was analysed. The rates of detection of MRSA using MSAO-direct, MSAO-broth and PCR were 10.2, 13.3 and 10.2%, respectively. For PCR, the sensitivity, specificity, positive predictive value and negative predictive values were 66.7% (95% CI 51.9 - 83.3%), 98.6% ( 95% CI 97.1 - 100%), 84.6% ( 95% CI 76.2 - 100%) and 95.2% ( 95% CI 92.4 - 98.0%), respectively, and these results were almost identical to those obtained from MSAO-direct. The agreement between MSAO-direct and PCR was 61.5% ( 95% CI 42.8 - 80.2%) for positive results, 95.6% ( 95% CI 93.0 - 98.2%) for negative results and overall was 92.2% ( 95% CI 88.9 - 95.5%). Conclusions: ( 1) The discriminatory power of PCR and MSAO-direct is similar but the level of agreement, especially for true positive results, is low. ( 2) The potential TAT for the PCR method provides a marked advantage over conventional methods. ( 3) Further modifications to the PCR method such as increased broth incubation time, use of selective broth and adaptation to real-time PCR may lead to improvement in sensitivity and TAT.

A rapid HPLC-mass spectrometry cyclosporin method suitable for current monitoring practices

Objectives: Cyclosporin is an immunosuppressant drug with a narrow therapeutic window. Trough and 2-h post-dose blood samples are currently used for therapeutic drug monitoring in solid organ transplant recipients. The aim of the current study was to develop a rapid HPLC-tandem mass spectrometry (HPLC-MS) method for the measurement of cyclosporin in whole blood that was not only suitable for the clinical setting but also considered a reference method. Methods: Blood samples (50 mu L) were prepared by protein precipitation followed by C-18 solid-phase extraction while using d(12) cyclosporin as the internal standard. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface in positive ionization mode. Results: The assay was linear from 10 to 2000 mu g/L (r(2) > 0.996, n = 9). Inter-day,analytical recovery and imprecision using whole blood quality control samples at 10, 30, 400, 1500, and 2000 mu g/L were 94.9-103.5% and

A new method of isometric dynamometry for the craniocervical flexor muscles

Background and Purpose. A new method of dynamometry has been developed to measure the performance of the craniocervical (CC) flexor muscles by recording the torque that these muscles exert on the cranium around the CC junction. This report describes the method, the specifications of the instrument, and the preliminary reliability data. Subjects and Methods. For the reliability study, 20 subjects (12 subjects with a history of neck pain, 8 subjects without a history of neck pain) performed, on 2 occasions, maximal voluntary isometric contraction (MVIC) tests of CC flexion in 3 positions within the range of CC flexion and submaximal sustained tests (20% and 50% of MVIC) in the middle range of CC flexion (craniocervical neutral position). Reliability coefficients were calculated to establish the test-retest reliability of the measurements. Results. The method demonstrated good reliability over 2 sessions in the measurement of MVIC (intraclass correlation coefficient [ICC] =.79-.93, SEM=0.6-1.4 N-m) and in the measurement of steadiness (standard deviation of torque amplitude) of a sustained contraction at 20% of NMC (ICC=.74-.80, SEM=0.01 N-m), but not at 50% of MVIC (ICC=.07-.76, SEM=0.04-0.13 N-m). Discussion and Conclusion. The new dynamometry method appears to have potential clinical application in the measurement of craniocervical flexor muscle performance.

A rapid and sensitive microscale HPLC method for the determination of indomethacin in plasma of premature neonates with patent ductus arteriousus

Indomethacin (IND) is the drug of choice for the closure of a patent ductus arteriosus (PDA) in neonates. This paper describes a simple, sensitive, accurate and precise microscale HPLC method suitable for the analysis of IND in plasma of premature neonates. Samples were prepared by plasma protein precipitation with acetonitrile containing the methyl ester of IND as the internal standard (IS). Chromatography was performed on a Hypersil C-18 column. The mobile phase of methanol, water and orthophosphoric acid (70:29.5:0.5, v/v, respectively), was delivered at 1.5 mL/min and monitored at 270 nm. IND and the IS were eluted at 2.9 and 4.3 min, respectively. Calibrations were linear (r > 0.999) from 25 to 2500 mu g/L. The inter- and intra-day assay imprecision was less than 4.3% at 400-2000 mu g/L, and less than 22.1% at 35 mu g/L. Inaccuracy ranged from -6.0% to +1.0% from 35 to 2000 mu g/L. The absolute recovery of IND over this range was 93.0-113.3%. The IS was stable for at least 36 h when added to plasma at ambient temperature. This method is suitable for pharmacokinetic studies of IND and has potential for monitoring therapy in infants with PDA when a target therapeutic range for IND has been validated. (c) 2005 Elsevier B.V. All rights reserved.

Shortcomings of protein removal prior to high performance liquid chromatographic analysis - A case study using method development for BAY 11-7082

During the analytical method development for BAY 11-7082 ((E)-3-[4-methylphenylsulfonyl]-2-propenenitrile), using HPLC-MS-MS and HPLC-UV, we observed that the protein removal process (both ultrafiltration and precipitation method using organic solvents) prior to HPLC brought about a significant reduction in the concentration of this compound. The use of a structurally similar internal standard, BAY 11-7085 ((E)-3-[4-t-butylphenylsulfonyl]-2-propenenitrile), was not effective in compensating for the loss of analyte as the extent of reduction was different to that of the analyte. We present here a systematic investigation of this problem and a new validated method for the determination of BAY 11-7082. (c) 2006 Elsevier B.V. All rights reserved.

Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10−6. The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.

A sensitive HPLC method for measuring bacterial proteolysis and proteinase activity in UHT milk

A sensitive quantitative reversed-phase HPLC method is described for measuring bacterial proteolysis and proteinase activity in UHT milk. The analysis is performed on a TCA filtrate of the milk. The optimum concentration of TCA was found to be 4%; at lower concentrations, non-precipitated protein blocked the HPLC while higher concentrations yielded lower amounts of peptides. The method showed greater sensitivity and reproducibility than a fluorescamine-based method. Quantification of the HPLC method was achieved by use of an external dipeptide standard or a standard proteinase. (c) 2006 Elsevier Ltd. All rights reserved.

A novel method for studying the cortical processing of human swallowing using Synthetic Aperture Magnetometry(SAM)

Background/Aims: Positron emission tomography has been applied to study cortical activation during human swallowing, but employs radio-isotopes precluding repeated experiments and has to be performed supine, making the task of swallowing difficult. Here we now describe Synthetic Aperture Magnetometry (SAM) as a novel method of localising and imaging the brain's neuronal activity from magnetoencephalographic (MEG) signals to study the cortical processing of human volitional swallowing in the more physiological prone position. Methods: In 3 healthy male volunteers (age 28–36), 151-channel whole cortex MEG (Omega-151, CTF Systems Inc.) was recorded whilst seated during the conditions of repeated volitional wet swallowing (5mls boluses at 0.2Hz) or rest. SAM analysis was then performed using varying spatial filters (5–60Hz) before co-registration with individual MRI brain images. Activation areas were then identified using standard sterotactic space neuro-anatomical maps. In one subject repeat studies were performed to confirm the initial study findings. Results: In all subjects, cortical activation maps for swallowing could be generated using SAM, the strongest activations being seen with 10–20Hz filter settings. The main cortical activations associated with swallowing were in: sensorimotor cortex (BA 3,4), insular cortex and lateral premotor cortex (BA 6,8). Of relevance, each cortical region displayed consistent inter-hemispheric asymmetry, to one or other hemisphere, this being different for each region and for each subject. Intra-subject comparisons of activation localisation and asymmetry showed impressive reproducibility. Conclusion: SAM analysis using MEG is an accurate, repeatable, and reproducible method for studying the brain processing of human swallowing in a more physiological manner and provides novel opportunities for future studies of the brain-gut axis in health and disease.

A longitudinal study of the diffusion of the ISO/IEC information resource dictionary system standard (IRDS.)

The IRDS standard is an international standard produced by the International Organisation for Standardisation (ISO). In this work the process for producing standards in formal standards organisations, for example the ISO, and in more informal bodies, for example the Object Management Group (OMG), is examined. This thesis examines previous models and classifications of standards. The previous models and classifications are then combined to produce a new classification. The IRDS standard is then placed in a class in the new model as a reference anticipatory standard. Anticipatory standards are standards which are developed ahead of the technology in order to attempt to guide the market. The diffusion of the IRDS is traced over a period of eleven years. The economic conditions which affect the diffusion of standards are examined, particularly the economic conditions which prevail in compatibility markets such as the IT and ICT markets. Additionally the consequences of the introduction of gateway or converter devices into a market where a standard has not yet been established is examined. The IRDS standard did not have an installed base and this hindered its diffusion. The thesis concludes that the IRDS standard was overtaken by new developments such as object oriented technologies and middleware. This was partly because of the slow development process of developing standards in traditional organisations which operate on a consensus basis and partly because the IRDS standard did not have an installed base. Also the rise and proliferation of middleware products resulted in exchange mechanisms becoming dominant rather than repository solutions. The research method used in this work is a longitudinal study of the development and diffusion of the ISO/EEC IRDS standard. The research is regarded as a single case study and follows the interpretative epistemological point of view.

A critical assessment of the finite element method for calculating electric and magnetic fields

The present dissertation is concerned with the determination of the magnetic field distribution in ma[.rnetic electron lenses by means of the finite element method. In the differential form of this method a Poisson type equation is solved by numerical methods over a finite boundary. Previous methods of adapting this procedure to the requirements of digital computers have restricted its use to computers of extremely large core size. It is shown that by reformulating the boundary conditions, a considerable reduction in core store can be achieved for a given accuracy of field distribution. The magnetic field distribution of a lens may also be calculated by the integral form of the finite element rnethod. This eliminates boundary problems mentioned but introduces other difficulties. After a careful analysis of both methods it has proved possible to combine the advantages of both in a .new approach to the problem which may be called the 'differential-integral' finite element method. The application of this method to the determination of the magnetic field distribution of some new types of magnetic lenses is described. In the course of the work considerable re-programming of standard programs was necessary in order to reduce the core store requirements to a minimum.

A method for the in-situ determination of the hydraulic conductivity of gravels as used in constructed wetlands for wastewater treatment

A new instrument and method are described that allow the hydraulic conductivities of highly permeable porous materials, such as gravels in constructed wetlands, to be determined in the field. The instrument consists of a Mariotte siphon and a submersible permeameter cell with manometer take-off tubes, to recreate in-situ the constant head permeameter test typically used with excavated samples. It allows permeability to be measured at different depths and positions over the wetland. Repeatability obtained at fixed positions was good (normalised standard deviation of 1–4%), and results obtained for highly homogenous silica sand compared well when the sand was retested in a lab permeameter (0.32 mm.s–1 and 0.31 mm.s–1 respectively). Practical results have a ±30% associated degree of uncertainty because of the mixed effect of natural variation in gravel core profiles, and interstitial clogging disruption during insertion of the tube into the gravel. This error is small, however, compared to the orders of magnitude spatial variations detected. The technique was used to survey the hydraulic conductivity profile of two constructed wetlands in the UK, aged 1 and 15 years respectively. Measured values were high (up to 900 mm.s –1) and varied by three orders of magnitude, reflecting the immaturity of the wetland. Detailed profiling of the younger system suggested the existence of preferential flow paths at a depth of 200 mm, corresponding to the transition between more coarse and less coarse gravel layers (6–12 mm and 3–6 mm respectively), and transverse drift towards the outlet.

A simple bioanalytical method for the quantification of antiepileptic drugs in dried blood spots

An increasing number of publications on the dried blood spot (DBS) sampling approach for the quantification of drugs and metabolites have been spurred on by the inherent advantages of this sampling technique. In the present research, a selective and sensitive high-performance liquid chromatography method for the concurrent determination of multiple antiepileptic drugs (AEDs) [levetiracetam (LVT), lamotrigine (LTG), phenobarbital (PHB)], carbamazepine (CBZ) and its active metabolite carbamazepine-10,11 epoxide (CBZE)] in a single DBS has been developed and validated. Whole blood was spotted onto Guthrie cards and dried. Using a standard punch (6 mm diameter), a circular disc was punched from the card and extracted with methanol: acetonitrile (3:1, v/v) containing hexobarbital (Internal Standard) and sonicated prior to evaporation. The extract was then dissolved in water and vortex mixed before undergoing solid phase extraction using HLB cartridges. Chromatographic separation of the AEDs was achieved using Waters XBridge™ C18 column with a gradient system. The developed method was linear over the concentration ranges studied with r ≥ 0.995 for all compounds. The lower limits of quantification (LLOQs) were 2, 1, 2, 0.5 and 1 μg/mL for LVT, LTG, PHB, CBZE and CBZ, respectively. Accuracy (%RE) and precision (%CV) values for within and between day were <20% at the LLOQs and <15% at all other concentrations tested. This method was successfully applied to the analysis of the AEDs in DBS samples taken from children with epilepsy for the assessment of their adherence to prescribed treatments.