An extended interval dosing method for gentamicin in neonates

Traditional gentamicin dosing every 8–24 h depending on age and weight in neonates does not provide the ideal concentration–time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8–24 h, aiming for peak concentrations (Cmax) of 6–10 mg/L and trough concentrations (Cmin) 10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0–24 was 93 mg•h/L (target = 100 mg•h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.

The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) - Results of an international collaborative study

Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal dominant condition accounting for 2–5% of all colorectal carcinomas as well as a small subset of endometrial, upper urinary tract and other gastrointestinal cancers. An assay to detect the underlying defect in HNPCC, inactivation of a DNA mismatch repair enzyme, would be useful in identifying HNPCC probands. Monoclonal antibodies against hMLH1 and hMSH2, two DNA mismatch repair proteins which account for most HNPCC cancers, are commercially available. This study sought to investigate the potential utility of these antibodies in determining the expression status of these proteins in paraffin-embedded formalin-fixed tissue and to identify key technical protocol components associated with successful staining. A set of 20 colorectal carcinoma cases of known hMLH1 and hMSH2 mutation and expression status underwent immunoperoxidase staining at multiple institutions, each of which used their own technical protocol. Staining for hMSH2 was successful in most laboratories while staining for hMLH1 proved problematic in multiple labs. However, a significant minority of laboratories demonstrated excellent results including high discriminatory power with both monoclonal antibodies. These laboratories appropriately identified hMLH1 or hMSH2 inactivation with high sensitivity and specificity. The key protocol point associated with successful staining was an antigen retrieval step involving heat treatment and either EDTA or citrate buffer. This study demonstrates the potential utility of immunohistochemistry in detecting HNPCC probands and identifies key technical components for successful staining.

Contradictions and institutional convergences: Genre as method

My purpose here is to put forward a conception of genre as a way to conduct Futures Studies. To demonstrate the method, I present some examples of contemporary political and corporate discourses and contextualise them in broader institutional and historical settings. I elaborate the method further by giving examples of ‘genre chaining’ and ‘genre hybridity’ (Fairclough 1992 2000) to show how past, present, and future change can be viewed through the lens of genre.

Ethanol-related adaptive changes and physical dependence in rats after exposure to ethanol

Adaptive changes that occur after chronic exposure to ethanol are an important component in the development of physical dependence. We have focused our research on ethanol-induced changes in the expression of several genes that may be important in adaptation. In this article, we describe adaptive changes at the level of the N-methyl-D-aspartate receptor, in the protein expression and activity of the Egr transcription factors, and in the expression of a novel gene of unknown function. (C) 2001 Elsevier Science Inc. All rights reserved.

The effects of time delays in adaptive phase measurements

It is not possible to make measurements of the phase of an optical mode using linear optics without introducing an extra phase uncertainty. This extra phase variance is quite large for heterodyne measurements, however it is possible to reduce it to the theoretical limit of log (n) over bar (4 (n) over bar (2)) using adaptive measurements. These measurements are quite sensitive to experimental inaccuracies, especially time delays and inefficient detectors. Here it is shown that the minimum introduced phase variance when there is a time delay of tau is tau/(8 (n) over bar). This result is verified numerically, showing that the phase variance introduced approaches this limit for most of the adaptive schemes using the best final phase estimate. The main exception is the adaptive mark II scheme with simplified feedback, which is extremely sensitive to time delays. The extra phase variance due to time delays is considered for the mark I case with simplified feedback, verifying the tau /2 result obtained by Wiseman and Killip both by a more rigorous analytic technique and numerically.

An occupational view of the Australian labour force - Patterns of job growth and decline

Generally employment has been studied in terms of changes in the types of goods and services that the economy is purchasing. Far less attention has been given to the occupational aggregates that go into producing these goods and services. The few studies that did investigate this area found that the mix of tabour inputs appear to have been changing over time in a systematic pattern. The increasing prevalence of white-collar, information workers gave rise to the assertion that many societies had entered a post-industrial information age. Deals first of aff with some issues of measurement in the context of the Australian labour force, then looks at trends in various occupational groups using a non-standard four-sector classification of the labour force. Finally suggests an application in relation to the link between education and training and its ability to reduce structural unemployment.

Power of the joint segregation analysis method for testing mixed major-gene and polygene inheritance models of quantitative traits

Understanding the genetic architecture of quantitative traits can greatly assist the design of strategies for their manipulation in plant-breeding programs. For a number of traits, genetic variation can be the result of segregation of a few major genes and many polygenes (minor genes). The joint segregation analysis (JSA) is a maximum-likelihood approach for fitting segregation models through the simultaneous use of phenotypic information from multiple generations. Our objective in this paper was to use computer simulation to quantify the power of the JSA method for testing the mixed-inheritance model for quantitative traits when it was applied to the six basic generations: both parents (P-1 and P-2), F-1, F-2, and both backcross generations (B-1 and B-2) derived from crossing the F-1 to each parent. A total of 1968 genetic model-experiment scenarios were considered in the simulation study to quantify the power of the method. Factors that interacted to influence the power of the JSA method to correctly detect genetic models were: (1) whether there were one or two major genes in combination with polygenes, (2) the heritability of the major genes and polygenes, (3) the level of dispersion of the major genes and polygenes between the two parents, and (4) the number of individuals examined in each generation (population size). The greatest levels of power were observed for the genetic models defined with simple inheritance; e.g., the power was greater than 90% for the one major gene model, regardless of the population size and major-gene heritability. Lower levels of power were observed for the genetic models with complex inheritance (major genes and polygenes), low heritability, small population sizes and a large dispersion of favourable genes among the two parents; e.g., the power was less than 5% for the two major-gene model with a heritability value of 0.3 and population sizes of 100 individuals. The JSA methodology was then applied to a previously studied sorghum data-set to investigate the genetic control of the putative drought resistance-trait osmotic adjustment in three crosses. The previous study concluded that there were two major genes segregating for osmotic adjustment in the three crosses. Application of the JSA method resulted in a change in the proposed genetic model. The presence of the two major genes was confirmed with the addition of an unspecified number of polygenes.

A new method of threshold voltage extraction via MOSFET gate-to-substrate capacitance measurement

A new method to extract MOSFET's threshold voltage VT by measurement of the gate-to-substrate capacitance C-gb of the transistor is presented. Unlike existing extraction methods based on I-V data, the measurement of C-gb does not require de drain current to now between drain and source thus eliminating the effects of source and drain series resistance R-S/D, and at the same time, retains a symmetrical potential profile across the channel. Experimental and simulation results on devices with different sizes are presented to justify the proposed method.

A practical method for identifying intermetallic phase particles in aluminium alloys by electron probe microanalysis

Aluminium alloys that contain Si, Mg, Fe, Mn and/or Cu usually contain one or more types of intermetallic phases that are not readily distinguishable in the microstructure by conventional microscopy methods. It has thus been a challenge to develop a method that will unambiguously identify them. A practical approach has been developed that is based on an inherent linear relationship revealed for the overall distribution of any two elements in a precipitate/matrix geometry and the first-order approximation of electron probe microanalysis (EPMA) results. Application of this approach to a direct chill cast 6082 alloy is demonstrated, and its major limitations are discussed.

A high efficient and consistent method for harvesting large volumes of high-titre lentiviral vectors

Lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) are emerging as the vectors of choice for in vitro and in vivo gene therapy studies. However, the current method for harvesting lentivectors relies upon ultracentrifugation at 50 000 g for 2 h. At this ultra-high speed, rotors currently in use generally have small volume capacity. Therefore, preparations of large volumes of high-titre vectors are time-consuming and laborious to perform. In the present study, viral vector supernatant harvests from vector-producing cells (VPCs) were pre-treated with various amounts of poly-L-lysine (PLL) and concentrated by low speed centrifugation. Optimal conditions were established when 0.005% of PLL (w/v) was added to vector supernatant harvests, followed by incubation for 30 min and centrifugation at 10 000 g for 2 h at 4 degreesC. Direct comparison with ultracentrifugation demonstrated that the new method consistently produced larger volumes (6 ml) of high-titre viral vector at 1 x 10(8) transduction unit (TU)/ml (from about 3000 ml of supernatant) in one round of concentration. Electron microscopic analysis showed that PLL/viral vector formed complexes, which probably facilitated easy precipitation at low-speed concentration (10 000 g), a speed which does not usually precipitate viral particles efficiently. Transfection of several cell lines in vitro and transduction in vivo in the liver with the lentivector/PLL complexes demonstrated efficient gene transfer without any significant signs of toxicity. These results suggest that the new method provides a convenient means for harvesting large volumes of high-titre lentivectors, facilitate gene therapy experiments in large animal or human gene therapy trials, in which large amounts of lentiviral vectors are a prerequisite.

An easy and reliable method for establishment and maintenance of leaf and root cell cultures of Arabidopsis thaliana

Cell suspension cultures are useful for a wide range of biochemical and physiological studies, yet their production can be technically demanding and often unreliable. Here we describe a protocol for producing Arabidopsis cell suspension cultures that is reliable and easy to use.

Repeatability of maximal voluntary force and of surface EMG variables during voluntary isometric contraction of quadriceps muscles in healthy subjects

The repeatability of initial values and rate of change of EMG signal mean spectral frequency (MNF), average rectified values (ARV), muscle fiber conduction velocity (CV) and maximal voluntary contraction (MVC) was investigated in the vastus medialis obliquus (VMO) and vastus lateralis (VL) muscles of both legs of nine healthy male subjects during voluntary, isometric contractions sustained for 50 s at 50% MVC. The values of MVC were recorded for both legs three times on each day and for three subsequent days, while the EMG signals have been recorded twice a day for three subsequent days. The degree of repeatability was investigated using the Fisher test based upon the ANalysis Of VAriance (ANOVA), the Standard Error of the Mean (SEM) and the Intraclass Correlation Coefficient (ICC). Data collected showed a high level of repeatability of MVC measurement (normalized SEM from 1.1% to 6.4% of the mean). MNF and ARV initial values also showed a high level of repeatability (ICC > 70% for all muscles and legs except right VMO). At 50% MVC level no relevant pattern of fatigue was observed for the VMO and VL muscles, suggesting that other portions of the quadriceps might have contributed to the generated effort. These observations seem to suggest that in the investigation of muscles belonging to a multi-muscular group at submaximal level, the more selective electrically elicited contractions should be preferred to voluntary contractions. (C) 2001 Elsevier Science Ltd. All rights reserved.

An inverse design method for elliptical MRI magnets

An inverse, current density mapping (CDM) method has been developed for the design of elliptical cross-section MRI magnets. The method provides a rapid prototyping system for unusual magnet designs, as it generates a 3D current density in response to a set of target field and geometric constraints. The emphasis of this work is on the investigation of new elliptical coil structures for clinical MRI magnets. The effect of the elliptical aspect ratio on magnet performance is investigated. Viable designs are generated for symmetric, asymmetric and open architecture elliptical magnets using the new method. Clinically relevant attributes such as reduced stray field and large homogeneous regions relative to total magnet length are included in the design process and investigated in detail. The preliminary magnet designs have several novel features.