bluuebunny/crossref_metadata_2025 huggingface dataset:
A two-stage heat transfer model for the peripheral layers of a grain store
Authors: Antic Alexsandar , Hill James M.
Published: March 2007

An understanding of the flow of heat in grain store structures, in particular, within the peripheral layer, is important from many industrial perspectives. To analyse the heat transfer within such regions a mathematical model known as the two-stage heat transfer model is proposed. This model makes a distinction between the air and grain within the grain bulk, and thus takes into consideration the fact that the rate of heat transfer through the grain is different to that through the interstitial air surrounding the grain. Such a model lends itself to a solution via Laplace transforms and approximate analytical results are obtained for small and large times. In addition, the Stehfest numerical algorithm is used for the inversions and very good agreement is obtained between the two approaches. The present model is compared to a previously developed double-diffusivity heat transfer model by the authors, and good agreement is obtained. At present, no experimental data is available to validate the model as it is very difficult to measure the air and grain temperatures separately, particularly in the peripheral layer. The proposed model provides insight into the potential difference existing between the air and grain temperatures.
Inequalities between hypergeometric tails
Authors: Phipps Mary C.
Published: March 2007

A special inequality between the tail probabilities of certain related hypergeometrics was shown by Seneta and Phipps [19] to suggest useful ‘quasi-exact’ alternatives to Fisher's [5] Exact Test. With this result as motivation, two inequalities of Hájek and Havránek [6] are investigated in this paper and are generalised to produce inequalities in the form required. A parallel inequality in binomial tail probabilities is also established.
Polya tree distributions for statistical modeling of censored data
Authors: Neath Andrew A.
Published: March 2007

Polya tree distributions extend the idea of the Dirichlet process as a prior for Bayesian nonparametric problems. Finite dimensional distributions are defined through conditional probabilities in P. This allows for a specification of prior information which carries greater weight where it is deemed appropriate according to the choice of a partition of the sample space. Muliere and Walker[7] construct a partition so that the posterior from right censored data is also a Polya tree. A point of contention is that the specification of the prior is partially dependent on the data. In general, the posterior from censored data will be a mixture of Polya trees. This paper will present a straightforward method for determining the mixing distribution.
Genetic algorithm for network cost minimization using threshold based discounting
Authors: Podnar Hrvoje , Skorin-Kapov Jadranka
Published: March 2007

We present a genetic algorithm for heuristically solving a cost minimization problem applied to communication networks with threshold based discounting. The network model assumes that every two nodes can communicate and offers incentives to combine flow from different sources. Namely, there is a prescribed threshold on every link, and if the total flow on a link is greater than the threshold, the cost of this flow is discounted by a factor α. A heuristic algorithm based on genetic strategy is developed and applied to a benchmark set of problems. The results are compared with former branch and bound results using the CPLEX® solver. For larger data instances we were able to obtain improved solutions using less CPU time, confirming the effectiveness of our heuristic approach.
Robustness to non-normality of various tests for the one-sample location problem
Authors: McDougall Michelle K. , Rayner Glen D.
Published: March 2007

This paper studies the effect of the normal distribution assumption on the power and size of the sign test, Wilcoxon's signed rank test and the t-test when used in one-sample location problems. Power functions for these tests under various skewness and kurtosis conditions are produced for several sample sizes from simulated data using the g-and-k distribution of MacGillivray and Cannon [5].
Single retrial queues with service option on arrival
Authors: Farahmand K. , Cooke N.
Published: March 2007

We analyze a queueing system in which customers can call in to request service. A proportion, say 1−p of them on their arrival test the availability of the server. If the server is free the customer enters service immediately. Otherwise, if the service system is occupied, the customer joins a source of unsatisfied customers called the orbit. The remaining p proportion of the initial customers enter the orbit directly, without examining the state of the server. We consider two models characterized by the discipline governing the order of re-requests for service from the orbit. First, all the customers from the orbit apply at a fixed rate. Secondly, customers from the orbit are discouraged and reduce their rate of demand as more customers join the orbit. The arrival at and the demands from the orbit are both assumed to be according to the Poisson Process. However, the service times for both primary customers and customers from the orbit are assumed to have a general distribution. We calculate several characteristic quantities of these queueing systems.
Extensions to the Kruskal-Wallis test and a generalised median
test with extensions
Authors: Rayner J. C. W. , Best D. J.
Published: March 2007

The data for the tests considered here may be presented in two-way contingency tables with all marginal totals fixed. We show that Pearson's test statistic XP2 (P for Pearson) may be partitioned into useful and informative components. The first detects location differences be tween the treatments, and the subsequent components detect dispersion and higher order moment differences. For Kruskal-Wallis-type data when there are no ties, the location component is the Kruskal-Wallis test. The subsequent components are the extensions. Our approach enables us to generalise to when there are ties, and to when there is a fixed number of categories and a large number of observations. We also propose a generalisation of the well-known median test. In this situation the location-detecting first component of XP2 reduces to the usual median test statistic when there are only two categories. Subsequent components detect higher moment departures from the null hypothesis of equal treatment effects
The predictive distribution in decision theory: a
case study
Authors: Jones Geoff
Published: March 2007

In the classical decision theory framework, the loss is a function of the decision taken
and the state of nature as represented by a parameter θ. Information about θ can be obtained
via observation of a random variable X. In some situations however the loss will depend not
directly on θ but on the observed value of another random variable Y whose distribution depends
on θ. This adds an extra layer to the decision problem, and may lead to a wider choice of actions.
In particular there are now two sample sizes to choose, for X and for Y, leading to a range of
behaviours in the Bayes risk. We illustrate this with a problem arising from the cleanup of sites
contaminated with radioactive waste. We also discuss some computational approaches.
On selecting the most reliable components
Authors: Shi Dylan
Published: March 2007

Consider a series system consisting of n components of k types. Whenever a unit fails,
it is replaced immediately by a new one to keep the system working. Under the assumption that
all the life lengths of the components are independent and exponentially distributed and that the
replacement policies depend only on the present state of the system at each failure, the system
may be represented by a birth and death process. The existence of the optimum replacement
policies are discussed and the ε-optimal policies axe derived. If the past experience of the system
can also be utilized, the process is not a Markov process. The optimum Bayesian policies are
derived and the properties of the resulting process axe studied. Also, the stochastic processes
are simulated and the probability of absorption, the mean time to absorption and the average
proportion of the retrograde motion are approximated.
Multi-class decision procedures for the inspection operation
Authors: Jaraiedi Majid , Segall Richard S. , Rajamohan Venkatramani
Published: March 2007

Increasing the amount of inspection activities and inspecting a large fraction of the
items are two approaches that are used to improve products' quality. In this paper, as in a precedent
article by Jaraiedi, et al.[5], 100% inspection in combination with multiple-criteria decision
(MCD) response is considered. Three different inspection procedures for the multi-stage inspection
are presented. Performance of these three procedures are derived and the Average Outgoing
Quality (AOQ), Average False Rejected (AFR), and Overall Average Fraction Inspected (SAFI)
for all procedures are compared. Two examples are discussed in depth to illustrate numerical
comparisons of these procedures.
A generalization of the convex-hull-and-line traveling salesman problem
Authors: Baki Md. Fazle , Kabadi S. N.
Published: March 2007

Two instances of the traveling salesman problem, on the same node set {1,2,…,n}
but with different cost matrices C
and C′
, are equivalent iff there exist {ai,bi: i=1,…, n} such
that for any 1≤i, j≤n,i≠j,C′(i,j)=C(i,j)+ai+bj [7]. One of the well-solved special cases
of the traveling salesman problem (TSP) is the convex-hull-and-line TSP. We extend the solution
scheme for this class of TSP given in [9] to a more general class which is closed with respect to
the above equivalence relation. The cost matrix in our general class is a certain composition of
Kalmanson matrices. This gives a new, non-trivial solvable case of TSP.
Robustness of the sample correlation - the bivariate lognormal case
Authors: Lai C. D. , Rayner J. C. W. , Hutchinson T. P.
Published: March 2007

The sample correlation coefficient R is almost universally used to estimate the
population correlation coefficient ρ. If the pair (X,Y)
has a bivariate normal distribution, this
would not cause any trouble. However, if the marginals are nonnormal, particularly if they
have high skewness and kurtosis, the estimated value from a sample may be quite different from
the population correlation coefficient ρ.

The bivariate lognormal is chosen as our case study for this robustness study. Two approaches
are used: (i) by simulation and (ii) numerical computations.

Our simulation analysis indicates that for the bivariate lognormal, the bias in estimating ρ can
be very large if ρ≠0, and it can be substantially reduced only after a large number (three to four
million) of observations. This phenomenon, though unexpected at first, was found to be
consistent to our findings by our numerical analysis.
Nonparametric tests for data in randomised blocks with Ordered
alternatives
Authors: Rayner J. C. W. , Best D. J.
Published: March 2007

For randomized block designs, nonparametric treatment comparisons
are usually made using the Friedman test for complete designs, and the Durbin test
for incomplete designs; see, for example, Conover (1998). This permits assessment
of only the mean rankings. Such comparisons are here extended to permit assessments
of bivariate effects such as the linear by linear effect and the quadratic by
linear, or umbrella effect.
Arsenic speciation in beverages by direct injection‐ion chromatography hydride generation atomic fluorescence spectrometry
Authors: Moreno E. , Cámara C , Corns W. T. , Bryce D. W. , Stockwell P. B.
Published: March 2007

The procedure developed allows the direct speciation of arsenic in these samples with good sensitivity, selectivity, precision and accuracy. Detection limits determined using the optimized conditions were found to be between 0.16 and 2.9 ng ml−1 for arsenite, dimethylarsinic acid, monomethylarsonic acid and arsenate, while standard addition studies showed that the procedure is free from matrix interferences. As no certified reference materials are available for these analytes or matrices, validation was carried out by studying spike recoveries and by comparison of results with an alternative technique.
Implementation of analytical technologies in a pharmaceutical development organization looking into the next millennium
Authors: North Nigel
Published: March 2007

Managing the implementation of new technology in a pharmaceutical development environment has provided challenges and opportunities to obtain benefits from technologies, e.g. laboratory automation. Successful application of new techniques requires a dedicated resource. Within Pharmaceutical Technologies, this was initially a single person, who has since evolved into a team dedicated to the investigation and development of robotics and non‐invasive analytical techniques. Pharmaceutical development is an important interface between research and commercial manufacturing. In research, the success of genomics and combinatorial chemistry will result in a significant increase in the number of development compounds, and this, combined with the desire of commercial manufacturing to move towards parametric release, puts an emphasis on the need for rapid analytical methods. Some ideas on the techniques that will be required to meet these goals will be described together with their impact on automation.
Multicentre evaluation of the Boehringer Mannheim/Hitachi 917 analysis system
Authors: van Suijlen Jeroen D. E. , Blijenberg Bert G. , Hofmann Jörg , Bauer Kurt , Zaman Zahur , Blanckaert Norbert , Degenhard Peter , Wielckens Klaus , Ferré Carmen , Torralba Antonio , Martyn Mary , Kelly Anne , Ceriotti Ferrucio , Bonini Pierangelo A. , Bablok Wolfgang , McGovern Margaret , Stockmann Wolfgang
Published: March 2007

The new selective access analysis system BM/Hitachi 917 was evaluated in an international multicentre study, mainly according to the ECCLS protocol for the evaluation of analysers in clinical chemistry. Forty‐three different analytes, covering 56 different methods enzymes, substrates, electrolytes, specific proteins, drugs and urine applications were tested in seven European clinical chemistry laboratories. Additionally, the practicability of the BM/ Hitachi 917 was tested according to a standardized questionnaire. Within‐run CVs (median of 3 days) for enzymes, substrates and electrolytes were <2% except for creatine‐kinase MB isoform and lipase at low concentration. For proteins, drugs and urine analytes the within‐run CVs were < 4% except for digoxin and albumin in urine. Between‐day median CVs were generally < 3% for enzymes, substrates and electrolytes, and < 6% for proteins, drugs and urine analytes, except for lipase, creatine kinase and MB isoform, D‐dimer, glycosylated haemoglobin, rheumatoid factors, digoxin, digitoxin, theophylline and albumin in urine in some materials. Linearity was found according to the test specifications or better and there were no relevant effects seen in drift and carry‐over testing. The interference results clearly show that also for the BM/Hitachi 917 interference exists sometimes, as could be expected because of the chemistries applied. It is a situation that can be found in equivalent analysers as well. The accuracy is acceptable regarding a 95–105% recovery in standard reference material, with the exception of the creatinine Jaffé method. Most of the 160 method comparisons showed acceptable agreement according to our criteria: enzymes, substrates, urine analytes deviation of slope ± 5%, electrolytes ± 3%, and proteins and drugs ± 10%. The assessment of practicability for 14 groups of attributes resulted in a grading of one–three scores better for the BM/Hitachi 917 than the present laboratory situation. In conclusion, the results of the study showed good analytical performance and confirmed the usefulness of the system as a consolidated workstation in medium‐sized to large clinical chemistry laboratories.
An improved leaping detector for flow analysis applied to iron speciation in drugs
Authors: Santos Sérgio R. B. , Araújo Mário C. U. , Honorato Ricardo S. , Zagatto Elias A. G. , Lima José F. C. , Lapa Rui A. S.
Published: March 2007

A low inner volume (ca. 64 ml) probe was built up in an injector‐commutator in order to behave as a photometric leaping detector in flow analysis. It comprises a bicolour light‐emitting diode (BLED), as a source of pulsed radiation in the red and green visible region, and two phototransistors as transducers. Sample injection, detector relocation, analytical signal recording, data treatment and definition of the spectral working range were computer‐controlled. The feasibility of the system was initially demonstrated in the flow‐injection speciation of iron, and the overall standard deviation of results was estimated as ± 1.6 and ± 1.4% for 1.6–4.0 mg l−1 Fe(II) or total iron after eightfold processing of synthetic samples. The system was further applied to drug analysis: the mean deviations of results for typical samples were estimated as ± 5.2 and ± 3.3%, and the relative standard deviation as ± 1.6 and ± 1.3% for Fe(II) and total iron, respectively. Results were compared with those obtained by a conventional spectrophotometric procedure and no statistic differences at the 95% confidence level were found. In relation to an earlier system with multi‐site detection, the proposed system is more stable, presenting low drift with a relative standard deviation of 0.026% and 0.039% for measurements (n=120 during 4 h of observation) with green and red emission. It is also faster with a sampling rate of 133 h−1 and carryover problems are not found. The possibility of compensating the Schlieren noise by dual‐wavelength spectrophotometry is discussed.
Dealing with the data deluge in high throughput screening
Authors: Skehan Philip
Published: March 2007

Numerical taxonomy and pattern recognition analysis offer powerful tools that can greatly reduce the information burden of multiple‐assay screening programs. These methods can be used to rationally design prescreens, identify assays that have similar chemical response patterns, select reporter assays for chemical response groups, evaluate drug selectivity, and predict a drug′s likely mechanism of action. When combined with assays designed to identify lead compounds that have characteristics likely to cause failure at a later and more expensive stage of development, a simple three‐stage primary discovery process consisting of a rational prescreen, reporters, and clinical failure assay can reduce the number of required culture wells by more than 20‐fold and can eliminate all but 1–2 drugs per 1000 tested as leads for further evaluation and development.
High throughput drug profiling
Authors: Entzeroth Michael , Chapelain Béatrice , Guilbert Jacques , Hamon Valérie
Published: March 2007

High throughput screening has significantly contributed to advances in drug discovery. The great increase in the number of samples screened has been accompanied by increases in costs and in the data required for the investigated compounds. High throughput profiling addresses the issues of compound selectivity and specificity. It combines conventional screening with data mining technologies to give a full set of data, enabling development candidates to be more fully compared.
A fully automated liquid–liquid extraction system utilizing interface detection
Authors: Maslana Eugene , Schmitt Robert , Pan Jeffrey
Published: March 2007

The development of the Abbott Liquid‐Liquid Extraction Station was a result of the need for an automated system to perform aqueous extraction on large sets of newly synthesized organic compounds used for drug discovery. The system utilizes a cylindrical laboratory robot to shuttle sample vials between two loading racks, two identical extraction stations, and a centrifuge. Extraction is performed by detecting the phase interface (by difference in refractive index) of the moving column of fluid drawn from the bottom of each vial containing a biphasic mixture. The integration of interface detection with fluid extraction maximizes sample throughput. Abbott‐developed electronics process the detector signals. Sample mixing is performed by high‐speed solvent injection. Centrifuging of the samples reduces interface emulsions. Operating software permits the user to program wash protocols with any one of six solvents per wash cycle with as many cycle repeats as necessary. Station capacity is eighty, 15 ml vials. This system has proven successful with a broad spectrum of both ethyl acetate and methylene chloride based chemistries. The development and characterization of this automated extraction system will be presented.
A centralized global automation group in a decentralized organization
Authors: Ormand James , Bruner Jimmy , Birkemo Larry , Hinderliter-Smith Judy , Veitch Jeffrey
Published: March 2007

In the latter part of the 1990s, many companies have worked to foster a ‘matrix’ style culture through several changes in organizational structure. This type of culture facilitates communication and development of new technology across organizational and global boundaries. At Glaxo Wellcome, this matrix culture is reflected in an automation strategy that relies on both centralized and decentralized resources. The Group Development Operations Information Systems Robotics Team is a centralized resource providing development, support, integration, and training in laboratory automation across businesses in the Development organization. The matrix culture still presents challenges with respect to communication and managing the development of technology. A current challenge for our team is to go beyond our recognized role as a technology resource and actually to influence automation strategies across the global Development organization. We shall provide an overview of our role as a centralized resource, our team strategy, examples of current and past successes and failures, and future directions.
Speciation of inorganic selenium and selenoamino acids by an HPLC‐UV‐HG‐AFS system
Authors: Ipolyi I. , Corns W. , Stockwell P. , Fodor P.
Published: March 2007

For the on‐line speciation of selenocystine (SeCys), selenomethionine (SeMet), selenoethionine (SeEt), selenite (Se(IV)) and selenate (Se(VI)), a high‐performance liquid chromatography‐UV irradiation‐hydride generation‐atomic fluorescence spectro‐ metric method is described. Separation was carried out on a conventional reversed‐phase C18 column modified with didodecyl‐ dimethylammonium bromide with gradient elution applying two concentrations of ammonium acetate as the mobile phase. UV irradiation and hydride generation parameters were optimized. The obtained detection limits for SeCys, SeMet, SeEt, Se(IV) and Se(VI) were 0.31, 0.43, 0.7, 0.44 and 0.32 ng ml−1, respectively, using a 100‐wl loop. The method was tested with spiked mineral water and two volunteers′ urine samples.
My continuing adventure with 21 CFR Part 11 ‐ the evolution of Zymark′s compliance
Authors: Dobro Stephen M.
Published: March 2007

A renewed focus has been given to the 3‐year‐old regulation 21 CFR Part 11, Electronic Records and Electronic Signatures. This paper gives a chronology of the process of an equipment vendor, Zymark Corporation, validating laboratory automation equipment for compliance to the regulation 21 CFR Part 11. Zymark′s Tablet Processing Workstation II™ (TPW™) and Prelude™ are the instruments chronicled. The first instrument, the TPW™, was developed before Zymark defined its strategy on how to meet its customer′s need for 21 CFR Part 11 compliant equipment. The TPW™ has been available for several years, and in the summer of 1999 it received a major software upgrade to improve its security. The second instrument, the Prelude™, is a new product. It had a design requirement to meet the regulation. Zymark′s Part 11 strategy was already in place and used for this development project. This chronology will include all aspects of the exercise, including familiarization with the standard, development of the protocols, review of the protocols by industry experts, review of the protocols by pharmaceutical users, execution of the tests, preparation of the exception reports, and the release of any necessary product revisions.
Development of a microprocessor‐based biochemical sampler
Authors: Randhawa S. S. , Chand G. , Ganju A. K.
Published: March 2007

Modern medicine requires patients to be treated on the basis of precise data, which are often obtained from electronic equipment. An inexpensive and portable microprocessor‐based sampler developed by the authors is described. It is comprised of the following units: sample plate assembly, probe‐drive linkage system, wash fluid receptacle, timing system and 8085A microprocessor.
Design of LabVIEW®‐based software for the control of sequential injection analysis instrumentation for the determination of morphine
Authors: Lenehan Claire E. , Barnett Neil W. , Lewis Simon W.
Published: March 2007

LabVIEW®‐based software for the automation of a sequential injection analysis instrument for the determination of morphine is presented. Detection was based on its chemiluminescence reaction with acidic potassium permanganate in the presence of sodium polyphosphate. The calibration function approximated linearity (range 5 × 10−10 to 5 × 10−6 M) with a line of best fit of y = 1.05x + 89164(R2 = 0.9959), where y is the log10 signal (mV) and x is the log10 morphine concentration (M). Precision, as measured by relative standard deviation, was 0.7% for five replicate analyses of morphine standard (5 × 10−8 M). The limit of detection (3σ) was determined as 5 × 10−11 M morphine.
Design and development of a multichannel potentiometer for monitoring an electrode array and its application in flow analysis
Authors: Rohwedder Jarbas J. R. , Pasquini Celio , Raimundo, Ivo M. , Conceiçao M. , Montenegro B. S. M. , Araújo Alberto N. , Couto Cristina M. C. M.
Published: March 2007

A versatile potentiometer that works with electrode arrays in flow injection and/or monosegmented flow systems is described. The potentiometer is controlled by a microcomputer that allows individual, sequential multiplexed or random accesses to eight electrodes while employing only one reference electrode. The instrument was demonstrated by monitoring an array of seven flow‐through ion‐selective electrodes for Ag+ and for three electrodes for Cl-, Ca2+ and K+. The figures of merit of the individual and multiplexed (summed) readings of the electrode array were compared. The absolute standard deviation of the measurements made by summing the potential of two or more electrodes was maintained constant, thus improving the precision of the measurements. This result shows that an attempt to combine the signals of the electrodes to produce a more intense signal in the Hadamard strategy is feasible and accompanied by a proportional improvement in the precision of individual measurements. The preliminary tests suggest that the system can allow for 270 determinations per hour, with a linear range from 1.0 × 10−2 to 1.0 × 10−4 mol l-1 for the three di¡erent analytes. Detection limits were estimated as 3.1 × 10−5 , 3.0 × 10−6 and 1.0 × 10−5 mol l-1 for Cl-, Ca2+ and K+, respectively.
Analysis of anions in beer using ion chromatography
Authors: Bruce Jonathan
Published: March 2007

The majority of anions found in beer are a consequence of impurities derived from the water used during the brewing process. The process of beer manufacture consists of malting, brewing and fermentation followed by maturation before filtration and finally storage. Strict quality control is required because the presence of certain anions outside strictly defined tolerance limits can affect the flavour characteristics of the finished product. The anions present were quantified using the technique of ion chromatography with the Metrohm modular system following sample preparation. The analysis produced a result of the order 200 mg l-1 for chloride, phosphate and sulphate and around 20 mg l-1 for nitrate. If the chloride level exceeds 250 mg l-1, then the sweetness of the beer is enhanced, but yeast flocculation can be hindered. An excess of sulphate can give a sharp, dry edge to hopped beers and excessive amounts of nitrate have been found to harm the yeast metabolism after conversion to the nitrite form. As water is a primary ingredient within beer, its quality and type is a fundamental factor in establishing many of the distinctive regional beers that can be found in the United Kingdom and is thus monitored carefully.
Automatic flow system for simultaneous determination of iron and chromium in steel alloys employing photometers based on LEDs as radiation source
Authors: Fernandes Ridvan N. , Reis Boaventura F. , Campos Luís Fernando P.
Published: March 2007

A multicommutated flow system for simultaneous determination of iron and chromium in steel alloys by photometry is described. The flow network consisted of an automatic injector and four solenoid valves assembled to form two independent analytical pathways, each one comprising reaction coils and a flow cell. The light source (LED) and detector (photodiode) were attached to the flow cells to form a compact unit. The flow system was microcomputer controlled by Quick BASIC 4.5 software, which carried out all steps of the analytical procedure. The feasibility of the system was proved by the determination of iron and chromium in steel alloys and its accuracy was accessed by comparing results with those obtained by plasma atomic emission spectrometry (ICP‐AES). No significant difference at the 95% confidence level was observed. Other profitable features such as low reagent consumption (0.33 mg 1,10‐phenantroline and 0.03 mg 1,5‐diphenylcarbazide per determination); relative standard deviations (n = 5) of 0.4% for iron and 1.2% for chromium; and an analytical throughput of 160 determinations per h were also achieved.
Automation of dissolution tests
Authors: Rolli Rolf
Published: March 2007

Dissolution testing of drug formulations was introduced in the 1960s and accepted by health regulatory authorities in the 1970s. Since then, the importance of dissolution has grown rapidly as have the number of tests and demands in quality‐control laboratories. Recent research works lead to the development of in‐vitro dissolution tests as replacements for human and animal bioequivalence studies. For many years, a lot of time and effort has been invested in automation of dissolution tests. There have been a number of in‐house solutions from pharmaceutical companies and many have created task forces or even departments to develop automation. Robotic solutions with sequential operation were introduced as well as the simultaneous operation concept developed by SOTAX. Today, pharmaceutical companies focus their resources mainly on the core business and in‐house engineering solutions that are very difficult to justify. Therefore, it is important to know the basic considerations in order to plan an automation concept and implement it together with a vendor.
CTAD as a universal anticoagulant
Authors: Yokota M. , Tatsumi N. , Tsuda I. , Nishioka T. , Takubo T.
Published: March 2007

The feasibility of CTAD (a mixture of citrate, theophylline, adenosine and dipyridamole) as a new anticoagulant for medical laboratory use was studied prospectively. Whole blood anticoagulated with CTAD exhibited results very similar to those of blood anticoagulated with EDTA on complete blood count and automated white cell differential except for a slight decrease in platelet count and mean platelet volume. Chemistry test data for plasma obtained from CTAD whole blood were close to those obtained for matched sera. Among coagulation tests, prothrombin time, activated partial thromboplastin time and fibrinogen concentrations were close to those obtained with citrate plasma. Based on the results, CTAD was judged to be a good candidate as a new anticoagulant.
Modelling of influential parameters on a continuous evaporation process by Doehlert shells
Authors: Fauduet Henri , Porte Catherine , Havet Jean-Louis , Daguet David
Published: March 2007

The modelling of the parameters that influence the continuous evaporation of an alcoholic extract was considered using Doehlert matrices. The work was performed with a wiped falling film evaporator that allowed us to study the influence of the pressure, temperature, feed flow and dry matter of the feed solution on the dry matter contents of the resulting concentrate, and the productivity of the process. The Doehlert shells were used to model the influential parameters. The pattern obtained from the experimental results was checked allowing for some dysfunction in the unit. The evaporator was modified and a new model applied; the experimental results were then in agreement with the equations. The model was finally determined and successfully checked in order to obtain an 8% dry matter concentrate with the best productivity; the results fit in with the industrial constraints of subsequent processes.
Implementation of a low‐cost Interim 21CFR11 compliance solution for laboratory environments
Authors: Greene Jack E.
Published: March 2007

In the recent past, compliance with 21CFR11 has become a major buzzword within the pharmaceutical and biotechnology industries. While commercial solutions exist, implementation and validation are expensive and cumbersome. Frequent implementation of new features via point releases further complicates purchasing decisions by making it difficult to weigh the risk of non‐compliance against the costs of too frequent upgrades. This presentation discusses a low‐cost interim solution to the problem. While this solution does not address 100% of the issues raised by 21CFR11, it does implement and validate: (1) computer system security; (2) backup and restore ability on the electronic records store; and (3) an automated audit trail mechanism that captures the date, time and user identification whenever electronic records are created, modified or deleted. When coupled with enhanced procedural controls, this solution provides an acceptable level of compliance at extremely low cost.
Quality control material for plasma fibrinogen test produced from purified human fibrinogen
Authors: Okuda Masahiro , Uemura Yahiro , Tatsumi Noriyuki
Published: March 2007

Plasma fibrinogen measurement is a routine laboratory procedure commonly performed on automated coagulation analysers. Its determination is quantitative, not quantitative. Yet, a lack of precision has been an issue for fibrinogen measurement. A control material derived from plasma comprises many proteins, inhibitors and fatty acids, any or all of which can interfere in the fibrinogen assay. This study has attempted to develop a quality control material using purified human fibrinogen and has compared measurement precision between both purified and plasma materials. Purified fibrinogen was prepared using Cohn fraction 1 and glycine precipitation. Purified fibrinogen clottability was greater than 95%, with no main plasma proteins, lipids or fibrinogen degradation products observed. Two purified control materials were lyophilized at normal (2.30 g lm1) and abnormal (1.20 g lm1) levels of fibrinogen concentration. Precision was evaluated using a liquid‐type reagent, Thrombocheck Fib(L), on automated coagulation analysers. Coefficient of variation for within‐run, intraday and between‐day precision of the purified materials was 0.7‐3.5%. In comparison, the coefficient of variation for plasma materials ranged from 1.2 to 5.3%. These results suggest that materials prepared from purified fibrinogen can be useful to laboratory quality control by improving overall precision of fibrinogen measurement and are applicable to automated coagulation analysers.
Automation of a flow injection system for the determination of dissolved silver at picomolar concentrations in seawater with inductively coupled plasma mass spectrometry
Authors: Barriada Jose L. , Truscott Jason B. , Achterberg Eric P.
Published: March 2007

An automated flow injection system for the determination of dissolved silver at ultratrace concentrations in seawater, and controlled under LabVIEW™, is described. The flow injection system allows online processing of seawater samples before their analysis using a magnetic sector inductively coupled plasma mass spectrometry (MS‐ICP‐MS) instrument. Samples were analysed with a minimum amount of manipulation, thereby reducing the risk of contamination. In addition, the flow injection approach with incorporation of an anion exchange minicolumn allowed ready removal of analytical interferences caused by the saline matrix. The software allowed full control of all flow injection components (valves and pumps) and removed manual time control and, therefore, operator errors. The optimized system was capable of five sample injections per h, including preconcentration and wash steps. The limit of detection was 0.5 pM for a 240‐s sample load time, which allowed the determination of dissolved silver in open ocean waters, where picomolar concentration levels are typically encountered.
Proposed fibrinogen standard material with purified fibrinogen for plasma fibrinogen measurement on coagulation analyser
Authors: Okuda Masahiro , Uemura Yahiro , Tatsumi Noriyuki , Honda Susumu
Published: March 2007

A commercially available fibrinogen standard calibrated by a World Health Organization (WHO) reference material is widely used in Japan, and most clinical laboratories use the Clauss method for plasma fibrinogen measurement. However, a current issue in fibrinogen measurement is poor laboratory‐to‐laboratory variability. To improve the reliability of fibrinogen values and thereby solve the poor precision and accuracy of plasma fibrinogen testing, the present paper develops a simple and large preparation procedure for a suitable fibrinogen standard and quality control material and evaluates their basic performance. With a new procedure getting high purified fibrinogen by glycine precipitation, the calibrator determined by both the Clauss and Jacobson methods produced a fibrinogen concentration of 2.20 g l−1. The total precision of the calibrator was excellent (coefficient of variation 1.4‐2.1%) in comparison with current plasma fibrinogen materials from the WHO (#98/612) and with a commercial standard (CV 1.9‐3.9%). The within‐run precision of the calibrator on the coagulation analysers was 1.7‐2.8%. Within‐analyser variability among the five instruments had good consistency (mean 2.20 ± 0.022 g l−1; CV 1.0%). The degradation study of the calibrator suggested that storage at 9°C for two years was as predicted. In conclusion, the results show that the calibrator prepared herein can be useful as a candidate Japanese fibrinogen standard and is applicable to automated and semi‐automated coagulation analysers. Additionally, it is expected that it will be widely used in Japan by diagnostic manufacturers and clinical laboratories as a recommended secondary standard to estimate a fibrinogen value according to the WHO primary standard.
Statistical method for the determination of equivalence of automated test procedures
Authors: Lung K. Rick , Gorko Mary A. , Llewelyn Jennifer , Wiggins Norman
Published: March 2007

In the development of test methods for solid dosage forms, manual test procedures for assay and content uniformity often precede the development of automated test procedures. Since the mode of extraction for automated test methods is often slightly different from that of the manual test method, additional validation of an automated test method is usually required. In addition to compliance with validation guidelines, developers of automated test methods are often asked to demonstrate equivalence between the manual and automated test methods. There are problems associated with using the traditional zero‐difference hypothesis tests (such as the Student′s t‐test) for demonstrating equivalence. The use of the Westlake Interval and Schuirmann′s Two One‐sided test as more rigorous methods of demonstrating equivalence is discussed.
Development of a heating reactor for a continuous flow‐through application in urea measurement
Authors: Randhawa S. S. , Ganju A. K. , Bajpai R. P.
Published: March 2007

In most biochemical analyses, a flow‐through heating arrangement is needed to reduce the reaction time or maintain a constant temperature. A rectangular reactor is described that is constructed of aluminium, is hollow inside and is filled with silicone oil. The glass coil through which the solution flows is immersed in the silicone oil. The heater, a Peltier‐effect heat pump, on one side and the temperature sensor on the other side of the reactor body are embedded for heating and temperature control. The brief performance evaluation of the reactor is discussed by measuring the absorbance of urea concentration at different temperatures.
An evaluation of the Kemtek 1000 sample processor
Authors: Wheeler M. J. , Waiters Linzi
Published: March 2007

The Kemtek 1000 Sample Processor has been evaluated for precision, accuracy, speed and reliability. Precision was better than 1.0% at all volumes tested and accuracy within ±5%. A l00‐tube assay could be set up within 15 min when patient specimens plus two reagents were sampled using a two probe system. Carry‐over could be reduced to <0.01% by using a sufficient number of wash steps, the latter being related to the assay requirements. Evidence was found for adsorption of protein to the probe tubing but inaccuracies due to this could be reduced by introducing wash steps between samples. Problems over 12 months have been minor and quickly resolved. The authors were pleased with the way the processor performed and their staffhave confidence in leaving it to set up their assays.
Exploring multivariate clinical chemical routine data concerning three major disease groups
Authors: Hemel Jan B. , van der Voet Hilko , Hendriks Rolf , Hindriks Frans R. , van der Slik Willem
Published: March 2007

In preparation for multivariate analysis, an exploratory study has been undertaken to investigate the relative position, separability, homogeneity and shape of three major disease groups, using data from a clinical chemical routine package.

The data set consists of 46 hepatology patients, 50 nephrology patients and 46 cardiology patients, and the measured blood levels include 20 common clinical chemical routine assays. Missing value problems were avoided by deleting some of the variables and objects.

A univariate analysis was used as the basis ofa rescaling of the data.

Bivariate (pairwise) plots of some major assays each show limited separation. The set of three such plots of the three major principal components reveals more distinction between the groups than was offered by univariate analysis. Three‐dimensional extensions of these techniques allow better insight than any of the two‐dimensional plots, but these three‐dimensional versions require more plots for complete interpretation.

Non‐linear mapping of the data is the best way of retaining the distances and a fairly good separation is achieved in the plot. The plot is less informative about shape and relative position of the classes.

Representation of the data as pictures of faces does not offer additional information and visual clustering is worse than in any of the techniques mentioned.

During the analysis many assumed properties of the data are confirmed and a good starting pointfor multivariate classification is attained. Easy visual detection of outliers is offered by all techniques. Unfortunately, valuable information is lost in this data set by deleting some incomplete variables.
A computer‐controlled potentiometric/spectrophotometric titrator
Authors: Stong John D.
Published: March 2007

A laboratory computer controlled potentiometric titrator interfaced to a diode array spectrophotometer is described. The titrator consists of widely used, commercially available components; therefore, major attention is given to modes of interconnection and software implementation in data format and system control. Replicate potentiometric titrations of glycines gave a relative standard deviation in titre of 1.035% and a relative standard deviation in pH of 0.745%. Replicate spectrophotometric titrations of bromophenol blue were analysed at three wavelengths to yield pKa= 3.898 ± 0.075 (1.9% rsd).

Methods of data presentation and manipulation are presented.
Investigation of the steady state measurement process
Authors: Nagy J. L. , Leisztner L. , Hangos K. M.
Published: March 2007

Based on the role of steady state concept in the model of analytical chemical measurement and deduction, the definition of ‘practically sleady slate’ (PSS) has been inlroduced. The defnition does not require the process to be in steady state in a strictly mathematical sense. In order to fulfil the requiremenls of ‘practically steady state’ the random error and the syslematic error must vary within a suitable limit, and the expected fgure for the measured value must be within a specified range.

The goal of the present investigation was to detect the steady state of the measurement process with respect to the analytical information (peak area ratio) based on the measured values. The method proposed proved to be useful for the determination of the simultaneously present systematic error and random error. Control based on the measured values of the internal standard is useful, but additional information is necessary. There are several advantages to the method described: the results for the internal standard indicate possible sources of disturbances and allow the end of the steady state measurement process to be predicted.
Post‐column coulometric generation and cyclic voltammetric identification of the free radical of the antineoplastic agent etoposide (VP 16‐213)
Authors: Ploegmakers H. H. J. L. , van Oort W. J.
Published: March 2007

It has been suggested that etoposide can be transformed ‘in vivo’ into a radical intermediate, which may be involved in the irreversible binding of etoposide to microsomal proteins and in DNA damage. To investigate some physico‐chemical properties, the on‐line coulometric production of this free radical and its subsequent cyclic voltammetric detection is described. For the synthesis, a coulometric ESA Coulochem 5100A module, equipped with an ESA 5010 analytical cell, has been used. For its detection the computerized cyclic voltammetric detection system after HPLC controlled by an Apple IIe computer, using home‐made software and a home‐made glassy‐carbon wall‐jet detector, has been used. Application of a ramdisk allows storage of 68 cyclic voltammograms. In a methanol‐phosphate buffer (pH=8) (40:60 w/w) containing mobile phase, the forward scan of the on‐line cyclic voltammogram of etoposide shows two oxidation steps, caused by a double one‐electron transfer. Post‐column electrolysis at +500 mV versus the H+/H2 reference electrode results into total disappearance of the first oxidation step, whereas a reduction wave arises. The limiting current of this wave, and the remaining second oxidation wave, are of equal heights, indicating one‐electron processes. Under these conditions, the half‐life time of the product, and consequently the free radical, is 100 s, determined by stopped‐flow analysis. Decreasing the pH of the buffer in the mobile phase to pH 2.2 results in merging of the two oxidation steps to a single two‐electron transfer, disabling radical formation. Under physiological conditions (‘in vivo’) the established half‐life time of the radical enables participation of the intermediate in metabolic processes.
Confidence interval approach for evaluating bias in laboratory methods
Authors: Yee K. F.
Published: March 2007

A statistically significant difference in mean values between two laboratory quantitation methods is interpreted as a bias. Sometimes such a difference is so minute that it does not constitute any practical concern. An alternative approach is to test statistically whether the two methods are close enough, not for equality. This is to look at the confidence interval of the mean method difference and does not entail any additional statistical tests.