bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Programming Based Approximation Algorithms for Sequence Alignment with Constraints
Authors: Arslan Abdullah N. , Eğecioğlu Ömer
Published: October 2004

Given two sequences X and Y, the classical dynamic programming solution to the local alignment problem searches for two subsequences I ⊆ X and J ⊆ Y with maximum similarity score under a given scoring scheme. In several applications, variants of this problem arise with different objectives and with length constraints on the subsequences I and J. This constraint can be explicit, such as requiring | I | + | J | ≥ t, or | J | ≤ T, or may be implicit such as in cyclic sequence comparison, or as in the maximization of length-normalized scores, and driven by practical considerations. We present a survey of approximation algorithms for various alignment problems with constraints, and several new approximation algorithms. These approximations are in two distinct senses: In one the constraints are satisfied but the score computed is within a prescribed tolerance of the optimum instead of the exact optimum. In another, the alignment returned is assured to have at least the optimum score with respect to the given constraints, but the length constraints are satisfied to within a prescribed tolerance from the required values. The algorithms proposed involve applications of techniques from fractional programming and dynamic programming.
The Fine Structure of Galls in Phylogenetic Networks
Authors: Gusfield Dan , Eddhu Satish , Langley Charles
Published: October 2004

A phylogenetic network is a generalization of a phylogenetic tree, allowing properties that are not tree-like. With the growth of genomic data, much of which does not fit ideal tree models, there is greater need to understand the algorithmics and combinatorics of phylogenetic networks (Posada and Crandall 2001, Schierup and Hein 2000).

Wang et al. (2001) studied the problem of constructing a phylogenetic network for a set of n binary sequences derived from the all-zero ancestral sequence, when each site in the sequence can mutate from zero to one at most once in the network, and recombination between sequences is allowed. They showed that the problem of minimizing the number of recombinations in such networks is NP-hard, but introduced a special case of the problem, i.e., to determine whether the sequences could be derived on a phylogenetic network where the recombination cycles are node-disjoint. Wang et al. (2001) provide a sufficient, but not a necessary test, for such solutions. Gusfield et al. (2003, 2004) gave a polynomial-time algorithm that is both a necessary and sufficient test. In this paper, we study in much more detail the fine combinatorial structure of node-disjoint cycles in phylogenetic networks, both for purposes of insight into phylogenetic networks and to speed up parts of the previous algorithm. We explicitly characterize all the ways in which mutations can be arranged on a disjoint cycle, and prove a strong necessary condition for a set of mutations to be on a disjoint cycle.

The main contribution here is to show how structure in the phylogenetic network is reflected in the structure of an efficiently-computable graph, called the conflict graph. The success of this approach suggests that additional insight into the structure of phylogenetic networks can be obtained by exploring structural properties of the conflict graph.
DSS Effectiveness in Marketing Resource Allocation Decisions: Reality vs. Perception
Authors: Lilien Gary L. , Rangaswamy Arvind , Van Bruggen Gerrit H. , Starke Katrin
Published: October 2004

We study the process by which model-based decision support systems (DSSs) influence managerial decision making in the context of marketing budgeting and resource allocation. We focus on identifying whether and how DSSs influence the decision process (e.g., cognitive effort deployed, discussion quality, and decision alternatives considered) and, as a result, how these DSSs influence decision outcomes (e.g., profit and satisfaction both with the decision process and the outcome). We study two specific marketing resource allocation decisions in a laboratory context: sales effort allocation and customer targeting. We find that decision makers who use high-quality, model-based DSSs make objectively better decisions than do decision makers who only have access to a generic decision tool (Microsoft Excel). However, their subjective evaluations (perceptions) of both their decisions and the processes that lead to those decisions do not necessarily improve as a result of DSS use. And expert judges, serving as surrogates for top management, have a difficult time assessing the objective quality of those decisions.

Our results suggest that what managers get from a high-quality DSS may be substantially better than what they see. To increase the inclination for managerial adoption and use of DSS, we must get users to “see” the benefits of using a DSS. Our results also suggest two ways to bridge the perception-reality gap: (1) improve the perceived value of the decision process by designing DSSs both to encourage discussion (e.g., by providing explanation and support for alternative recommendations) as well as to reduce the perceived complexity of the problem so that managers invest more cognitive effort in exploring additional options and (2) provide feedback on the likely market/business outcomes of various decision options.
Toward Contextualized Theories of Trust: The Role of Trust in Global Virtual Teams
Authors: Jarvenpaa Sirkka L. , Shaw Thomas R. , Staples D. Sandy
Published: October 2004

Although trust has received much attention in many streams of information systems research, there has been little theorizing to explain how trust evokes sentiments and affects task performance in IT-enabled relationships. Many studies unquestionably assume that trust is intrinsically beneficial, and dismiss the possibility that the effects of trust may be dependent on the situation (or conditions) at present. This paper theoretically and empirically examines outcomes of an individual's trust in global virtual teams under differing situations (or conditions). In Study 1, we find that early in a team's existence, a member's trusting beliefs have a direct positive effect on his or her trust in the team and perceptions of team cohesiveness. Later on, however, a member's trust in his team operates as a moderator, indirectly affecting the relationships between team communication and perceptual outcomes. Study 2 similarly suggests that trust effects are sensitive to the particular situation or condition. Combined, the studies find that trust affects virtual teams differently in different situations. Future studies on trust will need to consider situational contingencies. This paper contributes to the literature on IT-enabled relationships by theorizing and empirically testing how trust affects attitudes and behaviors.
Managing Digital Piracy: Pricing and Protection
Authors: Sundararajan Arun
Published: October 2004

This paper analyzes the optimal choice of pricing schedules and technological deterrence levels in a market with digital piracy where sellers can influence the degree of piracy by implementing digital rights management (DRM) systems. It is shown that a monopolist's optimal pricing schedule can be characterized as a simple combination of the zero-piracy pricing schedule and a piracy-indifferent pricing schedule that makes all customers indifferent between legal usage and piracy. An increase in the quality of pirated goods, while lowering prices and profits, increases total surplus by expanding both the fraction of legal users and the volume of legal usage. In the absence of price discrimination, a seller's optimal level of technology-based protection against piracy is shown to be at the technologically maximal level, which maximizes the difference between the quality of the legal and pirated goods. However, when a seller can price discriminate, its optimal choice is always a strictly lower level of technology-based protection. These results are based on the following digital rights conjecture: that granting digital rights increases the incidence of digital piracy, and that managing digital rights therefore involves restricting the rights of usage that contribute to customer value. Moreover, if a digital rights management system weakens over time due to the underlying technology being progressively hacked, a seller's optimal strategic response may involve either increasing or decreasing its level of technology-based protection. This direction of change is related to whether the DRM technology implementing each marginal reduction in piracy is increasingly less or more vulnerable to hacking. Pricing and technology choice guidelines are presented, and some welfare implications are discussed.
Book Reviews
Authors: Stecopoulos Harilaos , Pfahlert Jeanine , Balasopoulos Antonis , Bennett G.H. , Briand R.J. , Burn Stephen J. , Patterson Anita
Published: October 2004

The Writing of America: Literature and Cultural Identity from the Puritans to the Present, Geoff Ward (2002) Oxford: Polity, 248 pp., ISBN 074562622X (pbk), £14.99.

Sister of the Road: The Autobiography of Boxcar Bertha, Dr Ben Reitman (2002) Edinburgh:
AK Press/Nabat, 205 pp., ISBN 1902593030 (pbk), £9.99 (original work published 1937).

Culture Agonistes: Debating Culture, Rereading Texts, Theodora Tsimpouki and Angeliki Spiropoulou (eds.) (2002) Bern; Berlin; Bruxelles; Frankfurt-am-Main; New York; Oxford; Wien: Peter
Lang, 230 pp., ISBN 3-906768-24-4, £27.

Discussing Hitler: Advisers of US Diplomacy in Central Europe 1934–1941, Tibor Frank (2003) Budapest and New York: Central European University Press, 360 pp., ISBN 9639241563 (hbk), £38.

John F. Kennedy: An
Unfinished Life, Robert Dallek (2003) London: Allen Lane/Penguin, 838 pp., ISBN 0-7139-9737-0 (hbk), £25.

UnderWords: Perspectives on Don DeLillo’s Underworld, Joseph Dewey, Steven G. Kellman and Irving Malin (eds.), (2002) Newark: University of Delaware
Press, 219 pp., ISBN 0874137853 (hbk), $39.50.

American Literature Before 1880, Robert Lawson-Peebles (2003) London: Longman, 352 pp., ISBN 0582495229 (pbk), £19.99.
Large Differences in Laboratory Utilisation between Hospitals in Sweden
Authors: Larsson Anders , Palmer Mats , Hultén Göran , Tryding Nils
Published: October 2004

There are large differences in the use of laboratory tests between hospitals in Sweden. These differences are not only due to differences between the patients treated but also to differences in practice. Use of laboratory test seems to reflect local traditions to a large extent. These large variations in practice are not compatible with the objective of providing care on equal terms and reduce the cost-effectiveness of clinical chemistry.

Recently, several intervention studies have been performed in Sweden with the aim to optimise the use of clinical chemistry tests in primary care. The results show that it is possible to reduce the cost in primary care by SEK 100 million per year while increasing the clinical usefulness. This constitutes approximately 10% of the total cost for clinical chemistry tests in primary care. It should also be possible to reduce the cost for clinical chemistry tests in secondary and tertiary care. Hospitals order more tests than primary care and the potential savings are thus greater.

We have studied the ordering habits for eleven Swedish hospitals. The comparison was made in the form of ratios between related laboratory tests to reduce the effects of differences in size between the studied laboratories. The large variation between hospitals indicates that a continuous discussion between the clinicians and the laboratories could reduce the cost. We have used the figures from the comparison and calculated the potential savings for seven frequently used tests. The potential yearly saving in Sweden for these tests is approximately SEK 150 million.
Development of a Method for Rapid Quantitation of Amino Acids by Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) in Plasma
Authors: Casetta Bruno , Tagliacozzi Debora , Shushan Bori , Federici Giorgio
Published: October 2004

A new analytical method has been developed and is proposed for the rapid determination of eighteen common amino acids, including tryptophan, in plasma and dried blood spots, by liquid chromatography coupled with ionspray tandem mass spectrometry. Potentially the method can include other amino acids and can be used for the diagnosis of metabolic disease. The use of the ionspray tandem mass spectrometry approach permits extremely rapid chromatographic separation of all amino acids requiring less than four minutes for the analysis of each sample, after a simple sample preparation procedure. The chromatographic separation of the analytes was achieved using a CN normal phase column and a water/acetonitrile/trifluoroacetic acid mobile phase at flow rate of 1 ml/min. The mass spectrometer was operated in multiple reaction monitoring mode, where each analyte had its own unique precursor and product ion setting. The quantitative analysis of amino acids was achieved using as internal standards just two representative isotopically labeled amino acids: D4-Ala and D5-Phe. Calibration is made externally by using aqueous solutions with the same labelled amino acids as internal standards. The high specificity of tandem mass spectrometry coupled with a fast chromatographic process is suitable for the rapid and reliable assay of metabolically significant amino acids. The liquid chromatography-tandem mass spectrometry method is more effective than other published tandem mass spectrometry methods at distinguishing isobaric amino acids like Leu, Ile and HO-Pro and certainly far more rapid than HPLC or ion-exchange chromatographic methods.
Adhesion Molecule Behavior during Rejection and Infection Episodes after Heart Transplantation
Authors: Weigel Günter , Grimm Michael , Griesmacher Andrea , Seebacher Gernot , Sichrovsky Tina , Wolner Ernst , Laufer Günter , Müller Mathias M.
Published: October 2004

In cardiac transplant recipients the release of soluble cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin into serum is pronounced during immune activation. It is uncertain whether there is a specific pattern of release during infection or cardiac allograft rejection. In a prospective study, 30 consecutive cardiac allograft recipients were followed for a median period of 11.4 months (range 1–34). Soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1) and soluble E-Selectin (sE-Selectin) were measured in addition to acute phase proteins (C-reactive protein, α1-antitrypsin), complement factors (C3, C4) and β2-microglobulin. The measured serum levels were correlated with the clinical status of the transplant recipient: 1) uneventful clinical status; 2) asymptomatic infection; 3) symptomatic infection and 4) rejection. Forty age-matched healthy subjects served as controls. Six days before biopsy-proven cardiac allograft rejection sICAM-1-release started to increase (p < 0.05) as compared to uneventful clinical status. The peak concentration of sICAM-1 was measured three days before rejection. On the day of rejection, serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were increased, whereas sE-Selectin was not markedly elevated. In symptomatic infections, the serum concentrations of sICAM-1 (p < 0.001) and sVCAM-1 (p < 0.05) were elevated at the day of diagnosis and both parameters reached peak levels three days after onset of chemotherapy. In multivariate analysis soluble adhesion molecules only weakly discriminated between rejection and infection (sensitivity: 13%, specificity: 95%). Although, in combination with routine blood parameters the discriminatory power could be improved (sensitivity: 85%, specificity: 85%) the clinical utility of these markers in non-invasive monitoring is limited.
Concentration of Lp(a) and other Apolipoproteins in Predialysis, Hemodialysis, Chronic Ambulatory Peritoneal Dialysis and Post-Transplant Patients
Authors: Kimak Elzbieta , Solski Janusz , Janicka Lucyna , Ksaziek Andrzej , Janicki Krzysztof
Published: October 2004

Serum levels of lipids, lipoprotein(a) Lp(a) and other apolipoproteins were determined in 47 predialysis patients, 40 hemodialysis (HD) patients, 39 chronic ambulatory peritoneal dialysis (CAPD) patients, 11 patients after kidney transplantation and 47 healthy subjects as reference group.

The predialysis, HD, and CAPD patients had disturbances in the concentration of serum triglyceride (TG), high density lipoprotein (HDL)-cholesterol, apolipoprotein AI (apoAI), total apoCIII, apoCIII present in the particles without apoB (apoCIII non B), and Lp(a) and HDL-cholesterol, low density lipoprotein (LDL)-cholesterol/HDL-cholesterol, HDL-cholesterol/apoAI, apoAI/apoB, and apoAI/apoCIII ratios. Predialysis patients had significantly lower concentrations of HDL-cholesterol and total apoE levels than CAPD patients and total apoE level than HD patients.

Moreover, both HD and CAPD patients had significantly increased levels of apoB containing apoE (apoB:E) and apoB containing apoCIII (apoB:CIII). The concentrations of serum TG, total cholesterol, LDL-cholesterol, apoB, Lp(a) in CAPD patients were statistically higher than in HD patients. The patients after transplantation demonstrated normalization of lipid and lipoprotein parameters and lipoprotein ratios except serum levels of TG, total apoCIII, apoCIII non B and the apoAI/apoCIII ratio.

We concluded that abnormal lipid and lipoprotein concentrations in patients with uremia may be the cause of their high risk of atherosclerosis, but post-transplant patients exhibited improved levels of serum lipids, Lp(a) and other lipoprotein parameters and lipoprotein composition, which could be an index of decreased atherogenic status.
Assessment of Iron Status with a New Fully Automated Assay for Transferrin Receptor in Human Serum
Authors: Vernet Michèle , Doyen Christine
Published: October 2004

Serum transferrin receptor is considered as a reliable marker of iron status particularly when iron deficiency is associated with chronic disorders such as inflammation, infection or malignancy. The present study aims to illustrate the performances of a new fully automated assay using immunonephelometry. The intra—and between-assay precision was found to be very good (CVs < 4%). In healthy subjects there was no statistically significant difference between men and women. With a cut-off of 1.76 mg/l for diagnosing iron deficiency either alone or combined with anemia of chronic diseases, the sensitivity and specificity were respectively 82% and 96.8%. Unlike conventional biochemical and hematological tests, soluble transferrin receptor was unaffected by confounding pathologies. In genetic hemochromatosis the concentration of soluble transferrin receptor was mostly decreased due to the regulatory effect of iron intracellular level. Our study confirms the reliability of soluble transferrin receptor for the assessment of iron status. It is now possible to assay soluble transferrin receptor, ferritin and transferrin on the same apparatus within 15 minutes.
Alterations in Laboratory Test Results during Adjuvant Breast Cancer Treatment
Authors: Kailajärvi Marita , Ahokoski Outi , Virtanen Arja , Salminen Eeva , Irjala Kerttu
Published: October 2004

An increasing number of women is treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy for breast cancer. The effects of the chemotherapy on many laboratory tests are, however, inadequately known. This study investigates the effects of the treatment on various laboratory tests. Fifteen premenopausal women receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy and optional radiotherapy were included in the study. Common hormonal, biochemical, hematological, protein and lipid laboratory tests were taken serially during a 10-month follow-up. Twelve women became amenorrheic. Their serum follicle stimulating hormone and luteinising hormone concentrations increased accordingly. Other serum hormones (testosterone, androstenedione, sex hormone-binding globulin, prolactin, dehydroepiandrosterone sulfate, cortisol, parathyroid hormone and thyroid hormones) changed only slightly. Hemoglobin concentration and white blood cell count decreased slightly. Serum alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, angiotensin-converting enzyme, amylase, glucose, potassium, phosphate, urea and triglycerides concentrations increased slightly whereas serum bilirubin, haptoglobin, and immunoglobulin A and M decreased slightly. Serum α1-antitrypsin fluctuated around the baseline concentration. Other test results remained at their pretreatment concentrations. With the exception of increases in serum gonadotrophins, the changes observed were slight and the mean concentrations remained within reference limits. Therefore, cyclophosphamide, methotrexate and 5-fluorouracil adjuvant treatment is unlikely to complicate the diagnosis of other diseases.
Comparison of Laboratory Parameters as Risk Factors for the Presence and the Extent of Coronary or Carotid Atherosclerosis: the Significance of Apolipoprotein B to Apolipoprotein AII Ratio
Authors: Cerne Darko , Ledinski Gerhard , Kager Gerd , Greilberger Joachim , Wang Xiasong , Jürgens Günther
Published: October 2004

We compared several “new” risk factors (autoantibodies to oxidatively modified low density lipoprotein (LDL), sialic acid content of LDL, bilirubin and C-reactive protein) with “conventional” risk factors (apolipoprotein (apo) AI, AII and B, lipoprotein(a), triglycerides, and total, LDL and high density lipoprotein (HDL) cholesterol) for the presence and the extent of coronary or carotid atherosclerosis. Forty male patients with angiographically proven coronary atherosclerosis and 31 male patients with ultrasound-proven extracranial carotid atherosclerosis were compared to 40 age matched (53 ± 5 years) healthy males as control subjects, with negative parental history of atherosclerosis, no clinical signs of systemic or organ-related ischemic disease and normal extracranial carotid arteries. The apo B/apo AII ratio most powerfully indicated the presence and the extent of coronary or carotid atherosclerosis. Elevated lipoprotein(a) contributed significant additional information in the assessment of the atherosclerotic risk. Increase in Creactive protein indicated the presence (but not the extent) of coronary or carotid atherosclerosis with a similar power as lipoprotein(a). Decreased values of total bilirubin indicated the presence of atherosclerosis only in smokers. Autoantibodies to oxidatively modified LDL additionally described the atherosclerotic process, but were less important than apolipoproteins, lipoprotein(a), C-reactive protein or bilirubin. Sialic acid content of LDL added no information to the parameters discussed above. We demonstrated that in male patients apolipoproteins, especially the apo B/apo AII ratio, were better indicators of the presence and the extent of coronary or carotid atherosclerosis than C-reactive protein, bilirubin, autoantibodies to oxidatively modified LDL or sialic acid content of LDL.
Concordance of Eight Kits for Antithyroid Peroxidase Autoantibodies Determination
Authors: d'Herbomez Michèle , Sapin Rémy , Gasser Françoise , Schlienger Jean Louis , Wémeau Jean Louis
Published: October 2004

Numerous methods are proposed to quantify antithyroid peroxidase autoantibodies. No standardization exists but most assays use the standard MRC 66/387 with a calibration factor. Costs of the tests vary between the different kits. We evaluated the concordance of eight peroxidase autoantibodies assay kits in two centres, using a panel of sera from 269 subjects: controls (n=100), patients with autoimmune thyroid disease (n=77; Graves' disease, Hashimoto's thyroiditis), patients with non-autoimmune thyroid disease (n=69; nodular goiter, differentiated thyroid carcinoma) and individual sera with thyroglobulin antibodies only (n=23). The concordance between the eight methods was high, ranging from 88.3% to 98.8% with the total panel of sera. The majority of assays demonstrated high diagnostic performance. We encountered some false-positive results at borderline positive levels, and the nonrecognition of some sera by competitive assays.
Evaluation of a Point-of-Care System for Quantitative Determination of Troponin T and Myoglobin
Authors: Müller-Bardorff Margit , Sylvén Christer , Rasmanis Gundars , Jørgensen Bo , Collinson Paul O. , Waldenhofer Ulla , Hirschl Michael M. , Laggner Anton N. , Gerhardt Willie , Hafner Gerd , Labaere Irene , Leinberger Robert , Zerback Rainer , Katus Hugo A.
Published: October 2004

We present the results of a multicenter evaluation of a new point-of-care system (Cardiac Reader) for the quantitative determination of cardiac troponin T (CARDIAC T Quantitative test) and myoglobin (CARDIAC M test) in whole blood samples.

The Cardiac Reader is a CCD camera that optically reads the immunochemical test strips. The measuring range is 0.1 to 3 μg/l for CARDIAC T Quantitative and 30 to 700 μg/l for CARDIAC M. Both tests are calibrated by the manufacturer. The reaction times of the tests are 12 or 8 minutes, respectively.

Method comparisons were performed with 281 heparinized blood samples from patients with suspected acute coronary syndromes. The results obtained with CARDIAC T Quantitative showed a good agreement compared with cardiac troponin T ELISA (r = 0.89; y = 0.93x + 0.02). The method comparison between CARDIAC M and Tina-quant Myoglobin also showed a good agreement between both assays (r = 0.98; y = 0.92x + 1.6). Test lot-to-lot comparisons yielded differences of 2% and 6% for CARDIACT Quantitative and of 0 to 11% for CARDIACM.

The within-run imprecision with blood samples and control materials was acceptable for CARDIAC T Quantitative (CV 10 to 15%) and good for CARDIAC M (CV 5 to 10%). The between-instrument CV was below 7% for CARDIACT Quantitative and below 5% for CARDIACM. The cross-reactivity of CARDIAC T Quantitative with skeletal troponin T was approximately 0.003%. No significant analytical interference was detected for any of the assays in investigations with biotin (up to 100 μg/l), hemoglobin (up to 0.125 mmol/l), hematocrit (26 to 52%), bilirubin (up to 340 μmol/l), triglycerides (up to 5.0 mmol/l), and 18 standard drugs.

With the Cardiac Reader reliable quantitative results can be easily obtained for both cardiac markers. The system is, therefore, particularly suitable for use in emergency rooms, coronary care units and small hospitals.
The Science of Systematic Reviewing Studies of Diagnostic Tests
Authors: Oosterhuis Wytze P. , Niessen René W.L.M , M.Bossuyt Patrick M.
Published: October 2004

Background: Systematic reviews have gradually replaced single studies as the highest level of documented effectiveness of health care interventions. Systematic reviewing is a new scientific method, concerned with the development and application of methods for identifying relevant literature, analysing the material while increasing validity and precision, and presenting and discussing the results in a way that does justice to the research question and to the available evidence. The objective of this study was to review the systematic reviews in laboratory medicine, to evaluate the methods applied in these reviews and the applicability of guidelines of the Cochrane Methods Working Group on Screening and Diagnostic Tests, and identify areas for future research.

Methods: All the systematic reviews in the field of clinical chemistry and laboratory haematology that could be identified in Medline, EMBASE and other literature databases up to December 1998, were evaluated.

Results: We studied 23 reviews of diagnostic trials. Although all reviews share the same basic methodology, there was a wide variation in the methods applied. There was no consensus on the quality criteria for inclusion of primary studies. The results of the primary studies were heterogeneous in most cases. This was partly due to design flaws in the primary studies, but was also inherent in the diverse study designs in diagnostic trials. We observed differences in the analysis of the factors that cause heterogeneity of the results, and in the summary statistics used to pool the data from the primary studies. The additional diagnostic value of a test, after other test results are taken into consideration, was only addressed in one study.

Conclusion: This overview of 23 reviews of diagnostic trials identifies areas in the methods of systematic reviewing where consensus is lacking, such as quality rating of primary studies, analysis of heterogeneity between primary studies and pooling of data. Guidelines need to be improved on these points.
Preeclampsia Is Associated with Alterations in Insulin-Like Growth Factor (IGF)-1 and IGF-Binding Proteins in Wharton's Jelly of the Umbilical Cord
Authors: Bankowski Edward , Palka Jerzy , Jaworski Stefan
Published: October 2004

Wharton's jelly is abundant in extracellular matrix, which is known as a storage site to concentrate and stabilise growth factors in the vicinity of cells. It was previously found that Wharton's jelly contains significant amounts of insulin-like growth factor (IGF)-1 and IGF-binding proteins (BPs). IGF-1 is a stimulator of biosynthetics of collagen and sulphated glycosaminoglycans. Preeclampsia (edema, proteinuria, hypertension (EPH)-gestosis) is accompanied by an accumulation of sulphated glycosaminoglycans in Whart on's jelly. IGF-1 and BPs may play an important role in such a remodelling of this tissue. It was decided to evaluate the alterations in amounts of IGF-1 and BPs in Wharton's jelly of newborns delivered by mothers with preeclampsia. Studies were performed on Wharton's jelly of 10 controls and 10 newborns delivered by mothers with preeclampsia (edema, proteinuria > 500 mg/l, arterial pressure: systolic > 140 mm Hg, diastolic >90 mmHg). Radioimmunological techniques were employed to determine IGF-1 and IGF-BPs (BP-1 and BP-3). It was found that preeclampsia is associated with a decrease in IGF-1-and IGF-BP-1 in Wharton's jelly. A slight increase in IGF-BP-3 was found. Ligand blotting demonstrated that BP-3 (not BP-1) is a main component of Wharton's jelly, which binds IGF-1. Heparin drastically inhibited the binding of IGF-1 by BP-3. It is known from our previous studies that preeclampsia is associated with an increase in the amount of sulphated glycosaminoglycans (heparin, heparan sulphate, dermatan sulphate) in Wharton's jelly. This may be a factor, which prevents the binding of IGF-1 by BPs and facilitates the binding of IGF-1 to cells, stimulating them to produce sulphated glycosaminoglycans in Wharton's jelly.
Evaluation of Emit® Tox Benzodiazepine and Barbiturate Assays on the Vitalab Viva Analyser and FPIA on the Abbott ADx Analyser
Authors: Charlier Corinne J. , Plomteux Guy J.
Published: October 2004

We evaluated the performance of the Emit® tox benzodiazepine and barbiturate assays (Dade Behring) and fluorescence polarisation immunoassay (FPIA) (Abbott) for use with serum determinations in preliminary therapeutic drug monitoring or acute drug intoxication detection.

Performance, as indicated by CVs, of the Emit® tox benzodiazepine and barbiturate assays and FPIA showed that both immunochemical techniques are precise and have good reproducibility.

For within-run studies, results from benzodiazepine determinations showed maximum CV values of 1.91% for the Emit® method and 2.65% for FPIA; results from barbiturate determinations showed maximum CV values of 2.01% for the Emit® method and 1.89% for FPIA.

For between-run studies, results from benzodiazepine determinations showed maximum CV values of 1.79% for the Emit® method and 1.12% for FPIA; results from barbiturate determinations showed maximum CV values of 2.09% for the Emit® method and 2.02% for FPIA.
Serum Eosinophil Cationic Protein in Active and Quiescent Ulcerative Colitis
Authors: Pronk-Admiraal Claudia J. , Linskens Ronald K. , Bodegraven Ad A. Van , Tuynman Hans A.R.E. , Bartels Piet C.M.
Published: October 2004

Inflammatory bowel disorders are characterized by an accumulation of eosinophilic granulocytes, mast cells, lymphocytes and neutrophilic granulocytes in the intestinal mucosa. The aim of this study was to examine the concentration of eosinophilic granulocytes in the blood of patients during active ulcerative colitis in comparison with patients during remission and apparently healthy control subjects. Besides counting, the activity grade of eosinophilic granulocytes has been studied by estimation of their degranulation product eosinophil cationic protein.

Subjects with active ulcerative colitis could be distinguished from patients with quiescent ulcerative colitis by establishment of the eosinophil cationic protein concentration, neutrophilic granulocyte count, erythrocyte sedimentation rate, C-reactive protein and albumin concentration.

After two weeks of corticosteroid treatment, serum eosinophil cationic protein concentrations and eosinophil counts in blood were significantly decreased. A decrease in blood eosinophil count was accompanied by a decrease in eosinophil cationic protein concentrations in serum in most subjects with ulcerative colitis. After twelve weeks of corticosteroid administration, serum albumin concentrations were significantly increased, whereas serum concentrations of C-reactive protein were significantly decreased.

During treatment with corticosteroids, serum eosinophil cationic protein concentrations and blood eosinophil counts are appropriate laboratory markers to detect the effect of medication in the course of ulcerative colitis.
Separation of Erythrocytes into Age-Related Fractions by Density or Size? Counterflow Centrifugation
Authors: Lasch Jürgen , Küllertz Gerhard , Opalka Jens Rüdiger
Published: October 2004

During the process of aging red blood cells become denser and smaller. Counterflow centrifugation separates particles of lower density and smaller diameter from those of higher density and bigger diameter. Thus, the question arises: which property of the red cells, density or size, governs the age-related separation by counterflow centrifugation? It is shown that it is the size which dominates the balance between sedimentation and streaming.

Age-related separation of human red blood cells by counterflow centrifugation (elutriation) was analysed by the standard hematological parameters (hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration), hemoglobin A1c and the membrane protein ratio 4.1a/(4.1a+4.1b). Red blood cells with a high hemoglobin A1c content and a high 4.1a/(4.1a+4.1b) ratio were found in the early fractions of the elutriation. This proves that old cells make up early fractions, while the “youngsters” constitute later ones.

The elutriation technique used (yielding human red blood cells in a “healthy state”) and the age parameters studied show that the membrane protein ratio 4.1a/(4.1a+4.1b) is another reliable age parameter for the assessment of red blood cell age.
Laboratory Support of the Clinical Nutrition Service
Authors: Gidden Fiona , Shenkin Alan
Published: October 2004

This article critically reviews the role of the laboratory services in assessment, monitoring and management of complications in patients requiring nutritional support. It has broadly been divided into three sections.

(i)

Assessment of protein and energy status: whilst it is stressed that clinical judgement and anthropometric measurements are the most effective methods of evaluation of nutritional requirements, laboratory tests which can be of use in assessment of protein energy status are discussed in detail, including an appraisal of the value of each test in various clinical situations.

(ii)

Assessment of micronutrient and electrolyte status: the clinical justification for assessment of the various micronutrients and electrolytes is considered. A few selected examples are discussed in detail including an evaluation of the tests of status available and examples of situations where measurement may be clinically helpful.

(iii)

Effective use of the laboratory: this section attempts to guide the clinician in the most appropriate use of laboratory tests, firstly in the assessment of requirement for aspects of nutritional support, secondly in the continued monitoring and evaluation of the support provided, and thirdly in prevention and treatment of metabolic complications.

It is emphasised that clinical nutrition is a multidisciplinary topic requiring input from the laboratory in conjunction with other specialities to provide the best available patient care.
A new Method for Fast Haptoglobin Phenotyping and Hemoglobin Binding Capacity Calculation Based on Capillary Zone Electrophoresis
Authors: Wuyts Birgitte , Delanghe Joris R. , Kasvosve Ishmael , Langlois Michel R. , Buyzere Marc L. De , Janssens Jacques
Published: October 2004

A capillary zone electrophoresis method was developed for haptoglobin (Hp) phenotyping in hemoglobin (Hb) supplemented serum. The method allows a complete resolution of the major haptoglobin phenotypes Hp 1-1, Hp 2-1, and Hp 2-2 based on the difference in charge-to-mass ratio of their Hb-Hp complexes. Identification of these phenotypes was achieved by their significant differences in migration times and their marked difference in electrophoretic pattern. Our method showed full agreement with starch gel electrophoresis. Furthermore, following neuraminidase treatment of the serum, the Hp subtypes Hp1-1FF, FS and SS could be resolved, based on the same criteria as the phenotyping. The new electrophoretic method allowed typing of the rare phenotypes Hp 2-1 modified (Hp 2-1M) and Hp Johnson. The calculated hemoglobin binding capacity of serum correlates well with the nephelometrically determined haptoglobin concentration. The new method for typing haptoglobin gives prospectives for fast haptoglobin typing and Hp 1-1 subtyping.
Apolipoprotein E Polymorphism and Serum Concentration in Alzheimer's Disease in Nine European Centres: the ApoEurope Study
Authors: Siest Gerard , Bertrand Philippe , Qin Bin , Herbeth Bernard , Serot Jean-Marie , Masana Luis , Ribalta Josep , Passmore A. Peter , Evans Alun , Ferrari Maurizio , Franceschi Massimo , Shepherd James , Cuchel Marina , Beisiegel Ulrike , Zuchowsky Katrin , Rukavina Ana Stavljenic , Sertic Jadranka , Stojanov Marina , Kostic Vladimir , Mitrevski Angel , Petrova Vera , Sass Catherine , Merched Aksam , Salonen Jukka T. , Tiret Laurence , Visvikis Sophie , group the ApoEurope
Published: October 2004

As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the ε4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p<0.001). In addition, serum total cholesterol and triglyceride concentrations were lower in Alzheimer's disease (p<0.001), while that of apo AI was not affected. The decrease in serum apo E concentration was not accounted for by the ε4 allele, age or gender, suggesting that apo E concentration might represent an additional risk factor for Alzheimer's disease, complementary and independent of the ε4 allele. Further analysis will be aimed at determining whether the quantitative link between apo E concentration and Alzheimer's disease occurs through the effect of apo E genotype on lipid parameters or by other mechanisms.
Association of the Apolipoprotein B Gene Polymorphisms with Cholesterol Levels and Response to Fluvastatin in Brazilian Individuals with High Risk for Coronary Heart Disease
Authors: Guzmán Elizabeth C.R. , Hirata Mario H. , Quintão Éder C.R. , Hirata Rosario D.C.
Published: October 2004

The influence of genetic polymorphism of the apolipoprotein B on lipid metabolism and coronary heart disease (CHD) risk has been demonstrated in different populations, but few studies have shown the contribution of this risk factor in individuals from Brazil. The Ins/del, XbaI and EcoRI polymorphisms of apo B were evaluated in 93 controls and in 104 Caucasian individuals presenting with a high risk lipid profile (HR1) for CHD; 54 of these subjects (HR2) were treated with fluvastatin during 16 weeks. DNA polymorphisms of the apo B gene were analyzed by polymerase chain reaction–restriction fragment length polymorphism. The X(−)X(−) genotype for XbaI polymorphism was associated with higher serum concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (p<0.01) in women of the HR1 group. The Ins/del and EcoRI polymorphisms were not associated with variation of lipid profile. After treatment with fluvastatin, TC and LDL-C levels of HR2 individuals were reduced by 23% and 30%, respectively. Individuals with II genotype had significantly greater reduction (34%) of LDL-C than those with ID/DD genotypes (27%). These results indicate that the XbaI polymorphism is associated with variation of serum TC and LDL-C levels in Brazilian women with lipid profile of risk for CHD and the Ins/del polymorphism is associated with the therapeutic response to fluvastatin.
Automated Enzymatic Mitochondrial Antibody Assay for the Diagnosis of Primary Biliary Cirrhosis
Authors: Jensen Wayne A. , Jois Jennifer A. , Murphy Peter , Giorgio Joseph De , Brown Belinda , Rowley Merrill J. , Mackay Ian R.
Published: October 2004

Primary biliary cirrhosis is a progressive autoimmune disease that affects middle aged women, resulting in liver cirrhosis. We describe here an automated enzymatic mitochondrial antibody assay adapted for performance on laboratory analysers for the serological diagnosis of primary biliary cirrhosis. This assay detects the characteristic autoantibody directed against the 74kDa E2 subunit of the pyruvate dehydrogenase complex.

Analysis of receiver operator characteristic curve data indicated that the automated enzymatic mitochondrial assay procedure discriminated clinically identified patients with primary biliary cirrhosis from normal subjects with a sensitivity of 83% and a specificity of 100%. This method compared favourably against a commercial ELISA method which had a sensitivity of 73% and a specificity of 100%. The automated enzymatic mitochondrial antibody assay is a high throughput assay of use for the routine diagnosis of patients with primary biliary cirrhosis with autoantibodies to the E2 subunit of the pyruvate dehydrogenase complex. The method is of potential value for economical and rapid screening to detect asymptomatic primary biliary cirrhosis in the at-risk segment of the population, namely middle aged women.
Study of IgM Aggregation in Serum of Patients with Macroglobulinemia
Authors: Sharma Loretta , Baker Jon , Brooks Annabelle M. , Sharma Ajit
Published: October 2004

The effect of solvent conditions on the aggregation of IgM in serum specimens from patients with macroglobulinemia was studied by a turbidimetric procedure. Aggregation of IgM varied considerably among the samples and was affected by a number of experimental parameters. In general, IgM aggregation was more pronounced under acidic conditions and in solvents with low ionic strength. The presence of watermiscible organic solvents also promoted aggregation. Based on these studies, it was concluded that the major force involved in the formation of immunoglobulin aggregates in the serum of patients with macroglobulinemia was electrostatic, rather than hydrophobic, interactions. A number of additives known to prevent protein aggregation were evaluated for their effectiveness in inhibiting IgM aggregation. The only additives that were shown to inhibit or reduce IgM aggregation were charged molecules, such as arginine, sodium chloride, ethylenediamintetraacetic acid and quaternary ammonium β-cyclodextrin. Some of these charged additives were also effective in dissociating the IgM aggregates once they were formed, even in the presence of detergent.
Comparison of Two Different Methods for Measurement of Phenylalanine in Dried Blood Spots
Authors: Rivero Adriana , Allué Juan Antonio , Grijalba Ana , Palacios Mercedes , Merlo Sergio García
Published: October 2004

Phenylketonuria is an inherited metabolic disorder caused by a defect in the hydroxylation of phenylalanine. Newborn screening is crucial for the diagnosis and treatment of this disease. A phenylalanine dehydrogenase-coupled enzymatic assay (Quantase) in microtiter plates for the screening of phenylketonuria was evaluated and compared with our routine method based on the modified fluorometric McCaman method. The test exhibited a linear calibration curve with a good slope as well as sufficient imprecision (< 10%), recovery (99.23 ± 4.86%) and limit of detection (54.5 μmol/l). One hundred and ninety dried blood spots were analysed by this enzymatic method and compared with McCaman's. Although Quantase (Teknovas, Bilbao, Spain) showed a phenylalanine mean level in dried blood spot 18.2 μmol/l higher than that obtained with our routine method, the agreement between both techniques was considered acceptable.
Voltammetric analysis of the bleachability of softwood kraft pulps
Authors: Bourbonnais Robert , Valeanu Loredana , Paice Michael G.
Published: October 2004

Kraft and oxygen delignified pulps with various kappa numbers were prepared from black spruce and western hemlock chips. The bleachability (ratio of kappa number decrease to chlorine dioxide applied) of the different pulps at the same kappa number varied with both wood furnish and delignification process. Thus, unbleached kappa number alone is not a reliable indicator of bleachability for these pulps. This may be due in part to the variable hexenuronic acid content of the pulps; those with higher ratio of hexenuronic acid content to kappa number (HexA/kappa) are harder to bleach. Voltammetric analysis of the same kraft pulps in the presence of redox mediators was found to measure both the content and reactivity of residual lignin. Peak current ratios of redox mediators correlated with pulp bleachability for all pulps. These ratios may therefore provide a more accurate prediction of bleachability than unbleached kappa number.
Alkaline degradation of model compounds related to beech xylan
Authors: Sartori Jürgen , Potthast Antje , Rosenau Thomas , Hofinger Andreas , Sixta Herbert , Kosma Paul
Published: October 2004

To address the chemical behavior of beech xylan (O-acetyl-4-O-methyl-glucuronoxylan) under alkaline conditions, three model compounds, 2-O-methylxylobiose (1), aldobiouronic acid (4-O-methyl-α-D-glucopyranosyluronic acid-(1→2)-xylose, 2), and aldotriouronic acid (4-Omethyl-α-D-glucopyranosyluronic acid-(1→2)-β-D-xylopyranosyl-(1→4)-D-xylose, 3), were subjected to strong alkaline conditions equal to those used for the industrial production of viscose (18% NaOH, 43°C). Kinetics of the degradation of the model compounds were monitored by capillary electrophoresis in combination with pre-column derivatization. It was demonstrated that substitution at O-2 of the reducing xylose unit strongly retarded the alkaline degradation reactions (1 and 2). By isotopic labeling experiments and isolation of degradation products it was shown that under the pertinent conditions deprotonation at C-2 occurs, followed by epimerization to the respective lyxo derivative. Aldotriouronic acid 3 was degraded to 2 as an intermediate according to classical peeling pathways. Genuine degradation reactions and epimerization processes were distinguished.