bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of violent behaviour in the correctional system using qualified risk assessments
Authors: Belfrage Henrik , Fransson Göran , Strand Susanne
Published: February 2004

Purpose. This study focused on whether institutional violence in a maximum‐security correctional institution could be prevented using comprehensive risk assessments followed by adequate risk management. And, could this be shown by a decrease in risk factors for violence according to the HCR‐20 Risk Assessment Scheme in the study group?

Methods. Offenders with a history of violent criminality were subject to real‐life assessments using the HCR‐20 Risk Assessment Scheme. The assessments were followed by discussions with members of staff, in which risk management strategies were designed. Thus, the members of staff were fully aware of every inmate's personality characteristics (e.g. psychiatric diagnoses), what risk factors for violence they displayed, and how best to manage those risk factors. With the aim of evaluating the possible effects of our interventions, approximately one third of the study group was reassessed after a mean of 12 months.

Results. The follow‐up showed no significant decrease in important risk factors for violence in the study group. However, the number of violent incidents showed a remarkable decrease during the study period.

Conclusions. Not being able to reduce important risk factors for violence does not necessarily mean that one cannot decrease the risk for, or the incidence of, violence. This study indicates that proper and adequate risk management, using the best protective factors available, can reduce violence even though important risk factors cannot be decreased. The study also supports the theoretical assumption that changes in risk factors are more possible in some populations (e.g. general psychiatric) than in others (e.g. correctional) depending on the nature of the study group and the risk factors that are at hand (e.g. dynamic vs. static). This seems to be important to bear in mind when performing evaluation research using risk assessment instruments.
Witnesses with intellectual disabilities in court: What questions are asked and what influence do they have?
Authors: Kebbell Mark R. , Hatton Christopher , Johnson Shane D.
Published: February 2004

Purpose. To identify the ways in which witnesses with and without intellectual disabilities are examined in court. Specifically to identify what questions are asked and what influence they have.

Methods. Court transcripts were obtained for 16 rape, sexual assault or assault trials involving witnesses with intellectual disabilities and 16 matched cases involving witnesses from the general population. The cases were assessed systematically concerning the questioning strategies of lawyers and the influence of those strategies on witness responses.

Results. Questioning of witnesses with intellectual disabilities was almost identical to that of witnesses from the general population indicating that lawyers are not altering their questioning behaviour for witnesses with intellectual disabilities, either positively or negatively. Cross‐examination is particularly poor for eliciting accurate memory reports, especially for witnesses with intellectual disabilities. The accounts of witnesses with intellectual disabilities are shorter and more likely to agree with a leading question than are accounts from the general population.

Conclusion. The way in which witnesses are examined does little to ensure that their memories are as accurate as possible. People with intellectual disabilities should be questioned in such a way that their ability to give accurate evidence in court is maximized.
The application of a ‘story‐telling’ framework to investigative interviews for suspected child sexual abuse
Authors: Westcott Helen L. , Kynan Sally
Published: February 2004

Purpose. This study investigated the usefulness of a ‘story‐telling’ approach to understanding investigative interviews with children suspected of being sexually abused.

Method. An innovative framework for understanding children's allegations of sexual abuse was devised from the ‘story‐telling’ literature, which examined the degree to which essential elements of a story, as well as order or disorder of narrative, were present in accounts of alleged abuse. Other features of the interview, such as the presence of free narrative, reliance on specific questions to elicit an account and bizarre or ‘off‐topic’ responses from the child, were also recorded. Transcripts of 70 interviews with children aged up to 12 years, from England and Wales, were coded using a scheme devised specifically for the purpose of the study.

Results. The results suggest that although, superficially, the accounts adhered to a story structure, they were often incomplete, ambiguous and disordered to a degree which would impact on understanding. Reliance on specific questions, and other digressionary or non verbal responses from the child also compounded difficulties. Age differences in responding were noted, with the youngest children responding differently from their older peers.

Conclusions. Implications for practice include the importance of careful questioning and the value of a second interviewer monitoring the interview. The story‐telling framework was a useful tool in suggesting where difficulties may arise for the child in presenting his/her account, and for an observer (e.g. juror) in making sense of the child's experience as elicited in the interview.
Predicting reconviction using the Psychological Inventory of Criminal Thinking Styles with English prisoners
Authors: Palmer Emma J. , Hollin Clive R.
Published: February 2004

Purpose. The purpose of this study was to investigate the utility of the Psychological Inventory of Criminal Thinking Styles (PICTS) in predicting reconviction in a sample of male prisoners.

Method. The PICTS was administered to 174 incarcerated male offenders at the point of their release from prison. Reconviction data were collected at a 2‐year follow‐up.

Results. Of the eight PICTS scales, only superoptimism differed significantly between reconvicted and non‐reconvicted prisoners, even when age and number of previous convictions were controlled for. Reconvicted offenders scored significantly higher on superoptimism, indicating a more criminal attitude. This finding was supported by a sequential logistic regression, where superoptimism contributed significant predictive power to predicting reconviction beyond a model containing age and number of previous convictions.

Conclusions. The results are compared with previous research using the PICTS to predict release outcome. The utility of the PICTS as a predictor for release outcome is discussed.
Motivation for offending and personality
Authors: Gudjonsson Gisli H. , Sigurdsson Jon Fridrik
Published: February 2004

Purpose. The main aim of the study was to examine the relationship between motivation for offending and personality.

Method. A specially constructed Offending Motivation Questionnaire (OMQ) was developed along the lines of Farrington's (1986, 1993) theoretical framework. The OMQ, the Mak Self‐Reported Delinquency Scale, the Gudjonsson Compliance Scale (GCS), the Gough Socialisation Scale, the Rosenberg Self‐Esteem Scale, and the Gudjonsson Blame Attribution Inventory (BAI‐R) were administered to two groups of students: college students and university students.

Results. Factor analysis of the OMQ revealed four motivational factors for offending (Compliance, Provocation, Financial, Excitement) and one further factor associated with the failure to appreciate the consequences of the criminal act. As predicted, the GCS correlated significantly with a compliance motive (i.e. being coerced, manipulated, or tricked into crime by a peer, or eagerness to please a peer), whereas the remaining four factors were associated with a low score on the Gough Socialisation Scale. External and Mental Element attributions were mainly found to be associated with provocation and consequences factors.

Conclusions. The findings support the view that there is a relationship between the motivation for offending, failure to appreciate the consequences of one's actions and personality. Further research should focus on studying this relationship among criminal populations.
The influence of courtroom questioning style on actual and perceived eyewitness confidence and accuracy
Authors: Wheatcroft Jacqueline M. , Wagstaff Graham F. , Kebbell Mark R.
Published: February 2004

Purpose. Little research has been conducted on the effects of courtroom examination/questioning styles on witness confidence and accuracy. Two studies were therefore conducted, one investigating the effects of examination style on witness confidence and accuracy, the other investigating observers/jurors perceptions of witness confidence and accuracy.

Method. In Study 1, after observing a video event, 60 witnesses were individually interviewed about the event according to one of three conditions: (1) simple questioning style, (2) lawyerese questioning style (containing leading and suppositional phrases), and (3) lawyerese with negative feedback style. In study 2, 60 observers/ jurors observed a good and a poor witness under examination by one of the three questioning styles. Measures of the perceived fairness of the examination were also taken in study 2.

Results. In the main, significant results were found only for question items classed as difficult to remember. The lawyerese style appeared to have an adverse affect on confidence‐accuracy relationships. Adding subtle negative feedback reduced the problem, but at the price of reduced overall accuracy. Observers (jurors) also seemed to be most affected by observing the negative feedback style; judging the witness overall to be less accurate. An unexpected result was that, regardless of questioning style, presenting the testimony of the least confident witness first appeared to spuriously boost confidence and thereby perceived accuracy, in that witness's testimony. No significant effects were found for perceived fairness.

Conclusions. In general, these results lend some support to those who have asserted that the lawyerese style of questioning may be unwise.
Imprisoned knowledge: Criminals' beliefs about deception
Authors: Granhag Pär Anders , Andersson Lars O. , Strömwall Leif A. , Hartwig Maria
Published: February 2004

Purpose. This paper is a survey examining beliefs about cues to deception held by prison inmates, prison personnel and students. In line with the ideas about more beneficial learning structures in the environment of criminals and findings from previous studies, we predicted that the beliefs held by prison inmates would be most consistent with the general pattern found in studies examining objective cues to deception.

Method. A total of 326 participants filled out a questionnaire containing questions about cues to deception. The sample consisted of 107 prison inmates from high‐security prisons, 103 prison personnel and 116 students. Both between‐group and within‐group analyses were conducted.

Results. In line with previous surveys, students and prison personnel held stereotypical and wrongful beliefs about cues to deception. Prison inmates' beliefs about deception were less stereotypical than the beliefs of prison personnel and students.

Conclusions. The results indicate that prison inmates have relatively more insight into the psychology of deception. A reasonable explanation for these findings is that the environment of criminals is beneficial in the sense that they receive more adequate outcome feedback than the other two groups. The results indicate that studying this group may generate useful knowledge about the dynamics of deception.
Confessions and denials and the relationship with personality
Authors: Gudjonsson Gisli H. , Sigurdsson Jon Fridrik , Bragason Olafur O. , Einarsson Emil , Valdimarsdottir Eva B.
Published: February 2004

Purpose. The main aim of the study was to examine the reasons and personality factors associated with confessions and denials. It was hypothesized that antisocial personality traits and active involvement in criminal behaviour would distinguish true confessors and true deniers from false confessors and false deniers.

Method. The participants were 1,080 students in further education in Iceland. Each was asked about false admissions made to teachers and parents in the past, as well as about confessions or denials (true and false) made to the police during questioning, and the reasons for having responded in the way they did. The participants also completed questionnaires relating to offending, personality and self‐esteem.

Results. One‐quarter (25%) of the participants stated that they had in the past been interrogated by the police in relation to a suspected offence, of whom 59% said they had confessed. A small minority of those interrogated (3.7%; 1% of the total sample) claimed to have made false confessions to the police, whereas 10% claimed to have made false confessions to teachers or parents. Males were significantly more likely to report false confessions than females. False confessions and false denials were significantly associated with antisocial personality traits, with Eysenck Personality Questionnaire Psychoticism being the single best predictor. Those participants who made true confessions and true denials were most normal in their personality.

Conclusions. Personality is a significant predictor of who makes false confessions and false denials.
Eysenck's theory of crime revisited: Factors or primary scales?
Authors: Levine Stephen Z. , Jackson Chris J.
Published: February 2004

Purpose. This study aims to advance the original formulation of Eysenck's theory of criminality from the factorial level to suggest that primary scales of personality best determine reports of delinquency.

Method. Two self‐report studies were conducted. The first consisted of 101 students and the second used an additional 101 students. The first study used measures of Self‐Reported Delinquency (SRD) and Socialisation (Gough & Peterson, 1952) and the Eysenck Personality Questionnaire Revised Edition (EPQ‐R; H.J. Eysenck & Eysenck, 1991). The second study complemented the first study to utilize the EPQ‐R and SRD only.

Results. A series of exploratory hierarchical multiple entry regressions of the factors in the first study demonstrate that high Psychoticism predicts SRD, whereas high Psychoticism and Neuroticism predict Under‐socialization. The primary scales of Disrespect for Rules, Depressed and Need for Stimulation significantly predict both criteria. The second study extends the first study through structural equation modelling to provide acceptable evidence of the concurrent validity of these primary scales with SRD.

Conclusions. We propose that the significant primary scales of personality provide a clear reformulation of Eysenck's original theory of criminality as they explain the variance in delinquency and socialization in a systematic manner. Furthermore, primary scales provide a theoretical framework for behavioural interventions, as required by Blackburn (2000).
Towards Complete and Accurate Reporting of Studies of Diagnostic Accuracy: The STARD Initiative
Authors: Bossuyt Patrick M , Reitsma Johannes B , Bruns David E , Gatsonis Constantine A , Glasziou Paul P , Irwig Les M , Lijmer Jeroen G , Moher David , Rennie Drummond , de Vet Henrica C W ,   for the STARD Group
Published: February 2004

Background: To comprehend the results of diagnostic accuracy studies, readers must understand the design, conduct, analysis, and results of such studies. That goal can be achieved only through complete transparency from authors.

Objective: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy to allow readers to assess the potential for bias in the study and to evaluate its generalisability.

Methods: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two-day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy.

Results: The search for published guidelines on diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. The consensus meeting shortened the list to 25 items, using evidence on bias whenever available. A prototypical flow diagram provides information about the method of patient recruitment, the order of test execution and the numbers of patients undergoing the test under evaluation, the reference standard or both.

Conclusions: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.
Quantitative Analysis of Tyrosine Hydroxylase mRNA for Sensitive Detection of Neuroblastoma Cells in Blood and Bone Marrow
Authors: Träger Catarina , Kogner Per , Lindskog Magnus , Ponthan Frida , Kullman Anita , Kågedal Bertil
Published: February 2004

Background: Sensitive monitoring of minimal residual disease may improve the treatment of neuroblastoma in children. To detect and monitor neuroblastoma cells in blood and bone marrow, we developed a quantitative method for the analysis of tyrosine hydroxylase mRNA.

Methods: We used real-time reverse transcription-PCR. The calibrator was constructed from a segment of tyrosine hydroxylase mRNA that included the target. Blood and bone marrow samples from 24 children with neuroblastoma and 1 child with ganglioneuroma were analyzed. Controls were blood samples from the cords of 40 babies, from 58 children 6 months to 15 years of age, and from 34 healthy adults, as well as from 12 children with other diseases.

Results: The detection limit was ∼70 transcripts/mL. All 144 blood controls were below this limit. At diagnosis, blood tyrosine hydroxylase mRNA was higher in children with widespread disease (stage 4/4S; n = 6; range, 203–46 000 transcripts/mL) than in patients with localized disease (stages 1–3; n = 6; ≤83 transcripts/mL; P = 0.002). Bone marrow from all five children with localized disease had concentrations <72 transcripts/mL, whereas five of six stage 4 patients had increased concentrations (6000–8 000 000 transcripts/mL; P <0.05). In nine children in whom tyrosine hydroxylase mRNA was measured repeatedly, the results corresponded to the clinical course.

Conclusion: Quantitative analysis of tyrosine hydroxylase mRNA in blood and bone marrow is reliable and easy to perform and may be used for upfront staging, prognostic assessment, and treatment monitoring of neuroblastoma.
Predictors of Change in Plasma Total Cysteine: Longitudinal Findings from the Hordaland Homocysteine Study
Authors: El-Khairy Lina , Vollset Stein E , Refsum Helga , Ueland Per M
Published: February 2004

Background: Total cysteine (tCys) in plasma has recently been linked to cardiovascular risk and is also associated with cardiovascular risk factors, including body mass index (BMI) and cholesterol. Changes and predictors of change in tCys concentrations over a mean follow-up time of 6.0 (5.2–7.2) years were assessed in this study.

Methods: Baseline data from the Hordaland Homocysteine Study recorded in 1992–1993 included tCys, total homocysteine (tHcy), and various lifestyle and cardiovascular risk factors. In 1998–1999, the same measurements were repeated in 3732 individuals born in 1950–1951 and 3339 individuals born in 1925–1927. Most of the statistical analyses were done separately in the four age and sex groups.

Results: The overall mean values of tCys were higher at follow-up [mean (SD), 296 (41) μmol/L] than at baseline [278 (36.5) μmol/L]; P <0.0001. The mean percentage of increase in tCys in the different age and sex groups ranged from 4.9% to 8.5%. There was a significant correlation between the tCys values measured on the two occasions (Spearman correlation coefficient, 0.55–0.59 in the different age and sex groups; P <0.0001). The change in tCys correlated with changes in BMI, cholesterol, and diastolic blood pressure in the younger age group, whereas only changes in BMI predicted changes in tCys in the older age group.

Conclusions: tCys increased in the 6 years between the two measurements. Factors related to the baseline tCys values, including BMI and the change in BMI, predicted the tCys changes over time.
Prevalence of Fatty Acid Ethyl Esters in Meconium Specimens
Authors: Moore Christine , Jones Joseph , Lewis Douglas , Buchi Karen
Published: February 2004

Background: Fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBDs), and alcohol-related neurodevelopment disorders (ARNDs) in neonates are often the result of maternal alcohol consumption during pregnancy. Facial characteristics are associated with FAS, but ARBDs and ARNDs are more difficult to diagnose. Fetal exposure to alcohol can cause central nervous system dysfunction, pre- and postnatal growth problems, cardiac defects in neonates, and attention deficit disorders and mental retardation in older children. To date, diagnosis of fetal alcohol effect has depended largely on maternal interview, although clinical tests are becoming more widely used. Fatty acid ethyl esters (FAEEs) are formed in the body by esterification of ethanol with free fatty acids and trans-esterification of glycerides and have been detected in the meconium of newborns. This report estimates the prevalence of fetal alcohol exposure in two populations by detecting FAEEs in meconium.

Methods: We analyzed the prevalence of FAEEs in the meconium of two separate groups of neonates by use of solid-phase extraction and analysis by gas chromatography–mass spectrometry in the chemical ionization mode. In the first study, meconium samples were taken anonymously from babies born in a large, regional perinatal center in Hawaii. In the second study, specimens were obtained from infants admitted to six different newborn intensive care units within the state of Utah.

Results: In the first study, 73 of 436 (16.7%) meconium specimens tested were considered positive for FAEEs. When broken down into quartiles, the mean total FAEEs measured were 1059, 3133, 6628, and 62115 ng/g. In the second study, 35 of 289 (12.1%) specimens were considered positive. When broken into quartiles, the mean total FAEEs were 1139, 3067, 7674, and 50 143 ng/g. The overall FAEE profiles of the two study sets were remarkably similar.

Conclusion: In an adequate meconium specimen, a total FAEE concentration >10 000 ng/g may indicate that the newborn has been exposed to significant amounts of alcohol during pregnancy.
Hemoglobin Görwihl [α2β25(A2)Pro→Ala], an Electrophoretically Silent Variant with Impaired Glycation
Authors: Bissé Emmanuel , Schauber Claude , Zorn Nathalie , Epting Thomas , Eigel Antonin , Van Dorsselaer Alain , Wieland Heinrich , Kister Jean , Kiger Laurent
Published: February 2004

Background: Some of the genetic variants of hemoglobin (Hb) and their chemically modified species are known to affect the measurement of Hb A1c. The purpose of this study was to characterize Hb species in the blood sample of a 74-year-old German male with an exceptionally low Hb A1c value.

Methods: Hemolysates from the propositus and a healthy individual were analyzed by electrophoresis, cation-exchange HPLC, boronate affinity chromatography, and electrospray ionization-mass spectrometry (ESMS). Genomic DNA was amplified by PCR, and the sequencing was performed on an ABI 310 sequencer. Functional properties of Hb were determined by oxygen equilibrium studies and CO recombination kinetics after flash photodissociation. Glycohemoglobin species were synthesized by incubating hemolysates with glucose.

Results: A novel, electrophoretically silent β chain, β5(A2)Pro→Ala or Hb Görwihl, was detected by cation-exchange HPLC. It accounted for ∼44% of the total Hb and had functional properties similar to those of normal Hb A and a mild degree of heat instability. During incubation with glucose, glycation of the β chains (assessed by ESMS) in the hemolysate of a healthy volunteer was twice as fast as in hemolysate from the propositus.

Conclusions: The substitution β5(A2)Pro→Ala seems to affect neither the functional properties nor the heterotropic interactions of Hb, but slows glycation of the N-terminal valine by an unknown mechanism.
Plasma Vitamin B6 Vitamers before and after Oral Vitamin B6 Treatment: A Randomized Placebo-controlled Study
Authors: Bor Mustafa Vakur , Refsum Helga , Bisp Marianne R , Bleie Øyvind , Schneede Jorn , Nordrehaug Jan Erik , Ueland Per Magne , Nygard Ottar Kjell , Nexø Ebba
Published: February 2004

Background: Vitamin B6 has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B6 vitamers, pyridoxal 5′-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B6 supplementation.

Methods: Patients (n = 90; age range, 38–80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B12 (0.4 mg), folic acid (0.8 mg), and vitamin B6 (40 mg); (B), vitamin B12 and folic acid; (C), vitamin B6; or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter.

Results: Before treatment, PLP (range, 5–111 nmol/L) and 4-PA (6–93 nmol/L) were the predominant B6 vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B6 (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were ∼10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment.

Conclusions: Vitamin B6 treatment has an immediate effect on the concentrations and the forms of B6 vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B6 vitamers in plasma reflect vitamin B6 intake.
Use of a Major Medical Center Clinical Laboratory as a Reference Laboratory for a Developing Country: Ordering Patterns Help Set Laboratory Priorities
Authors: Ladenson Jack H , Scott Mitchell G , Klarkowski Derryck , Seyoum Melles
Published: February 2004

Background: The test menus for developed and developing countries may differ, depending on many factors, including the expected volume of testing, disease frequency and therapies available, clinical impact of the test, technical skill and equipment needed, cost, the patient population served, and whether alternative testing sites are available, and some of them may not be exactly known. We assessed test priorities in a developing country by making a broad range of tests available and then assessing which tests were actually used by the physicians in the country for the care of their patients.

Methods: The Barnes-Jewish Hospital laboratory and Washington University Medical Center provided patients in the developing country of Eritrea access to the same tests as patients in St. Louis for all analytes that are stable at 4 °C, the lowest temperature that could be used for shipping.

Results: The use of the St. Louis laboratories increased steadily from 1998 to 2001. More than one-half of the physicians in Eritrea used the reference laboratories, with requests for thyroid function and female fertility representing 48–71% of the test requests over the 4 years evaluated. The high degree of utilization for these test batteries was not predicted. Testing for thyroid function, female fertility, and lipid panels are now performed, or soon will be performed, in Eritrea based on the experience of the reference laboratory system. The reference laboratory system is continuing so that the test priorities of the country can be evaluated on an ongoing basis and specialized tests can be made available at a low cost.

Conclusion: The experiences of a reference laboratory for a developing country can help to identify unanticipated priorities for medical testing within the country.
Use of High-Throughput DNA Microarrays to Identify Biomarkers for Bladder Cancer
Authors: Sánchez-Carbayo Marta
Published: February 2004

Background: Numerous markers have been described to correlate to some extent with tumor stage and prognosis of patients with bladder cancer. The power of many of these biomarkers in detecting superficial disease or predicting the clinical outcome of individual tumors is limited, and alternative markers are still in demand. High-throughput microarrays represent novel means for cancer research and tumor marker discovery.

Approach: The aim of this report was to discuss the application of DNA technologies to provide novel biomarkers for bladder cancer.

Content: Specific bladder tumor subtypes have distinct gene expression profiles. The use of high-throughput DNA microarrays allows identification of the most prevalent and relevant alterations within bladder tumors. Clusters of differentially expressed genes will become biomarkers to discriminate subgroups of patients with different histopathology or clinical outcome. Additionally, the identified individual molecular targets might be further validated and developed into novel serum or urinary biomarkers for the diagnosis and/or as prognostic factors to be applied in clinical practice. The diagnosis and prognosis of bladder cancer would be enhanced by the use of such markers, and the marker itself may constitute a therapeutic target when studied in appropriate patients and control groups.

Summary: Expression profiling with high-throughput DNA microarrays has the potential of providing critical clues for the management of bladder cancer patients. As the quality, standardization, and ease of use of the technology increase and the costs decrease, DNA microarrays will move from being a technology restricted to research to clinical laboratories in the near future.
Angiogenesis Assays: A Critical Overview
Authors: Auerbach Robert , Lewis Rachel , Shinners Brenda , Kubai Louis , Akhtar Nasim
Published: February 2004

Background: Angiogenesis, the formation of new blood vessels, is an integral part of both normal developmental processes and numerous pathologies, ranging from tumor growth and metastasis to inflammation and ocular disease. Angiogenesis assays are used to test efficacy of both pro- and antiangiogenic agents.

Methods: Most studies of angiogenesis inducers and inhibitors rely on various models, both in vitro and in vivo, as indicators of efficacy. In this report we describe the principal methods now in use: the in vivo Matrigel plug and corneal neovascularization assays, the in vivo/in vitro chick chorioallantoic membrane (CAM) assay, and the in vitro cellular (proliferation, migration, tube formation) and organotypic (aortic ring) assays. We include description of two new methods, the chick aortic arch and the Matrigel sponge assays.

Conclusions: In vitro tests are valuable, can be carried out expeditiously, and lend themselves to quantification, but must be interpreted with extreme caution. In vitro tests are best viewed as providing initial information, subject to confirmation by in vivo assays. Multiple tests should be used to obtain maximum benefit from in vitro tests. In vivo tests are more difficult and time-consuming to perform, thereby limiting the number of tests that can run at any one time. Quantification is generally more difficult as well. However, in vivo assays are essential because of the complex nature of vascular responses to test reagents, responses that no in vitro model can fully achieve.
Windows to the Ward: Graphically Oriented Report Forms. Presentation of Complex, Interrelated Laboratory Data for Electrophoresis/Immunofixation, Cerebrospinal Fluid, and Urinary Protein Profiles
Authors: Regeniter Axel , Steiger Jürg U , Scholer André , Huber Peter R , Siede Werner H
Published: February 2004

Background: Automated laboratory analyzers that mass produce data have been linked to information systems for more than two decades, but little progress has been made in developing more comprehensible report forms. Results are still reported in computer-generated printouts containing hundreds of numbers crowded into columns on each printed page.

Methods: We developed three software applications focusing on the graphic presentation of laboratory results.

Results: The first application summarizes data for a patient with a monoclonal gammopathy. The report provides a cumulative graphic presentation of immunofixation/electrophoresis data without any additional interpretation, focuses on a color-coded electrophoresis scan, and records up to 5 years on a single page. The second application deals with cerebrospinal fluid analysis. The report calculates relevant data and graphs the complex relationship between albumin and immunoglobulin results from paired serum and cerebrospinal fluid samples. Manually added interpretive text assures an output comprehensible to clinicians in all specialties. The third application produces a report summarizing quantitatively measured urinary marker protein profiles. The report form is generated by a flexible, completely user-definable knowledge-based system. It calculates numerous ratios and formulae, supports reflex testing, supplies an automated interpretation, and generates a specific graphic signature pattern of the results (MDI LabLink proteinuria differentiation).

Conclusions: Increased clinical demand for graphically oriented report forms 5 years after their introduction has provided evidence that these reports transfer complex laboratory data and results to the clinician more effectively. The highest (more than threefold) increase in demand has been for reports for urinary marker protein profiles that feature a largely self-explanatory graphic signature pattern.
Quantitative Real-Time PCR Method for Detection of B-Lymphocyte Monoclonality by Comparison of κ and λ Immunoglobulin Light Chain Expression
Authors: Ståhlberg Anders , Åman Pierre , Ridell Börje , Mostad Petter , Kubista Mikael
Published: February 2004

Background: An abnormal IgLκ:IgLλ ratio has long been used as a clinical criterion for non-Hodgkin B-cell lymphomas. As a first step toward a quantitative real-time PCR-based multimarker diagnostic analysis of lymphomas, we have developed a method for determination of IgLκ:IgLλ ratio in clinical samples.

Methods: Light-up probe-based real-time PCR was used to quantify IgLκ and IgLλ cDNA from 32 clinical samples. The samples were also investigated by routine immunohistochemical analysis and flow cytometry.

Results: Of 32 suspected non-Hodgkin lymphoma samples analyzed, 28 were correctly assigned from real-time PCR measurements assuming invariant PCR efficiencies in the biological samples. Four samples were false negatives. One was a T-cell lymphoma, one was a diffuse large B-cell lymphoma, and one was reanalyzed and found lymphoma-positive by in situ calibration, which takes into account sample-specific PCR inhibition. Twelve of the samples were fine-needle aspirates, and these were all correctly assigned.

Conclusions: This work is a first step toward analyzing clinical samples by quantitative light-up probe-based real-time PCR. Quantitative real-time PCR appears suitable for high-throughput testing of cancers by measuring expression of tumor markers in fine-needle aspirates.
C-Reactive Protein, Interleukin-6, and Procalcitonin in the Immediate Postnatal Period: Influence of Illness Severity, Risk Status, Antenatal and Perinatal Complications, and Infection
Authors: Chiesa Claudio , Pellegrini Gabriella , Panero Alessandra , Osborn John F , Signore Fabrizio , Assumma Marcello , Pacifico Lucia
Published: February 2004

Background: Studies of the diagnostic accuracy of most laboratory tests for early-onset neonatal sepsis have yielded variable results. We investigated whether some of this variation might be attributable to differences in population baseline severity and risk status as well as to specific ante- and perinatal variables, independent of the presence of neonatal infection.

Methods: The Score for Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP Perinatal Extension (SNAP-PE) used to define the combined physiologic and perinatal mortality risk. A total of 134 ill newborns (19 with early-onset infection and 115 with no infection) were available for simultaneous analysis of the association of SNAP, SNAP-PE, and maternal and perinatal variables with C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) concentrations at birth and at 24 and 48 h of life.

Results: Early-onset neonatal infection was associated with significant increases in CRP, IL-6, and PCT concentrations at all three time points, independent of illness severity. However, among babies without infection, higher SNAP and SNAP-PE scores were associated with higher IL-6 concentrations at birth. Certain maternal or perinatal variables altered IL-6 and PCT values in the infected as well as in the uninfected neonates. However, if different cutoff points were used at any of the three neonatal ages, PCT sensitivity and specificity were greater than those of CRP or IL-6.

Conclusions: Illness severity and risk status are unlikely to interfere with the use of CRP and PCT for detection of early-onset neonatal sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for the diagnosis of early-onset neonatal infection requires specific cutoff values for each evaluation time point over the first 48 h of life.
Outcome Validation of the Beckman Coulter Access Analyzer in a Second-Trimester Down Syndrome Serum Screening Application
Authors: MacRae Andrew R , Gardner H Allen , Allen Lynn C , Tokmakejian Sonya , Lepage Nathalie
Published: February 2004

Background: Mid-trimester maternal serum α-fetoprotein (AFP) and unconjugated estriol (uE3) are 30% lower and human chorionic gonadotropin (hCG) is twofold higher in Down syndrome pregnancies compared with unaffected pregnancies. In maternal serum screening, patient-specific risks are calculated using published gaussian frequency distribution parameters for these three markers obtained with previously available immunoassays. New immunoassays must generate similar distribution parameters if the accuracy of assigned risks and overall performance of prenatal screening are to be maintained.

Methods: Agreement between the Beckman Coulter Access and the Bayer Immuno 1 assays for AFP and hCG and the Amersham Amerlex-M RIA for uE3 was assessed in 558 fresh sera. Precision was measured over 6 weeks. Median concentrations were calculated by regression of 568 Caucasian singleton pregnancy samples against gestational age in days. Frozen mid-trimester sera from 44 confirmed Down syndrome singleton pregnancies (cases) were selected without conscious bias for reanalysis, and each case was matched with five control specimens from unaffected pregnancies. Serum markers were expressed as the multiple of the median (MoM) concentration derived from the control samples, cor-rected for maternal weight and converted to their log-equivalent values. Normality was assessed using probability plots and the Shapiro–Wilk W-test. Gaussian distribution parameters were compared with established values, and Down syndrome risk calculations were assessed with a commonly used risk algorithm.

Results: The Access AFP and hCG assays had consistent proportional agreement with the established assays, whereas agreement between the uE3 methods was less consistent. Analytical imprecision was 3–6% at mid-trimester concentrations. Normal distributions were obtained for the log MoM values of all three markers in both the Down syndrome and unaffected populations, and their gaussian distribution parameters compared well with established values. The performance of the Access assays in an established trivariate risk algorithm for Down syndrome was equal to the performance exhibited by traditional methods.

Conclusion: The Beckman Coulter Access analyzer provides valid mid-trimester serum AFP, uE3, and hCG results and risk assessments when applied in a prenatal Down syndrome screening service.
The STARD Statement for Reporting Studies of Diagnostic Accuracy: Explanation and Elaboration
Authors: Bossuyt Patrick M , Reitsma Johannes B , Bruns David E , Gatsonis Constantine A , Glasziou Paul P , Irwig Les M , Moher David , Rennie Drummond , de Vet Henrica C W , Lijmer Jeroen G
Published: February 2004

The quality of reporting of studies of diagnostic accuracy is less than optimal. Complete and accurate reporting is necessary to enable readers to assess the potential for bias in the study and to evaluate the generalisability of the results. A group of scientists and editors has developed the STARD (Standards for Reporting of Diagnostic Accuracy) statement to improve the reporting the quality of reporting of studies of diagnostic accuracy. The statement consists of a checklist of 25 items and flow diagram that authors can use to ensure that all relevant information is present. This explanatory document aims to facilitate the use, understanding and dissemination of the checklist. The document contains a clarification of the meaning, rationale and optimal use of each item on the checklist, as well as a short summary of the available evidence on bias and applicability. The STARD statement, checklist, flowchart and this explanation and elaboration document should be useful resources to improve reporting of diagnostic accuracy studies. Complete and informative reporting can only lead to better decisions in healthcare.
Human Kallikrein 13: Production and Purification of Recombinant Protein and Monoclonal and Polyclonal Antibodies, and Development of a Sensitive and Specific Immunofluorometric Assay
Authors: Kapadia Carl , Chang Albert , Sotiropoulou Georgia , Yousef George M , Grass Linda , Soosaipillai Antoninus , Xing Xuekun , Howarth David H C , Diamandis Eleftherios P
Published: February 2004

Background: The aims of this study were to develop immunologic reagents and a sensitive and specific immunoassay for human kallikrein 13 (hK13) and to examine the presence of hK13 in human tissues and biological fluids.

Methods: Recombinant hK13 protein was produced and purified with use of a Pichia pastoris yeast expression system. The protein was used as an immunogen to generate mouse monoclonal and rabbit polyclonal anti-hK13 antibodies. A sandwich-type immunoassay was developed with these antibodies. The assay was used to measure hK13 in various biological fluids and tissue extracts. Immunohistochemical analysis was also performed on nondiseased and cancerous prostatic sections.

Results: The hK13 immunoassay had a detection limit of 0.05 μg/L and showed no cross-reactivity with homologous kallikreins. The assay was linear at 0–20 μg/L, and within-and between-run CVs were <10% (n = 12). hK13 was detected in tissues, including esophagus, tonsil, trachea, lung, cervix, and prostate. hK13 was also found in seminal plasma, amniotic fluid, follicular fluid, ascites of ovarian cancer patients, breast milk, and cytosolic extracts of ovarian cancer tissues. hK13 was immunohistochemically localized in epithelial cells of both nondiseased and cancerous prostate. hK13 appears to be overexpressed in 50% of ovarian cancer tissues compared with healthy ovarian tissues. Recovery of active enzyme added to milk or amniotic fluid was 70–98%, but was <20% when added to serum, suggesting rapid sequestration by protease inhibitors. In fluids and tissue extracts, hK13 was found in its free (∼30 kDa) form.

Conclusions: This immunofluorometric assay for hK13 may be used to examine the value of hK13 as a disease biomarker and to further explore the physiologic and pathobiologic role of this enzyme in human disease.
Human Kallikrein 8: Immunoassay Development and Identification in Tissue Extracts and Biological Fluids
Authors: Kishi Tadaaki , Grass Linda , Soosaipillai Antoninus , Shimizu-Okabe Chigusa , Diamandis Eleftherios P
Published: February 2004

Background: The serine protease human kallikrein 8 (hK8; neuropsin), a new member of the human kallikrein family, was predicted to be secreted; thus, it is expected to be present in biological fluids. The aim of this study was to develop a sensitive and specific immunoassay for hK8 (hK8-ELISA) and establish the distribution of hK8 in tissue extracts and biological fluids.

Methods: Recombinant hK8 was produced in a baculovirus expression system and purified with a three-step chromatographic procedure. Purified hK8 was injected into mice and rabbits for antibody generation. A highly specific and sensitive sandwich-type immunoassay (ELISA) was developed using the rabbit and mouse antisera to hK8. The hK8-ELISA was then used to study the distribution of hK8 in various biological fluids and tissue extracts.

Results: The dynamic range of the hK8-ELISA was 0.2 (detection limit) to 20 μg/L, and imprecision (CV) was <10% within this range. This hK8-ELISA was specific for hK8 and had no detectable cross-reactivity with other members of the human kallikrein family. With this assay, hK8 was detected in tissue extracts of esophagus (highest concentrations), skin, testis, tonsil, kidney, breast, and salivary gland and in the biological fluids breast milk (highest concentrations), amniotic fluid, seminal plasma, and serum. Furthermore, in some cancer cell lines, the concentration of hK8 was regulated by steroid hormones.

Conclusions: We report for the first time production of recombinant hK8 protein, generation of antibodies, and development of a highly sensitive and specific immunoassay for quantification of hK8 in tissue extracts and biological fluids. This assay can be used to explore the potential of hK8 as a marker of cancer or other conditions.
Dual-Label Immunoassay for Simultaneous Measurement of Prostate-specific Antigen (PSA)-α1-Antichymotrypsin Complex Together with Free or Total PSA
Authors: Zhu Lei , Leinonen Jari , Zhang Wan-Ming , Finne Patrik , Stenman Ulf-Håkan
Published: February 2004

Background: A major portion of prostate-specific antigen exists in circulation as a complex with α1-antichymotrypsin (PSA-ACT), whereas a minor part is free (fPSA). The proportion of PSA-ACT is increased in prostate cancer (PCa), but immunologic determination of PSA-ACT is hampered by a background produced by nonspecific adsorption of ACT to the solid phase. To reduce the nonspecific interference, we produced an antibody specific for complexed ACT and developed immunofluorometric assays (IFMAs) for simultaneous measurement of fPSA + PSA-ACT (fPSA/PSA-ACT) and PSA-ACT + total PSA (tPSA, PSA-ACT/tPSA).

Methods: Monoclonal antibodies (MAbs) were produced by immunization with PSA-ACT. The dual-label time-resolved IFMAs for fPSA/PSA-ACT and PSA-ACT/tPSA used a capture MAb to tPSA, an Eu3+-labeled MAb to fPSA or complexed ACT, and an Sm3+-labeled MAb to complexed ACT or to tPSA as tracer antibodies. The clinical utility was evaluated using serum samples from individuals with or without PCa with PSA concentrations of 2.0–20.0 μg/L.

Results: One MAb (1D10) showed low cross-reactivity with free ACT and cathepsin G-ACT. A sandwich assay for PSA-ACT with 1D10 as tracer had a detection limit of 0.05 μg/L, and with this assay, PSA-ACT was undetectable in female sera. The detection limit for fPSA was 0.004 μg/L. Determinations of the ratio of fPSA to PSA-ACT and the proportions of fPSA/tPSA and PSA-ACT/tPSA provided the same clinical specificity for PCa and provided significantly better clinical specificity than did tPSA.

Conclusions: Background problems observed in earlier PSA-ACT assays are eliminated by the use of a MAb specific for complexed ACT as a tracer. The same clinical validity can be obtained by determination of fPSA or PSA-ACT together or in combination with tPSA.