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PubMed1986

Standardizing clinical laboratory data for the development of transferable computer-based diagnostic programs.

The existence of systematic differences between test results obtained at different laboratories can compromise the development of generally accessible reference databases for interpretive pathology. We review approaches to the elimination of inter-laboratory bias from pathology test results through the use of standard unit transformations. A general transform procedure is described that will permit laboratories serving a common population to make use of reference data, decision rules, and computer-based interpretive programs developed around a larger clinical database than each of these test centers could amass for themselves.

Clinical Laboratory Techniques↗
PubMed2006

Taxonomic reliability of DNA sequences in public sequence databases: a fungal perspective.

BACKGROUND: DNA sequences are increasingly seen as one of the primary information sources for species identification in many organism groups. Such approaches, popularly known as barcoding, are underpinned by the assumption that the reference databases used for comparison are sufficiently complete and feature correctly and informatively annotated entries. METHODOLOGY/PRINCIPAL FINDINGS: The present study uses a large set of fungal DNA sequences from the inclusive International Nucleotide Sequence Database to show that the taxon sampling of fungi is far from complete, that about 20% of the entries may be incorrectly identified to species level, and that the majority of entries lack descriptive and up-to-date annotations. CONCLUSIONS: The problems with taxonomic reliability and insufficient annotations in public DNA repositories form a tangible obstacle to sequence-based species identification, and it is manifest that the greatest challenges to biological barcoding will be of taxonomical, rather than technical, nature.

DNA, Fungal↗
PubMed2004

Bone mineral density by age, gender, pubertal stages, and socioeconomic status in healthy Lebanese children and adolescents.

Gender, ethnicity, and lifestyle factors affect bone mass acquisition during childhood, thus the need for age- and sex-adjusted Z scores using ethnic-specific data for bone mineral density (BMD) measurement. This study aimed at establishing normative data for BMD in healthy Lebanese children and adolescents. Three hundred sixty-three healthy children aged 10 to 17 years (mean+/-SD: 13.1+/-2.0) were studied. BMD, bone mineral content (BMC), and lean mass were measured by dual-energy X-ray absorptiometry (DXA) using a Hologic 4500A device, and apparent volumetric BMD (BMAD) of the lumbar spine and the femoral neck were calculated. BMD, BMC, and BMAD were expressed by age groups and Tanner stages for boys and girls separately. There was a significant effect of age and puberty on all bone parameters, except at the femoral neck BMAD in boys. BMC and BMD were higher at cortical sites in boys, including subtotal body and hip; whereas, in girls, it was higher at a site more enriched in trabecular bone, namely the lumbar spine. At several skeletal sites, girls had significantly higher BMD adjusted for lean mass than boys. By the end of puberty, adolescents had a mean BMD that was 43-66% higher at the lumbar spine and 25-41% higher at cortical sites than pre-pubertal children, depending on the gender. Mean BMD values in the study group were significantly lower (P<0.01) than Western normative values, with Z scores ranging between -0.2 and -1.1. In both genders, children of lower socioeconomic status tended to have lower BMD than those from a higher socioeconomic background. This study allows additional insight into gender dimorphism in mineral accretion during puberty. It also provides a valuable reference database for the assessment of BMD in children with pubertal or growth disorders who are of Middle Eastern origin.

Absorptiometry, Photon↗
PubMed2005

Pharmacokinetic parameters analyzed from mr contrast enhancement kinetics of multiple malignant and benign breast lesions detected in the same patients.

Ninety-nine patients with confirmed breast cancer were reviewed to identify patients who had two confirmed malignant lesions of identical pathology (Group-1, N = 17), and patients who had one malignant lesion and the second benign lesion (Group-2, N = 8). Contrast enhancement kinetics from every lesion was measured and analyzed using three different models to obtain fitting parameters related to up-slope, enhancement amplitude, and wash-out, including Model-1: modified Tofts model (v(p), Ktrans, k(ep)), Model-2: standard Tofts model (Ktrans, k(ep)), and Model-3: a 3-parameter heuristic model (Tc, A, C). By analyzing lesions from same patients, the differences in whole body hemodynamics thus the blood kinetics could be controlled. Two questions were addressed in this study: i) What is the association between pharmacokinetic parameters analyzed from multiple cancers of identical pathology in same patients?; and ii) What is the difference between secondary malignant lesions and secondary benign lesions with reference to the primary cancer? All three models could fit the enhancement kinetics satisfactorily. Regardless of the analysis model the parameter obtained from the primary cancer and the secondary cancer showed significant correlations. In comparison between Group-1 and Group-2 subjects, the wash-out parameter kep in Models-1 and 2 could significantly differentiate benign from malignant lesions, but not the magnitude parameters, Ktrans in Model-2 or the parameter A in Model-3. If analyzed using appropriate models the early up-slope parameters, v(p) in Model-1 and Tc in Model-3, might be able to distinguish between benign and malignant lesions. When more data are available a reference database can be established with the method described in this study, and from which to determine the likelihood of malignancy for each incidental lesion found in preoperative MRI, with reference to the primary cancer.

Breast Diseases↗
PubMed2005

Comparison of spine and femur reference data in native Chinese women from different regions of China.

The aim of this study is to explore the differences of BMD reference curves at various skeletal sites among Chinese women from different regions of China and to investigate the feasibility of establishing a unified national BMD reference database for Chinese women. We measured BMD at the posteroanterior (PA) lumbar spine, femoral neck, trochanter and Ward's triangle by dual-energy X-ray absorptiometry bone densitometer in 3,422 Changsha women of South Central China, aged 20-84 years. The documented BMDs of reference populations of women in all other areas included Shanghai ( n =2,111) and Nanjing ( n =3,174) in the East, Shenyang ( n =1,213) in the Northeast, Kunming ( n =523) in the Southwest, Chongqing ( n =811) in the Midwest and Xian ( n =1,320) in the Northwest. We adopted the cubic regression as the fitting model for reference curves of BMD that varied with age, conducted conversions of BMD measured by various bone densitometers from different manufacturers and compared the differences between standardized BMD (sBMD) reference curves and combined ones for women from different areas. Our results revealed that by comparing variances in women from different areas, the average variances of non-standard BMD were 0.8-30.8% at the PA spine, 0.7-24.5% at the femoral neck, 0.6-29.9% at the trochanter and 1.1-54.7% at Ward's triangle, while average variances of sBMD either significantly decreased or disappeared (0.8-3.9% at the PA spine, 0.7-8.6% at the femoral neck, 0.6-8.3% at the trochanter and 1.1-29.9% at Ward's triangle). The sBMD reference curves were highly positive-dependent with combined ones ( r =0.913-0.999, P =0.000). At the PA spine and trochanter, the effect of combined sBMD curves presented well in women from different areas, except for those from Shanghai at the PA spine and Shenyang at the trochanter, indicating that sBMD curves were significantly different from pooled ones; at the femoral neck and Ward's triangle, the effect of combined sBMD reference curves was poor, indicating that sBMD curves demonstrated significant differences from pooled ones in women from a majority of these areas. We conclude that, in high density population areas, sBMD reference curves showed no significant geographic differences in women from various regions. In women from different areas, sBMD reference curves present good pooled results at the PA spine and trochanter. The less ideal combining effect of the sBMD curves at both femoral neck and Ward's triangle might be caused by the intrinsic differences from the different measuring instruments.

Absorptiometry, Photon↗
PubMed1997

An Internet service for manipulating 3D models of human organs reconstructed from computer tomography and magnetic resonance imaging.

Our paper describes an integrated methodology addressing the development of an Internet service for medical professionals, medical students and generally, people interested in medicine. The service (currently developed in the framework of IAEVA, a Telematics Application Programme project of the European Union), incorporates a mechanism for retrieving from a relational database (reference library) 3D volumetric models of human organs reconstructed from computer tomography (CT) and/or magnetic resonance imaging (MRI). Retrieval is implemented in a way transparent to the actual physical location of the database. Prospective users are provided with a Solid Object Viewer that offers them manipulation (rotation, zooming, dissection etc.) of 3D volumetric models. The service constitutes an excellent foundation of understanding for medical professionals/students and a mechanism for broad and rapid dissemination of information related to particular pathological conditions; although pathological conditions of the knee and skin are supported currently, our methodology allows easy service extension into other human organs ultimately covering the entire human body. The service accepts most Internet browsers and supports MS-Windows 32 platforms; no graphics accelerators or any specialised hardware are necessary, thereby allowing service availability to the widest possible audience. Nevertheless, the service operates in near real-time not only over high speed expensive network lines but also over low/medium network connections.

Computer Communication Networks↗
PubMed2003

Cerebrospinal fluid lactate and pyruvate concentrations and their ratio in children: age-related reference intervals.

BACKGROUND: Lactate (L) and pyruvate (P) concentrations in cerebrospinal fluid (CSF) and the L/P ratio have diagnostic value in numerous primary and acquired disorders affecting the central nervous system, but age-related reference values are not available for children. METHODS: We analyzed CSF and blood lactate and pyruvate concentrations and their ratio in a 4-year retrospective survey of a children's hospital laboratory database. Reference intervals (10th-90th percentiles) were established from data on 197 hospitalized children. A recent regression modeling method was used to normalize and smooth values against age. The model equation of best fit was calculated for each variable. RESULTS: Slight age-related variations were shown by the model, with an increase in lactate, a decrease in pyruvate, and a resulting increase in the L/P ratio with increasing age. However, the SD did not vary with age. We defined the upper limit of the reference intervals as the 90th percentiles, which from birth to 186 months of age varied continuously from 1.78 to 1.88 mmol/L (6%), 148 to 139 micro mol/L (6%), and 16.9 to 19.2 (14%) for lactate, pyruvate, and the L/P ratio, respectively. At a threshold of 2 (in Z-score units), the sensitivity for a subgroup of inborn errors of metabolism (respiratory chain disorders) was 73%, 42%, and 31% for lactate, pyruvate, and the L/P ratio, respectively. CONCLUSIONS: In children, CSF lactate and pyruvate concentrations and their ratio appear to vary slightly with age. Average 90th percentile values of 1.8 mmol/L, 147 micro mol/L, and 17, respectively, could be used in infants up to 24 months of age. In older children, age-adjusted reference intervals should be used, especially when values are close to the 90th percentile.

Adolescent↗
PubMed2006

Landscape of current toxicity databases and database standards.

Having readily available historical information for modeling toxicity has become important throughout the various stages of research and development. The high cost of late-phase attrition and recent international regulatory legislations have made even more acute the need to be able to mine the fragmented data and information available across diverse databases. In addition, the general trend to accelerate regulatory processes globally makes the effective use of existing data an imperative. To achieve efficient screening, develop profiles and gain the ability to cross reference, databases must be interoperated to allow data exchange and integration. Several database standards and controlled vocabulary initiatives have been used in the development of toxicity data models to transform the current landscape. This review describes the major databases of toxicological information now available, and provides a simple example of standardization that demonstrates the benefits of a toxicity database containing such qualified data.

Animals↗
PubMed2004

Reference ballistic imaging database performance.

Ballistic imaging databases allow law enforcement to link recovered cartridge cases to other crime scenes and to firearms. The success of these databases has led many to propose that all firearms in circulation be entered into a reference ballistic image database (RBID). To assess the performance of an RBID, we fired 4200 cartridge cases from 600 9mm Para Sig Sauer model P226 series pistols. Each pistol fired two Remington cartridges, one of which was imaged in the RBID, and five additional cartridges, consisting of Federal, Speer, Winchester, Wolf, and CCI brands. Randomly selected samples from the second series of Remington cartridge cases and from the five additional brands were then correlated against the RBID. Of the 32 cartridges of the same make correlated against the RBID, 72% ranked in the top 10 positions. Likewise, of the 160 cartridges of the five different brands correlated against the database, 21% ranked in the top 10 positions. Generally, the ranking position increased as the size of the RBID increased. We obtained similar results when we expanded the RBID to include firearms with the same class characteristics for breech face marks, firing pin impressions, and extractor marks. The results of our six queries against the RBID indicate that a reference ballistics image database of new guns is currently fraught with too many difficulties to be an effective and efficient law enforcement tool.

Databases, Factual↗
PubMed2003

RTPrimerDB: the real-time PCR primer and probe database.

The real-time polymerase chain reaction (PCR) methodology has become increasingly popular for nucleic acids detection and/or quantification. As primer/probe design and experimental evaluation is time-consuming, we developed a public database application for the storage and retrieval of validated real-time PCR primer and probe sequence records. The integrity and accuracy of the data are maintained by linking to and querying other reference databases. RTPrimerDB provides free public access through the Web to perform queries and submit user based information. Primer/probe records can be searched for by official gene symbol, nucleotide sequence, type of application, detection chemistry, LocusLink or Single Nucleotide Polymorphism (SNP) identifier, and submitter's name. Each record is directly linked to LocusLink, dbSNP and/or PubMed to retrieve additional information on the gene/SNP for which the primers/probes are designed. Currently, the database contains primer/probe records for human, mouse, rat, fruit fly and zebrafish, and all current detection chemistries such as intercalating dyes (SYBR Green I), hydrolysis probes (Taqman), adjacent hybridizations probes and molecular beacons. Real-time PCR primer/probe records are available at http://www.realtimeprimerdatabase.ht.st.

DNA Primers↗
PubMed2007

High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease.

OBJECTIVE: Alpha-1-antitrypsin (A1AT) deficiency is the most common genetic cause of liver disease in children; however, the role of polymorphic heterogeneity in the A1AT gene as a modifier of other forms of pediatric liver disease is not clear. We hypothesized that non-M A1AT allele variants are more common in children with chronic liver disease than in the general population. METHODS: A retrospective, single-center study was performed in which A1AT phenotypes were obtained by reviewing charts of children with chronic liver disease. Chi-square analysis was used to compare allele frequencies in the population of children with liver disease with published epidemiologic data and to compare allele frequencies among disease subgroups. RESULTS: The frequency of A1AT Z and other alleles was increased in children with chronic liver disease (n = 241) when compared with the published reference database (P < 0.001). This increase remained significant when the population was divided into disease subsets: biliary atresia (n = 67) and other liver disease (n = 174) (P < 0.001 for both). Among children with biliary atresia referred for liver transplant evaluation, the presence of a non-M allele was associated with a lower mean age at transplant listing than the MM phenotype (235 vs 779 days, P = 0.036) and more frequent loss of native liver by 24 months of age (90% vs 65%, P = 0.04). CONCLUSIONS: A1AT non-M alleles are more frequent in children with chronic liver disease than in the general population. We speculate that these non-M alleles may act as genetic modifiers in pediatric liver disease in general and modulate disease progression in children with biliary atresia in particular.

Child↗
PubMed2005

Database mining for pKa prediction.

The acid dissociation constant (pKa) is the key parameter to define the extent of ionization of a drug molecule and is used for ADME properties evaluation via the pH-dependent distribution coefficient, logD. We present a method for pKa prediction using a predefined reference database and structural fingerprints based on a multilevel neighborhoods description of the ionizable atom(s). This database mining approach is suitable for screening large compound collections for HTS compound prioritization and external compound acquisition. In addition to pKa prediction it provides medicinal chemists rapid access to already available pKa measurements and hints for manipulating the chemical structure to increase or decrease pKa.

Chemical Phenomena↗
PubMed2003

Variation at 16 STR loci in Rwandans (Hutu) and implications on profile frequency estimation in Bantu-speakers.

A data set of 16 autosomal STRs (the 13 CODIS loci plus HumCD4, HumFES, HumF13A1) was obtained in a sample of 52 unrelated Hutus from Rwanda. Genotypes at all loci met Hardy-Weinberg expectations with the exception of HumCSF1PO. No significant evidence of association across alleles at independent loci was obtained. Statistical parameters demonstrated the forensic usefulness of the analysed systems (combined PE=0.9999996, combined PD=1:2.27 x 10(18)). Pairwise comparisons showed that the Hutu gene pool differs substantially from that of other Bantu-speaking populations suggesting the use of ethnic-specific population databases in forensic casework analysis. The introduction of a non-negligible bias was confirmed by calculating the differences between multiple-locus profile frequencies of western and eastern Bantoids using local and non-local reference databases.

Alleles↗
PubMed2005

Assessment of hepatotoxic liabilities by transcript profiling.

Male Wistar rats were treated with various model compounds or the appropriate vehicle controls in order to create a reference database for toxicogenomics assessment of novel compounds. Hepatotoxic compounds in the database were either known hepatotoxicants or showed hepatotoxicity during preclinical testing. Histopathology and clinical chemistry data were used to anchor the transcript profiles to an established endpoint (steatosis, cholestasis, direct acting, peroxisomal proliferation or nontoxic/control). These reference data were analyzed using a supervised learning method (support vector machines, SVM) to generate classification rules. This predictive model was subsequently used to assess compounds with regard to a potential hepatotoxic liability. A steatotic and a non-hepatotoxic 5HT(6) receptor antagonist compound from the same series were successfully discriminated by this toxicogenomics model. Additionally, an example is shown where a hepatotoxic liability was correctly recognized in the absence of pathological findings. In vitro experiments and a dog study confirmed the correctness of the toxicogenomics alert. Another interesting observation was that transcript profiles indicate toxicologically relevant changes at an earlier timepoint than routinely used methods. Together, these results support the useful application of toxicogenomics in raising alerts for adverse effects and generating mechanistic hypotheses that can be followed up by confirmatory experiments.

Animals↗
PubMed2002

Surgical procedure logging with use of a hand-held computer.

OBJECTIVE: To evaluate the feasibility of incorporating hand-held computing technology in a surgical residency program, by means of hand-held devices for surgical procedure logging linked through the Internet to a central database. SETTING: Division of General Surgery, University of Toronto. DESIGN: A survey of general surgery residents. METHODS: The 69 residents in the general surgery training program received hand-held computers with preinstalled medical programs and a program designed for surgical procedure logging. Procedural data were uploaded via the Internet to a central database. Survey data were collected regarding previous computer use as well as previous procedure logging methods. MAIN OUTCOME MEASURE: Utilization of the procedure logging system. RESULTS: After a 5-month pilot period, 38% of surgical residents were using the procedure-logging program successfully and on a regular basis. Program use was higher among more junior trainees. Analysis of the database provided valuable information on individual trainees, hospital programs and supervising surgeons, data that would assist in program development. CONCLUSIONS: Hand-held devices can be implemented in a large division of general surgery to provide a reference database and a procedure-logging platform. However, user acceptance is not uniform and continued training and support are necessary to increase acceptance. The procedure database provides important information for optimizing trainees' educational experience.

Attitude to Computers↗
PubMed2004

Utility of the Y-STR typing systems Y-PLEX 6 and Y-PLEX 5 in forensic casework and 11 Y-STR haplotype database for three major population groups in the United States.

The Y-PLEX 6 and Y-PLEX 5 systems enable analysis for 11 Y-STR loci. We present here the utility of these systems in forensic casework. A total of 188 samples, including 127 evidence samples, were analyzed using either or both of the systems. The evidence sample types included fingernail scrapings, sperm or seminal fluid, epithelial cells, blood and other tissues. The Y-STR typing systems provided useful probative results in difficult cases. A reference database for Caucasian (n = 517), African American (n = 535), and Hispanic (n = 245) population groups within the United States was generated for estimating the haplotype frequency in forensic casework. Among the individuals profiled, 311 Caucasians, 412 African Americans, and 194 Hispanics provided unique profiles in their respective population datasets. This is the first report describing the haplotype database for the set of 11 Y-STR loci recommended by the Scientific Working Group on DNA Analysis Methods (SWGDAM). Linkage analysis reveals that the frequencies from forensically important autosomal loci can be multiplied with the Y-STR haplotype frequency. The results from Y-PLEX systems have been accepted in courts in the United States.

Chromosomes, Human, Y↗
PubMed2000

Information systems: the key to evidence-based health practice.

Increasing prominence is being given to the use of best current evidence in clinical practice and health services and programme management decision-making. The role of information in evidence-based practice (EBP) is discussed, together with questions of how advanced information systems and technology (IS&T) can contribute to the establishment of a broader perspective for EBP. The author examines the development, validation and use of a variety of sources of evidence and knowledge that go beyond the well-established paradigm of research, clinical trials, and systematic literature review. Opportunities and challenges in the implementation and use of IS&T and knowledge management tools are examined for six application areas: reference databases, contextual data, clinical data repositories, administrative data repositories, decision support software, and Internet-based interactive health information and communication. Computerized and telecommunications applications that support EBP follow a hierarchy in which systems, tasks and complexity range from reference retrieval and the processing of relatively routine transactions, to complex "data mining" and rule-driven decision support systems.

Decision Support Systems, Clinical↗
PubMed1995

[Studies on biological indicator values in diagnosis for lead poisoning].

Blood lead levels, urine lead levels, indicators of porphyrin metabolism and other biological indicators were determined in 330 workers exposed to lead and 100 unexposed controls with national standardized methods for quality assurance. Data were analyzed with modern statistical methods in a microcomputer with SAS software. Criteria values for blood lead and urine lead were formulated with curve fitting and discriminant analysis, and local normal upper limit values were 1.43 and 0.25 mumol/L for blood lead and urine lead, respectively, acceptable upper limit values 1.93 and 0.35 mumol/L, respectively, and diagnostic values for poisoning 3.02 and 0.56 mumol/L, respectively. Correlation between workplace air lead concentrations and biological indicators, between blood lead levels and other indicators, and their specificity, sensitivity, accuracy and underdiagnosis and misdiagnosis were evaluated at the same time to provide a reference database for revising the national diagnostic criteria for lead poisoning.

Adult↗