Double cross-validation and improved sensitivity of the rapid screen of mild traumatic brain injury

This study aimed to replicate and cross-validate the Rapid Screen of Concussion (RSC) for diagnosing mild TBI (mTBI). One hundred (81 male, 19 female) cases of mTBI and 35 (23 male and 12 female) cases of orthopaedic injuries were tested within 24 hr of injury. Double cross-validation was used to examine whether total RSC scores obtained in the cur-rent sample, generalised to one previously reported. In the new sample, mTBI patients answered fewer orientation questions, recalled fewer words on the learning trial and after a delay, judged fewer sentences in 2 min, and completed fewer symbols in the Digit Symbol Substitution Test than orthopaedic controls. The formulae and cut-offs developed on the original and new samples produced similar sensitivity and overall correct classification rates. Inclusion of the Digit Symbol Substitution Test performance of the new sample improved the sensitivity (80.2%) and specificity (82.6%) in males. It did not improve the correct classification rate in females, which was 89.5% sensitivity and 91.7% specificity before the inclusion of the Digit Symbol Substitution Test. Taken together, these results indicate that a combined score on this 12-min screen yields a measure of level of brain impairment up to 24 hr after mTBI.

Customised birthweight: Coefficients for an Australian population and validation of the model

Background: Published birthweight references in Australia do not fully take into account constitutional factors that influence birthweight and therefore may not provide an accurate reference to identify the infant with abnormal growth. Furthermore, studies in other regions that have derived adjusted (customised) birthweight references have applied untested assumptions in the statistical modelling. Aims: To validate the customised birthweight model and to produce a reference set of coefficients for estimating a customised birthweight that may be useful for maternity care in Australia and for future research. Methods: De-identified data were extracted from the clinical database for all births at the Mater Mother's Hospital, Brisbane, Australia, between January 1997 and June 2005. Births with missing data for the variables under study were excluded. In addition the following were excluded: multiple pregnancies, births less than 37 completed week's gestation, stillbirths, and major congenital abnormalities. Multivariate analysis was undertaken. A double cross-validation procedure was used to validate the model. Results: The study of 42 206 births demonstrated that, for statistical purposes, birthweight is normally distributed. Coefficients for the derivation of customised birthweight in an Australian population were developed and the statistical model is demonstrably robust. Conclusions: This study provides empirical data as to the robustness of the model to determine customised birthweight. Further research is required to define where normal physiology ends and pathology begins, and which segments of the population should be included in the construction of a customised birthweight standard.

Impact of ethnicity upon body composition assessment in Sri Lankan Australian children

Objectives: Obesity is a disease with excess body fat where health is adversely affected. Therefore it is prudent to make the diagnosis of obesity based on the measure of percentage body fat. Body composition of a group of Australian children of Sri Lankan origin were studied to evaluate the applicability of some bedside techniques in the measurement of percentage body fat. Methods: Height (H) and weight (W) was measured and BMI (W/H-2) calculated. Bioelectrical impedance analysis (BIA) was measured using tetra polar technique with an 800 mu A current of 50 Hz frequency. Total body water was used as a reference method and was determined by deuterium dilution and fat free mass and hence fat mass (FM) derived using age and gender specific constants. Percentage FM was estimated using four predictive equations, which used BIA and anthropometric measurements. Results: Twenty-seven boys and 15 girls were studied with mean ages being 9.1 years and 9.6 years, respectively. Girls had a significantly higher FM compared to boys. The mean percentage FM of boys (22.9 +/- 8.7%) was higher than the limit for obesity and for girls (29.0 +/- 6.0%) it was just below the cut-off. BMI was comparatively low. All but BIA equation in boys under estimated the percentage FM. The impedance index and weight showed a strong association with total body water (r(2)= 0.96, P < 0.001). Except for BIA in boys all other techniques under diagnosed obesity. Conclusions: Sri Lankan Australian children appear to have a high percentage of fat with a low BMI and some of the available indirect techniques are not helpful in the assessment of body composition. Therefore ethnic and/or population specific predictive equations have to be developed for the assessment of body composition, especially in a multicultural society using indirect methods such as BIA or anthropometry.

Predicting functional capacity outcome 12 months after hospitalized injury

Background: There is a recognized need to move from mortality to morbidity outcome predictions following traumatic injury. However, there are few morbidity outcome prediction scoring methods and these fail to incorporate important comorbidities or cofactors. This study aims to develop and evaluate a method that includes such variables. Methods: This was a consecutive case series registered in the Queensland Trauma Registry that consented to a prospective 12-month telephone conducted follow-up study. A multivariable statistical model was developed relating Trauma Registry data to trichotomized 12-month post-injury outcome (categories: no limitations, minor limitations and major limitations). Cross-validation techniques using successive single hold-out samples were then conducted to evaluate the model's predictive capabilities. Results: In total, 619 participated, with 337 (54%) experiencing no limitations, 101 (16%) experiencing minor limitations and 181 (29%) experiencing major limitations 12 months after injury. The final parsimonious multivariable statistical model included whether the injury was in the lower extremity body region, injury severity, age, length of hospital stay, pulse at admission and whether the participant was admitted to an intensive care unit. This model explained 21% of the variability in post-injury outcome. Predictively, 64% of those with no limitations, 18% of those with minor limitations and 37% of those with major limitations were correctly identified. Conclusion: Although carefully developed, this statistical model lacks the predictive power necessary for its use as a basis of a useful prognostic tool. Further research is required to identify variables other than those routinely used in the Trauma Registry to develop a model with the necessary predictive utility.

Comparison of the reintroduced MEIA (R) assay with HPLC-MS/MS for the determination of whole-blood sirolimus from transplant recipients

Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA (R)) for sirolimus on the IMx (R) analyser has the potential to address this situation. This Study, using patient samples, has compared the MEIA (R) sirolimus method with an established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established HPLC-UV assay was used for independent cross-validation. For quality control materials (5, 11, 22 mu g/L), the MEIA (R) showed acceptable validation criteria based on intra-and inter-run precision (CV) and accuracy (bias) of < 8% and < 13%, respectively. The lower limit of quantitation was found to be approximately 3 mu g/L. The performance of the immunoassay was compared with HPLC-MS/MS using EDTA whole-blood samples obtained from various types of organ transplant recipients (n = 116). The resultant Deming regression line was: MEIA = 1.3 x HPLC-MS/MS+ 1.3 (r = 0.967, s(y/x) = 1) with a mean bias of 49.2% +/- 23.1 % (range, -2.4% to 128%; P < 0.001). The reason for the large and variable bias was not explored in this study, but the sirolimus-metabolite cross-reactivity with the MEIA (R) antibody could be a substantive contributing factor. Whereas the MEIA (R) sirolimus method may be an adjunct to sirolimus dosage individualization in transplant recipients, users must consider the implications of the substantial and variable bias when interpreting results. In selected patients where difficult clinical issues arise, reference to a specific chromatographic method may be required.

Gene expression in human alcoholism: Microarray analysis of frontal cortex

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism. Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays. Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were downregulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression. Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.

A comparison of different choices for the regularization parameter in inverse electrocardiography models

Calculating the potentials on the heart’s epicardial surface from the body surface potentials constitutes one form of inverse problems in electrocardiography (ECG). Since these problems are ill-posed, one approach is to use zero-order Tikhonov regularization, where the squared norms of both the residual and the solution are minimized, with a relative weight determined by the regularization parameter. In this paper, we used three different methods to choose the regularization parameter in the inverse solutions of ECG. The three methods include the L-curve, the generalized cross validation (GCV) and the discrepancy principle (DP). Among them, the GCV method has received less attention in solutions to ECG inverse problems than the other methods. Since the DP approach needs knowledge of norm of noises, we used a model function to estimate the noise. The performance of various methods was compared using a concentric sphere model and a real geometry heart-torso model with a distribution of current dipoles placed inside the heart model as the source. Gaussian measurement noises were added to the body surface potentials. The results show that the three methods all produce good inverse solutions with little noise; but, as the noise increases, the DP approach produces better results than the L-curve and GCV methods, particularly in the real geometry model. Both the GCV and L-curve methods perform well in low to medium noise situations.

Translation and validation of the Chinese version of the Charing Cross Venous Ulcer Questionnaire

No Abstract

Validation of self-reported cigarette smoking in a remote Australian Aboriginal community

Objective: To examine the relationship between self-reported tobacco smoking and urinary cotinine concentrations in the setting of a remote Aboriginal community. Methods: In a remote Northern Territory (NT) Aboriginal community the relationship between self-reported tobacco smoking and urinary cotinine concentrations was examined as part of a cross-sectional survey of cardiovascular risk factors. Current tobacco smoking was assessed as part of a questionnaire. The concentration of cotinine and cotinine/creatinine ratio (CCR) in a spot urine sample were used as a biochemical marker of nicotine exposure. Results: A total of 237 people took part in the survey, although completed questionnaires and urine results were available for 184 people. Current tobacco smoking was reported by 161 (69 [95% Cl 63 to 75]%) people, with higher rates among males (84/104, 81 [95% Cl 72 to 88]%) than females (77/129, 60 [95% Cl 51 to 68]%, p

Validation of assembled nucleic acid-based tests in diagnostic microbiology laboratories

Medical microbiology and virology laboratories use nucleic acid tests (NAT) to detect genomic material of infectious organisms in clinical samples. Laboratories choose to perform assembled (or in-house) NAT if commercial assays are not available or if assembled NAT are more economical or accurate. One reason commercial assays are more expensive is because extensive validation is necessary before the kit is marketed, as manufacturers must accept liability for the performance of their assays, assuming their instructions are followed. On the other hand, it is a particular laboratory's responsibility to validate an assembled NAT prior to using it for testing and reporting results on human samples. There are few published guidelines for the validation of assembled NAT. One procedure that laboratories can use to establish a validation process for an assay is detailed in this document. Before validating a method, laboratories must optimise it and then document the protocol. All instruments must be calibrated and maintained throughout the testing process. The validation process involves a series of steps including: (i) testing of dilution series of positive samples to determine the limits of detection of the assay and their linearity over concentrations to be measured in quantitative NAT; (ii) establishing the day-to-day variation of the assay's performance; (iii) evaluating the sensitivity and specificity of the assay as far as practicable, along with the extent of cross-reactivity with other genomic material; and (iv) assuring the quality of assembled assays using quality control procedures that monitor the performance of reagent batches before introducing new lots of reagent for testing.

Specification and validation of process constraints for flexible workflows

Workflow systems have traditionally focused on the so-called production processes which are characterized by pre-definition, high volume, and repetitiveness. Recently, the deployment of workflow systems in non-traditional domains such as collaborative applications, e-learning and cross-organizational process integration, have put forth new requirements for flexible and dynamic specification. However, this flexibility cannot be offered at the expense of control, a critical requirement of business processes. In this paper, we will present a foundation set of constraints for flexible workflow specification. These constraints are intended to provide an appropriate balance between flexibility and control. The constraint specification framework is based on the concept of pockets of flexibility which allows ad hoc changes and/or building of workflows for highly flexible processes. Basically, our approach is to provide the ability to execute on the basis of a partially specified model, where the full specification of the model is made at runtime, and may be unique to each instance. The verification of dynamically built models is essential. Where as ensuring that the model conforms to specified constraints does not pose great difficulty, ensuring that the constraint set itself does not carry conflicts and redundancy is an interesting and challenging problem. In this paper, we will provide a discussion on both the static and dynamic verification aspects. We will also briefly present Chameleon, a prototype workflow engine that implements these concepts. (c) 2004 Elsevier Ltd. All rights reserved.