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Internet teleconferencing method for telepathology consultations from lung and heart transplant patients.

Current Internet-based teleconferencing techniques allow a referring pathologist to transmit real-time images from a microscope to a consultant, while maintaining a verbal conversation using Internet telephony. In our study, 50 randomly selected transbronchial biopsies from lung allograft recipients and 58 randomly selected endomyocardial biopsies from heart transplant patients were diagnosed by consultant pathologists using Internet-based teleconferencing methods. The referring pathologists acquired the real-time video images from the biopsies using a light microscope equipped with a phototube adapter and a video camera. The consultant pathologists viewed the processed images on a video monitor at 800 x 600 resolution, using a standard microcomputer equipped with Netmeeting software, and directed the referring pathologist to move the slide under the microscopy and/or change image magnification. The validity of telepathology diagnoses was assessed with kappa coefficients. Consultations were completed in 5 to 15 minutes per case. Sound transmission was unreliable, and in approximately 25% of consultations the referring pathologist needed to "call back" to reestablish verbal communication. In all but 2 transbronchial biopsies there was agreement between the original diagnosis and the diagnosis by telepathology (kappa = 0.92). In 48 of 58 endomyocardial biopsies there was concordance between the 2 diagnoses (kappa = 0.692). Only 3 out of 10 of these discrepancies were clinically significant (kappa = 0.897). Internet-based teleconferencing techniques provide effective and relatively inexpensive tools for real time telepathology consultations. The technology is probably best suited for the study of small specimens from patients that require rapid diagnosis by a consultant.

Biopsy↗

Tonal vocalizations in a noisy environment: an approach to their semi-automatic analysis and examples of its application.

Vocalizations with an emphasized fundamental are common in many species of animals. Such calls can presumably be sufficiently described by measures of their fundamental shape or 'contour'. Here we describe a software we developed to analyze such vocalizations semi-automatically. The software is particularly designed to cope with vocalizations recorded in a noisy environment. Some of the algorithms implemented (e.g. signal detection, contour detection, contour measurement, validation) and some preliminary applications dealing with calls of different species of birds are presented. Finally, we briefly discuss the possible significance of such vocalizations.

Animals↗

Adverse effects of environmental noise on acoustic voice quality measurements.

An accurate analysis of voice quality is imperative when using acoustic measurements to diagnose vocal pathologies. It is known that noise has a significant effect on the reliability and validity of acoustic voice measurements, but the precise relationship has not been established. The purpose of this study was to investigate the influence of noise on the accuracy, reliability, and validity of acoustic voice quality measurements while balancing for gender, age, intersubject and intrasubject variability, microphones, computer hardware, analysis software, and type of noise. Level of noise was precisely controlled. The specific focus of interest was to determine the critical levels of noise that can invalidate voice quality measurements and to generate practical recommendations. Results suggest that the recommended, acceptable, and unacceptable levels of noise in the acoustic environment are above 42 dB, above 30 dB, and below 30 dB signal-to-noise ratio, respectively.

Acoustics↗

Analysis of finite element models for head injury investigation: reconstruction of four real-world impacts.

Previous studies have shown that both excessive linear and rotational accelerations are the cause of head injuries. Although the head injury criterion has been beneficial as an indicator of head injury risk, it only considers linear acceleration, so there is a need to consider both types of motion in future safety standards. Advanced models of the head/brain complex have recently been developed to gain a better understanding of head injury biomechanics. While these models have been verified against laboratory experimental data, there is a lack of suitable real-world data available for validation. Hence, using two computer models of the head/brain, the objective of the current study was to reconstruct four real-world crashes with known head injury outcomes in a full-vehicle crash laboratory, simulate head/brain responses using kinematics obtained during these reconstructions, and to compare the results predicted by the models against the actual injuries sustained by the occupant. Cases where the occupant sustained no head injuries (AIS 0) and head injuries of severity AIS 4, AIS 5, and multiple head injuries were selected. Data collected from a 9-accelerometer skull were input into the Wayne State University Head Injury Model (WSUHIM) and the NHTSA Simulated Injury Monitor (SIMon). The results demonstrated that both models were able to predict varying injury severities consistent with the difference in AIS injury levels in the real-world cases. The WSUHIM predicted a slightly higher injury threshold than the SIMon, probably due to the finer mesh and different software used for the simulations, and could also determine regions of the brain which had been injured. With further validation, finite element models can be used to establish an injury criterion for each type of brain injury in the future.

Journal Article↗

Evaluation of new software for angiographic determination of right ventricular volumes.

OBJECTIVES: The scope of the study was to evaluate a recent software for angiographic volume determination as compared to cardiovascular magnetic resonance imaging. BACKGROUND: A new right ventricular analysis software closes a diagnostic gap in quantitative angiography. Cardiovascular magnetic resonance imaging short axis multi slice summation is a validated reference standard. METHODS: Right ventricular angiograms were acquired in frontal and lateral projection in 15 pediatric and 17 adult patients. Additional angiograms were acquired in RAO30 degrees /LAO60 degrees projections in 10 adult patients. The tested models comprised area length with different regressions, multi-slice with different regressions, Boak, and pyramid method. Original regressions were used to calculate angiographic right ventricular volume. Right ventricular reference volumes were determined by multi-slice summation from cardiac magnetic resonance short-axis images. RESULTS: Mean inter-observer difference was -1 ml (95% confidence: -35-34 ml) and mean intra-observer difference was 0 ml (95% confidence: -22-22 ml). There was no significant difference (4 ml, 95% confidence: -22-30 ml) between geometric calibration and calibration by a sphere. The area length and multi-slice models demonstrated the best agreement with the cardiac magnetic resonance reference. Performance was best for the Onnasch Lange models. CONCLUSION: The evaluated software provides acceptably accurate volume estimates for the majority of ventricles. In a few cases larger errors may occur, however. The area length and multi-slice models preferably with Onnasch Lange regressions may be recommended. Inter- and intra-observer agreement were excellent. Geometric calibration using data from DICOM header files may be used.

Adolescent↗

Extending the simple linear regression model to account for correlated responses: an introduction to generalized estimating equations and multi-level mixed modelling.

Much of the research in epidemiology and clinical science is based upon longitudinal designs which involve repeated measurements of a variable of interest in each of a series of individuals. Such designs can be very powerful, both statistically and scientifically, because they enable one to study changes within individual subjects over time or under varied conditions. However, this power arises because the repeated measurements tend to be correlated with one another, and this must be taken into proper account at the time of analysis or misleading conclusions may result. Recent advances in statistical theory and in software development mean that studies based upon such designs can now be analysed more easily, in a valid yet flexible manner, using a variety of approaches which include the use of generalized estimating equations, and mixed models which incorporate random effects. This paper provides a particularly simple illustration of the use of these two approaches, taking as a practical example the analysis of a study which examined the response of portable peak expiratory flow meters to changes in true peak expiratory flow in 12 children with asthma. The paper takes the reader through the relevant practicalities of model fitting, interpretation and criticism and demonstrates that, in a simple case such as this, analyses based upon these model-based approaches produce reassuringly similar inferences to standard analyses based upon more conventional methods.

Adolescent↗

Developing a tracking system for coagulation factor concentrates in southern Ontario.

BACKGROUND: In response to the transfusion- transmitted AIDS epidemic, Canadian authorities recommended the development of tracking systems and improved reporting of adverse events. This study describes the development of a verifiable and comprehensive regional tracking system for coagulation factor concentrates. STUDY DESIGN AND METHODS: The Hamilton- Niagara Regional Hemophilia Program received distribution and utilization data from Canadian Blood Services, 26 regional hospitals, and 70 individuals with bleeding disorders on home-based therapy. Purpose-specific software, the Canadian Hemophilia Assessment and Resource Management System (CHARMS), was used to store, monitor, analyze, and validate data. RESULTS: During a 1-year period (2001), all factor concentrates distributed in this region were accounted for. A higher proportion of FVIII and FIX concentrates (88 vs. 12%) was infused at home than in hospitals, and a higher proportion (63 vs. 28%) was used to prevent than to treat bleeds. During a period of shortage, a 5-percent reduction in utilization of both FVIII and FIX concentrates was documented. One recall was managed swiftly and efficiently. Two patients reported allergic skin reactions. CONCLUSION: A verifiable tracking system has been developed that can provide ongoing data for both clinical and administrative purposes. Data collection from patients needs to be made more efficient and real-time recording is an important future objective. Such a system can be instituted locally for less than 1.5 percent of the cost of the factor concentrate used.

Adolescent↗

[Quality of data transfer in perinatal data -- experience of a centre].

BACKGROUND: A sufficient quality of data transfer from written patient records to electronic data processing is a precondition for a reasonable usage of perinatal data. However the quality of data transfer of the almost 200 characteristics routinely recorded at each delivery is largely unknown. MATERIALS AND METHODS: The quality of data transfer of 33 characteristics in 350 randomly selected singleton deliveries of the women's clinic of the University of Marburg from 2002 and 2003 has been checked by comparing electronically recorded data with the original written documents. RESULTS: The quality of data transfer of the tested characteristics turned out to be heterogeneous. Characteristics necessary to calculate quality indicators show a very high data quality when excluding the characteristic attendance of a paediatrician. The quality of data transfer of characteristics denoting time as well as blood gas analysis are heterogeneous. Characteristics with a low quality of data transfer are associated with ambiguous instructions, the fact that the coding obstetrician is not dealing in the first instance with the item being encoded and the characteristics are of no immediate relevance for delivery, as well as difficult application of the software. CONCLUSION: The quality of data transfer of the characteristics collected in perinatal surveys needs to be validated. The type and amount of data being collected should be reassessed considering improvements of data quality.

Documentation↗

Improved classification of mass spectrometry database search results using newer machine learning approaches.

Manual analysis of mass spectrometry data is a current bottleneck in high throughput proteomics. In particular, the need to manually validate the results of mass spectrometry database searching algorithms can be prohibitively time-consuming. Development of software tools that attempt to quantify the confidence in the assignment of a protein or peptide identity to a mass spectrum is an area of active interest. We sought to extend work in this area by investigating the potential of recent machine learning algorithms to improve the accuracy of these approaches and as a flexible framework for accommodating new data features. Specifically we demonstrated the ability of boosting and random forest approaches to improve the discrimination of true hits from false positive identifications in the results of mass spectrometry database search engines compared with thresholding and other machine learning approaches. We accommodated additional attributes obtainable from database search results, including a factor addressing proton mobility. Performance was evaluated using publically available electrospray data and a new collection of MALDI data generated from purified human reference proteins.

Amino Acid Sequence↗

Interpretation systems for genotypic drug resistance of HIV-1.

Genotypic assays are widely used tools for determining human immunodeficiency virus type 1 (HIV-1) drug resistance and for guiding treatment changes in patients failing antiretroviral therapy. Several systems have been developed to interpret the complex influence of key amino acid substitutions of the enzymes targeted by therapy on the phenotypic susceptibility or clinical response to available antiretroviral agents. This overview identifies 21 systems giving an interpretation on how amino acid substitutions affect phenotypic drug susceptibility or clinical activity of anti-HIV-1 agents. There was substantial variability in the mechanisms underlying the interpretations, the nature of the systems, their intended use, the source type of their knowledge base, and their update and output. Most of the systems could be accessed for free on the internet, functioned as rule-based algorithms updated by experts and at least partially based on literature evidence, and offered an automated report through a software. Nevertheless, the rule base was not always clarified. An update of the rules and the clinical validation of the systems are presented to help in the critical evaluation of their possible use. Importantly, only 8 systems were intended for clinical use and 5 of these had at least partially undergone clinical validation.

Anti-HIV Agents↗

HykGene: a hybrid approach for selecting marker genes for phenotype classification using microarray gene expression data.

MOTIVATION: Recent studies have shown that microarray gene expression data are useful for phenotype classification of many diseases. A major problem in this classification is that the number of features (genes) greatly exceeds the number of instances (tissue samples). It has been shown that selecting a small set of informative genes can lead to improved classification accuracy. Many approaches have been proposed for this gene selection problem. Most of the previous gene ranking methods typically select 50-200 top-ranked genes and these genes are often highly correlated. Our goal is to select a small set of non-redundant marker genes that are most relevant for the classification task. RESULTS: To achieve this goal, we developed a novel hybrid approach that combines gene ranking and clustering analysis. In this approach, we first applied feature filtering algorithms to select a set of top-ranked genes, and then applied hierarchical clustering on these genes to generate a dendrogram. Finally, the dendrogram was analyzed by a sweep-line algorithm and marker genes are selected by collapsing dense clusters. Empirical study using three public datasets shows that our approach is capable of selecting relatively few marker genes while offering the same or better leave-one-out cross-validation accuracy compared with approaches that use top-ranked genes directly for classification. AVAILABILITY: The HykGene software is freely available at http://www.cs.dartmouth.edu/~wyh/software.htm CONTACT: wyh@cs.dartmouth.edu SUPPLEMENTARY INFORMATION: Supplementary material is available from http://www.cs.dartmouth.edu/~wyh/hykgene/supplement/index.htm.

Algorithms↗

A quantitative determination of multi-protein interactions by the analysis of confocal images using a pixel-by-pixel assessment algorithm.

MOTIVATION: Recent advances in confocal microscopy have allowed scientists to assess the expression, and to some extent, the interaction/colocalization of multiple molecules within cells and tissues. In some instances, accurately quantifying the colocalization of two or more proteins may be critical. This can require the acquisition of multiple Z plane images (Z stacks) throughout a specimen and, as such, we report here the successful development of a freeware, open-source image analysis tool, IMAJIN_COLOC, developed in PERL (v. 5.8, build 806), using the PERLMagick libraries (ImageMagick). Using a pixel-by-pixel analysis algorithm, IMAJIN_COLOC can analyze images for antigen expression (any number of colors) and can measure all possible combinations of colocalization for up to three colors by analyzing a Z stack gallery acquired for each sample. The simultaneous (i.e. in a single pass) analysis of three-color colocalization, and batch analysis capabilities are distinctive features of this program. RESULTS: A control image, containing known individual and colocalized pixel counts, was used to validate the accuracy of IMAJIN_COLOC. As further validation, pixel counts and colocalization values from the control image were compared to those obtained with the software packaged with the Zeiss laser-scanning microscope (LSM AIM, version 3.2). The values from both programs were found to be identical. To demonstrate the applicability of this program in addressing novel biological questions, we examined the role of neurons in eliciting an immune reaction in response to viral infection. Specifically, we successfully examined expression of the chemokine RANTES in measles virus (MV) infected hippocampal neurons and quantified changes in RANTES production throughout the disease period. The resultant quantitative data were also evaluated visually, using a gif image created during the analysis. AVAILABILITY: PERL (ActivePerl, version 5.8) is available at activestate.com; the PERLMagick libraries are available at imagemagick.org, and IMAJIN_COLOC, the source code and user documentation can be downloaded from http://www.fda.gov/cber/research/imaging/imageanalysis.htm.

Algorithms↗

Proteomics uncovers ICAM2 (CD102) as a novel serum biomarker of proliferative lupus nephritis.

OBJECTIVES: This study aimed to identify novel, non-invasive biomarkers for lupus nephritis (LN) through serum proteomics. METHODS: Serum proteins were detected in patients with LN and healthy control (HC) groups through liquid chromatography-tandem mass spectrometry. The key networks associated with LN were screened out using Cytoscape software, followed by pathway enrichment analysis. The best candidate biomarkers were selected by machine learning models, further validated in a larger independent cohort. Finally, the expression of these candidate markers was verified in kidney tissue samples, and the mechanism was explored by knocking down the expression of intercellular adhesion molecule 2 (ICAM2) through in vitro cell transfection with siRNA. RESULTS: Following the serum proteomic screening of LN, a key network of 20 proteins was identified. Machine learning models were used to select ICAM2 (CD102), metalloproteinase inhibitor 1 (TIMP1) and thrombospondin 1 (THSB1) for validation in independent cohorts. ICAM2 exhibited the highest area under the curve (AUC) value in distinguishing LN from HC (AUC=0.92) and was significantly correlated with activity index, proteinuria, albumin and anti-dsDNA antibody levels. Particularly, ICAM2 was significantly elevated in proliferative LN and was associated with specific pathological attributes, outperforming conventional parameters in distinguishing proliferative LN from non-proliferative LN. ICAM2 expression was also elevated in renal tissue samples from patients with proliferative LN. In vitro, knockdown of ICAM2 expression can inhibit the activation of the PI3K/Akt pathway and alleviate the injury of glomerular endothelial cells. CONCLUSION: ICAM2 (CD102) may serve as a potential serum biomarker for proliferative LN that reflects renal pathology activity, potentially contributing to the progression of LN through the PI3K/Akt pathway.

Humans↗

A haplotype-based test of association using data from cohort and nested case-control epidemiologic studies.

Haplotype-based risk models can lead to powerful methods for detecting the association of a disease with a genomic region of interest. In population-based studies of unrelated individuals, however, the haplotype status of some subjects may not be discernible without ambiguity from available locus-specific genotype data. A score test for detecting haplotype-based association using genotype data has been developed in the context of generalized linear models for analysis of data from cross-sectional and retrospective studies. In this article, we develop a test for association using genotype data from cohort and nested case-control studies where subjects are prospectively followed until disease incidence or censoring (end of follow-up) occurs. Assuming a proportional hazard model for the haplotype effects, we derive an induced hazard function of the disease given the genotype data, and hence propose a test statistic based on the associated partial likelihood. The proposed test procedure can account for differential follow-up of subjects, can adjust for possibly time-dependent environmental co-factors and can make efficient use of valuable age-at-onset information that is available on cases. We provide an algorithm for computing the test statistic using readily available statistical software. Utilizing simulated data in the context of two genomic regions GPX1 and GPX3, we evaluate the validity of the proposed test for small sample sizes and study its power in the presence and absence of missing genotype data.

Algorithms↗

Evaluation of an ambulatory system for the quantification of cough frequency in patients with chronic obstructive pulmonary disease.

BACKGROUND: To date, methods used to assess cough have been primarily subjective, and only broadly reflect the impact of chronic cough and/or chronic cough therapies on quality of life. Objective assessment of cough has been attempted, but early techniques were neither ambulatory nor feasible for long-term data collection. We evaluated a novel ambulatory cardio-respiratory monitoring system with an integrated unidirectional, contact microphone, and report here the results from a study of patients with COPD who were videotaped in a quasi-controlled environment for 24 continuous hours while wearing the ambulatory system. METHODS: Eight patients with a documented history of COPD with ten or more years of smoking (6 women; age 57.4 +/- 11.8 yrs.; percent predicted FEV1 49.6 +/- 13.7%) who complained of cough were evaluated in a clinical research unit equipped with video and sound recording capabilities. All patients wore the LifeShirt system (LS) while undergoing simultaneous video (with sound) surveillance. Video data were visually inspected and annotated to indicate all cough events. Raw physiologic data records were visually inspected by technicians who remained blinded to the video data. Cough events from LS were analyzed quantitatively with a specialized software algorithm to identify cough. The output of the software algorithm was compared to video records on a per event basis in order to determine the validity of the LS system to detect cough in COPD patients. RESULTS: Video surveillance identified a total of 3,645 coughs, while LS identified 3,363 coughs during the same period. The median cough rate per patient was 21.3 coughs.hr-1 (Range: 10.1 cghs.hr(-1) - 59.9 cghs.hr(-1)). The overall accuracy of the LS system was 99.0%. Overall sensitivity and specificity of LS, when compared to video surveillance, were 0.781 and 0.996, respectively, while positive- and negative-predictive values were 0.846 and 0.994. There was very good agreement between the LS system and video (kappa = 0.807). CONCLUSION: The LS system demonstrated a high level of accuracy and agreement when compared to video surveillance for the measurement of cough in patients with COPD.

Journal Article↗

Individualising aminoglycoside dosage regimens after therapeutic drug monitoring: simple or complex pharmacokinetic methods?

Measurements of aminoglycoside concentration in serum are used to individualise dosage regimens (dose per administration and/or administration interval) with the goal of attaining the desired therapeutic range as quickly as possible. Therapeutic range is defined in terms of peak concentration (to monitor effectiveness) and trough concentration (to avoid toxicity). This article focuses on methods to individualise aminoglycoside dosage regimens in the context of extended dosage intervals. Simple pharmacokinetic methods involve linear dosage adjustment based on peak or trough concentrations or area under the concentration-time curve, or nomograms. The once daily aminoglycoside nomogram determines the dosage interval for aminoglycosides given as a fixed dose per administration, based on a single concentration measurement drawn 6 to 14 hours after the start of the first infusion. This is a preferred method because of its simplicity, strong pharmacodynamic rationale and prospective validation in a large population. However, it does not work when the fixed dose assumed is not relevant, for example for patients with burns, cystic fibrosis, ascites or pregnancy. Furthermore, it has not been validated in children. In these cases, a more sophisticated method is required. Complex pharmacokinetic methods require dedicated software. Non-Bayesian least-squares methods allow the optimisation of both the dose and the dosage interval, but require aminoglycoside concentrations from two or more samples taken in the post-distributive phase during a single dosage interval. With Bayesian least-squares methods, only one concentration measurement is required, although any number of samples can be taken into account. In the Bayesian maximum a posteriori (MAP) method, the parameter estimates are taken as the values corresponding to the maximum of the posterior density. In 'full' Bayesian approaches (also called stochastic control), all the information about the parameters revealed by the posterior distribution is taken into account, and the optimal regimen is found by minimising the expected value of the weighted sum of squared deviations between predicted and target concentrations. If the population model is reasonably well known, Bayesian methods (MAP or stochastic control) should be used because of their good predictive performance. Although only one concentration measurement is required, better precision is afforded by a two-sample strategy, preferably drawn 1 and 6 hours after the start of the first infusion. If the population model is not known, then the non-Bayesian least-squares method is the method of choice, because of its robustness and lack of requirement for prior information about the distribution of parameters in the population.

Aminoglycosides↗

[Study on factors affecting the quality of life to cancer patients at the community level in Shanghai].

OBJECTIVE: A survey on cancer patients at the community level in Shanghai was performed, in order to study the factors affecting the quality of life (QOL) on them. METHODS: To evaluate the QOL of cancer patients, self-administered Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and personal interview methods were used. Data analysis was performed by SPSS software (SPSS,Chicago, IL), including one-way ANOVA and linear regression methods. RESULTS: There were 7580 valid questionnaires retrieved. Many factors were certificated to have significant relationship with QOL of cancer patients,such as family incomes, education, occupation, awareness of disease, physical exercise, cost of health care and pain (P < 0.01). Some factors however, only affecting certain aspects of the QOL, of which age, marriage state, type of tumor and stage were also noticed. KPS had strong Linear correlation with every aspect of FACT-G (P < 0.000). CONCLUSION: Patients having a poor KPS, metastasis, low educational level, divorced or lost of spouse, pain, poor income, little exercise and old age would tend to have a poor QOL outcome.

Adult↗