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TB tools to tell the tale-molecular genetic methods for mycobacterial research.

In spite of the availability of drugs and a vaccine, tuberculosis--one of man's medical nemeses--remains a formidable public health problem, particularly in the developing world. The persistent nature of the tubercle bacillus, with one third of the world's population is estimated to be infected, combined with the emergence of multi drug-resistant strains and the exquisite susceptibility of HIV-positive individuals, has underscored the urgent need for in-depth study of the biology of Mycobacterium tuberculosis address the resurgence of TB. In aiming to understand the mechanisms by which mycobacteria react to their immediate environments, molecular genetic tools have been developed from naturally occurring genetic elements. These include protein expressing genes, and episomal and integrating elements, which have been derived mainly from prokaryotic but also from eukaryotic organisms. Molecular genetic tools that had been established as routine procedures in other prokaryotic genera were thus mimicked. Knowledge of the underlying mechanisms greatly expedited the harnessing of these elements for mycobacteriological research and has brought us to a point where these molecular genetic tools are now employed routinely in laboratories worldwide.

DNA Replication↗

Entity grammar systems: a grammatical tool for studying the hierarchical structures of biological systems.

The hierarchical structures of biological systems are the typical complex hierarchical dynamical structures in the physical world, the effective investigations on which could not be performed with the existing formal grammar systems. To meet the needs of the investigation on these kinds of systems, especially the emerging field of system biology, a grammatical tool was proposed in the present article. Because the grammatical tool mainly deals with the systems composed of structured entities, they are called entity grammar systems (EGSs). The structure of entities in EGSs have the general form of the objects in the physical world, which means EGSs could be used as a tool to study the complex system composed of many objects with different structures, just like the biological systems. The article contains the formal definition of EGSs and the hierarchy of EGSs, which is congruent with the Chomsky hierarchy. The relationship between EGSs and array grammar systems, graph grammar systems, tree grammar systems, multi-set grammar systems are discussed to show the generative power of EGSs. At the end of the present article, the steps to define new grammar systems with the form of EGS are provided and the possible applicable fields of EGSs are discussed.

Linguistics↗

Solid-phase chemical tools for glycobiology.

Techniques involving solid supports have played crucial roles in the development of genomics, proteomics, and in molecular biology in general. Similarly, methods for immobilization or attachment to surfaces and resins have become ubiquitous in sequencing, synthesis, analysis, and screening of oligonucleotides, peptides, and proteins. However, solid-phase tools have been employed to a much lesser extent in glycobiology and glycomics. This review provides a comprehensive overview of solid-phase chemical tools for glycobiology including methodologies and applications. We provide a broad perspective of different approaches, including some well-established ones, such as immobilization in microtiter plates and to cross-linked polymers. Emerging areas such as glycan microarrays and glycan sequencing, quantum dots, and gold nanoparticles for nanobioscience applications are also discussed. The applications reviewed here include enzymology, immunology, elucidation of biosynthesis, and systems biology, as well as first steps toward solid-supported sequencing. From these methods and applications emerge a general vision for the use of solid-phase chemical tools in glycobiology.

Adsorption↗

The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures.

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

Clinical Competence↗

Informatics tools to improve clinical research study implementation.

BACKGROUND: There are numerous potential sources of problems when performing complex clinical research trials. These issues are compounded when studies are multi-site and multiple personnel from different sites are responsible for varying actions from case report form design to primary data collection and data entry. METHODS: We describe an approach that emphasizes the use of a variety of informatics tools that can facilitate study coordination, training, data checks and early identification and correction of faulty procedures and data problems. The paper focuses on informatics tools that can help in case report form design, procedures and training and data management. CONCLUSION: Informatics tools can be used to facilitate study coordination and implementation of clinical research trials.

Clinical Trials as Topic↗

Characterisation of stationary phases in subcritical fluid chromatography by the solvation parameter model. II. Comparison tools.

This study is an investigation of numerical and graphical tools for the comparison of the chromatographic stationary phases previously characterized with the solvation parameter model [C. West, E. Lesellier, J. Chromatogr. A, in press]. Numerous methods are presented and discussed: the coefficient ratio comparison, principal component analysis (PCA) and calculation of the distance. The coefficient ratio comparison allows to estimate the weight of a particular type of interaction relative to dispersive interactions, but is not practical when a lot of chromatographic systems need to be compared. The principal component analysis is mainly used to reduce the set of correlated variables, but is not useful for non correlated variables such as the solvation parameters. The distance calculation is an interesting tool to measure the differences between two systems but suffers from a confusion between two notions: the difference in the type of interactions involved in the chromatographic system and the intensity of these interactions. Finally, we chose to associate each stationary phase to a vector in a five-dimensional space, according to a method proposed by Ishihama and Asakawa [Y. Ishihama, N. Asakawa, J. Pharm. Sci., 88(12) (1999) 1305] for the comparison of lipophilicity scales. Thus, the angles between the different vectors are used to compare the selectivities of the stationary phases, and the lengths of the vectors are used to compare the relative intensities of the interactions. This method was applied to different alkyl phases characterized in subcritical fluid chromatography (SubFC). The angle values are well suited to the description of the differences in chromatographic behaviour. As expected, a small angle value is obtained between C8, C12 and C18, when a greater one is noticed between C4 and the longer chain length alkyl bonded phases, showing the different acidity and basicity of the C4 phase. Moreover, a satisfactory correlation is obtained between the length of the vectors and the carbon number of the alkyl chain. The differences between classical alkyl-bonded silica phases and polar-embedded alkyl-bonded phases or fluorinated phases are also conveniently evidenced. Finally, graphical tools are investigated and a new type of representation, based in part on a radar plot, is proposed. This plot allows the comparison of stationary phases without reducing the number of studied variables. The comparisons based on this method are consistent with the observed chromatographic behaviour of the phases compared.

Adsorption↗

A new model validation tool using kernel regression and density estimation.

In physiological system modelling for control or decision support, model validation is a critical element. A nonparametric approach for assessing the validity of deterministic dynamic models against empirical data is developed, based on kernel regression and kernel density estimation, yielding visual graphical assessment tools as well as numerical metrics of compatibility between the model and the data. Nonparametric regression has been suggested for assessing a parametric statistical model by constructing a confidence band for the proposed model and then checking whether the nonparametric regression curve lies within the band. However, for deterministic models, there is no confidence band that can be constructed. A reversal of roles is therefore suggested--construct a probability band for the nonparametric regression curve and check whether the proposed model lies within the band. This approach extends the utility of nonparametric regression for model assessment to deterministic models. Weighted kernel density estimation is incorporated to derive a density profile for the regression curve, creating a local graphical validation tool. In addition, the density profile is used to define and compute two numerical measures--average normalized density (AND) and relative average normalized density (RAND), representing global statistical validity measures. These tools are demonstrated using a biomedical system model for agitation-sedation and sedation management control.

Humans↗

Finite element-based probabilistic analysis tool for orthopaedic applications.

Orthopaedic implants, as well as other physical systems, contain inherent variability in geometry, material properties, component alignment, and loading conditions. While complex, deterministic finite element (FE) models do not account for the potential impact of variability on performance, probabilistic studies have typically predicted behavior from simplified FE models to achieve practical solution times. The objective of this research was to develop an efficient and versatile probabilistic FE tool to quantify the effect of uncertainty in the design variables on the performance of orthopaedic components under relevant conditions. Key aspects of the computational tool developed include parametric and automated FE model creation for changes in dimensional variables, efficient solution using the advanced mean-value (AMV) reliability method, and identification of the most significant design variables. Two orthopaedic applications are presented to demonstrate the ability of the computational tool to efficiently and accurately represent component performance.

Finite Element Analysis↗

Specially adapted interactive tools for an improved 3D-segmentation of the spine.

For imaging purposes of the spine, segmented image data provides the basis for a variety of modern clinical applications. However, the anatomical complex structure of the spine as well as the extensive degenerative bony deformations apparent in the clinical situation, generally complicate the application of a fully automated segmentation. To serve the special needs for image segmentation of the spine anatomy a newly developed software system is presented, that implements specially adapted interactive tools, taking its 'axis'-skeletal structure into account. A standardized protocol combines the newly developed interactive tools (rotation transformation, warped dissection plane) with standard segmentation tools to provide both a fast and accurate segmentation procedure. The introduced software environment has been valuable for the segmentation of cervical, thoracic and lumbar spines segments based on clinical routine and research images.

Computers↗

Accuracy evaluation of image registration and segmentation tools used in conformal treatment planning of prostate cancer.

Segmentation and registration tools are commonly used in radiotherapy for target and at risk organs localisation. In this work the performances of three different segmentation tools and of a surface matching registration technique, used on computed tomography (CT) and magnetic resonance (MR) images for the treatment planning of conformal prostate carcinoma, are studied. The accuracy of the segmentation and registration tools was evaluated by phantom experiment and on patient data, respectively. A preliminary estimate of MR image distortion was also performed.

Humans↗

The neural origins and implications of imitation, mirror neurons and tool use.

Several recent studies report how laboratory-raised, non-human primates exposed to tool use can exhibit intelligent behaviors, such as imitation and reference vocal control, that are never seen in their wild counterparts. Tool-use training appears to forge a novel cortico-cortical connection that underlies this boost in capacity, which normally exists only as latent potential in lower primates. Although tool-use training is patently non-naturalistic, its marked effects on brain organization and behavior could shed light on the evolution of higher intelligence in humans.

Animals↗

Computer tools to assist the monitoring of outcomes in surgery.

OBJECTIVE: In recent years, there has been increasing use of analytical and graphical methods to assist the monitoring of outcomes in adult cardiac surgery. In this paper, we present extensions to the basic VLAD methodology that add flexibility and assist in its interpretation. METHODS: Using techniques from probability theory, we have devised graphical tools whereby deviations from expected outcomes can be monitored to see how likely they are to have occurred by chance. The methods are based upon pre-operative assessments of risk and use exact analytical techniques. RESULTS: These tools allow deviations from expected outcomes to be readily assessed and compared with the distribution of chance outcomes. Appropriate colour coding allows interpretation in terms of a temperature gradient. CONCLUSIONS: Exact analysis methods based on the use of pre-operative risk assessment provide a useful means for assisting the interpretation of VLAD charts. Such analysis has the advantage that it is applicable even for relatively short series of operations. Also, it takes specific account of the heterogeneity of case mix when quantifying the variability that is expected. By displaying the overall history of outcomes in a visually intuitive manner, it complements the more formal tools for detecting isolated good and bad runs that are available.

Cardiovascular Surgical Procedures↗

Terrestrial avoidance behaviour tests as screening tool to assess soil contamination.

To assess soil quality and risk assessment, bioassays can be useful tools to gauge the potential toxicity of contaminants focusing on their bioavailable fraction. A rapid and sublethal avoidance behaviour test was used as a screening tool with the earthworm Eisenia andrei and the isopod Porcellionides pruinosus, where organisms were exposed during 48 h to several chemicals (lindane, dimethoate and copper sulphate, for isopods and carbendazim, benomyl, dimethoate and copper sulphate for earthworms). Both species were also exposed to soils from an abandoned mine. For all bioassays a statistical approach was used to derive EC50 values. Isopods and earthworms were able to perceive the presence of toxic compounds and escaping from contaminated to clean soil. Furthermore the behaviour parameter was equally or more sensitive then other sublethal parameters (e.g. reproduction or growth), expressing the advantages of Avoidance Behaviour Tests as screening tools in ERA.

Animals↗

Use of brief depression screening tools in primary care: consideration of heterogeneity in performance in different patient groups.

Heterogeneity of performance of screening tools in different patient groups has rarely been considered in the literature on depression screening in primary care. The objectives of the present study were to assess and to compare diagnostic accuracy of three screening questionnaires (Brief Patient Health Questionnaire, General Health Questionnaire-12, WHO-5) in identifying depression across various patient subpopulations and to assess the accuracy of the unaided clinical assessment of primary care physicians in the same subgroups. We conducted a cross-sectional validation study in 448 primary care patients. Two-by-two tables as well as receiver operating characteristics were applied. Results indicated that diagnostic accuracy (sensitivity, specificity) of the three screening instruments as well as of the clinical diagnoses differed in the various patient groups. Superiority of one screening tool over the other depends on the subgroup considered. Gender, age, form (subtype), and severity of depression influence the test characteristics of a screening tool. This should be considered if routine depression screening should be widely introduced. Of course, the benefit of routine screening also depends on efforts made for treatment and monitoring of patients in whom depression was diagnosed.

Adult↗

Real-time monitoring of coronary care mortality: a comparison and combination of two monitoring tools.

BACKGROUND: Quality control in clinical care is becoming increasingly more prevalent, resulting in a need for tools that can be readily used by clinical teams for monitoring their own performance. The aim of this study was to devise a practical and effective scheme for monitoring coronary care mortality in real-time. METHODS: We obtained data for 2153 consecutive patients admitted after acute myocardial infarction between 1st September and 30th November 1995 to one of 20 acute hospitals in West Yorkshire participating in the NHS R and D funded EMMACE-1 study. We developed control charts for each centre to monitor 30-day mortality. These control charts used two complementary tools: the Risk-Adjusted Cumulative Sum chart (CUSUM) and a new 'Rocket Tail' chart based upon the Variable Life-Adjusted Display (VLAD). We also combined information from each of these to devise a further chart. RESULTS: Control charts are shown for two centres in order to illustrate the important features of the different but complimentary monitoring tools. The Risk-Adjusted CUSUM is shown to be useful for detecting isolated runs of unsatisfactory outcome results but is not 'intuitive', and does not give any indication of the preceding history of outcomes. The Rocket Tail chart is shown to give a good summary of outcome history and also how overall performance compares with what would be expected for the case-mix. A chart that combines both approaches appeals to the advantages of each. CONCLUSIONS: We propose a visual approach to health-care monitoring that beneficially combines and extends the different information of the previously used CUSUM and VLAD charts.

Data Collection↗

A tool for assessing 'readiness' in emergency obstetric care: the room-by-room 'walk-through'.

This article presents a tool that can be used to assess the readiness of a health facility to provide emergency obstetric care. The 'walk-through' tool is a checklist that follows the physical path that a woman and her caregivers might follow. The items on the checklist are critical to an enabling environment in which skilled providers can save lives. The article explains how the tool can be used and by whom, and it describes several experiences in the field.

Emergency Medical Services↗

Improving patient safety through informatics tools for shared decision making and risk communication.

This paper describes how informatics tools can support shared decision making and risk communication and thereby play an important role in enhancing patient safety. Using preference elicitation techniques and knowledge on risk communication, such tools can help patients understand their treatment options and associated short- and long-term benefits and risks, assist in the elicitation of patient preferences, and help patients and clinicians in making treatment choices with the highest likelihood of achieving desired patient outcomes. Important features of such tools are proposed, including: (1) Interactive tutorials to improve risk comprehension and prepare patients and clinicians for the decision making task; (2) choices between different presentation modes to meet patients' individual reading levels and presentation preferences; (3) risk calculations that account for individual risk profiles; (4) performance of necessary calculations to reach the actual decision; (5) automatic updates of evidence; and (6) the use of different preference-elicitation techniques.

Decision Making, Computer-Assisted↗

Screening for autism in pre-school children in primary care: systematic review of English Language tools.

OBJECTIVES: To review the accuracy of brief screening tools for autism in pre-school children. DESIGN: Systematic review of diagnostic accuracy studies. DATA SOURCES: Medline, Embase, Cinahl and Psychlit plus references of identified papers and contact with authors. SUBJECTS: Children and infants aged 5 years or less without a prior diagnosis of autism or pervasive development delay. INTERVENTIONS: Tools/checklists appropriate for use in screening for autism in primary care settings. OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive value of screening tools and likelihood ratios relative to a diagnostic assessment made using either DSM-III/IV or ICD 10 diagnosis. RESULTS: Three studies considering two tools were identified. The CHecklist for Autism in Toddlers (CHAT) was tested on an appropriate population sample with moderate long-term follow-up but demonstrated poor sensitivity and positive predictive value. Weaker evidence suggested that the Modified CHecklist for Autism in Toddlers (M-CHAT) had high sensitivity but follow-up was of shorter term and less comprehensive. CONCLUSIONS: The CHAT demonstrated a level of sensitivity unlikely to be useful for population screening purposes, however, its high specificity suggests it has utility in secondary screening. The M-CHAT is a parent only report and might be more sensitive, and therefore appropriate for population screening. However, full conclusions regarding its accuracy cannot be drawn until follow-up data has been collected.

Age Factors↗