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GENKI: A generative framework for scalable and robust metabolic kinetic modeling.

GENKI (Generative ENsemble KPI-Informed) is a variational autoencoder-based framework for large-scale kinetic modeling of metabolism. Developed for metabolic engineering applications, GENKI is designed to improve the recovery of kinetically feasible models that reproduce experimentally observed phenotypes under genetic and environmental perturbations. The framework is trained on feasible kinetic model ensembles and uses phenotype-based key performance indicators (KPIs), derived from multi-omics and bioprocess data, to label and enrich models according to their agreement with mutant and condition-specific observations. This enables targeted generation of biologically relevant parameter sets with improved predictive performance. Crucially, GENKI recovers kinetic parameter sets that jointly reproduce wild-type and multiple perturbed physiologies within a single model. We apply GENKI to large-scale kinetic models of Escherichia coli and Saccharomyces cerevisiae under enzyme perturbations and oxygen shifts. In both systems, GENKI enriches kinetic ensembles with models that more accurately reproduce experimentally observed physiologies across multiple perturbations and conditions. GENKI therefore provides a practical framework for perturbation-aware kinetic model refinement within iterative Design-Build-Test-Learn workflows.

DBTL↗

Algae-to-host horizontal gene transfer in Paramecium bursaria is associated with host adaptation during endosymbiosis.

Paramecium bursaria maintains a stable endosymbiosis with green algae, yet the evolutionary consequences of this association remain unclear. Here, we screened the host genome for algal-derived horizontally transferred genes (HTGs) using a lineage-aware workflow designed to detect horizontal gene transfer (HGT) between two defined lineages. We identified 16 candidate HTGs, including four putative newly transferred genes and 12 homologous transferred genes, most of which were functionally associated with redox homeostasis and metabolism. Five HTGs showed symbiosis-dependent expression. RNAi knockdown of GH32s and SATs reduced host proliferation, total cell area, and motility, while GH32s knockdown also reduced endosymbiont load. Duplication patterns suggest that most transfers may have occurred after the P. bursaria lineage diverged from the sampled Paramecium species but before its lineage-specific whole-genome duplication (WGD). The HTGs also showed host-associated shifts in GC content and gene length, while representative HTGs retained conserved domains and functional motifs. Together, our results support algae-to-host HGT in P. bursaria and suggest that some transferred genes may contribute to metabolic integration during endosymbiosis.

Gene Transfer, Horizontal↗

Concepts for the third generation of laboratory systems.

This paper briefly describes the history of laboratory systems and discusses some of the recent concepts. The third generation of laboratory systems, which appeared around 1990, encompasses most of the pre-analytical, analytical and post-analytical procedural steps of the laboratory workflow, thus eliminating much of the so-called "3 D tasks" (dull, dirty, dangerous). These automation systems enable humans to focus on work of higher value such as result validation or development of tests in emerging areas. The new development started in Japan in 1981 and reached the Western hemisphere around 1995. Currently there are between 800 and 900 installations world-wide that meet the above criteria. The majority of them automate hematology, whereas systems that automate more complex areas such as clinical chemistry, immunochemistry, coagulation and urinalysis, represent only about one third. More than 60% of the world-wide system base has been installed in Japan. Future growth in the West and high market saturation in Japan are likely to decrease this percentage during the next few years. The two key concepts of third generation systems are "consolidation" and "integration". The following definitions are suggested: * Consolidation: Combining different analytical technologies or strategies on one instrument or on one group of connected instruments. * Integration: Linking analytical instruments or groups of instruments with pre- and post-analytical devices. Examples for the technical realization of both concepts and practical aspects of how to apply them in an individual laboratory are given. Components, which are specifically new in the context of laboratory automation, are conveyor belts, stationary and floor-running robots, and software for process control. The most attractive options to be considered when automating a laboratory are primary tube sorting and the use of secondary samples to increase speed and to avoid sample carryover. Other applications include automatic centrifugation (esp. for hospital laboratories), decapping (esp. for clinical chemistry), automatic loading and unloading of analyzers (esp. for large laboratories), automatic rerun and reflex testing as well as computer-based sample retrieval, result validation, and interpretation. Specific recommendations for automation planning include the need to see and discuss working installations either during site visits or via video documentations, and to conduct computer simulation experiments on the basis of a "virtual laboratory" model.

Automation↗

Semi-automatic data processing in clinical chemistry.

A semi-automatic system for data processing in the Clinical Chemistry Department of the School of Pathology, Johannesburg, is outlined. Careful planning of workflow in the laboratory can provide a better interface of laboratory results with a manual cumulative reporting system in which technologists and clerks co-ordinate their activities. The system used provides a less tedious and less error-prone process via automatic printing facilities. This system achieves improved patient care in terms of quality control (data checks) and cumulative reporting of results. Facility for accounts and administration purpose are also incorporated. In our experience, semi-automatic data processing can provide a solution to the clerical problems generated by the introduction of automatic testing equipment. Hardware costs are minimal in comparison to fully automated systems, which utilize on-line or off-line computers.

Chemistry, Clinical↗

Marketing your practice on the Internet.

The Internet provides a unique opportunity for marketing a medical practice. By demonstrating a commitment to good doctor-patient communication, by providing helpful background information, and by facilitating office workflow, a Web site can be a cost-effective way to enhance any practice. This chapter examines the basics of implementing an Internet presence; the issues related to online communication with patients; and the ongoing utilization, promotion, and maintenance of a Web site.

Advertising↗

Digital imaging overview.

Digital imaging consists of digital acquisition modalities, image, and information management systems. All modalities are available to be purchased as digital acquisition devices. Image management has been the domain for PACSs. PACSs are complex systems designed to transmit, store, and display medical images. They use and rely on many types of different information and display technologies. The initial focus for PACSs has been on solving the engineering issues associated with the transfer of large image data sets and the suitability of softcopy displays for diagnosis particular to the human visual system. For operating within a centralized radiology department, these are largely solved. However, for enterprise wide dissemination and distribution, there are still challenges in the form of expedient transfer syntaxes and image quality, but these are also being effectively addressed. Information management is the domain of the RIS. One of the goals of radiology management should encompass the development of a robust practice environment that emphasizes workflow enhancements with seamless integration of decision support tools. The concept of "person-machine" systems emphasizes taking full advantage of both human and machine capabilities with a capacity to grow and change function. As the computer capabilities increase, more jobs can be relinquished to the machine. The physician can then focus on tasks that require more complex judgment and comprehension. The goal of this human-machine hybrid is to have more power than either of its components alone. This multifaceted role will most likely be embedded in the background having agents query and retrieve context specific information to be presented to the user. As augmenters of human talent, computers can turn data into information and information into knowledge. Medical imaging is a beneficiary of the information technology developments driven by the consumer and business sectors. Although these applications of information technologies are not a solution to every problem, it certainly can bring the radiology department much closer to the desired ideal operational model. Even though there are many challenges to overcome, the benefits derived from a successful RIS/PACS implementation can be instrumental toward achieving a level of excellence in clinical service, teaching, and research that is unrivaled. Strategies for change management and quality improvement should begin by considering the entire chain of events from image acquisition through display to communication of a report.

Computer Communication Networks↗

Automated liquid handling and high-throughput preparation of polymerase chain reaction-amplified DNA for microarray fabrication.

Genome-wide studies of gene expression and transcription factor-binding sites using DNA microarrays are leading to new systems level insights. The massively parallel nature of microarrays presents technical challenges: fabricating high-quality microarrays at the front end and data analysis and interpretation downstream. A principal challenge in fabricating microarrays is preparation of the DNA samples. This is particularly the case for polymerase chain reaction-amplified DNA samples. The challenge is to scale up efficiently to high-throughput preparation of tens of thousands of DNA samples while ensuring a uniform high quality. This chapter outlines strategic considerations, including automated liquid handling and workflow development to maximize efficiency, and quality control (QC) measures to ensure uniform quality. The protocols are presented with commentary to illustrate their logic and specific techniques. These principles and techniques are extensible to other high-throughput molecular biological applications.

Animals↗

An introduction to BioArray Software Environment.

BioArray Software Environment (BASE) is a web-based software package for storing, searching, and analyzing locally generated microarray data and information surrounding microarray production. The workflow begins in sample management and, optionally, microtiter plate tracking and ends in visualization and analysis of entire experiments. The relative ease with which new analysis plug-ins can be added has given rise to a plethora of third-party tools, and the licensing terms (GNU GPL) encourage local modifications of the software. This introduction to BASE describes the basics of working with the software, both in general and in more detail for the various parts. It also provides some hints about more advanced usage and a section on what is needed to set up your own BASE server. The information is current as of BASE version 1.2.17b, which was released on November 6, 2005.

Animals↗

Bioconductor: an open source framework for bioinformatics and computational biology.

This chapter describes the Bioconductor project and details of its open source facilities for analysis of microarray and other high-throughput biological experiments. Particular attention is paid to concepts of container and workflow design, connections of biological metadata to statistical analysis products, support for statistical quality assessment, and calibration of inference uncertainty measures when tens of thousands of simultaneous statistical tests are performed.

Animals↗

Complexity of biomedical data models in cardiology: the Intranet-based AF registry.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with major complications. Ongoing research is focused on new pacing devices for alternative treatment of this disease. The objective of an AF registry is to store prospectively all relevant data covering clinical information, quality of life and device parameters and by this means provide a platform for long-term follow-up. For statistical analysis, categorical and numerical items are required, thus a high-granular data structure must be defined and implemented in the clinical setting. Facing the limits of formalization, we developed an XML-based documentation scheme consisting of 619 items in eight tables and implemented it with state-of-the-art Intranet technology. At present detailed information on 88 patients is recorded. The pacing device generates per patient and follow-up visit a file consisting of approximately 400-500 parameters provided on a floppy disk, which are transferred by means of a specific interface into the database. Success factors for integration of a complex research database into the routine workflow of a busy university hospital are interfaces between data sources to enable non-redundant data entry, intensive fine tuning by iterative software engineering and benefit for the clinical users in form of clinical reports and patient-specific summaries. Data quality must be assured by plausibility checks. To get an overview of this complex dataset we developed a dedicated visualization tool. Due to the high number of items a large patient collective must be recruited for statistical evaluation. Interinstitutional cooperation is required for a consensus on common minimal documentation schemes to enable pooling of data.

Atrial Fibrillation↗

Quasi-automatic 3D finite element model generation for individual single-rooted teeth and periodontal ligament.

The paper demonstrates how to generate an individual 3D volume model of a human single-rooted tooth using an automatic workflow. It can be implemented into finite element simulation. In several computational steps, computed tomography data of patients are used to obtain the global coordinates of the tooth's surface. First, the large number of geometric data is processed with several self-developed algorithms for a significant reduction. The most important task is to keep geometrical information of the real tooth. The second main part includes the creation of the volume model for tooth and periodontal ligament (PDL). This is realized with a continuous free form surface of the tooth based on the remaining points. Generating such irregular objects for numerical use in biomechanical research normally requires enormous manual effort and time. The finite element mesh of the tooth, consisting of hexahedral elements, is composed of different materials: dentin, PDL and surrounding alveolar bone. It is capable of simulating tooth movement in a finite element analysis and may give valuable information for a clinical approach without the restrictions of tetrahedral elements. The mesh generator of FE software ANSYS executed the mesh process for hexahedral elements successfully.

Algorithms↗

An asynchronous co-operative model for co-ordinating medical unit activities.

CSCW is devoted to the analysis of interactions among human beings when performing their work together (Ellis et al., Commun. ACM 1 (34) (1991) 38-58). The main fields of application are work organisation, healthcare, education and training. Our main goal is to study the co-operative models allowing task co-ordination and conflict management between actors within a distributed environment, particularly in medical units. We do not aim to produce a practical system suitable for near-term deployment in the intensive care units (ICU), but rather an experimental system that performs and co-ordinates a range of intelligent planning tasks in ICU activities. The emphasis will be put especially on asynchronous co-operation. We apply the Workflow approach to ICU organisation through the analysis and the proposal of a co-operative model.

Computer Simulation↗

Initiation of a teleradiotherapeutic network for patients in German lymphoma studies.

PURPOSE: Deviations of radiation treatment portals and dose from prospective treatment plans are unfavorable prognostic factors for lymphoma patients. Therefore, an extensive radiotherapy quality assurance program is used in the ongoing German lymphoma studies. The introduction of teleradiotherapy offered the opportunity to optimize and simplify the workflow of these quality assurance programs. The purpose of this report was to evaluate the feasibility of teleradiotherapy and to describe our experiences with these innovative tools. METHODS AND MATERIALS: During this pilot phase, five radiotherapy centers were equipped with the hardware and software that guarantees a rapid and high-quality transfer of imaging data, as well as real-time teleconferences. The workstation consists of standard PCs with Windows NT as the operating system and the commercial telemedicine software Hipax. RESULTS: As a first step, imaging communication between the radiotherapy reference centers in Cologne and Homburg/Saar was established. Subsequently, three additional radiotherapy departments (Universities of Berlin, Münster, and Munich) with large numbers of lymphoma patients were connected. Other study centers delivered digital imaging on mobile data carriers or via an Integrated Services Digital Network point-to-point connection. Communication units were completed for interactive teleconferences. A facility for central online documentation was installed. Telemedical functions were integrated into the ongoing radiotherapy quality assurance program. Since the introduction of a teleradiotherapeutic workstation in the radiotherapy reference center in Cologne in January 2001, the images of 10% (n = 228 patients) of all reviewed cases of the ongoing Hodgkin's disease 10-12 trials were delivered digitally. The amount of digitally available imaging is continuously increasing. CONCLUSION: The introduction of teleradiotherapy improved the dialog between the radiotherapy reference centers and study centers and thus contributed toward high radiotherapy quality for lymphoma patients in Germany.

Feasibility Studies↗

Standardisation of imaging in neuroendocrine tumours: results of a European delphi process.

In 1998 and 1999, a delphi consensus procedure was performed to establish guidelines for standardised diagnostic imaging of neuroendocrine tumours. The procedure included four consecutive workshops of a European group of experts in neuroendocrine tumours as well as feedback given by specialists from the departments of radiology, nuclear medicine, surgery and internal medicine of the according home institutions. Diverging approaches among the centres, which became apparent during the discussion, reflect a lack of controlled studies specifically for rare subgroups of neuroendocrine tumours. This paper summarises the standards for diagnostic imaging as developed during the delphi process. In particular, the diagnostic workflows as well as the technical properties of different imaging modalities are described in detail.

Delphi Technique↗

The National Emergency Medical Extranet project.

The National Emergency Medical Extranet (NEME) project was a collaborative multi-center effort to create a plan for a networked system to improve emergency clinical care through real-time information support, and simultaneously provide benefit through information support for public health initiatives. This article presents a review of the NEME project and its recommendations, which are particularly relevant given the desire for improved communication and surveillance systems in today's healthcare and public health environments. Participants in the NEME project performed an environmental assessment and a proposed conceptual architecture for NEME. A consensus conference was held to review the NEME concept to obtain feedback and delineate priorities for future development and testing. The NEME consensus conference used a modified version of the nominal group method. Recommendations for the following areas were established: Business/Organizational Issues [1) create a compelling provider driven NEME model, 2) provide a comprehensive policy framework, 3) address economics]; Clinical/Caregiver Issues [1) develop a NEME system that is integrated with Emergency Medicine workflow, 2) provide incentives to caregivers, 3) generate a critical mass of participation for maximum benefit]; Technical Issues [1) incorporate a robust security and confidentiality architecture, 2) utilize a master person index, where appropriate, 3) evaluate or adopt existing data standards]; Heart Attack Alert Functional Priorities for NEME [1) continuous quality improvement and research, 2) regional electrocardiogram server, 3) past medical history and medication server]; Next Generation Internet Functional Priorities for NEME [1) real time epidemiology/surveillance, 2) patient education, 3) real time clinical alerting]. In conclusion, issues and consensus recommendations in the planning of a NEME are documented. These recommendations should be considered in future efforts to design, develop and implement wide area information networks to support Emergency Medicine. A review of current activities evolving from NEME is presented, and further research and development is encouraged to create and implement NEME systems.

Computer Communication Networks↗

Concept of a PACS and imaging informatics-based server for radiation therapy.

Radiation Therapy (RT) is an image-based treatment. It requires images from projection X-rays, computed tomography, magnetic resonance, positron emission tomography, Linear Accelerator for tumor localization, treatment planning and verification of treatment plans. During the treatment process, patient's images are transmitted to every necessary station in the RT department. However, images of the same patient are generally scattered and there is no permanent home base for them due to the nature and traditional organization of the RT department. The advance in diagnostic picture archiving and communication system and the establishment of RT DICOM Standard provide an opportunity to define and design an RT server as a means to organize RT images and related data. This paper describes the RT workflow and the concept of the DICOM RT server. An example of RT treatment of nasopharyngeal carcinoma based on the RT server concept is given.

Diagnostic Imaging↗

PACS-based functional magnetic resonance imaging.

The picture archiving and communication system (PACS) technology reaches its 10th anniversary. Retrospectively no one could foresee the impact the PACS would have to the health care enterprise, but it is common consent today, that PACS is the key technology crucial to daily clinical image operations and especially to image related basic and clinical research. During the past 10 years the PACS has been matured from a research and developmental stage into commercial products which are provided by all major modality and health care equipment vendors. The PACS, originally implemented in the Radiology Department, needs to grow and has already carried well beyond departmental limits conquering all image relevant areas inside the hospital. During the past 10 years a dramatic development in imaging techniques especially within MRI emerged. Advanced 3D- and 4D-MR imaging techniques result in much more images and more complex data objects than ever before which need to be implemented into the existing PACS. These new imaging techniques require intensive post-processing apart from the imaging modality which need to be integrated into the image workflow and the PACS implementation. Along with these new imaging techniques new clinical applications, e.g. stroke detection, and research applications, e.g. study of heart and brain function, in Neurology and Cardiology require changes to the traditional PACS concept. Therefore inter-disciplinary image distribution will become the high-water mark for the next 10 years in the PACS endeavor. This paper focuses on one new advanced imaging technique, functional magnetic resonance imaging (fMRI), and discusses how fMRI data is defined, what fMRI requires in terms of clinical and research applications and how to implement fMRI in the existing PACS.

Brain↗

Trends in PACS image storage and archive.

PACS is widely used in hospitals and is considered a mission critical system for around-the-clock daily clinical operation. Scheduled or unscheduled downtime of the main PACS archive storage or server could potentially cripple the entire PACS operation. This is especially the case in a filmless hospital environment. Therefore, in a downtime event, it is most desirable for users to have only a minimal performance impact without interruption of clinical data flow or loss of data and to have available historical PACS studies. This paper summarizes some of the developments in the design and implementation of a reliable PACS that insures maximum uptime for end users while preserving the integrity of the PACS data and making it available during downtime events. It also details strategy for developing proper clinical workflow contingency procedures when a scheduled downtime event to the main archive storage and server occurs. Specifically, the design and implementation of a fault-tolerant (FT) main archive server, the development of a FT back-up archive using an application service provider (ASP) model, and the clinical experiences while upgrading a main archive server and migrating the stored PACS data to new storage media will be discussed.

California↗