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Hospital-wide physiological surveillance-a new approach to the early identification and management of the sick patient.

Hospitalised patients, who suffer cardiac arrest and require unanticipated intensive care unit (ICU) admission or die, often exhibit premonitory abnormalities in vital signs. Sometimes, the deterioration is well documented, though there is little discernable evidence of intervention. In other cases, monitoring and recording of vital signs is infrequent or incomplete. Healthcare providers have introduced "track and trigger" systems to allow early identification of patients with physiological abnormalities, and rapid response teams to facilitate rapid and appropriate management. However, even when "track and trigger" systems are used, the recording of vital signs, patient chart completion and team activation remain sub-optimal. We have developed a system for collecting routine vital signs data at the bedside using standard personal digital assistants (PDA). The PDAs act as "thin clients" linked by a wireless local area network (W-LAN) to the hospital's intranet system, where raw and derived data are integrated with other patient information, e.g., name, hospital number, laboratory results. It is possible for raw physiology data, early warning scores (EWS), vital signs charts and oxygen therapy records to be made instantaneously available to any member of the hospital healthcare team via the W-LAN or hospital intranet. Early and direct contact with members of the patient's primary clinical team or rapid response team can be made through an automated alerting system, triggered by the EWS data. The ability to capture physiological data at the bedside, and to make these available to anyone with appropriate access rights at any time and in any place, should provide previously unattainable, clinical and administrative benefits. Analysis of the raw physiological data and patient outcomes will also make it possible to validate existing and future "track and trigger" systems.

Computers, Handheld↗

Reproducibility of 1H-NMR integrals: a collaborative study.

The quantitative use of NMR spectroscopy was investigated by a reproducibility study of 1H-NMR integrals involving five laboratories. A significant laboratory effect was found confirming the difficulty to obtain very precise data by integration of complex signals. The reproducibility of any NMR assay measurement, which requires a high precision should be validated by an interlaboratory study.

Evaluation Studies as Topic↗

Evaluation of the roles of apoptosis, autophagy, and mitophagy in the loss of plating efficiency induced by Bax expression in yeast.

We found recently that, in yeast cells, the heterologous expression of Bax induces a loss of plating efficiency different from that induced by acute stress because it is associated with the maintenance of plasma membrane integrity (Camougrand, N., Grelaud-Coq, A., Marza, E., Priault, M., Bessoule, J. J., and Manon, S. (2003) Mol. Microbiol. 47, 495-506). Bax effects were neither dependent on the presence of the yeast metacaspase Yca1p and the apoptosis-inducing factor homolog nor associated with the appearance of typical apoptotic markers such as metacaspase activation, annexin V binding, and DNA cleavage. Yeast cells expressing Bax instead displayed autophagic features, including increased accumulation of Atg8p, activation of vacuolar alkaline phosphatase, and the presence of autophagosomes and autophagic bodies. However, the inactivation of autophagy did not prevent and actually slightly accelerated Bax-induced loss of plating efficiency. On the other hand, Bax expression induced a fragmentation of the mitochondrial network, which retained, however, some level of organization in wild-type cells. However, when expressed in cells inactivated for the gene UTH1, previously shown to be involved in mitophagy, Bax induced a complete disorganization of the mitochondrial network. Interestingly, although mitochondrially targeted green fluorescent protein was slowly degraded in the wild-type strain, it remained unaffected in the mutant. Furthermore, the slow loss of plating efficiency in the mutant strain correlated with a loss of plasma membrane integrity. These data suggest that Bax-induced loss of growth capacity is associated with maintenance of plasma membrane integrity dependent on UTH1, suggesting that selective degradation of altered mitochondria is required for a regulated loss of growth capacity.

Apoptosis↗

Occupational exposure to inhalable wood dust in the member states of the European Union.

The aim of this study was to estimate occupational exposure to inhalable wood dust by country, industry, the level of exposure and type of wood dust in 25 member states of the European Union (EU-25) for the purposes of hazard control, exposure surveillance and assessment of health risks. National labour force statistics, a country questionnaire (in 15 member states, EU-15), a company survey (in Finland, France, Germany and Spain), exposure measurements (from Denmark, Finland, France, Germany, The Netherlands and the United Kingdom) and expert judgements were used to generate preliminary estimates of exposure to different types of wood dust. The estimates were generated according to industrial class (six wood industries, four other sectors) and level of exposure (five classes). These estimates were reviewed and finalized by national experts from 15 member states. Crude estimates were generated also for 10 new member states (EU-10). The basic data and final estimates were included in the WOODEX database. In 2000-2003, about 3.6 million workers (2.0% of the employed EU-25 population) were occupationally exposed to inhalable wood dust. Of those, construction employed 1.2 million exposed workers (33%), mostly construction carpenters. The numbers of exposed workers were 700,000 (20%) in the furniture industry, 300,000 (9%) in the manufacture of builders' carpentry, 200,000 (5%) in sawmilling, 150,000 (4%) in forestry and <100,000 in other wood industries. In addition, there were 700,000 exposed workers (20%) in miscellaneous industries employing carpenters, joiners and other woodworkers. The numbers of exposed workers varied by country ranging from <3,000 in Luxembourg and Malta to 700,000 in Germany. The highest exposure levels were estimated to occur in the construction sector and furniture industry. Due to limited exposure data there was considerable uncertainty in the estimates concerning construction woodworkers. About 560,000 workers (16% of the exposed) may be exposed to a level exceeding 5 mg m(-3). Mixed exposure to more than one species of wood and dust from wooden boards was very common, but reliable data on exposure to different species of wood could not be retrieved. This kind of assessment procedure integrating measurement data, company data, country-specific data and expert judgement could also serve as one model for the assessment of other occupational exposures.

Air Pollutants, Occupational↗

The temporal organization of life: the impact of multi-frequency non-linear biologic time structure upon the host-cancer balance.

The current scientific paradigm, based upon an erroneous assumption of linear biologic reality and simple cause and effect relationships, has outlived its usefulness. In order to begin to turn the voluminous data the reductive process provides us with daily into meaningful understanding of life, it is essential to integrate these data within a complex, multi-frequency temporo-spatial framework. This rhythmic chronobiology more accurately depicts the life process, as well as its evolutionary and ongoing vital interaction with the pulsating cosmic resonance structure. Examples of the kinds of thinking and experiments necessary to exploit this new paradigm are provided.

Antineoplastic Agents↗

Integrated volume visualization of functional image data and anatomical surfaces using normal fusion.

A generic method, called normal fusion, for integrated three-dimensional (3D) visualization of functional data with surfaces extracted from anatomical image data is described. The first part of the normal fusion method derives quantitative values from functional input data by sampling the latter along a path determined by the (inward) normal of a surface extracted from anatomical data; the functional information is thereby projected onto the anatomical surface independently of the viewpoint. Fusion of the anatomical and functional information is then performed with a color-encoding scheme based on the HSV model. This model is preferred over the RGB model to allow easy, rapid, and intuitive retrospective manipulation of the color encoding of the functional information in the integrated display, and two possible strategies for this manipulation are explained. The results first show several clinical examples that are used to demonstrate the viability of the normal fusion method. These same examples are then used to evaluate the two HSV color manipulation strategies. Furthermore, five nuclear medicine physicians used several other clinical cases to evaluate the overall approach for manipulation of the color encoded functional contribution to an integrated 3D visualization. The integrated display using the normal fusion technique combined with the added functionality provided by the retrospective color manipulation was highly appreciated by the clinicians and can be considered an important asset in the investigation of data from multiple modalities.

Adult↗

An integrated multidepartmental hospital imaging system: usage of data across specialties.

Development of automated medical information systems requires knowledge about the utilization of the system; both for design and as feedback during the development process. One of the significant advantages of computer systems is that they can provide an automatic log of system utilization. This paper reports the first study of utilization data collected automatically in an integrated image environment. System monitoring indicates that images are routinely used in clinical care and clinical conferences. Selected images are shown repeatedly for teaching, demonstration, and reference at locations throughout the hospital. Images are viewed both by the collecting service when producing procedure reports and consultations, as well as by the treating physicians from other hospital services. Medical departments have developed image collection policies to meet their internal needs and the needs of treating physicians.

Hospital Information Systems↗

A Grid-based HIV expert system.

OBJECTIVES: This paper addresses Grid-based integration and access of distributed data from infectious disease patient databases, literature on in-vitro and in-vivo pharmaceutical data, mutation databases, clinical trials, simulations and medical expert knowledge. METHODS: Multivariate analyses combined with rule-based fuzzy logic are applied to the integrated data to provide ranking of patient-specific drugs. In addition, cellular automata-based simulations are used to predict the drug behaviour over time. Access to and integration of data is done through existing Internet servers and emerging Grid-based frameworks like Globus. Data presentation is done by standalone PC based software, Web-access and PDA roaming WAP access. The experiments were carried out on the DAS2, a Dutch Grid testbed. RESULTS: The output of the problem-solving environment (PSE) consists of a prediction of the drug sensitivity of the virus, generated by comparing the viral genotype to a relational database which contains a large number of phenotype-genotype pairs. CONCLUSIONS: Artificial Intelligence and Grid technology are effectively used to abstract knowledge from the data and provide the physicians with adaptive interactive advice on treatment applied to drug resistant HIV. An important aspect of our research is to use a variety of statistical and numerical methods to identify relationships between HIV genetic sequences and antiviral resistance to investigate consistency of results.

Biometry↗

Information management of a department of diagnostic imaging.

It is well-known that while RIS allows the management of all input and output data of a Radiology service, PACS plays a major role in the management of all radiologic images. However, the two systems should be closely integrated: scheduling of a radiologic exam requires direct automated integration with the system of image management for retrieval of previous exams and storage of the exam just completed. A modern information system of integration of data and radiologic images should be based on an automated work flow management in al its components, being at the same time flexible and compatible with the ward organization to support and computerize each stage of the working process. Similarly, standard protocols (DICOM 3.0, HL7) defined for interfacing with the Diagnostic Imaging (D.I.) department and the other components of modules of a modern HIS, should be used. They ensure the system to be expandable and accessible to ensure share and integration of information with HIS, emergency service or wards. Correct RIS/PACS integration allows a marked improvement in the efficiency of a modern D.I. department with a positive impact on the daily activity, prompt availability of previous data and images with sophisticated handling of diagnostic images to enhance the reporting quality. The increased diffusion of internet and intranet technology predicts future developments still to be discovered.

Appointments and Schedules↗

Graphical simulation of early development of the cerebral cortex.

Much experimental data exists concerning the development of the cerebral cortex. There is a need for a common vehicle to integrate this data and to allow the testing of hypotheses concerning development. Computer simulation and visualization are powerful mechanisms for hypothesis testing. Our long-term goal is to create a robust, extensible, portable tool for simulation and visualization of cortical development to serve both research and educational purposes. This paper describes a simulation program, SimCortex, which models the early stages of development of the cerebral cortex of the mouse. Version 1.0 of SimCortex models the proliferation of progenitor cells in the pseudostratified ventricular epithelium (PVE), the generation of young neurons and their migration into the cortical plate, which is the forerunner of cell layers II through VI of the adult cortex. We present an overview of the design and implementation of SimCortex, sample output of the system and a comparison of our results with experimental data. We conclude with a brief overview of proposed future enhancements of the system.

Animals↗

Control of rapid aimed hand movements: the one-target advantage.

A series of 8 experiments examined the phenomenon that a rapid aimed hand movement is executed faster when it is performed as a single, isolated movement than when it is followed by a second movement (the 1-target advantage). Three new accounts of this effect are proposed and tested: the eye movement hypothesis, the target uncertainty hypothesis, and the movement integration hypothesis. Data are reported that corroborate the 3rd hypothesis, but not the first 2 hypotheses. According to the movement integration hypothesis, the first movement in a series is slowed because control of the second movement may overlap with execution of the first. It is shown that manipulations of target size and movement direction mediate this process and determine the presence and absence of the 1-target advantage. Possible neurophysiological mechanisms and implications for motor control theory are discussed.

Adult↗

Studying metabolic regulation in human muscle.

Phosphorus magnetic resonance spectroscopy, despite some limitations, is a valuable non-invasive window on muscle metabolism in vivo, particularly oxidative ATP synthesis. A number of experiments have shown this to be dominated by closed-loop feedback mechanisms: a well-known model posits regulation by ADP, but there are others, difficult to distinguish experimentally. Moreover the contribution of open-loop control mechanisms ('feed forward' or 'parallel activation') in vivo remains controversial. Progress will require more precise data, better integrated with other measurements (e.g. muscle oxygenation), and improvement of the conceptual tools appropriate to such studies, where data are limited and steady-state assumptions frequently inapplicable.

Adenosine Triphosphate↗

CERTOMICS: trusted single-cell multiomics pipeline for high-resolution profiling of adoptive cellular immunotherapies.

SUMMARY: Adoptive cellular immunontherapies, such as chimeric antigen receptor (CAR) T cell therapy, have transformed cancer treatment, yet challenges such as resistance, relapse, and high costs limit their efficacy and accessibility. A comprehensive understanding of cellular heterogeneity and molecular profiles is essential to improve these therapies. Advanced single-cell multiomics technologies have the power to analyze the complex interactions between CAR-engineered cells, immune cells, and tumor cells. However, standardized single-cell multiomics computational pipelines specifically tailored to CAR-engineered cell products are lacking. Due to the synthetic nature of CAR transgenes, additional steps for reliable identification and characterization of CAR-positive cells are required but not included in existing data-processing workflows. To address this, we present CERTOMICS, a Nextflow-based, CAR-aware pipeline offering enhanced CERTainty in immunophenotyping and data interpretation, tailored for single-cell multiOMICSprofiling of adoptive cellular immunotherapies. The pipeline standardizes processing 10x Genomics single-cell multiomics data and integrates CAR-specific identification and quality control. Additionally, a curated repository of CAR construct sequences and annotation data is provided, serving as an extensible resource to support the analysis and development of CAR T cell therapies. AVAILABILITY AND IMPLEMENTATION: Detailed documentation of this pipeline, along with a resource on latest FDA-approved CAR therapies is available on our website: https://fraunhofer-izi.github.io/Living-Drugs-Wiki/. The data underlying this article are available on GitHub at https://github.com/fraunhofer-izi/CERTOMICS. The code is also published on Zenodo at https://doi.org/10.5281/zenodo.18709693.

Multiomics↗

ClarID: A Human-Readable and Compact Identifier Specification for Biomedical Metadata Integration.

BACKGROUND: In biomedical research, subjects and biospecimens are commonly tracked using simple IDs or UUIDs, which guarantee uniqueness but convey no embedded semantic information. Contextual metadata (such as tissue type, diagnosis, or assay) is often stored separately, making integration, cohort selection, and downstream analysis cumbersome. While structured barcoding systems exist in large consortia (e.g., TCGA, GTEx) or domain-specific contexts (e.g., SPREC, GOLD), no unified, extensible framework currently spans both subjects and biosamples in a human- and machine-readable way. METHODS: We developed ClarID, a domain-agnostic specification that supports two identifier formats: (i) a human-readable form (e.g., 'CNAG_Test-HomSap-00001-LIV-TUM-RNA-C22.0-TRT-P1W' that encodes key metadata such as project, species, subject_id, tissue, assay, disease, timepoint and duration (from that event); and (ii) a compact version named 'stub' (e.g., 'CT01001LTR0N401T1W') optimized for filenames, pipelines, and labeling.ClarID is implemented through an open-source command-line tool, ClarID-Tools, which processes tabular metadata files (CSV/TSV) and uses a YAML-based codebook to generate, decode, and validate identifiers, as well as to create and read QR codes. The tool supports bulk and single-sample processing and allows easy integration with institutional workflows. RESULTS: To demonstrate ClarID's utility, we applied it to datasets from the Genomic Data Commons (GDC), generating interpretable identifiers for more than 113,000 clinical records (subjects) and 4,255 biospecimen records. All materials, including pre-processing scripts, input and encoded data, are publicly available and fully reproducible via the accompanying GitHub repository and Google Colab. CONCLUSIONS: ClarID fills a critical gap between opaque accession numbers and rich metadata schemas by embedding key context directly into structured identifiers. It enhances traceability, facilitates downstream analysis, and remains adaptable to project-specific needs through a configurable codebook. The accompanying ClarID-Tools software is freely available, together with full documentation and reproducible pipelines, at https://github.com/CNAG-Biomedical-Informatics/clarid-tools.

Biosample identifiers↗

The institute for genomic research Osa1 rice genome annotation database.

We have developed a rice (Oryza sativa) genome annotation database (Osa1) that provides structural and functional annotation for this emerging model species. Using the sequence of O. sativa subsp. japonica cv Nipponbare from the International Rice Genome Sequencing Project, pseudomolecules, or virtual contigs, of the 12 rice chromosomes were constructed. Our most recent release, version 3, represents our third build of the pseudomolecules and is composed of 98% finished sequence. Genes were identified using a series of computational methods developed for Arabidopsis (Arabidopsis thaliana) that were modified for use with the rice genome. In release 3 of our annotation, we identified 57,915 genes, of which 14,196 are related to transposable elements. Of these 43,719 non-transposable element-related genes, 18,545 (42.4%) were annotated with a putative function, 5,777 (13.2%) were annotated as encoding an expressed protein with no known function, and the remaining 19,397 (44.4%) were annotated as encoding a hypothetical protein. Multiple splice forms (5,873) were detected for 2,538 genes, resulting in a total of 61,250 gene models in the rice genome. We incorporated experimental evidence into 18,252 gene models to improve the quality of the structural annotation. A series of functional data types has been annotated for the rice genome that includes alignment with genetic markers, assignment of gene ontologies, identification of flanking sequence tags, alignment with homologs from related species, and syntenic mapping with other cereal species. All structural and functional annotation data are available through interactive search and display windows as well as through download of flat files. To integrate the data with other genome projects, the annotation data are available through a Distributed Annotation System and a Genome Browser. All data can be obtained through the project Web pages at http://rice.tigr.org.

Computational Biology↗

Integration of EEG, MRI, and SPECT in localizing the seizure focus for epilepsy surgery.

Several modalities are now available for detecting the structural and the functional abnormalities of a seizure focus. This article discusses the principles and techniques that can be used to integrate the data derived from different test modalities in delineating the seizure focus in epilepsy surgery candidates. An approach in integrating EEG, MRI, and SPECT abnormalities is described to demonstrate how the spatial relationships among them can be precisely determined by coregistering images of the abnormalities on the MRI. The recently developed technique of subtraction ictal SPECT coregistered to MRI (SISCOM) can reveal a discrete hyperperfusion focus with its relationship to the cerebral anatomy. The SISCOM focus can also serve as a target for intracranial electrode implantation and for subsequent surgical resection. This can be achieved by using a computer-based system of relating the image space to the surgical field. The limitations of each test in localizing the surgical seizure focus must be recognized when the value of each test is interpreted relative to those of other tests. In many patients, not all tests will show localizing abnormalities, and the foci determined by different tests may be incongruent. When the location of the focus is not compatible with the possible origin of the patient's habitual seizures, further evaluation with other tests, including intracranial EEG recordings, is necessary. The decision in determining which tests and how many to employ for localizing the surgical focus must be individualized for each patient.

Adult↗

A bioinformatics approach to investigating developmental pathways in the kidney and other tissues.

Over the past few years, large amounts of data linking gene-expression (GE) patterns and other genetic data with the development of the mouse kidney have been published, and the next task will be to integrate these data with the molecular networks responsible for the emergence of the kidney phenotype. This paper discusses how a start to this task can be made by using the kidney database and its associated search tools, and shows how the data generated by such an approach can be used as a guide to future experimentation. Many of the events taking place as the kidney develops do, of course, also take place in other tissues and organisms and it will soon be possible to incorporate relevant information from these systems into analyses of kidney data as well as the new information from microarray technology. The key to success here will be the ability to access over the internet data from the textual and graphical databases for the mouse and other organisms now being established. In order to do this, informatic tools will be needed that will allow a user working with one database to query another. This paper also considers both the types of tools that will be necessary and the databases on which they will operate.

Animals↗