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Providing dermatological photographs using the multimedia extension of the international computer database for radiation accident case histories.

The World Health Organisation (WHO) Radiation Emergency Medical Preparedness (REMPAN) centres have built up the International Computer Database for Radiation Accident Case Histories (ICDREC) to document the medical treatment of acute radiation syndrome (ARS) patients. Images play an increasing role as complementary information beside text and numerical data in medicine. In particular, retrieval and display of digitised skin photographs serve to improve patient care, medical education and scientific analysis concerning the cutaneous radiation syndrome (CRS). The ICDREC has been built up as a client/server system. Particular focus has been set on using commercial off-the-shelf software components. All the medical data including the multimedia data are stored in a relational database system. The database can be accessed by inexpensive personal computers in the physician's workplace. Retrieval of one photograph via local area network (LAN) requires approximately 3 s. Authorised institutions can access the database via the Internet. The current state of the ICDREC multimedia component is illustrated with the skin lesion treatment of a Chernobyl patient. An example is given on how the workflow in a dermatology department is supported by the ICDREC.

Databases, Factual↗

Rapid translation system: a novel cell-free way from gene to protein.

Proteome research has recently been stimulated by important technological advances in the field of recombinant protein expression. One major breakthrough was the development of a new generation of cell-free transcription/translation systems. The open and flexible character of these systems allows direct control over expression conditions via the addition of supplements to the expression reaction. The possibility of working with linear expression templates instead of cloned plasmids and the ease of downstream processing, circumventing the need for cell-lysis, makes them ideally suited for high-throughput screening applications. Among these novel cell-free systems, the Rapid Translation System (RTS) developed by Roche is the first one that is scalable from micrograms to milligrams of protein. This review describes the basic principles of RTS which differentiate it from traditional in vitro expression technologies, starting from template generation to high-end applications like labeling for structural biology research. Recent results obtained by RTS users from different institutions are presented to illustrate each step of a novel cell-free protein expression workflow and its benefits compared to traditional cell-based expression.

Cell Extracts↗

Building bridges from process R&D: from a customer-supplier relationship to full partnership.

A new and forward-looking way of running process R&D is introduced that integrates this core business in an efficient manner into the network of activities in different disciplines, which constitute the arena for the development of pharmaceutical products. The interfaces with surrounding areas are discussed in addition to the novel organizational principles implemented in process R&D and the workflow emanating from this. Furthermore, the Tollgate model used to keep track of the progress in a project and the pre-study concept are presented in detail. Finally, the main differences between operating modes in the past and in the future are highlighted.

Journal Article↗

Evidence-based careflow management systems: the case of post-stroke rehabilitation.

The activities of a care providers' team need to be coordinated within a process properly designed on the basis of available best practice medical knowledge. It requires a rethinking of the management of care processes within health care organizations. The current workflow technology seems to offer the most convenient solution to build such cooperative systems. However, some of its present weaknesses still require an intense research effort to find solutions allowing its exploitation in real medical practice. This paper presents an approach to design and build evidence-based careflow management systems, which can be viewed as components of a knowledge management infrastructure each health care organization should be provided with to increase its performance in delivering high quality care by efficiently exploiting the available knowledge resources. The post-stroke rehabilitation process has been taken as a challenging care problem to assess our methodology for designing and developing careflow management systems. Then a system was co-developed with a team of rehabilitation professionals who will be committed to use it in their daily work. The system's main goal is to deliver a full array of rehabilitation services provided by an interdisciplinary team. They are related to identify which patients are most likely to benefit from rehabilitation, manage a rehabilitation treatment plan, and monitor progress both during rehabilitation and after return to a community residence. A model of the rehabilitation process was derived from an international guideline and adapted to the local organization of work. It involves different organizational units, such as wards, rehabilitation units, clinical laboratories, and imaging services. Several organizational agents work within them and play one or more roles. Each role is defined by the goals' set that she/he must fulfill. Special effort has been given to the design and development of a knowledge-based system for managing exceptions, which may occur in daily medical work as any deviation from the normal flow of activities. It allows either avoiding or recovering automatically from expected exceptions. When they are not expected, organizational agents, with enough power to do that, are allowed to modify the scheduled flow of activities for an individual patient under the only constraint of justifying their decision. After an intensive testing in a research laboratory, the system is now in the process of being transferred in a real working setting with the full support of its future users.

Delivery of Health Care↗

Using a computerized sign-out system to improve physician-nurse communication.

BACKGROUND: Communication problems among health care workers are a common, preventable source of hospital-related morbidity and mortality. Internal medicine residents at Jacobi Medical Center (Bronx, NY) began using an electronic sign-out program that had been incorporated into the computerized medical record. This new system had been developed to improve the quality of information transfer between cross-covering residents. Eighteen months later, a pilot study was initiated to explore the potential benefits of offering inpatient nurses access to this sign-out data. METHODS: Nursing staff members were provided electronic access to the residents' sign-out information. Nurses received printouts of the computerized sign-outs at the start of each shift and were asked to use the sign-out program as a basis for their care plans and nursing change-of-shift "report." RESULTS: The 19 (of 20) nurses who completed the survey agreed that using the resident sign-out program positively affected their ability to care for their patients. In addition, the intervention improved nurses' understanding of the patients' reason for admission, helped to improve communication between physicians and nurses, and raised nursing morale. DISCUSSION: Incorporation of a housestaff electronic sign-out system into nursing daily workflow demonstrated multiple benefits and facilitated the transfer of valuable patient information from housestaff to nurses.

Communication↗

Implementing patient safety practices in small ambulatory care settings.

BACKGROUND: Improving patient safety in the outpatient setting poses unique challenges for patient safety leaders in clinics and hospitals. Even though ambulatory care may be less technologically complex than inpatient care, it is often more complex logistically. METHODS AND MATERIALS: From October 2002 to May 2003, Gundersen Lutheran Medical Center developed a tool kit of best practices and conducted a collaborative to institute these best practices within a regional health care network. All clinics evaluated patient safety standards and enhanced medication-related practices. RESULTS: Improvements were demonstrated in medication list accuracy. A number of policies were instituted, and medical and nursing staffs were educated in patient safety issues. Improvements were sustained after one year. DISCUSSION: The collaborative model of improvement efforts was an effective model for improving patient safety in small group practices. Structural and process changes often do not require major changes in workflow or large technology installations. Many of the projects allowed for, or required, local assessment and management. However, within a large system of clinics, some of the improvements in this study--verbal order policy, methodology and/or technology for assessment of medication and allergy list accuracy, warfarin care--required systemwide efforts. The degree of difficulty of achieving improvements was surprisingly low and barriers were minimal.

Ambulatory Care Facilities↗

A cooperative approach to standardizing care for patients with AMI or heart failure.

BACKGROUND: In fall 2003 the five hospitals in Wichita, Kansas, formed a collaborative to improve care for patients presenting with acute myocardial infarction or heart failure (HF). Standard order sets were developed from guidelines developed by the American College of Cardiology and the American Heart Association. THE WICHITA CITYWIDE HEART CARE COLLABORATIVE GETS TO WORK: The order sets, which highlighted the appropriate interventions and made their implementation a "checkbox" activity, were placed in the progress note section of the medical record. Booklets for patient education on heart care were developed. RESULTS: All five hospitals have experienced significant improvement in core measure data. For example, for angiotension-converting enzyme inhibitor for left ventricular systolic dysfunction, the overall compliance score improved from 70% to 85%, a 15% improvement in 18 months. Compliance for HF was perhaps more successful, given the low level of initial compliance (50%). DISCUSSION: Physician compliance was enhanced by incorporating the guidelines into practitioners' daily workflow needs, providing prompt feedback on their performance, incorporating their suggestions made at the point of care, and using process measurements.

Awards and Prizes↗

Implementing evidence-based psychosocial practices: lessons learned from statewide implementation of two practices.

OBJECTIVE: As part of this national project, we examined barriers and strategies to implementation of two evidence-based practices (EBPs) in Indiana. BACKGROUND: Despite many advances in the knowledge base regarding mental health treatment, the implementation of EBPs in real-world setting remains poorly understood. The National EBP Project is a multi-state study of factors influencing implementation of EBPs. METHODS: Over a 15-month period we observed eight assertive community treatment (ACT) programs and six integrated dual disorders treatment (IDDT) programs and noted pertinent actions taken by the state mental health agency influencing implementation. We created a database containing summaries of monthly visits to each program and interviews with key leaders. Using this database and clinical impressions, we rated barriers and strategies at each site on seven factors: Attitudes, Mastery, Leadership, Staffing, Policies, Workflow, and Program Monitoring. RESULTS: At the site level, the most frequently observed barriers were in the areas of leadership, staffing and policies for ACT, and mastery and leadership for IDDT. Overall, barriers were more evident for IDDT than for ACT. Strategies were less frequently noted but generally paralleled the areas noted for barriers. However, our central finding was that ACT was generally more successfully implemented than IDDT throughout the state, and that this difference could be traced in large part to state-level factors relating to historical preparation for the practice, establishment of standards, formation of a technical assistance center, and funding. CONCLUSION: In this case study, both state-level and site-specific factors influenced success of implementation of EBPs. To address these factors, the field needs systematic strategies to anticipate and overcome these barriers if full implementation is to be realized.

Community Mental Health Services↗

Model selection and optimal sampling in high-throughput experimentation.

The practical difficulties encountered in analyzing the kinetics of new reactions are considered from the viewpoint of the capabilities of state-of-the-art high-throughput systems. There are three problems. The first problem is that of model selection, i.e., choosing the correct reaction rate law. The second problem is how to obtain good estimates of the reaction parameters using only a small number of samples once a kinetic model is selected. The third problem is how to perform both functions using just one small set of measurements. To solve the first problem, we present an optimal sampling protocol to choose the correct kinetic model for a given reaction, based on T-optimal design. This protocol is then tested for the case of second-order and pseudo-first-order reactions using both experiments and computer simulations. To solve the second problem, we derive the information function for second-order reactions and use this function to find the optimal sampling points for estimating the kinetic constants. The third problem is further complicated by the fact that the optimal measurement times for determining the correct kinetic model differ from those needed to obtain good estimates of the kinetic constants. To solve this problem, we propose a Pareto optimal approach that can be tuned to give the set of best possible solutions for the two criteria. One important advantage of this approach is that it enables the integration of a priori knowledge into the workflow.

Journal Article↗

Revealing Hidden Variables in DESI-Based Spatial Metabolomics: Solvent Composition and Tissue Type as Critical Drivers.

In the development of a desorption electrospray ionization (DESI) workflow for spatial metabolomics, we investigated the impact of two commonly used solvent systems, 90% acetonitrile (ACN) and 90% methanol (MeOH), on the spatial metabolomic profiling of various murine tissues. The performance of both solvents was evaluated across several metabolite classes (central carbon metabolites, amino acids, and fatty acids). Although the ACN-based solvent system led to higher signal intensities for small polar metabolites involved in glycolysis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism, the MeOH-based solvent system provided superior signal intensities for fatty acids. These findings demonstrate that the solvent composition differentially influences metabolite extraction and ionization processes in DESI and should be carefully matched to the biological questions and metabolite classes of interest. As a proof-of-principle, the ACN solvent system was applied to a pilot study based on a rat model of renal ischemic injury, revealing region-specific metabolic changes between normoxic and ischemic conditions. Together, these results demonstrate the importance of solvent selection in DESI-based spatial metabolomics and showcase the ability of this approach to uncover spatially resolved metabolic adaptations associated with tissue injury.

Animals↗

Antibody-Based Proximity Labeling Reveals Bait-Proximal Proteomes in Paraffin-Embedded and Snap-Frozen Tissue Samples.

Proximity-based labeling approaches have proven highly valuable for uncovering protein-protein interactions, yet their application to primary patient material remains challenging. Here, we present a workflow enabling the use of the antibody-based ProtA-Turbo proximity labeling system in both formalin-fixed paraffin-embedded (FFPE) and snap-frozen tissue specimens. Our method efficiently directs biotinylation to diverse antibody baits across tissues of different origins. Downstream mass spectrometry-based proteomics analyses demonstrate the specificity of the method by profiling the proximal proteome of H3K27ac-marked chromatin, the nuclear lamina-associated protein EMD, and the Ser2-phosphorylated POLR2A subunit of RNA polymerase II. Using this method, we identified cell-type-specific factors and transcriptional regulators in salivary gland carcinoma, healthy testis, and testicular cancer tissue sections. The ability to detect disease-associated complexes directly within their native, spatially resolved cellular context using ProtA-Turbo can provide new insights into the molecular basis of human disease and may reveal novel, potentially actionable factors with translational relevance.

Humans↗

LCM-Enriched Proteomic Characterization of Antibody-Mediated Glomerular Damage and Complement Activation in Pre-Clinical Models.

Biologics, lipid nanoparticles, and other therapeutic modalities can result in adverse events, often detected as lesions during preclinical pathology assessments. Characterization of these lesions provides valuable information during drug development to contextualize mechanisms of injury and assess species translatability. Here, we investigated the utility of a laser capture microdissection (LCM)-enriched mass spectrometry proteomics approach to analyze two well-characterized preclinical models of regional (glomerular) injury: Passive Heyman Nephritis in rats and bovine gamma globulin-induced glomerular injury in nonhuman primates (NHPs). Using LCM-enriched proteomics, glomeruli were isolated from formalin-fixed paraffin-embedded kidney tissue in the rat model, enabling identification of 4,661 proteins and quantification of 3,410. Proteinuria measurements were compared with digital pathology metrics of glomerular morphology and proteomics results, with all modalities yielding concordant evidence of glomerular injury and proteomics confirming the role of complement activation. The same LCM- enriched proteomics workflow was applied to an NHP model of induced glomerular damage, identifying 4,623 proteins, quantifying 3,000, and confirming qualitative concordance with established features of complement-mediated glomerular injury. Together, these findings illustrate the applicability of LCM-enriched proteomics for region-specific characterization of antibody-mediated tissue injury and support its use as a hypothesis-generating platform in translational toxicologic pathology.

Animals↗

Analysis of Confounding Factors in Reactive Cysteine Profiling Reveals Enhanced Chromatin-Protein Association via CDK7 Inhibition by THZ1.

Recent advances in activity-based proteome profiling (ABPP) have enabled the global mapping of cysteine ligandability, uncovering novel biological insights and opportunities for identifying disease vulnerabilities. While both live-cell-based and native-lysate-based ABPP have been applied, how cysteine ligandability differs between these systems and what factors influence these measurements remain unclear. Building on our previous development of a high-throughput TMT-ABPP workflow for native lysates, here we adapt the protocol for live cells and systematically compare cysteine ligandability across both platforms. Our analysis reveals three major contributors to the discrepancies: in-cellular cysteine accessibility, protein abundance changes, and protein relocalization. Notably, we highlight that the CDK7 inhibitor THZ1 induces substantial protein relocalization and promotes chromatin binding. Together, these results provide a practical framework for ABPP experimental design and data interpretation, supporting the more accurate application of ABPP in functional proteomics and drug discovery.

Cysteine↗

A Rapid Poly(ethylene glycol)-Assisted Magnetic Isolation Approach for High-Throughput Extracellular Vesicle Isolation and Subsequent Biomarker Analysis.

Extracellular vesicles (EVs) are crucial mediators of intercellular communication and have the potential to serve as biomarkers for disease diagnosis and therapeutic monitoring. However, most EV isolation methods often require large sample volumes and specialized instruments or involve trade-offs between purity, yield, cost, and scalability. We developed MagPEG, a workflow that combines poly(ethylene glycol) (PEG)-mediated EV aggregation with magnetic beads to provide a simple, reproducible alternative to ultracentrifugation, size-exclusion chromatography, and commercial precipitation kits. Our optimization experiments clarified the PEG concentration, ionic strength, and bead surface chemistry that collectively influence EV aggregation, capture efficiency, and contaminant coprecipitation, allowing us to define conditions that improve purity while maintaining high recovery. Compared with commonly used methods, MagPEG produced EVs with comparable size distribution, EV markers, and proteomic profiles while relying only on standard laboratory supplies. A key feature of the platform is that EVs and EV-associated DNA, RNA, and proteins can be sequentially extracted from the same bead-bound material, reducing sample loss and hands-on time and enabling multiomic analysis for limited clinical or small animal samples. MagPEG is compatible with downstream applications including proteomics, bead-based assays, and miRNA quantification. When applied to human serum, the method supported high-throughput EV proteomic profiling and enabled the identification of Alzheimer's disease-associated protein signatures, illustrating its utility for biomarker discovery. Overall, our results establish MagPEG as a powerful, rapid, scalable, and high-throughput solution for translational applications in biomarker discovery.

Polyethylene Glycols↗

Automated MALDI-TOF-MS sample preparation in combinatorial polymer research.

A new automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) sample spotting technique that allows the integration of MALDI sample preparation in the workflow of combinatorial polymer research is described. The technique is performed utilizing a commercially available synthetic robot and was first evaluated with polymer standards of known composition and later on used for the monitoring of the living cationic ring-opening polymerization of 2-ethyl-2-oxazoline. The spotting was carried out as a multiple layer approach, which offers the ability of complex sample preparation without the requirement of premixing the different components. The described technique reduces the time required for sample preparation and offers the possibility of automated sample spotting during polymerization reactions performed in a synthetic robot. This allows the integration of molecular weight screening and polymer end/group determination utilizing MALDI-TOF-MS as a high-throughput tool in combinatorial polymer research.

Journal Article↗

SynCar: an approach to automated synthesis.

The automation of all aspects of manual solution-phase synthesis into one integrated, efficient, and reliable system could be regarded as something of an unmet challenge in organic chemistry. The requirements for modern solution-phase libraries in mainstream drug discovery is typically 50-250 high-purity compounds on a 10-100-mg scale, whether for target class libraries or lead optimization, and short cycle time in combination with high capacity is critical. To achieve these goals, in a codevelopment between Aventis and Accelab GmbH, Kusterdingen, Germany, we designed a completely novel system of independent workstations connected by a shuttle transfer system produced by Montech, Derendingen, Switzerland. Seven modular workstations process four reactions on each shuttle in parallel, with the ability to perform synthesis (temperature control and liquid reagent handling), filtration, liquid-liquid extraction, evaporation, weighing, solid-phase extraction, and HPLC/MS analysis. The modular design enables the continuous loading of shuttles at any time, and each shuttle can have its own workflow. The design also allows easy expansion for future needs. The result is a combination of high flexibility and high throughput.

Chemistry, Organic↗

Setup for high-throughput impedance screening of gas-sensing materials.

This paper reports on the setup for a high-throughput impedance measurement system that allows rapid screening of the electrical and dielectrical properties of solid-state sample libraries in variable atmospheres and temperatures. Using multielectrode arrays, most time-consuming steps in the workflow are parallelized. In addition, an approach for automated data evaluation of impedance spectra is presented. For reasons of verification of robust measuring results and reproducibility, screening results of a sample library composed of doped indium(III) oxide as a resistive-type gas-sensing material are discussed on the basis of the determined sensitivities focusing temperature and testing gas gradients.

Journal Article↗