Metabolic Regulation of Apoptosis in Cancer.

Apoptosis is a cellular suicide program that plays a critical role in development and human diseases, including cancer. Cancer cells evade apoptosis, thereby enabling excessive proliferation, survival under hypoxic conditions, and acquired resistance to therapeutic agents. Among various mechanisms that contribute to the evasion of apoptosis in cancer, metabolism is emerging as one of the key factors. Cellular metabolites can regulate functions of pro- and antiapoptotic proteins. In turn, p53, a regulator of apoptosis, also controls metabolism by limiting glycolysis and facilitating mitochondrial respiration. Consequently, with dysregulated metabolism and p53 inactivation, cancer cells are well-equipped to disable the apoptotic machinery. In this article, we review how cellular apoptosis is regulated and how metabolism can influence the signaling pathways leading to apoptosis, especially focusing on how glucose and lipid metabolism are altered in cancer cells and how these alterations can impact the apoptotic pathways.

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group.

Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given the potential role of infections in the aetiology of leukaemia in children without DS, we investigated whether there was an association between early-life infections and acute leukaemia in children with DS. Maternal infections during pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997 and 2002. DS controls (N=173) were selected from the cases' primary care clinics and frequency matched on age at leukaemia diagnosis. Data were collected on demographics, child's medical history, mother's medical history, and other factors by maternal interview. Analyses were conducted using unconditional logistic regression adjusted for potential confounders. A significant negative association was observed between acute leukaemia and any infection in the first 2 years of life (adjusted odds ratio (OR)=0.55, 95% confidence interval (CI) (0.33-0.92); OR=0.53, 95% CI (0.29-0.97); and OR=0.59, 95% CI (0.28-1.25) for acute leukaemia combined, ALL, and AML respectively). The association between acute leukaemia and maternal infections during pregnancy was in the same direction but not significant. This study offers support for the hypothesis that early-life infections may play a protective role in the aetiology of acute leukaemia in children with DS.

Mapping XML documents into databases: a Data-Driven Framework for bioinformatic data interchange.

The Data-Driven Framework (DDF) described here addresses two major problems for healthcare Electronic Data Interchange, data formats and software development costs. The use of a standard XML Document Type Definition (DTD) allows robust representation in any application area and leverages industry-standard tools and development directions. The DDF allows reduced software development and maintenance costs since all data-entry and database tools are generated from the DTD. The DTD can change and the tools can be regenerated. The case-study below uses the DDF for reporting cell assays to determine the roles of factors influencing cellular gene expression and regulation.

Improving interorganizational data interchange for drug development.

This paper presents a reengineered process that uses a markup language to do interorganizational data interchange between the participants in the US drug development process. The two major goals of this paper are to present (1) a detailed enough description of the reengineered version of this process that a practitioner will be able to use it and (2) a case-study of the reengineering of an interorganizational data interchange system that is applicable to other areas in health care. The detailed description is augmented with a companion web-site that shows all programs in a working prototype. The case-study uses an IDEF0 model to show the structure of benefits from markup standards for interorganizational data interchange.

A case study of the evolving software architecture for the FDA generic drug application process.

This primary goal of this project was to develop a software architecture to support the Food and Drug Administration (FDA) generic drug application process by making it more efficient and effective. The secondary goal was to produce a scalable, modular, and flexible architecture that could be generalized to other contexts in interorganizational health care communications. The system described here shows improvements over the old system for the generic drug application process for most of the defined design objectives. The modular, flexible design that produced this new system offers lessons for the general design of distributed health care information systems and points the way to robust application frameworks that will allow practical development and maintenance of a distributed infrastructure.

Collaborative bioinformatics: data warehouses for targeted experimental results.

Current functional bioinformatics approaches are handicapped by the inability to store functional data at all or by a scattering of data across heterogeneous databases that are difficult to link and query. The Cellular Response Database (CRD) (http://LHI5.umbc.edu/crd) is designed to store and retrieve data concerning changes in in vitro cellular functions associated with stimuli, such as cytokines and drugs. The database can store a broad range of data, including protein or mRNA expression, as well as functional cellular data, such as apoptosis or adherence. This unique ability to store heterogeneous data using a single data model will minimize difficulties associated with searching multiple databases. Authors with articles accepted by participating journals are invited to submit data to the CRD. Submission instructions are outlined, along with a review of the CRD's development.

Can the US minimum data set be used for predicting admissions to acute care facilities?

This paper is intended to give an overview of Knowledge Discovery in Large Datasets (KDD) and data mining applications in healthcare particularly as related to the Minimum Data Set, a resident assessment tool which is used in US long-term care facilities. The US Health Care Finance Administration, which mandates the use of this tool, has accumulated massive warehouses of MDS data. The pressure in healthcare to increase efficiency and effectiveness while improving patient outcomes requires that we find new ways to harness these vast resources. The intent of this preliminary study design paper is to discuss the development of an approach which utilizes the MDS, in conjunction with KDD and classification algorithms, in an attempt to predict admission from a long-term care facility to an acute care facility. The use of acute care services by long term care residents is a negative outcome, potentially avoidable, and expensive. The value of the MDS warehouse can be realized by the use of the stored data in ways that can improve patient outcomes and avoid the use of expensive acute care services. This study, when completed, will test whether the MDS warehouse can be used to describe patient outcomes and possibly be of predictive value.

Functional bioinformatics: the cellular response database.

Biological Scientists function in an increasingly data rich environment. The emerging field of bioinformatics is attempting to insure that this flow of information can be structured to support the generation of significant biological hypothesis and ultimately new knowledge. To date, most of the current databases have focused on protein and nucleic acid sequence information as the principle type of data stored for further interpretation. In this paper, we describe the Cellular Response Database. This database stores functional information regarding the changes of cellular gene expression associated with various stimuli, and supports queries linking cell types, expressed genes, and inducers. The database is designed to support information-intensive queries to aid in the determination of biological function, and is flexible enough to allow the storage of a broad range of experimental data such as cytotoxicity data, immunoassays of target gene protein expression, and others.

An intelligent information systems architecture for clinical decision support on the Internet.

This paper presents a prototype of an agent-based intelligent information systems architecture that can provide clinical decision support in a distributed, heterogeneous environment such as the Internet. After presenting the architecture, a specific transaction sequence is detailed and implemented to test the architecture. A transaction sequence is a detailed analysis of all actions by all entities to accomplish the system goal. In this case, the goal is to give decision support information access to a provider in the context of a computerized patient record. Based on the results of the prototype implementation, we argue that the system is scaleable and discuss other transactions, standards, and needed development.

Priming intelligent split menus with text corpora for computerized patient record data-entry.

This paper describes a methodology for using the knowledge in existing health care text corpora to prime intelligent split menus for provider data-entry. A split menu is one where the top portion of a menu list is organized by user-selection frequency and the bottom portion of the list is traditionally organized in alphabetical order. A simulation shows that data-entry with these intelligent split menus requires between two and five times less effort (in terms of user selections or mouse clicks) than menus arranged alphabetically. This paper uses a corpus from echocardiography to develop the simulation. The methodology uses statistical associations between word categories in the corpus such as 'anatomy' or 'pathology' to prime the frequency ordering of the menus. A dictionary of terms contains the categorical information. After the initial priming, actual user selections are used to update the frequencies used to adapt to providers' individual data-entry patterns.

The 'Learnmore' project: information acquisition solutions for the long-term care information system.

Research and development efforts on Long Term Care (LTC) information systems are only beginning to appear in the literature. For the past two years, a small, interdisciplinary team of researchers (the Learnmore Team) have designed information solutions to information acquisition problems in LTC systems. This paper provides an overview of the Learnmore Team's proposed solutions to acquisition problems experienced by end-users (clinicians, students, and patients) and human experts. Solutions addressing information acquisition costs of integrated expert systems are also discussed. Critical issues and experiences gained during the development of these solutions are presented.

Transforms of the computerized patient record data model: from transactions to analytical processing.

The design of Computerized Patient Record databases needs to be different depending on whether the focus of the database is transaction processing or analytical processing. Transaction processing includes the operational use of databases for single patient update during clinical encounters. Analytical processing includes cross-patient querying for research or clinical management. These different design needs are defined. A case study is presented for the methodology that transforms transaction databases to analytical ones. The resulting analytical design is argued to be successfully evaluated according to specific criteria of useability and maintainability. This methodology is easily replicated in any relational database environment.

Clinical resource auditing and decision support for computerized patient record systems: a mediated architecture approach.

This paper has three major goals: (1) Show by demonstration (in a currently implemented CPR) that for this case, the additional information entry required by providers to acquire the information for Clinical Decision Support (CDS) and Resource Auditing (RA) comes as a side effect of patient care documentation. (2) Use simple simulation to explore the practical issues of allowing users database access to this cross-patient information for CDS and RA. (3) Relate by argument the findings in 1 and 2 to the concept of mediated information systems architectures for CDS and RA. The primary finding of this paper is that a mediated architecture is the only practical way to offer distributed knowledge and data resources to the CPR user.

Information engineering for molecular diagnostics.

Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field.

Undergraduate health care informatics education: a needs analysis and proposed curriculum.

This paper describes a needs analysis and resulting curriculum in Health Care Informatics. It is implemented as a track for the BS degree within the Department of Information Systems at the University of Maryland, Baltimore County. The track in Health Care Informatics is an interdisciplinary specialty within the broader field of Information Systems which is itself an interdisciplinary field. The needs analysis shows current thinking by practitioners and educators in the new field of Health Care Informatics. It also presents a survey of undergraduate students to monitor interest in and knowledge of this field. A curriculum design is presented that addresses these needs.

The standard data model approach to patient record transfer.

This paper develops an approach to electronic data exchange of patient records from Ambulatory Encounter Systems (AESs). This approach assumes that the AES is based upon a standard data model. The data modeling standard used here is IDEFIX for Entity/Relationship (E/R) modeling. Each site that uses a relational database implementation of this standard data model (or a subset of it) can exchange very detailed patient data with other such sites using industry standard tools and without excessive programming efforts. This design is detailed below for a demonstration project between the research-oriented geriatric clinic at the Baltimore Veterans Affairs Medical Center (BVAMC) and the Laboratory for Healthcare Informatics (LHI) at the University of Maryland.

Improving the efficiency of patient recruitment with an automated telephone screening system in a client-server environment.

An automated telephone screening system was implemented at the Baltimore VA Hospital on a Local Area Network (LAN) to evaluate older adults for the GRECC research program. Using the system for decision support, a registered nurse (RN) placed 117 phone calls to older adults in the Baltimore community over a 3 month period. The modular design of the system allowed tracking of inclusion and exclusion criteria which was shared by clinicians and researchers. The design goal of the telephone screening system was to reduce time and personnel costs and increase the effectiveness of screening for recruitment for a major research project. Effectiveness is defined as avoiding under--or over--screening. Using the telephone system, it is estimated the research team saved over $6,000.00 in unnecessary medical evaluation in a 3 months period. As the system develops, the process by which older adults are assessed for research programs in the Geriatrics Service at the Baltimore VAMC will provide additional cost efficiencies.

Direct physician entry of injury information and automated coding via a graphical user interface.

Injury data in the paper medical record are often inaccurate or lack adequate specificity to evaluate trauma patient care. To improve the quality of recorded injury data, we are testing a graphical, anatomic-based interface for quick collection of detailed injury information directly from the trauma physician. Navigation and data collection throughout the interface are facilitated by anatomic illustrations, menus, lists, and "dialog boxes". Using a "point and click" method, the user selects a specific anatomic structure (i.e., the spleen) from drawings. Detailed injury information, specific to the selected structure, is then collected from the user in an "intelligent" modal dialog box. The software uses SNOMED III nomenclature to create and store ICD, AIS, and trauma registry codes for each injury. Users can review and print abbreviated and detailed injury information for each patient. This demonstration will walk viewers through the injury collection and review process for injuries to the abdomen. We plan to evaluate the interface for accuracy, speed, user satisfaction and resources expended by comparing it with current methods of data collection and injury coding at our level I trauma facility.