CytoAccess, a relational laboratory information management system for a clinical cytogenetics laboratory

We developed a CytoAccess laboratory management system based on the widely used Microsoft Access software to facilitate data processing, result reporting, and quality management for a full-service cytogenetics laboratory. The CytoAccess system consists of four functional modules. The data entry module is for logging in patient information. The result entry module is used to generate chromosome, fluorescent in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) reports. The administrative module enables periodic monitoring of quality control and quality improvement (QA/QI) parameters and produces billing forms. The maintenance module allows users to update clinical demographics, report templates, code tables, and to refresh data links. We have integrated into this system over 15,000 chromosome and FISH results from prenatal, postnatal, and cancer cases for the past six years. This system is cost-effective, user-friendly, flexible in updating, and potentially adaptable for data mining.     

Online self-administered training for post-traumatic stress disorder treatment providers: design and methods for a randomized, prospective intervention study

Background

Quality improvement (QI) programs focused on mastery of content by individual staff members are the current standard to improve resident outcomes in nursing homes. However, complexity science suggests that learning is a social process that occurs within the context of relationships and interactions among individuals. Thus, QI programs will not result in optimal changes in staff behavior unless the context for social learning is present. Accordingly, we developed CONNECT, an intervention to foster systematic use of management practices, which we propose will enhance effectiveness of a nursing home Falls QI program by strengthening the staff-to-staff interactions necessary for clinical problem-solving about complex problems such as falls. The study aims are to compare the impact of the CONNECT intervention, plus a falls reduction QI intervention (CONNECT + FALLS), to the falls reduction QI intervention alone (FALLS), on fall-related process measures, fall rates, and staff interaction measures.

Methods/design

Sixteen nursing homes will be randomized to one of two study arms, CONNECT + FALLS or FALLS alone. Subjects (staff and residents) are clustered within nursing homes because the intervention addresses social processes and thus must be delivered within the social context, rather than to individuals. Nursing homes randomized to CONNECT + FALLS will receive three months of CONNECT first, followed by three months of FALLS. Nursing homes randomized to FALLS alone receive three months of FALLs QI and are offered CONNECT after data collection is completed. Complexity science measures, which reflect staff perceptions of communication, safety climate, and care quality, will be collected from staff at baseline, three months after, and six months after baseline to evaluate immediate and sustained impacts. FALLS measures including quality indicators (process measures) and fall rates will be collected for the six months prior to baseline and the six months after the end of the intervention. Analysis will use a three-level mixed model.

Discussion

By focusing on improving local interactions, CONNECT is expected to maximize staff's ability to implement content learned in a falls QI program and integrate it into knowledge and action. Our previous pilot work shows that CONNECT is feasible, acceptable and appropriate.

Trial Registration

ClinicalTrials.gov: NCT00636675     

Functional dissection of LIS1 and NDEL1 towards understanding the molecular mechanisms of cytoplasmic dynein regulation

LIS1 and NDEL1 are known to be essential for the activity of cytoplasmic dynein in living cells. We previously reported that LIS1 and NDEL1 directly regulated the motility of cytoplasmic dynein in an in vitro motility assay. LIS1 suppressed dynein motility and inhibited the translocation of microtubules (MTs), while NDEL1 dissociated dynein from MTs and restored dynein motility following suppression by LIS1. However, the molecular mechanisms and detailed interactions of dynein, LIS1, and NDEL1 remain unknown. In this study, we dissected the regulatory effects of LIS1 and NDEL1 on dynein motility using full-length or truncated recombinant fragments of LIS1 or NDEL1. The C-terminal fragment of NDEL1 dissociated dynein from MTs, whereas its N-terminal fragment restored dynein motility following suppression by LIS1, demonstrating that the two functions of NDEL1 localize to different parts of the NDEL1 molecule, and that restoration from LIS1 suppression is caused by the binding of NDEL1 to LIS1, rather than to dynein. The truncated monomeric form of LIS1 had little effect on dynein motility, but an artificial dimer of truncated LIS1 suppressed dynein motility, which was restored by the N-terminal fragment of NDEL1. This suggests that LIS1 dimerization is essential for its regulatory function. These results shed light on the molecular interactions between dynein, LIS1, and NDEL1, and the mechanisms of cytoplasmic dynein regulation.     

A primer on rodent identification methods

Identifying laboratory rodents as a group may be sufficient if all the animals are to receive the same treatment and/or manipulation and if individual variations in response are not to be recorded separately. However, it is frequently necessary to be able to differentiate between individual animals used in a study. Identification of individual animals may also be necessary to maintain health records and to properly manage colonies of laboratory animals in compliance with regulatory agencies and research protocol requirements.     

A real-time and dynamic biological information retrieval and analysis system (BIRAS)

The aim of this study is to design a biological information retrieval and analysis system (BIRAS) based on the Internet. Using the specific network protocol, BIRAS system could send and receive information from the Entrez search and retrieval system maintained by National Center for Biotechnology Information (NCBI) in USA. The literatures, nucleotide sequence, protein sequences, and other resources according to the user-defined term could then be retrieved and sent to the user by pop up message or by E-mail informing automatically using BIRAS system. All the information retrieving and analyzing processes are done in real-time. As a robust system for intelligently and dynamically retrieving and analyzing on the user-defined information, it is believed that BIRAS would be extensively used to retrieve specific information from large amount of biological databases in now days. The program is available on request from the corresponding author.     

Expert systems for clinical pathology reporting

* Conventional automated interpretative reporting systems use standard or "canned" comments for patient reports. These are result-specific and do not generally refer to the patient context. * Laboratory information systems (LIS) are limited in their application of patient-specific content of reporting. * Patient-specific interpretation requires extensive cross-referencing to other information contained in the LIS such as previous test results, other related tests, and clinical notes, both current and previous. * Expert systems have the potential to improve reporting quality by enabling patient-specific reporting in clinical laboratories.     

Development and Evaluation of Patient‐Centered Software for a Weight‐Management Clinic

Objective: To describe a weight‐management clinic software system and to report on its preliminary evaluation. Research Methods and Procedures: The software system standardizes the collection of relevant patient information from an initial medical assessment, weekly clinic visits, and laboratory testing protocol of a medically supervised proprietary meal‐replacement program in a university‐based referral clinic. It then generates monthly patient feedback reports with graphs of clinical and laboratory parameters to support a patient‐centered approach to weight management. After patients and clinic physicians review the data to ensure accuracy, the database is used for subsequent patient feedback reports, reports to referring physicians, quality assurance, and research. Clinic physicians and referring physicians were asked to rate their acceptance of the system. In addition, in a retrospective analysis of data generated by the system, outcomes for patients who received system‐generated feedback (n = 620) were compared with those who participated in the program before the introduction of feedback (n = 130). Results: Clinic and referring physicians reported that they had high overall satisfaction with the software and that the system saved them time, and the latter group reported that it decreased laboratory use. Regarding patients, the feedback group had lower dropout rates in the latter half of the program, better rates of attendance, completion of laboratory tests, and weight loss after 8 weeks. Discussion: The software seems to facilitate the effectiveness of the treatment protocol for obesity and generates a high‐quality database for patient care, clinic administration, quality assurance, and research purposes.     

Genome-wide prediction,display and refinement of binding sites with information theory-based models

Background  

We present Delila-genome, a software system for identification, visualization and analysis of protein binding sites in complete genome sequences. Binding sites are predicted by scanning genomic sequences with information theory-based (or user-defined) weight matrices. Matrices are refined by adding experimentally-defined binding sites to published binding sites. Delila-Genome was used to examine the accuracy of individual information contents of binding sites detected with refined matrices as a measure of the strengths of the corresponding protein-nucleic acid interactions. The software can then be used to predict novel sites by rescanning the genome with the refined matrices.     

VSQual: a visual system to assist DNA sequencing quality control

A lack of pliant software tools that support small- to medium-scale DNA sequencing efforts is a major hindrance for recording and using laboratory workflow information to monitor the overall quality of data production. Here we describe VSQual, a set of Perl programs intended to provide simple and powerful tools to check several quality features of the sequencing data generated by automated DNA sequencing machines. The core program of VSQual is a flexible Perl-based pipeline, designed to be accessible and useful for both programmers and non-programmers. This pipeline directs the processing steps and can be easily customized for laboratory needs. Basically, the raw DNA sequencing trace files are processed by Phred and Cross_match, then the outputs are parsed, reformatted into Web-based graphical reports, and added to a Web site structure. The result is a set of real time sequencing reports easily accessible and understood by common laboratory people. These reports facilitate the monitoring of DNA sequencing as well as the management of laboratory workflow, significantly reducing operational costs and ensuring high quality and scientifically reliable results.     

Postapproval monitoring and the IACUC

Monitoring of the use of live vertebrate animals in research, teaching, and testing after approval of their use by an institutional animal care and use committee (IACUC) are receiving increased attention in the laboratory animal community. In this article the author provides his opinions on the value of postapproval monitoring (PAM) to the overall self-regulation that is the responsibility of an IACUC. PAM must never supersede or replace federally mandated IACUC responsibilities, but an efficient PAM process can provide significant additional information that enables an institution to be confident that it is meeting both the letter and the spirit of the federal regulations developed to ensure humane animal care. PAM personnel should be excellent communicators and able to maintain a professional demeanor in challenging circumstances. Their knowledge of laboratory animal care, invasive procedures, and regulations will enable them to align the pursuit of scientific research with adherence to these regulations. An effective PAM program involves knowledgeable individuals who can, on behalf of the IACUC, monitor new procedures and personnel and provide IACUC-mandated training or retraining.     

Avoiding biohazards in medical,veterinary and research laboratories

Personnel in medical, veterinary or research laboratories may be exposed to a wide variety of pathogens that range from deadly to debilitating. For some of these pathogens, no treatment is available, and in other cases the treatment does not fully control the disease. It is important that personnel in laboratories that process human or microbiological specimens follow universal precautions when handling tissues, cells, or microbiological specimens owing to the increasing numbers of individuals infected with hepatitis C and HIV in the US and the possibility that an individual may be asymptomatic when a specimen is obtained. Similar precautions must be followed in laboratories that use animal tissues owing to the possibility of exposure to agents that are pathogenic in humans. Personnel with conditions associated with immunosuppression should evaluate carefully whether or not specific laboratory environments put them at increased risk of disease. We offer here some general approaches to identifying biohazards and to minimizing the potential risk of exposure. The issues discussed can be used to develop a general safety program as required by regulatory or accrediting agencies, including the Occupational Safety and Health Administration.     

Avoiding biohazards in medical, veterinary and research laboratories

Personnel in medical, veterinary or research laboratories may be exposed to a wide variety of pathogens that range from deadly to debilitating. For some of these pathogens, no treatment is available, and in other cases the treatment does not fully control the disease. It is important that personnel in laboratories that process human or microbiological specimens follow universal precautions when handling tissues, cells, or microbiological specimens owing to the increasing numbers of individuals infected with hepatitis C and HIV in the US and the possibility that an individual may be asymptomatic when a specimen is obtained. Similar precautions must be followed in laboratories that use animal tissues owing to the possibility of exposure to agents that are pathogenic in humans. Personnel with conditions associated with immunosuppression should evaluate carefully whether or not specific laboratory environments put them at increased risk of disease. We offer here some general approaches to identifying biohazards and to minimizing the potential risk of exposure. The issues discussed can be used to develop a general safety program as required by regulatory or accrediting agencies, including the Occupational Safety and Health Administration.     

Development of a program model to evaluate the potential for reuse of single-use medical devices: results of a pilot test study

Single-use medical devices (SUDs, or disposables) have become a major expense in hospital budgets. The need for cost reduction and the availability of sterilization technologies other than the autoclave have prompted hospitals worldwide to begin reusing disposables, in many cases without proper assessment of the true costs (time, personnel, etc) and ease/difficulty of implementation of an institutional reuse program. Our group has developed a rigorous program model to evaluate SUDs for reuse. The program comprises 3 sequential protocols: (1) device audit, (2) laboratory evaluation, and (3) clinical evaluation. Use of this model can produce scientific and financial data sufficient for any institution interested in reuse to reach an initial decision about its feasibility. In addition to the testing outcomes, regulatory requirements, the position of manufacturers and third-party reprocessors, and legal and ethical concerns must be considered. A successful reuse program must include ongoing evaluations to ensure that the safety levels and cost savings established during the initial audit and evaluation phases continue. Herein, we give the rationale and details of our program model and discuss results of our pilot application of the "ideal" protocol in a real-world context.     

A sample postapproval monitoring program in academia

The primary goal of an animal care and use program (ACUP) should be to ensure animal well-being while fostering progressive science. Both the Animal Welfare Act (and associated regulations) and the Public Health Service (PHS) Policy require the institutional animal care and use committee (IACUC) to provide oversight of the animal program through continuing reviews to ensure that procedures are performed as approved by the committee. But for many committees the semiannual assessment does not provide an opportunity to observe research procedures being performed. Furthermore, IACUC members are typically volunteers with other full-time commitments and may not be able to dedicate sufficient time to observe protocol performance. Postapproval monitoring (PAM) is a tool that the IACUC can use to ensure that the institution fulfills its regulatory obligation for animal program oversight. When performed by attentive and observant individuals, PAM can extend the IACUC's oversight, management, training, and communication resources, regardless of program size or complexity. No defined PAM process fits all institutions or all situations; rather, the monitoring must match the program under review. Nonetheless, certain concepts, concerns, and conditions affect all PAM processes; they are described in this article. Regardless of the style or depth of PAM chosen for a given program, one thing is sure: failure of the IACUC to engage all available and effective oversight methods to ensure humane, compassionate, efficient, and progressive animal care and use is a disservice to the institution, to the research community and to the animals used for biomedical research, testing, or teaching.     

Direct association of LIS1, the lissencephaly gene product, with a mammalian homologue of a fungal nuclear distribution protein, rNUDE

LIS1 is a product of the causative gene for type I lissencephaly characterized by a smooth brain surface due to a defect in neuronal migration during brain development and a regulatory subunit of platelet-activating factor acetylhydrolase (PAF-AH). It is also a mammalian homologue of the fungal nuclear distribution (nud) gene, nudF, which controls the migration of fungal nuclei. Using the two-hybrid system, we identified a novel LIS1-interacting protein, rat NUDE (rNUDE), and found that it is a mammalian homologue of another fungal nud gene product, NUDE, and Xenopus mitotic phosphoprotein 43 which is phosphorylated in a cell cycle-dependent manner. rNUDE and the catalytic subunits of PAF-AH interact with the N- and C-termini of LIS1, respectively. However, these proteins, instead of simultaneously binding to LIS1, appeared to bind to LIS1 in a competitive manner. These results suggest that LIS1 functions in nuclear migration by interacting with multiple intracellular proteins in mammals.     

Clinical Chemistry Laboratory Automation in the 21st Century - Amat Victoria curam (Victory loves careful preparation)

The era of automation arrived with the introduction of the AutoAnalyzer using continuous flow analysis and the Robot Chemist that automated the traditional manual analytical steps. Successive generations of stand-alone analysers increased analytical speed, offered the ability to test high volumes of patient specimens, and provided large assay menus. A dichotomy developed, with a group of analysers devoted to performing routine clinical chemistry tests and another group dedicated to performing immunoassays using a variety of methodologies. Development of integrated systems greatly improved the analytical phase of clinical laboratory testing and further automation was developed for pre-analytical procedures, such as sample identification, sorting, and centrifugation, and post-analytical procedures, such as specimen storage and archiving. All phases of testing were ultimately combined in total laboratory automation (TLA) through which all modules involved are physically linked by some kind of track system, moving samples through the process from beginning-to-end. A newer and very powerful, analytical methodology is liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). LC-MS/MS has been automated but a future automation challenge will be to incorporate LC-MS/MS into TLA configurations. Another important facet of automation is informatics, including middleware, which interfaces the analyser software to a laboratory information systems (LIS) and/or hospital information systems (HIS). This software includes control of the overall operation of a TLA configuration and combines analytical results with patient demographic information to provide additional clinically useful information. This review describes automation relevant to clinical chemistry, but it must be recognised that automation applies to other specialties in the laboratory, e.g. haematology, urinalysis, microbiology. It is a given that automation will continue to evolve in the clinical laboratory, limited only by the imagination and ingenuity of laboratory scientists.     

The institutional official and postapproval monitoring: the view from 10,000 feet

The role of the institutional official (IO) in ensuring a high-quality program of laboratory animal care and use has received relatively little attention in the literature compared to that of the institutional animal care and use committee (IACUC) or attending veterinarian. Yet the IO is critical to institutional effectiveness. Often not a scientist, especially at colleges and universities, the IO is an executive who bears ultimate responsibility for the care and use of laboratory animals. An IO operates largely through delegation to the IACUC and the institutional veterinarian, yet must maintain a clear view of the program from the executive level--the "view from 10,000 feet." To do so, the IO must bring four critical leadership qualities to the position: (1) vision, (2) a commitment to quality and integrity, (3) strong planning and resource development, and (4) accountability to the laboratory animal program. The IO's ability to act on these qualities and to evaluate the effectiveness of the resulting program requires reliance on a strong program of postapproval monitoring (PAM). Summary data from PAM, based on metrics carefully defined by the IO in consultation with the IACUC and the institutional veterinarian, provide the feedback necessary to guide executive decisions and allow the IO to place the needs of the program of laboratory animal care and use successfully into the larger context of the mission of the institution.     

PHIRE, a deterministic approach to reveal regulatory elements in bacteriophage genomes

MOTIVATION: In silico genome analysis of bacteriophage genomes focuses mainly on gene discovery and functional assignment. The search for regulatory elements contained within these genome sequences is often based on prior knowledge of other genomic elements or on learning algorithms of experimentally determined data, potentially leading to a biased prediction output. The PHage In silico Regulatory Elements (PHIRE) program is a standalone program in Visual Basic. It performs an algorithmic string-based search on bacteriophage genome sequences to uncover and extract subsequence alignments hinting at regulatory elements contained within these genomes, in a deterministic manner without any prior experimental or predictive knowledge. RESULTS: The PHIRE program was tested on known phage genomes with experimentally verified regulatory elements. PHIRE was able to extract phage regulatory sequences correctly for bacteriophages T7, T3, YeO3-12 and lambda, based solely on the genome sequence. For 11 bacteriophages, new predictions of conserved phage-specific putative regulatory elements were made, further corroborating this approach. AVAILABILITY: http://www.agr.kuleuven.ac.be/logt/PHIRE.htm. Freely available for academic use. Commercial users should contact the corresponding author.