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PubMed2006

Open source tools and toolkits for bioinformatics: significance, and where are we?

This review summarizes important work in open-source bioinformatics software that has occurred over the past couple of years. The survey is intended to illustrate how programs and toolkits whose source code has been developed or released under an Open Source license have changed informatics-heavy areas of life science research. Rather than creating a comprehensive list of all tools developed over the last 2-3 years, we use a few selected projects encompassing toolkit libraries, analysis tools, data analysis environments and interoperability standards to show how freely available and modifiable open-source software can serve as the foundation for building important applications, analysis workflows and resources.

Algorithms↗

PubMed1995

The multicentre trial philosophy in stress echocardiography: lessons learned from the EPIC study. EPIC-EDIC Study Project. Echo Persantine International Cooperative Study. Echo-Dobutamine International Cooperative Study.

The scientific assessment of diagnostic tests should not be based upon a small series of results published by the best academic institutions, but ought to require large scale, multicentre validation founded on grass roots institutions with real doctors, real patients and real problems. To this purpose, an international network of stress echo laboratories has been organized, and within a few years has collected data from thousands of studies using pharmacological stress echocardiography, performed with either dipyridamole (EPIC: Echo Persantine International Cooperative Study) or dobutamine (EDIC: Echo Dobutamine International Cooperative Study) stresses. In a widely deregulated field, all network laboratories have agreed: to pass a quality control examination on stress echo reading before entering the study; to adopt an identical drug infusion protocol; to code similarly the LV segments; and to adopt a common scoring system for wall motion analysis. A minimum amount of historical, clinical, and-when available-stress electrocardiographic, angiographic and follow-up data have been collected on each patient, and disseminated in the various centres, facilitating the creation of an international stress echo language that will help, not only the production of high quality scientific data, but also the build up of a common stress echo lab, with a standardized way of making the studies, unifying the methods and terminology, and archiving data. To date, we have 50 echo laboratories from 15 nations across four continents (Europe, America, Asia and Africa) actively involved in this project. These data will ultimately fill the gap between the academic theory of journals and the pragmatic experience of daily life in a busy echocardiographic laboratory.

Echocardiography↗

PubMedDate not supplied

Testing for neutral-to-ground connections in new construction.

A study was performed to seek out inadvertent connections between neutral and ground in the power distribution system of a newly constructed hospital, prior to occupancy. Such connections are not only violations of code but could cause medical device problems. Ground wires are not intended to carry load currents except during faults. When currents do flow in grounds, medical device chassis voltages are elevated and some devices may respond unpredictably. Suitable acceptance testing is not commonly done. In this study, a simple test method was developed that helped reveal and correct many neutral-ground misconnections. The authors advocate incorporating such a test into building construction contract specifications.

Electric Power Supplies↗

PubMed2003

The role of certified nursing assistants in nursing homes.

UNLABELLED: OBJECTIVE Pilot study to examine the experiences of the certified nursing assistants (CNAs) in Colorado nursing homes. BACKGROUND DATA: CNAs provide 80% to 90% of the care to residents in nursing homes. Their reported turnover rate is as high as 400% in some studies, and the potential pool of CNAs is dwindling. As the demand for CNAs increases, their experiences must be understood to effectively address recruitment and retention issues. METHODS: Minimally structured interviews of 12 CNAs in 6 Colorado nursing homes and observations of care provided were conducted. Atlas/Ti software was used as a data management tool for analyzing and coding data. RESULTS: The overriding theme that emerged from the interviews was "we love our jobs." Three patterns of thought and behavior emerged: attributes of the CNA, working conditions of the CNA, and future success of the CNA and the nursing home. CONCLUSIONS: Issues important to CNAs revolved around basic motivational factors, such as job enrichment opportunities, personal growth opportunities, recognition, responsibility, and sense of achievement. Leadership must become creative and build on that base, providing CNAs with job mobility, job enrichment opportunities, recognition, and increased job responsibility, producing positive outcomes not only for the CNA but also for the resident and the facility.

Adult↗

PubMed2004

Structured representation of the pharmacodynamics section of the summary of product characteristics for antibiotics: application for automated extraction and visualization of their antimicrobial activity spectra.

OBJECTIVE: The aim of this study was to construct automatically a knowledge base concerning the pharmacodynamic properties of antibiotics and a visualization tool. DESIGN: The authors studied the various guidelines used to write the pharmacodynamics section of the Summary of Product Characteristics (SPC) for antibiotics and constructed a conceptual model of the information. Particular words, syntagms, and punctuation elements were marked in the SPC texts, and automatic extraction was then used to build a knowledge base. This base was used to create dynamic HTML tables displaying the activity spectra of the antibiotics. MEASUREMENTS: The authors analyzed the performances of automatic extraction (recall and precision). RESULTS: The conceptual pharmacodynamics model dealt with antibiotics, pathogens, susceptibility tests, and the prevalence of resistance. Automatic extraction had a recall rate of 97.9% and a precision of 96.2%. The tool displaying antibiotic spectra and resistance prevalences used color codes to identify differences in susceptibility. CONCLUSION: This tool can provide an overview of the prevalence of resistance as expressed in SPC in primary care settings. Its potential impact should be evaluated.

Anti-Bacterial Agents↗

PubMedDate not supplied

Designing a mixed methods study in primary care.

BACKGROUND: Mixed methods or multimethod research holds potential for rigorous, methodologically sound investigations in primary care. The objective of this study was to use criteria from the literature to evaluate 5 mixed methods studies in primary care and to advance 3 models useful for designing such investigations. METHODS: We first identified criteria from the social and behavioral sciences to analyze mixed methods studies in primary care research. We then used the criteria to evaluate 5 mixed methods investigations published in primary care research journals. RESULTS: Of the 5 studies analyzed, 3 included a rationale for mixing based on the need to develop a quantitative instrument from qualitative data or to converge information to best understand the research topic. Quantitative data collection involved structured interviews, observational checklists, and chart audits that were analyzed using descriptive and inferential statistical procedures. Qualitative data consisted of semistructured interviews and field observations that were analyzed using coding to develop themes and categories. The studies showed diverse forms of priority: equal priority, qualitative priority, and quantitative priority. Data collection involved quantitative and qualitative data gathered both concurrently and sequentially. The integration of the quantitative and qualitative data in these studies occurred between data analysis from one phase and data collection from a subsequent phase, while analyzing the data, and when reporting the results. DISCUSSION: We recommend instrument-building, triangulation, and data transformation models for mixed methods designs as useful frameworks to add rigor to investigations in primary care. We also discuss the limitations of our study and the need for future research.

Health Services Research↗

PubMed2004

Growth-rate recovery of Escherichia coli cultures carrying a multicopy plasmid, by engineering of the pentose-phosphate pathway.

Expression of plasmid-encoded genes in bacteria is the most common strategy for the production of specific proteins in biotechnological processes. However, the synthesis of plasmid-encoded proteins and plasmid-DNA replication often places a metabolic load (metabolic burden) into the cell's biochemical capacities that usually reduces the growth rate of the producing culture (Glick BR. Biotechnol Adv 1995;13:247-261). This metabolic burden may be related to a limited capacity of the cell to supply the extra demand of building blocks and energy required to replicate plasmid DNA and express foreign multicopy genes. Some of these required blocks are intermediaries of the pentose phosphate (PP) pathway, e.g., ribose-5-phosphate, erythrose-4-phosphate. Due to the important impact of metabolic burden on biotechnological processes, several groups have worked on developing strategies to overcome this problem, like reduction of plasmid copy number (Seo JH, Bailey JE. Biotechnol Bioeng 1985;27:1668-1674; Jones KL, Kim S, Keasling JD. Metab Eng 2000;3:328-338), chromosomal insertion of the gene which product is desired, or changing the plasmid-coded antibiotic resistance gene (Hong Y, Pasternak JJ, Glick BR. Can J Microbiol 1995;41:624-628). However, few efforts have been attempted to overcome the reduction of growth rate due to protein over-expression, by modifying central metabolic pathways (Chou C-H, Bennett GN, San KY. Biotechnol Bioeng 1994;44:952-960). We constructed a high-copy number plasmid carrying the gene for glucose-6-phosphate dehydrogenase, zwf, under the control of an inducible trc promoter (pTRzwf04 plasmid). By transforming a wild-type strain and inducing with IPTG, it was possible to recover growth-rate from 0.46 h(-1) (uninduced) to 0.64 h(-1) (induced). The same transformation in an Escherichia coli zwf(-), allows a growth-rate recovery from 0.43 h(-1) (uninduced) to 0.62 h(-1) (induced). We also studied this effect as part of a laboratory-scale biotechnology process: production of a recombinant insulin peptide by co-transforming E. coli JM101 strain with pTRzwf07, a low-copy-number plasmid that carries the same inducible construction as pTRzwf04, and with the pTEXP-MMRPI vector that carries a TrpLE-proinsulin hybrid gene. In this system, production of TrpLE-proinsulin strongly reduces growth rate; however, overexpression of zwf gene recovers with a growth rate from 0.1 h(-1) in the TrpLE-proinsulin induced strain, to 0.37 h(-1) when both zwf and TrpLE-proinsulin genes were induced. In this paper, we show that the engineering of the pentose phosphate pathway by modulation of the zwf gene expression level partially overcomes the possible bottleneck for the supply of building blocks and reducing power synthesized through the PP pathway, that are required for plasmid replication and plasmid-encoded protein expression.

Cell Proliferation↗

PubMed1994

M.phi 3TII: a new monospecific DNA (cytosine-C5) methyltransferase with pronounced amino acid sequence similarity to a family of adenine-N6-DNA-methyltransferases.

The temperate B.subtilis phages phi 3T and rho 11s code, in addition to the multispecific DNA (cytosine-C5) methyltransferases (C5-MTases) M. phi 3TI and M. rho 11sI, which were previously characterized, for the identical monospecific C5-MTases M. phi 3TII and M. rho 11sII. These enzymes modify the C of TCGA sites, a novel target specificity among C5-MTases. The primary sequence of M. phi 3TII (326 amino acids) shows all conserved motifs typical of the building plan of C5-MTases. The degree of relatedness between M. phi 3TII and all other mono- or multispecific C5-MTases ranges from 30-40% amino acid identity. Particularly M. phi 3TII does not show pronounced similarity to M. phi 3TI indicating that both MTase genes were not generated from one another but were acquired independently by the phage. The amino terminal part of the M. phi 3TII (preceding the variable region 'V'), which predominantly constitutes the catalytic domain of the enzyme, exhibits pronounced sequence similarity to the amino termini of a family of A-N6-MTases, which--like M.TaqI--recognize the general sequence TNNA. This suggests that recently described similarities in the general three dimensional organization of C5- and A-N6-MTases imply divergent evolution of these enzymes originating from a common molecular ancestor.

Amino Acid Sequence↗

PubMed2006

Innovations in mental health services implementation: a report on state-level data from the U.S. Evidence-Based Practices Project.

BACKGROUND: The Evidence-Based Practice (EBP) Project has been investigating the implementation of evidence-based mental health practices (Assertive Community Treatment, Family Psychoeducation, Integrated Dual Diagnosis Treatment, Illness Management and Recovery, and Supported Employment) in state public mental health systems in the United States since 2001. To date, Project findings have yielded valuable insights into implementation strategy characteristics and effectiveness. This paper reports results of an effort to identify and classify state-level implementation activities and strategies employed across the eight states participating in the Project. METHODS: Content analysis and Greenhalgh et al's (2004) definition of innovation were used to identify and classify state-level activities employed during three phases of EBP implementation: Pre-Implementation, Initial Implementation and Sustainability Planning. Activities were coded from site visit reports created from documents and notes from key informant interviews conducted during two periods, Fall 2002-Spring 2003, and Spring 2004. Frequency counts and rank-order analyses were used to examine patterns of implementation activities and strategies employed across the three phases of implementation. RESULTS: One hundred and six discreet implementation activities and strategies were identified as innovative and were classified into five categories: 1) state infrastructure building and commitment, 2) stakeholder relationship building and communications, 3) financing, 4) continuous quality management, and 5) service delivery practices and training. Implementation activities from different categories were employed at different phases of implementation. CONCLUSION: Insights into effective strategies for implementing EBPs in mental health and other health sectors require qualitative and quantitative research that seeks to: a) empirically test the effects of tools and methods used to implement EBPs, and b) establish a stronger evidence-base from which to plan, implement and sustain such efforts. This paper offers a classification scheme and list of innovative implementation activities and strategies. The classification scheme offers potential value for future studies that seek to assess the effects of various implementation processes, and helps establish widely accepted standards and criteria that can be used to assess the value of innovative activities and strategies.

Journal Article↗

PubMed1997

Emergence of template-and-sequence-directed (TSD) syntheses: II. A computer simulation model.

The initiation of the bio-geochemical scenario described in Part I serves in the present work as the basis for computer modeling, where the central process of the simulation algorithm. i.e., peptide-catalyzed oligomeric growth, is based on mass action equations. The computer model starts with a minimal system in which catalyzed growth processes of proto-RNA templates and small peptides take place, starting from their building blocks. The emerging populations of random oligomers also include a very small fraction of proto-tRNAs and a small fraction of catalytic peptides. Using simplifying assumptions regarding catalyzed proto-RNA template-replication, as well as selectivity of certain molecules and processes, the proportion of proto-tRNA in the proto-RNA molecular population increases rapidly; it is followed by TSD peptide synthesis, based on an ad hoc genetic code and specific peptide catalysts allocated for this synthesis. Consequently, a feedback system is initiated in which TSD peptides involved in the relevant catalytic reactions of the TSD syntheses also start to accumulate. The initial sporadic formation of TSD peptides is thus replaced gradually by cycles of positive feedback and autocatalysis characterized by accumulation of catalytic peptides and Proto-tRNAs and TSD-Reaction-Takeover. The model system which can be considered a 'toy model' can synthesize its templates and catalysts under a wide range of reaction parameters and initial concentrations, thus demonstrating a robustness which is essential for molecular evolution processes. The critical stage of the buildup of a molecular mechanism for the initiation of a minimal TSD reaction cycle has thus been described; because of the centrality of TSD reaction cycles in biology, it is assumed to be central also in the origin of life processes.

Adenosine Triphosphate↗

PubMed1996

Communication, accrual to clinical trials, and the physician-patient relationship: implications for training programs.

BACKGROUND: Previous studies have demonstrated that less than 20% of fully eligible patients participate in cancer clinical trials. One of the major factors determining whether patients will be successfully accrued to trials is the quality of the communication occurring between the physician and patient (and family members if present). The accrual process is embedded within the longer-term relationship between the physician and the patient. It is argued that the interaction occurring during the consent process is part of an "alliance building" that the physician and patient use to confront the uncertainty inherent in both the disease itself and the outcome of therapy. METHODS AND RESULTS: The authors describe the framework of a study currently under way in which they are tracking the variation in ways that this interaction is managed by a sample of oncologists and their patients. Physicians and patients are simultaneously filmed and viewed in a split-screen format. A coding system is being developed to analyze the congruence between physicians and patients as they encode and decode sequences of verbal and nonverbal messages. The goal is to understand how physicians and patients manage uncertainty related to the disease and its outcomes. CONCLUSIONS: The authors suggest implications of these observed patterns for the broader range of communicative competencies that medical students must learn.

Classification↗

PubMed2025

Tsbrowse: an interactive browser for ancestral recombination graphs.

SUMMARY: Ancestral recombination graphs (ARGs) represent the interwoven paths of genetic ancestry of a set of recombining sequences. The ability to capture the evolutionary history of samples makes ARGs valuable in a wide range of applications in population and statistical genetics. ARG-based approaches are increasingly becoming a part of genetic data analysis pipelines due to breakthroughs enabling ARG inference at biobank-scale. However, there is a lack of visualization tools, which are crucial for validating inferences and generating hypotheses. We present tsbrowse, an open-source, web-based Python application for the interactive visualization of the fundamental building blocks of ARGs, i.e. nodes, edges and mutations. We demonstrate the application of tsbrowse to various data sources and scenarios, and highlight its key features of browsability along the genome, user interactivity, and scalability to very large sample sizes. AVAILABILITY AND IMPLEMENTATION: Tsbrowse is installed as a Python package from PyPI (https://pypi.org/project/tsbrowse/), while a development version is maintained at https://github.com/tskit-dev/tsbrowse. Documentation is available at https://tskit.dev/tsbrowse/docs/. Source code is archived on Zenodo with DOI, https://doi.org/10.5281/zenodo.15683039.

Software↗

PubMed1998

SALSA: improved protein database searching by a new algorithm for assembly of sequence fragments into gapped alignments.

MOTIVATION: Optimal sequence alignment based on the Smith-Waterman algorithm is usually too computationally demanding to be practical for searching large sequence databases. Heuristic programs like FASTA and BLAST have been developed which run much faster, but at the expense of sensitivity. RESULTS: In an effort to approximate the sensitivity of an optimal alignment algorithm, a new algorithm has been devised for the computation of a gapped alignment of two sequences. After scanning for high-scoring words and extensions of these to form fragments of similarity, the algorithm uses dynamic programming to build an accurate alignment based on the fragments initially identified. The algorithm has been implemented in a program called SALSA and the performance has been evaluated on a set of test sequences. The sensitivity was found to be close to the Smith-Waterman algorithm, while the speed was similar to FASTA (ktup = 2). AVAILABILITY: Searches can be performed from the SALSA homepage at http://dna.uio.no/salsa/ using a wide range of databases. Source code and precompiled executables are also available. CONTACT: torbjorn.rognes@labmed.uio.no

Algorithms↗

PubMed1992

Estimation of median human lethal radiation dose computed from data on occupants of reinforced concrete structures in Nagasaki, Japan.

This paper presents an estimate of the median lethal dose for humans exposed to total-body irradiation and not subsequently treated for radiation sickness. The median lethal dose was estimated from calculated doses to young adults who were inside two reinforced concrete buildings that remained standing in Nagasaki after the atomic detonation. The individuals in this study, none of whom have previously had calculated doses, were identified from a detailed survey done previously. Radiation dose to the bone marrow, which was taken as the critical radiation site, was calculated for each individual by the Engineering Physics and Mathematics Division of the Oak Ridge National Laboratory using a new three-dimensional discrete-ordinates radiation transport code that was developed and validated for this study using the latest site geometry, radiation yield, and spectra data. The study cohort consisted of 75 individuals who either survived > 60 d or died between the second and 60th d postirradiation due to radiation injury, without burns or other serious injury. Median lethal dose estimates were calculated using both logarithmic (2.9 Gy) and linear (3.4 Gy) dose scales. Both calculations, which met statistical validity tests, support previous estimates of the median lethal dose based solely on human data, which cluster around 3 Gy.

Adult↗

PubMed2005

A 3D photon superposition/convolution algorithm and its foundation on results of Monte Carlo calculations.

Based on previous publications on a triple Gaussian analytical pencil beam model and on Monte Carlo calculations using Monte Carlo codes GEANT-Fluka, versions 95, 98, 2002, and BEAMnrc/EGSnrc, a three-dimensional (3D) superposition/convolution algorithm for photon beams (6 MV, 18 MV) is presented. Tissue heterogeneity is taken into account by electron density information of CT images. A clinical beam consists of a superposition of divergent pencil beams. A slab-geometry was used as a phantom model to test computed results by measurements. An essential result is the existence of further dose build-up and build-down effects in the domain of density discontinuities. These effects have increasing magnitude for field sizes < or =5.5 cm(2) and densities < or = 0.25 g cm(-3), in particular with regard to field sizes considered in stereotaxy. They could be confirmed by measurements (mean standard deviation 2%). A practical impact is the dose distribution at transitions from bone to soft tissue, lung or cavities.

Algorithms↗

PubMed1984

Role of strategic communication in nursing theory and research.

Linking the process of nursing with theory and research in interpersonal competence is important in building a comprehensive theory of nursing. One dimension of interpersonal competence is the ability to use communication as a strategic mode of nursing intervention. The study of strategic communication can proceed by identifying communication-relevant nursing objectives, obstacles that inhibit the accomplishment of these objectives, and interpersonal strategies that can be employed to address these obstacles and facilitate goal attainment. The use of free response data collection procedures and theoretically grounded and hierarchically ordered message coding systems represents a viable method to analyze strategic communication.

Communication↗

PubMed1989

Ribonucleotide reductase--new twists in an old tale.

Although they are proliferatively quiescent, the cells in the intact adult rat liver express the gene coding for the M1 subunit of ribonucleotide reductase. But since they do not need deoxyribonucleotides, they promptly inactivate the 88 to 90 kDa M1 products and degrade them into 40 kDa fragments. Partial hepatectomy signals the remaining cells to start proliferating. Two hours before the onset of DNA replication, around 16 to 18 hr after partial hepatectomy, the cells start accumulating a large pool of functional ribonucleotide reductase M2 subunits. Near the end of the G1 build-up the cells step up M1 gene expression, stop inactivating, and reduce the degradation of the M1 products. The accumulating functional 88 to 90 kDa M1 subunits, each with more than one catalytic site, couple with functional M2 subunits to produce active ribonucleotide reductase holoenzyme which accumulates in the outer nuclear membrane from which they supply deoxyribonucleotide precursors to intranuclear replication enzymes. At the end of the S phase, the cell reduces M1 gene expression and resumes degrading 88 to 90 kDa M1 subunits. At least some of the 40 kDa M1 fragments are still active and can form partially active "holoenzymes" when mixed with a standard preparation of functional M2 subunits. The M1 control mechanism appears not to operate in hepatoma cells and Ehrlich ascites tumor cells, both of which maintain a pool of undegraded 88 to 90 kDa M1 components.

Animals↗

PubMed1998

Challenges of establishing a nursing center in rural eastern Oregon.

The success of the center, in fact its very existence, is the result of cooperation among many persons and agencies. Financial gifts, loans and grants have given the clinic a three-year time period to learn valuable lessons on how to organize for self-sufficiency. Staff have learned how to market to increase patient visit and have obtained Federal Rural Health Clinic status which will increase revenues substantially. Nurse Practitioners are learning appropriate visit coding and hold regular brainstorming meetings to develop creative business opportunities to assure financial stability. As a result of these experiences, the NP faculty have been able to design learning experiences for the nurse practitioner students which introduce them to entrepreneurial realities. Challenges are being met by the NPs in this rural practice which require vigor, creativity, and vigilance. Once the center reaches the level of self-sufficiency, it is the intent of the community to build a facility which can support a significant increase in patient load and still have room for other social and health services to operate within the facility. Bridges to the medical community are being strengthened through better communication and more community involvement. Educating the public and the medical community about the role of nurse practitioners and the broad base of nursing centers is a continual challenge for both faculty and students at the School of Nursing.

Community Health Centers↗