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At least 343 records · Page 19Linked to original sources

Process redesign: making your film library work for you.

When Riverside Methodist Hospitals in Columbus, Ohio, experienced serious problems in its radiology film library, administrators recognized that poor processes were to blame and used quality management techniques to create a new system. A radiology information system was part of Riverside's long-range plan, but an effective manual process was implemented first. Riverside had decided that closing the library to referring physician access would result in more successful operations. An Operational Changes Planning Committee composed of file clerks, technologists, managers, radiologists and referring physicians planned the redesign. The committee identified four goals: Reduce unmet requests. Improve response time. Benchmark operations of comparable organizations. Implement an effective manual process prior to automation. Steps in the redesign process included identifying the problem, applying statistical tools to the situation and understanding customer requirements. Flow charts, benchmarking, data collection within the department and focus groups provided important quantitative information. Creating an improved process included the following actions: Work simplification. Work elimination (especially non-value-added work). Uncovering and removing causes of delay. Automation of repetitive tasks via the RIS. Reduction and elimination of any rework steps. One important change was to close the library to physician access. There were moderate gains in effectiveness as a result of redesign of the manual process. Results have continued to improve, and the redesign process provided greater commitment and cooperation for the more significant improvements that followed the RIS introduction.

Efficiency, Organizational↗

Synthesis of highly substituted 5-(trifluoromethyl)ketoimidazoles using a mixed-solid/solution phase motif.

Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS.

Databases as Topic↗

Use of statistical design of experiments in the optimization of amide synthesis utilizing polystyrene-supported N-hydroxybenzotriazole resin.

Two fields that routinely perform reaction optimization studies are chemical development (prior to scale-up) and medicinal or combinatorial chemistry (prior to analogue synthesis or library production). To date, the use of statistical design of experiments (DoE) in conjunction with automated synthesizers has been applied in process research to a greater extent than in the medicinal or combinatorial laboratories. We have applied DoE in conjunction with an automated synthesizer to optimize the synthesis of amides employing resin-bound N-hydroxybenzotriazole (PS-HOBt) active esters as intermediates. This methodology allowed the rapid development of an improved protocol for the parallel synthesis of amides by conversion of carboxylic acids to PS-HOBt esters followed by treatment with appropriate amines. Product isolation involved only simple filtration and evaporation.

Amides↗

An automated sample preparation system for large-scale DNA sequencing.

Recent advances in DNA sequencing technologies, both in the form of high lane-density gels and automated capillary systems, will lead to an increased requirement for sample preparation systems that operate at low cost and high throughput. As part of the development of a fully automated sequencing system, we have developed an automated subsystem capable of producing 10,000 sequence-ready ssDNA templates per day from libraries of M13 plaques at a cost of $0.29 per sample. This Front End has been in high throughput operation since June, 1997 and has produced > 400,000 high-quality DNA templates.

DNA↗

Electronic health record meets digital library: a new environment for achieving an old goal.

Linking the electronic health record to the digital library is a Web-era reformulation of the long-standing informatics goal of seamless integration of automated clinical data and relevant knowledge-based information to support informed decisions. The spread of the Internet, the development of the World Wide Web, and converging format standards for electronic health data and digital publications make effective linking increasingly feasible. Some existing systems link electronic health data and knowledge-based information in limited settings or limited ways. Yet many challenging informatics research problems remain to be solved before flexible and seamless linking becomes a reality and before systems become capable of delivering the specific piece of information needed at the time and place a decision must be made. Connecting the electronic health record to the digital library also requires positive resolution of important policy issues, including health data privacy, government encouragement of high-speed communications, electronic intellectual property rights, and standards for health data and for digital libraries. Both the research problems and the policy issues should be important priorities for the field of medical informatics.

Internet↗

Analyses of compound libraries obtained by high-throughput parallel synthesis: strategy of quality control by high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance techniques.

The growing interest in combinatorial chemistry has led to a new source of compounds from which a large number of leads has emerged over recent years. Parallel synthesis, in particular, allows a quick production of a wide number of individual compounds. A rapid analytical control is needed to determine their quality. A strategy using automated, fast reversed-phase C18 high-performance liquid chromatography with diode-array detection (LC-DAD-MS) followed by atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) and NMR has been developed for their characterisation and purity control. Complementary NMR analyses are done on selected compounds to provide a better structural characterisation of the expected compounds and their potential side-products. Validated libraries are then registered in ISIS databases using automated procedures.

Chemistry, Pharmaceutical↗

Molecular cloning of a phosphoinositide-specific phospholipase C from catfish olfactory rosettes.

A 2.7 kb clone encoding the partial (about 66%) sequence of a phosphoinositide-specific phospholipase C (PLC) was isolated from a cDNA library constructed from channel catfish (Ictalurus punctatus) olfactory rosettes. The clone, designated 30c7, was completely sequenced by automated DNA sequencing and was found to share significant homology with rat and bovine PLCs of the delta 1 isotype. In situ hybridization showed that 30c7 transcripts were expressed in a small subpopulation of olfactory neurons, as well as in other cell types in the olfactory epithelium. Polymerase chain reaction (PCR) analysis indicated that the enzyme was also expressed in several additional tissues, including brain, gill, heart, liver and skeletal muscle. These results suggest that the PLC encoded by clone 30c7 is expressed in several tissues and therefore may have a role in mediating transduction events in diverse tissues as well as in a small group of olfactory neurons.

Amino Acid Sequence↗

Comparative assessment of shockable ECG rhythm detection algorithms in automated external defibrillators.

The sensitivity and specificity to ventricular fibrillation (VF) and ventricular tachycardia (VT), classified as requiring immediate DC shock, of four automated external defibrillators (AEDs) and three advisory defibrillators were assessed using the Department of Health Arrhythmia library. This library collected mostly from patients in hospital, includes a wide variety of ECG rhythms including many with additional noise and interference artefact. The library comprised 278 16-s rhythms, 59 of which were VF, 36 were VT requiring cardioversion and 183 were deemed non-shockable. Non-shockable rhythms included asystole, pacing, slow VT, idioventricular rhythms, sinus and atrial based rhythms, some of which contained ventricular ectopic activity of differing grades. For the AEDs, a positive result (indicating detection of a shockable rhythm) was recorded if charging started or was able to be started at any time during the 16 s of rhythm output and energy subsequently available for discharge. For the advisory defibrillators, a positive result was recorded if a 'shock advised' alert was issued at any time during output of the rhythm. The AEDs exhibited sensitivities to VF in the range 81-94%, and to VF plus shockable VT 64-73%, or 72-83% depending whether VT > 150 beats/min or > 180 beats/min is considered to be shockable. The specificities recorded were in the range 90-94% and 86-92%, respectively. All but one of the advisory defibrillators performed similarly. Excluding the artefact rhythms, specificities in the range 79-91% were obtained. All figures stated are at the lower limit of the 95% confidence interval.

Algorithms↗

A novel frequency distribution selection method for efficient plate layout of a diverse combinatorial library.

A deterministic method (frequency distribution method) for selecting compounds from a partitioned virtual combinatorial library for efficient synthesis is presented here. The method is based on reagent frequency analysis and can be applied to any library of molecules distributed in any given partitioned chemical space (cluster, cell-based, etc.). Compound selection by reagent frequency distribution can produce a unique, diverse set of molecules that adequately represents the library while requiring the least amount of compounds to be synthesized and minimizing the number of different reagents that must be used. This method also provides a practical solution to the configuration of plate layout. Because the method essentially identifies "expensive" regions in the chemical space to synthesize for a desired diversity or similarity coverage, decisions concerning the necessity to synthesize these compounds can be addressed. Minimum compound generation and efficient plate layout results in savings both in time of synthesis and cost of materials. This method always results in a discrete solution, which can be used for any given library size as well as any combination of reagents and is also readily adaptable to robotic automation.

Journal Article↗

Efficiency of automated literature search mechanisms.

This article explores the efficiency of automated literature search techniques to facilitate literature accessibility. It presents three related studies using the National Library of Medicine ( NLM ) literature search on nurse practitioners (1980) as the point of reference. The studies investigate three questions: Is the search reproducible, does it locate the most important articles pertaining to nurse practitioner effectiveness, and can a system be developed to decide efficiently which articles in a voluminous search output should actually be obtained? Results indicate that the NLM search is reproducible but that it lists only a small proportion of available studies. Neither the NLM document nor a computer search using the parameters it cites located a high proportion of critically nominated studies. However, based upon classification of their titles, a workable system can be developed to identify those articles in a search output that are relevant and should be retrieved.

Bibliographies as Topic↗

HUBNET: Wide Area Network utilization of Local Area Network medical reference and communication resources.

The State University of New York at Buffalo School of Medicine and Biomedical Sciences and its associated teaching sites have developed and partially implemented a regional Wide Area Network (WAN) in Buffalo and Western New York. The school wishes to use this WAN to deliver reference and communication resources to students, residents and faculty. The richest pool of easy to use reference and communication resources are PC software programs that are intended for individual workstations or at best, client-server, Local Area Network (LAN) implementation. HUBNET (Hospitals and University at Buffalo Library Resource Network), a project of the School of Medicine and the Library Consortium of Health Institutions in Buffalo offers integrated presentation of many such LAN resources over this regional WAN. The system crosses many institutional boundaries and reaches physically remote sites in a complex mix of information systems environments with few issues related to performance. The system design provides a level of ease of use that has brought many new users into active computer use while addressing integration into diverse information systems settings and networking environments.

Computer Communication Networks↗

An automated method for DNA preparation from thousands of YAC clones.

We describe an automated method for the preparation of yeast genomic DNA capable of preparing thousands of DNAs in parallel from a YAC library. Briefly, the protocol involves four steps: (1) Yeast clones are grown in the wells of 96-well microtiter plates with filter (rather than plastic) well-bottoms, which are embedded in solid growth media; (2) These yeast cultures are resuspended and their concentrations determined by optical density measurement; (3) Equal numbers of cells from each well are embedded in low-melting temperature agarose blocks in fresh 96-well plates, again with filter bottoms; and (4) DNA is prepared in the agarose blocks by a protocol similar to that used for preparing DNA for pulsed-field gels, with the reagents being dialyzed through the (filter) bottoms of the microtiter plate. The DNA produced by this method is suitable for pulsed-field gel electrophoresis, for restriction enzyme digestion, and for the polymerase chain reaction (PCR). Using this protocol, we produced 3000 YAC strain DNAs in three weeks. This automated procedure should be extremely useful in many genomic mapping projects.

Blotting, Southern↗

An improved nonisotopic test to screen a large series of new inhibitor molecules of poly(ADP-ribose) polymerase activity for therapeutic applications.

A reliable ELISA for screening large numbers of poly(ADP-ribose) polymerase (PARP) inhibitors is described. The test is based upon the drop in PARP activity estimated by the decrease in poly(ADP-ribose) synthesis in the presence of inhibitor. This ELISA is easy to perform, rapid, and specific. It is extremely sensitive because a clear inhibition of the total reaction could be visualized with molecules used in the nanomolar range. The assay uses no radioactivity, and automation is possible with robots for large-scale investigations. This test is of great interest for the screening of chemical libraries and the discovery of new inhibitors (and possibly activators) of PARP. Such molecules have important applications in all abnormal situations involving DNA damage and oxidative stress, such as cancer, autoimmunity, diabetes, myocardial dysfunctions, certain infections, aging, and radiation/chemical exposure.

Apoptosis↗

A complete library of point substitution mutations in the glucocorticoid response element of mouse mammary tumor virus.

The glucocorticoid response element (GRE) of mouse mammary tumor virus (MMTV) was chemically synthesized as two complementary DNA strands bearing cohesive termini. During automated synthesis, random mutations were introduced into the DNA by "doping" each of the four nucleoside phosphoramidites (A, G, C, and T) with a low level of the other three. These preparations were annealed and cloned into an M13 phage vector to produce a library of GRE mutants. Mutations within the synthesized region were identified by sequencing phage isolates at random. All of the chemically distinct classes of transition and transversion mutations have been observed. Statistical considerations indicate that the library contains all of the possible 90 point substitution mutations within a 30-nucleotide mutagenic target. So far 88 of these substitutions have been isolated, 74 as single mutants. At least two of the three possible single mutants at each of the 30 positions have been identified.

Base Sequence↗

Fluorous Boc ((F)Boc) carbamates: new amine protecting groups for use in fluorous synthesis.

The first fluorous variants of the Boc (tert-butyloxycarbonyl) group have been prepared and tested for their suitability as nitrogen protecting groups. A group with two fluorous chains and an ethylene spacer, (RfCH2CH2)2(CH3)COC(O)-, was readily attached to a representative amine but was difficult to cleave. In contrast, groups with two fluorous chains and a propylene spacer, (RfCH2CH2CH2)2(CH3)COC(O)-, or one fluorous chain and an ethylene spacer, (RfCH2CH2)(CH3)2COC(O)-, were readily formed and cleaved. The fluorous alcohol component of the (F)Boc group can be removed by evaporation and can be recovered and reused. The utility of the new (F)Boc group (C8F17CH2CH2)(CH3)2COC(O)- was demonstrated in 16 and 96 compound library synthesis exercises. Separations can be achieved either by manual, parallel fluorous solid-phase extraction, or automated, serial fluorous chromatography. The results provide additional confirmation of the value of "light" fluorous synthesis techniques, and the new fluorous Boc groups expand the applicability of fluorous synthesis techniques to many classes of nitrogen-containing organic compounds.

Amines↗