Mechanization of Library Procedures in the Medium-sized Medical Library: II. Records.
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Journal Article↗
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Internet access in the libraries of the National Network of Libraries of Medicine.
[This corrects the article on p. iii in vol. 86.].
Journal Article↗
Interlibrary loan in primary access libraries: challenging the traditional view.
INTRODUCTION: Primary access libraries serve as the foundation of the National Network of Libraries of Medicine (NN/LM) interlibrary loan (ILL) hierarchy, yet few published reports directly address the important role these libraries play in the ILL system. This may reflect the traditional view that small, primary access libraries are largely users of ILL, rather than important contributors to the effectiveness and efficiency of the national ILL system. OBJECTIVE: This study was undertaken to test several commonly held beliefs regarding ILL system use by primary access libraries. HYPOTHESES: Three hypotheses were developed. HI: Colorado and Wyoming primary access libraries comply with the recommended ILL guideline of adhering to a hierarchical structure, emphasizing local borrowing. H2: The closures of two Colorado Council of Medical Librarians (CCML) primary access libraries in 1996 resulted in twenty-three Colorado primary access libraries' borrowing more from their state resource library in 1997. H3: The number of subscriptions held by Colorado and Wyoming primary access libraries is positively correlated with the number of items they loan and negatively correlated with the number of items they borrow. METHODS: The hypotheses were tested using the 1992 and 1997 DOCLINE and OCLC data of fifty-four health sciences libraries, including fifty primary access libraries, two state resource libraries, and two general academic libraries in Colorado and Wyoming. The ILL data were obtained electronically and analyzed using Microsoft Word 98, Microsoft Excel 98, and JMP 3.2.2. RESULTS: CCML primary access libraries comply with the recommended guideline to emphasize local borrowing by supplying each other with the majority of their ILLs, instead of overburdening libraries located at higher levels in the ILL hierarchy (H1). The closures of two CCML primary access libraries appear to have affected the entire ILL system, resulting in a greater volume of ILL activity for the state resource library and other DOCLINE libraries higher up in the ILL hierarchy and highlighting the contribution made by CCML primary access libraries (H2). CCML primary access libraries borrow and lend in amounts that are proportional to their collection size, rather than overtaxing libraries at higher levels in the ILL hierarchy with large numbers of requests (H3). LIMITATIONS: The main limitations of this study were the small sample size and the use of data collected for another purpose, the CCML ILL survey. CONCLUSIONS: The findings suggest that there is little evidence to support several commonly held beliefs regarding ILL system use by primary access libraries. In addition to validating the important contributions made by primary access libraries to the national ILL system, baseline data that can be used to benchmark current practice performance are provided.
Benchmarking↗
Proposed standards for professional health sciences library services in hospitals of New York State.
Hospital libraries are considered to be the basic unit of the medical information system. A major statewide effort was begun in 1978 to introduce and support legislation in the New York State Legislature which would encourage hospitals to establish and maintain libraries that meet minimum services standards. Included in this legislation is the concept that the Commissioner of Education in consultation with the Commissioner of Health shall have the power to establish standards for hospital libraries. The Ad Hoc Committee for the Promotion of Hospital Library Services, Western New York Library Resources Council, proposes The Standards for Professional Health Sciences Library Services in Hospitals of New York State to clarify and to strengthen existing hospital library standards. These standards differ specifically from the Joint Commission on Accreditation of Hospitals standards in that they place equal and specific emphasis on eleven points: administration, qualifications of library staff, continuing education of library staff, requirement for a library advisory committee, required library services, required library resources, library space requirements, library budget, library network and consortium membership, documentation of library policy, and continued evaluation of the needs of the hospital for library service. Detailed interpretations are provided. An appendix describes the qualifications of a hospital library consultant.
Libraries, Hospital↗
Using Six Sigma to improve the film library.
The film library of a film-based radiology department is a mission-critical component of the department that is frequently underappreciated and under-staffed. A poorly performing film library causes operational problems for not only the radiology department, but for the institution as a whole. Since Six Sigma techniques had proved successful in an earlier CT throughput improvement project, the University of Texas M.D. Anderson Cancer Center Division of Diagnostic Imaging decided to use Six Sigma techniques to dramatically improve the performance of its film library. Nine mini-project teams were formed to address the basic operating functions of the film library. The teams included film library employees, employees from other sections of radiology, employees from stakeholders outside of radiology, and radiologists and referring physicians, as appropriate to the team's mission. Each Six Sigma team developed a process map of the current process, reviewed or acquired baseline quantitative data to assess the current level of performance, and then modified the process map to incorporate their recommendations for improving the process. An overall project steering committee reviewed recommendations from each Six Sigma team to assure that all of the teams' efforts were coordinated and aligned with the overall project goals. The steering committee also provided advice on implementation strategies, particularly for changes that would have an immediate effect on stakeholders outside of the radiology department. After implementation of recommendations, quantitative data were collected again to determine if the changes were having the desired effect. Improvement in both quantitative metrics and in employee morale have been experienced. We continue to collect data as assurance that the improvements are being sustained over the long haul. Six Sigma techniques, which are as quantitatively-based as possible, are useful in a service-oriented organization, such as a film library. The primary problem we encountered was that most of the important film library customer services are not automatically captured in the RIS or in any other information system. We had to develop manual data collection methods for most of our performance metrics. These collection methods were burden-some to the frontline employees who were required to collect the data. Additionally, we had to invest many hours of effort into assuring that the data were valid since film library employees rarely have the educational background to readily grasp the importance of the statistical methods employed in Six Sigma. One of the most important lessons we learned was that film library employees, including supervisory personnel, must be held accountable for their performance in a manner that is objective, fair and constructive. The best methods involved feedback collected by the employees themselves in the ordinary course of their duties. Another important lesson we learned was that film library employees, as well as stakeholders outside of the film library, need to understand how important the film library is to the smooth functioning of the entire institution. Significant educational efforts must be expended to show film library employees how their duties affect their film library co-workers and the institution's patients. Physicians, nurses and employees outside of the film library must do their part too, which requires educational efforts that highlight the importance of compliance with film library policies.
Academic Medical Centers↗
Theoretical distribution of truncation lengths in incremental truncation libraries.
Incremental truncation is a method for constructing libraries of every one base pair truncation of a segment of DNA. Incremental truncation libraries can be created using a time-dependent nuclease method or through the incorporation of alpha-phosphothioate dNTPs by PCR or by primer extension (THIO(pcr) truncation and THIO(extension) truncation, respectively). Libraries created by the fusion of two truncation libraries, known as ITCHY libraries, can be created using the above methods or by the incremental truncation-like method SHIPREC. Knowing and being able to tailor the distribution of truncations in incremental truncation, ITCHY and SHIPREC libraries would be beneficial for their use in protein engineering and other applications. However, the experimental determination of the distributions would require extensive, cost-prohibitive, DNA sequencing to obtain statistically relevant data. Instead, a theoretical prediction of the distributions was developed. Time-dependent incremental truncation libraries had the most uniform distribution of truncation lengths, but were biased against longer truncations. Essentially uniform distribution over the desired truncation range (from zero to N(max) base pairs) required that truncations be prepared up to at least 1.2-1.5 N(max). THIO(pcr) and THIO(extension) truncation libraries had a very nonuniform distribution of truncation lengths with a bias against longer truncations. Such nonuniformity could be significantly diminished by decreasing the incorporation rate of alphaS-dNTPs but at the expense of having a large fraction of the DNA truncated beyond the desired range or completely degraded. ITCHY libraries created using time-dependent truncation had the most uniform distribution of possible fusions and had the highest fraction of the library being parental-length fusions. However, the distribution of parental-length fusions was biased against fusions near the beginning/ends of genes unless the truncation libraries are prepared with a uniform distribution up to N(max). In contrast, SHIPREC libraries and THIO(pcr) ITCHY libraries, by the very nature of the nonuniform distributions of the truncated DNA, are ensured of having a uniform distribution of fusion points in parental-length fusions. This comes at the expense of having a smaller fraction of the library being parental-length fusions; however, this limitation can be overcome by performing size selection on the library.
Computer Simulation↗
Complete set of eleven region-specific microdissection libraries for human chromosome 2.
The construction and characterization of 11 region-specific libraries for the entire human chromosome 2 have been completed, including four libraries for the short arm and six libraries for the long arm, plus a library for the centromere region. These libraries were constructed using the chromosome microdissection and microcloning technology. Eight libraries have been described previously. This paper presents the final three libraries: 2q21-q22 (designated 2Q5 library), 2q11-q14 (2Q6). and 2p11.1-q11.1 (2CEN). The sizes of the dissected regions ranged between 20 and 30 Mb, with the centromere region of about 4 Mb. All these libraries are large, potentially comprising hundreds of thousands of recombinant microclones. Between 77% and 97% of the microclones were shown to derive from respective dissected regions. From 26 to 66 unique sequence microlones were isolated and characterized in detail for each library. The microclones have short inserts, ranging between 50 and 600 bp, with a mean of about 200 bp. The short inserts can be conveniently sequenced as STSs to provide high density probes for the dissected region. A plasmid sub-library containing at least 20,000 microclones, and usually more, has been prepared from each library and deposited to ATCC for general distribution. The libraries have been used effectively in constructing high resolution physical maps and for contig assembly, as well as in positional cloning of disease genes assigned to the dissected region. Comparing to other chromosomes with detailed mapping information and densely populated probes, chromosome 2 remains largely under-exploited. The availability of a complete set of region-specific libraries and unique sequence microclones from the libraries should provide valuable resources for genome analysis, high resolution physical mapping, region-specific cDNA isolation, and positional cloning for chromosome 2.
Centromere↗
Transforming a set of biological flat file libraries to a fast access network.
SRS (Sequence Retrieval System), an indexing system for flat file libraries, provides fast access to individual library entries via retrieval by keywords from various data fields. SRS is now also able to build indices using cross-references that most libraries provide. Fifteen libraries of DNA and protein sequences and structures have been selected. These libraries interact with at least one other by means of cross-references. Indexing these cross-references allows a complete network of libraries to be built. In the network an entry from one library can be linked in principle to every other library. If two libraries are not directly cross-referenced, the linkage can be made with a succession of single links between neighbouring, cross-referenced libraries. A new operator has been added to the query language of SRS for convenient specification of links amongst complete libraries or entry sets generated by previous queries on particular libraries. All the information in the network can now be used to retrieve an entry in a specific library, e.g. the full information given in amino acid sequence entries from SwissProt can now be used to retrieve related tertiary structure entries from PDB. Furthermore, a search in a single library can be extended to a search in the complete library network, e.g. all entries in all databases pertaining to elastase can be found.
Algorithms↗
Application of combinatorial library methods in cancer research and drug discovery.
Combinatorial chemistry is now considered as one of the most important recent advances in medicinal chemistry. There are five general approaches in combinatorial peptide library methods: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the 'one-bead one-compound' library method; and synthetic library methods using affinity chromatography selection. Except for the biological library approach, which is limited to peptide libraries with eukaryotic amino acids, all the other four synthetic approaches are applicable to peptide, non-peptide oligomer or small molecule libraries. Although non-peptide or small molecule libraries are generally prepared by a synthetic approach, recent advances in biosynthetic methods using enzymes may enable one to prepare chemical libraries that are otherwise difficult to synthesize chemically. In the 'one-bead one-compound' library method every member of the library is screened in parallel, but the chemical structure of the positive compound-bead has to be determined either directly or via an encoding strategy. A reliable high-throughput biological assay is needed for a successful combinatorial library screen. Solid-phase binding or functional assays as well as solution phase assays have been used successfully in various library methods. There has been enormous progress in the technological advances of molecular biology and the fundamental understanding of the molecular basis of cancer in recent years. By applying combinatorial chemistry and computational chemistry to the many cancer targets that have recently been identified, it is hopeful that more potent, more specific and less toxic anti-cancer agents will be developed in the foreseeable future. In addition to being a great tool for drug discovery, combinatorial chemistry has also proven to be invaluable in basic research. A few specific examples of the applications of combinatorial chemistry in basic cancer research and drug discovery are described in this mini-review.
Antineoplastic Agents↗
Social inclusion and the City of Swan public libraries in Western Australia.
The focus of this paper is on an understanding of social exclusion/inclusion: the concept and how a specific public library service, namely the City of Swan Public Library service, has responded to this social issue. The terms social inclusion/exclusion are explored and clarified from an international, Western Australian State Government, and public library perspective. This is followed by a brief overview of Western Australia as an Australian state, and how public libraries operate based on a partnership with the State Library of Western Australia and Local Government. The City of Swan Public Libraries are described in some depth and also portrayed in their local setting namely the City of Swan, a city of extensive growth that offers a unique environment of both rural and urban areas. The concept of social inclusion is then applied to the City of Swan Public Library service and how the library service addresses social inclusion within its physical environment, policies, operations, future planning, programmes and services. This includes the results of a Library Non-user Survey that was conducted in 2001. The aims of this survey were to: ascertain why non-users within the City of Swan do not make use of the library facilities; explore why past members were not using the library services; examine the effectiveness of library promotions; and investigate the access to and usage of the Internet. The paper concludes with a list of the potential social conditions of which public libraries need to be aware in their strategic planning activities so that community members are not excluded from participating and accessing the public library service.
Community Networks↗
PROBLEMS OF MEDICAL LIBRARIES IN JAPAN.
Reference service in medical libraries should be considered more seriously by the members of the Japan Medical Library Association, as their interest so far has been focused mainly on interlibrary loan service, compilation of union lists and union catalogs, and the business side of library administration. The Association does not have enough funds to be very active, and its membership is limited to the libraries of medical and of some large dental schools. It should open its membership to other medical libraries, such as those of hospitals and medical laboratories, and eventually to individuals. Many of the member libraries do not have complete control of their own budget, as each department of the school earmarks part of its budget for the library while it still holds the right of deciding which books and journals are to be bought and keeps a large part of them in its departmental library. Lack of proper library school education among the library staff is one of the major problems. There are some training courses for medical librarians in the library schools and also some workshops held by the Association, but they are limited in their usefulness by the fact that there are not enough library school graduates who can take advantage of them.
Humans↗
Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.
Using 'oligo-capped' mRNA [Maruyama, K., Sugano, S., 1994. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 138, 171-174], whose cap structure was replaced by a synthetic oligonucleotide, we constructed two types of cDNA library. One is a 'full length-enriched cDNA library' which has a high content of full-length cDNA clones and the other is a '5'-end-enriched cDNA library', which has a high content of cDNA clones with their mRNA start sites. The 5'-end-enriched library was constructed especially for isolating the mRNA start sites of long mRNAs. In order to characterize these libraries, we performed one-pass sequencing of randomly selected cDNA clones from both libraries (84 clones for the full length-enriched cDNA library and 159 clones for the 5'-end-enriched cDNA library). The cDNA clones of the polypeptide chain elongation factor 1 alpha were most frequently (nine clones) isolated, and more than 80% of them (eight clones) contained the mRNA start site of the gene. Furthermore, about 80% of the cDNA clones of both libraries whose sequence matched with known genes had the known 5' ends or sequences upstream of the known 5' ends (28 out of 35 for the full length-enriched library and 51 out of 62 for the 5'-end-enriched library). The longest full-length clone of the full length-enriched cDNA library was about 3300 bp (among 28 clones). In contrast, seven clones (out of the 51 clones with the mRNA start sites) from the 5'-end-enriched cDNA library came from mRNAs whose length is more than 3500 bp. These cDNA libraries may be useful for generating 5' ESTs with the information of the mRNA start sites that are now scarce in the EST database.
Animals↗
Influence of the light chain repertoire on immunoglobulin genes encoding thyroid autoantibody Fab from combinatorial libraries.
The diversity of the immunoglobulin heavy (H) and light (L) gene libraries used to construct a combinatorial library is an important parameter in determining the characteristics of antigen-specific Fab obtained from the library. To investigate the role of library diversity, we compared Fab specific for the autoantigen thyroid peroxidase (TPO) isolated from two different combinatorial libraries. Both libraries contained the same H chain genes. The original combinatorial library (H/R) utilized kappa chains generated using a single kappa variable region oligonucleotide primer. We constructed a second combinatorial library (H/D) containing kappa chains amplified with a diverse panel of variable region primers. From the the original H/R library, only two groups of TPO-specific Fab had been obtained, involving two H chain types (V1-3B and hv1L1) but only one kappa chain type (012). In contrast, among the seven TPO Fab characterized from the second library (H/D) we observed five different VH/VL combinations, comprising three types of H chains (V1-3B, VH26 and DP7) and four types of kappa chains (O12, L12, L2/hv328H5 and B3). Besides differences in VH and VL genes, as well as VH/VL combinations, the new TPO Fab used different D regions and JH and JK elements. Nevertheless, the new kappa Fab resembled previously isolated TPO Fab in terms of their affinity for TPO (Kd approximately 10(-9)M) and preferential recognition of conformationally intact autoantigen. In summary, our studies demonstrate that the diversity of the L chain library repertoire, while having little effect on immunological properties, has a major influence on the genes encoding antigen-specific Fab selected from a combinatorial library. For the successful isolation of rare but clinically important autoantibodies (such as to the TSH receptor) by the combinatorial library approach, library diversity is likely to be a major factor.
Amino Acid Sequence↗
MEDICAL LIBRARY STATISTICS.
Four compilations of medical library statistics have been published to date, namely those by Louise Darling in 1956, by the Medical Library Association in its 1959 Directory, by Harold Bloomquist in 1962, and by the author in 1964. In addition to these sources and to the annual statistics compiled by the Library Services Branch of the U. S. Office of Education, surveys of pharmacy, hospital, and medical society libraries have been completed recently. Standards for medical and special libraries are being considered by the Medical Library Association through its Guidelines Survey and by the Special Libraries Association through its Statistics Coordinating Project and its Standards Survey. To coordinate the collection of medical library statistics and to make the information readily available to the profession, it is suggested that the Medical Library Association support the collection and publication of statistics of representative medical libraries until such time as the Library Services Branch is able to implement fully its program of library statistics.
Data Collection↗
New promise in combinatorial chemistry: synthesis, characterization, and screening of small-molecule libraries in solution.
BACKGROUND: The increasing interest in combinatorial chemistry as a tool for the development of therapeutics has led to many new methods of creating molecular libraries of potential lead compounds. Current methods have made it possible to develop libraries of several million compounds. As a result, the limiting factor in the screening of libraries has become the identification and characterization of active species. We have recently described a method for generating libraries of water-soluble compounds containing mixtures of 10(4) to 10(5) different small organic molecules by using generally applicable solution phase chemistry. We set out to develop new methods to characterize and decode these libraries. RESULTS: Libraries were generated by condensing a multi-acid-chloride core molecule with various amines, producing molecules with functional groups about a rigid backbone. Composition and complexity of the libraries was evaluated using electrospray mass spectrometry to analyze model libraries containing up to 55 different molecules. The number of peaks obtained in mass spectrometry is directly correlated with the complexity of the library, and we were therefore able to deduce which of the expected compounds had in fact been formed in the library, and which of the building blocks in the library were not efficiently used. An iterative selection procedure was developed using this information, which allowed the screening of libraries of up to 50,000 chemical species to produce a competitive inhibitor of the enzyme trypsin. CONCLUSIONS: Our strategy for the identification of active species should be broadly applicable to other methods of generating complex libraries of small molecules. The selection from the library of a compound with desired biological properties augurs well for the potential value of generating and screening complex mixtures of small molecules in solution.
Amines↗
Use of catalyst pharmacophore models for screening of large combinatorial libraries.
Using a data set comprised of literature compounds and structure-activity data for cyclin dependent kinase 2, several pharmacophore hypotheses were generated using Catalyst and evaluated using several criteria. The two best were used in retrospective searches of 10 three-dimensional databases containing over 1,000,000 proprietary compounds. The results were then analyzed for the efficiency with which the hypotheses performed in the areas of compound prioritization, library prioritization, and library design. First as a test of their compound prioritization capabilities, the pharmacophore models were used to search combinatorial libraries that were known to contain CDK active compounds to see if the pharmacophore models could selectively choose the active compounds over the inactive compounds. Second as a test of their utility in library design again the pharmacophore models were used to search the active combinatorial libraries to see if the key synthons were over represented in the hits from the pharmacophore searches. Finally as a test of their ability to prioritize combinatorial libraries, several inactive libraries were searched in addition to the active libraries in order to see if the active libraries produced significantly more hits than the inactive libraries. For this study the pharmacophore models showed potential in all three areas. For compound prioritization, one of the models selected active compounds at a rate nearly 11 times that of random compound selection though in other cases models missed the active compounds entirely. For library design, most of the key fragments were over represented in the hits from at least one of the searches though again some key fragments were missed. Finally, for library prioritization, the two active libraries both produced a significant number of hits with both pharmacophore models, whereas none of the eight inactive libraries produced a significant number of hits for both models.
Amino Acid Sequence↗
Structural aspects of antibody-antigen interaction revealed through small random peptide libraries.
Two small random peptide libraries, one composed of 4550 dodecapeptides and one of 8000 tripeptides, were synthesized in newly developed credit-card format miniPEPSCAN cards (miniPEPSCAN libraries). Each peptide was synthesized in a discrete well (455 peptides/card). The two miniPEPSCAN libraries were screened with three different monoclonal antibodies (Mabs). Two other random peptide libraries, expressed on the wall of bacteria (recombinant libraries) and composed of 10(7) hexa- and octapeptides, were screened with the same three Mabs. The aim of this study was to compare the amino acid sequence of peptides selected from small and large pools of random peptides and, in this way, investigate the potential of small random peptide libraries. The screening of the two miniPEPSCAN libraries resulted in the identification of a surprisingly large number of antibody-binding peptides, while the screening of the large recombinant libraries, using the same Mabs, resulted in the identification of only a small number of peptides. The large number of peptides derived from the small random peptide libraries allowed the determination of consensus sequences. These consensus sequences could be related to small linear and nonlinear parts of the respective epitopes. The small number of peptides derived from the large random peptide libraries could only be related to linear epitopes that were previously mapped using small libraries of overlapping peptides covering the antigenic protein. Thus, with respect to the cost and speed of identifying peptides that resemble linear and nonlinear parts of epitopes, small diversity libraries based on synthetic peptides appear to be superior to large diversity libraries based on expression systems.
Amino Acid Sequence↗
Bacterial diversity of metagenomic and PCR libraries from the Delaware River.
To determine whether metagenomic libraries sample adequately the dominant bacteria in aquatic environments, we examined the phylogenetic make-up of a large insert metagenomic library constructed with bacterial DNA from the Delaware River, a polymerase chain reaction (PCR) library of 16S rRNA genes, and community structure determined by fluorescence in situ hybridization (FISH). The composition of the libraries and community structure determined by FISH differed for the major bacterial groups in the river, which included Actinobacteria, beta-proteobacteria and Cytophaga-like bacteria. Beta-proteobacteria were underrepresented in the metagenomic library compared with the PCR library and FISH, while Cytophaga-like bacteria were more abundant in the metagenomic library than in the PCR library and in the actual community according to FISH. The Delaware River libraries contained bacteria belonging to several widespread freshwater clusters, including clusters of Polynucleobacter necessarius, Rhodoferax sp. Bal47 and LD28 beta-proteobacteria, the ACK-m1 and STA2-30 clusters of Actinobacteria, and the PRD01a001B Cytophaga-like bacteria cluster. Coverage of bacteria with > 97% sequence identity was 65% and 50% for the metagenomic and PCR libraries respectively. Rarefaction analysis of replicate PCR libraries and of a library constructed with re-conditioned amplicons indicated that heteroduplex formation did not substantially impact the composition of the PCR library. This study suggests that although it may miss some bacterial groups, the metagenomic approach can sample other groups (e.g. Cytophaga-like bacteria) that are potentially underrepresented by other culture-independent approaches.
Actinobacteria↗