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PubMed2006

An integrated BAC and genome sequence physical map of Phytophthora sojae.

Phytophthora spp. are serious pathogens that threaten numerous cultivated crops, trees, and natural vegetation worldwide. The soybean pathogen P. sojae has been developed as a model oomycete. Here, we report a bacterial artificial chromosome (BAC)-based, integrated physical map of the P. sojae genome. We constructed two BAC libraries, digested 8,681 BACs with seven restriction enzymes, end labeled the digested fragments with four dyes, and analyzed them with capillary electrophoresis. Fifteen data sets were constructed from the fingerprints, using individual dyes and all possible combinations, and were evaluated for contig assembly. In all, 257 contigs were assembled from the XhoI data set, collectively spanning approximately 132 Mb in physical length. The BAC contigs were integrated with the draft genome sequence of P. sojae by end sequencing a total of 1,440 BACs that formed a minimal tiling path. This enabled the 257 contigs of the BAC map to be merged with 207 sequence scaffolds to form an integrated map consisting of 79 superscaffolds. The map represents the first genome-wide physical map of a Phytophthora sp. and provides a valuable resource for genomics and molecular biology research in P. sojae and other Phytophthora spp. In one illustration of this value, we have placed the 350 members of a superfamily of putative pathogenicity effector genes onto the map, revealing extensive clustering of these genes.

Chromosomes, Artificial, Bacterial↗
PubMed2006

A journal club is an effective tool for assisting librarians in the practice of evidence-based librarianship: a case study.

OBJECTIVE: To establish a journal club for librarians, which aimed to develop appraisal skills and assist in the application of research to practice. METHODS: Fourteen health librarians were invited to attend a journal club. Each month a librarian was responsible for preparing a scenario, choosing a research paper, and selecting a checklist. The paper was appraised by the club, and a critically appraised topic (CAT) prepared. Six months later, a questionnaire was sent to all librarians. RESULTS: Six out of 14 librarians attended the journal club and five out of six returned the questionnaire. All five agreed that attending the journal club helped them develop appraisal skills, write a CAT and be more critical of research. Four agreed they always identified a research paper first, then formulated a question. One librarian agreed that applying results to their own practice was difficult, one disagreed and three were neutral. CONCLUSION: Journal clubs can be effective at developing appraisal skills and writing a CAT, as well as increasing the reading of library research. Librarians still need assistance in identifying and using questions directly from their own practice. The journal club has helped some librarians to apply evidence to practice, but others find the research is not always directly relevant.

Competency-Based Education↗
PubMed2001

Identification by subtractive hybridization of sequences specific for Salmonella enterica serovar enteritidis.

Salmonella enterica serovar Enteritidis, a major cause of food poisoning, can be transmitted to humans through intact chicken eggs when the contents have not been thoroughly cooked. Infection in chickens is asymptomatic; therefore, simple, sensitive, and specific detection methods are crucial for efforts to limit human exposure. Suppression subtractive hybridization was used to isolate DNA restriction fragments present in Salmonella serovar Enteritidis but absent in other bacteria found in poultry environments. Oligonucleotide primers to candidate regions were used in polymerase chain reactions to test 73 non-Enteritidis S. enterica isolates comprising 34 different serovars, including Dublin and Pullorum, two very close relatives of Enteritidis. A primer pair to one Salmonella difference fragment (termed Sdf I) clearly distinguished serovar Enteritidis from all other serovars tested, while two other primer pairs only identified a few non-Enteritidis strains. These primer pairs were also useful for the detection of a diverse collection of clinical and environmental Salmonella serovar Enteritidis isolates. In addition, five bacterial genera commonly found with Salmonella serovar Enteritidis were not detected. By treating total DNA with an exonuclease that degrades sheared chromosomal DNA but not intact circular plasmid DNA, it was shown that Sdf I is located on the chromosome. The Sdf I primers were used to screen a Salmonella serovar Enteritidis genomic library and a unique 4,060-bp region was defined. These results provide a basis for developing a rapid, sensitive, and highly specific detection system for Salmonella serovar Enteritidis and provide sequence information that may be relevant to the unique characteristics of this serovar.

Animals↗
PubMedDate not supplied

Things to come: postmodern digital knowledge management and medical informatics.

The overarching informatics grand challenge facing society is the creation of knowledge management systems that can acquire, conserve, organize, retrieve, display, and distribute what is known today in a manner that informs and educates, facilitates the discovery and creation of new knowledge, and contributes to the health and welfare of the planet. At one time the private, national, and university libraries of the world collectively constituted the memory of society's intellectual history. In the future, these new digital knowledge management systems will constitute human memory in its entirety. The current model of multiple local collections of duplicated resources will give way to specialized sole-source servers. In this new environment all scholarly scientific knowledge should be public domain knowledge: managed by scientists, organized for the advancement of knowledge, and readily available to all. Over the next decade, the challenge for the field of medical informatics and for the libraries that serve as the continuous memory for the biomedical sciences will be to come together to form a new organization that will lead to the development of postmodern digital knowledge management systems for medicine. These systems will form a portion of the evolving world brain of the 21st century.

Artificial Intelligence↗
PubMed2006

Application and utilization of chemoinformatics tools in lead generation and optimization.

The process of Drug Discovery is a complex and high risk endeavor that requires focused attention on experimental hypotheses, the application of diverse sets of technologies and data to facilitate high quality decision-making. All is aimed at enhancing the quality of the chemical development candidate(s) through clinical evaluation and into the market. In support of the lead generation and optimization phases of this endeavor, high throughput technologies such as combinatorial/high throughput synthesis and high throughput and ultra-high throughput screening, have allowed the rapid analysis and generation of large number of compounds and data. Today, for every analog synthesized 100 or more data points can be collected and captured in various centralized databases. The analysis of thousands of compounds can very quickly become a daunting task. In this article we present the process we have developed for both analyzing and prioritizing large sets of data starting from diversity and focused uHTS in support of lead generation and secondary screens supporting lead optimization. We will describe how we use informatics and computational chemistry to focus our efforts on asking relevant questions about the desired attributes of a specific library, and subsequently in guiding the generation of more information-rich sets of analogs in support of both processes.

Chemistry, Pharmaceutical↗
PubMed2003

The NITE XML Toolkit: flexible annotation for multimodal language data.

Multimodal corpora that show humans interacting via language are now relatively easy to collect. Current tools allow one either to apply sets of time-stamped codes to the data and consider their timing and sequencing or to describe some specific linguistic structure that is present in the data, built over the top of some form of transcription. To further our understanding of human communication, the research community needs code sets with both timings and structure, designed flexibly to address the research questions at hand. The NITE XML Toolkit offers library support that software developers can call upon when writing tools for such code sets and, thus, enables richer analyses than have previously been possible. It includes data handling, a query language containing both structural and temporal constructs, components that can be used to build graphical interfaces, sample programs that demonstrate how to use the libraries, a tool for running queries, and an experimental engine that builds interfaces on the basis of declarative specifications.

Communication↗
PubMed2003

The Association of Academic Health Sciences Libraries Annual Statistics: a thematic history.

The Annual Statistics of Medical School Libraries in the United States and Canada (Annual Statistics) is the most recognizable achievement of the Association of Academic Health Sciences Libraries in its history to date. This article gives a thematic history of the Annual Statistics, emphasizing the leadership role of editors and Editorial Boards, the need for cooperation and membership support to produce comparable data useful for everyday management of academic medical center libraries and the use of technology as a tool for data gathering and publication. The Annual Statistics' origin is recalled, and survey features and content are related to the overall themes. The success of the Annual Statistics is evident in the leadership skills of the first editor, Richard Lyders, executive director of the Houston Academy of Medicine-Texas Medical Center Library. The history shows the development of a survey instrument that strives to produce reliable and valid data for a diverse group of libraries while reflecting the many complex changes in the library environment. The future of the Annual Statistics is assured by the anticipated changes facing academic health sciences libraries, namely the need to reflect the transition from a physical environment to an electronic operation.

Annual Reports as Topic↗
PubMed2000

Vaccines for preventing typhoid fever.

BACKGROUND: Whole cell vaccines, consisting of relatively crude preparations of Salmonella typhi administered parenterally, are effective but have a high incidence of adverse effects. Two vaccines have been developed more recently. Ty21a (an attenuated strain of S. typhi administered orally) and Vi (the purified bacterial capsule, given parenterally), have appeared less toxic than the older whole cell vaccines and are thought to be equally effective. OBJECTIVES: The objective of this review was to assess the effects of typhoid fever vaccines. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Index Medicus, Embase and reference lists of articles. SELECTION CRITERIA: Randomised trials comparing typhoid vaccines to other types of vaccine or placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Seventeen studies, involving nearly two million people, were included. For the whole cell vaccines single dose regimens provided significant protection for the first two years. Two dose regimens provided significant protection for five years. For the Ty21a vaccine, both two and three dose regimens provided statistically significant protection for two years. The three dose regimen provided protection in the third and fourth years, but protection was not statistically significant in the fifth year. The Vi vaccine provided protection for two years, but the protection in the third year was not significant. The three year cumulative efficacy of two doses of whole cell vaccines was 73% (95% confidence interval 65-80), three doses of Ty21a was 51%, (95% confidence interval 35 to 63) and one dose of Vi was 55% (95% confidence interval 30 to 71). Data on adverse effects were limited, but indicate that whole cell vaccines are more toxic than the newer Ty21a and Vi vaccines. REVIEWER'S CONCLUSIONS: The whole cell vaccines provided more prolonged protection than either the Ty21a vaccine or the Vi vaccine. However whole cell vaccines are associated with higher toxicity.

Adolescent↗
PubMed2006

A dolphin peripheral blood leukocyte cDNA microarray for studies of immune function and stress reactions.

A microarray focused on stress response and immune function genes of the bottlenosed dolphin has been developed. Random expressed sequence tags (ESTs) were isolated and sequenced from two dolphin peripheral blood leukocyte (PBL) cDNA libraries biased towards T- and B-cell gene expression by stimulation with IL-2 and LPS, respectively. A total of 2784 clones were sequenced and contig analysis yielded 1343 unigenes (archived and annotated at ). In addition, 52 dolphin genes known to be important in innate and adaptive immune function and stress responses of terrestrial mammals were specifically targeted, cloned and added to the unigene collection. The set of dolphin sequences printed on a cDNA microarray comprised the 1343 unigenes, the 52 targeted genes and 2305 randomly selected (but unsequenced) EST clones. This set was printed in duplicate spots, side by side, and in two replicates per slide, such that the total number of features per microarray slide was 19,200, including controls. The dolphin arrays were validated and transcriptomic profiles were generated using PBL from a wild dolphin, a captive dolphin and dolphin skin cells. The results demonstrate that the array is a reproducible and informative tool for assessing differential gene expression in dolphin PBL and in other tissues.

Animals↗
PubMedDate not supplied

[The libraries of the public hospitals in Spain. An economic analysis. The Research Group on Libraries].

BACKGROUND: The continuous increase in scientific knowledge in the health field, the development of new technologies and the rising cost of publications means that libraries are essential for patient care, medical education and research. In Spain some deficiencies have been seen in hospital libraries, and their cost is unknown. OBJECTIVE: To analyze the cost of public hospital libraries in Spain and to estimate the cost of adapting them to international standards. METHODS: Cross-sectional survey of public hospitals larger than 100 beds, or smaller public hospitals with teaching accreditation. Information on the variables of interest was collected by questionnaire mailed to the libraries and followed up by telephone. Data collection was completed in 1996. The information on costs is for 1994. A sensitivity analysis was done to examine the effects of imprecise estimates and assumptions. RESULTS: Of the 314 hospitals identified, 211 (67.2%) had libraries. The 1994 cost of the of the 211 libraries was 3,060 million pesetas (mean cost: 14.5 million pesetas). Personnel costs were the most important item (38% of the total), followed by the cost of subscriptions (29%). The cost of hospital libraries represented 0.08% of national public expenditures on health. The cost of correcting inadequacies in accordance with international standards would increase spending by about 400 million pesetas the first year (0.01% of public spending on health). CONCLUSIONS: The cost of hospital libraries represents only a small fraction of public spending on health. Correction of the observed deficiencies and the importance of libraries in the health system would require increasing spending to about 0.1% of public spending on health.

Costs and Cost Analysis↗
PubMed2004

A short history of the William H. Welch Medical Library.

The William H. Welch Medical Library was founded in 1929 with the merger of three libraries, namely, the library of the School of Medicine, the library of the School of Hygiene and Public Health, and the library of the Johns Hopkins Hospital. Engendered by the dreams of Johns Hopkins University bibliophiles, such as founding Hopkins physicians William Osler, William Stewart Halsted, Howard Kelly, and William Henry Welch, the library flourished and expanded. At the same time as the founding of the central medical library, the Institute of the History of Medicine collection was established in the Welch Library building, with William H. Welch as its first director. Innovative leadership led to many exciting projects, such as the Welch Indexing Project, which was a prototype for the National Library of Medicine's medical subject headings, and the establishment of a laboratory for research into the application of information technologies to knowledge management. The Welch Library enters the 21st century as a dynamic library committed to the continuing delivery of information services, as well as ongoing research into the development of library services for the coming 100 years.

Academic Medical Centers↗
PubMed2005

Isolation and characterization of microsatellite loci from forest musk deer (Moschus berezovskii).

This study reported the isolation and characterization of eight polymorphic microsatellite loci in endangered forest musk deer Moschus berezovskii. An improved enrichment protocol was used to isolate microsatellites, and polymorphism was explored with samples from wild musk deer population collected in Miyalo of Sichuan Province in China. Approximately 70% of clones from the genomic library constructed in current study contained dinucleotide (AC) repeats. Eight microsatellite loci amplified were highly polymorphic within forest musk deer population. The number of alleles per locus ranged from 6 to 14, and the observed and expected heterozygosities ranged from 0.41 approximately 1.0 and from 0.8 approximately 0.9, respectively. The average polymorphic information content (PIC) value for these markers was 0.82. This demonstrated that the eight microsatellite loci developed here are highly polymorphic, and can be used as genetic markers for further investigation of musk deer. Also, the results showed that the musk deer distributed in Miyalo had a relatively higher level of genetic variation.

Alleles↗
PubMed1992

Electronic imaging of the human body.

The Human Engineering Division of the Armstrong Laboratory (USAF); the Mallinckrodt Institute of Radiology; the Washington University School of Medicine; and the Lister-Hill National Center for Biomedical Communication, National Library of Medicine are sponsoring a working group on electronic imaging of the human body. Electronic imaging of the surface of the human body has been pursued and developed by a number of disciplines including radiology, forensics, surgery, engineering, medical education, and anthropometry. The applications range from reconstructive surgery to computer-aided design (CAD) of protective equipment. Although these areas appear unrelated, they have a great deal of commonality. All the organizations working in this area are faced with the challenges of collecting, reducing, and formatting the data in an efficient and standard manner; storing this data in a computerized database to make it readily accessible; and developing software applications that can visualize, manipulate, and analyze the data. This working group is being established to encourage effective use of the resources of all the various groups and disciplines involved in electronic imaging of the human body surface by providing a forum for discussing progress and challenges with these types of data.

Computer Simulation↗
PubMed1987

A comparison of interlibrary loan requests received by the National Library of Medicine: 1959 and 1984.

In 1962, an analysis of interlibrary loan requests for serials filled by NLM in 1959 was published. In the twenty-five years following 1959, important changes occurred in the biomedical library community, which had a significant impact on interlibrary loan activities, including the development of MEDLARS and online searching, the Regional Medical Library (RML) network, and union listing for serials. To describe NLM's current interlibrary loan request traffic for serials and to identify any significant changes in traffic between 1959 and 1984, a comparative analysis of 1984 serial loan requests was performed, primarily by manipulation of automated request records. The changes in request traffic strongly suggest that the efforts to strengthen regional document delivery through the RML program have been successful and that NLM's collection is now used primarily as a last resort.

Interlibrary Loans↗
PubMed2003

The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.

Cell Adhesion Molecules, Neuronal↗
PubMed2001

Specialist epilepsy nurses for treating epilepsy.

BACKGROUND: Epilepsy is the most common serious neurological condition after stroke, with a 0.5 per cent prevalence, and a two to three per cent life time risk of being given a diagnosis of epilepsy in the developed world. As a result of the perceived deficiencies and suggestions to improve the quality of care offered to people with epilepsy, two models of service provision have been suggested by researchers: specialist epilepsy out-patient clinics (as opposed to the management of patients in general neurology clinics or general medical clinics) and nurse-based liaison services between primary (GP) and secondary/tertiary (hospital based) care. OBJECTIVES: The aim of this review is to overview the evidence from controlled trials investigating the effectiveness of specialist epilepsy nurses compared to routine care. SEARCH STRATEGY: The following databases were searched: The Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 1999), MEDLINE, GEARS, BIDS (EMBASE=Excepta Medica), ECRI, Effectiveness Healthcare Bulletin, Effectiveness Matters, Bandolier, Evidence Based Purchasing, National Research Register, Vignettes and expert panels from Standing Group on Health Technology Assessment, PsycLit database, World Wide Web sites and reference lists of articles. SELECTION CRITERIA: All randomized controlled and quasi-randomized trials which considered specialist epilepsy nurse interventions with standard or alternative care were included in this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) seizure frequency (b) appropriateness of medication prescribed (c) social or psychological functioning scores (d) knowledge about epilepsy scores (e) objective measures of general health status/quality of life (f) patients' reports of information received (g) number of days spent on sick leave/missing school and employment status (h) costs of care (i) adverse effects. MAIN RESULTS: Three trials were included, two based in general practice and one in a neurology centre. The population of patients differed between trials, for example one study excluded patients with learning disabilities, and one only recruited patients with a new diagnosis. In view of this heterogeneity we decided not to pool results in a meta-analysis. As yet, there is no convincing evidence that specialist epilepsy nurses improve outcomes for people with epilepsy overall. Important outcomes (e.g. seizure frequency, psychosocial functioning, knowledge of epilepsy, general health status, work days lost, depression and anxiety scores) show no significant improvement. There is some evidence that those patients who have not had an epileptic seizure in the last six months are less at risk for depression. There is also evidence that newly diagnosed patients whose knowledge about epilepsy is poor may improve their epilepsy knowledge scores after nurse intervention. REVIEWER'S CONCLUSIONS: It is clearly plausible that specialist epilepsy nurses could improve quality in epilepsy care. However, there is as yet little evidence to support this assumption as the present research base is small. Further research is needed to investigate the effectiveness of specialist epilepsy nurses before such recommendations can be made.

Epilepsy↗
PubMed2003

Early intravenous nutrition for the prevention of neonatal jaundice.

BACKGROUND: The early institution of enteral feeding in the first few days of life is known to impact on the development of unconjugated hyperbilirubinaemia. However, the effect of early intravenous nutrition on neonatal jaundice remains unknown. OBJECTIVES: To determine the effect of early intravenous nutrition on neonatal jaundice. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Controlled Trials Register (Cochrane Library: Issue 3, 2002), MEDLINE (1966-December 2002), and EMBASE (1974-December 2002). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating the effect of early intravenous nutrition on unconjugated bilirubin. DATA COLLECTION AND ANALYSIS: The search strategy identified no eligible studies, thus no data were collected. MAIN RESULTS: No studies were identified. REVIEWER'S CONCLUSIONS: Decisions regarding the institution of early intravenous nutrition must continue to be based upon factors others than its effect on neonatal jaundice.

Humans↗
PubMed2006

Biologically active molecules that reduce polyglutamine aggregation and toxicity.

Polyglutamine expansion in certain proteins causes neurodegeneration in inherited disorders such as Huntington disease and X-linked spinobulbar muscular atrophy. Polyglutamine tracts promote protein aggregation in vitro and in vivo with a strict length-dependence that strongly implicates alternative protein folding and/or aggregation as a proximal cause of cellular toxicity and neurodegeneration. We used an intracellular polyglutamine protein aggregation assay based on fluorescence resonance energy transfer (FRET) to identify inhibitors of androgen receptor (AR) aggregation in three libraries of biologically active small molecules: the Annotated Compound Library, the NINDS Custom Collection and a kinase inhibitor collection. In the primary screen 10 compounds reduced AR aggregation. While 10/10 also reduced huntingtin (Htt) exon 1 aggregation, only 2/10 reduced aggregation of pure polyglutamine peptides. In a PC-12 model 9/10 compounds reduced aggregation. Five out of nine compounds tested in an Htt exon 1 assay of neurodegeneration in Drosophila partially rescued the phenotype. Three of the five compounds effective in flies are FDA-approved drugs. These compounds provide new leads for therapeutic development for the polyglutamine diseases based on their efficacy in mammalian cells and a Drosophila model. The high predictive value of the primary screen suggests that the FRET-based screening assay may be useful for further primary and secondary screens for genes or small molecules that inhibit polyglutamine protein aggregation.

Androgen Receptor Antagonists↗