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Integrating learning into integrated delivery systems.

Integrated delivery systems that promote learning and flexibility will be better prepared to face the challenges imposed by a complex and competitive environment. The integration of learning into these systems requires a shared vision, facilitative leadership, and highly functioning communication channels within an organic structure. Strategies that promote positive attitudes toward change are necessary for learning as is the provision of resources, training, incentives, and rewards that support learning, and feedback on how new administrative and clinical practices advance the mission and goals of the system.

Communication↗

Just how integrated are integrated delivery systems? Results from a national survey.

This article examines three emergent processes in physician-hospital integrated delivery systems (IDSs). We find these processes are underdeveloped based on data gathered from a national sample of hospitals drawn from nine health care systems. These processes are also loosely coupled with the structures used to integrate physicians and hospitals, as well as with the environmental context in which they occur. Such loose coupling entails both advantages and disadvantages for IDSs.

Analysis of Variance↗

Interaction of integration host factor from Escherichia coli with the integration region of the Haemophilus influenzae bacteriophage HP1.

The specific DNA-binding protein integration host factor (IHF) of Escherichia coli stimulates the site-specific recombination reaction between the attP site of bacteriophage HP1 and the attB site of its host, Haemophilus influenzae, in vitro and also appears to regulate the expression of HP1 integrase. IHF interacts specifically with DNA segments containing the att sites and the integrase regulatory region, as judged by IHF-dependent retardation of relevant DNA fragments during gel electrophoresis. The locations of the protein-binding sites were identified by DNase I protection experiments. Three sites in the HP1 attP region bound IHF, two binding sites were present in the vicinity of the attB region, and one region containing three partially overlapping sites was present in the HP1 integrase regulatory segment. The binding sites defined in these experiments all contained sequences which matched the consensus IHF binding sequences first identified in the lambda attP region. An activity which stimulated the HP1 site-specific integration reaction was found in extracts of H. influenzae, suggesting that an IHF-like protein is present in this organism.

Bacterial Proteins↗

Characterization of genetic elements required for site-specific integration of the temperate lactococcal bacteriophage phi LC3 and construction of integration-negative phi LC3 mutants.

The genetic elements required for the integration of the temperate lactococcal bacteriophage phi LC3 into the chromosome of its bacterial host, Lactococcus lactis subsp. cremoris, were identified and characterized. The phi LC3 phage attachment site, attP, was mapped and sequenced. DNA sequence analysis of attP and of the bacterial attachment site, attB, as well as the two phage-host junctions, attR and attL, in the chromosome of a phi LC3 lysogen, identified a 9-bp common core region, 5'-TTCTTCATG'-3, within which the strand exchange reaction takes place during integration. The attB core sequence is located within the C-terminal part of an open reading frame of unknown function. The phi LC3 integrase gene (int), encoding the phi LC3 site-specific recombinase, was identified and is located adjacent to attP. The phi LC3 Int protein, as deduced from the nucleotide sequence, is a basic protein of 374 amino acids that shares significant sequence similarity with other site-specific recombinases of the integrase family. Phage phi LC3 int- and int-attP-defective mutants, conferring an abortive lysogenic phenotype, were constructed.

Amino Acid Sequence↗

Clinical integration and nursing leadership across an integrated delivery system.

As new health systems struggle to combine in today's challenging health care market, mechanisms that facilitate and enhance integration become increasingly important. This article describes the use of clinical paths in an integrated delivery system (IDS) as a methodology to establish a single standard of high-quality care. Through education and sharing of staff development resources across the IDS, the system nurse executive at one large IDS promotes professional practice. As clinical paths are developed across the system, the best clinical practice is put to paper, providing a framework for outcome-driven care. The nurse manager assesses staff's use of clinical paths as an evaluation of their skills and competency and to identify new educational and growth opportunities.

Benchmarking↗

Integrated Academic Information Management Systems (IAIMS). Part III. Implementation of integrated information services. Library/computer center partnership.

Information technologies are changing the traditional role of the library from that of a repository of information to that of an aggressive provider of information services utilizing electronic methods. In many cases, the library cannot realistically achieve this transformation independently but must work with the computer center to reach its objectives. Various models of the integration of libraries and computer centers are thus emerging. At the University of Maryland at Baltimore the Health Sciences Library and the Information Resources Management Division have developed a partnership based on functional relationships without changing the organizational structure. Strategic planning for an Integrated Academic Information Management System (IAIMS) acted as a catalyst in the process. The authors present the evolution of the partnership and discuss current projects being developed jointly by the two units.

Academic Medical Centers↗

The signal-anchor domain of adenovirus E3-6.7K, a type III integral membrane protein, can direct adenovirus E3-gp19K, a type I integral membrane protein, into the membrane of the endoplasmic reticulum.

Type III integral membrane proteins are oriented in the membrane with their C-terminus in the cytoplasm and their N-terminus extracytoplasmic. Such proteins are believed to have an internal hydrophobic sequence that functions both as an uncleaved signal for membrane insertion and also to anchor the protein in the membrane. However, type III proteins are relatively rare, and information about their putative signal-anchor (SA) domains is scant. The adenovirus E3-6.7K protein is a novel small type III protein. In order to study the insertion of 6.7K into membranes, we have constructed a fusion protein between 6.7K and adenovirus E3-gp19K; gp19K is a type I integral membrane protein that is known to form a complex with class I antigens of the major histocompatibility complex (MHC). The 6.7K-gp19K fusion protein lacks the gp19K signal sequence. We show that the 6.7K sequences can act as signal for membrane insertion of the 6.7K-gp19K fusion protein; however, the SA domain of 6.7K does not function as an anchor for the fusion protein. Thus, we have separated the signal function from the anchor function of the 6.7K SA domain. The transmembrane domain of gp19K is still acting as a stop-transfer sequence, and the ability of gp19K to bind MHC class I antigens is still intact. These data imply that sequences flanking a SA domain can influence whether the SA domain functions as a signal sequence only or as a dual signal-anchor sequence. The results also show that the signal for a type III membrane protein can direct a type I protein into the ER membrane. Finally, the data demonstrate that gp19K can retain its class I antigen binding function when gp19K has heterologous sequences fused to its N-terminus.

Adenovirus E3 Proteins↗

Characterization of purified gp 51 from bovine leukemia virus integrated into iscom. Physicochemical properties and serum antibody response to the integrated gp51.

It is proposed that the envelope glycoprotein, gp 51, is the protective antigen of bovine leukemia virus (BLV). An experimental iscom vaccine has been prepared from immunoaffinity purified gp 51. To overcome the problem of integrating a nonamphipathic protein, gp 51 was partially denatured at pH 2.4 before integration into the iscom. The recovery of gp 51 into the iscom was calculated to be 85%. The gp 51 incorporated into iscom retained its physicochemical properties and the neutralizing epitopes F, G and H were found to be intact. The iscom preparation was shown to induce a specific immune response to gp 51 after inoculation into mice and calves, as tested by ELISA and Western blotting. Sera from the immunized calves specifically inhibited the VSV-(BLV) pseudotypes. Thus the gp 51-iscom preparations appear to be highly immunogenic and to induce a gp 51 specific response.

Animals↗

Integrating human impacts and ecological integrity into a risk-based protocol for conservation planning.

Conservation planning aims to protect biodiversity by sustainng the natural physical, chemical, and biological processes within representative ecosystems. Often data to measure these components are inadequate or unavailable. The impact of human activities on ecosystem processes complicates integrity assessments and might alter ecosystem organization at multiple spatial scales. Freshwater conservation targets, such as populations and communities, are influenced by both intrinsic aquatic properties and the surrounding landscape, and locally collected data might not accurately reflect potential impacts. We suggest that changes in five major biotic drivers-energy sources, physical habitat, flow regime, water quality, and biotic interactions-might be used as surrogates to inform conservation planners of the ecological integrity of freshwater ecosystems. Threats to freshwater systems might be evaluated based on their impact to these drivers to provide an overview of potential risk to conservation targets. We developed a risk-based protocol, the Ecological Risk Index (ERI), to identify watersheds with least/most risk to conservation targets. Our protocol combines risk-based components, specifically the frequency and severity of human-induced stressors, with biotic drivers and mappable land- and water-use data to provide a summary of relative risk to watersheds. We illustrate application of our protocol with a case study of the upper Tennessee River basin, USA. Differences in risk patterns among the major drainages in the basin reflect dominant land uses, such as mining and agriculture. A principal components analysis showed that localized, moderately severe threats accounted for most of the threat composition differences among our watersheds. We also found that the relative importance of threats is sensitive to the spatial grain of the analysis. Our case study demonstrates that the ERI is useful for evaluating the frequency and severity of ecosystem-wide risk, which can inform local and regional conservation planning.

Agriculture↗

The role of scientific associations in promoting research integrity and deterring research misconduct. Commentary on 'Challenges in studying the effects of scientific societies on research integrity' (Levine and Iutcovitch).

The nature of scientific societies' relationships with their members limits their ability to promote research integrity. They must therefore leverage their strengths as professional organizations to integrate ethical considerations into their ongoing support of their academic disciplines. This paper suggests five strategies for doing so.

Ethics, Research↗

Fast method for computing the Fourier integral transform via Simpson's numerical integration.

A new algorithm for computing the Fourier transform is described. The method is based on the calculation of the Fourier integral transform (FIT) with the aid of the numerical Simpson's integration technique. Compared to the conventional fast Fourier transform (FFT), the new SFIT algorithm, gives results which are much closer to the analytic Fourier transform for discrete signals. Especially in the calculation of the phase spectra considerable improvement is obtained. The N-point SFIT can effectively be computed by using two N/2-point FFTs.

Biomedical Engineering↗

Integrated risk assessment or integrated risk management?

Problems of hazard assessment and risk assessment are at the present time the subjects of considerable discussion in the context of the Organisation for Economic Cooperation and Development (OECD) chemical management programs, within the European Community (EEC) and at national levels. A previous article (J. W. Hart and N. J. Jensen, 1990, Regul. Toxicol. Pharmacol. 11, 123-131) discussed the inherent limitations of the hazard assessment of chemicals. The elements of hazard and risk assessment have been described by Bro-Rasmussen (In Risk Assessment of Chemicals in the Environment, M. L. Richardson, Ed., Chap. 24, pp. 437-450, Royal Society of Chemistry, London, 1988). This article is an attempt to illustrate the different elements in hazard and risk assessments in specific risk management areas and to indicate the limitations in these processes. This analysis indicates that there are different requirements for a risk assessment, which depend on its specific purpose. In particular, problems related to the integration of different approaches--and the stage at which integration is possible--are discussed. While the principle subject of the discussion is risk assessment, many of the elements concerned are also a part of priority setting, and this subject is also discussed briefly.

Accidents, Occupational↗

Integrating HIV management for children into the Integrated Management of Childhood Illness guidelines.

The WHO/UNICEF strategy of Integrated Management of Childhood Illness (IMCI) has been adopted as a strategy for improving paediatric care in resource-poor settings. The original IMCI guidelines recommend referral of children with severe or recurrent illnesses such as those common in HIV/AIDS, however the specific identification and management was not included. In many countries, especially in sub-Saharan Africa, HIV/AIDS contributes significantly to child morbidity and mortality. There was a need to include the specific assessment and management of symptomatic HIV infection in IMCI guidelines. A draft HIV component of the IMCI guidelines was developed, which included management of symptomatic HIV cases with referral for counselling and testing, and was evaluated in South Africa. A revised version was then validated in Ethiopia and Uganda where HIV, malnutrition and malaria prevalence is different from South Africa. IMCI materials have been adapted to include an HIV component. Currently, very few children under 15 years of age receive antiretroviral therapy (ART). Chronic HIV care of children, including ART for children, has been developed within the Integrated Management of Adolescent and Adult Illness (IMAI) initiative of the WHO. Through this initiative, the WHO is assisting countries to facilitate care and treatment of children undergoing ART.

Adolescent↗

T-DNA integration patterns in co-transformed plant cells suggest that T-DNA repeats originate from co-integration of separate T-DNAs.

Nicotiana protoplasts and Arabidopsis leaf discs or roots were co-cultivated with two Agrobacterium strains each carrying a different T-DNA. Co-transformed plants were selected and the integration of the different T-DNAs was analysed at the genetic and genomic level. Genetic analysis showed that the T-DNAs derived from different bacteria were frequently integrated at the same locus, independent of the plant species or transformation method used. Southern analysis revealed that 12 out of 27 Arabidopsis transformants contained the co-transferred T-DNAs linked to each other in all possible configurations but with a preference for those with at least one right border involved in linkage. Overall, our data support the hypothesis that ligation of separate T-DNAs is a dominant mechanism in formation of the frequently observed repeats of identical T-DNAs. We propose a scheme which could explain the formation of T-DNA repeats and the preferential involvement of right borders in T-DNA linkages.

Arabidopsis↗

Germ line integration of Moloney leukemia virus: identification of the chromosomal integration site.

The chromosomal integration site of the structural gene of Moloney murine leukemia virus (M-MuLV) in the genome of BALB/Mo mice was mapped genetically. These mice transmit the exogenous M-MuLV as an endogenous virus at a single Mendelian locus. Two independent experimental approaches were used: (i) Non-virus-producing fibroblasts prepared from homozygous BALB/Mo embryos were fused to Chinese hamster Wg3-h-o cells. In an analysis of 30 independent mouse-Chinese hamster cell hybrid clones, the segregation of the viral genome measured by molecular hybridization and enzymes assigned to 16 different mouse chromosomes were compared. We found a highly concordant segregation of M-MuLV sequences and the mouse enzyme triosephosphate isomerase (TPI, EC 5.3.1.1), whose gene has been assigned to chromosome 6. A further karyotype analysis of 9 clones, in which the chromosomes were identified cytochemically, supported this result. (ii) The segregation of the viral genome was studied in backcrosses of BALB/Mo with ABP/J mice. In the backcross ABP/Jx(ABP/JxBALB/Mo) a linkage of the M-MuLV genome to the morphological marker wa-1 on mouse chromosome 6 was found. This confirmed the conclusion that the M-MuLV genome is integrated in mouse chromosome 6. These experiments define the genetic locus Mov-1, denoting the genetically transmitted structural gene of M-MuLV in BALB/Mo mice.

Animals↗

Self-organizing path integration using a linked continuous attractor and competitive network: path integration of head direction.

A key issue is how networks in the brain learn to perform path integration, that is update a represented position using a velocity signal. Using head direction cells as an example, we show that a competitive network could self-organize to learn to respond to combinations of head direction and angular head rotation velocity. These combination cells can then be used to drive a continuous attractor network to the next head direction based on the incoming rotation signal. An associative synaptic modification rule with a short term memory trace enables preceding combination cell activity during training to be associated with the next position in the continuous attractor network. The network accounts for the presence of neurons found in the brain that respond to combinations of head direction and angular head rotation velocity. Analogous networks in the hippocampal system could self-organize to perform path integration of place and spatial view representations.

Action Potentials↗

Modeling of the structural features of integral-membrane proteins reverse-environment prediction of integral membrane protein structure (REPIMPS).

The Profiles-3D application, an inverse-folding methodology appropriate for water-soluble proteins, has been modified to allow the determination of structural properties of integral-membrane proteins (IMPs) and for testing the validity of solved and model structures of IMPs. The modification, known as reverse-environment prediction of integral membrane protein structure (REPIMPS), takes into account the fact that exposed areas of side chains for many residues in IMPs are in contact with lipid and not the aqueous phase. This (1) allows lipid-exposed residues to be classified into the correct physicochemical environment class, (2) significantly improves compatibility scores for IMPs whose structures have been solved, and (3) reduces the possibility of rejecting a three-dimensional structure for an IMP because the presence of lipid was not included. Validation tests of REPIMPS showed that it (1) can locate the transmembrane domain of IMPs with single transmembrane helices more frequently than a range of other methodologies, (2) can rotationally orient transmembrane helices with respect to the lipid environment and surrounding helices in IMPs with multiple transmembrane helices, and (3) has the potential to accurately locate transmembrane domains in IMPs with multiple transmembrane helices. We conclude that correcting for the presence of the lipid environment surrounding the transmembrane segments of IMPs is an essential step for reasonable modeling and verification of the three-dimensional structures of these proteins.

Bacteriorhodopsins↗

Integration of heterologous DNA into the genome of Paracoccus denitrificans is mediated by a family of IS1248-related elements and a second type of integrative recombination event.

All members of the IS1248 family residing in the genome of Paracoccus denitrificans have been isolated by using a set of insertion sequence entrapment vectors. The family consists of five closely related members that integrate the entrapment vectors at distinct sites. One of these, IS1248b, was sequenced and, except for a single base change, shown to be identical to the previously isolated IS1248a. Southern analysis of genomic DNA with labeled IS1248 revealed different hybridization patterns for different isolates of P. denitrificans and Thiosphaera pantotropha. No hybridization was observed with DNA from Thiobacillus versutus and more distantly related species. From a comparison of the fingerprints it was shown that one of the members of the IS1248 family found in P. denitrificans DSM413 is absent in strain NCIB8944, although they are catalogued in international strain catalogues as identical strains. Furthermore, strains Pd1222 and Pd1235, both derivatives of P. denitrificans DSM413, were shown to have different patterns of IS1248 hybridizing restriction fragments. In 14 of 18 strains, the entrapment vectors used in this study were incorporated into the genome via IS1248-mediated cointegrate formation. In the other four strains, the entrapment vectors were shown to be integrated through a different mechanism not involving IS1248.

Base Sequence↗