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A new school's perspective on clinical curriculum.

The new predoctoral dental education program at the University of Nevada, Las Vegas, officially began on August 26, 2002. Key concepts identified as foundations for the UNLV clinical curriculum model include Student Active Integrated Learning (SAIL), the need to actively link oral health to systemic health, a sophisticated practice management model, a focus on culturally sensitive statewide outreach, establishing a strong biomedical research base, and development of future faculty. The predoctoral program will be comprised of five general practices. Students from each of the four academic years will be assigned to a practice group; each student will be expected to provide patient care within the scope of his or her current training.

Clinical Competence↗

Ties that bind.

Explore the source record for details and available documents.

Cooperative Behavior↗

[Variation and homologous analysis of parts of pig POU1F1 gene].

By PCR approach, exon4, exon5 and exon6 of POU1F1 gene of Landrace, Duroc, Yorkshire, Jiangquhai, Meishan, and w Xiangzhu are amplified, and PCR products contained exon 4,exon6 and the cloning product of exon5 were sequenced. The results showed that exon4 of POU1F1 gene had the Nla III polymorphisms characteristics, the mutation was T-->C. The sequences were digested by Nla III, and two different genotypes(GG and HH) were produced; but exon 5 and exon 6 of POU1F1 gene were high conservation in the six pig breeds. The result of homologous analysis showed that the homologous rate of nucleotide sequences of the exon4 in human, pig, mouse and cow was 93.9%,86.7%,92.1% respectively and the amino acid sequence of POU specific domain encoded by exon4 of POU1F1 gene in human, pig ,mouse and cow was identical. And the result of homologous analysis of nucleotide sequences encoding POU1F1 POU-homeo domain in human, pig, mouse, cow was 91.4%,85.1%,87.9% respectively, the homologous rate of the amino acid sequence of POU-homeo domain was 96.6%,94.8%,90.2% respectively. This showed that the sequences of the POU1F1 POU-homeo domain and the POU-specific domain encoded by exon4 in mammals were high conservation, pigs could be used to establish animal models of related diseases, providing scientific foundation and serving for human medicine.

Alleles↗

Life and death on the coral reef: an ecological perspective on scholarly publishing in the health sciences.

OBJECTIVE: Reflecting patterns evident in past Janet Doe lectures, the 2004 address draws on the foundations of biology to provide a model that offers insights into the advent of electronic publications and choices for the future. SETTING: The lecture sketches a picture of the fragile relationships found in complex ecosystems and illustrates how such interdependencies function in the environment of the coral reef. ANALYSIS: Deriving lessons from the marine world, the lecture then shifts to a description of similarities in the realm of scholarly publishing, the impact of digital innovations in the marketplace, and the controversies and choices inherent in open access publications. CONCLUSIONS: Lessons from ecology and publishing lead to the conclusion that librarians must take action and risks in this time of dramatic environmental change.

Ecosystem↗

[A histological innovative study of Balb/c mouse tooth germ transplanted to nude mouse in vivo].

PURPOSE: To observed the changes of the developed mouse's dental germs after transplanting into nude mouse and find some theoretical foundation for establishing an innovative experimental model. METHODS: Eight tooth germs from four 5th day postnatal Balb/c mice were transplanted to the back muscles of the adult nude mice. At seventh and fourteenth day after grafting, the germs were collected, fixed, demineralized, dehydrated, and embedded in wax. Serial sections of 5 microm thick were made following the routine methods, stained with haematoxylin-eosin dying solution, and observed under a light microscope. The mandibular first molars were taken out from the 12th and 19th day postnatal mouse. Serial sections of 5 microm thick were made following the routine methods, then compared with the germs after graft. RESULTS: All implantations were located in the superficial muscles with abundant capillary vessels. The dental germs could further developed after grafting under the microscope, but slower than dental germs self-development. The layer of dentin was thin, plenty of dentin with disorganized dentin tubule formed after grafting. Although the location of Hertwig's epithelial root sheath hardly moved, the roots developed further. The floor of pulp chamber could form and the pulp chambers were shrinking. The degree of calcification in the area of root increased very clearly. The inflammatory reaction was found at 7th day while hardly noted at 14th day after grafting. CONCLUSIONS: It suggests that late development of mouse tooth germs could further develop after heterotopic transplantation within the superficial muscles of the nude mouse. This model is useful for study of tooth root development in short time.

Animals↗

[Monoclonal antibodies in virology].

The application of hybridoma technology to the preparation of monoclonal antibodies has had a strong stimulatory effect on many areas of virological research. This development has expanded our knowledge with respect to antigenic variation among viruses and detailed analysis of complex antigenic structures of virus proteins and has also led to the elucidation of the molecular foundations of pathogenesis and virulence in model systems. The practical importance of these results spans many important areas of applied virology such as the development of new viral vaccines, passive immunization and diagnosis of viral infections.

Antibodies, Monoclonal↗

Neuropharmacology of methylphenidate and a neural substrate for childhood hyperactivity.

What began as a simple chemical question about the clinical utility of MPH SL measurement has led our group across a broad expanse of research endeavors, from the problem of nonintercorrelated stimulant effects to a theory of hyperactivity as a dysregulatory disorder based on frontal-striatal dysfunction or dysmaturation. The transition has been from a traditional and fairly circumscribed question in psychopharmacology to a new interest in the neuropsychological approach to hyperactivity and its treatment. Biologic psychiatry and neuropsychology have developed as distinct disciplines well insulated from one another, but a degree of cross-fertilization is beginning to occur. Rather than thinking of childhood hyperactivity in terms of vague metapsychological concepts such as "attention" or "arousal," it will be perhaps more constructive to base a model for the disorder on the foundation of known elements of brain function. Perhaps the most interesting research areas to pursue will be neuropsychological and neurodiagnostic (for example, PET). The specific locus of disorders, such as the HKS and the specific mechanisms of drug action, may not be so elusive after all.

Antipsychotic Agents↗

Construction, expression, and activity of a bivalent bispecific single-chain antibody.

This report describes the design, construction, and expression of a bivalent bispecific single-chain antibody (SCA) protein in Escherichia coli. The bispecificity of the bivalent protein was based on two previously constructed monovalent single-chain antibody molecules possessing distinct specificities, SCA 4-4-20 (anti-fluorescein) and SCA 04-01 (anti-single-stranded DNA). A flexible linker, modeled after a secreted fungal cellulase protein, was incorporated as the interdomain linker covalently joining the two active sites. Bivalent bispecific SCA protein that accumulated in bacteria as insoluble inclusion bodies was harvested, denatured, refolded, and affinity-purified in vitro. Affinity-purified bivalent bispecific SCA showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules. In both solid and solution phase binding assays, the bivalent bispecific single-chain antibody simultaneously bound both ligands (fluorescein and (dT)6). Construction of a model bivalent bispecific molecule provides a foundation for future assembly of similar molecules designed to identify parameters involved in enhanced binding of antibodies due to avidity and dual specificity.

Amino Acid Sequence↗

Registered nurse turnover and the changing health care system.

Changes in health care delivery and cyclic fluctuations in the registered nurse (RN) labor market affect health care costs, access, and quality. This study provides insight into one factor central to these issues, the job-change behavior of RNs. The theory of human capital provides the foundation to guide investigation, and econometric modeling is used to explore relationships among study variables. Model results show clear differences in job change behavior of nurses employed in hospital and nonhospital settings. These differences are a reflection, not only of individual nurse preferences, but also of wages, working conditions, and opportunities associated with various health care settings. Understanding these relationships is essential to leaders in the nursing profession as they plan for and respond to changes in health care delivery.

Adult↗

Meniscal repair using the outside-to-inside technique.

Research during the past decade has elucidated the structure and function of the knee joint meniscus, and both clinical and experimental studies have demonstrated the importance of this structure. Recent advances, such as the use of an exogenous fibrin clot, have allowed preservation of an increasingly greater proportion of injured menisci. The success of these methods will be established only by long-term follow-up studies demonstrating a lower incidence of progression to degenerative joint disease. It is hoped that an increasing understanding meniscal fibrochondrocytes biology and response to injury will result in the development of novel therapeutic strategies for repair of the injured meniscus. Basic studies clearly have demonstrated that meniscal fibrochondrocytes possess intrinsic repair capability. Both in vitro cell culture studies and in vivo animal models have provided the basic scientific foundation for the use of fibrin clot in tears in the avascular portion of the meniscus. The use of fibrin clot has allowed further expansion of the proportion of meniscal tears that are potentially reparable. Tears in the central, avascular zone of the meniscus, formerly thought to be irreparable, now may undergo repair with an enhanced opportunity for healing. The factors associated with a good prognosis in the meniscal repair include acute tear; peripheral tear; a stable knee; and the presence of serum or factors derived from serum, such as the presence of a fibrin clot, or vascular access channel, or hemarthrosis. Cell culture and molecular biologic techniques currently are being used to improve our understanding of meniscal biology. Particular challenges for future research include determination of the source of the reparative cells in meniscal repair, exploration of the biomechanical properties of the reparative tissue, and demonstration of the potential use of growth factors in meniscal healing. A further potential use of fibrin clot in the future is as a carrier vehicle both for the delivery of growth factors to injured meniscal and for the transplantation of autogenous fibrochondrocytes in meniscal defects. Other avenues of investigation include the use of cytokines to enhance meniscal healing, studies of meniscal replacement with allografts and collagen-based prostheses for meniscal regeneration, and the potential to augment meniscal cell proliferation and matrix synthesis by gene therapy techniques.

Animals↗

EFQM approach and the Dutch Quality Award.

Different approaches to improve quality are used in organizations delivering health care. Donabedian introduced structure, process and outcome, from which other approaches like self-assessment, accreditation, visitation, International Standards Organisation (ISO) and European Foundation for Quality Management (EFQM) can be aligned. The EFQM model is one such approach that has been adopted and adapted by the Dutch Institute for Quality Management. This article describes the background and progress relating to the use of the EFQM business excellence model within Dutch health care organizations. In addition the process for applying for the European Quality Award and the Dutch Quality Award are described in detail. Finally, the reader is enlightened regarding the work of the European ExPeRT research group who are promoting the use of quality models within health care.

Accreditation↗

The engineering of gene regulatory networks.

The rapid accumulation of genetic information and advancement of experimental techniques have opened a new frontier in biomedical engineering. With the availability of well-characterized components from natural gene networks, the stage has been set for the engineering of artificial gene regulatory networks with sophisticated computational and functional capabilities. In these efforts, the ability to construct, analyze, and interpret qualitative and quantitative models is becoming increasingly important. In this review, we consider the current state of gene network engineering from a combined experimental and modeling perspective. We discuss how networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo.

Animals↗

Analysis of molecular profile data using generative and discriminative methods.

A modular framework is proposed for modeling and understanding the relationships between molecular profile data and other domain knowledge using a combination of generative (here, graphical models) and discriminative [Support Vector Machines (SVMs)] methods. As illustration, naive Bayes models, simple graphical models, and SVMs were applied to published transcription profile data for 1,988 genes in 62 colon adenocarcinoma tissue specimens labeled as tumor or nontumor. These unsupervised and supervised learning methods identified three classes or subtypes of specimens, assigned tumor or nontumor labels to new specimens and detected six potentially mislabeled specimens. The probability parameters of the three classes were utilized to develop a novel gene relevance, ranking, and selection method. SVMs trained to discriminate nontumor from tumor specimens using only the 50-200 top-ranked genes had the same or better generalization performance than the full repertoire of 1,988 genes. Approximately 90 marker genes were pinpointed for use in understanding the basic biology of colon adenocarcinoma, defining targets for therapeutic intervention and developing diagnostic tools. These potential markers highlight the importance of tissue biology in the etiology of cancer. Comparative analysis of molecular profile data is proposed as a mechanism for predicting the physiological function of genes in instances when comparative sequence analysis proves uninformative, such as with human and yeast translationally controlled tumour protein. Graphical models and SVMs hold promise as the foundations for developing decision support systems for diagnosis, prognosis, and monitoring as well as inferring biological networks.

Bayes Theorem↗

Modeling the water use efficiency of soybean and maize plants under environmental stresses: application of a synthetic model of photosynthesis-transpiration based on stomatal behavior.

Understanding the variability of plant WUE and its control mechanism can promote the comprehension to the coupling relationship of water and carbon cycle in terrestrial ecosystem, which is the foundation for developing water-carbon coupling cycle model. In this paper, we made clear the differences of net assimilation rate, transpiration rate, and WUE between the two species by comparing the experiment data of soybean (Glycine max Merr.) and maize (Zea mays L.) plants under water and soil nutrient stresses. WUE of maize was about two and a half times more than that of soybean in the same weather conditions. Enhancement of water stresses led to the marked decrease of Am and Em of two species, but water stresses of some degree could improve WUE, and this effect was more obvious for soybean. WUE of the two species changed with psiL in a second-order curve relation, and the WUE at high fertilization was higher than that at low fertilization, this effect was especially obvious for maize. Moreover, according to the synthetic model of photosynthesis-transpiration based on stomatal behavior (SMPTSB) presented by Yu et al. (2001), the WUE model and its applicability were discussed with the data measured in this experiment. The WUE estimated by means of the model accorded well with the measured values. However, this model underestimated the WUE for maize slightly, thus further improvement on the original model was made in this study. Finally, by discussing some physiological factors controlling Am and WUE, we made clear the physiological explanation for differences of the relative contributions of stomata- and mesophyll processes to control of Am and WUE, and the applicability of WUE model between the two species. Because the requirement to stomatal conductance by unit change of net assimilation rate is different, the responses of opening-closing activity of stomata to environmental stresses are different between the two species. To obtain the same level of net assimilation rate, soybean has to open its stomata more widely to keep small stomatal resistance, as compared with maize.

Ecosystem↗

Polycystic kidney disease: genes, proteins, animal models, disease mechanisms and therapeutic opportunities.

An increased understanding of the genetic, molecular and cellular mechanisms responsible for the development of polycystic kidney disease has laid out the foundation for the development of rational therapies. Many animal models where these therapies can be tested are currently available. This review summarizes the rationale for these treatments, the results of preclinical trials and the prospects for clinical trials, some already in early phases of implementation.

Animals↗

Success factors for open access.

Open access to the peer-reviewed primary research literature would greatly facilitate knowledge transfer between the creators and the users of the results of research and scholarship. Criteria are needed to assess the impact of recent initiatives, such as the Budapest Open Access Initiative. For example, how many open-access research journals exist within a given field, and what is the reputation of each one? And, how many openly-accessible institutional e-print archives have been created and how many are actually are being used by researchers and scholars? A simple approach to an assessment of the open-access portion of the medical literature is described, and some preliminary results are summarized. These preliminary results point to the need for incentives to foster the implementation of initiatives such as the Budapest Open Access Initiative. An example of an incentive model is proposed, where an agency or foundation that provides peer-reviewed grants-in-aid to researchers establishes an e-print archive. Only current grantees of the agency would be eligible to post reports about the results of research projects or programs that have been supported by the agency. Some advantages and implications of this particular model are outlined. It is suggested that incentive models of this kind are needed to increase the likelihood that open access to the primary medical research literature will soon reach a "tipping point" and move quickly toward wide acceptance.

Access to Information↗

Factorial hidden Markov models and the generalized backfitting algorithm.

Previous researchers developed new learning architectures for sequential data by extending conventional hidden Markov models through the use of distributed state representations. Although exact inference and parameter estimation in these architectures is computationally intractable, Ghahramani and Jordan (1997) showed that approximate inference and parameter estimation in one such architecture, factorial hidden Markov models (FHMMs), is feasible in certain circumstances. However, the learning algorithm proposed by these investigators, based on variational techniques, is difficult to understand and implement and is limited to the study of real-valued data sets. This chapter proposes an alternative method for approximate inference and parameter estimation in FHMMs based on the perspective that FHMMs are a generalization of a well-known class of statistical models known as generalized additive models (GAMs; Hastie & Tibshirani, 1990). Using existing statistical techniques for GAMs as a guide, we have developed the generalized backfitting algorithm. This algorithm computes customized error signals for each hidden Markov chain of an FHMM and then trains each chain one at a time using conventional techniques from the hidden Markov models literature. Relative to previous perspectives on FHMMs, we believe that the viewpoint taken here has a number of advantages. First, it places FHMMs on firm statistical foundations by relating them to a class of models that are well studied in the statistics community, yet it generalizes this class of models in an interesting way. Second, it leads to an understanding of how FHMMs can be applied to many different types of time-series data, including Bernoulli and multinomial data, not just data that are real valued. Finally, it leads to an effective learning procedure for FHMMs that is easier to understand and easier to implement than existing learning procedures. Simulation results suggest that FHMMs trained with the generalized backfitting algorithm are a practical and powerful tool for analyzing sequential data.

Algorithms↗