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PubMed1989

Integration of general hospital psychiatric services with freestanding psychiatric hospitals.

General medical hospitals and freestanding psychiatric hospitals usually function independently. The authors review the relative strengths and weaknesses of the two settings and suggest a plan for a rational coordination of services. In an efficient integrated system, the general hospital would provide emergency psychiatric services and treat patients with combined medical and psychiatric conditions. The freestanding facility would offer inpatient and outpatient services, as well as partial hospitalization and transitional living arrangements, to psychiatric patients without medical complications. All facilities would share professional staff and data processing capabilities and would have common policies and procedures, reducing the cost of treatment and facilitating patient transfers.

Hospital Bed Capacity, 100 to 299↗

PubMed2006

Using NVDRS data for suicide prevention: promising practices in seven states.

OBJECTIVES: This article describes how seven states participating in a new public health surveillance system for violent death in the US, the National Violent Death Reporting System (NVDRS), have used data to support local suicide prevention activities. SETTING: The NVDRS is unique in that it augments death certificate data with event and circumstance information from death investigation reports filed by coroners, medical examiners, and law enforcement. These data illuminate why the victim ended his or her life, fatal injury patterns, and toxicological findings at death. RESULTS: Current suicide prevention efforts using these data fall into three categories: describing the problem of suicide and identifying opportunities for intervention; collaborating on statewide suicide prevention plans; and forming new partnerships for targeted prevention initiatives. Taken together, these three areas show early promise for state suicide prevention efforts. CONCLUSIONS: In each of the states, NVDRS data analyses are being shared with injury prevention colleagues, suicide prevention planning groups and policymakers, and adapted to respond to unique state and local suicide problems. A powerful surveillance tool, the NVDRS is bringing new clarity and direction to these state-based efforts. The NVDRS can serve as a model for other countries looking to establish timely suicide surveillance systems and data driven prevention strategies.

Adult↗

PubMed1997

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); program for persons with disabilities; basic program--DoD. Final rule.

This final rule simplifies the administration of benefits under the CHAMPUS Program for the Handicapped (PFTH) and changes the name of this benefit to Program for Persons with Disabilities (PFPWD); adds occupational therapists in independent practice to the list of authorized individual professional providers; provides criteria for cost-sharing certain procedures when data is transferred electronically from the patient's home to a medical practitioner; defines and limits plans recognized as supplemental insurance under CHAMPUS; and adopts the Federal Claims Collection Act and the Federal Claims Collection Standards by reference.

Cost Sharing↗

PubMed2006

Alien plant invasions--incorporating emerging invaders in regional prioritization: a pragmatic approach for Southern Africa.

Plant invasions are a serious threat to natural and semi-natural ecosystems worldwide. Most management-orientated research on invasions focuses on invaders that are already widespread and often have major impacts. This paper deals with "emerging" invaders-those alien species with the potential to become important problems without timely intervention. A climate matching procedure was developed to define areas of South Africa, Lesotho and Swaziland that could be invaded by 28 plant species that had previously been classified as emerging invaders. Information on the location of populations of these species in the study area was combined with information on their distributions (as native or alien) in parts of Australia and the United States of America. These two countries had the best available distribution data for this study. They also share many invasive alien plant species with South Africa. Climatic data obtained for weather stations near points of known occurrence in these countries were used to define the climatically suitable areas for each species in the study area. Almost 80% of the remaining natural environment in southern Africa was found to be vulnerable to invasion by at least one of these species, 50% by six or more and 24% by 16 or more species. The most vulnerable areas are the highveld grasslands and the eastern escarpment. The emerging invaders with the greatest potential range included Acacia podalyriifolia and Cortaderia selloana. The globally important invaders Ulex europaeus and Lythrum salicaria had a more limited invasion potential but could still become major invaders. There was no relationship between the extent of the climatically suitable areas for the different species and an expert ranking of their invasion potential, emphasising the uncertainties inherent in making expert assessments based on very little information. The methods used in this analysis establish a protocol for future modelling exercises to assess the invasion potential of other emerging invaders.

Acacia↗

PubMed2004

Is licofelone, a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase, a promising alternative in anti-inflammatory therapy?

As prostaglandins and leukotrienes are critical in inflammation, dual cyclo-oxygenase and 5-lipoxygenase enzymes inhibitors, especially licofelone, are being developed by pharmaceutical companies. Experimental data indicate that licofelone shares the antipyretic, analgesic, anti-inflammatory and anti-platelet activities of conventional nonsteroidal anti-inflammatory drugs (NSAIDs), and exhibits anti-allergic properties. Although licofelone may lead to similar adverse effects on the kidney than available NSAIDs, it appeared to induce less gastrointestinal damaging effects than nonselective NSAIDs in animals. Unfortunately, preliminary clinical studies provided less impressive data with respect to efficacy. Finally, the experimental promise of licofelone as a safe and potent anti-inflammatory and analgesic agent remains to be proved in humans.

Acetates↗

PubMed2025

Generating synthetic genotypes using diffusion models.

SUMMARY: In this paper, we introduce the first diffusion model designed to generate complete synthetic human genotypes, which, by standard protocols, one can straightforwardly expand into full-length, DNA-level genomes. The synthetic genotypes mimic real human genotypes without just reproducing known genotypes, in terms of approved metrics. When training biomedically relevant classifiers with synthetic genotypes, accuracy is near-identical to the accuracy achieved when training classifiers with real data. We further demonstrate that augmenting small amounts of real with synthetically generated genotypes drastically improves performance rates. This addresses a significant challenge in translational human genetics: real human genotypes, although emerging in large volumes from genome wide association studies, are sensitive private data, which limits their public availability. Therefore, the integration of additional, insensitive data when striving for rapid sharing of biomedical knowledge of public interest appears imperative. AVAILABILITY AND IMPLEMENTATION: All non proprietary data and the code to replicate the experiments is available on Github.

Humans↗

PubMed2005

The need of neuroinformatic approach in functional neurophysiology.

Despite the enormous growth in the number of facts and regularities observed in neuroscience, the current state of the field does not allow their integration in coherent theoretical frameworks. Neuroinformatics is a new research field devoted to development of neuroscience data bases together with computational models and analytical tools for sharing, integration and analysis of experimental data and the advancement of theories of nervous system function. From 1996 the OECD countries promote fostering neuroinformatics by eliminating the barriers that prevent cooperation and by providing incentives to potential participants. This activity was formulated in the Report on Neuroinformatics from The Global Science Forum Neuroinformatics Working Group of the OECD (2002) as well as in several printed publications by the Neuroinformatics group (Amari et al. 2002, Eckersley et al. 2003). This article summarizes the ideas presented in the Report and stresses the importance of analytical and modeling approach to functional neurophysiology.

Electroencephalography↗

PubMed1992

Obsessive and compulsive characteristics of craving for alcohol in alcohol abuse and dependence.

The purpose of this study was to quantify the extent to which subjective ratings of craving for alcohol in the alcohol-abusing or dependent person (herein, alcoholic) correlate with measurable and specific characteristics of obsessions and compulsions. The Yale-Brown Obsessive Compulsive Scale modified to reflect obsessionality and compulsivity specifically related to heavy drinking (Y-BOCS-hd) was used for this purpose. Highly significant correlations were found in the alcoholic population (n = 62) between subjectively rated craving for alcoholic beverages and several of the Y-BOCS-hd questions regarding alcohol-related thoughts and drinking behavior. Additionally, mean craving scores were considerably greater in the alcoholic population than in the matched control population (n = 62). The data suggest that craving shares specific features in common with the obsessions of obsessive-compulsive disorder and that the existence of craving is dependent on the presence of obsessive thoughts about drinking. Positive correlations between craving and measures of compulsive drinking behavior also were found; compulsive drinking behavior, however, may reflect the consequences of craving rather than a fundamental characteristic of craving itself. The data show that despite difficulties in defining the term craving, it is clearly a phenomenon that is experienced or endorsed by most alcoholic subjects and is not by most persons who do not abuse alcohol.

Adult↗

PubMed2004

The Allonemobius-Wolbachia host-endosymbiont system: evidence for rapid speciation and against reproductive isolation driven by cytoplasmic incompatibility.

Evidence for the evolution of fertilization incompatibilities and rapid speciation can be biased by the occurrence of hybridization and reproductive endosymbionts such as Wolbachia. For example, patterns of mitochondrial DNA (mtDNA) variation can be obscured by mitotypes hitchhiking on extrachromosomal elements like Wolbachia, while such endosymbionts can also induce phenotypes that mirror the operation of intrinsic fertilization incompatibilities between species. Therefore, before strong inferences can be drawn concerning the rates and processes of speciation in arthropod systems, we must first assess whether extrinsic endosymbionts obscure patterns of speciation. Here, I use the Allonemobius fasciatus-socius species complex to determine what role Wolbachia has played in the presumed rapid divergence of this complex by analyzing patterns of mtDNA and nuclear DNA variation in conjunction with sequence and cytoplasmic incompatibility data on Wolbachia. Data on molecular variation suggest that Wolbachia has not induced a strong selective sweep of the mitochondrial genome; nor does Wolbachia appear to induce cytoplasmic incompatibility. Preliminary evidence indicates that a third species identified within this complex, A. sp. nov. Tex, is partially reproductively isolated from A. socius, its closest relative, via conspecific sperm precedence or some form of postzygotic isolation. Moreover, shared mitotypes between A. sp. nov. Tex and A. socius may indicate the occurrence of a hybrid zone between these species near the border of Texas and Louisiana, although they may also represent shared ancestral polymorphisms. Molecular data also indicate that all three species in this complex diverged from a common ancestor as recently as 3000-30,000 years ago. Finally, the radiation of this complex from its ancestral population likely occurred in the presence of one strain of Wolbachia, thus suggesting a minimal role for Wolbachia during this burst of speciation. In total, barriers to gene flow do appear to have evolved very rapidly in this group of crickets.

Animals↗

PubMed1976

Development of monoclonal IgA and an apparent IgG in a patient with macroglobulinemia: sharing of individually specific antigenic determinants among IgM, IgA, and IgG.

Patient CM, who initially was diagnosed as having macroglobulinemia (IgM, kappa) was subsequently found to develop a monoclonal IgA(kappa) protein. Rabbit antisera directed against the patient's IgAm and IgM were rendered specific for individual antigenic (ind) determinants. The anti-IgAm and IgM ind sera reacted with both 131I labeled monoclonal proteins in a double antibody radioimmunoassay (RIA). In addition, both monoclonal immunoglobulins inhibited the reaction between labeled immunoglobulin and both ind antisera, and statistical analysis of the data suggested that the shared ind determinants were identical. The IgG fraction of patient CM's serum also contained a component which competed with both monoclonal IgA (CM) and IgM (CM) in the RIA specific for ind determinants. Analysis of serum samples taken over a 2-year period revealed that, in addition to IgM, both the IgA and IgG components possessing the shared ind determinant(s) were present in low concentrations in the earliest sample, although not detected by conventional techniques. The monoclonal IgA and the IgG component were found to increase in concentration over this time interval with a concomitant decrease in IgM. The regulation of immunoglobulin expression with respect to the proposed models of gene organization in antibody-producing cells was discussed.

Antibody-Producing Cells↗

PubMed2006

dbZach: A MIAME-compliant toxicogenomic supportive relational database.

Quantitative risk assessment and the elucidation of mechanisms of toxicity requires computational infrastructure and innovative analysis approaches that systematically consider available data at all levels of biological organization. dbZach (http://dbzach.fst.msu.edu) is a modular relational database with associated data insertion, retrieval, and mining tools that manages traditional toxicology and complementary toxicogenomic data to facilitate comprehensive data integration, analysis, and sharing. It consists of four Core Subsystems (i.e., Clones, Genes, Sample Annotation, and Protocols), four Experimental Subsystems (i.e., Microarray, Affymetrix, Real-Time PCR, and Toxicology), and three Computational Subsystems (i.e., Gene Regulation, Pathways, Orthology) that comply with the Minimum Information About a Microarray Experiment (MIAME) standard. It is capable of including emerging technologies and other model systems, including ecologically relevant species. dbZach represents an enterprise toxicogenomic data management system which facilitates data integration and analysis, and reduces uncertainties in the continuum from initial exposure to toxicity while facilitating more comprehensive elucidations of mechanisms of toxicity and supporting mechanistically-based quantitative risk assessment.

Animals↗

PubMed2003

The salience of the body: transition in sexual self-identity for women living with multiple sclerosis.

AIM: The purpose of this paper is to outline understandings about the construction of sexuality and the impact of a changing body for women living with multiple sclerosis (MS). We suggest that the process of transition towards incorporating the experience of chronic illness into one's life is influenced by the (re)construction of self-identity. DESIGN AND METHODS: A participatory action process guided the research. The women joined the authors for five group sessions that totalled 15 hours of contact time. In addition, we offered women the opportunity for one-to-one interviews at home. Nine women volunteered to participate. This allowed us to gain additional in-depth data about individual experiences. The interpretive framework was guided by the self-identity literature. When reading the transcripts we questioned: What is going on here? What does this say about the construction of self? What does this say about the construction of identity? What influence does the body have in the construction of self-identity? Analysis was collaborative (with the women) and the resultant emerging construction of sexuality is shared in this paper. Data generated during one-to-one interviews are privileged and we include two accounts from women who live with MS. The women's stories focus on sexuality, however, within this sexual context, we observed shifts in self-identity which we contend may shape the illness transition experience. FINDINGS: The rationale for privileging only two accounts is to expand understanding of Ordinariness and Extraordinariness with particular focus on the salience of the body in the 'sexual' lives of the women. Self-identity was shaped by how they felt about themselves as sexual beings, how they experienced their body, how they felt about sexual activities and by the way others reacted to them. Importantly, we view the women's sense of self, identity and the relationship to the body and find that shifts in self identity shape the woman's transition towards Ordinariness. CONCLUSIONS: This exploration of illness experiences is a reminder that our bodies are vehicles for our sense of self and identity. Cultural, educational, social, religious and family contexts all impact on women's capacity to shape the consequences of illness and the choices available to them. Facilitating women towards an awareness of the choices available in order to sustain or reclaim self may in turn expedite transition towards Ordinariness so that illness may become a part of their life.

Adaptation, Psychological↗

PubMed2004

Tests for covariate-associated heterogeneity in IBD allele sharing of affected relatives.

Linkage studies that aim to map susceptibility genes for complex diseases commonly test for excess allele sharing among affected relatives. Conventional methods based on identical-by-descent IBD allele sharing do not allow for possible differences among families, such as arise in the case of locus heterogeneity, and thus have reduced ability to detect linkage in the presence of such heterogeneity. We investigated two approaches to test for heterogeneity in allele sharing, using a family-level covariate that may be associated with different disease mechanisms leading to differences in allele sharing. Likelihood ratio tests for heterogeneity were formulated based on an extension of the linear and exponential likelihood models developed by Kong and Cox. Alternatively, we examined the asymptotic and permutation distributions of T-tests for differences between mean allele-sharing linkage scores from two covariate-defined family subgroups, assuming exchangeability. The size and power of heterogeneity tests were evaluated for S(all) and S(pairs) allele-sharing scoring functions using data sets of families with affected sibling and cousin pairs, generated under a model of locus heterogeneity. In certain simulation scenarios, the likelihood ratio test statistics did not follow the expected asymptotic distributions. The type I error estimates for the T-statistics conformed to nominal 5 and 1% levels in all scenarios considered, and corresponding power was comparable to that of the likelihood ratio tests. Application of these tests for heterogeneity detected significant differences in allele sharing between subgroups of families with inflammatory bowel disease.

Algorithms↗

PubMed1986

Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies.

The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the kappa light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated V kappa-(RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human V kappa germ-line genes that encode kappa light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a kappa V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.

Amino Acid Sequence↗

PubMed2001

Identification and classification of differentially expressed genes in renal cell carcinoma by expression profiling on a global human 31,500-element cDNA array.

We investigated the changes in gene expression accompanying the development and progression of kidney cancer by use of 31,500-element complementary DNA arrays. We measured expression profiles for paired neoplastic and noncancerous renal epithelium samples from 37 individuals. Using an experimental design optimized for factoring out technological and biological noise, and an adapted statistical test, we found 1738 differentially expressed cDNAs with an expected number of six false positives. Functional annotation of these genes provided views of the changes in the activities of specific biological pathways in renal cancer. Cell adhesion, signal transduction, and nucleotide metabolism were among the biological processes with a large proportion of genes overexpressed in renal cell carcinoma. Down-regulated pathways in the kidney tumor cells included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Our expression profiling data uncovered gene expression changes shared with other epithelial tumors, as well as a unique signature for renal cell carcinoma. [Expression data for the differentially expressed cDNAs are available as a Web supplement at http://www.dkfz-heidelberg.de/abt0840/whuber/rcc.]

Carcinoma, Renal Cell↗

PubMed2005

Translational crossroads for biomarkers.

A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute-supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.

Antineoplastic Agents↗

PubMed1995

Disciplined decision making in an interdisciplinary environment: some implications for clinical applications of statistical process control.

This paper explores some of the implications the statistical process control (SPC) methodology described by Pfadt and Wheeler (1995) may have for analyzing more complex performances and contingencies in human services or health care environments at an organizational level. Service delivery usually occurs in an organizational system that is characterized by functional structures, high levels of professionalism, subunit optimization, and organizational suboptimization. By providing a standard set of criteria and decision rules, SPC may provide a common interface for data-based decision making, may bring decision making under the control of the contigencies that are established by these rules rather than the immediate contingencies of data fluctuation, and may attenuate escalation of failing treatments. SPC is culturally consistent with behavior analysis, sharing an emphasis on data-based decisions, measurement over time, and graphic analysis of data, as well as a systemic view of organizations.

Behavior Therapy↗

PubMed1994

The urge to merge: linking vital statistics records and Medicaid claims.

This paper describes a procedure used to link Medicaid claims data to California vital statistics records for very low birthweight infants. The linkage involved about 53,000 infants born from 1980 to 1987 and 1.46 million claims for delivery/birth-related hospital admissions during the same period. Because the two data files did not share a unique identifier, record linkage required combining evidence across several linking variables: delivery hospital, delivery/birth date or hospitalization period, names, mother's age, and zip code. To combine the various pieces of evidence, we used record linkage theory to compute scores that measure the likelihood of a match, i.e., that two records correspond to the same delivery. These scores appropriately weight the various pieces of evidence for or against a match. Implementation required dealing with large amounts of missing data in one of the files, errors and variations in reported names, and the need to minimize the number of incorrect links. The approach applies to a wide range of linkage problems. The ability to combine existing datasets to form new datasets containing analysis variables from each facilitates analyses that would otherwise be impossible, or prohibitively expensive.

Bias↗