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A semantically enabled formalism for the knowledge management of Parkinson's disease.

Bio-ontology is a formal representation of biological concepts that is used in the interchange of communication between computers and humans alike. They can then be used in the formulation and retrieval of knowledge. In developing a knowledge-based system for Parkinson's Disease, a procedure of knowledge map was used to capture and harness the intellectual resources of an organization, and new paradigms for knowledge mapping were also formulated. Knowledge bases for symptoms and drugs, physiotherapy, speech and language therapy, and dieting that affect patient care were developed. Finally, the knowledge bases were merged to form a single central repository of knowledge base.

Diet↗

Toxicological evaluation and metal bioavailability in pregnant rats following exposure to clay minerals in the diet.

Silicate clays are frequently added to animal feeds to bind and reduce the bioavailability of mycotoxins in the gastrointestinal tract. However, the bioavailability of trace metals in these clay feed additives has not been thoroughly investigated. Clays that act nonselectively may interact with nutrients, minerals, and other feedborne chemicals to pose significant hidden risks. In this study, a calcium montmorillonite clay (Novasil Plus, NSP) commonly used as an enterosorbent for aflatoxins and a sodium montmorillonite clay (Swy-2) (Source Clay Minerals Repository, Columbia, MO) were examined. Clays were supplemented in the balanced diet of Sprague-Dawley rats during pregnancy at a level of 2% (w/w). Evaluations of toxicity were performed on gestation d 16 and included maternal body weights, maternal feed intakes, litter weights, and embryonic resorptions. Liver, kidneys, tibia, brain, uterus, pooled placentas, and pooled embryonic mass were collected and weighed. Tissues were lyophilized and neutron activation analysis (NAA) was performed. Elements considered by NAA included Al, Ba, Br, Ca, Ce, Co, Cr, Cs, Cu, Dy, Eu, Fe, Hf, K, La, Lu, Mg, Mn, Na, Nd, Ni, Rb, S, Sb, Sc, Se, Sm, Sr, Ta, Tb, Te, Th, Ti, Tl, U, V, Yb, Zn, and Zr. Inductively coupled plasma-mass spectroscopy further confirmed that Al was below detection limits (<0.5 ppm) in the brain. Animals supplemented with either NSP or Swy-2 were similar to controls with respect to toxicity evaluations and metal analysis, with the exception of decreased brain Rb following clay supplementation. Overall, the results of this study suggest that neither NSP nor Swy-2, at relatively high dietary concentrations, influences mineral uptake or utilization in the pregnant rat.

Animal Feed↗

The speciation of metals in mammals influences their toxicokinetics and toxicodynamics and therefore human health risk assessment.

Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal toxicokinetics and toxicodynamics in mammals, and therefore the adverse effects of metals, is reviewed to illustrate how the physicochemical characteristics of metals and their handling in the body (toxicokinetics) can influence toxicity (toxicodynamics). Generalizing from mercury, arsenic, lead, aluminum, chromium, and manganese, it is clear that metal speciation influences mammalian toxicity. Methods used in aquatic toxicology to predict the interaction among metal speciation, uptake, and toxicity are evaluated. A classification system is presented to show that the chemical nature of the metal can predict metal ion toxicokinetics and toxicodynamics. Essential metals, such as iron, are considered. These metals produce low oral toxicity under most exposure conditions but become toxic when biological processes that utilize or transport them are overwhelmed, or bypassed. Risk assessments for essential and nonessential metals should consider toxicokinetic and toxicodynamic factors in setting exposure standards. Because speciation can influence a metal's fate and toxicity, different exposure standards should be established for different metal species. Many examples are provided which consider metal essentiality and toxicity and that illustrate how consideration of metal speciation can improve the risk assessment process. More examples are available at a website established as a repository for summaries of the literature on how the speciation of metals affects their toxicokinetics.

Biotransformation↗

Excretion and placental and mammary transfer of hexachlorobenzene in the European ferret (Mustela putorius furo).

Female European ferrets (Mustela putorius furo) absorbed 98.5% of a single dietary exposure of hexachlorobenzene (HCB). The HCB was found to readily cross the placenta and to be excreted in the milk of pregnant/lactating ferrets. After consuming HCB-treated feed, ferrets raising offspring excreted 50% of the initial dose by 32 d, while unbred ferrets achieved this same degree of HCB elimination in 41 d. The percentages of HCB excreted via the urine and feces were approximately 5 and 45%, respectively, in both groups at the 50% stage of elimination. Adipose tissue was the most significant long-term repository for HCB in the ferret. The other tissues analyzed for [14C]HCB showed a general relationship of increased radioactivity with increased fat content of the tissue. The ferrets with nursing kits were able to significantly reduce their body burden of HCB when compared to unbred females. The developing ferret kits were subjected to HCB insult both in utero and via dam's milk. The ratio of milk to placental exposure in the growing offspring was calculated to be 31:1. Thus, in addition to any toxic effects HCB may have on the adult reproducing population, the placental and mammary transfer of HCB constitutes a potential threat to the developing and growing animal.

Animals↗

The New South Wales Inebriates Act: going, going, gone?

OBJECTIVE: To describe how the use of psychiatric hospitals as institutions for inebriates came about in New South Wales. CONCLUSIONS: A so-called 'temporary' solution to a political problem in 1929 led to the psychiatric hospitals in New South Wales becoming repositories for inebriates for the next 75 years. This unsatisfactory situation may be about to change.

Alcohol Drinking↗

Data collection in clinical toxicology: are there too many variables?

The evidence base of clinical toxicology suffers in comparison to other clinical disciplines. There is an excess of case reports and case series with little in the way of case control or cohort studies, and very few randomized controlled trials. While randomized controlled trials are rightly regarded as the gold standard for interventional studies, they have limitations that are particularly evident in the practice of clinical toxicology. Properly conducted observational studies using quantitative, epidemiological methods [nonrandomized trials, cohort studies (prospective and retrospective), case control methods] can provide answers that may be impossible to obtain from randomized controlled trials. Development of a strong evidence base is essential for progress in clinical toxicology. Whether that evidence base is derived from randomized controlled trials or observational studies, it is essential to collect data. Important observations can be made from basic clinical data and systematic collection of those data into some form of electronic database has siginificant advantages. A clinical database provides accurate information in the areas of clinical practice, quality assurance (audit), and research. In the area of research, an appropriately designed database can be both a source of hypotheses as well as a vehicle to test them. It can also serve as a repository of research data in subsequent randomized controlled trials.

Confounding Factors, Epidemiologic↗

Purification of electroplating wastewaters utilizing waste by-product ferrous sulfate and wood fly ash.

A new procedure for electroplating wastewater treatment using waste by-product (ferrous-sulfate) and waste (wood fly ash) is presented. Ferrous-sulfate was employed for Cr(VI) reduction whereas neutralization and heavy metal removal from electroplating wastewaters was performed using wood fly ash. Heavy metal removal efficiency varied from 97.5% for Cu to 99.973% for Zn. Satisfying results can be achieved already at the pH 8. The method is suitable for the purposes of wastewater treatment and disposal in compliance with environmental laws. Furthermore, it is technically simple, cost-efficient and requires less space compared to the classical methodology. According to the composition of its water extractable fraction remaining waste ash could be safely deposited on domestic waste repositories.

Chromium↗

Cytoplasmic lipid bodies of neutrophils: formation induced by cis-unsaturated fatty acids and mediated by protein kinase C.

Lipid bodies, nonmembrane-bound cytoplasmic inclusions, serve as repositories of esterified arachidonate and are increased in cells associated with inflammatory reactions. We have evaluated stimuli and mechanisms responsible for lipid body formation within human polymorphonuclear leukocytes (PMNs). Arachidonic acid and oleic acid stimulated dose-dependent formation of lipid bodies over 0.5-1 h. Other C20 and C18 fatty acids were less active and demonstrated rank orders as follows: cis-unsaturated fatty acids were much more active than trans-fatty acids, and activity diminished with decreasing numbers of double bonds. Lipid bodies elicited in vitro with cis-fatty acids were ultrastructurally identical to lipid bodies present in PMNs in vivo. Lipid body induction was not because of fatty acid-elicited oxidants or fatty acid-induced ATP depletion. Cis-fatty acid-induced activation of protein kinase C (PKC) was involved in lipid body formation as evidenced by the capacity of other PKC activators, 1-oleoyl-2-acetyl-glycerol and two active phorbol esters, phorbol myristate acetate, and phorbol 12,13 dibutyrate, but not an inactive phorbol, to induce lipid body formation. The PKC inhibitor, 1-O-hexadecyl-2-O-methyl-glycerol, inhibited PMN lipid body formation induced by oleic and arachidonic acids and by 1-oleoyl-2-acetyl-glycerol and phorbol myristate acetate. Other PKC inhibitors (staurosporine, H-7) also inhibited lipid body formation. Formation of lipid bodies in PMNs is a specific cellular response, stimulated by cis-fatty acids and diglycerides and apparently mediated by PKC, which results in the mobilization and deposition of lipids within discrete, ultrastructurally defined cytoplasmic domains.

Adenosine Triphosphate↗

Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation.

We used a morphometric and autoradiographic approach to analyze changes in specific cytoplasmic granules and cytoplasmic lipid bodies associated with human lung mast cell degranulation. Mast cells were dissociated from lung tissue by enzymatic digestion and were then enriched to purities of up to 99% by countercurrent centrifugation elutriation and recovery from columns containing specific antigen bound to Sepharose 6 MB. Degranulation was induced by goat anti-IgE. At various intervals after stimulation, parallel aliquots of cells were recovered for determination of histamine release or were fixed for transmission electron microscopy. We found that lipid bodies, electron-dense structures that lack unit membranes, were present in both control and stimulated mast cells. Autoradiographic analysis showed that lipid bodies represented the major repository of 3H-label derived from [3H]arachidonic acid taken up from the external milieu. By contrast, the specific cytoplasmic granules contained no detectable 3H-label. In addition, lipid bodies occurred in intimate association with degranulation channels during mast cell activation, but the total volume of lipid bodies did not change during the 20 min after stimulation with anti-IgE. This result stands in striking contrast to the behavior of specific cytoplasmic granules, the great majority of which (77% according to aggregate volume) exhibited ultrastructural alterations during the first 20 min of mast cell activation. These observations establish that mast cell cytoplasmic granules and cytoplasmic lipid bodies are distinct organelles that differ in ultrastructure, biochemistry, and behavior during mast cell activation.

Antibodies, Anti-Idiotypic↗

Production of auto-antiidiotypic antibody during the normal immune response. VII. Analysis of the cellular basis for the increased auto-antiidiotype antibody production by aged mice.

We have previously shown that old mice produce more hapten-augmentable plaque-forming cells (PFC) than do young animals, suggesting a greater auto-antiidiotype antibody (auto anti-Id) component in their immune response. In the present studies this is confirmed serologically. The marked auto-anti-Id response of aged mice can be transferred to lethally irradiated young recipients with spleen but not bone marrow cells from old donors, suggesting that it is an intrinsic property of their peripheral B cell population and that the distribution of Id arising from the bone marrow of old and young mice is similar. In contrast with young mice the auto-anti-Id response of old animals is relatively T cell-independent and old donors do not show an increase in their ability to transfer an auto-anti-Id response after priming with TNP-F. These observations suggest that old mice behave as if already primed for auto-anti-Id production. Irradiated mice reconstituted with bone marrow cells from either young or old donors together with splenic T cells from old donors generate a relatively large auto-anti-Id response, whereas mice reconstituted with bone marrow from either young or old donors together with splenic T cells from young donors produce few hapten-augmentable PFC. It is suggested that differences in Id expression and auto-anti-Id production are the consequences of the interaction of Id (and anti-Id) arising from the marrow with anti-Id (and Id) present in the peripheral T cell population which serves as a repository of information about shifts in Id distribution, resulting from lifelong interactions with environmental and self-antigens.

Aging↗

Calculations of ion-molecule deuterium fractionation reactions involving HD.

Gas-phase chemical models of deuterium fractionation in dense interstellar clouds utilize a small number of exothermic reactions to achieve fractionation. Although HD is a major repository of deuterium, it appears not to exchange deuterium with many molecular ions. Useful semiquantitative reasons have been given for the unusual lack of reactivity of exothermic ion-HD deuterium exchange systems, but quantum chemical studies are needed to understand these ideas in more detail and to determine if the lack of reactivity pertains at very low temperatures not studied in the laboratory, or whether tunneling can drive the reactions. Accordingly, the potential energy surfaces of three representative ion-molecule exchange reactions involving protonated ions (H3+, CH3+, HCO+) and HD have been investigated with ab initio quantum chemical techniques. Our results generally confirm the semiquantitative picture as to which reactions are likely to occur and show that tunneling at low temperatures is unlikely to alter this picture.

Astronomy↗

mtDNA diversity in Chukchi and Siberian Eskimos: implications for the genetic history of Ancient Beringia and the peopling of the New World.

The mtDNAs of 145 individuals representing the aboriginal populations of Chukotka-the Chukchi and Siberian Eskimos-were subjected to RFLP analysis and control-region sequencing. This analysis showed that the core of the genetic makeup of the Chukchi and Siberian Eskimos consisted of three (A, C, and D) of the four primary mtDNA haplotype groups (haplogroups) (A-D) observed in Native Americans, with haplogroup A being the most prevalent in both Chukotkan populations. Two unique haplotypes belonging to haplogroup G (formerly called "other" mtDNAs) were also observed in a few Chukchi, and these have apparently been acquired through gene flow from adjacent Kamchatka, where haplogroup G is prevalent in the Koryak and Itel'men. In addition, a 16111C-->T transition appears to delineate an "American" enclave of haplogroup A mtDNAs in northeastern Siberia, whereas the 16192C-->T transition demarcates a "northern Pacific Rim" cluster within this haplogroup. Furthermore, the sequence-divergence estimates for haplogroups A, C, and D of Siberian and Native American populations indicate that the earliest inhabitants of Beringia possessed a limited number of founding mtDNA haplotypes and that the first humans expanded into the New World approximately 34,000 years before present (YBP). Subsequent migration 16,000-13,000 YBP apparently brought a restricted number of haplogroup B haplotypes to the Americas. For millennia, Beringia may have been the repository of the respective founding sequences that selectively penetrated into northern North America from western Alaska.

Alaska↗

Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes.

Most common genetic disorders have a complex inheritance and may result from variants in many genes, each contributing only weak effects to the disease. Pinpointing these disease genes within the myriad of susceptibility loci identified in linkage studies is difficult because these loci may contain hundreds of genes. However, in any disorder, most of the disease genes will be involved in only a few different molecular pathways. If we know something about the relationships between the genes, we can assess whether some genes (which may reside in different loci) functionally interact with each other, indicating a joint basis for the disease etiology. There are various repositories of information on pathway relationships. To consolidate this information, we developed a functional human gene network that integrates information on genes and the functional relationships between genes, based on data from the Kyoto Encyclopedia of Genes and Genomes, the Biomolecular Interaction Network Database, Reactome, the Human Protein Reference Database, the Gene Ontology database, predicted protein-protein interactions, human yeast two-hybrid interactions, and microarray co-expressions. We applied this network to interrelate positional candidate genes from different disease loci and then tested 96 heritable disorders for which the Online Mendelian Inheritance in Man database reported at least three disease genes. Artificial susceptibility loci, each containing 100 genes, were constructed around each disease gene, and we used the network to rank these genes on the basis of their functional interactions. By following up the top five genes per artificial locus, we were able to detect at least one known disease gene in 54% of the loci studied, representing a 2.8-fold increase over random selection. This suggests that our method can significantly reduce the cost and effort of pinpointing true disease genes in analyses of disorders for which numerous loci have been reported but for which most of the genes are unknown.

Computational Biology↗

Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1.

To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗

Reference biospheres for post-closure performance assessment: inter-comparison of SHETRAN simulations and BIOMASS results.

Example Reference Biosphere 2B (ERB2B) is a hypothetical river catchment, described in the IAEA-sponsored BIOMASS study on biosphere aspects of post-closure radiological safety assessments for repositories for solid radioactive wastes. In ERB2B, a radioactively contaminated aquifer interacts with the soils and sediments of the river catchment. A 'semi-distributed', lumped-parameter model (SDLP) was set up for the site as part of the BIOMASS study. In the model, empirically derived transfer functions are used to reduce the complexity of real hydrological transport systems to readily calculable mass-balance accounting routines. In this work, a physically based, spatially distributed modelling system SHETRAN was set up for the site and comparison made with the existing SDLP model. The work has shown that, using standard soil properties in SHETRAN, the soil rapidly saturates and much of the hydrologically effective rainfall (precipitation less evapotranspiration) is lost as saturation-excess surface runoff. This is contrary to the assumptions in the SDLP model. The difficulty arose from the original formulation of catchment characteristics in BIOMASS. Specifically, there was a large water volume entering the soils from precipitation together with an upward flux of groundwater across the lower boundary of a substantial part of the catchment. This water had to be lost from the catchment in some way and the thinness of the soil zone precluded dominance of subsurface, lateral flow over surface runoff. Increasing the saturated conductivity from 1 to 20 m d(-1) reduced the surface flows to similar values to those assumed in the SDLP model (this could also have been achieved by increasing the soil depth). Even with the high saturated conductivity there were still major differences between the two representations. In the woodland on the upper slopes of the valley, the SHETRAN simulation was slightly wetter than the SDLP model, whereas in the shrubland and marshland near the river it was drier than the SDLP model. In the SDLP model, subsurface lateral flows are ignored if there is surface flow, and deep subsurface flows are ignored if there are shallow subsurface flows. In the SDLP model, there is a major assumed change in flow regime between summer and winter. This is not the case in the SHETRAN simulation. Overall, this work illustrates the problems of using 'semi-distributed', lumped-parameter models without prior calibration against a physically based model and the potential for implying unexpected and possibly implausible hydrological characteristics through the specification of flows without considering whether they could occur for realistic soil depths and properties. As there is a need for application of such SDLP models, particularly when undertaking probabilistic calculations, it is suggested that, in future, explicit hydrological modelling should be undertaken first, so that a physically realistic representation can be produced as a basis for assessment studies of the migration of radionuclides or other contaminants.

Fresh Water↗

Patient confidentiality, data security, and provider liabilities in diabetes management.

From inception, the electronic patient record has raised issues of data protection and patient confidentiality. These privacy issues have become more complicated with the introduction of electronic links to patient information held in databases sited on local and wide area networks. The first purpose of this paper is to review, from the provider's perspective, the issues surrounding patient confidentiality, data security, and consequential provider liabilities. The second is to propose possible immediate strategies and long-term solutions. Clinical procedures in diabetes practice create patient data from confidential information. This information is owned by the patient, received by the provider, enriched by a professional interpretation, and merged with other data into health records. Ownership, privacy, accountability, and responsibility issues are raised. Consequential data security and patient privacy are easily met by storage in a locked box or file cabinet. Conversion of such records into digital data in databases on local and wide area networks markedly increases the provider's exposure to liabilities. Current methods for securing remote data exist. These involve user authentication and secure transmission, but remote data storage is far less secure than a locked box. New tools for the secure storage of patient data are outlined. These involve encryption and decryption by the provider alone. A suite of computer protocols is presented that can restore security equivalent to a "locked box" and thus reduce liabilities for the provider. Providers should protect the privacy of their patients by encrypting all data that are stored in remote repositories. The tools to do this are urgently needed. A standardized digital protocol for verifying user identities, preserving patient confidentiality, and controlling data security by encryption will fully mitigate provider liabilities. Standardization and economies of scale promise future cost containment.

Confidentiality↗

Atlantic Telehealth Knowledge Exchange.

Atlantic Canada has some of the earliest, most comprehensive, well-established networks, and innovative applications for telehealth in the country. The region offers a range of models for telehealth, in terms of management structure, coordination, funding, equipment, utilization, and telehealth applications. Collectively, this diversity, experience, and wealth of knowledge can significantly contribute to the development of a knowledge base for excellence in telehealth services. There is no formal process in place for the sharing of information amongst the provinces. Information sharing primarily occurs informally through professional contacts and participation in telehealth organizations. A core group of organizations partnered to develop a process for knowledge exchange to occur. This type of collaborative approach is favored in Atlantic Canada, given the region's economy and available resources. The Atlantic Telehealth Knowledge Exchange (ATKE) project centred on the development of a collaborative structure, information sharing and dissemination, development of a knowledge repository and sustainability. The project is viewed as a first step in assisting telehealth stakeholders with sharing knowledge about telehealth in Atlantic Canada. Significant progress has been made throughout the project in increasing the profile of telehealth in Atlantic Canada. The research process has captured and synthesized baseline information on telehealth, and fostered collaboration amongst telehealth providers who might otherwise have never come together. It has also brought critical awareness to the discussion tables of governments and key committees regarding the value of telehealth in sustaining our health system, and has motivated decision makers to take action to integrate telehealth into e-health discussions.

Benchmarking↗

Brines in seepage channels as eluants for subsurface relict biomolecules on Mars?

Water, vital for life, not only maintains the integrity of structural and metabolic biomolecules, it also transports them in solution or colloidal suspension. Any flow of water through a dormant or fossilized microbial community elutes molecules that are potentially recognizable as biomarkers. We hypothesize that the surface seepage channels emanating from crater walls and cliffs in Mars Orbiter Camera images results from fluvial erosion of the regolith as low-temperature hypersaline brines. We propose that, if such flows passed through extensive subsurface catchments containing buried and fossilized remains of microbial communities from the wet Hesperian period of early Mars (approximately 3.5 Ga ago), they would have eluted and concentrated relict biomolecules and delivered them to the surface. Life-supporting low-temperature hypersaline brines in Antarctic desert habitats provide a terrestrial analog for such a scenario. As in the Antarctic, salts would likely have accumulated in water-filled depressions on Mars by seasonal influx and evaporation. Liquid water in the Antarctic cold desert analogs occurs at -80 degrees C in the interstices of shallow hypersaline soils and at -50 degrees C in salt-saturated ponds. Similarly, hypersaline brines on Mars could have freezing points depressed below -50 degrees C. The presence of hypersaline brines on Mars would have extended the amount of time during which life might have evolved. Phototrophic communities are especially important for the search for life because the distinctive structures and longevity of their pigments make excellent biomarkers. The surface seepage channels are therefore not only of geomorphological significance, but also provide potential repositories for biomolecules that could be accessed by landers.

Extraterrestrial Environment↗