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At least 1,153 records · Page 64Linked to original sources
PubMed2004

Coupled modeling of cement/claystone interactions and radionuclide migration.

The interactions between cement and a clayey host-rock of an underground repository for intermediate-level radioactive waste are studied with the reactive transport code HYTEC for supporting performance assessment. Care is taken in using relevant time scales (100,000 years) and dimensions. Based on a literature review, three hypotheses are considered with respect to the mineralogical composition of the claystone and the neo-formed phases. In the long term, the pH is buffered for all hypotheses and important mineral transformations occur both in cement and the host-rock. The destruction of the primary minerals is localized close to the cement/claystone interface and is characterized by the precipitation of secondary phases with retention properties (illite, zeolite). However, beyond the zone of intense mineral transformations, the pore water chemistry is also disturbed over a dozen meters due to an attenuated but continuous flux of hydroxyl, potassium and calcium ions. Four interdependent mechanisms control the profile in the whole system: diffusion of the alkaline plume, mineralogical buffering, ion exchange and clogging of the pore space at the cement/claystone interface. The migration of a selected group of radionuclides (Cs, Ra, Tc and U) is explicitly integrated in the simulations of the strongly coupled system. Theoretical profiles of distribution coefficient (Kd) and solubility limit values are derived from the simulations, and their sensitivity with respect to the system evolution is estimated.

Aluminum Silicates↗
PubMed2004

Use of X-ray absorption imaging to examine heterogeneous diffusion in fractured crystalline rocks.

Heterogeneous diffusion in different regions of a fractured granodiorite from Japan has been observed and measured through the use of X-ray absorption imaging. These regions include gouge-filled fractures, recrystallized fracture-filling material and hydrothermally altered matrix. With the X-ray absorption imaging technique, porosity, relative concentration, and relative mass of an iodine tracer were imaged in two dimensions with a sub-millimeter pixel size. Because portions of the samples analyzed have relatively low porosity values, imaging errors can potentially impact the results. For this reason, efforts were made to better understand and quantify this error. Based on the X-ray data, pore diffusion coefficients (Dp) for the different regions were estimated assuming a single diffusion rate and a lognormal multirate distribution of Dp. Results show Dp for the gouge-filled fractures are over an order of magnitude greater than those of the recrystallized fracture-filling material, which in turn is approximately two times greater than those for the altered matrix. The recrystallized fracture-filling material was found to exhibit the greatest degree of variability. The results of these experiments also provide evidence that diffusion from advective zones in fractures through the gouge-filled fractures and recrystallized fracture-filling material could increase the pore space available for matrix diffusion. This evidence is important for understanding the performance of potential nuclear waste repositories in crystalline rocks as diffusion is thought to be an important retardation mechanism for radionuclides.

Absorptiometry, Photon↗
PubMed2000

Etiologic and early marker studies in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial.

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which is randomizing 74,000 screening arm participants (37,000 men, 37,000 women; ages 55-74) and an equal number of nonscreened controls, is a unique setting for the investigation of the etiology of cancer and other diseases and for the evaluation of potential molecular markers of early disease. At entry, baseline information is collected by questionnaire on dietary intake, tobacco and alcohol use, reproductive history (for women), family history of cancer, use of selected drugs, and other selected risk factors. Blood samples collected at the baseline screening exam are aliquoted to serum, plasma, red blood cell, and buffy coat fractions. At the next two annual screening visits, serum samples are collected. At the third annual reexamination, cryopreserved whole blood is obtained, in addition to serum, plasma, red blood cell, and buffy coat fractions. At the fourth and fifth years, serum, plasma, and buffy coat are collected. All blood samples are shipped to a central repository for long-term storage at -70 degrees C. Dietary questionnaires and buccal cells for DNA analysis are obtained from nonscreened controls. Cancer cases are identified through annual follow-up questionnaires, and all deaths are identified through vital status tracing mechanisms. Procedures are being developed to obtain archival pathologic material for selected cases of cancer and related diseases. Initial investigations are focusing on the etiology of colorectal cancer and on the operative characteristics of tests for the early detection of colorectal and prostate cancer.

Aged↗
PubMed2002

Streamlining IRB review in multisite trials through single-study IRB Cooperative Agreements: experience of the Beta-Carotene and Retinol Efficacy Trial (CARET).

With their extensive data and specimen repositories, clinical trials are a long-term, valuable resource to health researchers. However, assuring protection of participants' rights can be challenging, particularly when such trials are conducted at multiple sites with multiple Institutional Review Boards (IRBs). One little-used mechanism that can streamline IRB review in multisite trials while maintaining participants' protections is the single-study IRB Cooperative Agreement. This agreement is entirely different from reciprocity agreements between institutions. Beginning in 1996, the Beta-Carotene and Retinol Efficacy Trial established single-study IRB Cooperative Agreements among its performance sites, which reduced the average time to complete IRB approval from over 6 months to 1 month for each of many substudies. We describe our experience and make recommendations for other multisite clinical trials.

Clinical Trials as Topic↗
PubMed1984

Clinical trials methods and the practice of medicine.

An important potential byproduct from clinical trials is validated clinical methods applicable to clinical practice. The potential for improved patient care is separate from the scientific and intellectual answers gained in such trials. The current mechanisms for the transfer of methodological information from clinical trials are inefficient and have identifiable barriers. Methods validated in clinical trials must be recognized and accentuated as a valuable resource. A central repository of clinical trials' methods and a retrieval system dedicated to this unique body of scientific literature is warranted. Reports of methodological advances from clinical trials should be published in the literature read by clinical practitioners. The effective transfer of methods information from clinical trials to the office of the clinical practitioner is possible but requires increased efforts on the part of clinical trials scientists.

Clinical Trials as Topic↗
PubMed1999

Distribution of adjuvant MF59 and antigen gD2 after intramuscular injection in mice.

MF59, which is an adjuvant approved for human use, typically elicits higher antibody titers than alum when used in combination with a variety of recombinant and natural subunit antigens. The mechanisms responsible for the adjuvant action of MF59 are not fully understood. In particular, little is known about the in vivo distribution of MF59 and of antigen after intramuscular (i.m.) injection. The goal of the present study was to determine the distribution of MF59 injected with soluble antigen gD2 from type 2 herpes simplex virus (HSV) and to compare the distribution of gD2 injected with or without MF59. At 4 h, 36% of the injected dose of labeled MF59 was in the quadriceps muscle and about 50% was in the inguinal fat surrounding the muscle. Half of the initial amount of labeled MF59 in muscle was detected 42 h after injection. The amount of labeled MF59 in the draining lymph nodes was maximal 2 d after injection, which represented 0.1-0.3% of the injected dose. At 4 h, 12% of the injected dose of labeled gD2 was found in the muscle. The presence of MF59 did not significantly modify the distribution of gD2. The results indicate that MF59 and gD2 distribute and are cleared independently after i.m. injection. Importantly, MF59 is unlikely to have a repository effect, whereby it slowly releases the antigen.

Adjuvants, Immunologic↗
PubMed2003

The biokinetics of uranium migrating from embedded DU fragments.

Military uses of depleted uranium (DU) munitions have resulted in casualties with embedded DU fragments. Assessment of radiological or chemical health risks from these fragments requires a model relating urinary U to the rate of migration of U from the fragments, and its accumulation in systemic tissues. A detailed biokinetic model for U has been published by the International Commission on Radiological Protection (ICRP), but its applicability to U migrating from embedded DU fragments is uncertain. Recently, Pellmar and colleagues (1999) conducted a study at the Armed Forces Radiobiology Research Institute (AFRRI) on the redistribution and toxicology of U in rats with implanted DU pellets, simulating embedded fragments. This paper compares the biokinetic data from that study with the behavior of commonly studied forms of U in rats (e.g., intravenously injected U nitrate). The comparisons indicate that the biokinetics of U migrating from embedded DU is similar to that of commonly studied forms of U with regard to long-term accumulation in kidneys, bone, and liver. The results provide limited support for the application of the ICRP's model to persons with embedded DU fragments. Additional information is needed with regard to the short-term behavior of migrating U and its accumulation in lymph nodes, brain, testicles, and other infrequently studied U repositories.

Animals↗
PubMed2003

Soil availability, plant uptake and soil to plant transfer of 99Tc--a review.

The fission yield of 99Tc from 239Pu and 235U is similar to that of 137Cs or 90Sr and it is therefore an important component of nuclear weapons fall-out, nuclear waste and releases from nuclear facilities. There is particular current interest in 99Tc transfer from soil to plants for: (a) environmental impact assessments for terrestrial nuclear waste repositories, and (b) assessments of the potential for phytoextraction of radionuclides from contaminated effluent and soil. Vascular plants have a high 99Tc uptake capacity, a strong tendency to transport it to shoot material and accumulate it in vegetative rather than reproductive structures. The mechanisms that control 99Tc entry to plants have not been identified and there has been little discussion of the potential for phytoextraction of 99Tc contaminated effluents or soil. Here we review soil availability, plant uptake mechanisms and soil to plant transfer of 99Tc in the light of recent advances in soil science, plant molecular biology and phytoextraction technologies. We conclude that 99Tc might not be highly available in the long term from up to 50% of soils worldwide, and that no single mechanism that might be easily targeted by recombinant DNA technologies controls 99Tc uptake by plants. Overall, we suggest that Tc might be less available in terrestrial ecosystems than is often assumed but that nevertheless the potential of phytoextraction as a decontamination strategy is probably greater for 99Tc than for any other nuclide of radioecological interest.

Biological Availability↗
PubMed2003

The volatilisation and sorption of (129)I in coniferous forest, grassland and frozen soils.

129I is a potentially important radionuclide in safety assessments of proposed deep geological radioactive waste repositories due to its radiotoxicity, high mobility and long physical half-life (15.7 million years). In soils, iodine is present both in an inorganic form and in organohalide complexes, some of which are volatile under natural environmental conditions. This study has examined volatilisation, sorption and the effect of freezing on sorption and loss of (125)I (physical half-life 60.2 days), as a surrogate for (129)I, within coniferous forest and grassland soils. The results do not suggest that volatilisation from these soils is a significant pathway for the transport of (129)I. Strong and specific sorption of iodine to humic substances has been demonstrated, which is reduced at freezing temperatures. It is hypothesised that rapid sorption to soil humic substances can significantly reduce volatilisation rates. The effect of freezing conditions on iodine extractability from soils suggests a microbially mediated sorption process.

Ecosystem↗
PubMed2003

Availability of 99Tc in undisturbed soil cores.

Models for safety assessment of radioactive waste repositories need accurate values of the soil-to-plant transfer of radionuclides. In oxidizing environments, (99)Tc is expected to occur as pertechnetate ((99)TcO(4)(-)). Due to its high mobility, leaching of this element in the field might be important, potentially affecting the reliability of estimated transfer parameters of (99)Tc as measured in closed experimental systems such as hydroponics or pot experiments. The aim of this experiment was to measure the leaching of (99)Tc in undisturbed irrigated soil cores under cultivation as well as plant uptake and to study the possible competition between the two transfer pathways. Undisturbed soil cores (50 x 50 cm) were sampled from a Rendzic Leptosol (R), a colluvial Fluvic Cambisol (F) and a Dystric Cambisol (D) using PVC tubes (three cores sampled per soil type). Each core was equipped with a leachate collector at the bottom, allowing the monitoring of (99)Tc leaching through the cores. Cores were placed in a greenhouse and maize (Zea mays L., cv. DEA, Pioneer) was sown. After 135 d, maize was harvested and radioactivity determined in both plant and water samples. Results showed that during the growing period, leaching of (99)Tc was limited, due to the high evapotranspiration rate of maize. After harvest, leaching of (99)Tc went on because of the absence of evapotranspiration. Effective uptake (EU) of (99)Tc in leaves and grains was calculated. EU reached 70% of the input in the leaves and was not significantly different among soils. These results confirmed those obtained from pot experiments, even though leaching was allowed to occur in close-to-reality hydraulical conditions. As a consequence, it was concluded that pot experiments are an adequate surrogate for more complex "close-to-reality" experimental systems for measuring transfer factors.

Biological Availability↗
PubMed2003

Estimation of animal transfer factors for radioactive isotopes of iodine, technetium, selenium and uranium.

In post-closure radiological safety assessments of repositories for solid radioactive wastes, transfers of radionuclides to animal products are typically characterised using Transfer Factors (TFs), defined as the ratio of the concentration of the radionuclide in the animal product of interest to the rate of intake in diet. Such transfer factors can be measured directly in experimental studies, but they can also be estimated by use of biokinetic models for uptake and retention of radionuclides in animals. Based on a review of the literature, biokinetic models have been developed for the uptake and retention of iodine, technetium, selenium and uranium. These biokinetic models allow TF values to be estimated for different types of animals and for different animal lifetimes. For each radionuclide considered, reference values and ranges of TF values are estimated. These are summarised in Table 1.

Animals↗
PubMed1990

The use of glucocorticosteroids to lessen the inflammatory sequelae following third molar surgery.

Acceptance of the use of glucocorticosteroids in density to control postsurgical inflammation has been impaired by concerns over side effects, adrenal suppression, and efficacy. The pattern of administration generally used is characterized as short-term, high-dose or pulse therapy, which has not been associated with significant side effects or adrenal suppression beyond 10 days. The selection of an appropriate glucocorticosteroid with minimal mineralocorticoid activity and extended biological activity is desirable. Oral and parenteral dosing are possible, and the latter can be administered as acetates (repository) or esters. The efficacy of glucocorticosteroids in reducing pain, swelling, and trismus after third molar surgery is difficult to ascertain because of methodological inconsistencies between investigations. In general, studies that used low dosing schedules have failed to produce dramatic and prolonged results. High-dosing intravenous (IV) studies have demonstrated significant short-term improvements, but the effects were not sustained. Combining IV administration with multiple oral dosing or a single intramuscular (IM) dose may be required to extend short-term improvement. High-dosing IM studies have shown significant and sustained anti-inflammatory effects with a single dose administered either pre- or post-operatively.

Glucocorticoids↗
PubMed1993

Dosage effects of pulsed steroid therapy on serum cortisol levels in oral and maxillofacial surgery patients.

The purpose of this study was to determine the effects of two dosage regimens of dexamethasone on the serum cortisol levels of a group of patients undergoing major maxillofacial surgical procedures. Analysis of the data demonstrated that the use of dexamethasone, 10 to 20 mg intravenously given every 3 hours intraoperatively and every 4 hours postoperatively over 24 hours, followed by a repository dose of 80 mg of intramuscular methylprednisolone, causes short-term serum cortisol suppression. The maximum depression occurred on postoperative day 3; normal levels were restored by postoperative day 7. Therefore, pulsed therapy can be considered relatively safe when known contraindications have been considered.

Adolescent↗
PubMed1997

Statistical planning and analysis considerations in the evaluation of in vitro alternatives to whole animal use for eye irritation testing.

Reports from the IRAG Working Groups assessing the current status of in vitro alternatives to whole animal eye irritation tests reflect some common approaches. Although each Working Group studied a particular class of assay, typically all Groups evaluated the in vitro alternatives on the basis of correlation with an in vivo test and the statistical significance of that correlation. However, the data furnished to them by the testing organizations had been obtained with little or no standardization of procedures for testing and evaluation of results. This paper presents issues of design and execution of such test programs that are of statistical concern, including objectives of the evaluation process; limitations of correlation; sources of variation and distinction between actual replication and repeated measurements; evaluation of the predictive ability of in vitro tests; association criteria; and other approaches to such evaluation programs. The distinction between statistical significance and toxicological significance is pointed out. Suggestions are presented for standardization of test protocols, test materials and evaluation programs for both in vitro and in vivo tests. A central repository for such standardization, under the aegis of a government agency, professional standards organization, university or research institute, would be a valuable asset. An addendum is furnished to illustrate assertions about a number of factors influencing correlations and their statistical significance.

Animal Testing Alternatives↗
PubMed2001

Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9.

OBJECTIVE: Fanconi anemia (FA) is an autosomal-recessive cancer susceptibility syndrome with seven complementation groups. Six of the FA genes have been cloned (corresponding to subtypes A, C, D2, E, F, and G) and the encoded proteins interact in a common pathway. Patient-derived mutations in FA genes have been helpful in delineating functional domains of FA proteins. The purpose of this work was to subtype FA patient-derived cell lines in our repository and to identify FA gene mutations. METHODS: We subtyped 62 FA patients as type A, G, C, or non-ACG by using a combination of retroviral gene transfer and immunoblot analysis. Among these FA patients, we identified six FA-G patients for further analysis. We used a strategy involving amplification of FANCG/XRCC9 exons and direct sequencing to identify novel FANCG mutations in cell lines derived from these FA-G patients. We functionally analyzed FANCG mutant alleles by transducing the corresponding cDNAs into a known FA-G indicator cell line and scoring correction of MMC sensitivity. RESULTS: Our results demonstrate a wide range of mutations in the FANCG gene (splice, nonsense, and missense mutations). Based on this mutational screen, a carboxy terminal functional domain of the FANCG protein appears to be required for complementation of FA-G cells and for normal assembly of the FANCA/FANCG/FANCC protein complex. CONCLUSION: The identification of patient-derived mutant alleles of FA genes can provide important insights to the function of FA proteins. FA subtyping is also a necessary precondition for gene therapy.

Adolescent↗
PubMed2001

Linkage analysis of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and systemic lupus erythematosus.

Previous studies have suggested an association between systemic lupus erythematosus (SLE) and an insertion/deletion polymorphism in the angiotensin-converting enzyme gene (ACE). This polymorphism consists of a 250-bp insertion/deletion of an alu repeat in the 16th intron of the ACE gene. Individuals homozygous for the deletion have a higher level of circulating enzyme. Due to the important role of this enzyme in regulating the renin--angiotensin and kallikrein--kininogen systems, it is possible that the ACE insertion/deletion may play a role in SLE, which can include vasculitis and vascular changes. Using primers flanking the insertion/deletion site, we have examined the ACE gene in lupus patients and family members using genomic DNA obtained from the Lupus Multiplex Registry and Repository (LMRR). We were unable to detect significant linkage or genetic association between the ACE gene and SLE.

Family Health↗
PubMed2002

Neuronal replacement in adult brain.

The discovery of spontaneous neuronal replacement in the adult vertebrate brain has changed the way in which we think about the biology of memory. This is because neuronal replacement is likely to have an impact on what a brain remembers and what it learns. Neuronal replacement has also changed the way in which we go about exploring new strategies for brain repair. Our new outlook on both these matters is all the more remarkable because of the pervasiveness of the earlier dogma, which for warm-blooded vertebrates relegated neurogenesis to embryonic development and, for a few neuronal classes, early postnatal life. The discovery of constant neuronal replacement in the adult brain was remarkable, too, in that it was not required by what we thought to be the logic of nervous system function. Moreover, no previous facts prepared us for it. Much of the modern theory of learning embraced the view of modifiable synapses as the key players in learning and as the repositories of memory. But if this were so, what would be the point of neuronal replacement in healthy brain tissue? In what follows, I will briefly review the work of Joseph Altman, because he was the first one to challenge the notion that new neurons were not produced in adulthood. I will then review what we know about neuronal replacement in the song system of birds, which my laboratory has studied for many years. In closing, I will offer a general theory of long-term memory that, if true, might explain why adult nervous systems constantly replace some of their neurons.

Aging↗
PubMed1997

Clonability and gene distribution on human chromosome 21: reflections of junk DNA content?

Data from transcriptional mapping of human chromosome 21 have been compiled from a number of sources. Regardless of the gene identification technique used, a consistent picture has developed: the centromere proximal half of 21q, which contains 50% of the DNA (20 Mb), harbors only 10% of the expressed sequences. Because of the variety of gene isolation techniques used, this result is unlikely to arise simply from methodological artefacts, biases in clonability or tissue specificity of expression. This region is known to be AT-rich and to contain APP, the largest gene (spanning 300 kb) currently analyzed on 21q. Interesting preliminary data from analysis of the Fugu rubripes homolog of APP has shown an unusually high, 50-fold, compaction of intron size, raising the intriguing possibility that >90% of the DNA in the human gene may be functionless. Thus, data from a variety of approaches suggest that a large part of 21q very likely has neither coding capacity nor associated regulatory function. By these criteria, it is a good candidate for a repository of junk DNA.

Animals↗