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The saturated zone at Yucca Mountain: an overview of the characterization and assessment of the saturated zone as a barrier to potential radionuclide migration.

The US Department of Energy is pursuing Yucca Mountain, Nevada, for the development of a geologic repository for the disposal of spent nuclear fuel and high-level radioactive waste, if the repository is able to meet applicable radiation protection standards established by the US Nuclear Regulatory Commission and the US Environmental Protection Agency (EPA). Effective performance of such a repository would rely on a number of natural and engineered barriers to isolate radioactive waste from the accessible environment. Groundwater beneath Yucca Mountain is the primary medium through which most radionuclides might move away from the potential repository. The saturated zone (SZ) system is expected to act as a natural barrier to this possible movement of radionuclides both by delaying their transport and by reducing their concentration before they reach the accessible environment. Information obtained from Yucca Mountain Site Characterization Project activities is used to estimate groundwater flow rates through the site-scale SZ flow and transport model area and to constrain general conceptual models of groundwater flow in the site-scale area. The site-scale conceptual model is a synthesis of what is known about flow and transport processes at the scale required for total system performance assessment of the site. This knowledge builds on and is consistent with knowledge that has accumulated at the regional scale but is more detailed because more data are available at the site-scale level. The mathematical basis of the site-scale model and the associated numerical approaches are designed to assist in quantifying the uncertainty in the permeability of rocks in the geologic framework model and to represent accurately the flow and transport processes included in the site-scale conceptual model. Confidence in the results of the mathematical model was obtained by comparing calculated to observed hydraulic heads, estimated to measured permeabilities, and lateral flow rates calculated by the site-scale model to those calculated by the regional-scale flow model. In addition, it was confirmed that the flow paths leaving the region of the potential repository are consistent with those inferred from gradients of measured head and those independently inferred from water-chemistry data. The general approach of the site-scale SZ flow and transport model analysis is to calculate unit breakthrough curves for radionuclides at the interface between the SZ and the biosphere using the three-dimensional site-scale SZ flow and transport model. Uncertainties are explicitly incorporated into the site-scale SZ flow and transport abstractions through key parameters and conceptual models.

Forecasting↗

Vestibular deficits in deaf children.

Considerable knowledge has been accumulated regarding acquired and congenital deafness in children. However, despite the intimate relationship between the auditory and vestibular systems, data are limited regarding the status of the balance system in these children. Using a test population of 15 children, aged 8 to 17 years, we performed electronystagmography testing. The test battery consisted of the eye-tracking (gaze nystagmus, spontaneous nystagmus, saccade, horizontal pursuit and optokinetic) tests, positional/positioning (Dix-Hallpike and supine) tests, and rotational chair tests. With age-matched controls, five children were tested in each of the following three categories: normal hearing, hereditary deafness, and acquired deafness. The children in the hereditary deafness category were congenitally deaf and had a family history of deafness. Those subjects in the acquired deafness category had hearing loss before the age of 2 years, after meningitis. Analysis of variance demonstrated significant differences between the two deaf groups and the control subjects in the gaze nystagmus test, saccade latencies, horizontal pursuit phase, and Dix-Hallpike and supine positionally provoked nystagmus. Also, significant differences were found in rotational chair gain and phase between the deaf and normal-hearing children. The children with acquired deafness exhibited the most profound results. In addition, there were significant differences in rotational chair gain between the acquired and congenitally deaf children. No differences were noted in horizontal pursuit gains, saccade accuracies, or saccade asymmetries. These preliminary data demonstrate that the etiologic factors responsible for congenital and acquired deafness in children may indeed affect the balance system as well. These findings of possible balance disorders in conjunction with the profound hearing loss in this patient population will have prognostic implications in the future evaluation, treatment, and rehabilitation of these patients.

Adolescent↗

Protoporphyrin IX production and its photodynamic effects on glioma cells, neuroblastoma cells and normal cerebellar granule cells in vitro with 5-aminolevulinic acid and its hexylester.

5-Aminolevulinic acid (ALA) has shown promising in photodynamic detection and therapy of brain tumor. However, the knowledge on selective accumulation of ALA-induced protoporphyrin IX (PpIX) in brain tumor tissue is still fragment. In the present study, the rat C6 glioma cells, human SK-N-SH neuroblastoma cells, and rat normal cerebellar granule cells (RCG) were used to investigate the PpIX production and photocytotoxicity in vitro. The C6 cells and SK-N-SH cells showed a similar kinetics of PpIX accumulation after exposure to ALA or ALA hexyl ester (ALA-H), with an initial increase up to 6-8 h and then saturated. In the case of RCG cells, the PpIX accumulation slowly increased until 12 h studied. However the cellular PpIX content was more than 10 times higher in the C6 and SK-N-SH cells than that in the normal RCG cells. The intracellular localization of PpIX measured by cofocal laser scanning microscopy was in same pattern in the C6 glioma cells and RCG normal cells with a diffuse cytoplasm distribution. The sensitivity of the C6 cells and SK-N-SH cells to ALA or ALA-H PDT was similar. It appears that ALA-H could achieve similar or slightly better results than ALA with respect to PpIX production and photoinactivation of cells, although a 10 times lower concentration of ALA-H was used.

Aminolevulinic Acid↗

Genetic influences on reproductive performance.

The potential for genetic improvement of reproductive performance in pigs is great. Improvement can be achieved by increased commercial use of F1 hybrid females produced by crossing lines with excellent reproductive performance and by selection within nucleus populations of these lines for improved reproduction as well a for growth and carcass characteristics. The value of incorporating reproductive traits in selection programs is critically dependent on the relative economic values of fat (or lean) and of extra pigs produced. There is widespread agreement that litter size is the first choice as both the selection objective and the criterion to improve reproductive performance, on economic, genetic, and ease of measurement grounds. Although there are few examples of successful response to selection for increased litter size in pigs (exceptions being the University of Nebraska selection experiment and results achieved by hyperprolific selection schemes), overall results do not suggest that selection for litter size is impossible, only that it is difficult with limited resources. Artificial insemination is being used increasingly by pig breeding companies to accelerate rates of genetic improvement and to improve dissemination. Combining data from genetically connected herds and analyzing with BLUP computer programs to make efficient use of information on relatives makes selection for litter size feasible while maintaining selection pressure for growth and carcass traits. Although selection for lifetime productivity is impractical today, the knowledge and data accumulated from successful breeding programs for litter size may help make it the selection objective of the future. Meanwhile, the search continues for useful indirect criteria for selection, from testis size to molecular markers, and scientists are working with highly prolific breeds of Chinese pigs to better understand the physiologic and genetic basis of large litter size.

Animals↗

Tight transcriptional control of the ETS domain factors Erm and Pea3 by Fgf signaling during early zebrafish development.

Several molecules of the Fibroblast growth factor family have been implicated in the development of the vertebrate brain, but the effectors of these molecules remain largely unknown. Here we study Erm and Pea3, two ETS domain transcription factors, and show that their expression correlates closely with the domains of fgf8 and fgf3 expression. In situ hybridization analysis in wild-type and acerebellar (ace) mutant embryos defective for fgf8 demonstrates a requirement of Fgf8 for normal expression levels of erm and pea3 transcripts in and close to various domains of Fgf8 action, including the prospective midbrain-hindbrain region, the somites, the neural crest, the forebrain, and developing eyes. Morpholino-oligomer-assisted gene knock-down experiments targeted against fgf8 and fgf3 suggest that Fgf3 and Fgf8 are co-regulators of these genes in the early forebrain anlage. Furthermore, inhibition of Fgf signaling by overexpression of sprouty4 or application of the Fgf inhibitor SU5402 leads to a loss of all erm and pea3 expression domains. Conversely, ectopically provided fgf3 mRNA or implanted beads coated with Fgf8 elicit ectopic transcription of erm and pea3. Both activation and loss of transcripts can be observed within short time frames. We conclude that both the transcriptional onset and maintenance of these factors are tightly coupled to Fgf signaling and propose that erm and pea3 transcription is a direct readout of cells to Fgf levels. Given the knowledge that has accumulated on the posttranslational control of ETS domain factors and their combinatorial interactions with other transcription factors, we suggest that the close coupling of erm and pea3 transcription to Fgf signaling might serve to integrate Fgf signaling with other signals to establish refined patterns in embryonic development.

Animals↗

HIV immunopathogenesis.

The challenges of human immunodeficiency virus type 1 (HIV-1) infection are related to the evolving scientific knowledge that has accumulated regarding the pathogenesis of the HIV illness trajectory. HIV-1 infection results in the clinical presentation of a disease process that encompasses a spectrum of illness from asymptomatic infection to acquired immune deficiency syndrome (AIDS). This article will provide a review of the human immune system, the structure, life cycle, and kinetics of HIV including its effects on the immune system, as well as the transmission, diagnosis, and current treatment recommendations.

Disease Progression↗

State-of-the-art screening for lung cancer: (part 2): CT scanning.

There have been dramatic improvements in technology in the past decade. In conjunction there have also been advances in our clinical knowledge that have led to changes in the screening regimen. These changes are expected to continue in the future as CT scanners continue to improve and knowledge about screening accumulates, and computer-assisted techniques are expected to play an ever more important role. This dynamic process will lead to continued improvements in the diagnostic distribution of lung cancers detected under CT screening.

Adult↗

The acquisition of auxiliaries BE and HAVE: an elicitation study.

Auxiliary syntax is recognized to be one of the more complex aspects of language that children must acquire. However, there is much disagreement among researchers concerning children's early understanding of auxiliaries, with some researchers advocating a relatively abstract grammar as the basis for auxiliary syntax, while others view the acquisition of auxiliary syntax as the gradual accumulation of linguistic knowledge, initially tied to individual lexical items. To investigate the status of children's early knowledge of auxiliary syntax, two studies were carried out. In study 1, 28 children (M= 3;1) were tested for their use of the auxiliaries BE and HAVE in declaratives, while in study 2, 19 children (M=3;3) were tested for their use of these auxiliaries in questions. Although overall error rates were low, there were differences between BE and HAVE in the proportion and types of errors observed in declaratives and questions, and some individual children showed very high error rates. The implications of these findings for different models of auxiliary syntax in children's early utterances are discussed.

Child Language↗

"If you got everything, it's good enough": perspectives on successful aging in a Canadian Inuit community.

Structured interviews with 38 Inuit in the community of Holman were conducted to examine Inuit definitions of successful and unsuccessful aging. Qualitative analysis of the interview data suggests that (1) contrary to much of the literature about culture change in the Canadian North, there appear to be no perceivable differences in the ways Inuit of different age cohorts view aging and elderhood; (2) a successful old age is not one necessarily characterized by individual good health, but rather by the ability of the individual to successfully manage declining health; and (3) for Inuit, the most important determinants of a successful elderhood are not material but ideological. That is, an individual's attitudes in late life, and in particular their willingness to transmit their accumulated wisdom and knowledge to their juniors, are the critical determinants of whether an elder is viewed as having a successful old age.

Journal Article↗

Clinical health psychology: a specialty for the 21st century.

To meet its potential in the 21st century, clinical health psychology must develop an accumulated body of knowledge relevant to practice, disseminate this knowledge, use this knowledge in practice and policy, and provide appropriate education and training for future psychologists. In this Division of Health Psychology Presidential Address, the author articulates issues in each of these areas, highlighting changes in health care and problems in research as well as issues in the development of practice guidelines and policies relevant to organized psychology.

Behavioral Medicine↗

Evolutionary conservation of biogenesis of beta-barrel membrane proteins.

The outer membranes of mitochondria and chloroplasts are distinguished by the presence of beta-barrel membrane proteins. The outer membrane of Gram-negative bacteria also harbours beta-barrel proteins. In mitochondria these proteins fulfil a variety of functions such as transport of small molecules (porin/VDAC), translocation of proteins (Tom40) and regulation of mitochondrial morphology (Mdm10). These proteins are encoded by the nucleus, synthesized in the cytosol, targeted to mitochondria as chaperone-bound species, recognized by the translocase of the outer membrane, and then inserted into the outer membrane where they assemble into functional oligomers. Whereas some knowledge has been accumulated on the pathways of insertion of proteins that span cellular membranes with alpha-helical segments, very little is known about how beta-barrel proteins are integrated into lipid bilayers and assembled into oligomeric structures. Here we describe a protein complex that is essential for the topogenesis of mitochondrial outer membrane beta-barrel proteins (TOB). We present evidence that important elements of the topogenesis of beta-barrel membrane proteins have been conserved during the evolution of mitochondria from endosymbiotic bacterial ancestors.

Circular Dichroism↗

RAS oncogenes: the first 30 years.

From the pioneering work with acute transforming retroviruses to the current post-genomic era, RAS genes have always been at the leading edge of signal transduction and molecular oncology. Yet, a complete understanding of RAS function and dysfunction - mainly in human cancer - is still to come. The knowledge that has accumulated since their discovery 30 years ago has, however, been remarkable, and should pave the way for not only solving the outstanding issues regarding RAS biology, but also for developing efficacious drugs that could have a significant impact on cancer treatment.

Animals↗

Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression.

Accumulation of neurobiological knowledge points to neurodevelopmental origins for certain psychotic and mood disorders. Recent landmark postmortem reports implicate Reelin, a secretory glycoprotein responsible for normal lamination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin protein in various compartments of hippocampal formation in subjects diagnosed with schizophrenia, bipolar disorder and major depression compared to normal controls. Significant reductions were observed in Reelin-positive adjusted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 area (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Reelin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs controls. Adjusted Reelin-positive cell densities were also reduced in CA4 areas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificantly in those with major depression. CA4 areas were also significantly reduced in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of confounding variables were found. The exception was that family history of psychiatric illness correlated strongly with Reelin reductions in several areas of hippocampus (CA4, adjusted cell density, F = 13.77, P = 0.001). We present new immunocytochemical evidence showing reductions in Reelin expression in hippocampus of subjects with schizophrenia, bipolar disorder and major depression and confirm recent reports documenting a similar deficit involving Reelin expression in brains of subjects with schizophrenia and bipolar disorder.

Adult↗

Tracking nitrate reducers and denitrifiers in the environment.

The ability to respire nitrate when oxygen is limited has been described in taxonomically diverse microorganisms including members of the alpha-, beta-, gamma- and epsilon-proteobacteria, high and low GC Gram-positive bacteria and even Archaea. Respiratory nitrate reduction is the first step of the denitrification pathway, which is important since it is the main biological process responsible for the return of fixed nitrogen to the atmosphere, thus completing the nitrogen cycle. During the last decade, considerable knowledge has been accumulated on the biochemistry and genetics of the nitrate reductases. In this paper, we summarize the recent progress in molecular approaches for studying the ecology of the nitrate-reducing community in the environment.

Bacteria↗

Defining characteristics of expertise in Japanese clinical nursing using the Delphi technique.

A four-round Delphi technique was conducted on 127 experienced Japanese nurses to develop a consensus of opinion on the defining characteristics underlying expertise, and the prime requirements for the development of expertise in clinical nursing. Sixteen statements identified as the prime defining characteristics underlying expertise indicated that experienced Japanese nurses' picture of expertise is general, comprehensive and focused on task expertise. Four prime requirements for the development of expertise identified indicated that neither experience nor accumulation of theoretical knowledge alone is sufficient to develop expertise; but that motivation and attitude do play an essential role in the development of expertise.

Attitude of Health Personnel↗

Autoimmune pancreatitis.

The recommended treatment for a focal mass in the head of the pancreas is pancreaticoduodenectomy. Preoperative biopsy is not advised in patients who are candidates for resection because of the documented risk of tumour dissemination along the needle tract and significant false negative results.1 Autoimmune pancreatitis is a relatively uncommon condition that can present as a pancreatic mass and mimic malignancy. It may respond to glucocorticoid therapy, and further assessment of such treatment is indicated.2 Such experience will only accumulate if wider knowledge of this condition leads to clinical suspicion.

Adult↗

National Institutes of Health Consensus Development Conference Statement on Celiac Disease, June 28-30, 2004.

NIH consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of (1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); (2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; (3) questions and statements from conference attendees during open discussion periods that are part of the public session; and (4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.

Biomedical Research↗

Mechanical cardiac support in the young with the Berlin Heart EXCOR pulsatile ventricular assist device: 15 years' experience.

The pediatric-size pneumatically driven pulsatile extracorporeal ventricular assist device (VAD) Berlin Heart EXCOR (Berlin Heart Mediprodukt GmbH, Berlin, Germany) was introduced into clinical practice by the German Heart Institute Berlin in 1992. Until July 1, 2005, Berlin Heart EXCOR systems have been used for circulatory support in 68 children up to 18 years of age with severe circulatory failure resistant to pharmacologic therapy. These were patients suffering from cardiomyopathy, fulminant myocarditis, end-stage congenital cardiac defects, and acute heart failure following congenital heart surgery. Mean VAD support time was 35 days (range, 0 to 420 days). Forty-two patients (62%) survived to transplantation or after weaning; 37 patients (54%), including eight infants, were discharged home. These results in patients with very advanced disease have improved significantly in recent years because of technical developments and growing experience in the treatment of patients on the device, in postoperative care and optimal timing for VAD implantation. Timely implantation of the Berlin Heart EXCOR in the course of progressive heart failure now appears to be justified because the system has undergone the necessary modifications and the accumulation of clinical knowledge has made its use highly reliable and safe.

Adolescent↗