Integral Fast Reactor Program annual progress report, FY 1994

This report summarizes highlights of the technical progress made in the Integral Fast Reactor (IFR) Program in FY 1994. Technical accomplishments are presented in the following areas of the IFR technology development activities: metal fuel performance; pyroprocess development; safety experiments and analyses; core design development; fuel cycle demonstration; and LMR technology R&D

Cognitive analysis of schizophrenia risk genes that function as epigenetic regulators of gene expression

Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription. Evidence now supports some shared genetic aetiology between schizophrenia and intellectual disability. GWAS have identified 108 chromosomal regions associated with schizophrenia risk that span 350 genes. This study identified genes mapping to those loci that have epigenetic functions, and tested the risk alleles defining those loci for association with cognitive deficits. We developed a list of 350 genes with epigenetic functions and cross‐referenced this with the GWAS loci. This identified eight candidate genes: BCL11B, CHD7, EP300, EPC2, GATAD2A, KDM3B, RERE, SATB2 . Using a dataset of Irish psychosis cases and controls (n = 1235), the schizophrenia risk SNPs at these loci were tested for effects on IQ, working memory, episodic memory, and attention. Strongest associations were for rs6984242 with both measures of IQ (P  = 0.001) and episodic memory (P  = 0.007). We link rs6984242 to CHD7 via a long range eQTL. These associations were not replicated in independent samples. Our study highlights that a number of genes mapping to risk loci for schizophrenia may function as epigenetic regulators of gene expression but further studies are required to establish a role for these genes in cognition

Rapidly measured indicators of recreational water quality and swimming-associated illness at marine beaches: a prospective cohort study

<p>Abstract</p> <p>Introduction</p> <p>In the United States and elsewhere, recreational water quality is monitored for fecal indicator bacteria to help prevent swimming-associated illnesses. Standard methods to measure these bacteria take at least 24 hours to obtain results. Molecular approaches such as quantitative polymerase chain reaction (qPCR) can estimate these bacteria faster, in under 3 hours. Previously, we demonstrated that measurements of the fecal indicator bacteria <it>Enterococcus </it>using qPCR were associated with gastrointestinal (GI) illness among swimmers at freshwater beaches. In this paper, we report on results from three marine beach sites.</p> <p>Methods</p> <p>We interviewed beach-goers and collected water samples at marine beaches affected by treated sewage discharges in Mississippi in 2005, and Rhode Island and Alabama in 2007. Ten to twelve days later, we obtained information about gastrointestinal, respiratory, eye, ear and skin symptoms by telephone. We tested water samples for fecal indicator organisms using qPCR and other methods.</p> <p>Results</p> <p>We enrolled 6,350 beach-goers. The occurrence of GI illness among swimmers was associated with a log₁₀-increase in exposure to qPCR-determined estimates of fecal indicator organisms in the genus <it>Enterococcus </it>(AOR = 2.6, 95% CI 1.3-5.1) and order <it>Bacteroidales </it>(AOR = 1.9, 95% CI 1.3-2.9). Estimates of organisms related to <it>Clostridium perfringens </it>and a subgroup of organisms in the genus <it>Bacteroides </it>were also determined by qPCR in 2007, as was F+ coliphage, but relationships between these indicators and illness were not statistically significant.</p> <p>Conclusions</p> <p>This study provides the first evidence of a relationship between gastrointestinal illness and estimates of fecal indicator organisms determined by qPCR at marine beaches.</p

On the track for an efficient detection of Escherichia coli in water : A review on PCR-based methods

Ensuring water safety is an ongoing challenge to public health providers. Assessing the presence of fecal contamination indicators in water is essential to protect public health from diseases caused by waterborne pathogens. For this purpose, the bacteria Escherichia coli has been used as the most reliable indicator of fecal contamination in water. The methods currently in use for monitoring the microbiological safety of water are based on culturing the microorganisms. However, these methods are not the desirable solution to prevent outbreaks as they provide the results with a considerable delay, lacking on specificity and sensitivity. Moreover, viable but non-culturable microorganisms, which may be present as a result of environmental stress or water treatment processes, are not detected by culture-based methods and, thus, may result in false-negative assessments of E. coli in water samples. These limitations may place public health at significant risk, leading to substantial monetary losses in health care and, additionally, in costs related with a reduced productivity in the area affected by the outbreak, and in costs supported by the water quality control departments involved. Molecular methods, particularly polymerase chain reaction-based methods, have been studied as an alternative technology to overcome the current limitations, as they offer the possibility to reduce the assay time, to improve the detection sensitivity and specificity, and to identify multiple targets and pathogens, including new or emerging strains. The variety of techniques and applications available for PCR-based methods has increased considerably and the costs involved have been substantially reduced, which together have contributed to the potential standardization of these techniques. However, they still require further refinement in order to be standardized and applied to the variety of environmental waters and their specific characteristics. The PCR-based methods under development for monitoring the presence of E. coli in water are here discussed. Special emphasis is given to methodologies that avoid pre-enrichment during the water sample preparation process so that the assay time is reduced and the required legislated sensitivity is achieved. The advantages and limitations of these methods are also reviewed, contributing to a more comprehensive overview toward a more conscious research in identifying E. coli in water.Diana Mendes (SFRH/BDE/33752/2009) was recipient of a fellowship from the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and Frilabo, Lda. The authors thank Tatiana Aguiar (Centre of Biological Engineering) for English proofreading, the financial support from the Project "Desenvolvimento de um kit de detecao e quantificacao de E. coli e bacterias coliformes em aguas", Ref. 2009/5787, Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER, the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "Biolnd-Biotechnology and Bioengineering for improved Industrial and processes", REF. NORTE-07-0124-FEDER-000028 Co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER

A randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology

The numerous species that make up the oral microbiome are now understood to play a key role in establishment and maintenance of oral health. The ability to taxonomically identify community members at the species level is important to elucidating its diversity and association to health and disease. We report the overall ecological effects of using a toothpaste containing enzymes and proteins compared to a control toothpaste on the plaque microbiome. The results reported here demonstrate that a toothpaste containing enzymes and proteins can augment natural salivary defences to promote an overall community shift resulting in an increase in bacteria associated with gum health and a concomitant decrease in those associated with periodontal disease. Statistical analysis shows significant increases in 12 taxa associated with gum health including Neisseria spp. and a significant decrease in 10 taxa associated with periodontal disease including Treponema spp. The results demonstrate that a toothpaste containing enzymes and proteins can significantly shift the ecology of the oral microbiome (at species level) resulting in a community with a stronger association to health

Considerations for management strategy evaluation for small pelagic fishes

Management strategy evaluation (MSE) is the state-of-the-art approach for testing and comparing management strategies in a way that accounts for multiple sources of uncertainty (e.g. monitoring, estimation, and implementation). Management strategy evaluation can help identify management strategies that are robust to uncertainty about the life history of the target species and its relationship to other species in the food web. Small pelagic fish (e.g. anchovy, herring and sardine) fulfil an important ecological role in marine food webs and present challenges to the use of MSE and other simulation-based evaluation approaches. This is due to considerable stochastic variation in their ecology and life history, which leads to substantial observation and process uncertainty. Here, we summarize the current state of MSE for small pelagic fishes worldwide. We leverage expert input from ecologists and modellers to draw attention to sources of process and observation uncertainty for small pelagic species, providing examples from geographical regions where these species are ecologically, economically and culturally important. Temporal variation in recruitment and other life-history rates, spatial structure and movement, and species interactions are key considerations for small pelagic fishes. We discuss tools for building these into the MSE process, with examples from existing fisheries. We argue that model complexity should be informed by management priorities and whether ecosystem information will be used to generate dynamics or to inform reference points. We recommend that our list of considerations be used in the initial phases of the MSE process for small pelagic fishes or to build complexity on existing single-species models.publishedVersio

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe