Enhanced safeguards via solution monitoring

Solution monitoring is defined as the essentially continuous monitoring of solution level, density, and temperature in all tanks in the process that contain, or could contain, safeguards-significant quantities of nuclear material. This report describes some of the enhancements that solution monitoring could make to international safeguards. The focus is on the quantifiable benefits of solution monitoring, but qualitatively, solution monitoring can be viewed as a form of surveillance. Quantitatively, solution monitoring can in some cases improve diversion detection probability. For example, the authors show that under certain assumptions, solution monitoring can be used to reduce the standard deviation of the annual material balance, {sigma}{sub MB}, from approximately 17 kg to approximately 4 kg. Such reduction in {sigma}{sub MB} will not always be possible, as they discuss. However, in all cases, solution monitoring would provide assurance that the measurement error models are adequate so that one has confidence in his estimate of {sigma}{sub MB}. Some of the results in this report were generated using data that were simulated with prototype solution monitoring software that they are developing. An accompanying document describes that software

Development and evaluation of methods for safeguards use of solution monitoring data

This report describes the effort to develop, implement, and evaluate data analysis methods for solution-monitoring measurements in the plutonium nitrate storage at the Tokai Reprocessing Plant (TRP). The intent is to address TRP-specific issues to some extent, as well as to anticipate the data analysis needs at future reprocessing plants (especially the new Rokkasho reprocessing plant (RRP)) in Japan. The essential difference between a plant like TRP and a more modern plant like RRP is that one expects more and better instrumentation in the tanks in a modern plant. Because the TRP solution monitoring hardware is scheduled to be upgraded, the authors de-emphasized the effort to handle information-poor plants like TRP. This report mostly describes the analysis methods and software for finding and identifying all key tank events. To a large extent they have to experiment with several candidate methods for implementing their analysis objectives. Therefore, they chose to use a prototyping software system called S-PLUS, which is an object-oriented statistical programming and graphics package. The intent is to eventually implement selected portions of their current solution-monitoring toolkit in a more robust and user-friendly system. The authors describe their current software system as being far more than they needed for their own in-house use (menus are provided for the user who doesn`t want to type any S-PLUS commands), but less than is needed for a fieldable system. Mostly as a result of working on this project, they have come to conclude that solution monitoring is a potentially very valuable asset to nuclear safeguards at a modern reprocessing plant

Implementation strategies to promote community-engaged efforts to counter tobacco marketing at the point of sale

The US tobacco industry spends $8.2 billion annually on marketing at the point of sale (POS), a practice known to increase tobacco use. Evidence-based policy interventions (EBPIs) are available to reduce exposure to POS marketing, and nationwide, states are funding community-based tobacco control partnerships to promote local enactment of these EBPIs. Little is known, however, about what implementation strategies best support community partnerships' success enacting EBPI. Guided by Kingdon's theory of policy change, Counter Tools provides tools, training, and other implementation strategies to support community partnerships' performance of five core policy change processes: document local problem, formulate policy solutions, engage partners, raise awareness of problems and solutions, and persuade decision makers to enact new policy. We assessed Counter Tools' impact at 1 year on (1) partnership coordinators' self-efficacy, (2) partnerships' performance of core policy change processes, (3) community progress toward EBPI enactment, and (4) salient contextual factors. Counter Tools provided implementation strategies to 30 partnerships. Data on self-efficacy were collected using a pre-post survey. Structured interviews assessed performance of core policy change processes. Data also were collected on progress toward EBPI enactment and contextual factors. Analysis included descriptive and bivariate statistics and content analysis. Following 1-year exposure to implementation strategies, coordinators' self-efficacy increased significantly. Partnerships completed the greatest proportion of activities within the “engage partners” and “document local problem” core processes. Communities made only limited progress toward policy enactment. Findings can inform delivery of implementation strategies and tests of their effects on community-level efforts to enact EBPIs

Authentication of reprocessing plant safeguards data through correlation analysis

This report investigates the feasibility and benefits of two new approaches to the analysis of safeguards data from reprocessing plants. Both approaches involve some level of plant modeling. All models involve some form of mass balance, either applied in the usual way that leads to material balances for individual process vessels at discrete times or applied by accounting for pipe flow rates that leads to material balances for individual process vessels at continuous times. In the first case, material balances are computed after each tank-to-tank transfer. In the second case, material balances can be computed at any desired time. The two approaches can be described as follows. The first approach considers the application of a new multivariate sequential test. The test statistic is a scalar, but the monitored residual is a vector. The second approach considers the application of recent nonlinear time series methods for the purpose of empirically building a model for the expected magnitude of a material balance or other scalar variable. Although the report restricts attention to monitoring scalar time series, the methodology can be extended to vector time series

Combined cognitive and vocational interventions after mild to moderate traumatic brain injury: study protocol for a randomized controlled trial

Background A considerable proportion of patients with mild to moderate traumatic brain injury (TBI) experience long-lasting somatic, cognitive, and emotional symptoms that may hamper their capacity to return to work (RTW). Although several studies have described medical, psychological, and work-related factors that predict RTW after TBI, well-controlled intervention studies regarding RTW are scarce. Furthermore, there has traditionally been weak collaboration among health-related rehabilitation services, the labor and welfare sector, and workplaces. Methods/design This study protocol describes an innovative randomized controlled trial in which we will explore the effect of combining manualized cognitive rehabilitation (Compensatory Cognitive Training [CCT]) and supported employment (SE) on RTW and related outcomes for patients with mild to moderate TBI in real-life competitive work settings. The study will be carried out in the southeastern region of Norway and thereby be performed within the Norwegian welfare system. Patients aged 18–60 years with mild to moderate TBI who are employed in a minimum 50% position at the time of injury and sick-listed 50% or more for postconcussive symptoms 2 months postinjury will be included in the study. A comprehensive assessment of neurocognitive function, self-reported symptoms, emotional distress, coping style, and quality of life will be performed at baseline, immediately after CCT (3 months after inclusion), following the end of SE (6 months after inclusion), and 12 months following study inclusion. The primary outcome measures are the proportion of participants who have returned to work at 12-month follow-up and length of time until RTW, in addition to work stability as well as work productivity over the first year following the intervention. Secondary outcomes include changes in self-reported symptoms, emotional and cognitive function, and quality of life. Additionally, a qualitative RTW process evaluation focused on organizational challenges at the workplace will be performed. Discussion The proposed study will combine cognitive and vocational rehabilitation and explore the efficacy of increased cross-sectoral collaboration between specialized health care services and the labor and welfare system. If the intervention proves effective, the project will describe the cost-effectiveness and utility of the program and thereby provide important information for policy makers. In addition, knowledge about the RTW process for persons with TBI and their workplaces will be provided. Trial registration ClinicalTrials.gov, NCT03092713. Registered on 10 March 2017

Development of a PROTAC-Based Targeting Strategy Provides a Mechanistically Unique Mode of Anti-Cytomegalovirus Activity

Human cytomegalovirus (HCMV) is a major pathogenic herpesvirus that is prevalent worldwide and it is associated with a variety of clinical symptoms. Current antiviral therapy options do not fully satisfy the medical needs; thus, improved drug classes and drug-targeting strategies are required. In particular, host-directed antivirals, including pharmaceutical kinase inhibitors, might help improve the drug qualities. Here, we focused on utilizing PROteolysis TArgeting Chimeras (PROTACs), i.e., hetero-bifunctional molecules containing two elements, namely a target-binding molecule and a proteolysis-inducing element. Specifically, a PROTAC that was based on a cyclin-dependent kinase (CDK) inhibitor, i.e., CDK9-directed PROTAC THAL-SNS032, was analyzed and proved to possess strong anti-HCMV AD169-GFP activity, with values of EC50 of 0.030 µM and CC50 of 0.175 µM (SI of 5.8). Comparing the effect of THAL-SNS032 with its non-PROTAC counterpart SNS032, data indicated a 3.7-fold stronger anti-HCMV efficacy. This antiviral activity, as illustrated for further clinically relevant strains of human and murine CMVs, coincided with the mid-nanomolar concentration range necessary for a drug-induced degradation of the primary (CDK9) and secondary targets (CDK1, CDK2, CDK7). In addition, further antiviral activities were demonstrated, such as the inhibition of SARS-CoV-2 replication, whereas other investigated human viruses (i.e., varicella zoster virus, adenovirus type 2, and Zika virus) were found insensitive. Combined, the antiviral quality of this approach is seen in its (i) mechanistic uniqueness; (ii) future options of combinatorial drug treatment; (iii) potential broad-spectrum activity; and (iv) applicability in clinically relevant antiviral models. These novel data are discussed in light of the current achievements of anti-HCMV drug development

Short Lag Times for Invasive Tropical Plants: Evidence from Experimental Plantings in Hawai'i

Background: The lag time of an invasion is the delay between arrival of an introduced species and its successful spread in a new area. To date, most estimates of lag times for plants have been indirect or anecdotal, and these estimates suggest that plant invasions are often characterized by lag times of 50 years or more. No general estimates are available of lag times for tropical plant invasions. Historical plantings and documentation were used to directly estimate lag times for tropical plant invasions in Hawai’i. Methodology/Principal Findings: Historical planting records for the Lyon Arboretum dating back to 1920 were examined to identify plants that have since become invasive pests in the Hawaiian Islands. Annual reports describing escape from plantings were then used to determine the lag times between initial plantings and earliest recorded spread of the successful invaders. Among 23 species that eventually became invasive pests, the average lag time between introduction and first evidence of spread was 14 years for woody plants and 5 years for herbaceous plants. Conclusions/Significance: These direct estimates of lag times are as much as an order of magnitude shorter than previous, indirect estimates, which were mainly based on temperate plants. Tropical invaders may have much shorter lag times than temperate species. A lack of direct and deliberate observations may have also inflated many previous lag time estimates. Although there have been documented cases of long lag times due to delayed arrival of a mutualist or environmenta

Changes in habitat associations during range expansion: disentangling the effects of climate and residence time

The distributions of many species are not at equilibrium with their environment. This includes spreading non-native species and species undergoing range shifts in response to climate change. The habitat associations of these species may change during range expansion as less favourable climatic conditions at expanding range margins may constrain species to use only the most favourable habitats, violating the species distribution model assumption of stationarity. Alternatively, changes in habitat associations could result from density-dependent habitat selection; at range margins, population densities are initially low so species can exhibit density-independent selection of the most favourable habitats, while in the range core, where population densities are higher, species spread into less favourable habitat. We investigate if the habitat preferences of the non-native common waxbill Estrilda astrild changed as they spread in three directions (north, east and south-east) in the Iberian Peninsula. There are different degrees of climatic suitability and colonization speed across range expansion axes, allowing us to separate the effects of climate from residence time. In contrast to previous studies we find a stronger effect of residence time than climate in influencing the prevalence of common waxbills. As well as a strong additive effect of residence time, there were some changes in habitat associations, which were consistent with density-dependent habitat selection. The combination of broader habitat associations and higher prevalence in areas that have been colonised for longer means that species distribution models constructed early in the invasion process are likely to underestimate species’ potential distribution

Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial

BACKGROUND: Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens. This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women. MATERIALS AND METHODS: This clinical trial of before-after type was carried out on 15 women 45–64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed. RESULTS: Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant. CONCLUSION: In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis