Age-Related Differences in Susceptibility to Carcinogenesis: A Quantitative Analysis of Empirical Animal Bioassay Data

In revising cancer risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) analyzed animal cancer bioassay data over different periods of life. In this article, we report an improved analysis of these data (supplemented with some chemical carcinogenesis observations not included in the U.S. EPA’s original analysis) and animal bioassay studies of ionizing radiation. We use likelihood methods to avoid excluding cases where no tumors were observed in specific groups. We express dosage for animals of different weights on a metabolically consistent basis (concentration in air or food, or per unit body weight to the three-quarters power). Finally, we use a system of dummy variables to represent exposures during fetal, preweaning, and weaning–60-day postnatal periods, yielding separate estimates of relative sensitivity per day of dosing in these intervals. Central estimate results indicate a 5- to 60-fold increased carcinogenic sensitivity in the birth–weaning period per dose ÷ (body weight(0.75)-day) for mutagenic carcinogens and a somewhat smaller increase—centered about 5-fold—for radiation carcinogenesis per gray. Effects were greater in males than in females. We found a similar increased sensitivity in the fetal period for direct-acting nitrosoureas, but no such increased fetal sensitivity was detected for carcinogens requiring metabolic activation. For the birth–weaning period, we found an increased sensitivity for direct administration to the pups similar to that found for indirect exposure via lactation. Radiation experiments indicated that carcinogenic sensitivity is not constant through the “adult” period, but the dosage delivered in 12- to 21-month-old animals appears a few-fold less effective than the comparable dosage delivered in young adults (90–105 days of age)

An evidence base to optimise methods for involving patient and public contributors in clinical trials: a mixed-methods study

BACKGROUND: In comparison with other study designs, randomised trials are regarded as particularly likely to benefit from patient and public involvement (PPI). Using mixed-methods research we investigated PPI from the perspectives of researchers and PPI contributors. METHODS: Randomised trials in receipt of funding from the Health Technology Assessment (HTA) programme between 2006 and 2010 were identified. Funding applications and board and referee comments were obtained and data relevant to PPI extracted. Chief investigators (CIs), PPI contributors and UK Clinical Research Collaboration Registered Clinical Trials Units (RCTUs) were surveyed. Interviews were conducted with researchers and PPI contributors. RESULTS: A total of 111 trials were included. Text relevant to PPI was identified in half of the trials for which the first-stage applications were available, but only one-quarter described PPI within their development. In the second stage of the application, the majority provided some text relevant to PPI, with over half having PPI in their development. Fewer than half of referees commented on PPI, and funding boards rarely provided comments in relation to PPI. Seventy-three per cent (81 of 111) of CIs responded to the survey and 98% (79 of 81) included PPI at some stage in their trial. CIs considered high impact from PPI contributors to occur more frequently in trial setup, with low or no impact being more common during trial conduct, analysis and dissemination. Only one-third of CIs provided PPI contributor contact details but all contributors contacted completed the survey. The majority of contributors felt engaged and valued by the research team. Interviews were conducted with researchers and/or PPI contributors for 28 trials identifying two main influences on perception of PPI impact: whether or not CIs expressed personal goals and plans for PPI; and the quality of their relationship with the PPI contributors. The importance of early engagement was identified, with opportunity for input thereafter limited. Three PPI roles were identified: oversight, managerial and responsive. Oversight roles, as required by funders, were associated with low impact in comparison with responsive or managerial roles. Most researchers could see some value in PPI training for researchers, although those that had received such training themselves expressed concerns about its purpose and evidence base. Training for PPI contributors was considered unnecessary, with conversational approaches preferred, although this did not appear to provide an opportunity for role negotiation. The RCTU survey response rate was 85% (39 of 46). The majority (37 of 39) reported PPI within trials co-ordinated by their unit. Trial characteristics were used by half to determine the approach to PPI. Two-thirds reported recent developments or changes in implementing plans for PPI (21 of 33). Support to PPI contributors was commonly offered through members of staff at the unit. CONCLUSIONS: PPI is occurring in the majority of trials funded by the HTA programme, but uncertainty remains about how it is assessed and valued. Early involvement, building a relationship between researchers and contributors, responsive or managerial roles, and having defined goals for PPI were associated with impact. Efficiency could be gained by utilising the RCTU network to identify and tackle challenges, and develop a risk-based approach utilising trial characteristics. Recommendations are made to trial funders and the research community. Given the difficulties for some informants in recalling PPI contributions, future research using a prospective approach would be valuable. Ethnographic research that combines observation and multi-informant interviews is likely to be informative in identifying impact. The research community needs to give further consideration to processes for selecting PPI contributors and models of implementing PPI

Long-term outcomes of early childhood science education: insight from a cross-national comparative case study on conceptual understanding of science

The purpose of this research was to explore the long term outcomes of either participating or not participating in early childhood science education on Grade 6 students’ conceptual understanding of science. The research is situated in a conceptual framework that evokes Piagetian developmental levels as both potential curriculum constraints and potential models of efficacy. The research design was a multiple case study of Grade 6 children from three schools in China (n=140) who started formal science education in the third grade, and Grade 6 children from three matched schools in Australia (n=105) who started learning science in kindergarten. The students’ understanding was assessed by a science quiz and in-depth interview. The data showed that participating children from the high socio-economic schools in China and Australia had similar understandings of science. Divergence between the medium and low socio-economic schools, however, indicated that the grounding in early childhood science education in Australia may have placed these children at an advantage. Alternative explanations for the divergence including the nature of classroom instruction in the two countries are discussed

Impact of Production Variability on Balanced Mix Designs in Virginia

116425The objective of this study was to evaluate the influence of production variability on performance test results to determine if mixtures balanced during design could become unbalanced during production. Fourteen currently accepted mixture designs, 10 BMD mixtures and 4 Superpave mixtures (to serve as a comparison between current standards and BMD designs), were recreated in the laboratory. Additionally, the mixes were adjusted to produce coarse and fine gradations and high and low binder contents according to currently accepted tolerance limits to simulate production variability. Two interaction mixtures assessing changes in gradation and binder content were evaluated as well as two critically aged mixtures

Nanotechnology, governance, and public deliberation: What role for the Social Sciences?

In this article we argue that nanotechnology represents an extraordinary opportunity to build in a robust role for the social sciences in a technology that remains at an early, and hence undetermined, stage of development. We examine policy dynamics in both the United States and United Kingdom aimed at both opening up, and closing down, the role of the social sciences in nanotechnologies. We then set out a prospective agenda for the social sciences and its potential in the future shaping of nanotechnology research and innovation processes. The emergent, undetermined nature of nanotechnologies calls for an open, experimental, and interdisciplinary model of social science research

Exposure Assessment Approaches for Engineered Nanomaterials

Products based on nanotechnology are rapidly emerging in the marketplace, sometimes with little notice to consumers of their nanotechnology pedigree. This wide variety of nanotechnology products will result (in some cases) in unintentional human exposure to purposely engineered nanoscale materials via the dermal, inhalation, ingestion, and ocular pathways. Occupational, consumer, and environmental exposure to the nanomaterials should be characterized during the entire product lifecycle—manufacture, use, and disposal. Monitoring the fate and transport of engineered nanomaterials is complicated by the lack of detection techniques and the lack of a defined set of standardized metrics to be consistently measured. New exposure metrics may be required for engineered nanomaterials, but progress is possible by building on existing tools. An exposure metric matrix could organize existing data by relating likely exposure pathways (dermal, inhalation, ocular, ingestion) with existing measurements of important characteristics of nanoscale materials (particle number, mass, size distribution, charge). Nanomaterial characteristics not commonly measured, but shown to initiate a biological response during toxicity testing, signal a need for further research, such as the pressing need to develop monitoring devices capable of measuring those aspects of engineered nanomaterials that result in biological responses in humans. Modeling the behavior of nanoparticles may require new types of exposure models that individually track particles through the environment while keeping track of the particle shape, surface area, and other surface characteristics as the nanoparticles are transformed or become reactive. Lifecycle analysis could also be used to develop conceptual models of exposure from engineered nanomaterials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79200/1/j.1539-6924.2010.01446.x.pd

Identifying a Typology of High Schools Based on Their Orientation Toward STEM: A Latent Class Analysis of HSLS:09

The purpose of this study is to investigate the extent that there is a typology of high schools based on their orientation toward STEM, as well as the extent to which school-level demographic variables and student high school outcomes are associated with subgroup membership in the typology, by analyzing data from a large nationally representative sample of high schools (n=940) from the High School Longitudinal Study of 2009 (HSLS:09) using latent class analysis (LCA). We used a three-step LCA approach to identify significantly different subgroups of STEM-oriented high schools, what covariates predict subgroup membership, and how subgroup membership predicts observed distal outcomes. We find that there are four significantly different subgroups of STEM-oriented high schools based on their principal’s perceptions: Abundant (12.3%), Support (23.3%), Bounded (10.1%), and Comprehensive (54.3%). In addition, we find that these subgroups are associated with school demographics, such as the percent of students eligible for free and reduced-price lunch, school locale, and control (public or private). Subgroup membership is also associated with student outcomes, such as postsecondary program enrollment and intent to pursue a STEM degree. Keywords: STEM Education, High Schools, Multivariate Analysi

Life cycle assessment of the Seagen marine current turbine

The world's first commercial‐scale grid‐connected tidal current energy installation will feature the Seagen marine current turbine developed by Marine Current Turbines Ltd. With potential for the manufacture of significant numbers of such devices there is a need to assess their environmental impact and, in particular, their life cycle energy and carbon dioxide (CO2) performance. This paper presents an analysis of the life cycle energy use and CO2 emissions associated with the first generation of Seagen turbines. The detailed assessment covers the embodied energy and CO2 in the materials and manufacturing of components, device installation, and operation along with those for decommissioning. With relatively conservative assumptions, and despite the early stage of development, the study shows that at 214 kJ/kWh and 15 g CO2/kWh, the respective energy and carbon intensities are comparable with large wind turbines and very low relative to the 400 to 1000 g CO2/kWh typical of fossil‐fuelled generation. The energy payback period is approximately 14 months and the CO2 payback is around 8 months. The embodied energy and carbon show limited sensitivity to assumptions with environmental performance remains excellent even under the most adverse scenarios considered. Materials use is identified as the primary contributors to embodied energy and carbon with shipping also significant. Improvements in the environmental impact of the Seagen can be achieved primarily by increased structural efficiency and the use of alternative installation methods to increase recovery of steel at decommissioning

Creating an Instrument to Measure Student Response to Instructional Practices

BackgroundCalls for the reform of education in science, technology, engineering, and mathematics (STEM) have inspired many instructional innovations, some research based. Yet adoption of such instruction has been slow. Research has suggested that students’ response may significantly affect an instructor’s willingness to adopt different types of instruction.PurposeWe created the Student Response to Instructional Practices (StRIP) instrument to measure the effects of several variables on student response to instructional practices. We discuss the step‐by‐step process for creating this instrument.Design/MethodThe development process had six steps: item generation and construct development, validity testing, implementation, exploratory factor analysis, confirmatory factor analysis, and instrument modification and replication. We discuss pilot testing of the initial instrument, construct development, and validation using exploratory and confirmatory factor analyses.ResultsThis process produced 47 items measuring three parts of our framework. Types of instruction separated into four factors (interactive, constructive, active, and passive); strategies for using in‐class activities into two factors (explanation and facilitation); and student responses to instruction into five factors (value, positivity, participation, distraction, and evaluation).ConclusionsWe describe the design process and final results for our instrument, a useful tool for understanding the relationship between type of instruction and students’ response.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136692/1/jee20162_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136692/2/jee20162.pd