Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes.

Pediatric diencephalic tumors represent a histopathologically and molecularly diverse group of neoplasms arising in the central part of the brain and involving eloquent structures, including the hypothalamic-pituitary axis (HPA), optic pathway, thalamus, and pineal gland. Presenting symptoms can include significant neurological, endocrine, or visual manifestations which may be exacerbated by injudicious intervention. Upfront multidisciplinary assessment and coordinated management is crucial from the outset to ensure best short- and long-term functional outcomes. In this review we discuss the clinical and pathological features of the neoplastic entities arising in this location, and their management. We emphasize a clear move towards 'function preserving' diagnostic and therapeutic approaches with novel toxicity-sparing strategies, including targeted therapies.

Evidence of Chemoresponsiveness in Unresectable Metastatic Angiomatoid Fibrous Histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue neoplasm of intermediate biological potential. Typically a slow-growing tumor, it can recur locally. Rarely, it manifests as a soft tissue sarcoma capable of metastasis. When metastases are nonamenable to local therapy, it is believed uniformly fatal. We present 3 patients with metastatic AFH who demonstrated a sustained response to chemotherapy; including one who achieved complete remission with cryoablation. These cases reinforce the potential value of chemotherapy in some patients with unresectable metastatic AFH and provide the first case in the literature of cryoablation in AFH.

Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma.

Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for ACVR1-mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 (K d = 150 nmol/L) and reduce DIPG cell viability in vitro but has limited ability to cross the blood-brain barrier. In addition to mTOR, everolimus inhibited ABCG2 (BCRP) and ABCB1 (P-gp) transporters and was synergistic in DIPG cells when combined with vandetanib in vitro. This combination was well tolerated in vivo and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Four patients with ACVR1-mutant DIPG were treated with vandetanib plus an mTOR inhibitor, informing the dosing and toxicity profile of this combination for future clinical studies. SIGNIFICANCE: Twenty-five percent of patients with the incurable brainstem tumor DIPG harbor somatic activating mutations in ACVR1, but there are no approved drugs targeting the receptor. Using artificial intelligence, we identify and validate, both experimentally and clinically, the novel combination of vandetanib and everolimus in these children based on both signaling and pharmacokinetic synergies.This article is highlighted in the In This Issue feature, p. 275.

Opposing ends of the spectrum: Exploring trust in scientific and religious authorities.

Given the ethical questions that surround emerging science, this study is interested in studying public trust in scientific and religious authorities for information about the risks and benefits of science. Using data from a nationally representative survey of American adults, we employ regression analysis to better understand the relationships between several variables-including values, knowledge, and media attention-and trust in religious organizations and scientific institutions. We found that Evangelical Christians are generally more trusting of religious authority figures to tell the truth about the risks and benefits of science and technology, and only slightly less likely than non-Evangelicals to trust scientific authorities for the same information. We also found that many Evangelicals use mediated information and science knowledge differently than non-Evangelicals, with both increased knowledge and attention to scientific media having positive impacts on trust in scientific authorities among the latter, but not the former group.

Scientists' Ethical Obligations and Social Responsibility for Nanotechnology Research.

Scientists' sense of social responsibility is particularly relevant for emerging technologies. Since a regulatory vacuum can sometimes occur in the early stages of these technologies, individual scientists' social responsibility might be one of the most significant checks on the risks and negative consequences of this scientific research. In this article, we analyze data from a 2011 mail survey of leading U.S. nanoscientists to explore their perceptions the regarding social and ethical responsibilities for their nanotechnology research. Our analyses show that leading U.S. nanoscientists express a moderate level of social responsibility about their research. Yet, they have a strong sense of ethical obligation to protect laboratory workers (in both universities and industry) from unhealthy exposure to nanomaterials. We also find that there are significant differences in scientists' sense of social and ethical responsibility depending on their demographic characteristics, job affiliation, attention to media content, risk perceptions and benefit perceptions. We conclude with some implications for future research.

Another (methodological) look at knowledge gaps and the Internet's potential for closing them.

Members of the World Economic Forum recently identified the economic, health and knowledge disparities between the "haves" and "have-nots" in the world as one of the central risks in the global risk landscape. However, research on the role of communication in reducing knowledge disparities for emerging technologies is rare. More importantly, little research has tracked knowledge gaps about emerging technologies in representative populations over time. In this study we examine U.S. public knowledge levels across different levels of education and media use using data from two nationally representative telephone surveys. Our results show that increased science Internet and television use among low education groups can help narrow, or significantly reduce the growth of knowledge gaps that are forming based on educational disparities.

Factors influencing public risk-benefit considerations of nanotechnology: Assessing the effects of mass media, interpersonal communication, and elaborative processing.

This study examines the influence of mass media, interpersonal communication, and elaborative processing on public perception of benefits and risks of nanotechnology, based on a large-scale nationally representative telephone survey of U.S. adult citizens. Results indicate that cognitive processes in the form of news elaboration had a significant positive main effect on benefits outweigh risks perception. The influences of attention to science in newspapers, attention to science news on television, and interpersonal communication about science on public perception of benefits outweigh risks were moderated by elaborative processing, after controlling for socio-demographic variables, religious beliefs, trust in scientists, and scientific knowledge. The findings highlight the importance of elaborative processing when it comes to understanding how the mass media differentially influence public benefits outweigh risks perception of emerging technologies. Specifically, high elaborative processing emphasizes higher levels of perceived benefits outweigh risks than low elaborative processing. This study explores explanations for this phenomenon and offers implications for future research and policy.

Measuring risk/benefit perceptions of emerging technologies and their potential impact on communication of public opinion toward science.

This study presents a systematic comparison of two alternative measures of citizens' perceptions of risks and benefits of emerging technologies. By focusing on two specific issues (nanotechnology and biofuels), we derive several insights for the measurement of public views of science. Most importantly, our analyses reveal that relying on global, single-item measures may lead to invalid inferences regarding external influences on public perceptions, particularly those related to cognitive schema and media use. Beyond these methodological implications, this analysis suggests several reasons why researchers in the area of public attitudes toward science must revisit notions of measurement in order to accurately inform the general public, policymakers, scientists, and journalists about trends in public opinion toward emerging technologies.

Federally sponsored multidisciplinary research centers: Learning, evaluation, and vicious circles.

Despite the increasing investment in multi-year federally funded science and technology centers in universities, there are few studies of how these centers engage in learning and change based on information submitted from various agents in the oversight and evaluation process. One challenge is how to manage and respond to this evaluative information, especially when it is conflicting. Although the center can learn and adapt in response to this information, it can also become subject to a vicious circle of continuous restructuring and production of documentation to address various and potentially inconsistent recommendations. In this paper we illustrate the effects of such a dynamic based on our experiences as external evaluators of the $25 million NSF-funded Learning in Informal and Formal Environments (LIFE) Center. The case study presents an analysis of annual reports and strategic planning documents along with other sources of evidence to illustrate the evolution of center organizational approaches in response to evaluations by external review panels, center evaluators, program managers, and other external stakeholders. We conclude with suggestions for how evaluators may help centers ease the cost of learning and reduce the likelihood of a vicious circle.

Making sense of policy choices: understanding the roles of value predispositions, mass media, and cognitive processing in public attitudes toward nanotechnology.

Using a nationally representative telephone survey of 1,015 adults in the United States, this study examines how value predispositions, communication variables, and perceptions of risks and benefits are associated with public support for federal funding of nanotechnology. Our findings show that highly religious individuals were less supportive of funding of nanotech than less religious individuals, whereas individuals who held a high deference for scientific authority were more supportive of funding of the emerging technology than those low in deference. Mass media use and elaborative processing of scientific news were positively associated with public support for funding, whereas factual scientific knowledge had no significant association with policy choices. The findings suggest that thinking about and reflecting upon scientific news promote better understanding of the scientific world and may provide a more sophisticated cognitive structure for the public to form opinions about nanotech than factual scientific knowledge. Finally, heuristic cues including trust in scientists and perceived risks and benefits of nanotech were found to be associated with public support for nanotech funding. We conclude with policy implications that will be useful for policymakers and science communication practitioners.

Religious beliefs and public attitudes toward nanotechnology in Europe and the United States.

How do citizens make sense of nanotechnology as more applications reach the market and the mainstream media start to debate the potential risks and benefits of technology? As with many other political and scientific issues, citizens rely on cognitive shortcuts or heuristics to make sense of issues for which they have low levels of knowledge. These heuristics can include predispositional factors, such as ideological beliefs or value systems, and also short-term frames of reference provided by the media or other sources of information. Recent research suggests that 'religious filters' are an important heuristic for scientific issues in general, and nanotechnology in particular. A religious filter is more than a simple correlation between religiosity and attitudes toward science: it refers to a link between benefit perceptions and attitudes that varies depending on respondents' levels of religiosity. In surveys, seeing the benefits of nanotechnology is consistently linked to more positive attitudes about nanotechnology among less religious respondents, with this effect being significantly weaker for more religious respondents. For this study, we have combined public opinion surveys in the United States with Eurobarometer surveys about public attitudes toward nanotechnology in Europe to compare the influence of religious beliefs on attitudes towards nanotechnology in the United States and Europe. Our results show that respondents in the United States were significantly less likely to agree that nanotechnology is morally acceptable than respondents in many European countries. These moral views correlated directly with aggregate levels of religiosity in each country, even after controlling for national research productivity and measures of science performance for high-school students.

Of risks and regulations: how leading U.S. nanoscientists form policy stances about nanotechnology.

Even though there is a high degree of scientific uncertainty about the risks of nanotechnology, many scholars have argued that policy-making cannot be placed on hold until risk assessments are complete (Faunce, Med J Aust 186(4):189-191, 2007; Kuzma, J Nanopart Res 9(1):165-182, 2007; O'Brien and Cummins, Hum Ecol Risk Assess 14(3):568-592, 2008; Powell et al., Environ Manag 42(3):426-443, 2008). In the absence of risk assessment data, decision makers often rely on scientists' input about risks and regulation to make policy decisions. The research we present here goes beyond the earlier descriptive studies about nanotechnology regulation to explore the heuristics that the leading U.S. nanoscientists use when they make policy decisions about regulating nanotechnology. In particular, we explore the relationship between nanoscientists' risk and benefit perceptions and their support for nanotech regulation. We conclude that nanoscientists are more supportive of regulating nanotechnology when they perceive higher levels of risks; yet, their perceived benefits about nanotechnology do not significantly impact their support for nanotech regulation. We also find some gender and disciplinary differences among the nanoscientists. Males are less supportive of nanotech regulation than their female peers and materials scientists are more supportive of nanotechnology regulation than scientists in other fields. Lastly, our findings illustrate that the leading U.S. nanoscientists see the areas of surveillance/privacy, human enhancement, medicine, and environment as the nanotech application areas that are most in need of new regulations.

A use-and-transformation model for evaluating public R&D: illustrations from polycystic ovarian syndrome (PCOS) research.

Evaluating federally funded research and development (R&D) presents unique challenges to both federal science agencies and evaluators. Often focusing only on outcome evaluative measures (such as productivity or economic value) can shortchange the true value of the federal investment. For example, program directors at the National Science Foundation (NSF) and National Institutes of Health (NIH) talk about the "value added" of the new interdisciplinary science centers that they have funded-and they hope to be able to capture how funding can generate increased capacity for new cutting-edge research in the future. The purpose of this paper is to present a use-and-transformation model for evaluating public R&D, which explicitly focuses on measuring capacity-based metrics for evaluation instead of outcome-based metrics. The theory for the model presented here explicitly uses the concept of a Knowledge Value Collective that was introduced by Bozeman and Rogers [Bozeman, B., & Rogers, J. D. (2002). A churn model of scientific knowledge value: Internet researchers as a knowledge value collective. Research Policy, 31(5), 769-794; Rogers, J. D., & Bozeman, B. (2001). "Knowledge value alliances": An alternative to the R&D project focus in evaluation. Science Technology & Human Values, 26(1), 23-55].

Inspection/maintenance program evaluation: replicating the Denver Step Method for an Atlanta fleet.

The research presented in this paper employs the Step Method of Inspection/Maintenance (I/M) program evaluation to estimate the emissions reduction for an Atlanta I/M program. Stedman et al. (Stedman, D. H.; Bishop, G. A.; Aldrete, P.; Slott, R. S. Environ. Sci. Technol. 1997, 31, 927-931) introduced the Step Method of evaluation when they presented the results of a 1995 Denver I/M program evaluation. The research presented here replicates the original Denver Step Method analysis for a 1997 Atlanta I/M program. This evaluation was conducted separately for the nine outlying Atlanta counties and the four counties that are closest to the center of the city. The results of the analysis are similar to those found by Stedman et al. in Denver. While the Denver carbon monoxide (CO) weighted program benefit was 6.9%, the Atlanta area CO weighted program benefit is found to be 11.5% and 4.9% for the nine-county and four-county Atlanta areas, respectively. We conclude that the 1997 I/M program change in Atlanta yielded a noteworthy and observable change in fleet emissions.