Evolution of universal review and disclosure of MRI reports to research participants.

BACKGROUND: Although incidental findings (IF) are commonly encountered in neuroimaging research, there is no consensus regarding what to do with them. Whether researchers are obligated to review scans for IF, or if such findings should be disclosed to research participants at all, is controversial. Objective data are required to inform reasonable research policy; unfortunately, such data are lacking in the published literature. This manuscript summarizes the development of a radiology review and disclosure system in place at a neuroimaging research institute and its impact on key stakeholders. METHODS: The evolution of a universal radiology review system is described, from inception to its current status. Financial information is reviewed, and stakeholder impact is characterized through surveys and interviews. RESULTS: Consistent with prior reports, 34% of research participants had an incidental finding identified, of which 2.5% required urgent medical attention. A total of 87% of research participants wanted their magnetic resonance imaging (MRI) results regardless of clinical significance and 91% considered getting an MRI report a benefit of study participation. A total of 63% of participants who were encouraged to see a doctor about their incidental finding actually followed up with a physician. Reasons provided for not following-up included already knowing the finding existed (14%), not being able to afford seeing a physician (29%), or being reassured after speaking with the institute's Medical Director (43%). Of those participants who followed the recommendation to see a physician, nine (38%) required further diagnostic testing. No participants, including those who pursued further testing, regretted receiving their MRI report, although two participants expressed concern about the excessive personal cost. The current cost of the radiology review system is about $23 per scan. CONCLUSIONS: It is possible to provide universal radiology review of research scans through a system that is cost-effective, minimizes investigator burden, and does not overwhelm local healthcare resources.

Reasoning about knowledge: Children's evaluations of generality and verifiability.

In a series of experiments, we examined 3- to 8-year-old children's (N=223) and adults' (N=32) use of two properties of testimony to estimate a speaker's knowledge: generality and verifiability. Participants were presented with a "Generic speaker" who made a series of 4 general claims about "pangolins" (a novel animal kind), and a "Specific speaker" who made a series of 4 specific claims about "this pangolin" as an individual. To investigate the role of verifiability, we systematically varied whether the claim referred to a perceptually-obvious feature visible in a picture (e.g., "has a pointy nose") or a non-evident feature that was not visible (e.g., "sleeps in a hollow tree"). Three main findings emerged: (1) young children showed a pronounced reliance on verifiability that decreased with age. Three-year-old children were especially prone to credit knowledge to speakers who made verifiable claims, whereas 7- to 8-year-olds and adults credited knowledge to generic speakers regardless of whether the claims were verifiable; (2) children's attributions of knowledge to generic speakers was not detectable until age 5, and only when those claims were also verifiable; (3) children often generalized speakers' knowledge outside of the pangolin domain, indicating a belief that a person's knowledge about pangolins likely extends to new facts. Findings indicate that young children may be inclined to doubt speakers who make claims they cannot verify themselves, as well as a developmentally increasing appreciation for speakers who make general claims.

Arum Palaestinum with isovanillin, linolenic acid and ß-sitosterol inhibits prostate cancer spheroids and reduces the growth rate of prostate tumors in mice.

BACKGROUND: Arum palaestinum is a plant commonly found in the Middle East that is ingested as an herbal remedy to fight cancer. However, no studies have examined the direct effect of the plant/plant extract on tumor growth in an animal model. METHODS: Verified prostate cancer cells were plated as 3D spheroids to determine the effect of extract from boiled Arum Palaestinum Boiss roots. In addition, male NU/NU mice (8 weeks old) with xenograft tumors derived from the prostate cancer cell line were treated daily with 1000 mg/kg body weight gavage of the suspension GZ17. The tumor growth was measured repeatedly with calipers and the excised tumors were weighed at the termination of the 3 week study. Control mice (10 mice in each group) received vehicle in the same manner and volume. RESULTS: The number of live prostate cancer cells declined in a dose/dependent manner with a 24 h exposure to the extract at doses of 0.015 to 6.25 mg/mL. A fortified version of the extract (referred to as GZ17) that contained higher levels of isovanillin, linolenic acid and ß-sitosterol had a stronger effect on the cell death rate, shifting the percentage of dead cells from 30 % to 55 % at the highest dose while the vehicle control had no effect on cell numbers. When GZ17 was applied to non-cancer tissue, in this case, human islets, there was no cell death at doses that were toxic to treated cancer cells. Preliminary toxicity studies were conducted on rats using an up-down design, with no signs of toxic effect at the highest dose. NU/NU mice with xenograft prostate tumors treated with GZ17 had a dramatic inhibition of tumor progression, while tumors in the control group grew steadily through the 3 weeks. The rate of tumor volume increase was 73 mm(3)/day for the vehicle group and 24 mm(3)/day for the GZ17 treated mice. While there was a trend towards lower excised tumor weight at study termination in the GZ17 treatment group, there was no statistical difference. CONCLUSIONS: Fortified Arum palaestinum Boiss caused a reduction in live cells within prostate cancer spheroids and blocked tumor growth in xenografted prostate tumors in mice without signs of toxicity.

'Ethical responsibility' or 'a whole can of worms': differences in opinion on incidental finding review and disclosure in neuroimaging research from focus group discussions with participants, parents, IRB members, investigators, physicians and community members.

PURPOSE: To identify the specific needs, preferences and expectations of the stakeholders impacted by returning neuroimaging incidental findings to research participants. METHODS: Six key stakeholder groups were identified to participate in focus group discussions at our active neuroimaging research facility: Participants, Parents of child participants, Investigators, Institutional Review Board (IRB) Members, Physicians and Community Members. A total of 151 subjects attended these discussions. Transcripts were analysed using principles of Grounded Theory and group consensus coding. RESULTS: A series of similar and divergent themes were identified across our subject groups. Similarities included beliefs that it is ethical for researchers to disclose incidental findings as it grants certain health and emotional benefits to participants. All stakeholders also recognised the potential psychological and financial risks to disclosure. Divergent perspectives elucidated consistent differences between our 'Participant' subjects (Participants, Parents, Community Members) and our 'Professional' subjects (IRB Members, Investigators and Physicians). Key differences included (1) what results should be reported, (2) participants' autonomous right to research information and (3) the perception of the risk-benefit ratio in managing results. CONCLUSIONS: Understanding the perceived impact on all stakeholders involved in the process of disclosing incidental findings is necessary to determine appropriate research management policy. Our data further demonstrate the challenge of this task as different stakeholders evaluate the balance between risk and benefit related to their unique positions in this process. These findings offer some of the first qualitative insight into the expectations of the diverse stakeholders affected by incidental finding disclosure.

Stakeholder Opinions And Ethical Perspectives Support Complete Disclosure Of Incidental Findings In MRI Research.

How far does a researcher's responsibility extend when an incidental finding is identified? Balancing pertinent ethical principles such as beneficence, respect for persons, and duty to rescue is not always straightforward, particularly in neuroimaging research where empirical data that might help guide decision-making is lacking. We conducted a systematic survey of perceptions and preferences of 396 investigators, research participants and IRB members at our institution. Using the partial entrustment model as described by Richardson, we argue that our data supports universal reading by a neuroradiologist of all research MRI scans for incidental findings and providing full disclosure to all participants.

Can't stop believing: inhibitory control and resistance to misleading testimony.

Why are some young children consistently willing to believe what they are told even when it conflicts with first-hand experience? In this study, we investigated the possibility that this deference reflects an inability to inhibit a prepotent response. Over the course of several trials, 2.5- to 3.5-year-olds (N = 58) heard an adult contradict their report of a simple event they had both witnessed, and children were asked to resolve this discrepancy. Those who repeatedly deferred to the adult's misleading testimony had more difficulty on an inhibitory control task involving spatial conflict than those who responded more skeptically. These results suggest that responding skeptically to testimony that conflicts with first-hand experience may be challenging for some young children because it requires inhibiting a normally appropriate bias to believe testimony.

Young children have a specific, highly robust bias to trust testimony.

Why are young children so willing to believe what they are told? In two studies, we investigated whether it is because of a general, undifferentiated trust in other people or a more specific bias to trust testimony. In Study 1, 3-year-olds either heard an experimenter claim that a sticker was in one location when it was actually in another or saw her place an arrow on the empty location. All children searched in the wrong location initially, but those who heard the deceptive testimony continued to be misled, whereas those who saw her mark the incorrect location with an arrow quickly learned to search in the opposite location. In Study 2, children who could both see and hear a deceptive speaker were more likely to be misled than those who could only hear her. Three-year-olds have a specific, highly robust bias to trust what people--particularly visible speakers--say.