Bioethicists Today: Results of the Views in Bioethics Survey.

Bioethicists influence practices and policies in medicine, science, and public health. However, little is known about bioethicists' views. We recently surveyed 824 U.S. bioethicists on a wide range of ethical issues, including topics related to abortion, medical aid in dying, and resource allocation, among others. We also asked bioethicists about their demographic, religious, academic, and professional backgrounds. We find that bioethicists' normative commitments predict their views on bioethical issues. We also find that, in important ways, bioethicists' views do not align with those of the U.S. public: for instance, bioethicists are more likely than members of the public to think abortion is ethically permissible but are less likely to believe compensating organ donors is. Our demographic results indicate the field of bioethics is far less diverse than the U.S. population-less diverse even than other academic disciplines-suggesting far more work needs to be done to build an inclusive field.

Exploring the motivations of research participants who chose not to learn medically actionable secondary genetic findings about themselves.

PURPOSE: Proposals to return medically actionable secondary genetic findings (SFs) in the clinical and research settings have generated controversy regarding whether to solicit individuals' preferences about their "right not to know" genetic information. This study contributes to the debate by surveying research participants who have actively decided whether to accept or refuse SFs. METHODS: Participants were drawn from a large National Institutes of Health (NIH) environmental health study. Participants who had accepted SFs (n = 148) or refused SFs (n = 83) were given more detailed information about the types of SFs researchers could return and were given an opportunity to revise their original decision. RESULTS: Forty-one of 83 initial refusers (49.4%) opted to receive SFs following the informational intervention. Nearly 75% of these "reversible refusers" thought they had originally accepted SFs. The 50.6% of initial refusers who continued to refuse ("persistent refusers") demonstrated high levels of understanding of which SFs would be returned postintervention. The most prominent reason for refusing was concern about becoming worried or sad (43.8%). CONCLUSION: This study demonstrates the need for a more robust informed consent process when soliciting research participants' preferences about receiving SFs. We also suggest that our data support implementing a default practice of returning SFs without actively soliciting preferences.

Generation of a microglial developmental index in mice and in humans reveals a sex difference in maturation and immune reactivity.

Evidence suggests many neurological disorders emerge when normal neurodevelopmental trajectories are disrupted, i.e., when circuits or cells do not reach their fully mature state. Microglia play a critical role in normal neurodevelopment and are hypothesized to contribute to brain disease. We used whole transcriptome profiling with Next Generation sequencing of purified developing microglia to identify a microglial developmental gene expression program involving thousands of genes whose expression levels change monotonically (up or down) across development. Importantly, the gene expression program was delayed in males relative to females and exposure of adult male mice to LPS, a potent immune activator, accelerated microglial development in males. Next, a microglial developmental index (MDI) generated from gene expression patterns obtained from purified mouse microglia, was applied to human brain transcriptome datasets to test the hypothesis that variability in microglial development is associated with human diseases such as Alzheimer's and autism where microglia have been suggested to play a role. MDI was significantly increased in both Alzheimer's Disease and in autism, suggesting that accelerated microglial development may contribute to neuropathology. In conclusion, we identified a microglia-specific gene expression program in mice that was used to create a microglia developmental index, which was applied to human datasets containing heterogeneous cell types to reveal differences between healthy and diseased brain samples, and between males and females. This powerful tool has wide ranging applicability to examine microglial development within the context of disease and in response to other variables such as stress and pharmacological treatments.

A Proposed Process for Reliably Updating the Common Rule.

The recent Common Rule revision process took almost a decade and the resulting changes are fairly modest, particularly when compared to the ambitious ideas proposed in the advance notice of proposed rulemaking (ANPRM) and notice of proposed rulemaking (NPRM). Furthermore, the revision process did not even attempt to tackle any of the Common Rule subparts pertaining to vulnerable populations (i.e., pregnant women and fetuses, prisoners, children) where commentators think the rules unduly restrict important research. We believe that this was a missed opportunity to make desirable changes, and that given the usual process the next opportunity to revisit the Common Rule is unacceptably remote. In this article, we argue that the Common Rule should be regularly reassessed, with a mechanism for making substantive (and expeditious) changes. Drawing on lessons learned from the recent revision process, we make recommendations about ways to structure future attempts to maximize the ability to make timely and necessary changes.

Evaluating the Ability to Consent to Research: A Twenty-Year Track Record.

Occasionally, the ability of prospective research participants to consent may be uncertain. Yet standardized capacity-assessment tools may not suffice to determine the ability to consent to a particular research protocol. This study consisted of a retrospective review of the outcomes of an alternative approach used by the Ability to Consent Assessment Team at the National Institutes of Health. Of 944 individuals evaluated over 20 years (1999-2019), 70.1% were determined to have capacity to consent to participate in research. Of those who lacked capacity to consent and were subsequently evaluated for their ability to assign a surrogate, 86.0% had the ability to do so. The findings demonstrate that establishing a task-specific approach for assessing the capacity of potential participants to consent to a variety of research protocols can facilitate safe and ethically justifiable inclusion of individuals whose ability to consent is initially uncertain.

Sounding out stability of enteric coated dosage forms using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS).

Stability testing is essential in the pharmaceutical industry to determine product shelf- life and the conditions under which drug products should be stored. Stability testing involves a complex set of procedures, considerable cost, time, and scientific expertise to build quality, efficacy and safety in a drug formulation. This paper highlights a new complementary approach to stability testing called Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS). BARDS measurements are based on reproducible changes in the compressibility of a solvent during dissolution. It is monitored acoustically via associated changes in the frequency of induced acoustic resonances. This study presents a novel approach to track the change of various drug formulations to determine the formulation's stability. Pellets, tablet and multiple-unit pellet system (MUPS) formulations were investigated to examine the effect of polymer coating and formulation core degradation over time. In combination with minimal usage of Ultra Violet - Visible Spectroscopy, BARDS can effectively track these changes. The technique offers a rapid approach to characterizing pharmaceutical formulations. BARDS can enable rapid development of solid drug formulation dissolution and disintegration testing as an In-Process Control test and drug stability analysis. The data show that a solid oral dose formulation has an intrinsic acoustic signature specific to the method of manufacture, excipient composition and elapsed time since the production of a product. BARDS data are also indicative of which aspect of a formulation may be unstable, whether a coating, sub-coating or core. It is potentially a time-efficient, cost-effective and greener approach to testing coating stability, disintegration and overall formulation stability.

Noninvasive Prenatal Whole Genome Sequencing: Pregnant Women's Views and Preferences.

OBJECTIVE: To assess pregnant women's views and preferences on noninvasive prenatal whole genome sequencing. METHODS: A survey was offered to 805 pregnant women receiving prenatal care in practices affiliated with a large, tertiary care maternity hospital. Respondents were asked to envision undergoing prenatal whole genome sequencing and discuss their preferences and reasons for receiving different categories of genomic results, organized by actionability, severity, prevalence, and age of onset. The survey also queried respondents on their preferred role for clinicians in prenatal whole genome sequencing decision-making, and on their demographics and genetic literacy. RESULTS: From June to August 2017, a total of 553 respondents returned the survey (response rate=68.7%). Respondents were most likely to want information regarding serious treatable childhood-onset conditions (89.7%) and least likely to want to receive information about nonmedical traits from prenatal whole genome sequencing (40%). The most frequently cited reason for wanting medical prenatal whole genome sequencing results was "to prepare financially, medically, or psychologically for a child with special needs." In total, 10.5% of respondents wanted clear recommendations from clinicians about the categories of information that are most appropriate to test for, 44.7% wanted clear recommendations plus all options presented, 26.2% wanted all options presented and joint decision-making, and 13.2% wanted all options presented and independent decision-making. CONCLUSION: Respondents generally preferred to receive all categories of genetic results pertaining to medical conditions and wanted the information to prepare. More than half of respondents wanted (at minimum) clear recommendations from clinicians when deciding which prenatal whole genome sequencing results to receive.

Incidental Findings in Low-Resource Settings.

Much new global genetic research employs whole genome sequencing, which provides researchers with large amounts of data. The quantity of data has led to the generation and discovery of more incidental or secondary findings and to vigorous theoretical discussions about the ethical obligations that follow from these incidental findings. After a decade of debate in the genetic research community, there is a growing consensus that researchers should, at the very least, offer to return incidental findings that provide high-impact, medically relevant information, when it is not unduly burdensome to the research enterprise to do so. Much as genetic research has been limited to U.S. and European settings, the incidental findings debate has primarily focused on research conducted in high-income countries. In a 2015 paper, Alberto Ortiz-Osorno, Linda Ehler, and Judith Brooks note salient differences between the circumstances of research participants in low- and high-resource settings that alter the analysis of when and why incidental findings should be offered to research participants. In this article, we expand on their analysis and present a framework for thinking about how investigators' obligations to return genomic data might change in low-resource settings, particularly in settings where participants do not have access to the medical care needed to treat, assess, or monitor incidental findings that are actionable in settings with plentiful resources.