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Objective: Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [ 11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site., Methods: Thirty-one unilateral MTLE patients and 30 healthy controls underwent [ 11 C]ABP688 PET. We compared partial volume corrected [ 11 C]ABP688 nondisplaceable binding potentials (BP ND ) between groups using region-of-interest and whole-brain voxelwise analyses. [ 18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [ 11 C]ABP688 BP ND and [ 18 F]FDG uptake to compare lateralization and localization differences., Results: [ 11 C]ABP688 BP ND was focally reduced in the epileptogenic hippocampal head and amygdala (p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex (p = 0.006). [ 11 C]ABP688 BP ND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [ 18 F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [ 11 C]ABP688 BP ND in the ipsilateral entorhinal cortex., Interpretation: [ 11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [ 18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1-11 ANN NEUROL 2019;85:218-228., (© 2018 American Neurological Association.)

Serious ethical violations in medicine, such as sexual abuse, criminal prescribing of opioids, and unnecessary surgeries, directly harm patients and undermine trust in the profession of medicine. We review the literature on violations in medicine and present an analysis of 280 cases. Nearly all cases involved repeated instances (97%) of intentional wrongdoing (99%), by males (95%) in nonacademic medical settings (95%), with oversight problems (89%) and a selfish motive such as financial gain or sex (90%). More than half of cases involved a wrongdoer with a suspected personality disorder or substance use disorder (51%). Despite clear patterns, no factors provide readily observable red flags, making prevention difficult. Early identification and intervention in cases requires significant policy shifts that prioritize the safety of patients over physician interests in privacy, fair processes, and proportionate disciplinary actions. We explore a series of 10 questions regarding policy, oversight, discipline, and education options. Satisfactory answers to these questions will require input from diverse stakeholders to help society negotiate effective and ethically balanced solutions.

Background: Overlapping surgery is attracting increased scrutiny. The American College of Surgeons states that the attending surgeon must be present for all critical portions of a surgical procedure; however, critical portions of surgical procedures are not defined. We hypothesized that a Delphi panel process would measure consensus on critical portions of 3 common hand surgical procedures., Methods: We used a Delphi process to achieve consensus on the critical portions of carpal tunnel release, ulnar nerve transposition, and open reduction and internal fixation of the distal part of the radius. The panelists were 10 hand surgeons (7 fellowship-trained surgeons and 3 fellows). Following an in-person discussion to finalize steps for each procedure, 2 online rounds were completed to rate steps from 1 (not critical) to 9 (extremely critical). We operationalized consensus as ≥80% of ratings within the same range: 1 to 3 (not critical), 4 to 6 (somewhat critical), and 7 to 9 (critical). Because of a lack of consensus on some steps after round 2, another in-person discussion and a third online round were conducted to rate only steps involving disagreement or somewhat critical ratings using a dichotomous scale (critical or not critical)., Results: Following the first 2 rounds, there was consensus on 19 of 24 steps (including 3 steps being somewhat critical) and no consensus on 5 of 24 steps. At the end of round 3, there was consensus on all but 2 steps (identification of the medial antebrachial cutaneous nerve in ulnar nerve transposition and clinical assessment of joint stability in open reduction and internal fixation of the distal part of the radius), with moderate disagreement (3 compared with 7) for both., Conclusions: The panel reached consensus on the designation of critical or noncritical for all steps of a carpal tunnel release, all but 1 step of an ulnar nerve transposition, and all but 1 step of open reduction and internal fixation of the distal part of the radius. The lack of consensus on whether 2 of the steps are critical leaves this determination at the discretion of the attending surgeon. The findings of our Delphi panel provide guidance to our division on which portions of the surgical procedure are critical and thus require the attending surgeon's presence.

This article reports the consensus recommendations of a working group that was convened at the end of a 4-year research project funded by the National Institutes of Health that examined 280 cases of egregious ethical violations in medical practice. The group reviewed data from the parent project, as well as other research on sexual abuse of patients, criminal prescribing of controlled substances, and unnecessary invasive procedures that were prosecuted as fraud. The working group embraced the goals of making such violations significantly less frequent and, when they do occur, identifying them sooner and taking necessary steps to ensure they are not repeated. Following review of data and previously published recommendations, the working group developed 10 recommendations that provide a starting point to meet these goals. Recommendations address leadership, oversight, tracking, disciplinary actions, education of patients, partnerships with law enforcement, further research and related matters. The working group recognized the need for further refinement of the recommendations to ensure feasibility and appropriate balance between protection of patients and fairness to physicians. While full implementation of appropriate measures will require time and study, we believe it is urgent to take visible actions to acknowledge and address the problem at hand.

Policies by the National Institutes of Health and the National Science Foundation, as well as scandals surrounding failures to reproduce the findings of key studies in psychology, have generated increased calls for sharing research data. Most of these discussions have focused on quantitative, rather than qualitative, research data. This paper examines scientific, ethical, and policy issues surrounding sharing qualitative research data. We consider advantages of sharing data, including enabling verification of findings, promoting new research in an economical manner, supporting research education, and fostering public trust in science. We then examine standard procedures for archiving and sharing data, such as anonymizing data and establishing data use agreements. Finally, we engage a series of concerns with sharing qualitative research data such as the importance of relationships in interpreting data, the risk of re-identifying participants, issues surrounding consent and data ownership, and the burden of data documentation and depositing on researchers. For each concern, we identify options that enable data sharing or describe conditions under which select data might be withheld from a data repository. We conclude by suggesting that the default assumption should be that qualitative data will be shared unless concerns exist that cannot be addressed through standard data depositing practices such as anonymizing data or through data use agreements.

According to "Research Exemplars," research requires attending to matters of heart as much as mind. The human dimension in research-relationships, passion, resilience, and leadership-was the common thread in their advice for a successful career. We discuss strategies to cultivate intra- and inter-personal skills fostering these aspects of research., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The authors explore five dimensions of research ethics: (1) normative ethics, which includes meta-ethical questions; (2) compliance with regulations, statutes, and institutional policies; (3) the rigor and reproducibility of science; (4) social value; and (5) workplace relationships. Each of the five dimensions is important not only because it addresses an aspect of good research done in a good manner but also because it addresses the concerns of key stakeholders in the research enterprise. The five-dimension framework can guide institutions as they answer three questions central to any research ethics program: (1) Who should champion research ethics? (2) What should interventions look like? and (3) Who should participate in the interventions? The framework is valuable because the answers to these three questions are radically different depending on the dimension under consideration. An expanded vision of research ethics does not entail that institutions should require additional online training or approvals from institutional review boards. However, without acknowledging all five dimensions, programs risk missing an important aspect of research ethics or ignoring the interests of important stakeholders.

Successfully navigating the norms of a society is a complex task that involves recognizing diverse kinds of rules as well as the relative weight attached to them. In the United States (U.S.), different kinds of rules-federal statutes and regulations, scientific norms, and professional ideals-guide the work of researchers. Penalties for violating these different kinds of rules and norms can range from the displeasure of peers to criminal sanctions. We proposed that it would be more difficult for researchers working in the U.S. who were born in other nations to distinguish the seriousness of violating rules across diverse domains. We administered a new measure, the evaluating rules in science task (ERST), to National Institutes of Health-funded investigators (101 born in the U.S. and 102 born outside of the U.S.). The ERST assessed perceptions of the seriousness of violating research regulations, norms, and ideals, and allowed us to calculate the degree to which researchers distinguished between the seriousness of each rule category. The ERST also assessed researchers' predictions of the seriousness that research integrity officers (RIOs) would assign to the rules. We compared researchers' predictions to the seriousness ratings of 112 RIOs working at U.S. research-intensive universities. U.S.-born researchers were significantly better at distinguishing between the seriousness of violating federal research regulations and violating ideals of science, and they were more accurate in their predictions of the views of RIOs. Acculturation to the U.S. moderated the effects of nationality on accuracy. We discuss the implications of these findings in terms of future research and education.

In this paper we describe the development and initial psychometric evaluation of a new measure, the values in scientific work (VSW). This scale assesses the level of importance that investigators attach to different VSW. It taps a broad range of intrinsic, extrinsic, and social values that motivate the work of scientists, including values specific to scientific work (e.g., truth and integrity) and more classic work values (e.g., security and prestige) in the context of science. Notably, the values represented in this scale are relevant to scientists regardless of their career stage and research focus. We administered the VSW and a measure of global values to 203 NIH-funded investigators. Exploratory factor analyses suggest the delineation of eight VSW, including autonomy, research ethics, social impact, income, collaboration, innovation and growth, conserving relationships, and job security. These VSW showed predictable and distinct associations with global values. Implications of these findings for work on research integrity and scientific misconduct are discussed.

Violations of rules and regulations in research can cause significant problems for human participants, animal subjects, data integrity, institutions, and investigators. The Professionalism and Integrity in Research Program (PI Program) provides remediation training that addresses the root causes of violations of rules and regulations in research. Through assessments, a three-day workshop, and follow-up coaching calls, the PI Program teaches evidence-based decision-making strategies designed to help researchers to compensate for bias, uncertainty, and work-related stress, and foster the skills needed to oversee research projects in today's complex regulatory environments. Across its first three years (2013-2015), the program trained 39 researchers from 24 different institutions in the United States. Participant evaluations of the program's faculty and workshop content were highly positive (4.7-4.8 and 4.5-4.6, respectively, on a 5-point scale). Preliminary program outcome assessment using validated measures of professional decision making and cognitive distortions in a pre- and postworkshop design indicated significant improvements. A follow-up survey of participants found statistically significant increases in a variety of target behaviors, including training research staff members to foster compliance and research quality, using standard operating procedures to support compliance and research integrity, performing self-audits of research operations, reducing job stressors, actively overseeing the work of the research team, and seeking help when experiencing uncertainty. Assessment of the PI Program was conducted with modest sample sizes, yet evaluation, outcome assessment, and self-reported survey data provided statistically significant evidence of effectiveness in achieving program goals.

Qualitative data provide rich information on research questions in diverse fields. Recent calls for increased transparency and openness in research emphasize data sharing. However, qualitative data sharing has yet to become the norm internationally and is particularly uncommon in the United States. Guidance for archiving and secondary use of qualitative data is required for progress in this regard. In this study, we review the benefits and concerns associated with qualitative data sharing and then describe the results of a content analysis of guidelines from international repositories that archive qualitative data. A minority of repositories provide qualitative data sharing guidelines. Of the guidelines available, there is substantial variation in whether specific topics are addressed. Some topics, such as removing direct identifiers, are consistently addressed, while others, such as providing an anonymization log, are not. We discuss the implications of our study for education, best practices, and future research.

Background: Unnecessary invasive procedures risk harming patients physically, emotionally, and financially. Very little is known about the factors that provide the motive, means, and opportunity (MMO) for unnecessary procedures., Methods: This project used a mixed-methods design that involved five key steps: (1) systematically searching the literature to identify cases of unnecessary procedures reported from 2008 to 2016; (2) identifying all medical board, court, and news records on relevant cases; (3) coding all relevant records using a structured codebook of case characteristics; (4) analyzing each case using a MMO framework to develop a causal theory of the case; and (5) identifying typologies of cases through a two-step cluster analysis using variables hypothesized to be causally related to unnecessary procedures., Results: Seventy-nine cases met inclusion criteria. The mean number of documents or sources examined for each case was 36.4. Unnecessary procedures were performed for at least five years in most cases (53.2%); 56.3% of the cases involved 30 or more patients, and 37.5% involved 100 or more patients. In nearly all cases the physician was male (96.2%) and working in private practice (92.4%); 57.0% of the physicians had an accomplice, 48.1% were 50 years of age or older, and 40.5% trained outside the U.S. The most common motives were financial gain (92.4%) and suspected antisocial personality (48.1%), followed by poor problem-solving or clinical skills (11.4%) and ambition (3.8%). The most common environmental factors that provided opportunity for unnecessary procedures included a lack of oversight (40.5%) or oversight failures (39.2%), a corrupt moral climate (26.6%), vulnerable patients (20.3%), and financial conflicts of interest (13.9%)., Conclusions: Unnecessary procedures usually appear motivated by financial gain and occur in settings that have oversight problems. Preventive efforts should focus on early detection by peers and institutions, and decisive action by medical boards and federal prosecutors., Competing Interests: Not applicable.Not applicable.James DuBois serves as a paid medical ethics consultant to Centene Corp. No funding for this project was provided by Centene Corp.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The shortage of primary care providers and the provisions of the Affordable Care Act (ACA) have spurred discussion about expanding the number, scope of practice (SOP), and independence of primary care nurse practitioners (NPs). Such discussions in the media and among professional organizations may insinuate that changes to the laws governing NP practice will engender acrimony between practicing physicians and NPs. However, we lack empirical, descriptive data on how practicing professionals view NP independence in primary care., Objective: The aim of the present study was to explore and describe the attitudes about NP independence among physicians and NPs working in primary care., Design: A qualitative study based on the principles of grounded theory., Participants: Thirty primary care professionals in Missouri, USA, including 15 primary care physicians and 15 primary care NPs., Approach: Semi-structured, in-depth interviews, with data analysis guided by grounded theory., Key Results: Participants had perspectives that were not well represented by professional organizations or the media. Physicians were supportive of a wide variety of NP roles and comfortable with high levels of NP independence and autonomy. Physicians and NPs described prerequisites to NP independence that were complementary. Physicians generally believed that NPs needed some association with physicians for patient safety, and NPs preferred having a physician readily accessible as needed. The theme "knowing your limits" was important to both NPs and physicians regarding NP independence, and has not been described previously in the literature., Conclusions: NP and physician views about NP practice in primary care are not as divergent as their representative professional organizations and the news media would suggest. The significant agreement among NPs and physicians, and some of the nuances of their perspectives, supports recommendations that may reduce the perceived acrimony surrounding discussions of NP independent practice in primary care.

Due to issues related to informed research consent, older adults with cognitive impairments are often excluded from high-quality studies that are not directly related to cognitive impairment, which has led to a dearth of evidence for this population. The challenges to including cognitively impaired older adults in research and the implications of their exclusion are a transdisciplinary issue. The ethical challenges and logistical barriers to conducting research with cognitively impaired older adults are addressed from the perspectives of three different fields-social work, emergency medicine, and orthopaedic surgery. Issues related to funding, study design, intervention components, and outcomes are discussed through the unique experiences of three different providers. A fourth perspective-medical research ethics-provides alternatives to exclusion when conducting research with cognitively impaired older adults such as timing, corrective feedback and plain language, and capacity assessment and proxy appointments. Given the increasing aging population and the lack of evidence on cognitively impaired older adults, it is critical that researchers, funders, and institutional review boards not be dissuaded from including this population in research studies.

Principal investigators are responsible for a myriad of leadership and management activities in their work. The practices they use to navigate these responsibilities ultimately influence the quality and integrity of research. However, leadership and management roles in research have received scant empirical examination. Semi-structured interviews with 32 National Institutes of Health (NIH)-funded genetic researchers revealed that they considered leadership and management essential for effective research, but their scientific training inadequately prepared them. We also report management practices that the researchers described using in their labs, as well as their perceptions of a proposed intervention to enhance laboratory leadership. These findings suggest best practices for the research community, future directions for scientific training, and implications for research on leadership and management in science., Competing Interests: Disclaimers The authors have no conflicts of interests or disclaimers to report.

Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses., (© The Author 2016. Published by Oxford University Press.)

Improper prescribing of controlled substances contributes to opioid addictions and deaths by overdose. Studies conducted to-date have largely lacked a theoretical framework and ignored the interaction of individual with environmental factors. We conducted a mixed-method analysis of published reports on 100 cases that occurred in the United States. An average of 17 reports (e.g., from medical boards) per case were coded for 38 dichotomous variables describing the physician, setting, patients, and investigation. A theory on how the case occurred was developed for each case. Explanatory typologies were developed and then validated through hierarchical cluster analysis. Most cases involved physicians who were male (88%), >40 years old (90%), non-board certified (63%), and in small private practices (97%); 54% of cases reported facts about the physician indicative of self-centered personality traits. Three explanatory typologies were validated. Increasing oversight provided by peers and trainees may help prevent improper prescribing of controlled substances., Competing Interests: The authors have no financial conflicts of interests to declare.

In the world of research, compliance with research regulations is not the same as ethics, but it is closely related. One could say that compliance is how most societies with advanced research programs operationalize many ethical obligations. This paper reports on the development of the How I Think about Research (HIT-Res) questionnaire, which is an adaptation of the How I Think (HIT) questionnaire that examines the use of cognitive distortions to justify antisocial behaviors. Such an adaptation was justified based on a review of the literature on mechanisms of moral disengagement and self-serving biases, which are used by individuals with normal personalities in a variety of contexts, including research. The HIT-Res adapts all items to refer to matters of research compliance and integrity rather than antisocial behaviors. The HIT-Res was administered as part of a battery of tests to 300 researchers and trainees funded by the US National Institutes of Health. The HIT-Res demonstrated excellent reliability (Cronbach's alpha = .92). Construct validity was established by the correlation of the HIT-Res with measures of moral disengagement (r = .75), cynicism (r = .51), and professional decision-making in research (r = -.36). The HIT-Res will enrich the set of assessment tools available to instructors in the responsible conduct of research and to researchers who seek to understand the factors that influence research integrity., Competing Interests: Compliance with Ethical Standards Ethical Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

In this paper, we report on the development and validity of the Professional Decision-Making in Research (PDR) measure, a vignette-based test that examines decision-making strategies used by investigators when confronted with challenging situations in the context of empirical research. The PDR was administered online with a battery of validity measures to a group of NIH-funded researchers and research trainees who were diverse in terms of age, years of experience, types of research, and race. The PDR demonstrated adequate reliability (alpha = .84) and parallel form correlation (r = .70). As hypothesized, the PDR was significantly negatively correlated with narcissism, cynicism, moral disengagement, and compliance disengagement; it was not correlated with socially desirable responding. In regression analysis, the strongest predictors of higher PDR scores were low compliance disengagement, speaking English as a native language, conducting clinical research with human subjects, and low levels of narcissism. Given that the PDR was written at an eighth grade reading level to be suitable for use with English as a second language participants and that only one-fourth of items focused on clinical research, further research into the possible roles of culture and research ethics training across specialties is warranted. This initial validity study demonstrates the potential usefulness of the PDR as an educational outcome assessment measure and a research instrument for studies on professionalism and integrity in research.

After gas atomization, a quasicrystalline powder based on aluminium was used to prepare a thick coating by high-velocity oxygen-fuel flame torch spraying. This layer was deposited on top of a bond-coat layer on a steel plate. A post-spraying annealing treatment turned the two layers to their stable state, a γ-brass crystal and an icosahedral quasicrystal, respectively. The projection parameters were selected in such a way that the coating behaved like a self-lubricating material, which offered very good wear resistance (duration of pin-on-disk tests superior to 5 km with negligible material loss) and low friction (µ ≤ 6% against sintered tungsten carbide), in contrast to the state of the art. This property was achieved thanks to, on the one hand, excellent bonding to the substrate via the bound coat, and on the other hand, presence at the boundaries between quasicrystalline flakes of a mixture of both threefold and fourfold coordinated carbon originating from spray processing. Application to hard materials used in mechanical devices is appealing, especially because soft, lubricating additives may not be needed, thus considerably increasing the lifetime of the devices and reducing waste of materials.

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

The professional decision-making in research (PDR) measure was administered to 400 National Institutes of Health (NIH)-funded and industry-funded investigators, along with measures of cynicism, moral disengagement, compliance disengagement, impulsivity, work stressors, knowledge of responsible conduct of research (RCR), and socially desirable response tendencies. Negative associations were found for the PDR and measures of cynicism, moral disengagement, and compliance disengagement, while positive associations were found for the PDR and RCR knowledge and positive urgency, an impulsivity subscale. PDR scores were not related to socially desirable responding, or to measures of work stressors and the remaining impulsivity subscales. In a multivariate logistic regression analysis, lower moral disengagement scores, higher RCR knowledge, and identifying the United States as one's nation of origin emerged as key predictors of stronger performance on the PDR. The implications of these findings for understanding the measurement of decision-making in research and future directions for research and RCR education are discussed.

Twelve personal narratives address the impact of political influence on bioethics. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, medicine, educational psychology, health care management, and philosophy.

Prescription opioids are an important tool for physicians in treating pain but also carry significant risks of harm when prescribed inappropriately or misused by patients or others. Recent increases in opioid-related morbidity and mortality has reignited scrutiny of prescribing practices by law enforcement, regulatory agencies, and state medical boards. At the same time, the predominant 4D model of misprescribers is outdated and insufficient; it groups physician misprescribers as dated, duped, disabled, or dishonest. The weaknesses and inaccuracies of the 4D model are explored, along with the serious consequences of its application. This Article calls for development of an evidence base in this area and suggests an alternate model of misprescribers, the 3C model, which more accurately characterizes misprescribers as careless, corrupt, or compromised by impairment.

Purpose: Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [(11)C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals., Methods: Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [(11)C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BPND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere., Results: We found the highest [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [(11)C]ABP688 BPND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction., Conclusions: The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span.

Can scientists self-regulate effectively? The controversial select agent regulations, the recent implementation of U.S. dual-use research of concern policies, the funding moratorium on gain of function experiments, and the 2014 incidents at the Centers for Disease Control and Prevention all seem to suggest that the answer is a resounding "no." Yet history tells us that it is feasible. In this comprehensive history of the first iteration of the National Institutes of Health (NIH) Recombinant DNA Guidelines, we examine the principles, thoughts, and behaviors that resulted in successful self-regulation of scientific research for the past four decades and how engagement of scientists made it possible. Starting with a willingness on the part of researchers all over the world to pause exciting experiments, and with a genuine concern for public health, the individuals involved demonstrated unprecedented (and thus far never replicated) openness to dialogue with others from different disciplines, the media, and the public.

Aaron Antonovsky, the medical sociologist, defined the sense of coherence as a pervasive sense that the events in one's life are comprehensible, manageable, and meaningful or worthwhile. Research on the sense of coherence indicates that it is positively correlated with resilience and adaptive coping with disabilities and illnesses. The collection of first-person narratives published in Narrative Inquiry in Bioethics on genetic testing can be understood as expressions of the human effort to restore or sustain a sense of coherence in the face of illness, uncertainty, or even curiosity about one's origins and future wellbeing. While the medical usefulness of the genetic testing that was discussed in the collection of narratives was often modest, the contribution of testing to the sense of coherence was often greater. Understanding the sense of coherence as a possible motive for genetic testing might reshape the way that we conceive of the benefits and the burdens of genetic testing and the disclosure of incidental findings.

Twelve personal narratives address the challenges, benefits, and pitfalls of genetic testing. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, public health, psychology, and philosophy.

Surgeons share their challenges and dilemmas in making ethical decisions in these twelve personal stories. The three commentary articles draw out the lessons the stories address. The commentators come from diverse backgrounds including sociology, bioethics, nursing, and surgery.

Efforts to advance research integrity in light of concerns about misbehavior in research rely heavily on education in the responsible conduct of research (RCR). However, there is limited evidence for the effectiveness of RCR instruction as a remedy. Assessment is essential in RCR education if the research community wishes to expend the effort of instructors, students, and trainees wisely. This article presents key considerations that instructors and course directors must consider in aligning learning objectives with instructional methods and assessment measures, and it provides illustrative examples. Above all, in order for RCR educators to assess outcomes more effectively, they must align assessment to their learning objectives and attend to the validity of the measures used.

Background: No published curricula in the area of medical business ethics exist. This is surprising given that physicians wrestle daily with business decisions and that professional associations, the Institute of Medicine, Health and Human Services, Congress, and industry have issued related guidelines over the past 5 years. To fill this gap, the authors aimed (1) to identify the full range of medical business ethics topics that experts consider important to teach, and (2) to establish curricular priorities through expert consensus., Methods: In spring 2012, the authors conducted an online Delphi survey with two heterogeneous panels of experts recruited in the United States. One panel focused on business ethics in medical practice (n = 14), and 1 focused on business ethics in medical research (n = 12)., Results: Panel 1 generated an initial list of 14 major topics related to business ethics in medical practice, and subsequently rated 6 topics as very important or essential to teach. Panel 2 generated an initial list of 10 major topics related to business ethics in medical research, and subsequently rated 5 as very important or essential. In both domains, the panel strongly recommended addressing problems that conflicts of interest can cause, legal guidelines, and the goals or ideals of the profession., Conclusions: The Bander Center for Medical Business Ethics at Saint Louis University will use the results of the Delphi panel to develop online curricular resources for each of the highest rated topics.

Background: In recent years, issues in medical business ethics (MBE), such as conflicts of interest (COI), Medicare fraud and abuse, and the structure and functioning of reimbursement systems, have received significant attention from the media and professional associations in the United States. As a result of highly publicized instances of financial interests altering physician decision-making, major professional organizations and government bodies have produced reports and guidelines to encourage self-regulation and impose rules to limit physician relationships with for-profit entities. Nevertheless, no published curricula exist in the area of MBE. This study aimed to establish a baseline level of knowledge and the educational goals medical students and residents prioritize in the area of MBE., Methods: 732 medical students and 380 residents at two academic medical centers in the state of Missouri, USA, completed a brief survey indicating their awareness of major MBE guidance documents, knowledge of key MBE research, beliefs about the goals of an education in MBE, and the areas of MBE they were most interested in learning more about., Results: Medical students and residents had little awareness of recent and major reports on MBE topics, and had minimal knowledge of basic MBE facts. Residents scored statistically better than medical students in both of these areas. Medical students and residents were in close agreement regarding the goals of an MBE curriculum. Both groups showed significant interest in learning more about MBE topics with an emphasis on background topics such as "the business aspects of medicine" and "health care delivery systems"., Conclusions: The content of major reports by professional associations and expert bodies has not trickled down to medical students and residents, yet both groups are interested in learning more about MBE topics. Our survey suggests potentially beneficial ways to frame and embed MBE topics into the larger framework of medical education.

The discovery in 1987 of stable quasicrystals in the Al-Cu-Fe system was soon exploited to patent specific coatings that showed reduced friction in ambient air against hard antagonists. Henceforth, it was possible to develop a number of applications, potential or commercially exploited to date, that will be alluded to in this topical review. A deeper understanding of the characteristics of complex metallic alloys (CMAs) may explain why material made of metals like Al, Cu and Fe offers reduced friction; low solid-solid adhesion came later. It is linked to the surface energy being significantly lower on those materials, in which translational symmetry has become a weak property, that is determined by the depth of the pseudo-gap at the Fermi energy. As a result, friction is anisotropic in CMAs that builds up according to the translation symmetry along one direction, but is aperiodic along the other two directions. A review is given in this article of the most salient data found along these lines during the past two decades or so.

Importance: Risk communication and management are essential to the ethical conduct of research, yet addressing risks may be time consuming for investigators and institutional review boards may reject study designs that seem too risky. This can discourage needed research, particularly in higher-risk protocols or those enrolling potentially vulnerable individuals, such as those with some level of suicidality. Improved mechanisms for addressing research risks may facilitate much needed psychiatric research., Objective: To provide mental health researchers with practical approaches to (1) identify and define various intrinsic research risks, (2) communicate these risks to others (eg, potential participants, regulatory bodies, and society), (3) manage these risks during the course of a study, and (4) justify the risks., Evidence Review: As part of a National Institute of Mental Health-funded scientific meeting series, a public conference and a closed-session expert panel meeting were held on managing and disclosing risks in mental health clinical trials. The expert panel reviewed the literature with a focus on empirical studies and developed recommendations for best practices and further research on managing and disclosing risks in mental health clinical trials. No institutional review board-review was required because there were no human subjects., Findings: Challenges, current data, practical strategies, and topics for future research are addressed for each of 4 key areas pertaining to management and disclosure of risks in clinical trials: identifying and defining risks, communicating risks, managing risks during studies, and justifying research risks., Conclusions and Relevance: Empirical data on risk communication, managing risks, and the benefits of research can support the ethical conduct of mental health research and may help investigators better conceptualize and confront risks and to gain institutional review board-approval.

Atomic oxygen adsorption on a pure aluminum terminated Al9Co2(001) surface is studied by first-principle calculations coupled with STM measurements. Relative adsorption energies of oxygen atoms have been calculated on different surface sites along with the associated STM images. The local electronic structure of the most favourable adsorption site is described. The preferential adsorption site is identified as a 'bridge' type site between the cluster entities exposed at the (001) surface termination. The Al-O bonding between the adsorbate and the substrate presents a covalent character, with s-p hybridization occurring between the states of the adsorbed oxygen atom and the aluminum atoms of the surface. The simulated STM image of the preferential adsorption site is in agreement with experimental observations. This work shows that oxygen adsorption generates important atomic relaxations of the topmost surface layer and that sub-surface cobalt atoms strongly influence the values of the adsorption energies. The calculated Al-O distances are in agreement with those reported in Al2O and Al2O3 oxides and for oxygen adsorption on Al(111).

Virtues define how we behave when no one else is watching; accordingly, they serve as a bedrock for professional self-regulation, particularly at the level of the individual physician. From the time of William Osler through the end of the 20th century, physician virtue was viewed as an important safeguard for patients and research participants. However, the Institute of Medicine, Association of American Medical Colleges, and other policy groups-relying on social science data indicating that ethical decisions often result from unconscious and biased processes, particularly in the face of financial conflicts of interest-have increasingly rejected physician virtue as an important safeguard for patients.The authors argue that virtue is still needed in medicine-at least as a supplement to regulatory solutions (such as mandatory disclosures). For example, although rarely treated as a reportable conflict of interest, standard fee-for-service medicine can present motives to prioritize self-interest or institutional interests over patient interests. Because conflicts of interest broadly construed are ubiquitous, physician self-regulation (or professional virtue) is still needed. Therefore, the authors explore three strategies that physicians can adopt to minimize the influence of self-serving biases when making medical business ethics decisions. They further argue that humility must serve as a crowning virtue-not a meek humility but, rather, a courageous willingness to recognize one's own limitations and one's need to use "compensating strategies," such as time-outs and consultation with more objective others, when making decisions in the face of conflicting interests.

With supplement funding to the Washington University CTSA, the Restoring Professionalism and Integrity in Research (RePAIR) program was developed at Saint Louis University to meet the remediation needs of institutions nationwide regarding investigators who violate research regulations. With the aim of determining the frequency and kinds of wrongdoing at leading research institutions in the United States, as well as institutional responses and levels of interest in a formal remediation program, an online questionnaire was distributed by email to a research integrity officer (RIO) and institutional review board (IRB) chair at all medical schools and comprehensive doctoral institutions in the United States (N = 194). One hundred sixty-one individuals responded (44%) representing 66% of institutions. For those institutions that had both RIOs and IRB chairs responding, 96% had investigated at least one case over the past 2 years; the modal individual response was 3-5 cases, with a range from 0 to more than 16 cases. The most common forms of wrongdoing were violations of procedure, informed consent, research integrity (fabrication, falsification, plagiarism), privacy, and conflict of interest policies. Most RIOs and IRB chairs expressed interest in the RePAIR program, despite concerns about costs and faculty resistance., (© 2013 Wiley Periodicals, Inc.)