Calls to abolish race as a proxy for biology or genetics in clinical care have reached a fever pitch in the latter half of 2020, including articles in the New England Journal of Medicine, and urgent letters from prominent Senators.

At first glance the three eukaryotic protein translocation machineries – the ER‐associated degradation (ERAD) transport apparatus of the endoplasmic reticulum, the peroxisomal importomer and SELMA, the pre‐protein translocator of complex plastids – appear quite different. However, mechanistic comparisons and phylogenetic analyses presented here suggest that all three translocation machineries share a common ancestral origin, which highlights the recycling of pre‐existing components as an effective evolutionary driving force.Editor's suggested further reading in BioEssays ERAD ubiquitin ligases Abstract.

Intra- and intergroup conflict are likely to have been recurrent features of human evolutionary history; however, little research has investigated the factors that affect men’s combat alliance decisions. The current study investigated whether features of previous one-on-one combat with an opponent affect men’s interest in allying with that opponent for future group combat. Fifty-eight undergraduate men recruited from a psychology department subject pool participated in a one-on-one laboratory fight simulation. We manipulated fight outcome, perceived fighter health asymmetry, and the presence (...) of a witness over six sets of five rounds of fighting. Following each set, we asked men how interested they would be in allying with their opponent for future group combat. We found that men were more interested in allying with their opponent for future group combat if their opponent won the fight or if a witness was present, but perceived fighter-health asymmetry did not affect men’s decision to ally with their opponent. Exploratory analyses revealed a two-way interaction between fight outcome and the presence of a witness, such that winners without a witness present expressed less interest in allying with their opponent for future group combat. Our findings suggest that men attend to the benefits of allying with a man who has demonstrated relatively superior fighting ability. Alliance with a previous opponent for group combat may vary with the relationship value of the opponent and the utility of demonstrating cooperativeness to third-party observers. These findings inform our understanding of coalition formation. (shrink)

Big data and artificial intelligence (“AI”) promise to transform virtually all aspects of biomedical research and health care (Matheny et al. 2019), through facilitation of drug development, diagno...

The mechanisms by which delusion and anxiety affect the tendency to make hasty decisions (Jumping-to-Conclusions bias) remain unclear. This paper proposes a Bayesian computational model that explores the assignment of evidence weights as a potential explanation of the Jumping-to-Conclusions bias using the Beads Task. We also investigate the Beads Task as a repeated measure by varying the key aspects of the paradigm. The Bayesian model estimations from two online studies showed that higher delusional ideation promoted reduced belief updating but the (...) impact of general and social anxiety on evidence weighting was inconsistent. The altered evidence weighting as a result of a psychopathological trait appeared insufficient in contributing to the Jumping-to-Conclusions bias. Variations in Beads Task aspects significantly affected subjective certainty at the point of decisions but not the number of draws to decisions. Repetitions of the Beads Task are feasible if one assesses the Jumping-to-Conclusions bias using number of draws to decisions. (shrink)

We explore how principles predicting the success of a medical information commons advantaged or disadvantaged three MIC initiatives in three Canadian provinces. Our MIC case examples demonstrate that practices and policies to promote access to and use of health information can help improve individual healthcare and inform a learning health system. MICs were constrained by heterogenous health information protection laws across jurisdictions and risk-averse institutional cultures. A networked approach to MICs would unlock even more potential for national and international data (...) collaborations to improve health and healthcare. (shrink)

Digital contact tracing, in combination with widespread testing, has been a focal point for many plans to “reopen” economies while containing the spread of Covid‐19. Most digital contact tracing projects in the United States and Europe have prioritized privacy protections in the form of local storage of data on smartphones and the deidentification of information. However, in the prioritization of privacy in this narrow form, there is not sufficient attention given to weighing ethical trade‐offs within the context of a public (...) health pandemic or to the need to evaluate safety and effectiveness of software‐based technology applied to public health. (shrink)

McCradden et al. propose to close the “AI chasm” between algorithms and clinically meaningful application using the norms of evidence-based medicine and clinical research, with the rat...

Background In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal.Methods Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for.Results We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant (...) consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. Critical differences emerged when engagement and research decisionmaking were integrated with each other versus occurring in parallel, separate parts of the study organization, and whether community members had the ability to determine which issues would be brought to them for consideration or to revise or even veto proposals made upstream based on criteria that mattered to them. CE was understood to have a range of purposes, from instrumentally facilitating recruitment and data collection, to advancing community priorities and concerns, to furthering long-term investments in relationships with and changes in communities. These choices about who to engage, what engagement activities to support, how to solicit and integrate community input into the workflow of the study, and what CE was for were often conditioned upon preexisting perceptions and upstream decisions about study goals, competing priorities, and resource availability.Conclusions Upstream choices about CE and constraints of time and resources cascade into tradeoffs that often culminated in “pantomime community engagement.” This approach can create downstream costs when engagement is experienced as improvised and sporadic. Transformations are needed for CE to be seen as a necessary scientific investment and part of the scientific process. (shrink)

Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact sources in recordings (...) from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices. (shrink)

Background Over the last decade, the return of results (ROR) in precision medicine research (PMR) has become increasingly routine. Calls for individual rights to research results have extended the “duty to report” from clinically useful genetic information to traits and ancestry results. ROR has thus been reframed as inherently beneficial to research participants, without a needed focus on who benefits and how. This paper addresses this gap, particularly in the context of PMR aimed at increasing participant diversity, by providing investigator (...) and researcher perspectives on and questions about the assumed value of ROR in PMR.Methods Semi-structured interviews with a purposive sample of investigators and researchers across federally funded PMR studies in three national consortia, as well as observations of study activities, focused on how PM researchers conceptualize diversity and implement inclusive practices across research stages, including navigating ROR.Results Interviewees (1) validated the value of ROR as a benefit of PMR, while others (2) questioned the benefit of clinically actionable results to individuals in the absence of sufficient resources for translating findings into health care for diverse and disadvantaged populations; (3) expressed uncertainties in applying the presumed value of ROR as a benefit for non-clinical results; and (4) and debated when the promise of the value of ROR may undermine trust in PMR, and divert efforts to return value beyond ROR.Conclusions Conceptualizations of diversity and inclusion among PM researchers and investigators raise unique ethical questions where unexamined assumptions of the value of ROR inform study recruitment efforts to enroll minoritized and under-represented populations. A lack of consideration for resources and infrastructure necessary to translate ROR into actionable information may hinder trustworthy community-research relationships. Thus, we argue for a more intentional interrogation of ROR practices as an offer of benefit and for whom. (shrink)

Human cooperation is highly unusual. We live in large groups composed mostly of non-relatives. Evolutionists have proposed a number of explanations for this pattern, including cultural group selection and extensions of more general processes such as reciprocity, kin selection, and multi-level selection acting on genes. Evolutionary processes are consilient; they affect several different empirical domains, such as patterns of behavior and the proximal drivers of that behavior. In this target article, we sketch the evidence from five domains that bear on (...) the explanatory adequacy of cultural group selection and competing hypotheses to explain human cooperation. Does cultural transmission constitute an inheritance system that can evolve in a Darwinian fashion? Are the norms that underpin institutions among the cultural traits so transmitted? Do we observe sufficient variation at the level of groups of considerable size for group selection to be a plausible process? Do human groups compete, and do success and failure in competition depend upon cultural variation? Do we observe adaptations for cooperation in humans that most plausibly arose by cultural group selection? If the answer to one of these questions is “no,” then we must look to other hypotheses. We present evidence, including quantitative evidence, that the answer to all of the questions is “yes” and argue that we must take the cultural group selection hypothesis seriously. If culturally transmitted systems of rules that limit individual deviance organize cooperation in human societies, then it is not clear that any extant alternative to cultural group selection can be a complete explanation. (shrink)

Mathematics word problems provide students with an opportunity to apply what they are learning in their mathematics classes to the world around them. However, students often neglect their knowledge of the world and provide nonsensical responses (e.g., they may answer that a school needs 12.5 buses for a field trip). This study examined if the question design of word problems affects students' mindset in ways that affect subsequent sense‐making. The hypothesis was that rewriting standard word problems to introduce inherent uncertainty (...) about the result would be beneficial to student performance and sense‐making because it requires students to reason explicitly about the context described in the problem. Middle school students (N = 229) were randomly assigned to one of three conditions. In the standard textbook condition, students solved a set of six word problems taken from current textbooks. In the modified yes/no condition, students solved the same six problems rewritten so the solution helped answer a “yes” or “no” question. In the disfluency control condition, students solved the standard problems each rewritten in a variety of fonts to make them look unusual. After solving the six problems in their assigned condition, all students solved the same three “problematic” problems designed to assess sense‐making. Contrary to predictions, results showed that students in the modified yes/no condition solved the fewest problems correctly in their assigned condition problem set. However, consistent with predictions, they subsequently demonstrated more sense‐making on the three problematic problems. Results suggest that standard textbook word problems may be able to be rewritten in ways that mitigate a “senseless” mindset. (shrink)

Recent advances in wireless data transmission technology have the potential to revolutionize clinical neuroscience. Today sensing-capable electrical stimulators, known as “bidirectional devices”, are used to acquire chronic brain activity from humans in natural environments. However, with wireless transmission come potential failures in data transmission, and not all available devices correctly account for missing data or provide precise timing for when data losses occur. Our inability to precisely reconstruct time-domain neural signals makes it difficult to apply subsequent neural signal processing techniques (...) and analyses. Here, our goal was to accurately reconstruct time-domain neural signals impacted by data loss during wireless transmission. Towards this end, we developed a method termed Periodic Estimation of Lost Packets. PELP leverages the highly periodic nature of stimulation artifacts to precisely determine when data losses occur. Using simulated stimulation waveforms added to human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Then, we applied PELP to local field potential recordings collected using an implantable, bidirectional DBS platform operating at various telemetry bandwidths. By effectively accounting for the timing of missing data, PELP enables the analysis of neural time series data collected via wireless transmission—a prerequisite for better understanding the brain-behavior relationships underlying neurological and psychiatric disorders. (shrink)

Biobanks are increasingly being created specifically for research purposes. Concomitantly, we are seeing significant and evolving shifts in research ethics in relation to biobanking. Three discrete shifts are identified in this article. The first extends the ethical focus beyond the protection of human subjects to the promotion of broader community benefits of research utilizing biobanked resources, and an expectation that these benefits will be shared. The second involves the evolution of the traditional consent paradigm for future research uses of biobanks (...) resources that are not in contemplation at the time of donation. The third involves a move away from single project management to more dynamic governance accountability to research participants and the public. These shifts may take different local and institutional forms but share common recognizable elements. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. (...) The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

We describe and report on results of employing a new method for analyzing lay conceptions of intentional and unintentional action. Instead of asking people for their conceptual intuitions with regard to construed scenarios, we asked our participants to come up with their own scenarios and to explain why these are examples of intentional or unintentional actions. By way of content analysis, we extracted contexts and components that people associated with these action types. Our participants associated unintentional actions predominantly with bad (...) outcomes for all persons involved and linked intentional actions more strongly to positive outcomes, especially concerning the agent. People’s conceptions of intentional action seem to involve more aspects than commonly assumed in philosophical models of intentional action that solely stress the importance of intentions, desires, and beliefs. The additional aspects include decisions and thoughts about the action. In addition, we found that the criteria that participants generated for unintentional actions are not a mere inversion of those used in explanations for intentional actions. Associations between involuntariness and unintentional action seem to be stronger than associations between aspects of voluntariness and intentional action. (shrink)

The vestibular system encodes motion and orientation of the head in space and is essential for negotiating in and interacting with the world. Recently, random waveform electric vestibular stimulation has become an increasingly common means of probing the vestibular system. However, many of the methods used to analyze the behavioral response to this type of stimulation assume a linear relationship between frequencies in the stimulus and its associated response. Here we examine this stimulus-response frequency linearity to determine the validity of (...) this assumption. Forty-five university-aged subjects stood on a force-plate for 4 min while receiving vestibular stimulation. To determine the linearity of the stimulus-response relationship we calculated the cross-frequency power coupling between a 0 and 25 Hz bandwidth limited white noise stimulus and induced postural responses, as measured using the horizontal forces acting at the feet. Ultimately, we found that, on average, the postural response to a random stimulus is linear across stimulation frequencies. This result supports the use of analysis methods that depend on the assumption of stimulus-response frequency linearity, such as coherence and gain, which are commonly used to analyze the body’s response to random waveform electric stimuli. (shrink)

Takes some of the most prominent theoretical approaches used in Cultural Studies and demonstrates the ways in which they are used to evaluate, analyse and interpret recent events, debates, topics and texts in contemporary society. N. Anderson, Macquarie University; K. Schlunke, University of Technology, Sydney, Australia.

A robust body of research supports the centrality of K-12 education to health and well-being. Critical perspectives, particularly Critical Race Theory (CRT) and Dis/ability Critical Race Studies (DisCrit), can deepen and widen health justice’s exploration of how and why a range of educational inequities drive health disparities. The CRT approaches of counternarrative storytelling, race consciousness, intersectionality, and praxis can help scholars, researchers, policymakers, and advocates understand the disparate negative health impacts of education law and policy on students of color, students (...) with disabilities, and those with intersecting identities. Critical perspectives focus upon and strengthen the necessary exploration of how structural racism, ableism, and other systemic barriers manifest in education and drive health disparities so that these barriers can be removed. (shrink)

The application of neurostimulation techniques such as deep brain stimulation —often called a brain pacemaker for neurological conditions like Parkinson's disease —has generated “currents of hope.” Building on this hope, there is significant interest in applying neurostimulation to psychiatric disorders such as major depression and obsessive-compulsive disorder. These emerging neurosurgical practices raise a number of important ethical and social questions in matters of resource allocation, informed consent for vulnerable populations, and commercialization of research.

Can sentence comprehension impairments in aphasia be explained by difficulties arising from dependency completion processes in parsing? Two distinct models of dependency completion difficulty are investigated, the Lewis and Vasishth (2005) activation-based model and the direct-access model (DA; McElree, 2000). These models' predictive performance is compared using data from individuals with aphasia (IWAs) and control participants. The data are from a self-paced listening task involving subject and object relative clauses. The relative predictive performance of the models is evaluated using k-fold (...) cross-validation. For both IWAs and controls, the activation-based model furnishes a somewhat better quantitative fit to the data than the DA. Model comparisons using Bayes factors show that, assuming an activation-based model, intermittent deficiencies may be the best explanation for the cause of impairments in IWAs, although slowed syntax and lexical delayed access may also play a role. This is the first computational evaluation of different models of dependency completion using data from impaired and unimpaired individuals. This evaluation develops a systematic approach that can be used to quantitatively compare the predictions of competing models of language processing. (shrink)

Can sentence comprehension impairments in aphasia be explained by difficulties arising from dependency completion processes in parsing? Two distinct models of dependency completion difficulty are investigated, the Lewis and Vasishth (2005) activation‐based model and the direct‐access model (DA; McElree, 2000). These models' predictive performance is compared using data from individuals with aphasia (IWAs) and control participants. The data are from a self‐paced listening task involving subject and object relative clauses. The relative predictive performance of the models is evaluated using k‐fold (...) cross‐validation. For both IWAs and controls, the activation‐based model furnishes a somewhat better quantitative fit to the data than the DA. Model comparisons using Bayes factors show that, assuming an activation‐based model, intermittent deficiencies may be the best explanation for the cause of impairments in IWAs, although slowed syntax and lexical delayed access may also play a role. This is the first computational evaluation of different models of dependency completion using data from impaired and unimpaired individuals. This evaluation develops a systematic approach that can be used to quantitatively compare the predictions of competing models of language processing. (shrink)

Late Mamlūk Military Equipment. By David Nicolle. Travaux et études de la mission archéologique syro-française, Citadelle de Damas, vol. 3. Damascus: Institut Français du Proche-Orient, 2011. Pp. 396. €45.

This book presents a timely reconfiguration of the relations between art, philosophy, ethics, and aesthetics. Through connection with a range of contemporary social and philosophical issues and movements, this collection of essays highlights the imperative of sensorial aesthetics. The book focuses on the radical philosophical approach to aesthetics enabled by the works of Jean-François Lyotard and Gilles Deleuze. From these philosophers an older meaning of aesthetic has been recalled. Before it indicated primarily the theory of art and beauty, “aesthetic” referred (...) to the sensibility, the capacity to receive sensations. In summoning this “sensorial” meaning of aesthetics in their respective works, Lyotard, Deleuze, and other recent thinkers turn the philosophical theory of aesthetics away from the dominance of cognitivist and reception theories, and towards a thinking of aesthetics through considerations of the movements of matter, affect, and sensation. (shrink)

Carnal Knowledge is an outcome of the renewed energy and interest in moving beyond the discursive construction of reality to understand the relationship between what is conceived of as reality and materiality, described as the "material turn." It draws together established and emerging writers, whose research spans dance, music, film, fashion, design, photography, literature, painting and stereo-immersive VR, to demonstrate how art allows us to map the complex relations between nature and culture, between the body, language and knowledge. These writings (...) are unique in the field because they represent the authors' commitment to a new materialism through the creative arts. The questions they address include: Does the material turn in the creative arts take a different turn from continental epistemology, philosophy and the humanities? How does the agency of matter, the material nature of artistic practice and the notion of "truth to materials" affect what we understand as the "new materialism?" In engaging with these questions the book offers perspectives on the emergence of this exciting fresh field of new materialism. (shrink)

Beta‐oxidation of fatty acids and detoxification of reactive oxygen species are generally accepted as being fundamental functions of peroxisomes. Additionally, these pathways might have been the driving force favoring the selection of this compartment during eukaryotic evolution. Here we performed phylogenetic analyses of enzymes involved in beta‐oxidation of fatty acids in Bacteria, Eukaryota, and Archaea. These imply an alpha‐proteobacterial origin for three out of four enzymes. By integrating the enzymes' history into the contrasting models on the origin of eukaryotic cells, (...) we conclude that peroxisomes most likely evolved non‐symbiotically and subsequent to the acquisition of mitochondria in an archaeal host cell. (shrink)