Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Moral emotions are evolved mechanisms that function in part to optimize social relationships. We discuss two moral emotions— disgust and the “cuteness response”—which modulate social-engagement motives in opposite directions, changing the degree to which the eliciting entity is imbued with mental states (i.e., mentalized). Disgust-inducing entities are hypo-mentalized (i.e., dehumanized); cute entities are hyper-mentalized (i.e., “humanized”). This view of cuteness—which challenges the prevailing view that cuteness is a releaser of parental instincts (Lorenz, 1950/1971)—explains (a) the broad range of affiliative behaviors (...) elicited by cuteness, (b) the marketing of cuteness to children (by toy makers and animators) to elicit play, and (c) the apparent ease and frequency with which cute things are anthropomorphized. (shrink)

The neural basis of progress monitoring has received relatively little attention compared to other sub-processes that are involved in goal directed behavior such as motor control and response inhibition. Studies of error-monitoring have identified the dorsal anterior cingulate cortex (dACC) as a structure that is sensitive to conflict detection, and triggers corrective action. However, monitoring goal progress involves monitoring correct as well as erroneous events over a period of time. In the present research, 20 healthy participants underwent fMRI while playing (...) a game that involved monitoring progress towards either a numerical or a visuo-spatial target. The findings confirmed the role of the dACC in detecting situations in which the current state may conflict with the desired state, but also revealed activations in the frontal and parietal regions, pointing to the involvement of processes such as attention and working memory in monitoring progress over time. In addition, activation of the cuneus was associated with monitoring progress towards a specific target presented in the visual modality. This is the first time that activation in this region has been linked to higher-order processing of goal-relevant information, rather than low-level anticipation of visual stimuli. Taken together, these findings identify the neural substrates involved in monitoring progress over time, and how these extend beyond activations observed in conflict and error monitoring. (shrink)

Literacy is an essential skill. Learning to read is a requirement for becoming a self-providing human being. However, while spoken language is acquired naturally with exposure to language without explicit instruction, reading and writing need to be taught explicitly. Decades of research have shown that well-structured teaching of phonological awareness, letter knowledge, and letter-to-sound mapping is crucial in building solid foundations for the acquisition of reading. During the COVID-19 pandemic, children worldwide did not have access to consistent and structured teaching (...) and are, as a consequence, predicted to be behind in the development of their reading skills. Subsequent evidence confirms this prediction. With the best evidence-based practice in mind, we developed an online version of a well-structured early literacy training program for 5-year-old children. This 2-week online Reading Camp program is designed for pre-K children. It incorporates critical components of the fundamental skills essential to learning to read and is taught online in an interactive, multi-sensory, and peer-learning environment. We measure the participants’ literacy skills and other related skills before and after participating in the online Reading Camp and compare the results to no-treatment controls. Results show that children who participated in the online Reading Camp improved significantly on all parameters in relation to controls. Our results demonstrate that a well-structured evidence-based reading instruction program, even if online and short-term, benefits 5-year-old children in learning to read. With the potential to scale up this online program, the evidence presented here, alongside previous evidence for the efficacy of the in-person program, indicates that the online Reading Camp program is effective and can be used to tackle a variety of questions regarding structural and functional plasticity in the early stages of reading acquisition. (shrink)

This is a field-based disguised case which describes a dilemma faced by the protagonists; do they continue to do business with a land developer who has assisted them in the past when now the developer chooses to, against their recommendations, also do business with their ex-business partner? The problem for the characters in question is whether or not to work on a project that will yield them a net profit of $4 million dollars given the fact it would require them (...) to work in the same development as their former business associate. The central characters are afraid that their ex-partner will be a destabilizing factor in the development of the project and that their work sites will be in jeopardy of being vandalized. Several factors complicate this situation including: the developer’s desire for a quick land purchase, the developer’s changing the discount rate from 20% to 10% perhaps based upon difficulties that surrounded the first land deal, the protagonists’ plans to build their own homes in this new development, and the negative relationship between the protagonists and the ex-business partner. The case has a difficulty level appropriate for a sophomore or junior level course. The case is designed to be taught in one class period and is expected to require between three to five hours of outside preparation by students. (shrink)

The COVID-19 pandemic laid bare systemic inequities shaped by social determinants of health (SDoH). Public health agencies, legislators, health systems, and community organizations took notice, and there is currently unprecedented interest in identifying and implementing programs to address SDoH. This special issue focuses on the role of medical-legal partnerships (MLPs) in addressing SDoH and racial and social inequities, as well as the need to support these efforts with evidence-based research, data, and meaningful partnerships and funding.

ABSTRACTFeelings and cognitions influence judgment through attribution. For instance, the attribution of positive feelings and cognitions to a stimulus leads to a positive judgment of that stimulus. We examined whether misattribution is moderated by the applicability of a distractor to the judgment question. For instance, when are people more likely to attribute to a target person the affective and cognitive experiences triggered by a kitten – when trying to judge the person’s cuteness or trustworthiness? The kitten triggers experiences specifically relevant (...) to cuteness, but people might more easily suspect the kitten’s potential influence when judging cuteness rather than trustworthiness. Using the Affect Misattribution Procedure, we found that applicability increases the effect of misattribution on valenced judgments. The results emphasise the importance of specific information in attribution and suggest that high applicability of distractors to the judgment question d... (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

La monnaie symbolise la valeur, le souverain, ou le Peuple, bref la Totalité. Mais quelle fonction a cette symbolisation? Au plus strict, la fonction symbolique de la monnaie c’est de quantifier. Or la quantification est déjà épaisse de nombreux problèmes philosophiques. Alors, le propos tentera ici de montrer une problématisation foucaldienne de la fonction symbolique de la monnaie, en termes de pouvoir-savoir. Car la considération de la fonction symbolique de la monnaie ouvre, au niveau théorique, le problème de l’articulation de (...) la valeur (intensive) à sa manifestation (extensive), et au niveau épistémologique, un problème d’objectivation de l’objectivation, un problème réflexif de valeur de vérité des jugements de valeurs (bulle spéculative). (shrink)

RésuméL'authenticité et la diversité font aujourd'hui figure de slogans dans les sociétés contemporaines de part et d'autre de l'Atlantique nord. En revanche, on a peu exploré les liens entre ces deux idées. À cette fin, cet article aborde les écrits tantôt convergents, tantôt divergents de Charles Taylor et Martin Heidegger pour prolonger leurs réflexions respectives sur l'authenticité et montrer en quoi elles peuvent servir defondement à une nouvelle forme de diversité culturelle. Pour tous deux, l'être-au-monde authentique nous permet d'accider au (...) tréfonds du matériel culturel dont nous devons disposer pour que se nouent des rapports fructueux avec les autres cultures. (shrink)

If there is to be any progress in the debate about what sort of positive moral status Kant can give the emotions, we need a taxonomy of the terms Kant uses for these concepts. It used to be thought that Kant had little room for emotions in his ethics. In the past three decades, Marcia Baron, Paul Guyer, Barbara Herman, Nancy Sherman, Allen Wood and others have argued otherwise. Contrary to what a cursory reading of the Groundwork may indicate, (...) Kant thinks the emotions play an important role in the moral life. I want to extend the work of Baron, Guyer, Herman, Sherman and Wood in three ways. First, I will set out in a diagram Kant's taxonomy of feelings and emotions. Agreement on such a taxonomy should make it easier to evaluate debates about Kant and the emotions. Second, I will focus on a certain subclass of emotions – reason-caused affects – that have previously received little attention, even from these Kant scholars. Third, these scholars base much of their defence of Kant on his later works – especially the Metaphysics of Morals and the Anthropology – but Kant's fairly rich taxonomy of the emotions, including reason-caused affects, is clearly in place at least as early as the Critique of Judgment . I believe that the Critique of Judgment is an importantly ignored resource for understanding the moral role of the emotions for Kant. The third Critique makes positive, philosophically interesting claims about the emotions and morality. Kant emphasizes certain roles for emotions in this work that he develops to the same extent nowhere else. Nevertheless, the Critique of Judgment goes all but unmentioned by many who write on these issues. In what follows, I will defend as many of my claims as possible using the third Critique. (shrink)

John McDowell’s ethical writings interpret ethical experience as intentional, socially-conditioned, virtuous responsiveness to situations and develop a modest account of practical rationality. His work converges with investigations of ethical experience by recent Kant scholars (Sherman, Brewer, Herman) and Emmanuel Levinas. The Kantian interpreters and Levinas locate the categorical demands of ethical experience in rational agents’ demands for respect, while McDowell finds it in noble adherence to the demands of virtuous living. For McDowell, moral-practical rational efforts to justify ethics cannot (...) transcend one’s form of life and are motivated by desires to coerce others under a veneer of rationality or an unnecessary modern anxiety to protect community beliefs. He overlooks how such justifications can be motivated by a desire to give an account of one’s beliefs out of responsibility to others different from oneself, a responsibility elicited by others in ethical experience as depicted by the Kantian interpreters and Levinas. (shrink)

We present a population density and moment-based description of the stochastic dynamics of domain $${\text{Ca}}^{2+}$$ -mediated inactivation of L-type $${\text{Ca}}^{2+}$$ channels. Our approach accounts for the effect of heterogeneity of local $${\text{Ca}}^{2+}$$ signals on whole cell $${\text{Ca}}^{2+}$$ currents; however, in contrast with prior work, e.g., Sherman et al. :985–995, 1990), we do not assume that $${\text{Ca}}^{2+}$$ domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain (...) model of an L-type $${\text{Ca}}^{2+}$$ channel introduced by Greenstein and Winslow :2918–2945, 2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell $${\text{Ca}}^{2+}$$ current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of $${\text{Ca}}^{2+}$$ inactivation that may occur via slow heterogeneous domain [ $${\text{Ca}}^{2+}$$ ]. Next, we find that when channel permeability is held constant, $${\text{Ca}}^{2+}$$ -mediated inactivation of L-type channels increases as the domain time constant increases, because a slow domain collapse rate leads to increased mean domain [ $${\text{Ca}}^{2+}$$ ] near open channels; conversely, when the maximum domain [ $${\text{Ca}}^{2+}$$ ] is held constant, inactivation decreases as the domain time constant increases. Comparison of simulation results using population densities and moment equations confirms the computational efficiency of the moment-based approach, and enables the validation of two distinct methods of truncating and closing the open system of moment equations. In general, a slow domain time constant requires higher order moment truncation for agreement between moment-based and population density simulations. (shrink)

Inside What Would Plato Do?, you'll find the basics of philosophy, written in an easy, digestible way we can all understand, along with questions to help you apply these important theories to your own life. So, after you've learned about a philosophical concept, you'll then be challenged to test yourself and see how the results can impact your daily life. For instance, after learning about Kant's theory of morality and the importance of intention you're challenged with questions like: Can good (...) people do bad things? Was there a time when you intended to do something helpful that ended up being hurtful? Does that make you a good person (because you intended to do good) or a bad person (because the results were bad)? What Would Plato Do? will not only help you better understand some of the greatest thinkers ever but will also help you think of the world around you in a whole new way! (shrink)

We perceive smells as perduring complex entities within a distal array that might be conceived of as smellscapes. However, the philosophical orthodoxy of Odor Theories has been to deny that smells are perceived as having a distal location. Recent challenges have been mounted to Odor Theories’ veracity in handling the timescale of olfactory perception, how it individuates odors as a distal entities, and their claim that olfactory perception is not spatial. The paper does not aim to dispute these criticisms. Rather, (...) what will be shown is that Molecular Structure Theory, a refinement of Odor Theory, can be further developed to handle these challenges. The theory is further refined by focusing on distal perception that requires considering the perceptual object as mereologically complex persisting odor against a background scene conceived of as a smellscape. What will be offered is an expansion of Molecular Structure Theory to account for distal smell perception within natural environments. (shrink)

When it originated in the late 19th century, psychometrics was a field with both a scientific and a social mission: psychometrics provided new methods for research into individual differences, and at the same time, these psychometric instruments were considered a means to create a new social order. In contrast, contemporary psychometrics - due to its highly technical nature and its limited involvement in substantive psychological research - has created the impression of being a value-free discipline. In this article, we develop (...) a contrasting characterization of contemporary psychometrics as a value-laden discipline. We expose four such values: that individual differences are quantitative (rather than qualitative), that measurement should be objective in a specific sense, that test items should be fair, and that utility of a model is more important than its truth. Our goal is not to criticize psychometrics for employing these values, but rather to bring them into the open and to show that these values are not inevitable and are in need of systematic evaluation. (shrink)

We are immersed within an odorous sea of chemical currents that we parse into individual odors with complex structures. Odors have been posited as determined by the structural relation between the molecules that compose the chemical compounds and their interactions with the receptor site. But, naturally occurring smells are parsed from gaseous odor plumes. To give a comprehensive account of the nature of odors the chemosciences must account for these large distributed entities as well. We offer a focused review of (...) what is known about the perception of odor plumes for olfactory navigation and tracking, which we then connect to what is known about the role odorants play as properties of the plume in determining odor identity with respect to odor quality. We end by motivating our central claim that more research needs to be conducted on the role that odorants play within the odor plume in determining odor identity. (shrink)