Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers “coming back to life” upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. However, some desiccation tolerant organisms do not produce this sugar, hinting that additional mediators, and potentially novel mechanisms exist. It has become apparent that (...) a common theme among such organisms is the production and use of intrinsically disordered proteins to mediate survival in this dry state. However, the basic biology of these proteins – which unlike globular proteins lack persistent three-dimensional structure – is poorly understood, as are the functional mechanisms utilized by these enigmatic proteins that allow them to mediate desiccation tolerance. We purpose that probing the biochemical and biophysical nature of stress-related IDPs will provide mechanistic insights into these fascinating proteins. Remarkably, organisms from every kingdom of life can survive losing nearly all their intracellular water. A hallmark of desiccation tolerance is the use of intrinsically disordered proteins, but how IDPs contribute to tolerance is poorly understood. Here, we discuss possible mechanisms and avenues for studying these enigmatic proteins. (shrink)

Generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry about everyday life. Prior neuroimaging studies have demonstrated that GAD is associated with disruptions in specific brain regions; however, little is known about the global functional connectivity maps in adolescents with GAD. Here, first-episode, medication-naive, adolescent GAD patients ( N = 36) and healthy controls ( N = 28) (HCs) underwent resting-state functional MRI (R-fMRI) and completed a package of questionnaires to assess clinical symptoms. Functional connectivity strength and seed-based (...) functional connectivity were employed to investigate the functional connectivity architecture. GAD patients showed reduced functional connectivity strength in right supramarginal gyrus (SMG) and right superior parietal gyrus (SPG) compared with HCs. Further seed-based functional connectivity analysis revealed that GAD patients displayed decreased functional connectivity between right SMG and left fusiform gyrus, inferior temporal gyrus, parahippocampal gyrus, bilateral precuneus and cuneus, and between right SPG and bilateral supplementary motor area and middle cingulate gyrus, as well as between the SMG-based network and the SPG-based network. Moreover, the disrupted intra-network connectivity (i.e., the SMG-based network and the SPG-based network) and inter-network connectivity between the SMG-based network and the SPG-based network accounted for 25.5% variance of the State and Trait Anxiety Inventory (STAI) and 39.5% variance of the trait subscale of STAI. Our findings highlight the abnormal functional architecture in the SMG-based network and the SPG-based network in GAD, providing novel insights into the pathological mechanisms of this disorder. (shrink)

Objectives: Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state.Methods: A total of 42 unaffected parents of ASD children (pASD) and 39 age-, sex-, (...) and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well.Results: ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD (ρ1 = 0.298, P1 = 0.007; ρ2 = 0.220, P2 = 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ3 = −0.334, P3 = 0.002).Conclusion: rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents. (shrink)

Protein–protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein–protein recognition mechanism, mediated by disordered regions longer than 20–30 residues. Bioinformatics predictions and well‐characterized examples, such as the kinase‐inhibitory domain of Cdk inhibitors and the Wiskott–Aldrich syndrome protein (...) (WASP)‐homology domain 2 of actin‐binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains. (shrink)

This chapter highlights the complexity of the relationship between enhancement of mood and cognition on the one hand and the improvement of people's well‐being on the other. To do so, two psychiatric conditions, Asperger's syndrome and bipolar disorder, are presented in the chapter. Even though there are both negative and positive aspects to Asperger's syndrome or to bipolar disorders, taking away even these negative aspects would not necessarily promote well‐being. It might also be impossible to isolate the positive aspects of (...) these disorders. An increase in specific forms of cognition might be intrinsically connected to a decrease in specific aspects of mood. A decrease in specific aspects of mood might be intrinsically connected to an increase in creativity. Neither is necessarily linked to any changes in some general form of “well‐being.”. (shrink)

The rare phenomenon in which a person desires amputation of a healthy limb, now often termed body integrity identity disorder, raises central questions for biomedical ethics. Standard bioethical discussions of surgical intervention in such cases fail to address the meaning of bodily integrity, which is intrinsic to a theological understanding of the goodness of the body. However, moral theological responses are liable to assume that such interventions necessarily represent an implicitly docetic manipulation of the body. Through detailed attention to the (...) ethics of mutilation and of surgery for psychiatric disorders, this article explores the theological and ethical significance of the body for human identity. (shrink)

Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the ‘‘extrinsic’’ system); and (...) (ii) a system of inward-oriented networks (the ‘‘intrinsic’’ or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected — associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor ‘‘absorption’’ or ‘‘lost self.’’ In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during ‘‘resting state’’ fMRI acquisitions.. (shrink)

N‐type inactivation of potassium channels is controlled by cytosolic loops that are intrinsically disordered. Recent experiments have shown that the mechanism of N‐type inactivation through disordered regions can be stereospecific and vary depending on the channel type. Variations in mechanism occur despite shared coarse grain features such as the length and amino acid compositions of the cytosolic disordered regions. We have adapted a phenomenological model designed to explain how specificity in molecular recognition is achieved through (...) class='Hi'>disordered regions. We propose that the channel‐specific observations for N‐type inactivation represent distinct mechanistic choices for achieving function through conformational selection versus induced fit. It follows that the dominant mechanism for binding and specificity can be modulated through subtle changes in the amino acid sequences of disordered regions, which is interesting given that specificity in function is realized in the absence of autonomous folding. (shrink)

Just fifteen years ago, the common non-religious consensus was that homosexual acts were immoral. Within one decade, however, this consensus waned. The secular majority no longer held, as they previously did, that such actions are morally bad. What explains this sudden change? One explanation is that many conservatives lacked adequate philosophical tools to explain the foundations of the earlier historical consensus. Another is that modern research has shown that there never existed any solid philosophical grounds for calling such actions immoral (...) in the first place. This book questions the latter narrative; for prior to this book no exhaustive historical treatment of philosophical thought on the moral question of homosexual acts existed. Both liberals and conservatives failed to research adequately the long history of thought on this issue. The current author not only argues that the earlier non-religious philosophical consensus has largely been ignored, but that the proliferation of arguments in favor of acting on homosexual inclinations reveal a strong desire to justify what isn't possible to justify morally. The non-religious arguments of the great philosopher Thomas Aquinas are then examined; they reveal that his reasoning can soundly show that acting on homosexual inclinations is morally wrong, and also that the same argument rightly entails that every untruthful assertive speech act is morally problematic. If conservatives wish to be consistent, they ought to reject lying too. And if liberals expect conservatives to believe that what they preach is true, then they ought to stand with Aquinas and reject all lying as intrinsically evil. (shrink)

Background: Although previous studies have shown an inverse relation between life meaning and eating disorder symptoms, the correlational nature of this evidence precludes causal inferences. Therefore, this study used an experimental approach to test the causal impact of life meaning on individuals' weight and shape concerns.Methods: Female students at risk for developing an eating disorder were randomly assigned to the control or the meaning condition, which involved thinking about and committing to pursue intrinsically valued life goals. A color-naming interference (...) task was used to assess the motivational salience of body-related stimuli, and self-report measures were used to assess participants' overvaluation of weight and shape.Results: The meaning manipulation was effective in activating intrinsically valued life goals. However, it did not result in lower self-reported overvaluation of weight and shape or lower color-naming interference effects of body-related stimuli, compared to the control condition. Post-hoc analyses suggested that baseline meaning in life was related to the impact of the manipulation.Conclusions: This experimental study did not provide evidence for a causal influence of life meaning on the overvaluation of weight and shape in a high-risk group. The current findings suggest that we first need to examine the relationship between life meaning and eating disorder symptoms in more detail, before implementing brief meaning manipulations in clinical practice. (shrink)

The phenomenology of inner temporalizing developed by Edmund Husserl provides a helpful framework for understanding a type of experiencing that can be part of the Post-Traumatic Stress Disorder (PTSD). My paper extrapolates hints from Husserl's work in order to describe those memories — flashbacks — that come so strongly to consciousness as to overtake the experiencer. Husserl's work offers several clues: his view of inner temporalization by which conscious experiences flow in both a serial and a nonserial manner; a characterization (...) of process memory as distinct from representational memory; and the notion of telos, which takes human subjectivity as intrinsically changeable, for example, by means of a retroactive cancellation that would allow the PTSD experiencer to re-process the original meaning of the traumatic experience into a meaning that fits the current situation and thus allows a recovery. (shrink)

Awareness of internal bodily sensations and its connection to complex socioemotional abilities like empathy has been postulated, yet the functional neural circuitry they share remains poorly understood. The present fMRI study employs independent component analysis to investigate which empathy facet shares resting-state functional connectivity and/or BOLD variability with IA. Healthy participants viewed an abstract nonsocial movie demonstrated to evoke strong rsFC in brain networks resembling rest, and resultant rsFC and rsBOLD data were correlated with self-reported empathy and IA questionnaires. We (...) demonstrate a bidirectional behavioral and neurobiological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA share both rsFC and rsBOLD, while Cognitive empathy and IA only share rsBOLD. Specifically, increased rsFC in the right inferior frontal operculum of a larger attention network was associated with increased vicarious experience but decreased awareness of inner body sensations. Furthermore, increased rsBOLD between brain regions of an interoceptive network was related to increased sensitivity to internal sensations along with decreased Affective empathy. Finally, increased rsBOLD between brain regions subserving a mentalizing network related to not only an improved ability to take someone’s perspective, but also a better sense of mind-body interconnectedness. Overall, these findings suggest that the awareness of one’s own internal body changes is related to the socioemotional ability of feeling and understanding another’s emotional state and critically, that this relationship is reflected in the brain’s resting state neuroarchitecture. Methodologically, this work highlights the importance of utilizing rsBOLD as a complementary window alongside rsFC to better understand neurological phenomena. Our results may be beneficial in aiding diagnosis in clinical populations such as autism spectrum disorder, where participants may be unable to complete tasks or questionnaires due to the severity of their symptoms. (shrink)

Protein misfolding is a topic that is of primary interest both in biology and medicine because of its impact on fundamental processes and disease. In this review, we revisit the concept of protein misfolding and discuss how the field has evolved from the study of globular folded proteins to focusing mainly on intrinsically unstructured and often disordered regions. We argue that this shift of paradigm reflects the more recent realisation that misfolding may not only be an adverse event, (...) as originally considered, but also may fulfil a basic biological need to compartmentalise the cell with transient reversible granules. We nevertheless provide examples in which structure is an important component of a much more complex aggregation behaviour that involves both structured and unstructured regions of a protein. We thus suggest that a more comprehensive evaluation of the mechanisms that lead to aggregation might be necessary. (shrink)

Recent advances in the neuroscience of episodic memory provide a framework to integrate object relations theory, a psychoanalytic model of mind development, with potential neural mechanisms. Object relations are primordial cognitive-affective units of the mind derived from survival- and safety-level experiences with caretakers during phase-sensitive periods of infancy and toddlerhood. Because these are learning experiences, their neural substrate likely involves memory, here affect-enhanced episodic memory. Inaugural object relations are encoded by the hippocampus-amygdala synaptic plasticity, and systems-consolidated by medial prefrontal cortex (...) (mPFC). Self- and object-mental representations, extracted from these early experiences, are at first dichotomized by contradictory affects evoked by frustrating and rewarding interactions (“partial object relations”). Such affective dichotomization appears to be genetically hardwired the amygdala. Intrinsic propensity of mPFC to form schematic frameworks for episodic memories may pilot non-conscious integration of dichotomized mental representations in neonates and infants. With the emergence of working memory in toddlers, an activated self- and object-representation of a particular valence can be juxtaposed with its memorized opposites creating a balanced cognitive-affective frame (conscious “integration of object relations”). Specific events of object relations are forgotten but nevertheless profoundly influence the mental future of the individual, acting (i) as implicit schema-affect templates that regulate attentional priorities, relevance, and preferential assimilation of new information based on past experience, and (ii) as basic units of experience that are, under normal circumstances, integrated as attractors or “focal points” for interactive self-organization of functional brain networks that underlie the mind. A failure to achieve integrated object relations is predictive of poor adult emotional and social outcomes, including personality disorder. Cognitive, cellular-, and systems-neuroscience of episodic memory appear to support key postulates of object relations theory and help elucidate neural mechanisms of psychodynamic psychotherapy. Derived through the dual prism of psychoanalysis and neuroscience, the gained insights may offer new directions to enhance mental health and improve treatment of multiple forms of psychopathology. (shrink)

Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our consensus domain dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1,695 folds in the CDD as being non‐autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, (...) the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predictions suggest that 40% of proteins have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. (shrink)

Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related to (...) local protein flexibility and disorder, large‐scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution. (shrink)

Work Integration Social Enterprises (WISE) are a means of redressing injustices that People With Mental Illness and/or Intellectual Disability (PWMI/ID) face in the labor market. As the field’s understanding of WISE improves, many have argued for the need to study their underlying philosophies and ethical foundations. We present a case study of a WISE for PWMI/ID that responds to a humanistic-personalist framework. This framework is based on the consideration of several features of the person: their wholeness, uniqueness, intrinsic dignity, innate (...) rights, and capacity for permanent development. Under this perspective, human work entails dignity because it is a potential source of meaning and personal growth. The humanistic-personalist framework is more comprehensive than other approaches presented in the literature, based on justice and human rights or care ethics, thereby advancing our knowledge of how WISE may provide economically viable and meaningful work experiences to underserved communities. Drawing from this humanistic-personalist perspective, we provide six criteria that can serve as a normative framework for organizations, particularly WISE for PWMI/ID. The case study focuses on La Fageda, a 40-year-old Spanish WISE that has achieved significant social and economic success. La Fageda is based on a sound understanding of the human person. From its foundations and practices, three pillars are identified: the rehabilitating power of work, the practice of designing individual itineraries, and the pursuit of economic success as a means to social success, which is the project’s mission. (shrink)

Targeted gene alteration (TGA) is a strategy for correcting single base mutations in the DNA of human cells that cause inherited disorders. TGA aims to reverse a phenotype by repairing the mutant base within the chromosome itself, avoiding the introduction of exogenous genes. The process of how to accurately repair a genetic mutation is elucidated through the use of single‐stranded DNA oligonucleotides (ODNs) that can enter the cell and migrate to the nucleus. These specifically designed ODNs hybridize to the target (...) sequence and act as a beacon for nucleotide exchange. The key to this reaction is the frequency with which the base is corrected; this will determine whether the approach becomes clinically relevant or not. Over the course of the last five years, workers have been uncovering the role played by the cells in regulating the gene repair process. In this essay, we discuss how the impact of the cell on TGA has evolved through the years and illustrate ways that inherent cellular pathways could be used to enhance TGA activity. We also describe the cost to cell metabolism and survival when certain processes are altered to achieve a higher frequency of repair. (shrink)

Cis‐regulatory elements govern gene expression programs to determine cell identity during development. Recently, the possibility that multiple enhancers are orchestrated in clusters of enhancers has been suggested. How these elements are arranged in the 3D space to control the activation of a specific promoter remains unclear. Our recent work revealed that the TGFβ pathway drives the assembly of enhancer clusters and precise gene activation during neurogenesis. We discovered that the TGFβ pathway coactivator JMJD3 was essential in maintaining these structures in (...) the 3D space. To do that, JMJD3 required an intrinsically disordered region involved in forming phase‐separated biomolecular condensates found in the enhancer clusters. Our data support the existence of a relationship between 3D‐conformation of the chromatin, biomolecular condensates, and TGFβ‐driven response during mammalian neurogenesis. In this review, we discuss how signaling (TGFβ), epigenetics (JMJD3), and biochemical properties (biomolecular condensates nucleation) are coordinated to modulate the genome structure to guarantee proper neural development. Moreover, we comment on the potential underlying mechanisms and implications of the enhancer‐mediated regulation. Finally, we point out the knowledge gaps that still need to be addressed. (shrink)

Fission of cellular membranes is ubiquitous and essential for life. Complex protein machineries, such as the dynamin and ESCRT spirals, have evolved to mediate membrane fission during diverse cellular processes, for example, vesicle budding. A new study suggests that non-specialized membrane-bound proteins can induce membrane fission through mass action due to protein crowding. Because up to 2/3 of the mass of cellular membranes is contributed by proteins, membrane protein crowding is an important physiological parameter. Considering the complexity of membrane shape (...) transitions during a fission reaction, spatial and temporal variability in protein distribution, and the abundance of intrinsically disordered regions in proteins on an invaginating membrane, protein crowding can have diverse consequences for fission in the cell. The question is, how and to what extent this mechanism combines with the action of dedicated fission machineries. Membrane fission, which is required for formation of vesicles or cytokinesis, can be carried out by specialized proteins like dynamin and the ESCRT complex. Recent work suggests that fission of cellular membranes, which are densely packed with proteins, can also be induced by protein crowding due to high entropic tension. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The 2007 Meeting of the Society for Buddhist-Christian StudiesSan Diego, California, November 16–17, 2007Peter A. HuffThe Society for Buddhist-Christian Studies sponsored two sessions in conjunction with the 2007 annual meeting of the American Academy of Religion (AAR). Each session highlighted themes related to the work of a major figure in Buddhist-Christian dialogue. The first session, addressing the topic “Homosexuality, the Church, and the Sangha,” was organized in honor of (...) Roger Corless (1938–2007), longtime member of the society, dual practitioner of Roman Catholicism and Vajrayana Buddhism, and a well-known voice for “queer sangha.” The second session, a panel discussion titled “The Thought and Legacy of Masao Abe,” focused on the career achievements of Abe (1915–2006), widely acknowledged as one of the most innovative and influential scholars in modern Zen studies, interreligious dialogue, and comparative philosophy.The first session, moderated by Harry Wells (Humboldt State University), featured three papers on issues of gender, sexual ethics, and religious identity. Robert Fastiggi, professor of systematic theology at Sacred Heart Major Seminary (Detroit), presented the paper “The Catholic Church and Homosexuality.” Arguing that the Catholic tradition avoids an “either/or” approach to homosexuality, he outlined the church’s official distinction between morally neutral homoerotic identity and what Vatican documents call “intrinsically disordered” homosexual acts. He also noted that Catholic researchers differ significantly on the question of the genetic origins of same-sex attraction. The key to Catholic moral teaching on homosexuality, he explained, is a “theology of the body” that envisions male-female complementarity as the divinely ordained pattern of creation. Fastiggi suggested that further discussion of related ideas such as celibacy, chastity, desire, and concupiscence would enhance future Buddhist-Christian dialogue on homosexuality.Ilene Stanford, a ThD candidate in religion, gender, and culture at Harvard University, presented the next paper, “In or Out? Marriage as a Social Practice.” Describing marriage in the United States as a “site of contestation,” she explored the conflicting [End Page 137] models of sexual union that currently inform public debates in political and ecclesiastical contexts. Using William Johnson’s A Time to Embrace: Same-Gender Relationships in Religion, Law, and Politics (2006) as a point of departure, she argued that many contemporary examinations of sexual relationships, even some of the most inclusive, fail to reckon with the way in which the West’s Augustinian legacy continues to make heterosexual marriage the norm for all moral reflection on sexual identity and expression. The escalating controversy in the international Anglican community, she said, exposes the weaknesses of Johnson’s “deliberative democracy” model and other theoretical models that minimize the role of political and social power in the construction of sexual ideals.José Ignacio Cabezón, who holds the XIV Dalai Lama Chair in Tibetan Buddhism at the University of California, Santa Barbara, presented the final paper: “Is Homosexual Sex ‘Sexual Misconduct’? Critical Reflections on Some Classical Indo-Tibetan Sources.” Analyzing the changing portraits of sexual immorality in the Pali canon, Indian Sanskrit texts, and Tibetan scholastic treatises, Cabezón traced the evolution of monastic commentary on lay sexuality over the course of several centuries. What originated primarily as a simple prohibition against some forms of male adulterous activity, he explained, eventually became an unprecedented attempt to regulate intricate details of sexual behavior. Identifying Ansanga (fourth century ce) as the first Buddhist writer to proscribe same-sex activity between men, Cabezón suggested that changing social mores, intra-Buddhist debates, and the fertile monastic imagination contributed to the gradual elaboration of moral teaching in ancient and classical Buddhist literature.After the paper presentations, Richard Reilly, professor of philosophy at St. Bonaventure University, responded with provocative comments. He raised critical points about the significance of the distinction between sexual acts and erotic relationships, the strategic though limited value of “deliberative democracy” in multicultural faith communities, and the need for more rigorous comparative study of homophobic legislation in Buddhist and Abrahamic religious traditions. Sparking an engaging discussion among presenters and members of the audience, Reilly’s remarks underscored the importance of ongoing interdisciplinary investigations into homosexuality, the church, and the sangha.The society’s second session at the AAR provided a venue for former... (shrink)

Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the (...) formation and dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI‐dependent transport on to the cis‐Golgi. The mechanisms underlying formation and (...) maintenance of ERGIC membranes are poorly defined. However, recent evidence suggests an important role for Trk‐fused gene (TFG) in regulating the integrity of the ER/ERGIC interface. Moreover, in the absence of cytoskeletal elements to scaffold tracks on which COPII carriers might move, TFG appears to promote anterograde cargo transport by locally tethering COPII carriers adjacent to ERGIC membranes. This action, regulated in part by the intrinsically disordered domain of TFG, provides sufficient time for COPII coat disassembly prior to heterotypic membrane fusion and cargo delivery to the ERGIC. -/- . (shrink)

Changes in the abundance of protein and RNA molecules can impair the formation of complexes in the cell leading to toxicity and death. Here we exploit the information contained in protein, RNA and DNA interaction networks to provide a comprehensive view of the regulation layers controlling the concentration‐dependent formation of assemblies in the cell. We present the emerging concept that RNAs can act as scaffolds to promote the formation ribonucleoprotein complexes and coordinate the post‐transcriptional layer of gene regulation. We describe (...) the structural and interaction network properties that characterize the ability of protein and RNA molecules to interact and phase separate in liquid‐like compartments. Finally, we show that presence of structurally disordered regions in proteins correlate with the propensity to undergo liquid‐to‐solid phase transitions and cause human diseases. Also see the video abstract here https://youtu.be/kfpqibsNfS0. (shrink)

Following new scientific evidence, removal of the fallopian tubes or the ovaries, or both, are options for reducing the risk of ovarian cancer. This paper examines the new scientific evidence on the origin of ovarian cancer and argues that the removal of fallopian tubes or ovaries in high-risk patients for the purpose of reducing risk of cancer is not intrinsically disordered. Although a present and serious pathology may not exist, this removal constitutes an indirect sterilization, because the immediate (...) and primary effect is the reduction in risk of a pathological condition. This effect occurs immediately, directly, and effectively, and sterilization is a secondary effect. The paper then reflects on the subsequent inadequacy of the language of “present and serious pathology” given the new evidence on ovarian cancer. National Catholic Bioethics Quarterly 14.1 : 67–79. (shrink)

In Genesis 27 Jacob is depicted as lying to Isaac. Jacob, however, was held in Christian tradition to be both a moral exemplar and to be speaking prophetically in this episode with his father. This raises the question of how Doctors of the Church such as St. Augustine and St. Thomas Aquinas were able reconcile these interpretive commitments with their stance on the intrinsically disordered nature of lying. In examining their resolution of this tension, we discover an important (...) exegetical distinction for interpreting troubling words as nevertheless being divinely inspired. Yet, it is only in light of another interpretive distinction, recently highlighted by Nicholas Lombardo OP, that we can both hold to the inspired nature of Jacob's words and also a natural reading of the account in Genesis 27. The detailed examination of Genesis 27 by both Augustine and Aquinas is an important case study for understanding how we can interpret troubling language as still being the word of God. This undertaking, spanning centuries between Augustine and Aquinas, is now taken one step further thanks to the exegetical proposal of Fr. Lombardo. (shrink)

Se realiza un análisis crítico de la denominada ¿sociedad del conocimiento¿ al objeto de mostrar de qué modo el Espacio Europeo de Educación Superior constituye la culminación paradójica de dicha sociedad. La "sociedad del conocimiento" comienza a fraguar en el momento en el que las tecnologías, progresivamente especializadas y desprendidas del posible control científico básico de sus consecuencias, comienzan a hacer posible un proceso de optimización económica entre la inversión y la rentabilidad productiva que resulta realimentado a su vez por (...) un consumo tendencialmente imparable. Dicho proceso requiere en principio promover el mapa sociológico que provea el soporte educativo para un mercado de trabajo acorde con dicha sociedad económico-tecnológicamente optimizada y consumista. Pero debido a la dinámica consumista tendencialmente imparable sobre la que gira todo este proceso, las relaciones entre la oferta y la demanda del mercado de consumo, y con ellas las exigencias del mercado de trabajo, comenzarán a tornarse previsiblemente aleatorias o imprevisibles, lo cual demandará la creación del correspondiente soporte educativo que genere un nuevo tipo de profesional máxima e indefinidamente versátil. Ésta sería la necesidad a la que pretende responder básicamente el proyecto del EEES, el cual se verá envuelto de este modo en la tarea paradójica de intentar gobernar lo ingobernable, o sea lo previsiblemente imprevisible. A su vez, dicho proceso de suyo desordenado se verá sometido, por efecto de la intervención pedagógica, a una dinámica incesante de reproducción ampliada por realimentación negativa que cumplirá la singular función de sostener en marcha lo que en realidad no conduce a ningún sitio. We carry out a critical analysis of the so-called "knowledge society" in order to show in what way the European Space for Higher Education constitutes the paradoxical culmination of this society. The "knowledge society" begins to solidify when the technologies, progressively specialized and separated from the possible basic scientific control of their consequences, begin to make possible a process of economic optimization between the investment and the productive profitability that is in turn feedbacked for a consumption increasingly unstoppable. This process requires in principle to promote the sociological map that provides the educational... support for a labor market in agreement with this economic-technologically optimized and full of consumerism society. But due to the increasingly unstoppable dynamics of consumerism which is the axis of rotation of all this process, the relationships between supply and demand within the consumption market, and with them the requirements of the labor market, will begin foreseeably to become random or unforeseeable, which will requires the creation of the corresponding educational support that generates a new type of maximum and indefinitely versatile professional. This one would be the necessity to which the project of the ESHE seeks basically to respond, but this project will thus be wrapped in the paradoxical task of trying to govern that which is ungovernable, that is to say that which is foreseeably unforeseeable. In turn, this process intrinsically disordered will be subjected, for effect of the pedagogic intervention, to an incessant dynamics of enlarged reproduction by negative feedback that will complete the singular function of sustaining in progress that which in fact do not take to any place. (shrink)

Psychopaths are often regarded as a scourge of contemporary society and, as such, are the focus of much public vilification and outrage. But, arguably, psychopaths are both sinned against as well as sinners. If that is true, then their status as the victims of abusive subcultures partially mitigates their moral responsibility for the harms they cause. We argue, from the neuroethics of psychopathy and antisocial personality disorder (ASPD), that communities have a moral obligation to psychopaths as well as a case (...) against them. A reflection on the genesis and developmental epidemiology of psychopathy reveals an individualist, attribution-type error evident in much Western psychological and legal thinking—an error that obscures important moral truths about psychopaths. The resulting analysis makes us reconsider the distinction between disorders and moral failings and the ethical significance of the biological or neurocognitive mechanisms underpinning psychopathy. We claim that casting aside the deficit model (based on the presupposition that psychopaths are intrinsically unlike the rest of us) in favor of a relational and holistic view of personality potentiates a more informed and inclusive set of ethical, forensic, and therapeutic attitudes. (shrink)

In his paper “Whatever next? Predictive brains, situated agents, and the future of cognitive science,” Andy Clark seminally proposed that the brain's job is to predict whatever information is coming “next” on the basis of prior inputs and experiences. Perception fundamentally subserves survival and self-preservation in biological agents, such as humans. Survival however crucially depends on rapid and accurate information processing of what is happening in the here and now. Hence, the term “next” in Clark's seminal formulation must include not (...) only the temporal dimension (i.e., what is perceivednow) but also the spatial dimension (i.e., what is perceivedhereor next-to-my-body). In this paper, we propose to focus on perceptual experiences that happen “next,” i.e., close-to-my-body. This is because perceptual processing of proximal sensory inputs has a key impact on the organism's survival. Specifically, we focus on tactile experiences mediated by the skin and what we will call the “extended skin” or “second skin,” that is, immediate objects/materials that envelop closely to our skin, namely, clothes. We propose that the skin and tactile experiences are not a mere border separating the self and world. Rather, they simultaneously and inherently distinguishandconnect the bodily self to its environment. Hence, these proximal and pervasive tactile experiences can be viewed as a “transparent bridge” intrinsically relating and facilitating exchanges between the self and the physical and social world. We conclude with potential implications of this observation for the case of Depersonalization Disorder, a condition that makes people feel estranged and detached from their self, body, and the world. (shrink)

Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between resting-state brain signal variability and ADHD symptom severity. The current study examined the relationship between a measure of moment-to-moment brain (...) signal variability called mean-square successive difference (MSSD) and ADHD symptomatology in a group of children (7–12 years old) with ( n = 40) and without ( n = 30) a formal diagnosis of ADHD. A categorical analysis comparing subjects with and without a clinical diagnosis of ADHD showed no differences in MSSD between groups. A dimensional analysis revealed a positive relationship between MSSD and overall ADHD symptom severity and inattention across children with and without an ADHD diagnosis. Specifically, this positive relationship was found in medial prefrontal areas comprising the default mode network. These results demonstrate a link between intrinsic brain signal variability and ADHD symptom severity that cuts across diagnostic categories, and point to a locus of dysfunction consistent with previous neuroimaging literature. (shrink)

The neurodiversity paradigm is presented by its proponents as providing a philosophical foundation for the activism of the neurodiversity movement. Its central claims are that autism and other neurodivergent conditions are not disorders because they are not intrinsically harmful, and that they are valuable, natural and/or normal parts of human neurocognitive variation. This paper: (a) identifies the non‐disorder claim as the most central of these, based on its prominence in the literature and connections with the practical policy claims that (...) the paradigm is supposed to support; (b) describes the heterogeneity of autism at the behavioural and causal levels, and argues that at the behavioural level this encompasses ways of being autistic that are harmful in ways that cannot be not wholly attributed to discrimination or unjust social arrangements, challenging the claim that autism is not a disorder; (c) considers and rejects responses to this challenge based on separation of high‐ and low‐functioning autism, separation of autism from co‐occurring conditions, and viewing autism as part of an individual’s identity. Two of these responses fail for reasons that are themselves connected with the behavioural and/or causal heterogeneity of autism. (shrink)

This book defends the much-disputed view that emotions are what Hume referred to as ‘original existences’: feeling states that have no intentional or representational properties of their own. In doing so, the book serves as a valuable counterbalance to the now mainstream view that emotions are representational mental states. Beginning with a defence of a feeling theory of emotion, Whiting opens up a whole new way of thinking about the role and centrality of emotion in our lives, showing how emotion (...) is key to a proper understanding of human motivation and the self. Whiting establishes that emotions as types of bodily feelings serve as the categorical bases for our behavioural dispositions, including those associated with moral thought, virtue, and vice. The book concludes by advancing the idea that emotions make up our intrinsic nature - the characterisation of what we are like in and of ourselves, when considered apart from how we are disposed to behave. The conclusion additionally draws out the implications of the claims made throughout the book in relation to our understanding of mental illness and the treatment of emotional disorders. (shrink)

Cognitive functions are directly related to interactions between the brain's functional networks. This functional organization changes in the autism spectrum disorder (ASD). However, the heterogeneous nature of autism brings inconsistency in the findings, and specific pattern of changes based on the cognitive theories of ASD still requires to be well-understood. In this study, we hypothesized that the theory of mind (ToM), and the weak central coherence theory must follow an alteration pattern in the network level of functional interactions. The main (...) aim is to understand this pattern by evaluating interactions between all the brain functional networks. Moreover, the association between the significantly altered interactions and cognitive dysfunctions in autism is also investigated. We used resting-state fMRI data of 106 subjects (5–14 years, 46 ASD: five female, 60 HC: 18 female) to define the brain functional networks. Functional networks were calculated by applying four parcellation masks and their interactions were estimated using Pearson's correlation between pairs of them. Subsequently, for each mask, a graph was formed based on the connectome of interactions. Then, the local and global parameters of the graph were calculated. Finally, statistical analysis was performed using a two-sample t-test to highlight the significant differences between autistic and healthy control groups. Our corrected results show significant changes in the interaction of default mode, sensorimotor, visuospatial, visual, and language networks with other functional networks that can support the main cognitive theories of autism. We hope this finding sheds light on a better understanding of the neural underpinning of autism. (shrink)

In this article, I consider the structure of interpersonal emotional relations. I argue that current cognitive-developmental theory has overestimated the role of conceptual thinking, and underestimated the role of intrinsic social-emotional organization, in the early development of such feelings as jealousy, shame, and concern. I suggest that human forms of social experience are shaped by a process through which one individual identifies with the bodily expressed attitudes of other people, and stress the diversity of self–other relational states. I draw on (...) studies in developmental psychopathology, and specifically research in autism and borderline personality disorder, to illustrate some implications of this viewpoint. (shrink)

I hypothesize that people engage in religious practices, in part, because such practices activate the frontal lobes. Activation of the frontal lobes is both intrinsically rewarding and necessary for acquisition of many of the behaviors that religions seek to foster, including self‐responsibility, impulse and emotion modulation, empathy, moral insight, hope, and optimism. Although direct tests of the hypothesis are as yet nonexistent, there is reasonably strong circumstantial evidence (reviewed herein) for it. Recent brain‐imaging studies indicate greater anterior activation values (...) and increased blood flow to frontal sites during prayer and meditation. Regular prayer is positively correlated with better overall mental health. Religiosity is correlated with higher levels of self‐monitoring, empathy, and moral insight and other positive behaviors and negatively correlated with depression and impulsive and risky behaviors. Independent data show that self‐monitoring, empathy, hope, and moral insight are all selectively associated with intact frontal function, whereas depression, impulsiveness, and drug and alcohol abuse are associated selectively with frontal dysfunction. If religious practices do indeed preferentially activate and stimulate development of the frontal lobes, (a) religious practices should be considered as possible adjuncts for some patients in treatment for mental health disorders, and (b) the frontal lobes (rather than the temporal lobes) should be considered the major brain site that supports the core components of religious experience. (shrink)

IntroductionDespite the fact that group fitness instructors serve as significant role models with potentially great impact on class participants' motivation for exercise, they are a very under-researched group. The aim of this study was therefore to examine group fitness instructors' motivational regulations for exercise, and how these motivational regulations can predict symptoms of exercise dependence and body image concerns.MethodsGroup fitness instructors from the largest fitness companies in Norway completed an online survey with reference to the Situational Motivation Scale, the Exercise (...) Dependence Scale, the Eating Disorders Inventory subscales drive for thinness and body dissatisfaction, and their weekly amount of exercise and instruction.ResultsThe instructors scored high on identified regulation and intrinsic regulation for exercise. EDS total score was positively correlated with all SIMS subscales and weekly instruction was positively correlated with Intrinsic regulation. Multiple hierarchical regression analyses found that both self-determined motivational regulations as well as external regulation positively predicted their EDS score. External regulation positively predicted EDI-DT, and EDI-BD.ConclusionGroup fitness instructors seem highly intrinsically motivated for exercise, which is hypothesized to have a positive impact on group fitness class participants. High self-determined exercise behavior does not seem to buffer against symptoms of exercise dependence within this specific population. There is a need for awareness of group fitness instructors who show high exercise dependency scores due to the link to body image concerns, amotivation and external regulated motivation. (shrink)

In this paper we suggest the existence of a generalized task-related cortical network that is up-regulated whenever the task to be performed requires the allocation of generalized non-specific cognitive resources, independent of the specifics of the task to be performed. We have labeled this general purpose network, the extrinsic mode network (EMN) as complementary to the default mode network (DMN), such that the EMN is down-regulated during periods of task-absence, when the DMN is up-regulated, and vice versa. We conceptualize the (...) EMN as a cortical network for extrinsic neuronal activity, similar to the DMN as being a cortical network for intrinsic neuronal activity. The EMN has essentially a fronto-temporo-parietal spatial distribution, including the inferior and middle frontal gyri, inferior parietal lobule, supplementary motor area, inferior temporal gyrus. We hypothesize that this network is always active regardless of the cognitive task being performed. We further suggest that failure of network up- and down-regulation dynamics may provide neuronal underpinnings for cognitive impairments seen in many mental disorders, such as, e.g., schizophrenia. We start by describing a common observation in functional imaging, the close overlap in fronto-parietal activations in healthy individuals to tasks that denote very different cognitive processes. We now suggest that this is because the brain utilizes the EMN network as a generalized response to tasks that exceeds a cognitive demand threshold and/or requires the processing of novel information. We further discuss how the EMN is related to the DMN, and how a network for extrinsic activity is related to a network for intrinsic activity. Finally, we discuss whether the EMN and DMN networks interact in a common single brain system, rather than being two separate and independent brain systems. (shrink)

Birds are not commonly admired for emotional expression, and when they are, the focus is typically on negative states; yet vocal behavior is considered a direct reflection of an individual’s emotional state. Given that over 4000 species of songbird produce learned, complex, context-specific vocalizations, we make the case that songbirds are conspicuously broadcasting distinct positive emotional states and that hearing songs can also induce positive states in other birds. Studies are reviewed that demonstrate that that the production of sexually motivated (...) song reflects an emotional state of anticipatory reward-seeking (i.e., mate-seeking), while outside the mating context song in gregarious flocks reflects a state of intrinsic reward. Studies are also reviewed that demonstrate that hearing song induces states of positive anticipation and reward. This review brings together numerous studies that highlight a potentially important role for the songbird nucleus accumbens, a region nearly synonymous with reward in mammals, in positive emotional states that underlie singing behavior and responses to song. It is proposed that the nucleus accumbens is part of an evolutionarily conserved circuitry that contributes context-dependently to positive emotional states that motivate and reward singing behavior and responses to song. Neural mechanisms that underlie basic emotions appear to be conserved and similar across vertebrates. Thus, these findings in songbirds have the potential to provide insights into interventions that can restore positive social interactions disrupted by mental health disorders in humans. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Commentary on “Epistemic Value Commitments”W. John Livesley (bio)A disquieting feature of contemporary psychiatric nosology is the tendency to adopt positions that imply that current classifications are simply statements of fact. Clinicians and researchers alike seem to assume that the DSM diagnostic concepts are factual descriptions based only on scientific analysis that reflect the essential nature of psychiatric disorders. The architects of the DSM acknowledge in various ways that this (...) is not the case. Frances et al. (1991), for example, noted the provisional and pragmatic nature of DSM-IV. Nevertheless, these cautions are largely ignored. The DSM is partly responsible. The assertion that the DSM is atheoretical with regard to etiology, although clearly incorrect, tends to generalize to other aspects of the system. Similarly, the emphasis on description that has proved so valuable in improving diagnosis is presented as if clinical description is unencumbered by values and assumptions. Moreover, the failure to state explicitly the assumptions underlying the classification encourages the conclusion that the system is free from theoretical and other influences.In fact the DSM is theory laden. Implicit theoretical models and etiological concepts lie behind many diagnoses, including adjustment, dissociative, and posttraumatic stress disorders. Assumptions about the nature of mental disorders and the way psychopathology is organized underlie the entire system (Livesley and Jackson 1992). Pragmatic and political considerations influenced the final structure. Moreover, as Dr. Sadler and others working on the same issues (Fulford 1989, 1994; Agich 1994) point out, the DSM is also value laden. It is value laden not only in the obvious sense that some diagnostic concepts are highly evaluative or biased against certain groups (Kaplan 1983), but also in the fundamental sense that values are built into the very structure of the system (Agich 1994; Russell 1994; Wakefield 1992).Value influences begin with the definition of mental disorder. As Wakefield (1992) and others have argued, the concept of disorder cannot be value free. Values are also involved in the descriptive terms adopted as diagnostic criteria (Agich 1994) and, as Dr. Sadler convincingly demonstrates, they are intrinsic to the way that the classification is constructed and evaluated—the very aspects of the classification that are generally assumed to be value free. By emphasizing this aspect, Dr. Sadler draws attention to the fact that despite being implicit and informal, these values exert a major influence. They influence kinds of information considered relevant to the classification, the way this information is weighted and evaluated, and the way it is organized into diagnostic concepts. Thus, values shape the classification and the research agenda. This point has not [End Page 223] been fully recognized, or at least not fully acknowledged, by those responsible for developing contemporary classifications. There is a tendency to assume that any values involved in the DSM are largely evaluative and incidental, as if they crept into the system inadvertently due to our limited knowledge. The implication is that their presence is merely a temporary embarrassment to be eliminated automatically as clinical description and phenomenology are refined. But this is not the case; any classification of mental disorders inevitably consists of fact plus value (Fulford 1994). Acknowledgment of the evaluative element does not detract from the achievements of the DSM. It is not a limitation but an essential component.The general failure to attend to the non-factual or non-descriptive aspects of classification means that important aspects of classifications are neglected. The impact of pragmatic considerations, political and economic factors, and ethical and epistemic values on the organization and evaluation of scientific information has not received appropriate attention given the social, clinical, and scientific consequences of contemporary psychiatric classifications. In essence, only a limited aspect of classification has been studied, and even this has been studied in isolation from its context. Under these circumstances there is much to be gained from explicit acknowledgment and analysis of the value component. We are more likely to make progress in resolving nosological issues if we take a broad perspective.For the nosologist, Dr. Sadler makes two useful contributions to understanding the broader view. First, the analysis of value is extended beyond discussion of evaluative or ethical values into a detailed analysis of the epistemic values that... (shrink)

Retinopathy of prematurity (ROP) is a complex neonatal disorder with multiple contributing factors. In this paper we have mounted the evidence in support of the proposal that neonatal sepsis meets all requirements for being a cause of ROP (not a condition, mechanism, or even innocent bystander) by means of initiating the early stages of the pathomechanism of ROP occurrence, systemic inflammation. We use the model of etiological explanation, which distinguishes between two overlapping processes in ROP causation. It can be shown (...) that sepsis can initiate the early stages of the pathomechanism via systemic inflammation (causation process) and that systemic inflammation can contribute to growth factor aberrations and the retinal characteristics of ROP (disease process). The combined contribution of these factors with immaturity at birth (as intrinsic risk modifier) and prenatal inflammation (as extrinsic facilitator) seems to provide a cogent functional framework of ROP occurrence. Finally, we apply the Bradford Hill heuristics to the available evidence. Taken together, the above suggests that neonatal sepsis is a causal inducer of ROP. (shrink)

Bold approaches to data collection and large-scale quantitative advances have long been a preoccupation for social science researchers. In this commentary we further debate over the use of large-scale survey data and official statistics with ‘Big Data’ methodologists, and emphasise the ability of these resources to incorporate the essential social and cultural heredity that is intrinsic to the human sciences. In doing so, we introduce a series of new data-sets that integrate approximately 30 years of survey data on victimisation, fear (...) of crime and disorder and social attitudes with indicators of socio-economic conditions and policy outcomes in Britain. The data-sets that we outline below do not conform to typical conceptions of ‘Big Data’. But, we would contend, they are ‘big’ in terms of the volume, variety and complexity of data which has been collated and ‘big’ also in that they allow us to explore key questions pertaining to how social and economic policy change at the national level alters the attitudes and experiences of citizens. Importantly, they are also ‘small’ in the sense that the task of rendering the data usable, linking it and decoding it, required both manual processing and tacit knowledge of the context of the data and intentions of its creators. (shrink)

Ugar and Malele 1 critique the use of ‘generic’ technologies like artificial intelligence (AI) and machine learning (ML) for mental health diagnoses, particularly in sub-Saharan African countries. They highlight how these AI medical tools often overlook traditional perspectives and local contexts. The article has the merit of working on ethical issues regarding the particularities and risks of using AI and ML for health diagnosis in the Global South, an urgent and neglected topic. According to the authors, the use of these (...) AI technologies leads to overgeneralisation in diagnosing mental disorders, which could be especially problematic in the mental health field because of value-laden judgements intrinsic to the definition of mental health disorders. This argument is theoretically grounded in the hybrid conceptualisation of mental disorders proposed by Wakefield. 2 This author’s perspective incorporates both factual and value components in defining mental disorders, framing them as context-dependent ‘harmful dysfunctions’... (shrink)

Music-based interventions (MBI) have become increasingly widely adopted for dementia and related disorders. Previous research shows that music engages reward-related regions through functional connectivity with the auditory system, but evidence for the effectiveness of MBI is mixed in older adults with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This underscores the need for a unified mechanistic understanding to motivate MBIs. The main objective of the present study is to characterize the intrinsic connectivity of the auditory and reward systems in (...) healthy aging individuals with MCI, and those with AD. Using resting-state fMRI data from the Alzheimer’s Database Neuroimaging Initiative, we tested resting-state functional connectivity within and between auditory and reward systems in older adults with MCI, AD, and age-matched healthy controls (N = 105). Seed-based correlations were assessed from regions of interest (ROIs) in the auditory network (i.e., anterior superior temporal gyrus, posterior superior temporal gyrus, Heschl’s Gyrus), and the reward network (i.e., nucleus accumbens, caudate, putamen, and orbitofrontal cortex). AD individuals were lower in both within-network and between-network functional connectivity in the auditory network and reward networks compared to MCI and controls. Furthermore, graph theory analyses showed that the MCI group had higher clustering and local efficiency than both AD and control groups, whereas AD individuals had lo... (shrink)

The concepts of hope and its absence, hopelessness, are seen as crucial in palliative care for people with motor neurone disease. A primary measure in psychological research on hopelessness in people with motor neurone disease is the Beck Hopelessness Scale. This scale can be understood as being conceptually based on the philosophical standard account of hope, which understands hope as an intentional expectancy. This essay argues that this is a misconstruction of hopelessness in palliative care. Rather, pre-intentional hope is essential (...) for palliative care of people with motor neurone disease. Pre-intentional hope enables the formation of intentional hopes and is intrinsically relational. Finally, it is argued that the absence of pre-intentional hope should not be subjected to psychiatric diagnosis, for example, in the form of demoralization disorder. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Commentary on “Epistemic Value Commitments”Michael Luntley (bio)Keywordsvalue, classificationThe case for treating the underdetermination of psychiatric classification with just the same tools as are employed in solving the more general underdetermination of theory by data is well made by Sadler. Quite what that treatment amounts to, however, raises a number of issues that are not only central to any philosophical conception of the rationality of theory choice, but cut deep (...) into issues about the appropriate model for rational clinical practice.On the face of it, Sadler’s recommendation is plain and looks to clarify the central problems confronting the authors of DSM nosology. The central problem for the construction of DSM guidelines is that there is no algorithm for turning input data concerning observables (behavior patterns) into theoretical classification. A simple-minded positivism would have had us expect that the production of an adequate nosology by symptoms as a mechanical algorithm—plug in the data at one end and the nosology pops out the other end. The interesting philosophical issue concerns how we respond to this underdetermination. I want to note two stages to the response we make.The first stage turns on deciding between thinking (a), that with sufficient further non-observational input some sort of modified algorithm can be produced for psychiatric classification, and thinking (b), that no such modified algorithm is available and that psychiatric classification irredeemably involves an element of judgment. The second stage that I want to explore concerns whether taking option (b) at the first stage seriously undermines the rationality of psychiatric classification and theory choice in general.Sadler seems to favor option (a). He notes that some have responded to the Kuhnian diagnosis of the lack of effective decision procedure for the production of theory by impugning the possibility of any rationality to theory choice and by seeing the activity of theory choice as thoroughly soaked in value commitments that bear the hallmark of ideology rather than rationality. Sadler’s response, however, is to draw attention to a set of values that he calls “epistemic values” that are “intrinsic to the theorizing about and construction of the classification itself.” I see this as a version of what I have called option (a) because Sadler seems to treat these values as extra “bolt-ons” to the algorithm that turns observation into classification. His aim is to clarify the character of these non-observational constraints and then plot the way that their application renders tractable a current dispute in psychiatric nosology between categorical vs. dimensional classifications of personality disorders.Suppose this is the option (a) strategy. The option (a) strategy involves a universalist model [End Page 227] of rationality. What I mean by “universalist” is this: A universalist model of rationality holds that if a transition from input to theory (input to classification) is rational, it is subsumable under a typology of such transitions that issues universal guides such as: Given inputs i 1, i 2... under constraints c 1, c 2..., conclude output/theory T n. A universalist model is distinct from a generalist model, for it accommodates the thought that the permissible routes from input to theory may include routes that are heavily conditioned by all sorts of particularities in the constraints cited in the transition rule. What the universalist does require, however, is that all rational transitions are instances of such a rule, even though the rule is not generalizable to cover all eventualities but is specific to certain particular circumstances. Sadler’s account of epistemic values is then an account that locates the place of these values as constraints that, in tandem with the inputs, determine output in a rule-governed manner.There are a number of problems with this approach that I want to touch on before turning to the main philosophical moral that I would like to draw from Sadler’s paper. The universalist model is a model in which judgment plays no role in the transition from input to output. It is, however, unclear that such a model will really work on the evidence of Sadler’s investigations for a number of reasons. First, his initial definition of a “value” is that of a descriptor... (shrink)