Glycosylation refers to the co‐ and post‐translational modification of protein and lipids by monosaccharides or oligosaccharide chains. The surface of mammalian cells is decorated by a heterogeneous and highly complex array of protein and lipid linked glycan structures that vary significantly between different cell types, raising questions about their roles in development and disease pathogenesis. This review will begin by focusing on recent findings that define roles for cell surface protein and lipid glycosylation in pluripotent stem cells and (...) their functional impact during normal development. Then, we will describe how patient derived induced pluripotent stem cells are being used to model human diseases such as congenital disorders of glycosylation. Collectively, these studies indicate that cell surface glycans perform critical roles in human development and disease. (shrink)

Disorders of sexual development are a heterogeneous group of disorders in which chromosomal, gonadal or anatomical sex development is atypical. The majority of these children are recognized at birth by ambiguous genitalia. Legal and societal pressures require the physician and parents to assign sex rapidly. Though sex assignment is undebated in several disorders of sexual development, many others need an individualized approach to gender-related concerns. Gender dysphoria is prevalent in disorders of sexual development, and early gender-defining (...) surgeries have potentially lifelong consequences. We use two cases, one of partial androgen insensitivity and another of simple virilizing congenital adrenal hyperplasia to illustrate that in disorders of sexual development, the ethical management principles remain the same at their core despite the vast differences in phenotypes. Sex assignment should maximize functional, psychological and sexual needs. Sex assigned should coincide with gender identity. We propose that we manage such children with the mutual participation of the physician, parents and the child. Though the parents and the physician have the child's best interests when making a decision, the child's developing autonomy should be protected. The communication of the health provider to the parent must be honest if early sex assignment is difficult. (shrink)

In this critical, feminist account of the management of intersex conditions under 2006's controversial “Disorders of Sex Development” (DSD) treatment model, I argue that like the “Optimal Gender of Rearing” (OGR) treatment model it replaced, DSD aims at securing a cisgendered future for the intersex patient, referring to a normalized trajectory of development across the lifespan in which multiple sexed, gendered, and sexual characteristics remain in “coherent” alignment. I argue this by critically analyzing two ways that intersex management has (...) changed between OGR and DSD: 1) regarding sex‐assignment recommendations for three patient populations and, 2) with the prenatal treatment of pregnant individuals at risk of conceiving a fetus with congenital adrenal hyperplasia with the steroid hormone dexamethasone. I conclude that like OGR before it, DSD also unjustifiably presumes that typical genitalia are necessary for cisgendered development. However, unlike OGR, it appeals to the empirically inadequate, theoretically suspect, and biologically determinist model of gender development known as brain‐organization theory. Given this, I conclude that the treatment of intersex people under DSD continues to be driven by problematically heterosexist and transphobic assumptions regarding the value and normalcy of cisgendered life, while practically and discursively constituting it as such. (shrink)

Human chromosome 11p15 comprises two imprinted domains important in the control of fetal and postnatal growth. Novel studies1-3 establish that imprinting at one of these, the IGF2-H19 domain, is epigenetically deregulated (with loss of DNA methylation) in Silver-Russell Syndrome (SRS), a congenital disease of growth retardation and asymmetry. Previously, the exact opposite epigenetic alteration (gain of DNA methylation) had been detected at the domain's ‘imprinting control region’ (ICR) in patients with Beckwith-Wiedemann Syndrome (BWS), a complex disorder of fetal overgrowth. (...) However, more frequently, BWS is caused by loss of DNA methylation at the ICR that regulates the second imprinted domain at 11p15. Interestingly, a similar epigenetic alteration (with loss of methylation) at a putative ICR on human chromosome 6q24, is involved in transient neonatal diabetes mellitus (TNDM), a congenital disease with intrauterine growth retardation and a transient lack of insulin. Thus, fetal and postnatal growth is epigenetically controlled by different ICRs, at 11p15 and other chromosomal regions. BioEssays 28: 453–459, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Congenital amusia in its most common form is a disorder characterized by a musical pitch processing deficit. Although pitch is involved in conveying emotion in music, the implications for pitch deficits on musical emotion judgements is still under debate. Relatedly, both limited and spared musical emotion recognition was reported in amusia in conditions where emotion cues were not determined by musical mode or dissonance. Additionally, assumed links between musical abilities and visuo-spatial attention processes need further investigation in congenital (...) amusics. Hence, we here test to what extent musical emotions can influence attentional performance. Fifteen congenital amusic adults and fifteen healthy controls matched for age and education were assessed in three attentional conditions: executive control, alerting, and orienting while music expressing either joy, tenderness, sadness, or tension was presented. Visual target detection was in the normal range for both accuracy and response times in the amusic relative to the control participants. Moreover, in both groups, music exposure produced facilitating effects on selective attention that appeared to be driven by the arousal dimension of musical emotional content, with faster correct target detection during joyful compared to sad music. These findings corroborate the idea that pitch processing deficits related to congenital amusia do not impede other cognitive domains, particularly visual attention. Furthermore, our study uncovers an intact influence of music and its emotional content on the attentional abilities of amusic individuals. The results highlight the domain-selectivity of the pitch disorder in congenital amusia, which largely spares the development of visual attention and affective systems. (shrink)

N- and O-linked glycan structures of cell surface and secreted glycoproteins serve a variety of functions related to cell–cell communication in systems affecting development and disease. The more sophisticated N-glycan biosynthesis pathway of metazoans diverges from that of yeast with the appearance of the medial-Golgi β-N-acetylglucosaminyltransferases (GlcNAc-Ts). Tissue-specific regulation of medial- and trans-Golgi glycosyltransferases contribute structural diversity to glycoproteins in metazoans, and this can affect their molecular properties including localization, half-life, and biological activity. Null mutations in glycosyltransferase genes positioned later (...) in the biosynthetic pathway disrupt expression of smaller subsets of glycan structures and are progressively milder in phenotype. In this review, we examine data on targeted mutations affecting glycosylation in mice and congenital mutations in man, with a view to understanding the molecular functions of glycan structures as modulators of glycoprotein activity. Finally, pathology associated with the expression of GlcNAc-Ts in cancer and diabetes-induced cardiac hypertrophy suggest that inhibitors of these enzymes may have therapeutic value. BioEssays 21:412–421, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The recently uncovered role of Fukutin‐related protein (FKRP) in fibronectin glycosylation has challenged our understanding of the basis of disease pathogenesis in the muscular dystrophies. FKRP is a Golgi‐resident glycosyltransferase implicated in a broad spectrum of muscular dystrophy (MD) pathologies that are not fully attributable to the well‐described α‐Dystroglycan hypoglycosylation. By revealing a new role for FKRP in the glycosylation of fibronectin, a modification critical for the development of the muscle basement membrane (MBM) and its associated muscle linkages, (...) new possibilities for understanding clinical phenotype arise. This modification involves an interaction between FKRP and myosin‐10, a protein involved in the Golgi organization and function. These observations suggest a FKRP nexus exists that controls two critical aspects to muscle fibre integrity, both fibre stability at the MBM and its elastic properties. This review explores the new potential disease axis in the context of our current knowledge of muscular dystrophies. (shrink)

Introduction: Congenital myasthenic syndromes refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies on disease progression and treatment-response in pediatric patients are rare.Patients and Methods: We analyzed retrospective clinical and medication data in a cohort of 32 CMS-patients including the application of a standardized, not yet validated test to examine muscular strength and endurance in 21 patients (...) at the last follow-up. Findings obtained in our cohort were compared with long-term follow-up studies of CMS-cohorts from the literature by considering the underlying molecular mechanisms. Outcomes of CMS-ST were compared to results of normal clinical assessment.Results: Thirty-two pediatric patients with defects in eight different CMS-genes were followed by a median time of 12.8 years. Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants. While 53% of patients presented a reduced walking distance, 34% were wheelchair-bound. Even under adequate therapy with pyridostigmine and 3,4-diaminopyridine, CHAT-mutations led to the progression of muscular weakness partly in combination with persistent respiratory and bulbar symptoms. RAPSN, CHRND, and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. CHAT and CHRNE patients required higher PS dosages, whereas RAPSN patients needed a lower mean dosage at the last follow-up. The benefits of short-term medication and long-term progression of symptoms were highly dependent on the specific genetic defect. CMS-ST was carried out in 17/21 patients, determined affected muscle groups including bulbar and ocular symptoms, some of which were not reported by the patients.Conclusions: Our findings and comparison with the literature- suggest a better treatment-response and less severe progression of symptoms present in patients suffering from mutations in CMS-genes directly associated with receptor deficiency, while patients with defects leading to synaptopathy and presynaptic defects tend to have worse outcomes. Assessment of affected muscular groups and clinical symptoms by CMS-ST may be a useful tool for optimal therapeutic management of the patients, especially for future clinical studies. (shrink)

8. Eckhart's why and Heidegger's what: beyond subjectivistic thought to groundless ground -- I -- II -- III -- Notes -- 9. Meister Eckhart's speculative grammar: a foreshadowing of Heidegger's Der Satz vom Grund? -- A problem of expression -- Language in modism -- Spiral-vortex metaphor -- Concluding remarks -- Notes -- 10. Pay attention!: exploring contemplative pedagogies between Eckhart and Heidegger -- Paying attention -- The paradox of intention -- Intended attention -- Conclusion -- Notes -- PART IV: Re-readings (...) and new boundaries -- 11. Mysterium secretum et silentiosum: praying the apophatic self -- The secret prayer of apophasis -- Breaching the silent sanctuary in Fear and Trembling -- Exteriority and interiority: the scandal of self and other -- Praying the apophatic self -- Notes -- 12. Becoming mystic, becoming monster: the logic of the infinite in Kierkegaard, Cusa and Deleuze -- Kierkegaard: thinking the unthinkable -- Cusa: the repetition of unity -- Conclusion -- Notes -- 13. Non-philosophical immanence, or immanence without secularization -- I Immanence and philosophy -- II Eckhart's unrestrained immanence -- III Non-philosophical immanence -- Notes -- 14. 'Not peace but a sword': Žižek, Dionysius and the question of ancestry in theology and philosophy -- The sins of the fathers: the congenital disorders of Christian-Neoplatonism -- Unto the third and fourth generation: Žižek and the mutation of Christian inheritance -- Conclusion: miscegenous liaisons -- Notes -- Index. (shrink)

This article discusses the ethics of the use of preimplantation genetic diagnosis to prevent the birth of children with intersex conditions/disorders of sex development , such as congenital adrenal hyperplasia and androgen insensitivity syndrome . While pediatric surgeries performed on children with ambiguous genitalia have been the topic of intense bioethical controversy, there has been almost no discussion to date of the ethics of the use of PGD to reduce the prevalence of these conditions. I suggest that PGD (...) for those conditions that involve serious medical risks for those born with them is morally permissible and that PGD for other “cosmetic” variations in sexual anatomy is more defensible than might first appear. However, importantly, the arguments that establish the latter claim have radical and disturbing implications for our attitude toward diversity more generally. (shrink)

During recent decades various researchers from health and social sciences have been debating what it means for a person to be disabled. A rather overlooked approach has developed alongside this debate, primarily inspired by the philosophical tradition called phenomenology. This paper develops a phenomenological model of disability by arguing for a different methodological and conceptual framework from that used by the existing phenomenological approach. The existing approach is developed from the phenomenology of illness, but the paper illustrates how the case (...) of congenital disabilities, looking at the congenital disorder called cerebral palsy (CP), presents a fundamental problem for the approach. In order to understand such congenital cases as CP, the experience of disability is described as being gradually different from, rather than a disruption of, the experience of being abled, and it is argued that the experience of disability is complex and dynamically influenced by both intrinsic and extrinsic factors. Different experiential aspects of disability— pre-reflective, attuned and reflective aspects—are described, demonstrating that the experience of disability comes in different degrees. Overall, this paper contributes to the debates about disability by further describing the personal aspects and experience of persons living with disabilities. (shrink)

The law of unintended consequences is generally applied to technological advances that solve one problem but cause another. In this view, the problem created may be worse than that which was solved, hence the law is used as an argument against technological advances. Concern about intent and consequence comes to mind when reading the article by Ronald Green on parental decision making and prenatal genetics. Green's analysis, combined with the realities of genetic practice, raises questions about parental power, eugenics, and (...) the interests of children affected by genetic or congenital disorders. Green proposes rules and draws conclusions that are not useful for clinicians and that promise harm to families and individuals affected by genetic disorders. Green's analysis may be an example of a corollary that could be viewed as the Law of Unintended Ethics.Green's paper begins with an apparently contradictory dual thesis. First, he supports unfettered parental decision making about their fetuses and children. Second, he suggests that we should strive to give our children lives unimpaired by serious genetic disorders. (shrink)

The law of unintended consequences is generally applied to technological advances that solve one problem but cause another. In this view, the problem created may be worse than that which was solved, hence the law is used as an argument against technological advances. Concern about intent and consequence comes to mind when reading the article by Ronald Green on parental decision making and prenatal genetics. Green's analysis, combined with the realities of genetic practice, raises questions about parental power, eugenics, and (...) the interests of children affected by genetic or congenital disorders. Green proposes rules and draws conclusions that are not useful for clinicians and that promise harm to families and individuals affected by genetic disorders. Green's analysis may be an example of a corollary that could be viewed as the Law of Unintended Ethics.Green's paper begins with an apparently contradictory dual thesis. First, he supports unfettered parental decision making about their fetuses and children. Second, he suggests that we should strive to give our children lives unimpaired by serious genetic disorders. (shrink)

With this manifesto, John Dupré systematically attacks the ideal of scientific unity by showing how its underlying assumptions are at odds with the central conclusions of science itself.

Carole Pateman is one of the leading political theorists writing today. This wide-ranging volume brings together for the first time a selection of her work on democratic theory and feminist criticism of mainstream political theory. The volume includes substantial discussions of problems of democracy, citizenship and the welfare state, including the largely unrecognized difficulties surrounding women's participation. The inclusion of essays from both a mainstream and feminist perspective provides concrete examples of the differences between these two approaches to democracy, to (...) questions of consent and political obligation, and to the relationship between the private and public spheres. This scholarly and highly challenging work will be of interest to students and researchers in political theory, political science, women's studies and sociology. (shrink)

The developing infant can accomplish all important perceptual tasks that an adult can, albeit with less skill or precision. Through infant perception research, infant responses to experiences enable researchers to reveal perceptual competence, test hypotheses about processes, and infer neural mechanisms, and researchers are able to address age-old questions about perception and the origins of knowledge.In Development of Perception in Infancy: The Cradle of Knowledge Revisited, Martha E. Arterberry and Philip J. Kellman study the methods and data of scientific research (...) on infant perception, introducing and analyzing topics through philosophical, theoretical, and historical contexts. Infant perception research is placed in a philosophical context by addressing the abilities with which humans appear to be born, those that appear to emerge due to experience, and the interaction of the two. The theoretical perspective is informed by the ecological tradition, and from such a perspective the authors focus on the information available for perception, when it is used by the developing infant, the fit between infant capabilities and environmental demands, and the role of perceptual learning. Since the original publication of this book in 1998, Arterberry and Kellman address in addition the mechanisms of change, placing the basic capacities of infants at different ages and exploring what it is that infants do with this information. Significantly, the authors feature the perceptual underpinnings of social and cognitive development, and consider two examples of atypical development - congenital cataracts and Autism Spectrum Disorder. Professionals and students alike will find this book a critical resource to understanding perception, cognitive development, social development, infancy, and developmental cognitive neuroscience, as research on the origins of perception has changed forever our conceptions of how human mental life begins. (shrink)

The issue of wrongful disability arises when parents face the choice whether to produce a child whose life will be unavoidably flawed by a serious disease or disorder (Down syndrome, for example, or Huntington’s disease) yet clearly worth living. The authors of From Chance to Choice claim, with certain restrictions, that the choice to produce such a child is morally wrong. They then argue that an intuitive moral approach––a “person-affecting” approach that pins wrongdoing to the harming of some existing or (...) future person––cannot account for that wrong since the choice to produce such a child cannot, under the logic of the nonidentity problem, harm that child. The authors propose that we supplement the person-affecting approach with an “impersonal” principle that takes the form of their well-known principle N. In this paper, I argue that the authors are mistaken to suppose that a plausibly articulated person-affecting approach cannot account for the wrong of wrongful disability. We can retain an intuitive, comparative, “worse for” account of harm and still identify serious harms imposed by the choice of wrongful disability. In particular, I argue that harm, both to the impaired child and to others, comes not in the form of that procreative choice’s procreative effect but rather in the form of its many distributive effects. I also argue that the rare, residual case in which a person-affecting approach would approve of the choice of wrongful disability does not function as a counterexample to that approach. As a separate matter, I address legal claims for wrongful disability, which are closely akin to claims for wrongful life. The legal claim is brought by the impaired child, not against the parents, but rather against health care providers whose negligent failure to diagnose or inform parents of an increased risk of a genetic or congenital impairment results in the birth of the impaired child. The authors’ treatment of the moral wrong that is done as impersonal in nature suggests that courts are correct to dismiss any such claim. Once we identify harm, however, the person-affecting approach can identify a clear foundation in the law for the wrongful disability claim. (shrink)

The papers in this volume reflect much of the current unease of a world that perceives itself once more at the edge of chaos. The authors present different vistas of that experience and their inherent dialectic, expressed in numerous and ceaseless conflicts between ordering and disordering processes. They can be read as comments on the ongoing processes that lead toward greater complexity.

Visual Agnosia is a comprehensive and up-to-date review of disorders of higher vision that relates these disorders to current conceptions of higher vision from cognitive science, illuminating both the neuropsychological disorders and the nature of normal visual object recognition.Brain damage can lead to selective problems with visual perception, including visual agnosia the inability to recognize objects even though elementary visual functions remain unimpaired. Such disorders are relatively rare, yet they provide a window onto how the normal (...) brain might accomplish the complex task of vision. Visual Agnosia reviews a century of case studies of higher-level visual deficits following brain damage, places them in the general context of current neuroscience, and draws relevant conclusions about the organization of normal visual processing. It is unique in drawing on research in cognitive psychology, computational vision, visual neurophysiology, and neuropsychology to interpret the agnosias and draw inferences from them about visual object recognition.Following a historical account of agnosia research, Visual Agnosia offers a taxonomy of a wide range of agnosia syndromes, describing and interpreting the syndromes in terms of the latest theoretical models of visual processing and ultimately bringing them to bear as evidence on a variety of questions in the study of higher vision.Martha J. Farah is Associate Professor of Psychology at Carnegie Mellon University. Visual Agnosia is included in the Issues in Biology of Language and Cognition series, edited by John Marshall. (shrink)

This review aimed at exploring the psychosocial disorders of Nigeria as a nation, its effect on the citizens and the remedy. Psychosocial disorder is a mental illness induced by life experiences, stress, as well as maladaptive cognitive and behavioural processes. The prevalence of these disorders include depression, schizophrenia, anxiety disorders, substance use disorder, personality disorder and autism spectrum disorders have rapidly increase over the past years in Nigeria with its negative impact on the socioeconomic status, psychological (...) well-being; peaceful coexistence and mental health of the entire society. These have precipitated some social anomalies such as bribery and corruption, antisocial behaviour, religious fanaticism, terrorism and so on. The study therefore recommends the need for government to implement effective mental health interventions program that would facilitate easy access to mental healthcare services in Nigeria. There is also an urgent need to improve the mental health awareness of Nigerians through education and public mental health campaign. (shrink)

Philosophers, psychologists, neuroscientists, and psychiatrists examine the will and its pathologies from theoretical and empirical perspectives, offering a conceptual overview and discussing schizophrenia, depression, prefrontal lobe damage, and substance abuse as disorders of volition. Science tries to understand human action from two perspectives, the cognitive and the volitional. The volitional approach, in contrast to the more dominant "outside-in" studies of cognition, looks at actions from the inside out, examining how actions are formed and informed by internal conditions. In (...) class='Hi'>Disorders of Volition, scholars from a range of disciplines seek to advance our understanding of the processes supporting voluntary action by addressing conditions in which the will is impaired. Philosophers, psychologists, neuroscientists, and psychiatrists examine the will and its pathologies from both theoretical and empirical perspectives, offering a conceptual overview and discussing specific neurological and psychiatric conditions as disorders of volition. After presenting different conceptual frameworks that identify agency, decision making, and goal pursuit as central components of volition, the book examines how impairments in these and other aspects of volition manifest themselves in schizophrenia, depression, prefrontal lobe damage, and substance abuse. Contributors George Ainslie, Tim Bayne, Antoine Bechara, Paul W. Burgess, Anna-Lisa Cohen, Daniel Dennett, Stéphanie Dubal, Philippe Fossati, Chris Frith, Sam J. Gilbert, Peter Gollwitzer, Jordan Grafman, Patrick Haggard, Jay G. Hull, Marc Jeannerod, Roland Jouvent, Frank Krueger, Neil Levy, Peter F. Liddle, Kristen L. Mackiewitz, Thomas Metzinger, Jack B. Nitschke, Jiro Okuda, Adrian M. Owen, Chris Parry, Wolfgang Prinz, Joëlle Proust, Michael A. Sayette, Werner X. Schneider, Natalie Sebanz, Jon S. Simons, Laurie B. Slone, Sean A. Spence. (shrink)

The problems of contemporary states are in large part “affective disorders”; they are failures of states to properly understand and coordinate the emotions of the individuals within and in some instances outside the state. By excluding, imprisoning, and marginalizing members of their societies, states create internal enemies who ultimately enervate their own power and the possibility of peace and freedom within the state. Spinoza’s political theory, based on the notion that the best forms of state are those that coordinate (...) the power and emotions of those within a state, offers us both a diagnosis of and a cure for these affective disorders. In this paper I will outline Spinoza’s notion of the power of the state as a function of the power and coordination of the emotions of its citizens, and show that when the state contracts an affective disorder, such as excessive crime, rebellion, terrorism, etc. the state has failed to properly empower, include and coordinate the passions of the multitude of its citizens and subjects. (shrink)

Among other issues, Peterson and colleagues (2021) raise the crucial but vexing question of how to assess the well-being of patients with disorders of consciousness (DoCs). I provide some suggestio...

This article explores some of the normative commitments which persist in the literature on behavioural interventions for disorders of inattention and hyperactivity. These programmatic texts grapple with a contradiction: on one hand, they posit individuals who cannot be held responsible for their behaviour on the grounds that it is pathological, rather than wilful; on the other hand, these texts are written for individuals diagnosed with these disorders and for related authorities, obliged to mitigate said behaviour on the grounds (...) that it is disvalued and impairing. Facing the practical problem of alleviating impairing and disruptive behaviours, this literature has also consistently expressed a goal of producing individuals who demonstrate self-control. Self-control, in this context, however, is not simply the manifestation of wilful autonomy over one’s body, but the capacity to be ascribed responsibility for one’s actions. In the move from bodily control to self-control, institutions responsible for treating those diagnosed with these disorders produce what Foucault has called a ‘political economy of illegality’, where the management of disvalued behaviour is not the eradication of said behaviour, but a redistribution of the right to reward and punish based on the individualization of action. (shrink)

Advocates of the Person-Centered Healthcare (PCH) approach say that PCH is a response to a failure of caring for patients as persons. Nevertheless, there are many human subjects falling to fulfill the requirements of a traditional philosophical definition of personhood. Hence, if we take, PCH seriously, a greater clarification of the key terminology of PCH is urgently needed. It seems necessary, for instance, that the concept of the person should be extended in order to include those individuals with insipient or (...) immature levels of consciousness, as well as those who are severely and permanently mentally handicapped. In this article, we will depart from some well-known philosophical concepts of what it means to be a person and try to offer a broader and more inclusive meaning. We suggest that persons are human beings with a socially recognized biography, which implies to recognize as persons individuals with necessities, but also with narratives about their interests and claims, expressed sometimes by other people related to them. This is particularly the case of individuals that suffer from severe disorders of consciousness. For those, is not only care that matters; respect matters too. Caregivers should therefore not only sympathetically care for the well-being of these people; they should also be concerned to respect their interests and claims by interpreting them empathetically, in the light of their biographical story. Our conclusion is that, in order to be coherent, PCH must consider individuals with severe disorders of consciousness as persons and we think that our revised concept of personhood fits with this requirement. (shrink)

Epistemic peer disagreement raises interesting questions, both in epistemology and in philosophy of science. When is it reasonable to defer to the opinion of others, and when should we hold fast to our original beliefs? What can we learn from the fact that an epistemic peer disagrees with us? A question that has received relatively little attention in these debates is the value of epistemic peer disagreement—can it help us to further epistemic goals, and, if so, how? We investigate this (...) through a recent case in paleoanthropology: the debate on the taxonomic status of Homo floresiensis remains unresolved, with some authors arguing the fossils represent a novel hominin species, and others claiming that they are Homo sapiens with congenital growth disorders. Our examination of this case in the recent history of science provides insights into the value of peer disagreement, indicating that it is especially valuable if one does not straightaway defer to a peer’s conclusions, but nevertheless remains open to a peer’s evidence and arguments. (shrink)

First-person reports of Major Depressive Disorder reveal that when an individual becomes depressed a profound change or ‘shift’ to one’s conscious experience occurs. The depressed person reports that something fundamental to their experience has been disturbed or shifted; a change associated with the common but elusive claim that when depressed one finds oneself in a ‘different world’ detached from reality and other people. Existing attempts to utilise these phenomenological observations in a psychiatric context are challenged by the fact that this (...) experiential ‘shift’ characteristic of depression appears mysterious and resists analysis in scientific terms. This paper offers a way out of this predicament. The hypothesis proposed is that when an individual becomes depressed, the individual departs from a state of ordinary wakeful consciousness and enters a distinctive global state of consciousness akin to dreaming and the psychedelic state. After unpacking and motivating this hypothesis in the context of research in consciousness science, I outline two of its important implications for the neurobiology of depression and psychedelic psychiatry. The upshot is a promising and conceptually well-motivated hypothesis about depression which is apt for empirical uptake and development. (shrink)