The public debate on voluntary termination of life by elderly people, which has been an intensely controversial subject in the Netherlands for some time, has centered around the issue of “completed life” in recent years. In 2016, an ad hoc governmental advisory committee concluded that the already existing Euthanasia Act provided sufficient scope to resolve most of the problems related to the issue. Most of the older adults who feel they no longer have anything to look forward to in their (...) lives and who have developed a wish to die as a result would be able to invoke this Act. Partly for this reason, the committee considered broadening the legal options relating to assisted suicide undesirable. Analysis of the assessment practice of the regional euthanasia review committees reveals that the room for interpretation offered by the Euthanasia Act is indeed considerable. (shrink)

Even in the Netherlands, where the practice of physician-assisted death (PAD) has been legalized for over 20 years, there is no such thing as a ‘right to die’. Especially patients with extraordinary requests, such as a wish for PAD based on psychiatric suffering, advanced dementia, or (a limited number of) multiple geriatric syndromes, encounter barriers in access to PAD. In this paper, we discuss whether these barriers can be justified in the context of the Dutch situation where (...) PAD is legally permitted for those who suffer unbearably and hopelessly as a result of medical conditions. Furthermore, we explore whether there are options to address some of the barriers or their consequences, both within the Dutch legal framework or by adjusting the legal framework, and whether these options are feasible. We conclude that although there are insufficient arguments to overrule the doctor’s freedom of conscience in the Netherlands, there are ways to address some of the barriers, mainly by offering support to doctors that would be willing to support a request. Moreover, we believe it is morally required to reduce or mitigate where possible the negative consequences of the barriers for patients, such as the long waiting time for those who suffer from psychiatric disorders, because it is unlikely the adjustments suggested to the system will ensure reasonable access for these patient groups. (shrink)

The article maintains that chronic fatigue syndrome can be properly understood only by taking an integrated perspective in which evolutionary, developmental and ecological aspects are considered. The integrative approach, supplemented by a complexity theory and psychoneuroimmunological research, is capable of explaining why there are so few structural aberrations to be found in chronic fatigue syndrome and why specific treatment is so difficult to establish. A major outcome of the investigation, that all individuals with chronic fatigue syndrome are diseased in their (...) own way, emphasises the need to study the development of personalised life histories. It also highlights an ethical dimension; personalised disease defies essentialist thinking on patient management. Another major outcome, which follows from the developmental systems perspective, is the dissolution of ontological mind-body dualism. This in turn allows for a methodological complementation of the biological and phenomenological approaches to knowledge. New research strategies that may help to resolve chronic fatigue syndrome, grounded in the revised perspective on individual development, are suggested. (shrink)

Various psychopathologies of self-awareness, such as somatoparaphrenia and thought insertion in schizophrenia, might seem to threaten the viability of the higher-order thought (HOT) theory of consciousness since it requires a HOT about one’s own mental state to accompany every conscious state. The HOT theory of consciousness says that what makes a mental state a conscious mental state is that there is a HOT to the effect that “I am in mental state M.” I have argued in previous work that a (...) HOT theorist can adequately respond to this concern with respect to somatoparaphrenia and thought insertion. There is also Cotard syndrome which is a rare neuropsychiatric disorder in which people hold the delusional belief that they are dead, do not exist, or have lost their blood or internal organs. In this paper, I argue that HOT theory has nothing to fear from it either and can consistently account for what happens in such unusual cases. I analyze Cotard syndrome in light of my previous discussion of somatoparaphrenia and thought insertion, and argue that HOT theory can provide a somewhat analogous account without the worry of inconsistency. It is crucial to recognize that there are multiple “self-concepts” and levels of HOTs which can help to provide a more nuanced explanation. With regard to the connection between consciousness and self-consciousness, it is proposed that Cotard patients are indeed capable of having some “I-thoughts” about their bodies and mental states. (shrink)

The functions of the Bloom syndrome helicase and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role (...) of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination. In meiotic recombination, Blm utilizes its helicase activity to disassemble early recombination intermediates, thereby retaining a pool of recombination sites from which some can be selected to enter the Class I crossover pathway while simultaneously promoting SDSA and preventing the use of the Class II pathway. (shrink)

Down syndrome (DS), the most common genetic cause of intellectual disability, results from the partial or complete triplication of chromosome 21. Individuals with DS are impaired at using a high-resolution, allocentric spatial representation to learn and remember discrete locations in a controlled environment. Here, we assessed the capacity of individuals with DS to perform low-resolution spatial learning, depending on two competing memory systems: (1) the place learning system, which depends on the hippocampus and creates flexible relational representations of the environment; (...) and (2) the response learning system, which depends on the striatum and creates fixed stimulus-response representations of behavioral actions. Individuals with DS exhibited a preservation of the low-resolution spatial learning capacities subserved by these two systems. In place learning, although the average performance of individuals with DS was lower than that of typically-developing (TD) mental age-matched children and TD young adults, the number of individuals with DS performing above chance level did not differ from TD children. In response learning, the average performance of individuals with DS was lower than that of TD adults, but it did not differ from that of TD children. Moreover, the number of individuals with DS performing above chance level did not differ from TD adults, and was higher than that of TD children. In sum, whereas low-resolution place learning appears relatively preserved in individuals with DS, response learning appears facilitated. Our findings are consistent with the hypothesis that the neural pathways supporting low-resolution place learning and response learning are relatively preserved in DS. (shrink)

Abstract The phenomenology of Multiple Personality (MP) syndrome is used to derive an Aristotelian explanation of the failure to achieve rational integration of mental content. An MP subject is best understood as having failed to master the techniques of integrating conative and cognitive aspects of her mental life. This suggests that in irrationality the subject may lack similar skills basic to the proper articulation and use of mental content in belief formation and control of action. The view that emerges (...) centres mind on the activity of a subject rather than a structured causal nexus. (shrink)

“Excited Delirium Syndrome” (ExDS) is a controversial diagnosis. The supposed syndrome is sometimes considered to be a potential cause of death. However, it has been argued that its sole purpose is to cover up excessive police violence because it is mainly used to explain deaths of individuals in custody. In this paper, we examine the epistemic conditions giving rise to the controversial diagnosis by discussing the relation between causal hypotheses, evidence, and data in forensic medicine. We argue that the practitioners’ (...) social context affects causal inquiry through background assumptions that enter inquiry at multiple stages. This analysis serves to better understand the wide usage of the controversial diagnosis of ExDS. (shrink)

A few years ago no one would have suspected that the well‐known disorder of connective tissue, Marfan syndrome, could be caused by mutations in a recently discovered extracellular component, fibrillin. Likewise, nobody would have predicted that fibrillin represents a small family of proteins that are associated with several pheno‐typically overlapping disorders. The fibrillins are integral constituents of the non‐collagenous microfibrils, with an average diameter of 10 nm. These aggregates are distributed in the extracellular matrix of virtually every tissue. Microfibrillar bundles (...) provide the external coating to elastin in elastic fibers, and serve an anchoring function in non‐elastic tissues. At higher resolution, individual microfibrils have a “beads‐on‐a‐string” appearance resulting from the head‐to‐tail polymerization of multiple fibrillin aggregates. Structurally, fibrillin contains a series of repeated sequences homologous to the epidermal growth factor calcium‐binding motif. Characterization of fibrillin mutations in Marfan syndrome patients, together with the elucidation of the structure of the fibrillin proteins, have provided new insights, and raised new questions, about the function of the 10 nm microfibrils. For example, it is possible that the fibrillins, in addition to serving a structural function, might also be involved in regulating cellular activities and morphogenetic programs. It is fitting that the long search for the Marfan syndrome gene has brought a novel group of proteins to the forefront of extracellular matrix biology. (shrink)

This article focuses on the ways that sexual risk behaviors are related to race, class, and gender among low-income, culturally diverse women in South Florida. Data concerning sexual risk and gender are presented in terms of race and class variations. Results indicate that, in general, these women have a high degree of knowledge about acquired immune deficiency syndrome, a quite contemporary awareness of women's gendered subordination, and a lack of trust in heterosexual relationships. Attitudes, beliefs, and knowledge, however, are not (...) translated into sexual behaviors with men partners that would reduce their vulnerability to infection with the human immunodeficiency virus. The data indicate that race is a major factor that places women into an underclass position. Consequently, without socioeconomic resources, gendered behaviors have a direct influence on sexual risk. Multivariate analyses indicate that those women who are sex workers are significantly more likely to negotiate safe sex with clients than with main partners. The research not only challenges mainstream thinking about race, class, and gender but also provides overdue information on the vulnerability of women to HIV infection. (shrink)

This study aimed to elucidate the withdrawal behaviors syndrome (lateness, absence, and intent to leave work) among nurses by examining interrelations between these behaviors and the mediating effect of organizational commitment upon ethical perceptions (caring climate, formal climate, and distributive justice) and withdrawal behaviors. Two-hundred and one nurses from one hospital in northern Israel participated. Data collection was based on questionnaires and hospital records using a two-phase design. The analyses are based on Hierarchical Multiple Regressions and on Structural Equation (...) Modeling with AMOS. Affective commitment was found to mediate the relationship between different dimensions of nurses’ ethical perceptions (caring climate, formal climate, and distributive justice) and their intent to leave work. Lateness was found to be positively related to absence frequency which was found negatively related to intent to leave. Males were late more frequently than females, while seniority was related only to absence frequency. The findings indicated that each withdrawal behavior exhibits unique relationships. The results may help policy makers to focus on improving the ethical environment in order to increase nurses’ commitment and reduce their intent to leave. Improving the ethical environment may be achieved through ethical education for nurses which may promote ethical considerations becoming an integral part of nurses’ work. (shrink)

How can we provide the best care for the growing population of older adults, many of whom are either very frail or very sick? The traditional medical model of care is focused on treatment of single diseases. This can work well for pneumonia, cancer, or diabetes in younger patients. It does not, however, work as well for frail older adults who have accumulated multiple chronic conditions and disabilities. These elders often depend on family or paid caregivers to provide assistance (...) with taking medications, transportation, and other activities of daily living, such as dressing and bathing. A practitioner in the traditional medical model might prescribe medications that make sense in isolation but have harmful... (shrink)

The DNA hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DAC) improve survival and transfusion independence in myelodysplastic syndrome (MDS) and enable a low intensity cytotoxic treatment for aged AML patients unsuitable for intensive chemotherapy, particularly in combination with novel agents. The proposed mechanism of AZA and DAC relies on active DNA replication and therefore patient responses are only observed after multiple cycles of treatment. Although extended dosing may provide the optimal scheduling, the reliance of injectable formulation of the drug (...) limits it to intermittent treatment. Recently, an oral formulation of AZA demonstrated significantly improved patient relapse free survival (RFS) and overall survival (OS) when used as maintenance after chemotherapy for AML. In addition, both DAC and AZA were found to be highly effective to improve survival in elderly patients with AML through combination with other drugs. These recent exciting results have changed the therapeutic paradigm for elderly patients with AML. In light of this, we review current knowledge on HMA mechanism of action, clinical trials exploring dosing and scheduling, and recent HMA combination therapies to enhance efficacy. (shrink)

Patient portals are poised to transform health communication by empowering patients with rapid access to their own health data. The 21st Century Cures Act is a US federal law that, among other provisions, prevents health entities from engaging in practices that disrupt the exchange of electronic health information—a measure that may increase the usage of patient health portals. Caregiver access to patient portals, however, may lead to breaches in patient privacy and confidentiality if not managed properly through proxy accounts. We (...) present an ethical framework that guides policy and clinical workflow development for healthcare institutions to support the best use of patient portals. Caregivers are vital members of the care team and should be supported through novel forms of health information technology (IT). Patients, however, may not want all information to be shared with their proxies so healthcare institutions must support the development and use of separate proxy accounts as opposed to using the patient’s own account as well provide controls for limiting the scope of information displayed in the proxy accounts. Lastly, as socioeconomic barriers to adoption of health IT persist, healthcare providers must work to ensure multiple streams of patient communication, to prevent further propagating health inequities. (shrink)

There is an increasing suspicion that Multiple Personality Disorder is one extreme along a continuum of dissociative phenomena, ranging from children’s pretend play and dreams at one end, through borderline personality disorder, posttraumatic stress syndrome, dissociative disorders not originally specified to a severe and complete personality fragmentation at the other. In this essay, we address the questions of whether a continuum view is correct and how to characterize the differences among the various disorders through distinguishing multiplex from multiple (...) selves. This analysis has implications for how the symptoms of MPD should be characterized and treated as well as shedding some light on the relation between conscious experience and selfhood. (shrink)

AimIn case of extremely rare diseases, case reports are often the only experience to draw from for evidence-based management. Carmi syndrome is a rare, mostly lethal combination of junctional epidermolysis bullosa and pyloric atresia. During an ethical board, there were differences in perception of mortality rate. We tested the hypothesis that the cumulative mortality of single case reports is lower than that of multiple case series.CaseA baby girl was born at 33 weeks gestation with Carmi syndrome. The treatment options (...) discussed in an interdisciplinary ethics board were a palliative approach versus surgical gastrojejunostomy. Because about one third of operated children described in case reports survived, we opted for surgical treatment. The patient died a painful death 4 weeks later.MethodsThe PubMed database was systematically searched for reports of Carmi syndrome. Single case reports were compared to case series in terms of outcome.ResultsA total of 102 cases of Carmi syndrome were identified in the literature. Mortality of single case reports was 17 out of 27 patients (63%), while that of case series was higher at 62 out of 74 patients (84%,p = 0.036).ConclusionsSelection and publication bias may lead to inflation of survival rates in single case reports because successful cases are more likely to be published in the literature. These biases may lead to inappropriately aggressive treatment in futile cases. Clinicians should be cautious when discussing prognosis and making decisions based on the cumulative experience of case reports of extremely rare or novel diseases. (shrink)

The term ‘locked-in’ syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain–computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, (...) sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow–based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants’ capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level–dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, realtime data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method.. (shrink)

The aim of the study was verifying, whether speech development is conditioned by a preterm birth, multiple pregnancy or pregnancy complicated with TTTS. We examined 52 preterm children, 15 of which were born after a single pregnancy and 42 after a multiple pregnancy. 23 children came from a pregnancy complicated by TTTS. The average age of the subjects was 32.5 months. The research methods used in our study were as follows: analysis of medical documentation, a structured clinical interview (...) and psychological conversation. Speech development of a child was assessed using BSID-III. An analysis of the results we obtained showed that there was a lower level of EC in the TTTS children in comparison to multiple-birth children without TTTS and single-birth children. We also found statistically significant relations between the EC scores and gender, age at the time of testing, disability, gestational age, birth weight. (shrink)

ObjectiveTo elucidate the clinical, radiologic characteristics of Leber’s hereditary optic neuropathy (LHON) associated with the other diseases.Materials and methodsClinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital (PLAGH) from December 2014 to October 2018.ResultsA total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 (...) &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time.ConclusionLeber’s hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile. (shrink)

Researchers have found undeniable variability and irrefutable evidence of consistencies in emotional responses across situations, individuals, and cultures. Both must be acknowledged in constructing adequate, enduring models of emotional phenomena. In this article I outline an empirically-grounded model of the structure of the emotion system, in which relatively variable actions may be used to pursue relatively consistent goals within discrete emotion syndromes; the syndromes form a stable, coherent set of strategies for coping with crises and opportunities. I also (...) discuss a framework that can integrate dimensional and discrete perspectives on emotions. (shrink)

The ubiquitin–proteasome system (UPS) is the major proteolytic pathway that degrades intracellular proteins in a regulated manner. Deregulation of the UPS has been implicated in the pathogenesis of many neurodegenerative disorders like Alzheimer's disease, Parkinson's diseases, Huntington disease, Prion‐like lethal disorders, in the pathogenesis of several genetic diseases including cystic fibrosis, Angelman's syndrome and Liddle syndrome and in many cancers. Multiple lines of evidence have already proved that UPS has the potential to be an exciting novel therapeutic target for (...) the treatment of these diseases. Here I review how aberrant functions of various genes have implicated UPS in many human disorders including neurodegeneration and cancers. I also discuss the finding that some proteasome inhibitors possess a therapeutic potential as drugs against many such diseases. BioEssays 30:1172–1184, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Self-injurious behavior is associated with diverse psychiatric conditions. Sometimes, SIB is the most dominant symptom, severely restricting the psychosocial functioning and quality of life of the patients and inhibiting appropriate patient care. In severe cases, it can lead to permanent physical injuries or even death. Primary therapy consists of medical treatment and if implementable, behavioral therapy. For patients with severe SIB refractory to conventional therapy, neuromodulation can be considered as a last recourse. In scientific literature, several successful lesioning and deep (...) brain stimulation targets have been described that can indicate a common underlying neuronal pathway. The objectives of this study were to evaluate the short- and long-term clinical outcome of patients with severe, therapy refractory SIB who underwent DBS with diverse underlying psychiatric disorders and to correlate these outcomes with the activated connectivity networks. We retrospectively analyzed 10 patients with SIB who underwent DBS surgery with diverse psychiatric conditions including autism spectrum disorder, organic personality disorder after hypoxic or traumatic brain injury or Tourette syndrome. DBS targets were chosen according to the underlying disorder, patients were either stimulated in the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus or ventrolateral thalamus. Clinical outcome was measured 6 months after surgery and at long-term follow-up after 10 or more years using the Early Rehabilitation Barthel index and time of restraint. Connectivity patterns were analyzed using normative connectome. Based on previous literature the orbitofrontal cortex, superior frontal gyrus, the anterior cingulate cortex, the amygdala and the hippocampus were chosen as regions of interest. This analysis showed a significant improvement in the functionality of the patients with DBS in the short- and long-term follow-up. Good clinical outcome correlated with higher connectivity to the amygdala and hippocampus. These findings may suggest a common pathway, which can be relevant when planning a surgical procedure in patients with SIB. (shrink)

Frailty is a complex geriatric syndrome with multifactorial associated mechanisms that need to be examined more deeply to help reverse the adverse health-related outcomes. Specific inflammatory and physical health markers have been associated with the onset of frailty, but the associations between these factors and psycho-social health outcomes seem less studied. This systematic review aimed to identify, in the same study design, the potential associations between frailty and markers of inflammation, and physical or psycho-social health. A literature search was (...) performed from inception until March 2021 using Medline, Psycinfo, and EMBASE. Three raters evaluated the articles and selected 22 studies, using inclusion and exclusion criteria. Regarding biomarkers, 95% of the included studies showed significant links between inflammation [especially the higher levels of C-reactive protein and interleukin-6 ], and frailty status. Approximately 86% of the included studies showed strong links between physical health decline, and frailty status. At most, 13 studies among the 22 included ones evaluated psycho-social variables and mixed results were observed regarding the relationships with frailty. Results are discussed in terms of questioning the medical perception of global health, centering mostly on the physical dimension. Therefore, the development of future research studies involving a more exhaustive view of frailty and global health is strongly encouraged. (shrink)

Aging is characterized by the decline and deterioration of functional cells and results in a wide variety of molecular damages and reduced physical and mental capacity. The knowledge on aging process is important because life expectancy is expected to rise until 2050. Aging cannot be considered a homogeneous process and includes different trajectories characterized by states of fitness, frailty, and disability. Frailty is a dynamic condition put between a normal functional state and disability, with reduced capacity to cope with stressors. (...) This geriatric syndrome affects physical, neuropsychological, and social domains and is driven by emotional and spiritual components. Sarcopenia is considered one of the determinants and the biological substrates of physical frailty. Physical and cognitive frailty are separately approached during daily clinical practice. The concept of motoric cognitive syndrome has partially changed this scenario, opening interesting windows toward future approaches. Thus, the purpose of this manuscript is to provide an excursus on current clinical practice, enforced by aneddoctical cases. The analysis of the current state of the art seems to support the urgent need of comprehensive organizational model incorporating physical and cognitive spheres in the same umbrella. (shrink)

The unified framework for addiction (UFA) formulated by Redish et al. is a tour de force. It uniquely predicts that there should be multiple addiction syndromes and pathways – a diversity that would reflect the complexity of the mammalian brain decision system. Here I explore some of the evolutionary and developmental ramifications of UFA and derive several new avenues for research.

This book's dedication reads “to the man I married.” The phrase is a nice incitement to reflect on the book's topic: is the man she married identical with her present husband? Does the dedication imply a subtle reproach? a note of resignation before the inevitable fact that the man I married cannot be the one I'm married to? By the end of her book, Radden concludes that we can't get away from “normative demands of individuality” that remain anchored to common (...) sense. The challenge she takes up is to articulate the intuitions evoked by a wide spectrum of questions about unity and disunity of the person, both diachronic and synchronic. The latter include the dramatic case of Multiple Personality Syndrome or MPD, but also milder cases of dissociation. Radical amnesia, personality changes including those brought about by religious conversions, and disintegration of personality consequent on senile dementia suggest disunity through time. In all cases, Radden opts for a Rawlsian reflective equilibrium, though she rightly notes that “drawing philosophical conclusions from empirical descriptions, on the one hand, and contributing philosophical distinctions and theories to an understanding of those facts, on the other, [are] fraught with methodological dangers.”. (shrink)

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of “self” and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate “self,” and employed it to explain some psychopathological symptoms. In those studies, “self” is understood in a minimalist sense, sheer “for-me-ness.” Unfortunately, explication of the “minimal self” (MS) has relied on conceptual analysis, and applications to psychopathology have (...) been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS’s current scientific status is analogous to that of the “atom,” at the time when “atom” was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for “MS.” Discovery of the brain’s Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit “MS” can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that “levels of consciousness” (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation—a bifurcation point—for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness. (shrink)

It is hypothesized that repeated, non‐invasive stimulation of the vestibular (balance) system, via a small electrical current to the skin behind the ears, will cause the brain centers that control energy homeostasis to shift the body toward a leaner physique. This is because these centers integrate multiple inputs to, in effect, fix a set‐point for body fat, which though difficult to alter is not immutable. They will interpret repeated stimulation of the parts of the vestibular system that detect acceleration (...) as a state of chronic activity. During such a physiologically challenging time it is preferable, from an energy homeostasis viewpoint, to both utilize fat reserves, and reduce the volume of these reserves and thus the energy cost of carrying them around. Hence, this type of vestibular stimulation could potentially be a therapeutic option for metabolic syndrome disorders such as obesity. This hypothesis is eminently testable via a clinical trial. (shrink)

Classical theories of emotion have long debated the extent to which human emotion is a universal or culturally constructed experience. Recent advances in emotion research in cultural neuroscience highlight several aspects of emotional generation and experience that are both phylogenetically conserved as well as constructed within human cultural contexts. This review highlights theories and methods from cultural neuroscience that examine how cultural and biological processes shape emotional generation, experience, and regulation across multiple time scales. Recent advances in the neurobiological (...) basis of culture-bound syndromes, such as Hwa-Byung (fire illness), provide further novel insights into emotion and mental health across cultures. Implications for emotion research in cultural neuroscience for population health disparities in psychopathology and global mental health will be discussed. (shrink)

The broad issue in this paper is the relationship between cognitive psychology and neuroscience. That issue arises particularly sharply for cognitive neurospsychology, some of whose practitioners claim a methodological autonomy for their discipline. They hold that behavioural data from neuropsychological impairments are sufficient to justify assumptions about the underlying modular structure of human cognitive architecture, as well as to make inferences about its various components. But this claim to methodological autonomy can be challenged on both philosophical and empirical grounds. A (...) priori considerations about (cognitive) multiple realisability challenge the thesis on philosophical grounds, and neuroscientific findings from developmental disorders substantiate that challenge empirically. The conclusion is that behavioural evidence alone is inadequate for scientific progress since appearances of modularity can be thoroughly deceptive, obscuring both the dynamic processes of neural development and the endstate network architecture of real cognitive systems. (shrink)

RationaleSurrogates of critically ill patients often have inaccurate expectations about prognosis. Yet there is little research on how intensive care unit clinicians should discuss prognosis, and existing expert opinion-based recommendations give only general guidance that has not been validated with surrogate decision makers.ObjectiveTo determine the perspectives of key stakeholders regarding how prognostic information should be conveyed in critical illness.MethodsThis was a multicenter study at three academic medical centers in California, Pennsylvania, and Washington. One hundred eighteen key stakeholders completed in-depth semistructured (...) interviews. Participants included 47 surrogates of adult patients with acute respiratory distress syndrome; 45 clinicians working in study ICUs, including physicians, nurses, social workers, and spiritual care providers; and 26 experts in health communication, decision science, ethics, family-centered care, geriatrics, healthcare disparities, palliative care, psychology, psychiatry, and critical care.Measurements and main resultsThere was broad support among surrogates for existing expert recommendations, including truthful prognostic disclosure, emotional support, tailoring the disclosure strategy to each family's needs, and checking for understanding. In addition, stakeholders offered suggestions that add specificity to existing recommendations, including: In addition to conveying prognostic estimates, clinicians should help families "see the prognosis for themselves" by showing families radiographic images and explaining the clinical significance of physical manifestations of severe disease at the bedside. Many physicians did not support using numeric estimates to convey prognosis to families, whereas many surrogates, clinicians from other disciplines, and experts believed numbers could be helpful. Clinicians should conceptualize prognostic communication as an iterative process that begins with a preliminary mention of the possibility of death early in the ICU stay and becomes more detailed as the clinical situation develops. Although prognostic information should be initially disclosed by physicians, other members of the multidisciplinary team-nurses, social workers, and spiritual care providers-should be given explicit role responsibilities to reinforce physicians' prognostications and help families process a poor prognosis emotionally.ConclusionsFamily members, clinicians, and experts identified specific communication behaviors that clinicians should use to discuss prognosis in the critical care setting. These findings extend existing opinion-based recommendations and should guide interventions to improve communication about prognosis in ICUs. (shrink)

Myofascial Pain Syndrome is somatic pain due to muscular tension associated with muscular-skeletal imbalance. The pain and discomfort of the patient is not simply due to some isolated tension, but in the dynamic relationships between related structures. As the body adjusts to reestablish balance and symmetry, the tension and pain in one area “diagonalizes,” creating a tense correlate along a diagonal axis. This diagonalization of tension exacerbates and perpetuates the initial condition of pain and dysfunction. The purpose of this paper (...) is to argue that there are moral and social analogues to MFPS with their own forms of diagonalized asymmetry. Following the Aristotelian model of virtue and vice, whereby moral traits and dispositions become vice as a result of a loss of balance in conduct, and George Herbert Mead’s social psychology, which describes the self in terms of dynamic interrelation and co-operation of multiple sub-selves, I maintain that otherwise positive strengths in personal character, when overemphasized or exaggerated, can be juxtaposed to analogous weaknesses in related areas of personal health and conduct. I will argue that the descriptive analogy of MFPS has a corollary set of prescriptions for restoring balance in a moral subject. (shrink)

We present a theory of human artistic experience and the neural mechanisms that mediate it. Any theory of art has to ideally have three components. The logic of art: whether there are universal rules or principles; The evolutionary rationale: why did these rules evolve and why do they have the form that they do; What is the brain circuitry involved? Our paper begins with a quest for artistic universals and proposes a list of ‘Eight laws of artistic experience’ -- a (...) set of heuristics that artists either consciously or unconsciously deploy to optimally titillate the visual areas of the brain. One of these principles is a psychological phenomenon called the peak shift effect: If a rat is rewarded for discriminating a rectangle from a square, it will respond even more vigorously to a rectangle that is longer and skinnier that the prototype. We suggest that this principle explains not only caricatures, but many other aspects of art. Example: An evocative sketch of a female nude may be one which selectively accentuates those feminine form-attributes that allow one to discriminate it from a male figure; a Boucher, a Van Gogh, or a Monet may be a caricature in ‘colour space’ rather than form space. Even abstract art may employ ‘supernormal’ stimuli to excite form areas in the brain more strongly than natural stimuli. Second, we suggest that grouping is a very basic principle. The different extrastriate visual areas may have evolved specifically to extract correlations in different domains , and discovering and linking multiple features into unitary clusters -- objects -- is facilitated and reinforced by direct connections from these areas to limbic structures. In general, when object-like entities are partially discerned at any stage in the visual hierarchy, messages are sent back to earlier stages to alert them to certain locations or features in order to look for additional evidence for the object . Finally, given constraints on allocation of attentional resources, art is most appealing if it produces heightened activity in a single dimension rather than redundant activation of multiple modules. This idea may help explain the effectiveness of outline drawings and sketches, the savant syndrome in autists, and the sudden emergence of artistic talent in fronto-temporal dementia. In addition to these three basic principles we propose five others, constituting a total of ‘eight laws of aesthetic experience’. (shrink)

Mutations in enhancer‐associated chromatin‐modifying components and genomic alterations in non‐coding regions of the genome occur frequently in cancer, and other diseases pointing to the importance of enhancer fidelity to ensure proper tissue homeostasis. In this review, I will use specific examples to discuss how mutations in chromatin‐modifying factors might affect enhancer activity of disease‐relevant genes. I will then consider direct evidence from single nucleotide polymorphisms, small insertions, or deletions but also larger genomic rearrangements such as duplications, deletions, translocations, and inversions (...) of specific enhancers to demonstrate how they have the ability to impact enhancer activity of disease genes including oncogenes and tumor suppressor genes. Considering that the scientific community only fairly recently has begun to focus its attention on “enhancer malfunction” in disease, I propose that multiple new enhancer‐regulated and disease‐relevant processes will be uncovered in the near future that will constitute the mechanistic basis for novel therapeutic avenues. (shrink)

Mutations in enhancer‐associated chromatin‐modifying components and genomic alterations in non‐coding regions of the genome occur frequently in cancer, and other diseases pointing to the importance of enhancer fidelity to ensure proper tissue homeostasis. In this review, I will use specific examples to discuss how mutations in chromatin‐modifying factors might affect enhancer activity of disease‐relevant genes. I will then consider direct evidence from single nucleotide polymorphisms, small insertions, or deletions but also larger genomic rearrangements such as duplications, deletions, translocations, and inversions (...) of specific enhancers to demonstrate how they have the ability to impact enhancer activity of disease genes including oncogenes and tumor suppressor genes. Considering that the scientific community only fairly recently has begun to focus its attention on “enhancer malfunction” in disease, I propose that multiple new enhancer‐regulated and disease‐relevant processes will be uncovered in the near future that will constitute the mechanistic basis for novel therapeutic avenues. (shrink)

Vascular development entails multiple cell‐fate decisions to specify a diverse array of vascular structures. Notch proteins are signaling receptors that regulate cell‐fate determination in a variety of cell types. The finding that Notch genes are robustly expressed in the vasculature suggests roles for Notch in guiding endothelial and associated mural cells through the myriad of cell‐fate decisions needed to form the vasculature. In fact, mice with defects in genes encoding Notch, Notch ligands, and components of the Notch signaling cascade (...) invariably display vascular defects. Human Notch genes are linked to Alagille's Syndrome, a developmental disorder with vascular defects, and CADASIL, a cerebral arteriopathy. Studies in zebrafish, mice and humans indicate that Notch works in conjunction with other angiogenic pathways to pattern and stabilize the vasculature. Here, we will focus on established functions for Notch in vascular remodeling and arterial/venous specification and more speculative roles in vascular homeostasis and organ‐specific angiogenesis. BioEssays 26:225–234, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Human beings have the unique ability to consciously reflect on the nature of the self. But reflection has its costs. We can ask what the self is, but as David Hume pointed out, the self, once reflected upon, may be nowhere to be found. The favored view is that we are material beings living in the material world. But if so, a host of destabilizing questions surface. If persons are just a sophisticated sort of animal, then what sense is there (...) to the idea that we are free agents who control our own destinies? What makes the life of any animal, even one as sophisticated as Homo sapiens, worth anything? What place is there in a material world for God? And if there is no place for a God, then what hold can morality possibly have on us--why isn't everything allowed? Flanagan's collection of essays takes on these questions and more. He continues the old philosophical project of reconciling a scientific view of ourselves with a view of ourselves as agents of free will and meaning-makers. But to this project he brings the latest insights of neuroscience, cognitive science, and psychiatry, exploring topics such as whether the conscious mind can be explained scientifically, whether dreams are self-expressive or just noise, the moral socialization of children, and the nature of psychological phenomena such as multiple personality disorder and false memory syndrome. What emerges from these explorations is a liberating vision which can make sense of the self, agency, character transformation, and the value and worth of human life. Flanagan concludes that nothing about a scientific view of persons must lead to nihilism. (shrink)

Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto‐oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in (...) neural crest lineages and whose ligand, glial‐cell‐line‐derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two ‘faces’ of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect. (shrink)

If a brain is uploaded into a computer, will consciousness continue in digital form or will it end forever when the brain is destroyed? Philosophers have long debated such dilemmas and classify them as questions about personal identity. There are currently three main theories of personal identity: biological, psychological, and closest continuer theories. None of these theories can successfully address the questions posed by the possibility of uploading. I will argue that uploading requires us to adopt a new theory of (...) identity, psychological branching identity. Psychological branching identity states that consciousness will continue as long as there is continuity in psychological structure. What differentiates this from psychological identity is that it allows identity to continue in multiple selves. According to branching identity, continuity of consciousness will continue in both the original brain and the upload after nondestructive uploading. Branching identity can also resolve long standing questions about split-brain syndrome and can provide clear predictions about identity in even the most difficult cases imagined by philosophers. (shrink)

Alzheimer’s disease is an insidious onset neurodegenerative syndrome without effective treatment or cure. It is rapidly becoming a global health crisis that is overwhelming healthcare, society, and individuals. The clinical nature of neurocognitive decline creates significant challenges in bidirectional communication between caregivers and persons with Alzheimer’s disease that can negatively impact quality-of-life. This paper sought to understand how and to what extent would awareness training about the levels of consciousness in AD influence the quality-of-life interactions in the caregiver-patient dyad. A (...) literature review of multiple databases was conducted utilizing a transdisciplinary approach. The sum of findings indicates a positive relationship between enhanced caregiver awareness and training, positive interactions, and improved QOL measures among patients and caregivers. A multidirectional relationship was found among healthcare policies, training and education resources, caregivers, and persons with AD. Specifically, the current lack of policy and inadequate training and educational resources has various detrimental effects on patients and caregivers, while improvements in training and education of caregivers yields positive outcomes in communication and QOL. Furthermore, evidence of preserved consciousness in persons with AD was demonstrated from multiple disciplines, including neurobiological, psychological, and biopsychosocial models. The literature further revealed several methods to access the preserved consciousness in persons with AD and related dementias, including sensory, emotional, and cognitive stimulations. The evidence from the literature suggests a reframed approach to our understanding and treatment of persons with AD is not only warranted, but crucial to address the needs of those affected by AD. (shrink)

Health professionals increasingly face patients with complex health problems and this pressurizes them to cooperate. The authors have analyzed how the complexity of health care problems relates to two types of cooperation: consultation and multidisciplinary teamwork (MTW). Moreover, they have analyzed the impact of these two types of cooperation on perceived professional autonomy. Two teams were studied, one team dealing with geriatric patients and another treating oncology patients. The authors conducted semi-structured interviews, studied written documents, held informal discussions and (...) observed the teams at work. Consultation was most likely to take place when a patient had multiple problems. However, if these problems were interrelated, i.e. the solution for one problem interfered with solving another, then MTW was favored. The same was true when the available information was equivocal such that there were conflicting interpretations of a problem. How the professionals perceived the relationship between complexity and the need to cooperate depended on their expertise, their occupational background, and their work orientation. Consultation did not affect the professional autonomy of the health care professionals. MTW however did decrease the perceived level of professional autonomy. The extent to which this occurred seemed to depend on the quality of the interpersonal relations within the team. The findings can help in selecting the most appropriate and efficient type of cooperation based on the complexity of a patient’s problems. They can also help team leaders to stimulate reflection and feedback processes, and medical trainers to develop competencies among students related to such teamwork behaviors. (shrink)

The notions of at-risk and subthreshold conditions are increasingly discussed in psychiatry to describe mild, brief, or otherwise atypical syndromes that fail to meet the criteria for clinical relevance. However, the concept of vulnerability is still underexplored in philosophy of psychiatry. This article discusses psychiatric vulnerability to clarify some conceptual issues about the various factors contributing to vulnerability, the notions of risk and protection, and the idea that there are multiple ways of crossing the threshold to clinical relevance. (...) My goal is to lay the groundwork for a finer-grained discussion on psychiatric vulnerability that reflects the complex nature of mental conditions and illustrates the kind of thinking needed in clinical practice. (shrink)

Smajdor addresses the problem of inferior clinical outcomes among adults with impairments of capacity to give informed consent (AWIC). She notes that AWIC are generally excluded from clinical trials to protect them against harms and avoid exploitation and claims there is a causal link between involvement in clinical trials and favourable outcomes. She argues, given this link, that we should increase AWIC representation in clinical trials and can justifiably do so by recognising the capacity of AWIC to assent. AWIC form (...) a diverse group, with multiple aetiologies, including, for example, Down syndrome, traumatic brain injury and dementia. In some cases, the inability to consent may fluctuate so that the same person could be AWIC only at certain times. Yet despite these differences, the group has a shared unmet need. We agree with Smajdor that AWIC outcomes should be improved, but question whether simply increasing representation in clinical trials is sufficient to achieve this. We identify the following points: 1. AWIC are under-represented in clinical trials. There is evidence of widespread exclusion of AWIC in clinical trials within the UK and abroad and it is often a specific exclusion criterion.1 2. AWIC have worse clinical outcomes and a lower life expectancy. The life expectancy …. (shrink)