In the last few years, the molecular and genetic nature of the granulocyte colonystimulating factor, which controls proliferation and differentiation of neutrophils, has been characterized. Recent clinical application of G‐CSF proves that this hormone is effective in the treatment of patients suffering from neutropenia.

Once hematopoiesis is established in the bone marrow, a continuous egress of hematopoietic stem cells (HSCs) to the periphery occurs at a low frequency. It has been proposed that this phenomenon is part of a regenerative homeostatic mechanism that ensures the maintenance of hematopoiesis through the life of the individual. The administration of certain cytotoxic drugs or cytokines can enhance the mobilization of hematopoietic progenitors to the periphery. During the past 15 years, granulocyte‐colony stimulating factor (G‐CSF) (...) has been used as a standard cytokine for mobilization protocols in experimental models and in humans. Despite extensive efforts by multiple groups, a definitive mechanism explaining its role in mobilization has not been provided. In a recent paper, Katayama et al.,1 through a series of clever associations supported by well‐defined experimental systems, proposed that signals through the sympathetic nervous system modify the activity of the hematopoietic niche, acting as regulators of the mobilization of hematopoietic progenitors. This surprising finding adds a new level of complexity to the cellular milieu responsible for generation and maintenance of the hematopoietic niche. BioEssays 28: 687–691, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Stem cells and their malignant counterparts require the support of a specific microenvironment or “niche”. While various anti‐cancer therapies have been broadly successful, there are growing opportunities to target the environment in which these cells reside to further improve therapeutic efficacy and outcome. This is particularly true when the aim is to target normal or malignant stem cells. The field aiming to target or use the niches that harbor, protect, and support stem cells could be designated as “nichotherapy”. In this (...) essay, we provide a few examples of nichotherapies. Some have been employed for decades, such as hematopoietic stem cell mobilization, whereas others are emerging, such as chemosensitization of leukemia stem cells by targeting their niche. (shrink)

Stem cells and their malignant counterparts require the support of a specific microenvironment or “niche”. While various anti‐cancer therapies have been broadly successful, there are growing opportunities to target the environment in which these cells reside to further improve therapeutic efficacy and outcome. This is particularly true when the aim is to target normal or malignant stem cells. The field aiming to target or use the niches that harbor, protect, and support stem cells could be designated as “nichotherapy”. In this (...) essay, we provide a few examples of nichotherapies. Some have been employed for decades, such as hematopoietic stem cell mobilization, whereas others are emerging, such as chemosensitization of leukemia stem cells by targeting their niche. (shrink)

Mouse pre‐implantation development appears to be under the control of paracrine and autocrine growth factors. The epithelium of the oviduct and the uterus together, with the population of macrophages and lymphocytes present in the reproductive tract from the onset of pregnancy, are thought to be the major sources of paracrine growth factors targeted to the developing embryos. Some of the growth factors are synthesized by both uterine epithelial cells and activated lympho‐hematopoietic cells, suggesting a partial overlap of the regulatory signals (...) used by the reproductive and lympho‐hematopoietic systems. Such growth factors may be the long sought‐after mediators of the synchrony between the pre‐implantation embryo and the sex‐steroid hormone‐induced changes in the uterus. (shrink)

Pain has not only sensory, but also emotional and cognitive, components. Some studies have explored the effect of pain on time perception, but the results remain controversial. Whether individual pain-related emotional and cognitive factors play roles in this process should also be explored. In this study, we investigated the effect of electrical stimulation–induced pain on interval timing using a temporal bisection task. During each task session, subjects received one of five types of stimulation randomly: no stimulus and 100 and 300 (...) ms of non-painful and painful stimulation. Pain-related emotional and cognitive factors were measured using a series of questionnaires. The proportion of “long” judgments of a 1,200-ms visual stimulus duration was significantly smaller with 300 ms painful stimulation than with no stimulus and 100 ms and 300 ms non-painful stimulation. The point of subjective equality did not differ among sessions, but the average Weber fraction was higher for painful sessions than for no-stimulus session. The pain fear score correlated positively with the PSE under 100 ms non-painful and painful and 300 ms painful stimulation. Pain catastrophizing and pain anxiety scores correlated significantly with the WF under no stimulus and 100 ms non-painful stimulation, respectively. These results suggest that electrical stimulation–induced pain affects temporal sensitivity, and that pain-related emotional and cognitive factors are associated with the processing of time perception. (shrink)

The paper has two complementary objectives. First, it sustains an analysis of the concept of ‘coloniality’ that accounts for the epistemic imbalance in the modern world, demonstrating precisely how Africa is adversely affected, having been caught up in the throes of coloniality and its epistemic implications. Second – and complementarily – the paper attempts to bring this very concept of ‘coloniality’ into the discourse on Africa’s emigration crisis, arguing that Africa’s emigration crisis is traceable, inter alia, to the epistemic imbalance (...) in the very structure of modernity. This imbalance results from the stifling of Africa’s epistemic resources under Western epistemic hegemony. Epistemic coloniality, of course interacting with some material factors, creates a sufficient condition for emigration. It is further theorized that the apparent lack of epistemic will on the part of Africans to mobilize some surviving epistemic resources to address some problems on their own is also a function of coloniality. (shrink)

Ant colony optimization, which is one of the metaheuristics imitating real ant foraging behavior, is an effective method to find a solution for the traveling salesman problem. The rank-based ant system has been proposed as a developed version of the fundamental model AS of ACO. In the ASrank, since only ant agents that have found one of some excellent solutions are let to regulate the pheromone, the pheromone concentrates on a specific route. As a result, although the ASrank can (...) find a relatively good solution in a short time, it has the disadvantage of being prone falling into a local solution because the pheromone concentrates on a specific route. This problem seems to come from the loss of diversity in route selection according to the rapid accumulation of pheromones to the specific routes. Some ACO models, not just the ASrank, also suffer from this problem of loss of diversity in route selection. It can be considered that the diversity of solutions as well as the selection of solutions is an important factor in the solution system by swarm intelligence such as ACO. In this paper, to solve this problem, we introduce the ant system using individual memories aiming to improve the ability to solve TSP while maintaining the diversity of the behavior of each ant. We apply the existing ACO algorithms and ASIM to some TSP benchmarks and compare the ability to solve TSP. (shrink)

The goal of this article is to shed light on Deep Brain Stimulation (DBS) postoperative suicidality risk factors within Treatment Resistant Depression (TRD) patients, in particular by focusing on the ethical concern of enrolling patient with history of self-estrangement, suicide attempts and impulsive–aggressive inclinations. In order to illustrate these ethical issues we report and review a clinical case associated with postoperative feelings of self-estrangement, self-harm behaviours and suicide attempt leading to the removal of DBS devices. Could prospectively identifying and excluding (...) patients with suicidality risk factors from DBS experimental trials—such as history of self-estrangement, suicide attempts and impulsive–aggressive inclinations—lead to minimizing the risk of suicidality harm? (shrink)

The use of head-mounted displays (HMD) for virtual reality (VR) application-based purposes including therapy, rehabilitation, and training is increasing. Despite advancements in VR technologies, many users still experience sickness symptoms. VR sickness may be influenced by technological differences within HMDs such as resolution and refresh rate, however, VR content also plays a significant role. The primary objective of this systematic review and meta-analysis was to examine the literature on HMDs that report Simulator Sickness Questionnaire (SSQ) scores to determine the impact (...) of content. User factors associated with VR sickness were also examined. A systematic search was conducted according to PRISMA guidelines. Fifty-five articles met inclusion criteria, representing 3,016 participants (mean age range 19.5-80; 41% female). Findings show gaming content recorded the highest total SSQ mean 34.26 (95%CI 29.57-38.95). VR sickness profiles were also influenced by visual stimulation, locomotion and exposure times. Older samples (mean age ≥35 years) scored significantly lower total SSQ means than younger samples, however, these findings are based on a small evidence base as a limited number of studies included older users. No sex differences were found. Across all types of content, the pooled total SSQ mean was relatively high 28.00 (95%CI 24.66-31.35) compared with recommended SSQ cut-off scores. These findings are of relevance for informing future research and the application of VR in different contexts. (shrink)

Mechanical stimulation has a critical role in the development and maintenance of the skeleton. This function requires the perception of extracellular stimuli as well as their conversion into intracellular biochemical responses. This process is called mechanotransduction and is mediated by a plethora of molecular events that regulate bone metabolism. Indeed, mechanoreceptors, such as integrins, G protein‐coupled receptors, receptor protein tyrosine kinases, and stretch‐activated Ca2+ channels, together with their downstream effectors coordinate the transmission of load‐induced signals to the nucleus and the (...) expression of bone‐related genes. During the past decade, scientists have gained increasing insight into the molecular networks implicated in bone mechanotransduction. In the present paper, we consider the major signaling cascades and transcription factors that control bone and cartilage mechanobiology and discuss the influence of the mechanical microenvironment on the determination of skeletal morphology. (shrink)

It has been shown that various types of stress initiate different physiological and neuroendocrine disorders. Oxytocin is mainly produced in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. Hypothalamic OT has antistress effects and attenuates the hypothalamic–pituitary–adrenal axis. One mechanism behind the antistress effects of OT is mediated through the inhibition from GABAA receptors on corticotropin-releasing factor expression at the PVN. Various manual therapies such as acupuncture, transcutaneous electrical nerve stimulation, and massage initiate the stimulation of somatosensory neurons (...) of the body. It is well-known that TENS simulates OT expression, while it inhibits CRF expression at the PVN following chronic stress loading in rodents. Upregulation of OT expression at the hypothalamus is activated by the somatosensory stimulation, which is mediated via the spinothalamic pathway. Thus, somatosensory stimulation is beneficial in treating stress-associated symptoms. Hypothalamic OT is associated with the social behaviors, including maternal care and affiliation. Childhood neglect and/or child abuse are severely responsible for deleterious long-term effects on the cognitive/social activity and behavioral development. At parturition, a profound amount of OT is released into the systemic circulation in response to vaginal and cervical stimulation caused by the body of fetus, which induces the onset of maternal behavior. Peridural anesthesia effectively impairs the sensitivity to vaginal and cervical stimulation at parturition. OT levels in cerebrospinal fluid is significantly reduced following peridural anesthesia. The vaginal delivery mothers had significantly more OT pulses than the caesarian section mothers. Due to low levels of endogenous OT, maternal behavior could be interrupted by epidural anesthesia and CS at parturition because of the reduction of the usual sensory input from the genitalia. (shrink)

Deep Brain Stimulation (DBS) is an invasive therapeutic method involving the implantation of electrodes and the electrical stimulation of specific areas of the brain to modulate their activity. DBS brings therapeutic benefits, but can also have adverse side effects. Recently, neuroethicists have recognized that DBS poses a threat to the very fabric of human existence, namely, to the selves of patients. This article provides a review of the neuroethical literature examining this issue, and identifies the crucial dimensions related to the (...) self which DBS may endanger—personal identity, authenticity, and autonomy. The most influential theories accounting for these dimensions are analyzed herein, and it is argued that most of these theories require further refinement. This paper also demonstrates the interrelation between personal identity, authenticity, and autonomy, and concludes that one can only fully understand the impact of DBS on the self when all of these factors are taken into account. (shrink)

Apoptosis is now widely recognized as a common form of cell death and represents a mechanism of cell clearance in many physiological situations where deletion of cells is required. Peptide growth factors, initially characterised as stimulators of cell proliferation, have now been shown to inhibit death in many cell types. Deprivation of growth factors leads to the induction of apoptosis, i.e. condensation of chromatin and degradation in oligonucleosomesized fragments, formation of plasma and nuclear membrane blebs and cell fragmentation into apoptotic (...) bodies which can be taken up by neighbouring cells. Here we discuss the mechanism(;s) by which growth factors may inhibit apoptosis. (shrink)

This review article enters into discussion with Peter Kallaway, in his work, The Changing Face of Colonial Education in Africa: Education, Science and Development, who raises serious issues related to the historical development of South Africa’s education during the first half of the 19th century and its current situation and future prospects in the broader context of African education. Education is a dynamic process that encompasses the formal and informal sectors historically. In South Africa, the informal was the norm for (...) centuries before the intrusion of Western influences and formal education needs to work alongside the informal processes based in the home, the church and the community. Formal education is a product of the West and came to occupy the determinative place in the period covered by this book, while the informal sector was relegated to a subservient role despite its inherent value. Kallaway discusses these issues by analysing the contributions of external factors such as the International Missionary Council in the religious sphere and the New Education Fellowship and the British colonial service in the secular sphere. These played a significant role in the movement from ‘culture-bound’ to a universalised approach to education in Africa and particularly South Africa. Alongside this, the role of mission education is discussed as a source of tension with external forces and as a significant contributor to the development of education not restricted to the religious domain. Mission education emerges as an innovative force in educational development as a part of the international movement within the context of an emerging ‘development’ paradigm. The external and internal forces and the cultural and universalising are not necessarily in opposition to one another but often in conversation with and in tension with one another’s assumptions. Kallaway undertakes two case studies of South African scholars, Donald M’Timkulu and SEK Mqhayi in order to refine his analysis. It has been alleged with truth that the trader and settler followed the missionary, who was the agent of European imperialism, working hand in hand with the colonial powers for the subjugation of the black people and the territorial extension of the imperialist power. This view has been challenged by Brian Stanley who cautions against a too simplistic interpretation of the relationship between colonisation and Christianisation reached through ideological means rather than intensive historical research. He concludes that the process first appears more complex and seeks to avoid generalisations. This provides an appropriate starting point for this review article, which attempts to go beyond the historical by raising contemporary issues related to the concept of Africanisation.Contribution: This article contributes to the ongoing debate regarding developments in education in a colonial context from a historical perspective. This is relevant to current debates and challenges to the ongoing effects of colonisation in education in a democratic society and the prospect of an epistemological shift towards the Africanisation of education. (shrink)

Introduction As deep brain stimulation (DBS) has shifted to being used earlier during Parkinson’s disease (PD), data is lacking regarding patient specific attitudes, preferences, and factors which may influence the timing of and decision to proceed with DBS in the United States. This study aims to identify and compare attitudes and preferences regarding the earlier use of DBS in Parkinson’s patients who have and have not undergone DBS. Methods We developed an online survey concerning attitudes about DBS and its timing (...) in PD. The survey was distributed nationally in the United States via the Michael J. Fox Foundation Trial Finder, the American Parkinson Disease Association flyers, and as a link on the Parkinson Alliance website. Differences in responses between PD DBS and non-DBS patients were assessed. Results A total of 445 patients with PD met eligibility criteria for the survey of which 160 self-identified as having undergone DBS. Fifty-five percent (n = 124) of non-DBS patients believed that DBS for PD should only be considered after all medication options have been tried. Patients favoring early DBS had fewer concerns regarding the surgery than those favoring later DBS. Conclusion Our findings highlight a variety of important considerations and concerns patients have regarding DBS and its timing. These viewpoints are important aspects of shared decision-making, as they help to identify patients’ preferences, values, and goals, which should enable providers to better navigate, with their patients, the decision path for therapeutic options to consider. (shrink)

Ambiguity surrounding the effect of external engagement on academic research has raised questions about what motivates researchers to collaborate with third parties. We argue that what matters for society is research that can be absorbed by users. We define ‘openness’ as a willingness by researchers to make research more usable by external partners by responding to external influences in their own research practices. We ask what kinds of characteristics define those researchers who are more ‘open’ to creating usable knowledge. Our (...) empirical study analyses a sample of 1583 researchers working at the Spanish Council for Scientific Research. Results demonstrate that it is personal factors that determine which researchers have open behaviours. The paper concludes that policies to encourage external engagement should focus on experiences which legitimate and validate knowledge produced through user encounters, both at the academic formation career stage as well as through providing ongoing opportunities to engage with third parties. (shrink)

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease. Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBSper sefrom concurrent reduction of dopamine replacement therapy, from underlying PD pathology or from disease (...) progression. To this end, pre-clinical models allow for the dissociation of each of these factors, and to establish neural substrates underlying the emergence of motivational symptoms following STN-DBS. Here, we performed a systematic analysis of rodent studies assessing the effects of STN-DBS on reward seeking, reward motivation and reward consumption across a variety of behavioral paradigms. We find that STN-DBS decreases reward seeking in the majority of experiments, and we outline how design of the behavioral task and DBS parameters can influence experimental outcomes. While an early hypothesis posited that DBS acts as a “functional lesion,” an analysis of lesions and inhibition of the STN revealed no consistent pattern on reward-related behavior. Thus, we discuss alternative mechanisms that could contribute to the amotivational effects of STN-DBS. We also argue that optogenetic-assisted circuit dissection could yield important insight into the effects of the STN on motivated behavior in health and disease. Understanding the mechanisms underlying the effects of STN-DBS on motivated behavior-will be critical for optimizing the clinical application of STN-DBS. (shrink)

Since the 19th century, artist colonies around the world have provided solitary time and space for creative individuals to work, often surrounded by inspiring natural beauty and, alternatively, the stimulating company of other artists. A brief discussion of five such colonies in the United States—Yaddo, MacDowell, Hambidge Center, Dorland Mountain Arts Colony, and the Vermont Studio Center—reveals that, for all the differences, each is the legacy of visionary founders who believed it essential for society to ensure creativity by (...) supporting creative individuals, a need more urgent the less other social institutions call us to our highest selves. (shrink)

The adaptive BCI known as ‘closed-loop deep brain stimulation’ (clDBS) is a device that stimulates the brain in order to prevent pathological neural activity and automatically adjusts stimulation levels based on computational algorithms that detect or predict those pathological processes. One of the prominent ethical concerns raised by clDBS is that, by inhibiting or modulating the undesirable neural states of a cognitive agent automatically, the device potentially undermines her autonomy. It has been argued that clDBS is not a threat because (...) autonomy is fundamentally relational, i.e., it essentially depends on external (e.g., social or cultural) factors. If the relational approach to autonomy includes human-computer interaction, then the mechanisms of clDBS, even if external to the brain and exerting some degree of control over the individual, may support her autonomy. However, DBS applications are substantially different from one another, each involving a specific neurological or psychiatric condition, neural target, mechanism and symptom(s), and therefore at least some of them may not fit into the relational analysis. I examine different clDBS applications for treatment resistant depression and claim that while internal capsule/ventral striatum (VC/VS) clDBS is a case of relational autonomy, subgenual cingulate gyrus (Cg25) clDBS is not. Autonomy (relational or otherwise) requires some degree of self-regulation of our motivational states, which is supported by VC/VS DBS but is absent in Cg25 DBS. In Cg25 DBS the device itself directly influences motivational states, thus substituting or overriding (instead of supporting) the auto-regulatory cognitive processes required for autonomous action. (shrink)

It has always been a mantra of Habsburg history that Austria-Hungary never had colonies. This article investigates why Bosnia-Herzegovina can be regarded as such indeed, developing a check list of factors from critical colonial history, showing that it is a Eurocentric view actually that prevents us from recognizing colonialism on European soil.

This article adopts a population-level bioethics approach to analyzing the ethical implications of novel deep-brain stimulation (DBS) technologies. I claim that a microlevel focus on costs and benefits is necessary but insufficient to address the concerns of social justice and health equity that attend the potential utilization of DBS technologies. A macrosocial, population-based analysis notes two ethically significant trends regarding novel health technologies: (1) that they are the prime mover of hyperinflationary health cost trajectories, and (2) that even where they (...) improve overall population health such technologies may expand health inequalities. Such an expansion could exacerbate what Powers and Faden have identified as “densely-woven patterns of disadvantage,” and therein could contravene mandates of social justice. Such concerns of justice and equity are sharpened by the fact that those populations that bear the highest risk of suffering the injuries and illnesses for which DBS technologies might be warranted are among the most disadvantaged groups in American society. Accordingly, ethical analysis of DBS technologies must include an assessment of the evidence suggesting that in their capacity to improve health and compress health inequalities, whole-population approaches that address the upstream factors that shape distributions of neuropsychiatric injuries and illness may be preferable to acute health interventions. However, the article warns against the false-choice fallacy, and notes that whole-population policies and acute care interventions can be simultaneously endorsed. The article concludes by suggesting that the ethical issue of relative priority between these approaches is best framed via a population-level analysis. (shrink)

ObjectivesSeveral studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM.MethodsIn this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants (...) completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS).ResultsThere was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction.ConclusionOur prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis. (shrink)

Gilbert et al. argue that the neuroethics literature discussing the putative effects of Deep Brain Stimulation on personality largely ignores the scientific evidence and presents distorted claims that personality change is induced by the DBS stimulation. This study contributes to the first-hand primary research on the topic exploring DBS clinicians’ views on post-DBS personality change among their patients and its underlying cause. Semi-structured interviews were conducted with sixteen clinicians from various disciplines working in Australian DBS practice for movement disorders and/or (...) psychiatric conditions. Thematic analysis of the interviews revealed five primary themes: 1) types, frequency and duration of personality change, 2) causes of personality change, 3) impact on patient and family, 4) communication, comprehension and awareness, and 5) management. Clinicians described a variety of personality changes in Parkinson’s disease following DBS including irritability, impulsivity and impaired decision-making. The frequency of personality change seen in patients varied amongst clinicians, but changes were overwhelmingly transient. Clinicians considered both DBS stimulation and additional factors as inducing personality change. For DBS patients with major depressive disorder, a restoration of pre-morbid personality was associated with alleviation of illness. Considerations for future research of personality change following DBS include selecting suitable tools for quantitative examination and developing a common language between the scientific and ethics communities. Clinical implications including recommendations for the informed consent process for patients and families and clinicians’ management of personality change are discussed. (shrink)

Gilbert et al. argue that the neuroethics literature discussing the putative effects of Deep Brain Stimulation on personality largely ignores the scientific evidence and presents distorted claims that personality change is induced by the DBS stimulation. This study contributes to the first-hand primary research on the topic exploring DBS clinicians’ views on post-DBS personality change among their patients and its underlying cause. Semi-structured interviews were conducted with sixteen clinicians from various disciplines working in Australian DBS practice for movement disorders and/or (...) psychiatric conditions. Thematic analysis of the interviews revealed five primary themes: 1) types, frequency and duration of personality change, 2) causes of personality change, 3) impact on patient and family, 4) communication, comprehension and awareness, and 5) management. Clinicians described a variety of personality changes in Parkinson’s disease following DBS including irritability, impulsivity and impaired decision-making. The frequency of personality change seen in patients varied amongst clinicians, but changes were overwhelmingly transient. Clinicians considered both DBS stimulation and additional factors as inducing personality change. For DBS patients with major depressive disorder, a restoration of pre-morbid personality was associated with alleviation of illness. Considerations for future research of personality change following DBS include selecting suitable tools for quantitative examination and developing a common language between the scientific and ethics communities. Clinical implications including recommendations for the informed consent process for patients and families and clinicians’ management of personality change are discussed. (shrink)

Gilbert et al. argue that the neuroethics literature discussing the putative effects of Deep Brain Stimulation on personality largely ignores the scientific evidence and presents distorted claims that personality change is induced by the DBS stimulation. This study contributes to the first-hand primary research on the topic exploring DBS clinicians’ views on post-DBS personality change among their patients and its underlying cause. Semi-structured interviews were conducted with sixteen clinicians from various disciplines working in Australian DBS practice for movement disorders and/or (...) psychiatric conditions. Thematic analysis of the interviews revealed five primary themes: 1) types, frequency and duration of personality change, 2) causes of personality change, 3) impact on patient and family, 4) communication, comprehension and awareness, and 5) management. Clinicians described a variety of personality changes in Parkinson’s disease following DBS including irritability, impulsivity and impaired decision-making. The frequency of personality change seen in patients varied amongst clinicians, but changes were overwhelmingly transient. Clinicians considered both DBS stimulation and additional factors as inducing personality change. For DBS patients with major depressive disorder, a restoration of pre-morbid personality was associated with alleviation of illness. Considerations for future research of personality change following DBS include selecting suitable tools for quantitative examination and developing a common language between the scientific and ethics communities. Clinical implications including recommendations for the informed consent process for patients and families and clinicians’ management of personality change are discussed. (shrink)

BackgroundConventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality (“non-focal”). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality.AimTo determine the regional volume parameters that differentiate the focal and (...) non-focal groups.MethodsT1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV’s showed a significant main effect or interaction involving the focality group, then that ROI was classified as a “focal ROI.”ResultsRegional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ –0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses.ConclusionThe CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL). (shrink)

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before (...) surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response. (shrink)

ABSTRACT Between April 1820 and April 1822, stimulated by the restoration of the Cádiz Constitution, Bentham devoted himself to writing a number of works on the constitutional reform and colonial rule of Spain, which have been sources of a scholarly debate over Bentham's views on colony. By examining those works, this essay aims to supplement the scholarly debate by drawing attention to a thesis that Bentham developed in his criticism and evaluation of the Cádiz Constitution: a thesis concerning the (...) irreconcilable incompatibilities of liberal constitution and colonisation. I focus on Bentham's critical analyses of the Constitution, and indicate that Spain's colonial rule of Ultramaria not only intensified the weaknesses of the Constitution, but also rendered its merits useless, if not harmful, to the public in both hemispheres. Moreover, I explore the tension that Bentham detected between liberal constitutionalism and colonialism. I maintain that, in Bentham's observation, the civil rights granted by the Cádiz Constitution to the Ultramarians stood to facilitate the enlightenment of citizens and the formation of civil society. As a consequence, the delusion of the Spanish ruling few would be exposed, and the Ultramarians’ discontent with exploitation by such foreign rulers would sow the seeds of disobedience and resistance. (shrink)

Advocates of moral enhancement through pharmacological, genetic, or other direct interventions sometimes explicitly argue, or assume without argument, that traditional moral education and development is insufficient to bring about moral enhancement. Traditional moral education grounded in a Kohlbergian theory of moral development is indeed unsuitable for that task; however, the psychology of moral development and education has come a long way since then. Recent studies support the view that moral cognition is a higher-order process, unified at a functional level, and (...) that a specific moral faculty does not exist. It is more likely that moral cognition involves a number of different mechanisms, each connected to other cognitive and affective processes. Taking this evidence into account, we propose a novel, empirically informed approach to moral development and education, in children and adults, which is based on a cognitive-affective approach to moral dispositions. This is an interpretative approach that derives from the cognitive-affective personality system (Mischel and Shoda, 1995). This conception individuates moral dispositions by reference to the cognitive and affective processes that realise them. Conceived of in this way, moral dispositions influence an agent's behaviour when they interact with situational factors, such as mood or social context. Understanding moral dispositions in this way lays the groundwork for proposing a range of indirect methods of moral enhancement, techniques that promise similar results as direct interventions whilst posing fewer risks. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing (...) the 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

The objective in this paper is to demonstrate the indispensability of Peirce’s double consciousness to foster abductive reasoning, so that internal/external dialogue inform the worthiness of hunches. These forms of dialogue establish a mental give-and-take forum in which novel meanings/effects are particularly highlighted and noticed. Such attentional shifts are compelled by surprising states of affairs within the beholder’s internal, interpretive competencies, or from external factors (pictures, gestural or linguistic performatives). The dialogic nature of these signs pre-forms operations not possible non-dialogically; (...) they command, interrogate, or suggest alterations to established conduct/beliefs in contexts in which propositional/argumentative conflicts are obviated. This inquiry proposes experimental methodologies to measure when double consciousness (via private/inner speech) mediates hypothesis-making. Vygotsky’s conflict of motive at four distinct developmental stages constitutes the foundation for the proposed experiments. Designs draw upon Vygotsky’s ‘double stimulation’ paradigms that force decision-making processes when conflicts of motive surface. Paradigms include forced imitation of one model while ignoring another (imitating bear, not dragon), and altering a visual array to depict logical sequencing accurately (the “Cycles Test”; “The Odd One Out”). These conflicts require children to change their conduct/beliefs to accommodate to atypical states of affairs. (shrink)

Modern cognitive and clinical psychology offer insight into how people deal with natural disasters. In my methodological paper, I make a strong case for incorporating experimental findings and theoretical concepts of modern psychology into environmental historical disaster research. I show how psychological factors may influence the production and interpretation of historical sources with respect to perceptions of and responses to disasters. While previous psychological approaches to history mostly involve psychoanalysis, I focus on empirical psychology. Specifically, I review a number of (...) well documented heuristics, biases, and memory modulations as described by cognitive psychology. Moreover, I argue that including investigations on disaster related mental disorders would complement the environmental historical research of natural disasters. My approach highlights a strong potential for interdisciplinary collaborations among environmental historians and psychologists. (shrink)

In this article I analyze some of the cultural factors that have determined and influenced the teaching profession and its evolution in African countries. Firstly, I use an historical approach to review conceptual issues on teachers, teaching and learning; secondly, I examine salient features of the idea and practices of teachers and teaching in the pre-colonial and less Westernized contemporary African contexts and elements of Quranic schools; thirdly, I offer an account of how teachers were introduced to formal learning of (...) European education in the colonial era; and, fourthly, I examine the declining prestige and other outstanding issues of teaching and the teaching profession amidst the call of quality Education for All. In the main, most African countries have to grapple with the daunting challenges of providing quality education to the entire school-age populations in African countries, especially with the approaching 2015 date for meeting the second Millennium Development Goal (MDG) of achieving universal primary education and Education For All (EFA). At the secondary level and even more clearly articulated for higher education, there is a sense of urgency in providing quality education particularly in science and technology to position Africa with competent human resources in the global economy. Paradoxically, however, the perceived and actual prestige of the teaching profession and the social status of the teacher as a professional category, especially at the lower levels of the educational systems, have not consistently been positive. (shrink)

This essay examines theoretical arguments surrounding the use of post-colonial theory as a way to fill in the epistemological lacuna in the studies of post-socialism. It reviews the various streams of this theoretical development and employs Edward Said’s notion of “traveling theory” to demonstrate that theoretical claims made by proponents and opponents of this particular comparative perspective are historically, socially, and geographically situated, although not fixed. Disciplinary, national, and institutional affiliations, instead of theoretical justifications, are identified as important factors in (...) the propensity to accept or resist the introduction of post-colonial perspective on Central and Eastern Europe and the former Soviet Union. The essay concludes by acknowledging the potential usefulness as well as the limits of post-colonialism in the conceptualization of the post- socialist space. (shrink)

IntroductionDeep brain stimulation has become a standard treatment option for select patients with Parkinson’s disease. The selection process and surgical procedures employed have, to date, not been standardized.MethodsA comprehensive 58-question web-based survey was developed with a focus on DBS referral practices and peri-operative management. The survey was distributed to the Parkinson’s Foundation Centers of Excellence, members of the International Parkinson’s Disease and Movement Disorders Society, and the Parkinson Study Group between December 2015 and May 2016.ResultsThere were 207 individual respondents drawn (...) from 59 countries and 6 continents, of whom 64% received formal training in DBS. Thirteen percent of centers reported that DBS could proceed despite a confidence level of < 50% for PD diagnosis. A case-based approach to DBS candidacy was applied in 51.3% of centers without a cut-off for levodopa-responsiveness. Surprisingly, 33% of centers regularly used imaging for diagnostic confirmation of idiopathic PD. Thirty-one percent of centers reported that neuropsychological evaluation did not affect DBS target selection. Approximately half of the respondents reported determination of DBS candidacy based on a multidisciplinary committee evaluation and 1/3rd reported that a committee was used for target selection. Eight percent of respondents felt that psychosocial factors should not impact DBS candidacy nor site selection. Involvement of allied health professionals in the preoperative process was sparse. There was high variability in preoperative education about DBS outcome expectations. Approximately half of the respondents did not utilize a “default brain target,” though STN was used more commonly than GPi. Specific DBS procedure techniques applied, as well as follow-up timelines, were highly variable.ConclusionResults revealed high variability on the best approaches for DBS candidate selection, brain target selection, procedure type, and postoperative practices. Cognitive and mood assessments were underutilized. There was low reliance on multidisciplinary teams or psychosocial factors to impact the decision-making process. There were small but significant differences in practice across global regions, especially regarding multidisciplinary teams. The wide variability of responses across multiple facets of DBS care highlights the need for prospective studies to inform evidence-based guidelines. (shrink)

The heterogeneity of transcranial direct current stimulation protocols and clinical profiles may explain variable results in modulating excitability in the motor cortex after stroke. However, the cortical electrical effects induced by different tDCS protocols remain unclear. Here, we aimed to compare rhythm changes in electroencephalography induced by three tDCS position protocols and the association between tDCS effects and clinical factors in stroke. Nineteen patients with chronic ischemic stroke underwent four experimental sessions with three tDCS protocols [anodal, cathodal, and bilateral ] (...) and a sham protocol, according to a single-blind randomized crossover design. Resting-state EEG was acquired before and after each protocol. First, a paired-sample t-test was used to examine the difference in spectral power between pre- and post-stimulation. Then, linear and quadratic regression models were used separately to describe the association between the clinical factors of stroke and changes in spectral power which was significantly different between pre- and post-tDCS. Finally, repeated measures analysis of variance with lesion hemisphere, stimulation protocol, and the location was performed to investigate the effects of tDCS over time. The induced effect of tDCS was mainly reflected in the alpha rhythms. The alpha power was increased by atDCS, especially low-alpha, in localized areas of the central and distant areas of the frontal and parietal lobes. Bi-tDCS also affected alpha power but in a smaller area that mainly focused on high-alpha rhythms. However, ctDCS and sham had no significant effects on any EEG rhythm. The clinical factors of time since stroke and motor impairment level were related to the change in high-alpha induced by atDCS and bi-tDCS following quadratic regression models. The above-mentioned modulation effect lasted for 20 min without attenuation. In conclusion, our findings provide evidence that the alpha rhythm of EEG is modulated differently by different tDCS protocols and that high alpha is affected by clinical characteristics such as post-stroke time and motor deficits, which is of great significance for understanding the modulation effect of different tDCS protocols on stroke and the guidance of protocols to promote motor recovery following stroke. (shrink)

Contents of online websites and advertisements by real estate companies operating in Goa suggest that newly developed properties are meant to attract urban elites from Indian metros. These investors from urban metros, such as Delhi, seek a tranquil getaway from the pollution and pressures of city life. However, more than simply Goa’s idyllic location, second homeowners desire to indulge in the region’s difference from the rest of India—Goa, after all, was a Portuguese territory for 451 years. For the Indian urban (...) elites, investing in the state is not just about buying ‘a piece of Goa’ on which to sojourn; rather, it is about buying into what this land signifies: an exotic ‘laidback’ Goan lifestyle. Essentially, I aim to suggest that the contemporary image of Goa through real estate advertisements is fashioned for the consumption of elite buyers from Indian metros who are sold a version of Goa’s culture that evokes the Portuguese colonial past while instantiating an idyllic present. Even as the elements from colonial-era architectural style of Goa are sustained or replicated, and Goan land appropriated, Goans themselves are not factored into the commercial imaginings of the sale of these exclusive and exclusionary properties. (shrink)

Poly(ADP‐ribosyl)ation is a post‐translational modification occurring in the nucleus. The most abundant and best‐characterized enzyme catalyzing this reaction, poly(ADP‐ribose) polymerase 1 (PARP1), participates in fundamental nuclear events. The enzyme functions as molecular “nick sensor”. It binds with high affinity to DNA single‐strand breaks resulting in the initiation of its catalytic activity. Activated PARP1 promotes base excision repair. In addition, PARP1 modifies several transcription factors and thereby precludes their binding to DNA. We propose that a major function of PARP1 includes the (...) silencing of transcription preventing expression of damaged genes. Concomitant stimulation of DNA repair suggests that PARP1 acts as a switch between transcription and DNA repair. Another PARP‐type enzyme, tankyrase, is involved in the regulation of telomere elongation. Tankyrase modifies a telomere‐associated protein and thereby prevents it masking telomeric repeats providing access of telomerase for telomere elongation. Therefore, poly(ADP‐ribosyl)ation reactions may act as molecular switches in DNA metabolism. BioEssays 23:543–548, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Two of the most important modern Indian Buddhist pioneers are the polyglot explorer and Marxist revolutionary, Rāhul Sāṅk tyāyan (1893–1963), and the Pali scholar and Gandhian nationalist, Dharmānand Kosambī (1876–1947). Although best known as scholars of Buddhism, it is their lesser-known personal lives—namely, their political involvement in anti-colonial efforts, social reform projects, and travels abroad—that are of primary focus in this study. Through an examination of their activities and writings, this essay reveals the methods they employed and the networks of (...) support they utilized in order to propagate Buddhism. In particular, it focuses on two features common to both of their lives: first, their relations with transnational Buddhist organizations and Euro-American and other Asian intellectuals, and second, their collaborative efforts with Indian elites whom they shared similar social, educational and national concerns. These two factors, I argue, were essential to their reconfiguration of a modern Indian Buddhism that was relevant to contemporary Indian concerns. (shrink)

Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation. While recording the electroencephalogram, we applied single-pulse TMS and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. We assessed local and global (...) modulation of phase dynamics using the phase-locking factor. sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony. (shrink)

Transcranial alternating current stimulation and neurofeedback are two different types of non-invasive neuromodulation techniques, which can modulate brain activity and improve brain functioning. In this review, we compared the current state of knowledge related to the mechanisms of tACS and NFB and their effects on electroencephalogram activity and on aftereffects, including the duration of their persistence and potential behavioral benefits. Since alpha bandwidth has been broadly studied in NFB and in tACS research, the studies of NFB and tACS in modulating (...) alpha bandwidth were selected for comparing the online and offline effects of these two neuromodulation techniques. The factors responsible for variability in the responsiveness of the modulated EEG activity by tACS and NFB were analyzed and compared too. Based on the current literature related to tACS and NFB, it can be concluded that tACS and NFB differ a lot in the mechanisms responsible for their effects on an online EEG activity but they possibly share the common universal mechanisms responsible for the induction of aftereffects in the targeted stimulated EEG band, namely Hebbian and homeostatic plasticity. Many studies of both neuromodulation techniques report the aftereffects connected to the behavioral benefits. The duration of persistence of aftereffects for NFB and tACS is comparable. In relation to the factors influencing responsiveness to tACS and NFB, significantly more types of factors were analyzed in the NFB studies compared to the tACS studies. Several common factors for both tACS and NFB have been already investigated. Based on these outcomes, we propose several new research directions regarding tACS and NFB. (shrink)

ObjectiveTo explore the effect of independently developed transcranial pulsed current stimulation on alleviating athlete’s mental fatigue.MethodsA total of 60 college athletes were randomly divided into the active stimulation group and the sham stimulation group. Subjective questionnaires, behavior test, and functional near-infrared spectroscopy test were conducted before and after the experiment. Two-way ANOVA with repeated measures was used to compare the differences in mental fatigue indexes before and after the two experimental conditions.ResultsAfter 7 days of exercise training, there was a significant (...) difference in the main effect of the time factor in all indexes of the two groups. The scores of rated perceived exertion scale, positive and negative affect schedule, critical flicker frequency, and reaction time, in the tPCS treatment group, were better than those in the sham stimulation group. After 7 days of exercise training, all the subjects had different degrees of athlete’s mental fatigue; the subjects in the active stimulation group have a good evaluation of the tPCS developed by the research group without adverse actions.ConclusiontPCS intervention can improve emotional state, reduce the subjective evaluation of fatigue, improve behavioral levels such as attention and reaction time and increase cerebral prefrontal blood flow and oxygen supply. (shrink)