Gap junction intercellular communication channels permit the exchange of small regulatory molecules and ions between neighbouring cells and coordinate cellular activity in diverse tissue and organ systems. These channels have short half‐lives and complex assembly and degradation pathways. Much of the recent work elucidating gap junction biogenesis has featured the use of connexins (Cx), the constituent proteins of gap junctions, tagged with reporter proteins such as Green Fluorescent Protein (GFP) and has illuminated the dynamics of channel assembly in live cells (...) by high‐resolution time‐lapse microscopy. With some studies, however, there are potential short‐comings associated with the GFP chimeric protein technologies. A recent report by Gaietta et al., has highlighted the use of recombinant proteins with tetracysteine tags attached to the carboxyl terminus of Cx43, which differentially labels ‘old’ and ‘new’ connexins thus opening up new avenues for studying temporal and spatial localisation of proteins and in situ trafficking events.1 BioEssays 24:876–880, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Prior research has demonstrated that antisocial behavior, substance-use disorders, and personality dimensions of aggression and impulsivity are indicators of a highly heritable underlying dimension of risk, labeled externalizing. Other work has shown that individual trait constructs within this psychopathology spectrum are associated with reduced self-monitoring, as reflected by amplitude of the error-related negativity (ERN) brain response. In this study of undergraduate subjects, reduced ERN amplitude was associated with higher scores on a self-report measure of the broad externalizing construct that links (...) these various indicators. In addition, the ERN was associated with a response-locked increase in anterior theta (4–7 Hz) oscillation; like the ERN, this theta response to errors was reduced among high-externalizing individuals. These findings suggest that neurobiologically based deficits in endogenous action monitoring may underlie generalized risk for an array of impulse-control problems. (shrink)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A home-sent (...) questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)

PurposeTo explore the mindfulness practice, its long-term effects, facilitators and barriers, in clinical clerkship students 2 years after participation in an 8-week mindfulness-based stress reduction training.MethodA qualitative study was performed by semi-structured in-depth interviews with 16 clinical clerkship students selected by purposive sampling. Students had participated in a MBSR training 2 years before and were asked about their current mindfulness practice, and the long-term effects of the MBSR training. Thematic analysis was conducted using the constant comparison method. Data saturation was (...) reached after 16 interviews.ResultsMost interviewees were still engaged in regular, predominantly informal, mindfulness practice, although some discontinued mindfulness practice and reported an “unchanged lifestyle.” Three main themes came forward; “focused attention and open awareness” during daily activities as core elements of long-term mindfulness practice; “changes in behavior and coping” that resulted from taking a pause, reflecting, recognizing automatic behavioral patterns and making space for a conscious response; “integration in personal and professional life” by enhanced enjoyment of daily activities, improved work-life-balance and making different career choices. Barriers and facilitators in starting and maintaining mindfulness practice were understanding and intention as “pre-conditions”; practical, personal, and professional factors of students in maintaining practice.ConclusionTwo years after participation in a MBSR training, many interviewees were still engaged in mindfulness practice contributing to both personal and professional changes. In light of the high clerkship demands, MBSR training could be a valuable addition to medical curricula, supporting medical students in developing necessary competencies to become well-balanced professionals. (shrink)

Ludwig Wittgenstein was born in 1889, son of parents of Jewish extraction but not Jewish religion. Asked how his family came by the name ‘Wittgenstein’ Ludwig said they had been court Jews to the princely family and so had taken the name when Jews were required by law to have European-style names. The father, Karl, was a Protestant, the mother a Catholic. The Jewish blood was sufficient to bring the family later on into danger under Hitler's Nuremberg Laws. They did (...) not think of themselves as Jews or belong to the Jewish community in Vienna. The children were brought up sort-of Catholic though so far as I know only the eldest, Hermine, towards the end of her life, took this seriously and made a profession of faith before friends and household. At 9 years of age Ludwig and Paul, a year or two older than Ludwig, talked together and decided that their religion was all nonsense. Paul became a pianist of some fame, but soon after his debut in Vienna he became a wounded prisoner on the Russian front and his arm was lopped off by a surgeon who did not know he was a pianist. (shrink)

The comparative analysis of the approaches to philosophy and philosophizing by the two prominent Russian thinkers of the Soviet era: Evald V. Ilyenkov and Merab K. Mamardashvili. The author discusses specific methodological and conceptual features of Ilyenkov's dialectic and Mamardashvili's phenomenology, showing their theoretical and topical affinity.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity recorded with extraoperative electrocorticography during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha and beta bands could further (...) improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy. (shrink)

BackgroundAdverse childhood experiences can cause serious mental problems in adolescents and therefore may expected to be associated with higher use of psychosocial care, potentially varying by type of specific ACE. The aim of our study is to explore the association of the number of ACE and types of specific ACE with entering and using psychosocial care.MethodsWe used data from the Slovak Care4Youth cohort study, comprising 509 adolescents from 10 to 16 years old. We used logistic regression models adjusted for age, (...) gender, and family affluence to explore the associations of number and type of specific ACE with the use of psychosocial care.ResultsHaving three or more ACE as well as experiencing some specific ACE increased the likelihood of using psychosocial care. Regarding experience with the death of somebody else you love, we found a decreased likelihood of the use of psychosocial care.ConclusionExperiencing ACE above a certain threshold and parent-related ACE increase the likelihood of adolescent care use. (shrink)

G. E. M. Anscombe; I *—The Presidential Address: Existence and Truth, Proceedings of the Aristotelian Society, Volume 88, Issue 1, 1 June 1988, Pages 1–12, http.

Contextual learning pervades our perception and cognition and plays a critical role in adjusting to aversive and stressful events. Our ability to memorise spatial context has been studied extensive...

Featuring nine new articles chosen by coeditor, Steven M. Cahn, the third edition of E. D. Klemke's The Meaning of Life offers twenty-two insightful selections that explore this fascinating topic. The essays are primarily by philosophers but also include materials from literary figures and religious thinkers. As in previous editions, the readings are organized around three themes. In Part I the articles defend the view that without faith in God, life has no meaning or purpose. In Part II the selections (...) oppose this claim, defending instead a nontheistic, humanistic alternative--that life can have meaning even in the absence of theistic commitment. In Part III the contributors ask whether the question of the meaning of life is itself meaningful. The third edition adds substantial essays by Moritz Schlick, Joel Feinberg, and John Kekes as well as selections from the writings of Louis P. Pojman, Emil L. Fackenheim, Robert Nozick, Susan Wolf, and Steven M. Cahn. The only anthology of its kind, The Meaning of Life: A Reader, Third Edition, is ideal for courses in introduction to philosophy, human nature, and the meaning of life. It also offers general readers an accessible and stimulating introduction to the subject. (shrink)

Dubbed “Nietzsche without his hammer” by literary critic James Wood, the Romanian philosopher E. M. Cioran is known as much for his profound pessimism and fatalistic approach as for the lyrical, raging prose with which he communicates them. Unlike many of his other works, such as On the Heights of Despair and Tears and Saints, The New Gods eschews his usual aphoristic approach in favor of more extensive and analytic essays. Returning to many of Cioran’s favorite themes, The New Gods (...) explores humanity’s attachment to gods, death, fear, and infirmity, in essays that vary widely in form and approach. In “Paleontology” Cioran describes a visit to a museum, finding the relatively pedestrian destination rife with decay, death, and human weakness. In another chapter, Cioran explores suicide in shorter, impressionistic bursts, while “The Demiurge” is a shambolic exploration of man’s relationship with good, evil, and God. All the while, The New Gods reaffirms Cioran’s belief in “lucid despair,” and his own signature mixture of pessimism and skepticism in language that never fails to be a pleasure. Perhaps his prose itself is an argument against Cioran’s near-nihilism: there is beauty in his books. (shrink)

Interpretation of the classics in political theory seems to go in waves. For a while we had John Locke, the bourgeois thinker. Now we seem to be in a Locke-as-radical-democrat phase. Locke-the-bourgeois had problems of its own, but a radically democratic Locke -- not just the old Locke as liberal democrat but Locke as quasi-Leveller -- strains the interpretative imagination more than most; yet in recent years, several different kinds of argument have been advanced in support of it, both textual (...) and contextual. The most effective argument has proceeded by situating Locke in the context of radical Whig politics in the 1670s and '80s, the struggles over religious toleration and the royal succession, in particular the �Exclusion Crisis� of 1679-81. This contextual argument has been accompanied by various textual interpretations having to do with Locke's conceptions of property, consent, representation, the right of revolution and natural law. Among other things, these are supposed to show that while Locke had nothing explicit to say about the extent of the franchise, the weight of evidence suggests that he would have supported a fairly wide franchise, perhaps even something like the (almost) manhood suffrage advocated by the Levellers (at least according to some, and probably the most convincing, interpretations of their ideas). Most recently, in these pages, Martin Hughes, building on the work of James Tully and Richard Ashcraft in particular, has pushed the argument as far as it can probably go. His argument on taxation and suffrage has provided a motivation here for a wider exploration of Locke's views on representation, consent and the franchise. (shrink)

Rescher has presented a proof that a completed science is logically impossible; not every truth can be known. I show that the proof is valid only if it is read de re. One of its premises, however, is an obvious truth only on a de dicto reading; read de re it is false. What the proof shows, therefore, is that science has no limits and any true proposition can be known. We can, however, know it only in the meagre de (...) re, and not in the informationally rich de dicto, sense of 'know'. (shrink)

This paper has two aims: to explore the affective dimensions of moral shock and the way it relates to normative marginalization of those furthest from dominant society and also, more specifically, to articulate the trans experience of constantly being under moral attack because the dominant ‘world’ normatively defines trans individuals out of existence. Toward these ends, I build on Katie Stockdale's recent work on moral shock, arguing that moral shock needs to be contextualized to ‘worlds’ of sense to understand how (...) marginalized people affectively experience shocking events. My focus is the trans experience of moral shock due to the way trans people are positioned outside of dominant society, which creates the conditions to experience cyclical, chronic shock. These affective conditions point to a collective responsibility to ease the affective stress that the most marginalized experience. (shrink)

_Zettel, _ an en face bilingual edition, collects fragments from Wittgenstein's work between 1929 and 1948 on issues of the mind, mathematics, and language.

In the summer of 1997 one could scarcely enter a bookstore in Beijing without encountering Wang Xiaobo's pensive and defiant look on the cover of dozens of books displayed at the entrance. Wang had suddenly died in the spring of that year at the age of forty-five. Born in Beijing in 1952 to a family of intellectuals, he remained attached to China's capital despite periods of separation, such as during the Cultural Revolution, when he was sent to Yunnan to "learn (...) from the peasants" and taught in a "people-run-school" in Shandong, and also during the 1980s, when he studied in the United States . Wang always returned to Beijing, in the late 1970s to study economy and business at the People's University and in the late 1980s to teach there. After retiring in 1993, he devoted his time to writing: poetry, novels, essays, non-fiction, and a movie script. (shrink)

Recently, the concept of "gender identity" has enjoyed a great deal of attention in gender metaphysics. This seems to be motivated by the goal of creating trans-inclusive theory, by explaining trans people's genders. In this paper, we aim to unmotivate this project. Notions of "gender identity" serve important pragmatic purposes for trans people, such as satisfying the curiosity of non-trans people, and, relatedly, securing our access to important goods like legal rights and medical care. However, we argue that this does (...) not mean that "gender identity" is a metaphysically substantial thing that deserves extensive theoretical attention. There are reasons to be skeptical of such a concept. We trace the history of "gender identity," primarily to identify its roots in trans-antagonistic medical theory and its connections to the problematic "wrong-body" model--a legacy that has pathologized and flattened trans experience. Moreover, we argue that trans people primarily use "gender identity" to explain ourselves to non-trans people, rather than to discuss ourselves among ourselves. Thus, we urge theorists to resist the urge to substantiate gender identity. Instead, we encourage the development of new and better concepts, ones that attend to the lived realities of trans community and the flourishing gender terms and practices that are constructed there. If these lived realities are taken seriously, there is no need to “explain” trans people’s genders; we can simply see them as they are. (shrink)