This study aimed to evaluate if eye blinks can be used to discriminate players with different performance in a session of Nintendo Entertainment System (NES) Tetris. To that end, we developed a state-of-the-art method for blink extraction from EAR measures, which is robust enough to be used with data collected by a low-grade webcam such as the ones widely available on laptop computers. Our results show a significant decrease in blink rate per minute (blinks/m) during the first minute of playing (...) Tetris. After having defined 3 groups of proficiency based on in-game performance (Novices, Intermediates, and Experts) we found out that expert players display a significantly lower decrease in blinks/m compared to novices during the first minute of gameplay, which shows that Tetris players' proficiency can be detected by looking at eye blinks/m variations during the early phase of a game session. This difference in blinks/m is observed throughout the entire game session, which supports the general conclusion that proficient Tetris players have a lower decrease in blinks/m, even when playing more difficult levels. Finally, we offer some interpretations of this effect and the relationship that our results may have with the visual cognitive workload experienced during the gameplay. (shrink)

In another paper, one of us argued that emergence and reduction are compatible, and presented four examples illustrating both. The main purpose of this paper is to develop this position for the example of phase transitions. We take it that emergence involves behaviour that is novel compared with what is expected: often, what is expected from a theory of the system's microscopic constituents. We take reduction as deduction, aided by appropriate definitions. Then the main idea of our reconciliation of (...) emergence and reduction is that one makes the deduction after taking a limit of an appropriate parameter $N$. Thus our first main claim will be that in some situations, one can deduce a novel behaviour, by taking a limit $N\to\infty$. Our main illustration of this will be Lee-Yang theory. But on the other hand, this does not show that the $N=\infty$ limit is physically real. For our second main claim will be that in such situations, there is a logically weaker, yet still vivid, novel behaviour that occurs before the limit, i.e. for finite $N$. And it is this weaker behaviour which is physically real. Our main illustration of this will be the renormalization group description of cross-over phenomena. (shrink)

While risk of harm is an important focus for whether clinical research on humans can and should proceed, there is uncertainty about what constitutes harm to a trial participant. In Phase I trials on healthy volunteers, the purpose of the research is to document and measure safety concerns associated with investigational drugs, and participants are financially compensated for their enrollment in these studies. In this article, we investigate how characterizations of harm are narrated by healthy volunteers in the context (...) of the adverse events they experience during clinical trials. Drawing upon qualitative research, we find that participants largely minimize, deny, or re-attribute the cause of these AEs. We illustrate how participants' interpretations of AEs may be shaped both by the clinical trial environment and their economic motivation to participate. While these narratives are emblematic of the larger ambiguity surrounding harm in the context of clinical trial participation, we argue that these interpretations also problematically maintain the narrative of the safety of clinical trials, the ethics of testing investigational drugs on healthy people, and the rigor of data collected in the specter of such ambiguity. (shrink)

Background Disclosure of obtaining informed consent from patients (ICP) and research ethics committee (REC) approval in published reports is sometimes omitted. To date, no disclosure data are available on surgical research. Objective Our aim was to assess whether REC approval and ICP were documented in surgical trials. Study design Overall, 657 randomised trials, published between 2005 and 2010 in 10 international journals, were included. We collected the report rate of REC approval and ICP and contacted the corresponding author when ethical (...) information was lacking. Results Among the 657 randomised controlled trials (RCT), 576 (87.7%) stated that an REC had approved the research, and 606 (92.2%) stated that ICP had been requested. Furthermore, 28 RCTs (4.3%) reported neither REC nor ICP. Conclusions The phase III randomised surgical trials that were analysed were shown to have respected fundamental ethical principles in approximately 90% of the cases examines. (shrink)

Lowering compensation to research subjects to protect them from “undue inducement” is a misguided attempt to shoehorn a concern about exploitation into the framework of autonomy. We suggest that oversight bodies should be less concerned about undue influence than about exploitation of subjects. Avoiding exploitation in human subjects research requires not only increasing compensation, but enhancing the dignity of research participation.

In many research studies, tumor biopsies are an unavoidable requirement for achieving key scientific aims. Yet some commentators view mandatory research biopsies as coercive and suggest they should be optional, or at least optional until further data are obtained regarding their scientific usefulness. Further complicating the ethical picture is the fact that some research biopsies offer a potential for clinical benefit to trial participants. We interviewed and surveyed a convenience sample of participants in phase I clinical trials at a (...) single institution. Our primary aim was to describe phase I participants’ understanding of whether a research biopsy offered them the prospect of medical benefit. We also endeavored to describe participants’ views about biopsies—specifically, the benefits of biopsies, if any, and whether biopsies were acceptable, risky, or discouraged trial participation. Finally, we collected data on demographics and attitudes to see if any strong correlations with misunderstanding, acceptability, or riskiness existed. Overall, the respondents tended to view research biopsies as acceptable, though they did not succeed in identifying the lack of benefit of a research biopsy. These findings call for renewed efforts in consent conversations and documents to carefully describe the benefits, or lack thereof, of research biopsies. (shrink)

We consider an oscillator subjected to a sudden change in equilibrium position or in effective spring constant, or both—to a “squeeze” in the language of quantum optics. We analyze the probability of transition from a given initial state to a final state, in its dependence on final-state quantum number. We make use of five sources of insight: Bohr-Sommerfeld quantization via bands in phase space, area of overlap between before-squeeze band and after-squeeze band, interference in phase space, Wigner function (...) as quantum update of B-S band and near-zone Fresnel diffraction as mockup Wigner function. (shrink)

Phase separation underlies the formation of biomolecular condensates. We hypothesize the cellular processes that occur within condensates shape their structural features. We use the example of transcription to discuss structure–function relationships in condensates. Various types of transcriptional condensates have been reported across the evolutionary spectrum in the cell nucleus as well as in mitochondrial and bacterial nucleoids. In vitro and in vivo observations suggest that transcriptional activity of condensates influences their supramolecular structure, which in turn affects their function. Condensate (...) organization thus becomes driven by differences in miscibility among the DNA and proteins of the transcription machinery and the RNA transcripts they generate. These considerations are in line with the notion that cellular processes shape the structural properties of condensates, leading to a dynamic, mutual interplay between structure and function in the cell. (shrink)

BackgroundIn this manuscript, we argue that within the context of phase IV, physician-researchers retain their fiduciary obligation to treat the patient-participants.DiscussionWe first clarify why the perspective that research ethics ought to be differentiated from clinical ethics is not applicable in phase IV, and therefore, why therapeutic orientation is most convivial in this phase. Next, assuming that ethics guidelines may be representative of common morality, we show that ethics guidelines see physician-researchers primarily as physicians and only secondarily as (...) researchers. We then elaborate on what a fiduciary obligation is and how some of the obligations are default duties. Lastly, we look at the fiduciary obligation of the physician-researcher in phase IV interventional trials.ConclusionThe fiduciary obligation to treat is not as easily waived as in earlier trials. Assuming the entwinement of research and practice in phase IV, physician-researchers, in collaboration with other researchers, investigators, and research ethics committees, should ensure that in terms of study design, methodology, and research practice, the therapeutic value of the research to the patient-participants is not diminished. (shrink)

Infinite idealizations appear in our best scientific explanations of phase transitions. This is thought by some to be paradoxical. In this paper I connect the existing literature on the phase transition paradox to work on the concept of indispensability, which arises in discussions of realism and anti-realism within the philosophy of science and the philosophy of mathematics. I formulate a version of the phase transition paradox based on the idea that infinite idealizations are explanatorily indispensable to our (...) best science, and so ought to attract a realist attitude. I go on to offer a solution to the paradox by drawing a distinction between two types of indispensability: constructive and substantive indispensability. I argue that infinite idealizations are constructively indispensable to explanations of phase transitions, but not substantively indispensable. This helps to resolve the paradox, I maintain, since realist commitment tracks substantive, and not constructive, indispensability. (shrink)

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in (...) class='Hi'>phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. *Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government. (shrink)

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in (...) class='Hi'>phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. *Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government. (shrink)

Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers (...) participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. (shrink)

Tremendous development in recent medical science and the consequent discoveries resulting in successful prevention and also cure of different diseases are shared by clinical research involving the human volunteers. Preceding the trials in the human subjects, and to ensure safety, the proposed drug and other interventions are either tested in animals (vivo) or in laboratory (vitro) to evaluate initial safe starting dose for the human beings and to key out the benchmarks for the clinical monitoring for the potential unfavorable effects. (...) These pre human trials might not necessarily protect against the untoward effects in the human beings as happened in the case of thalidomide tragedy, which caused disability and killed thousands of babies born to the mothers, those who took this medicine. Use of healthy human volunteers in the preliminary experiments or phase I clinical trials either reduces or excludes risks of subsequent undesirable effects in the future trails (1). Phase-1 trials are conducted in order to test the safety, reactions and immunogenicity of vaccines in volunteers. Novel treatments for the cancer are first tested in phase 1 trials enrolling the patients with advanced disease, who have exhausted the standard treatment options. Phase-1 oncology trials are the pivot point in the translation of new cancer therapies from bench to bedside. Nevertheless, these trials remain ethically controversial. The controversy stems from the fact that, classically, phase-1 oncology clinical trials involve first-in-human testing of experimental treatment candidates in patients with a terminal diagnosis, who typically have exhausted standard treatment options. Commentators on the ethics of phase-1 clinical trials make diametrically opposed claims about the prospect of direct medical benefit from participation in these trials-benefits that can be attributed to receiving the experimental treatment intervention. One camp of benefit skeptics, inhabited mainly by bioethicists, characterizes this form of research as lacking any reasonable prospect of direct medical benefit. They see an ethical cloud hovering over phase-1 trials, because the vast majority of patients volunteer for phase-1 trials out of a motivation to receive medical benefit. In the view of these skeptics, such patients therefore harbor a ‘therapeutic misconception’ about research participation. This misconception calls into question the validity of informed consent and thereby undercuts the ethical basis of these trials (2). In this paper, I will discuss the ethical justification of the participation of human volunteers in phase-1 trials. (shrink)

In phase I clinical trials, healthy volunteers are dosed with investigational drugs and subjected to blood draws and other bodily monitoring procedures. In exchange, they are paid. Healthy volunteers are, in a very direct sense, selling access to their bodies for pharmaceutical companies and their associates to run drugs through. In his ethnographic study of socalled professional guinea pigs, Roberto Abadie writes, "Paid volunteers are well aware of the demand for an idealized, perfectly healthy volunteer. They also realize that (...) their body is a valued commodity in clinical trials research". It is perhaps surprising, then, that commodification is little discussed in the bioethics literature on phase I... (shrink)

Clinical investigators must engage in just subject recruitment and selection and avoid unduly influencing research participation. There may be tension between the practice of keeping payments to participants low to avoid undue influence and the requirements of justice when recruiting normal healthy volunteers for phase 1 drug studies. By intentionally keeping payments low to avoid unduly influenced participation, investigators, on the recommendation or insistence of institutional review boards, may be targeting or systematically recruiting healthy adult members of lower socio-economic (...) groups for participation in phase 1 studies. Investigators are at risk of routinely failing to fulfill the obligation of justice, which prohibits the systematic targeting and recruiting of subjects for reasons unrelated to the nature of the study. Insofar as we take seriously the obligation to engage in just subject recruitment and selection, I argue that we must acknowledge the implications low payments might have for subject recruitment and selection and examine the effect of low payments. If low payments de facto target the less well-off for phase 1 studies, we must defend the priority ranking of the obligation to avoid undue influence over the obligation of justice or adopt an alternative recruitment approach. This paper identifies a number of alternatives to the current system of low-value payments to research participants. (shrink)

Background: The approval of a research ethics committee and obtaining informed consent from patients could be considered the main issues in the ethics of research with human beings. The aim of this study was to assess both methodological quality and ethical quality, and also to assess the relationship between these two qualities in randomised phase III cancer trials.Method: Methodological quality and ethical quality were assessed for all randomised controlled trials published in 10 international journals between 1999 and 2001 .Results: (...) The mean Jadad score was 9.86 ± 1.117. The methodological quality was poor in 75 RCTs . The mean Berdeu score was 0.42 ± 0.133. The mean ethical quality score for poor methodological quality RCTs was 0.39 ± 0.133; it was 0.43 ± 0.133 for good methodological quality RCTs . There was improvement in ethical quality according to the year of commencement of the trials . There was no correlation between methodological quality and the number of participating patients , between ethical quality and the number of participating patients , or between ethical quality and methodological quality . ICP and REC approval were not obtained for 21 and 77 trials respectively.Conclusion: The association between methodological quality and the reporting of ethical requirements probably reflects the respect shown for patients during the whole research process. These results suggest that closer attention to the conduct of clinical research, as well as the reporting of its ethical aspects, is needed. (shrink)

Philologus, founded in 1846, is one of the oldest and most respected periodicals in the field of Classics. It publishes articles on Greek and Latin literature, historiography, philosophy, history of religion, linguistics, reception, and the history of scholarship. The journal aims to contribute to our understanding of Greco-Roman culture and its lasting influence on European civilization. The journal Philologus, conceived as a forum for discussion among different methodological approaches to the study of ancient texts and their reception, publishes original scholarly (...) contributions with a strong international focus. Publications languages are: German, English, Italian, French. As of 2014 the publication of supplementary volumes will be resumed. The series Philologus. Supplemente / Philologus. Supplementary Volumes will publish monographs and edited volumes pertaining to all aspects of the study of ancient literature and its reception, with a special focus on topics concerning literary theory, philosophy and the history of scholarship from an interdisciplinary perspective. (shrink)

We study the notion of logical relation in the coherence space semantics of multiplicative-additive linear logic . We show that, when the ground-type logical relation is “closed under restrictions”, the logical relation associated to any type can be seen as a map associating facts of a phase space to families of points of the web of the corresponding coherence space. We introduce a sequent calculus extension of whose formulae denote these families of points. This logic admits a truth-value semantics (...) in the previously mentioned phase space, and this truth-value semantics faithfully describes the logical relation model we started from. Then we generalize this notion of phase space, we prove a truth-value completeness result for and we derive from any phase model of a denotational model for . Using the truth-value completeness result, we obtain a weak denotational completeness result based on this new denotational semantics. (shrink)

Most models of response time (RT) in elementary cognitive tasks implicitly assume that the speed-accuracy trade-off is continuous: When payoffs or instructions gradually increase the level of speed stress, people are assumed to gradually sacrifice response accuracy in exchange for gradual increases in response speed. This trade-off presumably operates over the entire range from accurate but slow responding to fast but chance-level responding (i.e., guessing). In this article, we challenge the assumption of continuity and propose a phase transition model (...) for RTs and accuracy. Analogous to the fast guess model (Ollman, 1966), our model postulates two modes of processing: a guess mode and a stimulus-controlled mode. From catastrophe theory, we derive two important predictions that allow us to test our model against the fast guess model and against the popular class of sequential sampling models. The first prediction—hysteresis in the transitions between guessing and stimulus-controlled behavior—was confirmed in an experiment that gradually changed the reward for speed versus accuracy. The second prediction—bimodal RT distributions—was confirmed in an experiment that required participants to respond in a way that is intermediate between guessing and accurate responding. (shrink)

— We prescnt here a comparative study on the decay of chlorophyll a fluorescence yield in thylakoid membranes and photosystem 11 ‐enriched samples, measured with multifrequency cross‐correlation phase fluorometry. These measurements confirm the general conclusions of Van Mieghem ef al., obtained with a flash method, on the effects of reduction of the primary quinone acceptor on ChI a fluorescence yield of PSI. Different states of the reaction centers of PSII were produced by: pretreatment with sodium dithionite and mcthyl viologen (...) followed by laser illumination: the doubly reduced QA centers: with laser illumination or pretreatment with diuron: QA‐ centers; and the addition of micromolar concentration of dichlorobenzoquinonc : oxidized QA centers. The data were analyzed with Lorentzian distribution as well as with multiexponential fluorescence decay functions. The analysis with Lorcntzian distribution function showed that upon formation of QA. the major lifetime distribution peak shifted to longer lifetimes: from 0.25 ns to 1.66 ns and from 0.24 ns to 1.31 ns. However, when QAHZ was formed, the lifetime distribution peaks shifted back to shorter lifetimes both in thylakoids and PSIl membranes. Multiexponential analysis showed three lifetime components: fast, middle and slow. When QA was formed in PS11 centers, the amplitude of the fast Component decreased, but both thc amplitude and the lifetime of the middle component increased severalfold. However, when QA was doubly reduccd, the amplitude of the fast component increased and the amplitude of the middle component decreased: in addition, the lifetime of the slow component increased. All of the above results are consistent with the conclusions that PS11 charge separation is decreased when QA is formed and increased when doubly reduced QA is formed. Copyright © 1993, Wiley Blackwell. All rights reserved. (shrink)

When the COVID-19 surge hit New York City hospitals, the Division of Medical Ethics at Weill Cornell Medical College, and our affiliated ethics consultation services, faced waves of ethical issues sweeping forward with intensity and urgency. In this article, we describe our experience over an eight-week period (16 March through 10 May 2020), and describe three types of services: clinical ethics consultation (CEC); service practice communications/interventions (SPCI); and organizational ethics advisement (OEA). We tell this narrative through the prism of time, (...) describing the evolution of ethical issues and trends as the pandemic unfolded. We delineate three phases: anticipation and preparation, crisis management, and reflection and adjustment. The first phase focused predominantly on ways to address impending resource shortages and to plan for remote ethics consultation, and CECs focused on code status discussions with surrogates. The second phase was characterized by the dramatic convergence of a rapid increase in the number of critically ill patients, a growing scarcity of resources, and the reassignment/ redeployment of staff outside their specialty areas. The third phase was characterized by the recognition that while the worst of the crisis was waning, its medium- and long-term consequences continued to pose immense challenges. We note that there were times during the crisis that serving in the role of clinical ethics consultant created a sense of dis-ease as novel as the coronavirus itself. In retrospect we learned that our activities far exceeded the familiar terrain of clinical ethics consultation and extended into other spheres of organizational life in novel ways that were unanticipated before this pandemic. To that end, we defined and categorized a middle level of ethics consultation, which we have termed service practice communication intervention (SPCI). This is an underappreciated dimension of the work that ethics consult services are capable of in times of crisis. We believe that the pandemic has revealed the many enduring ways that ethics consultation services can more robustly contribute to the ethical life of their institutions moving forward. (shrink)

We found that phase cone clustering patterns in EEG ripple bands demonstrate an increased turnover rate in epileptogenic zones compared to adjacent regions. We employed 256 channel EEG data collected in four adult subjects with refractory epilepsy. The analysis was performed in the 80–150 and 150–250 Hz ranges. Ictal onsets were documented with intracranial EEG recordings. Interictal scalp recordings, free of epileptiform patterns, of 240-s duration, were selected for analysis for each subject. The data was filtered, and the instantaneous (...) phase was extracted after the Hilbert transformation. Spatiotemporal contour plots of the unwrapped instantaneous phase with 1.0 ms intervals were constructed using a montage layout of the 256 electrode positions. Stable phase cone patterns were selected based on criteria that the sign of spatial gradient did not change for a minimum of three consecutive time samples and the frame velocity was consistent with known propagation velocities of cortical axons. These plots exhibited increased dynamical formation and dissolution of phase cones in the ictal onset zones, compared to surrounding cortical regions, in all four patients. We believe that these findings represent markers of abnormally increased cortical excitability. They are potential tools that may assist in localizing the epileptogenic zone. (shrink)

The concept of probability space is generalized to that of stochastic probability space. This enables the introduction of representations of quantum mechanics on stochastic phase spaces. The resulting formulation of quantum statistical mechanics in terms of Γ-distribution functions bears a remarkable resemblance to its classical counterpart. Furthermore, both classical and quantum statistical mechanics can be formulated in one and the same master Liouville space overL 2(Γ). A joint derivation of a classical and quantum Boltzman equation provides an illustration of (...) the practical uses of these formalisms. (shrink)

Originally published in 1962. This book discusses and interprets the main themes of Buddhist thought in India and is divided into three parts: Archaic Buddhism: Tacit assumptions, the problem of "original Buddhism", the three marks and the perverted views, the five cardinal virtues, the cultivation of the social emotions, Dharma and dharmas, Skandhas, sense-fields and elements. The Sthaviras: the eighteen schools, doctrinal disputes, the unconditioned and the process of salvation, some Abhidharma problems. The Mahayana: doctrines common to all Mahayanists, the (...) Madhyamikas, the Yogacarins, Buddhist logic, the Tantras. (shrink)