A non-inferiority design accepts the possibility of some efficacy loss, as part of a “successful”, statistically significant result. That loss may be excessive when the non-inferiority threshold is lenient. However, even stringent significance thresholds and safety monitoring may fail to adequately protect study participants when the primary outcome is death. The OPTIMAAL trial, a large randomized clinical trial performed in high-risk patients, is discussed as an example, using the Belmont Report principles as an ethical frame of reference. OPTIMAAL (...) compared losartan, a new drug, to captopril, a drug known to reduce the risk of death in patients with heart failure after a myocardial infarction. Serious ethical challenges occurred in that study. Firstly, subjects had to tolerate captopril to participate, meaning that participation implied the possibility of higher risk of death if randomized to the losartan arm, as compared to the standard of care. Additionally, the stopping rules had to ensure enough powe... (shrink)

Discussions about the merits and shortcomings of non-inferiority trials are becoming increasingly common in the medical community and among regulatory agencies. However, criticisms targeting the ethical standing of non-inferiority trials have often been mistargeted. In this article we review the ethical standing of trials of non-inferiority. In the first part of the article, we outline a consequentialist position according to which clinical trials are best conceived as epistemic tools aimed at fostering the proper ends of medicine. According (...) to this view, clinical trials are means to ends, and thus their moral status depends both on how well they perform as means to reach desired ends and on which ends they are meant to achieve. Building upon this normative framework in the next two sections we analyze the specific ethical issues raised by non-inferiority trials. By making it clear that clinical trials are just epistemic tools – i.e. means to certain ends – it is possible not only to clarify the conceptual debate over a fundamental issue in clinical research, but also to identify which ethically relevant considerations ought to be addressed in setting up a non-inferiority trial. (shrink)

Background: People with traumatic brain injury face a range of mental health challenges during the adjustment process post-injury, but access to treatment can be difficult, particularly for those who live in regional and remote regions. eHealth provides the potential to improve access to evidence-based psychological therapy for people with a severe TBI. The aim of the current study is to assess the efficacy of a psychological intervention delivered via video consulting to reduce psychological distress in people with TBI.Methods: This paper (...) outlines the protocol for a multi-center, three-arm, parallel, non-inferiority randomized controlled trial of an evidence-based manualized psychological intervention, ACT-Adjust. ACT-Adjust provides nine sessions for adults with a moderate to severe TBI experiencing clinical levels of psychological distress. Fifty-six participants referred from Brain Injury Rehabilitation Units across New South Wales and the NSW icare scheme will be randomly allocated to three conditions; video consulting, face-to-face and, a waitlist control.Discussion: This is the first RCT to evaluate the efficacy of a psychological therapy delivered via video consulting for individuals with a moderate to severe TBI.Trial Registration:www.anzctr.org.au, Australian New Zealand Clinical Trials Registry ANZCTRN2619001602112. (shrink)

Introduction: Falls are the leading cause of fatal and nonfatal injuries among older adults. Studies showed that older adults can reduce the risk of falls after participation in an unexpected perturbation-based balance training, a relatively novel approach that challenged reactive balance control. This study aims to investigate the effect of the practice schedule on reactive balance function and its transfer to proactive balance function. Our primary hypothesis is that improvements in reactive balance control following block PBBT will be not inferior (...) to the improvements following random PBBT.Methods and Analysis: This is a double-blind randomized controlled trial. Fifty community-dwelling older adults will be recruited and randomly allocated to a random PBBT group or a block PBBT group. The random PBBT group will receive eight training sessions over 4 weeks that include unexpected machine-induced perturbations of balance during hands-free treadmill walking. The block PBBT group will be trained by the same perturbation treadmill system, but only one direction will be trained in each training session, and the direction of the external perturbations will be announced. Both PBBT groups will receive a similar perturbation intensity during training, the same training period, and the same concurrent cognitive tasks during training. The generalization and transfer of learning effects will be measured by assessing the reactive and proactive balance control during standing and walking before and after 1 month of PBBT, for example, step and multiple steps and fall thresholds, Berg balance test, and fear of falls. The dependent variable will be rank transformed prior to conducting the analysis of covariance to allow for nonparametric analysis.Discussion: This research will explore which of the balance retraining paradigms is more effective to improve reactive balance and proactive balance control in older adults over 1 month. The research will address key issues concerning balance retraining: older adults’ neuromotor capacities to optimize training responses and their applicability to real-life challenges.Clinical Trial Registration: Helsinki research ethics approval has been received. (shrink)

BackgroundFigure-disembedding is one of the most discussed visuo-cognitive functions, in which individuals with Autism Spectrum Disorder have been reported to outperform non-autistic individuals. A local processing bias has been assumed to underlie such superior performance patterns. The aim of the current study is to investigate whether processing preferences can be modified by procedural priming.MethodThe current study used a procedural priming task to induce more local or global processing in 25 autistic and 21 typically developing control participants, using hierarchical figures preceding (...) the figure-disembedding task.ResultsParticipants with ASD outperformed non-autistic individuals in the unprimed baseline task version. The performance was not modulated by priming in either direction in both groups. However, the performance of TD control participants was improved by training to the same level as that observed in the ASD group.ConclusionFigure-disembedding performance in ASD is superior to that in TD control participants and robust against procedural priming or training. In contrast, performance in the TD control group can be improved up to the level of the ASD group. Any studies reporting superiority in individuals with ASD in figure-disembedding should consider training effects when evaluating group differences. (shrink)

It is fairly well known that Hume added a footnote to his essay ‘Of National Characters’ in which he asserts that all non-white peoples are naturally inferior to white people. Subsequently, he revised the note to assert only that black people are naturally inferior to white people. But while the view expressed in this footnote has been described as ‘shockingly bigoted’, and even as his ‘racial law,’ it is still commonly thought that in Hume's voluminous writings it is apparently just (...) this single passage which is definitely racist in its import. My aim in this paper is to show how American Indians are thought to be naturally inferior to white people in An Enquiry Concerning the Principles of Morals. There are, therefore, passages in Hume's second Enquiry which are also definitely racist in their import. (shrink)

Informed consent is considered by many to be a moral imperative in medical research. However, it is increasingly acknowledged that in many actual instances of consent to participation in medical research, participants do not employ the provided information in their decision to consent, but rather consent based on the trust they hold in the researcher or research enterprise. In this article we explore whether trust-based consent is morally inferior to information-based consent. We analyse the moral values essential to valid consent (...) – autonomy, voluntariness, non-manipulation, and non-exploitation – and assess whether these values are less protected and promoted by consent based on trust than they are by consent based on information. We find that this is not the case, and thus conclude that trust-based consent if not morally inferior to information-based consent. (shrink)

This paper suggests a new principle for confirmation theory which is called the principle of explanatory surplus. This principle is shown to be non-Bayesian in character, and to lead to a treatment of simplicity in science. Two cases of the principle of explanatory surplus are considered. The first (number of parameters) is illustrated by curve-fitting examples, while the second (number of theoretical assumptions) is illustrated by the examples of Newton's Laws and Adler's Theory of the Inferiority Complex.

By analysing the two relevant psychological phenomena of "endurance" and "non-endurance," this essay aims to reveal the ethical implications of a Confucian approach, namely regarding non-endurance as an impulse of primary virtue. Based on this case study, the author then explores the significance of moral cultivation or psychological training in establishing moral personality and the complexities of such a process. Meanwhile, "love" in Confucian ethics means sympathy for the inferior rather than affection for the revered. Hopefully, this study may deepen (...) our understanding of virtue ethics. /// 通过对忍与不忍这两种相关的心理现象的分析，可揭示儒家把不忍人之心作 为首善之端加以强调的伦理学含义。以此为例，探讨修养功夫即心理训练对道德人 格形成的重要性及复杂性，进而可得出儒家伦理讲求的爱是对弱者的怜爱而非对崇 敬者的热爱。这项研究有助于深化我们对德性伦理的认识。. (shrink)

Many people experience feelings of inferiority in their life. The concept of striving to avoid inferiority is a belief associated with the unwanted fear of being overlooked, missing out on opportunities for advancement, and active rejection. This study examined the effect of striving to avoid inferiority on mental health and well-being. We hypothesized that striving to avoid inferiority would modify the relationship among socioeconomic status, mental health, and well-being, therefore examined the effect of striving to avoid (...) inferiority on the relationship between annual income, mental health, and well-being. The participants were 491 adults. The results indicated that insecure striving in competition with others positively correlated with depression, anxiety, and stress, whereas secure non-striving in acceptance of inferiority positively correlated with the satisfaction with life and negatively correlated with depression. The effect of striving to avoid inferiority on the relationship among annual income, mental health, and well-being indicated that SNS affected the relationships between annual income and well-being, annual income and depression, income and anxiety, and the interaction between IS and SNS. Moreover, the relationship between income and stress was influenced by SNS and the interaction between IS and SNS. These results indicated that SNS or the interaction between IS and SNS were the only variables regulating the relationship among annual income, mental health, and well-being. These findings suggested that accepting feelings of inferiority or striving to avoid inferiority influences the mental health and well-being of people. (shrink)

Aristotle’s discussions of natural slavery, ‘barbarian kingship’, and the natural characteristics of barbarians or non-Greeks are usually read as calling into question the intellectual, ethical, and political accomplishments of non-Greeks. Such accounts of non-Greek inferiority or inability to self-govern also appear to presuppose a climatic or environmental account that on the whole would imply severe limitations on the possibility of political flourishing for peoples living outside the Greek Mediterranean basin. In light of such accounts, it is somewhat astounding to (...) find Aristotle praising the social and political institutions of Carthage within his discussion of the best constitution in the second book of the Politics. In the 4th century BCE, Carthage (modern day Tunis) was a Phoenician commercial empire that culturally and linguistically was Semitic and clearly non-Greek. That Aristotle contrasts Carthage, a non-Greek polis, favorably with both Sparta and Crete undermines both the claim that Aristotle embraced a categorical opposition between Greeks and non-Greeks and the claim that he was dismissive of the achievements of non-Greeks. (shrink)

The key concept in Kant’s aesthetics is “aesthetic reflective judgment,” a critique of which is found in Part 1 of the Critique of the Power of Judgment (1790). It is a critique inasmuch as Kant unravels previous assumptions regarding aesthetic perception. For Kant, the comparative edge of a “judgment” implicates communicability, which in turn gives it a public face; yet “reflection” points to autonomy, and the “aesthetic” shifts the emphasis away from objective properties to the subjective response evoked by the (...) object. Contrary to the view he had inherited, Kant did not treat aesthetic judgments as confused perceptions or inferior cognitions, but rather put them in a category of their own. For Kant, aesthetic reflective judgments implicated not only the processes involved in understanding the empirical world but also the processes involved in ascribing ideas or meaning to experience (which go beyond what is given in perception/cognition). This “going beyond cognition” may have been referred to by Kant as non-cognitive, but it is conditioned on a way of cognizing the object. Kant describes the features of such judgments in the Analytic of the Beautiful before addressing their possibility in subtle ways throughout the Deduction of Pure Aesthetic Judgments. Kant’s critique gives rise to three apparent dichotomies: immediate intuition and prior learning; autonomy and communicability; and non-cognitive response and aesthetic ideas. An interpretation of Kant’s theory can be deemed correct to the degree that it succeeds in showing that the contradictions are only apparent. I will argue that the resulting positive account of Kant’s aesthetic theory offers an understanding of aesthetic reflective judgment that is quite different from the standard formalism that the critics of formalism usually target and by which they misrepresent Kant’s aesthetic theory. When I refer to Kant’s formalism, then, I mean something quite different by this than what is meant by “standard formalism.” The latter is the representation given Kant’s formalism by its contemporary critics and is the typical account of formalism found in the art theory and philosophy of art literature, as will be demonstrated. (shrink)

Scientists and their supporters often portray as exasperatingly irrational all those laypersons who refuse to accede to practical recommendations issued by expert scientists and 'science appliers'. After first considering the latter groups’ standard explanations for such non-deference, which focus upon irrationalities besetting the laity, I will propose that a better explanation for at least some of the non-deference is that many laypersons are rationally electing to substitute their own judgments for those urged upon them by the scientific community. Science-based recommendations, (...) as I treat them, have the general form In light of the science on X, if you seek outcome O, you ought to V. Non-deferring laypersons deny the soundness or cogency of the V-supporting argumentation—though they are supposedly not competent to do so, given their gross epistemic inferiority to the scientific authorities who create and endorse the arguments. On account of thus being epistemically irrational, they end up being instrumentally irrational, pursuing courses of action that are poor choices for serving their own interests. The non-deferring laypersons are thought to violate two mandates of rationality: for internal deference to the underlying science as true enough to constitute an unproblematic background for decisionmaking, and for external deference to the practical application of that science to the concrete extra-scientific circumstances in question. I claim that rationality does not require categorical adherence to these mandates. In any given case, non-deference by some laypersons might be warranted by one or more of four distinct rationales. 1. Value-ladenness: The science-based recommendation discernibly includes non-scientific value-choice or value-weighting assumptions. It embodies a certain prioritizing of the plurality of specific values packed within its O parameter, and some laypersons may permissibly substitute their own. 2. Non-scientific-reasoning-ladenness: The science-based recommendation discernibly relies upon reasoning moves that are not distinctive to science, moves whose critical assessment demands no scientific expertise. Error-free reasoning is difficult to attain, and the laypersons may justifiably take themselves to have found weaknesses in the V-supporting argumentation that undermine the case for conformity to the recommendation. 3. Overgeneralization: The science-based recommendation discernibly is not adequately tailored to the specific situation of the laypersons in question. 4. Untrustworthy science: The science-based recommendation discernibly is based upon scientific research that is of doubtful quality. The first three rationales cast doubt upon the External Deference Mandate, questioning not the existence of sound underlying research but the recommendation’s judgments about how this research ought to be applied. The fourth is a challenge to the Internal Deference Mandate. (shrink)

It has been shown that quantum mechanics in its orthodox interpretation violates four different formulations of causality principle endowed with empirical meaning. The present work aims to highlight how even a realistic non-standard interpretation of the theory conflicts with causality in its Cartesian formulation of the principle of the non-inferiority of causes over effects. Such an interpretation, which attributes some form of weak physical reality to the wave function (called empty wave, regarded as a zero-energy wave-like phenomenon), is a (...) sort of precursor of the more recent so-called wavefunction realism. We also discuss a more radical realistic interpretation according to which physical properties can also be assigned to non-metaphysical relative nothing, seen as the simple absence of a particle such as a photon, but not of its corresponding state (no-photon), which is considered real. By interpreting the wave function collapse as a consequence of an interaction with empty waves or of a detection of the no-photon, we will highlight how more real physical effects can derive from lower causes, including relative nothing. Finally, we will show how these interpretations, while violating Cartesian causality in its two variants, do not seem to affect the validity of the principle of a rational explanation that nothing can derive from (absolute) nothing, which does not seem satisfied by the orthodox interpretation. (shrink)

In this paper we suggest the existence of a generalized task-related cortical network that is up-regulated whenever the task to be performed requires the allocation of generalized non-specific cognitive resources, independent of the specifics of the task to be performed. We have labeled this general purpose network, the extrinsic mode network (EMN) as complementary to the default mode network (DMN), such that the EMN is down-regulated during periods of task-absence, when the DMN is up-regulated, and vice versa. We conceptualize the (...) EMN as a cortical network for extrinsic neuronal activity, similar to the DMN as being a cortical network for intrinsic neuronal activity. The EMN has essentially a fronto-temporo-parietal spatial distribution, including the inferior and middle frontal gyri, inferior parietal lobule, supplementary motor area, inferior temporal gyrus. We hypothesize that this network is always active regardless of the cognitive task being performed. We further suggest that failure of network up- and down-regulation dynamics may provide neuronal underpinnings for cognitive impairments seen in many mental disorders, such as, e.g., schizophrenia. We start by describing a common observation in functional imaging, the close overlap in fronto-parietal activations in healthy individuals to tasks that denote very different cognitive processes. We now suggest that this is because the brain utilizes the EMN network as a generalized response to tasks that exceeds a cognitive demand threshold and/or requires the processing of novel information. We further discuss how the EMN is related to the DMN, and how a network for extrinsic activity is related to a network for intrinsic activity. Finally, we discuss whether the EMN and DMN networks interact in a common single brain system, rather than being two separate and independent brain systems. (shrink)

By analysing the two relevant psychological phenomena of “endurance” and “non-endurance,” this essay aims to reveal the ethical implications of a Confucian approach, namely regarding non-endurance as an impulse of primary virtue. Based on this case study, the author then explores the significance of moral cultivation or psychological training in establishing moral personality and the complexities of such a process. Meanwhile, “love” in Confucian ethics means sympathy for the inferior rather than affection for the revered. Hopefully, this study may deepen (...) our understanding of virtue ethics. (shrink)

In Nietzsche and Embodiment Kristen Brown reveals the smartness of bodies, challenging the traditional view in the West that bodies are separate from and morally inferior to minds. Drawing inspiration from Nietzsche, Brown vividly describes why the interdependence of mind and body matters, both in Nietzsche's writings and for contemporary debates (non-dualism theory, Merleau-Ponty criticism, and metaphor studies), activities (spinal cord research and fasting), and specific human experiences (menses, trauma, and guilt). Brown's theories about the dynamic relationship between body and (...) mind provide new possibilities for self-understanding and experience. (shrink)

We argue that planning and control may not be separable entities, either at the behavioural level or at the neurophysiological level. We review studies that show the involvement of superior and inferior parietal cortex in both planning and control. We propose an alternative view to the localization theory put forth by Glover.

The linguistic complexity of words has largely been studied on the behavioral level and in experimental settings. Only little is known about the neural processes underlying it in uninstructed, spontaneous conversations. We built up a multimodal neurolinguistic corpus composed of synchronized audio, video, and electrocorticographic (ECoG) recordings from the fronto-temporo-parietal cortex to address this phenomenon based on uninstructed, spontaneous speech production. We performed extensive linguistic annotations of the language material and calculated word complexity using several numeric parameters. We orthogonalized the (...) parameters with the help of a linear regression model. Then, we correlated the spectral components of neural activity with the individual linguistic parameters and with the residuals of the linear regression model, and compared the results. The proportional relation between the number of consonants and vowels, which was the most informative parameter with regard to the neural representation of word complexity, showed effects in two areas: the frontal one was at the junction of the premotor cortex, the prefrontal cortex, and Brodmann area 44. The postcentral one lay directly above the lateral sulcus and comprised the ventral central sulcus, the parietal operculum and the adjacent inferior parietal cortex. Beyond the physiological findings summarized here, our methods may be useful for those interested in ways of studying neural effects related to natural language production and in surmounting the intrinsic problem of collinearity between multiple features of spontaneously spoken material. (shrink)

QUALITY AND QUANTITY are fairly generally regarded as complementary terms, although the profound reason for their comple- mentarism is often far from being understood, this reason lying in the 'polar' correspondence referred to toward ...

A study of the constitution and development of the human being from the metaphysical point of view, with special reference to Vedantic doctrine.

The Reign of Quantity gives a concise but comprehensive view of the present state of affairs in the world, as it appears from the point of view of the 'ancient wisdom', formerly common both to the East and to the West, but now almost entirely lost sight of. The author indicates with his fabled clarity and directness the precise nature of the modern deviation, and devotes special attention to the development of modern philosophy and science, and to the part played (...) by them, with their accompanying notions of progress and evolution, in the formation of the industrial and democratic society which we now regard as 'normal'. Guénon sees history as a descent from Form (or Quality) toward Matter (or Quantity); but after the Reign of Quantity-modern materialism and the 'rise of the masses'-Guénon predicts a reign of 'inverted quality' just before the end of the age: the triumph of the 'counter-initiation', the kingdom of Antichrist. This text is considered the magnum opus among Guénon's texts of civilizational criticism, as is Symbols of Sacred Science among his studies on symbols and cosmology, and Man and His Becoming according to the Vedanta among his more purely metaphysical works. (shrink)

Publié pour la première fois en 1945, ce texte oppose aux religions historiques la tradition unique et originelle de la connaissance ésotérique. Le monde moderne est décrit comme une monstruosité qui ne reconnaît aucune transcendance et privilégie le règne de la contingence, du quantitatif et de l'individualisme.

Description: Contents: Preface 1. General Remarks on the Vedanta 2. Fundamental Distinction Between The Self and the Ego 3. The Vital Centre of the Human Being, Seat of Brahma 4. Purusha and Prakriti 5. Purusha Unaffected by Individual Modifications 6. The Degrees of Individual Manifestation 7. Buddhi or the Higher Intellect 8. Manas or the Inward Sense : The Ten External Faculties of Sensation and Action 9. The Envelopes of the Self ; The Five Vayus or Vital Functions 10. The (...) Essential Unity and Identity of the Self in all the States of the Being 11. The Different Conditions of Atma in the Human Being 12. The Waking State or the Condition of Vaishwanara 13. The Dream State or the Condition of Taijasa 14. The State of Deep Sleep or the Condition of Prajna 15. The Unconditioned State of Atma 16. The Symbolical Representation of Atma and its Conditions by the Sacred Monosyllable Om 17. The Posthumous Evolution of the Human Being 18. The Reabsorption of the Individual Faculties 19. Differences in the Posthumous Conditions According to the Degrees of Knowledge 20. The Coronal Artery and the Solar Ray 21. The Divine Journey of the Being on the Path of Liberation 22. Final Deliverance 23. Videha-mukti and Jivana-mukti 24. The Spiritual State of the Yogi : The Supreme Identity. (shrink)

Buddhist concepts of personal life and responsibilities.

The concluding chapter lays down the essential conditions for any genuine understanding between East and West, which can only come through the work of those who have attained, at least in some degree, to the realization of 'wisdom uncreate' ...

The quest for effective medicines is very old. In modern times two important tools have been developed to evaluate efficacy of drugs: superiority and non-inferiority types of clinical trials. The former tests the null hypothesis of μ (the difference between a tested drug and comparator) ≤ 0 against μ > 0; the latter tests the null hypothesis of μ ≤ - Δ against, μ > - Δ, where Δ is the clinical difference from the comparator. In a superiority trial, (...) a new drug is tested against a placebo; in a non-inferiority trial, a new drug is tested against active treatment. In this paper, arguments are presented to show that a superiority trial against a placebo is scientifically sound but ethically unacceptable, whereas a non-inferiority trial against active treatment is ethically sound but scientifically not reliable. Switching from a superiority type of trial with placebo to a non-inferiority trial with an active-control — following the latest revision of Declaration of Helsinki — is in practice switching from the violation of the uncertainty principle to uncertainty of results. Given human and financial resources, it appears an academic question as to which is more unethical: to violate patients’ rights or to produce results without scientific value. All presented considerations lead to the conclusion that the use of a superiority trial of design with an active control instead of placebo will satisfy scientific needs, expectation of patients, and the ancient quest for effective medicines. In the era of Good (Clinical, Laboratory, Manufacture) Practice, the attention of those performing clinical trials is focused on the procedure, not always on its essence. However even the excellent performance of a trial which is not worth doing is fruitless. (shrink)

An increasing number of drugs removed from the market because of unacceptable toxicity raises concerns regarding preapproval testing of drug safety. In the present paper it is postulated that the non-inferiority type of trial should be abandoned in favor of the superiority trial with active controls and less stringent (p<0.1, both for efficacy and toxicity) statistics. This approach will increase sensitivity of detection of drug-induced adverse effects at the expense of increasing false positive results regarding the difference in efficacy (...) between the tested and reference drug. Such a move will increase the protection of future patients. In addition, the proposed design is far more acceptable from the clinical (e.g. no need to specify the statistically expected “unimportant” number of deaths) and ethical points of view, as well as being favored by the strong incentive of involved parties. In the second part of this paper arguments are presented in favor of the hypothesis that placebo (still used in some superiority trials) does not induce adverse effects. The assertion that placebo may induce adverse effects is probably biased by the nature of the clinical experiment. Such a conclusion is supported by studies indicating that placebo-induced adverse effects are disease — and treatment — specific. The modification of clinical trials according to the proposed changes may increase the trials’ sensitivity at detecting adverse effects of drugs. (shrink)