Key elements of Randolph Clarke's libertarian account of freedom that requires both agent-causation and non-deterministic event-causation in the production of free action is assessed with an eye toward determining whether agent-causal accounts can accommodate the truth of judgments of moral obligation.

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)

1 INSERM-CEA Unit 562, Cognitive Neuroimaging, Service Hospitalier Fre´de´ric Joliot, Orsay, France, 2 CNRS URA2182 Re´cepteurs and Cognition, Institut Pasteur, Paris, France.

The current study is a pilot trial to examine the effects of a nonelective, classroom-based, teacher-implemented, mindfulness meditation intervention on standard clinical measures of mental health and affect in middle school children. A total of 101 healthy sixth-grade students (55 boys, 46 girls) were randomized to either an Asian history course with daily mindfulness meditation practice (intervention group) or an African history course with a matched experiential activity (active control group). Self-reported measures included the Youth Self Report (YSR), (...) a modified Spielberger State-Trait Anxiety Inventory, and the Cognitive and Affective Mindfulness Measure –Revised. Both groups decreased significantly on clinical syndrome subscales and affect but did not differ in the extent of their improvements. Meditators were significantly less likely to develop suicidal ideation or thoughts of self-harm than controls. These results suggest that mindfulness training may yield both unique and non-specific benefits that are shared by other novel activities. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best (...) methods will favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best (...) methods will favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)

According to Howick (2009a), the three main reasons for believing that placebo-controlled trials (PCTs) are methodologically superior to active-controlled trials (ACTs)—sensitivity, absolute effect...

Cognitive control of physical activity and sedentary behavior is receiving increased attention in the neuroscientific and behavioral medicine literature as a means of better understanding and improving the self-regulation of physical activity. Enhancing individuals’ cognitive control capacities may provide a resilient means to increase physical activity and reduce sedentary behavior. First, this paper reviews emerging evidence of the antecedence of cognitive control abilities in successful self-regulation of physical activity, and in precipitating self-regulation failure that predisposes to sedentary (...) behavior. We then highlight the brain networks that may underpin the cognitive control and self-regulation of physical activity, including the default mode network, prefrontal cortical networks and brain regions and pathways associated with reward. We then discuss research on cognitive training interventions that document improved cognitive control and that suggest promise of influencing physical activity regulation. Key cognitive training components likely to be the most effective at improving self-regulation are also highlighted. The review concludes with suggestions for future research. (shrink)

Despite ample evidence that speech production is associated with extensive trial-to-trial variability, it remains unclear whether this variability represents merely unwanted system noise or an actively regulated mechanism that is fundamental for maintaining and adapting accurate speech movements. Recent work on upper limb movements suggest that inter-trial variability may be not only actively regulated based on sensory feedback, but also provide a type of workspace exploration that facilitates sensorimotor learning. We therefore investigated whether experimentally reducing or magnifying inter-trial formant variability (...) in the real-time auditory feedback during speech production leads to adjustments in formant production variability that compensate for the manipulation, changes the temporal structure of formant adjustments across productions, and enhances learning in a subsequent adaptation task in which a predictable formant-shift perturbation is applied to the feedback signal. Results show that subjects gradually increased formant variability in their productions when hearing auditory feedback with reduced variability, but subsequent formant-shift adaptation was not affected by either reducing or magnifying the perceived variability. Thus, findings provide evidence for speakers’ active control of inter-trial formant variability based on auditory feedback from previous trials, but–at least for the current short-term experimental manipulation of feedback variability–not for a role of this variability regulation mechanism in subsequent auditory-motor learning. (shrink)

Disgust is reasoned to operate in conjunction with the immune system to help protect the body from illness. However, less is known about the factors that impact the degree to which individuals invest in pathogen avoidance (disgust) versus pathogen management (prophylactic immunological activity). Here, we examine the role that one’s control over pathogen contact plays in resolving such investment trade-offs, predicting that (a) those from low control environments will invest less in pathogen-avoidance strategies and (b) investment in each (...) of these two strategies will occur in a compensatory fashion (i.e. they will be traded off with one other). Across four studies, we found support for these predictions, using a variety of manipulations and measures. By providing novel insights into how one’s control over pathogen exposure influences disgust sensitivity and immune system activity, the current research poses an important contribution to the literature on disgust, pathogen avoidance, and the immune system. (shrink)

In this paper, an active frequency control strategy of wind turbines based on model predictive control is proposed by using the power margin of wind turbines operating in load shedding mode. The frequency response model of the microgrid system with the load shedding of the wind turbines is used to predict the output power and system frequency deviation of the wind turbine. According to the prediction information, the output power control signal of the model predictive controller (...) in the wind turbine can be optimized. On this basis, a wind turbine active participation frequency control strategy based on model predictive control is designed by rolling prediction and optimization. The wind turbine power control signal after the strategy is used to adjust the output power of the wind turbine and balance the change of the active power of the system to reduce the frequency deviation. (shrink)

Both glycemic control and handgrip strength affect microvascular function. Multiscale entropy of photoplethysmographic pulse amplitudes may differ by diabetes status and hand activity. Of a middle-to-old aged and right-handed cohort without clinical cardiovascular disease, we controlled age, sex, and weight to select the unaffected,the well-controlled diabetes, and the poorly controlled diabetes groups. MSEs were calculated from consecutive 1,500 PPG pulse amplitudes of bilateral index fingertips. Thesmall-, medium-,and large-scale MSEs were defined as the average of scale 1, scales 2–4, and (...) scales 5–10, respectively. Intra- and intergroups were compared by one- and two-samplet-tests, respectively. The dominant handMSE5–10was lower in the poorly controlled diabetes group than the well-controlled diabetes and the unaffected groups, whereas the nondominant handMSE5–10was lower in the well- and poorly controlled diabetes groups than the unaffected group. TheMSE1of dominant hand was higher than that of nondominant hand in the well-controlled diabetes. In conclusion, diabetes status and hand dominance may affect the MSE of PPG pulse amplitudes. (shrink)

Since the outbreak of the COVID-19 pandemic, the physical and mental health of older adults has been threatened. Promoting physical and mental health through physical activity has therefore become a strategy for healthy aging. In order to better understand the impact of the participation of older adults in physical activity, this paper selects different types of physical activity, and examines the relationship between them and subjective well-being through the analysis of the mediation effect of outdoor exercise environment and the regulating (...) effect of exercise form. In this cross-sectional study, a questionnaire survey was conducted in mainland China. The main data come from 903 older adults in five urban areas in Chengdu, Sichuan Province. The surveys were carried out using the Physical Activity Rating Scale, Newfoundland Subjective Well-Being Scale, Exercise Environment Scale, and Exercise Form Scale. SPSS was used for statistical analysis, linear regression analysis was adopted for processing data, and AMOS was used to establish a mediation model. The mediating variable is the outdoor exercise environment, and the moderating variable is exercise form; gender, age, education level, and monthly income were used as control variables. The study results showed that different physical activities were significantly, positively correlated with the subjective well-being of older adults ; among the activities, tai chi had the strongest effect on the subjective well-being of older adults. Outdoor exercise environment played a mediating role between different physical activity types and subjective well-being of older adults [tai chi: β = 0.030, 95% CI ; health qigong: β = 0.018, 95% CI ; walking and jogging: β = 0.034, 95% CI ]. Exercise form moderated the subjective well-being of older adults in different physical activities. The results of this study demonstrate that the outdoor exercise environment plays a mediating role between different physical activities and the subjective well-being of older adults, and the form of exercise can also moderate the impact of different physical activities on the subjective well-being of older adults. This study has enlightening significance for psychological intervention with older adults facing stress, anxiety and depression. (shrink)

It has been argued that the explanation of self-control requires positing special motivational powers. Some think that we need will-power as an irreducible mental faculty; others that we need to think of the active self as a dedicated and depletable pool of psychic energy or – in today more respectable terminology – mental resources; finally, there is the idea that self-control requires postulating a deep division between reason and passion – a deliberative and an emotional motivational system. (...) This essay argues that no such special motivational powers are necessary. Yet, at the same time, self-control does powerfully illustrate the importance of a feature of the mind. What it illustrates, I argue, is the importance of the mental activity of attention in the control of all action. It is by appeal to this mental activity that we can dispense with special motivational powers. If we think of Humeanism as the view that there is fundamentally only one kind of motivational system and that all action is based in that system, then this essay contributes to a defense of Humeanism. On the other hand, the essay also shows that any model of agency in terms of only beliefs and desires, motivational and representational states, or preferences and credences is incomplete. A different conception of Humeanism as the view that every mental state is either motivational, representational, or a combination of them, is false. (shrink)

There is evidence from neuropsychological and psychophysical measurements that conscious sensory information is processed in discrete time segments. The segmentation process may be described as neuronal activity at a frequency of 40 Hz. Stimulus-induced neuronal activities of this frequency are found in the middle latency range of the auditory evoked potential . First, we have studied the effects of different general anesthetics on MLAEP and auditory evoked 40-Hz activity. Second, we investigated MLAEP and explicit and implicit memory for information presented (...) during cardiac anesthesia. In the awake patients peak latencies of the MLAEP were in the normal range. An auditory evoked 40-Hz activity was present 20–100 ms poststimulus. Under nonspecific anesthetics MLAEP and the 40-Hz activity were suppressed, and under receptor-specific agents MLAEP and the 40-Hz activity were partly preserved. None of the cardiac patients had conscious explicit recall of the intraoperative events, whereas some patients showed unconscious implicit memory for an intraoperative tape message. The implicit memory could be related to midlatency auditory evoked potentials. No implicit memory was detectable when MLAEP and the primary cortical processing of the auditory stimuli and 40-Hz activity were blocked. Implicit memory could be detected in more than 50% of the cases when MLAEP, a 30-Hz activity, and the primary cortical stimulus processing were preserved. In conclusion, our observations support the view that a high frequency oscillatory mechanisms, recorded as a grouped neuronal activity in the MLAEP, may be part of a basic neuronal program for conscious sensory information processing. (shrink)

This review will discuss how STAT (Signal Transducers and Activators of Transcription) proteins, a group of transcription factors that transmit signals from the extracellular surface of cells to the nucleus, are involved in growth control. I will discuss the anatomy of a STAT protein, how it works as a transcription factor, the molecules that regulate its “activity”, the phenotypes of mice that lack individual STAT proteins and their involvement in growth, differentiation, apoptosis, and transformation. Finally, a number of examples (...) will be presented of how dysregulated STAT signaling may be involved in the pathogenesis of cancer. BioEssays 23:161–169, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Binding of antigen or lectin to the surface of a T lymphocyte initiates a complex sequence of events which result in both T cell proliferation and the acquisition of immunologic functions. This complex sequence of events is most likely programmed and precisely timed by a series of contingent gene activations in which one member of this series activates the next. The two most obvious examples of these stages are the set of genes activated when antigen interacts with the antigen receptor (...) and the set of genes activated when IL‐2 interacts with its receptor. However, it is likely that several other parallel pathways of gene activation are necessary to bring about T‐cell division. An example would be the antigen‐induced activation of the c‐myc gene, which in turn is likely to be involved in regulating an additional group of genes not directly controlled by either IL‐2 or antigen. A fundamental understanding of T‐lymphocyte activation necessitates identification of the factors involved in initiating each of these contingent levels of gene activation. (shrink)

Social media plays a vital role in consumers’ purchasing decision making. There are still gaps in existing research on the relationship between divided dimensions of social media use and impulse buying, as well as the mediating and moderating effects therein. This study explored the mediation and moderation effects in the relationship between different social media usage patterns, emotional responses, and consumer impulse buying. Data from 479 college students who were social media users in China were analyzed using structural equation modeling. (...) The results showed that active and passive social media use were significantly and positively associated with users’ enjoyment, whereas passive social media use significantly increased depression. Both enjoyment and depression were significantly and positively associated with users’ impulse buying. Materialism positively moderated the relationship between enjoyment and impulsive consumption, while self-control significantly reduced the effect of depression on impulse buying. These findings that emotion mediated and personality traits moderated relationships between social media use and impulse buying expand impulsive purchase literature and provide insights for guiding college students’ healthy use of social media and rational consumption. (shrink)

Unstable Accumulating Activator models for cellular size control propose an activator that accumulates in a size-dependent manner and triggers cell cycle progression once it has reached a certain threshold. Having a short half life makes such an activator responsive to changes in cell size and makes specific predictions for how cells respond to perturbation. In particular, it explains the curious phenomenon of excess mitotic delay. Excess mitotic delay, first observed in Tetrahymena in the '50s, is a phenomenon in which (...) a pulse of protein synthesis inhibition causes a delay in mitotic entry that is longer than the pulse and that gets longer the later in the cell cycle the pulse is delivered. The interpretation of this phenomenon championed by Zeuthen and Mitchison in the '60s and '70s is that an unstable activator of mitosis is degraded during the pulse and has to be resynthesized to a threshold level to trigger mitosis; small cells have more time to resynthesize the activator before mitosis and so suffer less excess delay, whereas, large cells have less time thus suffer greater excess delay. Fifty years later, with our detailed understanding of cell cycle biochemistry, we can identify and test candidate Unstable Accumulating Activators. Here I review the field and further develop this concept. Excess mitotic delay, the phenomenon in which inhibition of protein synthesis causes a longer delay than the pulse of inhibition, is consistent with cell size control by an unstable accumulating activator, but not a stable activator. (shrink)

There is a conceptual knot at the intersection of moral responsibility and action theory. This knot can be expressed as the following question: What is the relationship between an agent’s openness to moral responsibility and the intentional status of her behaviour? My answer to this question is developed in three steps. I first develop a control-backed account of intentional agency, one that borrows vital insights from the cognitive sciences – in the form of Dual Process Theory – in understanding (...) the control condition central to the account, and demonstrate that this account fares at least as well as its rivals in the field. Secondly, I investigate the dominant positions in the discussion surrounding the role of control in moral responsibility. After consideration of some shortcomings of these positions – especially the inability to properly account for so-called ambivalence cases – I defend an alternative pluralist account of moral responsibility, in which there are two co-extant variants of such responsibility: attributability and accountability. The latter of these will be shown to have a necessary control condition, also best understood in terms of a requirement for oversight, and in terms of the workings of the dual system mechanism. I then demonstrate how these two accounts are necessarily related through the shared role of this kind of control, leading to my answer to the original question: if an agent is open to moral accountability based on some activity or outcome, this activity or outcome must necessarily have positive intentional status. I then apply this answer in a consideration of certain cases of the use of the Doctrine of Double Effect. (shrink)

This paper introduces a novel method to control the operation of the active suspension system. In this research, a quarter-dynamic model is used to simulate the vehicle’s vibrations. Besides, the sliding mode-PID-integrated algorithm with five state variables is proposed to be used. This is a completely original and novel algorithm. The process of establishing the control algorithm is clearly described. The simulation is performed by the MATLAB software. The results of the paper have shown the advantages of (...) the sliding mode-PID algorithm used in this research. Accordingly, the displacement and acceleration of the sprung mass were significantly reduced when this algorithm was used. The maximum and average values of the displacement of the sprung mass are only 1.31% and 1.29%, respectively, compared with the situation of the vehicle using a passive suspension. Similarly, the value of the acceleration is 6.98% and 2.94%, respectively. In addition, the phenomenon of “chattering” has also been significantly reduced when using this controller. In the future, some more complex algorithms can be proposed. (shrink)

The gap between the decision to engage in physical activity and subsequent behavioral enactment is considerable for many. Action control theories focus on this discordance in an attempt to improve the translation of intention into behavior. The purpose of this mini-review was to overview one of these approaches, the multi-process action control framework, which has evolved from a collection of previous works. The main concepts and operational structure of M-PAC was overviewed followed by applications of the framework in (...) physical activity, and concluded with unanswered questions, limitations, and possibilities for future research. In M-PAC, it is suggested that three layered processes build upon each other from the formation of an intention to a sustained profile of physical activity action control. Intention-behavior discordance is because of strategic challenges in goal pursuit and automatic tendencies. Regulatory processes are employed to hold the relationship between reflective processes and behavior concordant by countering these strategic challenges and automatic tendencies until the development of reflexive processes begin to co-determine action control. Results from 29 observational and preliminary experimental studies generally support the proposed M-PAC framework. Future research is needed to explore the temporal dynamic between reflexive and regulatory constructs, and implement M-PAC interventions in different forms, and at different levels of scale. (shrink)

Multiple sensory signals from visual, somatosensory and vestibular systems are used for human postural control. To maintain postural stability, the central nervous system keeps the center of mass (CoM) within the base of support. The influence of the stomatognathic motor system on postural control has been established under static conditions, but it has not yet been investigated during dynamic steady-state balance. The purpose of the study was to investigate the effects of controlled stomatognathic motor activity on the (...) class='Hi'>control and stability of the CoM during dynamic steady-state balance. A total of 48 physically active and healthy adults were assigned to three groups with different stomatognathic motor conditions: jaw clenching, tongue pressing and habitual stomatognathic behavior. Dynamic steady-state balance was assessed using an oscillating platform and the kinematic data were collected with a 3D motion capturing system. The path length (PL) of the 3D CoM trajectory was used for quantifying CoM sway. Temporal dynamics of the CoM movement was assessed with a detrended fluctuation analysis (DFA). An uncontrolled manifold (UCM) analysis was applied to assess the stability and control of the CoM with a subject-specific anthropometric 3D model. The statistical analysis revealed that the groups did not differ significantly in PL, DFA scaling exponents or UCM parameters. The results indicated that deliberate jaw clenching or tongue pressing did not seem to affect the sway, control or stability of the CoM on an oscillating platform significantly. Because of the task-specificity of balance, further research investigating the effects of stomatognathic motor activities on dynamic steady-state balance with different movement tasks are needed. Additionally, further analysis by use of muscle synergies or co-contractions may reveal effects on the level of muscles, which were not visible on the level of kinematics. This study can contribute to the understanding of postural control mechanisms, particularly in relation to stomatognathic motor activities and under dynamic conditions. (shrink)