Fourteen healthy children (13.8±2.2 years, range 10 to 16; M:F=5:9) received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300 (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to Transcranial Magnetic Stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were expressed as a ratio (...) and assessed from 1 to 10 minutes (BLOCK1) and 1 to 30 minutes (BLOCK2) using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1) without any clinically reported adverse events. ITBS300 produced significant M1 facilitation (F5,65=3.165, p=0.01) at BLOCK1 and trend level M1 facilitation at BLOCK2 (F10,129=1.69, p=0.089). Although iTBS300 (stimulation duration of 92 seconds at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability. (shrink)

Purpose: This study is aimed to preliminary investigate whether transcranial alternating current stimulation could affect explosive power considering genetic background in sport subjects.Methods: Seventeen healthy sports volunteers with at least 3 years of sports activities participated in the experiment. After 2 weeks of familiarization performed without any stimulation, each participant received either 50 Hz-tACS or sham-tACS. Before and after stimulation, subjects performed the following tests: the squat jump with the hands on the hips ; countermovement jump with the hands on (...) the hips ; countermovement jump with arm swing ; 15-s Bosco’s test; seated backward overhead medicine ball throw ; seated chest pass throw with a 3-kg rubber medicine ball; and hand-grip test. Additionally, saliva samples were collected from each participant. Genotyping analysis was carried out by polymerase chain reaction.Results: No significant differences were found in sport performance of subjects after 50 Hz-tACS. Additionally, we did not find any influence of genetic background on tACS-related effect on physical performance. These results suggest that tACS at gamma frequency is not able to induce an after-effect modulating sport performance. Further investigations with larger sample size are needed in order to understand the potential role of non-invasive brain stimulation techniques in motor performances.Conclusions: Gamma-tACS applied before the physical performance fails to improve explosive power in sport subjects. (shrink)

The use of transcranial Electrical Stimulation in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation, identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework and tES application, (...) hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex. The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial. Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics. (shrink)

Deep brain stimulation — a novel surgical procedure — is emerging as a treatment of last resort for people diagnosed with neuropsychiatric disorders such as severe obsessive-compulsive disorder. The US Food and Drug Administration granted a so-called humanitarian device exemption to allow patients to access this intervention, thereby removing the requirement for a clinical trial of the appropriate size and statistical power. Bypassing the rigors of such trials puts patients at risk, limits opportunities for scientific discovery, and gives device (...) manufacturers unique marketing opportunities. We argue that Congress and federal regulators should revisit the humanitarian device exemption to ensure that it is not used to sidestep careful research that can offer valuable data with appropriate patient safeguards. (shrink)

The ability to learn sequential contingencies of actions for predicting future outcomes is indispensable for flexible behavior in many daily decision-making contexts. It remains open whether such ability may be enhanced by transcranial direct current stimulation. The present study combined tDCS with functional near-infrared spectroscopy to investigate potential tDCS-induced effects on sequential decision-making and the neural mechanisms underlying such modulations. Offline tDCS and sham stimulation were applied over the left and right dorsolateral prefrontal cortex in young male adults in a (...) double-blind between-subject design using a three-state Markov decision task. The results showed an enhanced dlPFC hemodynamic response during the acquisition of sequential state transitions that is consistent with the findings from a previous functional magnetic resonance imaging study; a tDCS-induced increase of the hemodynamic response in the dlPFC, but without accompanying performance-enhancing effects at the behavioral level; and a greater tDCS-induced upregulation of hemodynamic responses in the delayed reward condition that seems to be associated with faster decision speed. Taken together, these findings provide empirical evidence for fNIRS as a suitable method for investigating hemodynamic correlates of sequential decision-making as well as functional brain correlates underlying tDCS-induced modulation. Future research with larger sample sizes for carrying out subgroup analysis is necessary in order to decipher interindividual differences in tDCS-induced effects on sequential decision-making process at the behavioral and brain levels. (shrink)

Background: There is increasing evidence to support the efficacy of transcranial direct current stimulation applications in cognitive augmentation and rehabilitation. Neuromodulation achieved with tDCS may further regulate regional cerebral perfusion affiliated through the neurovascular unit; however, components of cerebral perfusion decrease across aging. A novel neuroimaging approach, functional near-infrared spectroscopy, can aid in quantifying these regional perfusional changes. To date, the interaction of the effects of tDCS on cognitive performance across the lifespan and obtained fNIRS hemodynamic responses remain unknown.Objective: This (...) review aims to examine the effects of tDCS on cognitive performance and fNIRS hemodynamic responses within the context of cognitive aging.Methods: Six databases were searched for studies. Quality appraisal and data extraction were conducted by two independent reviewers. Meta-analysis was carried out to determine overall and subgroup effect sizes.Results: Eight studies met inclusion criteria. The overall effect size demonstrates that tDCS can alter cognitive performance and fNIRS signals, with aging being a potential intermediary in tDCS efficacy.Conclusion: From the studies included, the effects of tDCS on cognitive performance and fNIRS metrics are most prominent in young healthy adults and appear to become less robust with increasing age. Given the small number of studies included in this review further investigation is recommended. (shrink)

The need for new “pull” incentives to stimulate antibiotic R&D is widely recognized. Due to the global diversity of health systems, combined with different challenges faced by antibiotics used in different types of healthcare settings, there is no one-size-fits-all solution. Instead, different “pull” incentives should be tailored to local contexts, priorities, and antibiotic types. Policymakers and industry should collaborate to identify appropriate solutions at the local, regional, and global levels.

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson’s disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in (...) eight patients with advanced Parkinson’s disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = −0.81, p < 0.0218, Spearman’s correlation coefficient) between left side local field potentials of the low beta band (11–20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface. (shrink)

The purpose of the study is to analyze the features of the placement of small and medium-sized enterprises on the example of the Ural Federal District. It is revealed that the development of small and medium-sized businesses in the Ural Federal District is uneven. The scientific novelty is to identify the key factors influencing the placement of small and medium-sized businesses. As a result, it is proved that factors such as the number of cities, population density and density of railways (...) have a positive effect on the placement of SMEs. As recommendations for the uniform placement of SMEs on the example of the Ural Federal District, the following are proposed: 1) stimulating urban development; 2) conducting demographic policy aimed at supporting population growth; 3) implementing major infrastructure projects, such as the construction of a railway track. (shrink)

ObjectiveThis systematic review aims to analyze existing literature of the effects of transcranial direct current stimulation (tDCS) on motor skills learning of healthy adults and discuss the underlying neurophysiological mechanism that influences motor skills learning.MethodsThis systematic review has followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The PubMed, EBSCO, and Web of Science databases were systematically searched for relevant studies that were published from database inception to May 2022. Studies were included based on the Participants, (...) Intervention, Comparison, Outcomes, and Setting inclusion strategy. The risk of bias was evaluated by using the Review manager 5.4 tool. The quality of each study was assessed with the Physiotherapy Evidence Database (PEDro) scale.ResultsThe electronic search produced 142 studies. Only 11 studies were included after filtering. These studies performed well in terms of distribution, blinding availability and selective reporting. They reported that tDCS significantly improved motor skills learning. The main outcomes measure were the improvement of the motor sequence tasks and specific motor skills. Nine studies showed that tDCS interventions reduced reaction time to complete motor sequence tasks in healthy adults and two studies showed that tDCS interventions improved golf putting task performance.ConclusionThe included studies showed that tDCS can help healthy adults to improve the motor skills learning by activating different brain regions, such as the primary motor cortex, left dorsolateral prefrontal cortex and right cerebellum. However, the number of included studies was limited, and the sample sizes were small. Therefore, more studies are urgently needed to validate the results of current studies and further explore the underlying neurophysiological mechanisms of tDCS in the future. (shrink)

New technologies coupled with high energy prices, a desire for energy independence, and cleaner energy, have led to many energy companies investing large amounts of capital into rural places. In the last decade, along with solar and wind, unconventional shale oil and gas production has risen steeply throughout the United States boosting economic growth and stimulating wealth creation in many communities. Because farmers own or operate over half of rural lands in the lower 48 states, the possibility is high for (...) shale development to contribute to the financial well-being of farmers with land in shale regions. However, by focusing on the large royalties of some landowners, environmental and social risks that farmers encounter may be overlooked. To address the gap of farmer impacts, I examine the experiences and perceptions of crop farm owners who reside in two established shale plays: the Bakken region in North Dakota and the Marcellus region in Pennsylvania and in one emerging shale play: the New Albany region in Southern Illinois. I survey farm owners of both large and small crop farms, who farm a variety of crops both by conventional and organic methods. By having such a diverse sample of farm owners in both established shale plays and emerging shale plays, I explore how farmers’ experiences differ with respect to their finances and investments, environmental degradation as well as how their perceptions of trust in oil and gas companies and community rifts differ. (shrink)

Chronic migraine is a difficult disease to diagnose, and its pathophysiology remains undefined. Its symptoms affect the quality of life and daily living tasks of the affected person, leading to momentary disability. This is a pilot, randomized, controlled, double-blind clinical trial study with female patients between 18 and 65 years old with chronic migraine. The patients underwent twelve mindfulness sessions paired with anodal transcranial direct-current stimulation over the left dorsolateral prefrontal cortex, with current intensity of 2 mA applied for 20 (...) min, three times a week for 4 weeks. In addition, 20 min of mindfulness home practices were performed by guided meditation audio files. A total of 30 participants were evaluated after the treatment, and these were subdivided into two groups—active tDCS and sham tDCS, both set to mindfulness practice. The FFMQ-BR, MIDAS, and HIT-6 questionnaires were used to evaluate the outcomes. After the treatment, the active mindfulness and tDCS group showed better results in all outcomes. The sham group also showed improvements, but with smaller effect sizes compared to the active group. The only significant difference in the intergroup analysis was the outcome evaluated by HIT-6 in the post treatment result. Our results provide the first therapeutic evidence of mindfulness practices associated with left DLPFC anodal tDCS with a consequent increase in the level of full attention and analgesic benefits in the clinical symptoms of patients with chronic migraine. (shrink)

Background: Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy. The high prevalence of EMDR in clinical practice and the dramatic increase (...) in EMDR research in recent years, with more than 26 randomized controlled trials published to date, highlight the need for a better understanding of its mechanism of action. Methods: We conducted a thorough systematic search of studies published until October 2017, using PubMed, ScienceDirect, Web of Knowledge and Scopus databases that examined the mechanism of action of EMDR or provided conclusions within the framework of current theoretical models of EMDR functioning. Results: Seventy-five studies were selected for review and classified into three overarching models; (i) psychological models (ii) psychophysiological models and (iii) neurobiological models. The evidence available from each study was analysed and discussed. Results demonstrated a reasonable empirical support for the working memory hypothesis and for the physiological changes associated with successful EMDR therapy. Recently, more sophisticated structural and functional neuroimaging studies using high resolution structural and temporal techniques are starting to provide preliminary evidence into the neuronal correlates before, during and after EMDR therapy. Discussion: Despite the increasing number of studies that published in recent years, the research into the mechanisms underlying EDMR therapy are still in its infancy. Studies in well-defined clinical and non-clinical populations, larger sample sizes and tighter methodological control are further needed in order to establish firm conclusions. (shrink)

Every perceptual experience has an objective and a subjective side. We see object size, independent of distance, but we also see that distant objects project smaller images. Early modern conceptions focused on local stimulation and thus on the subjective aspect. Helmholtz and Hering emphasized the objective aspect. Helmholtz split visual experience into two stages, with sensation representing the subjective side and perception, through cognitive processes, the objective side. Gestalt theory denied this dualism, rejecting both sensory and cognitive stages. Despite (...) contrary evidence, the sensation/perception dualism persists, in brightness models and past experience theories. That we can detect visual angle and luminance does not mean that these are raw sensations out of which perception of size and lightness is built. Size and color constancy are truly visual, not cognitive. Instructions to subjects in vision experiments must avoid the proximal mode on the one hand and cognitive judgments on the other. (shrink)

Introduction: Motor evoked potentials (MEPs) to transcranial magnetic stimulation are known to be susceptible to several sources of variability. However, conflicting evidences on individual characteristics in relatively small sample sizes have been reported. We investigated the effect of age, height, and sex on MEPs of the motor cortex and spinal roots in a large cohort. Methods: A total of 587 subjects clinically and neuroradiologically intact were included. MEPs were recorded during mild tonic contraction through a circular coil applied over the (...) “hot spot” of the first dorsal interosseous and tibialis anterior muscles, bilaterally. Central motor conduction time (CMCT) was estimated as the difference between MEP cortical latency and the peripheral motor conduction time by cervical or lumbar magnetic stimulation. Peak-to-peak MEP amplitude to cortical stimulation and right-to-left difference of each parameter were also measured. Results: After Bonferroni correction, general linear (multiple) regression analysis showed that both MEP cortical latency and peripheral motor conduction time at four limbs positively correlated with age and height. At lower limbs, an independent effect of sex on the same measures was also observed (with females showing smaller values than males). CMCT correlated with both age (negatively) and height (positively) when analyzed by a single regression; however, with a multiple regression analysis this significance disappeared, due to the correction for the multicollinearity within the dataset. Conclusions: Physical individual features need to be considered for a more accurate and meaningful MEPs interpretation. Both in clinical practice and in research setting, patients and controls should be matched for age, height, and sex. (shrink)

Our think tank tasked by the Dutch Health Council, consisting of Radboud University Nijmegen Honours Academy students with various backgrounds, investigated the implications of Deep Brain Stimulation for psychiatric patients. During this investigation, a number of methodological, ethical and societal difficulties were identified. We consider these difficulties to be a reflection of a still fragmented field of research that can be overcome with improved organization and communication. To this effect, we suggest that it would be useful to found a centralized (...) DBS organization. Such an organization makes it possible to 1) set up and maintain a repository, 2) facilitate DBS studies with a larger sample size, 3) improve communication amongst researchers, clinicians and ethical committees, and 4) improve communication between DBS experts and the public at large. (shrink)

Seeing happens effortlessly and yet is endlessly complex. Among the most fascinating aspects of visual perception is its stability and constancy. As we shift our gaze or move about the world, the light projected onto the retinas is constantly changing. Yet the surrounding objects appear stable in their properties. Psychologists have long been interested in the constancies. They have asked questions such as: How good is constancy? Is constancy a fact about how things look, or is it a product of (...) our beliefs and judgments about how things look? How can the contents of visual experience be studied experimentally? Philosophers have long been interested in characterizing visual experience and have become widely interested in the constancies more recently. As psychologists and philosophers have interacted, new questions have arisen: If experience is not as of retinal stimulation (proximal mode), but does not always exhibit constancy (or at least not in all respects), how shall we describe this intermediate state? Also, should we regard any departure from constancy as a failure of the visual system, or might it be a reasonable or adaptive response? In what circumstances is seeing highly conditioned by cognitive factors such as background assumptions, and in what circumstances not? Our volume focuses on size constancy and color constancy. It considers methodologies for studying conscious visual perception, efforts to describe visual experience in relation to constancy, what it means that constancy is not always perfect, and the conceptual resources needed for explaining visual experience. (shrink)

Tax payments stimulate business enterprises to choose tax management through tax avoidance activities, which is the legal practice to reduce the amount of tax payable. In developing economies, taxation is considered more critical for budget and revenues of a country. This paper investigates whether various business strategies influence corporate tax avoidance decisions of firms by adopting business strategies. Besides, it explores how gender diversity can ease this relationship. This study has chosen a sample of organizations from non-financial sector in Pakistan. (...) The time frame is 5 years, including once a year. The present model employed a generalized moment method and tested the proposed hypothesis to draw the results. The study has taken the size, leverage, and business profitability as control variables of firms. The study outcomes by using the GMM method demonstrate that the presence of female directors reduces tax avoidance behavior in prospector companies. This study provides insight into future research for stakeholders, government officials, tax authorities, and policymakers. The findings offer valuable recommendations and practical insights and implications. The findings provide future directions for research to test different frameworks to attain beneficial results to promote the responsibility of tax payment culture. (shrink)

This paper is devoted to computer modelling of the development and regeneration of multicellular biological structures. Some species are able to regenerate parts of their body after amputation damage, but the global rules governing cooperative cell behaviour during morphogenesis are not known. Here, we consider a simplified model organism, which consists of tissues formed around special cells that can be interpreted as stem cells. We assume that stem cells communicate with each other by a set of signals, and that the (...) values of these signals depend on the distance between cells. Thus the signal distribution characterizes location of stem cells. If the signal distribution is changed, then the difference between the initial and the current signal distribution affects the behaviour of stem cells—e.g. as a result of an amputation of a part of tissue the signal distribution changes which stimulates stem cells to migrate to new locations, appropriate for regeneration of the proper pattern. Moreover, as stem cells divide and form tissues around them, they control the form and the size of regenerating tissues. This two-level organization of the model organism, with global regulation of stem cells and local regulation of tissues, allows its reproducible development and regeneration. (shrink)

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number (...) of subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

In barely the space of one generation, Athens was transformed from a conventional city-state into something completely new--a region-state on a scale previously unthinkable. This book sets out to answer a seemingly simple question: How and when did the Athenian state attain the anomalous size that gave it such influence in Greek politics and culture in the classical period? Many scholars argue that Athens's incorporation of Attica was a gradual development, largely completed some two hundred years before the classical (...) era. Anderson, however, suggests that it is not until the late sixth century that we see the first systematic attempts by the Athenian polis to integrate all of Attica. Anderson first takes issue with the prevailing view of Cleisthenes' landmark political reforms of 508-7 b.c., arguing that they were animated by a more comprehensive vision of regional political community in Attica. The Athenians' strengthened the state by establishing institutional mechanisms that would allow inhabitants of the Attic periphery to participate as never before in the life of the center. The creation of a suitable physical setting for the new order was accompanied by religious, military, and symbolic innovations. Regional participation in Athenian affairs was stimulated by encouraging the Attic populace to imagine themselves, for the first time ever, as members of a single, like-minded, self-governing political community. Greg Anderson is Assistant Professor of Classics and History, University of Illinois at Chicago. (shrink)

Merging the information from different senses is essential for successful interaction with real-life situations. Indeed, sensory integration can reduce perceptual ambiguity, speed reactions, or change the qualitative sensory experience. It is widely held that integration occurs at later processing stages and mostly in higher association cortices; however, recent studies suggest that sensory convergence can occur in primary sensory cortex. A good model for early convergence proved to be the auditory cortex, which can be modulated by visual and tactile stimulation; however, (...) given the large number and small size of auditory fields, neither human imaging nor microelectrode recordings have systematically identified which fields are susceptible to multisensory influences. To reconcile findings from human imaging with anatomical knowledge from nonhuman primates, we exploited high-resolution imaging (functional magnetic resonance imaging) of the macaque monkey to study the modulation of auditory processing by visual stimulation. Using a functional parcellation of auditory cortex, we localized modulations to individual fields. Our results demonstrate that both primary (core) and nonprimary (belt) auditory fields can be activated by the mere presentation of visual scenes. Audiovisual convergence was restricted to caudal fields [prominently the core field (primary auditory cortex) and belt fields (caudomedial field, caudolateral field, and mediomedial field)] and continued in the auditory parabelt and the superior temporal sulcus. The same fields exhibited enhancement of auditory activation by visual stimulation and showed stronger enhancement for less effective stimuli, two characteristics of sensory integration. Together, these findings reveal multisensory modulation of auditory processing prominently in caudal fields but also at the lowest stages of auditory cortical processing. (shrink)

To be effective, whistleblowing policies should be adapted to the organisational culture. They need to be custom-made and not follow a one-size-fits-all logic, specifically when they are installed to stimulate responsible peer reporting, a highly sensitive and value-laden type of whistleblowing. This paper attempts to illustrate that grid-group cultural theory could help to construct a whistleblowing policy by linking reporting styles to the organisational culture. First, we will identify four types of policy measures that are hypothesized to be effective (...) in four types of organisational culture. Second, we develop the hypothesis that certain organisational cultures can induce peer reporting that is harmful for the organisation. The whistleblowing policy can then be used as a catalyst for cultural change. (shrink)

This article is intended to guide online course developers and teachers. A brief review of the literature on the misconceptions of beginning online teachers reveals that most accept the notion that putting one’s lecture notes online produces effective learning, or that technology will make education more convenient and cost-effective for all concerned. Effective online learning requires a high level of responsibility for learning on the part of students and a reduction of the teacher-student power differential. This, in turn, has major (...) implications for faculty and course development, student selection criteria, the cost of instruction, and the outcomes of education. Effective online teaching focuses on processes of learning rather than outcomes, and is consistent with modern principles of learning that emphasize focusing on issues of high interest to learners, teaching students to use skills of active and effective learning, providing prompt feedback, and enabling students to establish learning goals and employ alternative paths to achieving those goals. Multiple ways of operationalizing these goals online are presented. Tips are offered concerning selection of students who are capable of benefiting from the online experience, developing curriculum that is user-friendly, using resources that stimulate good writing and critical thinking, and limiting class size to a manageable number. (shrink)

In 2000, US Secretary of Health and Human Services Secretary Tommy Thompson mobilized the US public health infrastructure to deal with escalating trends of excess body weight. A cornerstone of this effort was a report entitled The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity. The report stimulated a great deal of public discussion by utilizing the distinctive public health terminology of an epidemic to describe the growing prevalence of obesity in the US population. We suggest (...) that the ensuing controversy was fueled in part by the report's ambiguous usage of the evocative term “epidemic.” In some passages, the report seems to use “epidemic” in a literal sense, suggesting that rising prevalence of excess body weight should be defined technically as a disease outbreak. Other passages of the report present the same key term metaphorically, leaving readers with the impression that the epidemic language is invoked primarily for rhetorical effect. Here, we explore dynamics and implications of both interpretations. This analysis sheds light on the ongoing public argument about the appropriate societal response to steadily increasing body sizes in the US population; likewise, it capitalizes on the accumulated knowledge that the field of public health has garnered from combating diverse historic epidemics. Our interdisciplinary approach deploys critical tools from the fields of rhetoric, sociology and epidemiology. In particular, we draw from metaphor theory and public address scholarship to elucidate how the Call to Action frames public deliberation on obesity. We turn to the applied public health literature to develop a reading of the report that suggests a novel approach to the problem—application of the Epidemic Investigation protocol to streamline the public health response and reframe the public argument about obesity. (shrink)

This paper is devoted to computer modelling of the development and regeneration of multicellular biological structures. Some species are able to regenerate parts of their body after amputation damage, but the global rules governing cooperative cell behaviour during morphogenesis are not known. Here, we consider a simplified model organism, which consists of tissues formed around special cells that can be interpreted as stem cells. We assume that stem cells communicate with each other by a set of signals, and that the (...) values of these signals depend on the distance between cells. Thus the signal distribution characterizes location of stem cells. If the signal distribution is changed, then the difference between the initial and the current signal distribution affects the behaviour of stem cells—e.g. as a result of an amputation of a part of tissue the signal distribution changes which stimulates stem cells to migrate to new locations, appropriate for regeneration of the proper pattern. Moreover, as stem cells divide and form tissues around them, they control the form and the size of regenerating tissues. This two-level organization of the model organism, with global regulation of stem cells and local regulation of tissues, allows its reproducible development and regeneration. (shrink)

Acid fracturing is the most important stimulation method in the carbonate reservoir. Due to the high cost and high risk of acid fracturing, it is necessary to predict the reservoir productivity before acid fracturing, which can provide support to optimize the parameters of acid fracturing. However, the productivity of a single well is affected by various construction parameters and geological conditions. Overfitting can occur when performing productivity prediction tasks on the high-dimension, small-sized reservoir, and acid fracturing dataset. Therefore, this study (...) developed a stacking heterogeneous ensemble model with a hybrid wrapper-based feature selection strategy to forecast reservoir productivity, resolve the overfitting problem, and improve productivity prediction. Compared to other baseline models, the proposed model was found to have the best predictive performances on the test set and effectively deal with the overfitting. The results proved that the hybrid wrapper-based feature selection strategy introduced in this study reduced data acquisition costs and improved model comprehensibility without reducing model performance. (shrink)

Background: Hospitals are experiencing an estimated 16.5% turnover rate of registered nurses costing from $44,380 - $63,400 per nurse—an estimated $4.21 to $6.02 million financial loss annually for hospitals in the United States of America. Attrition of all nurses is costly. Most past research has focused on the new graduate nurse with little focus on the mid-career nurse. Attrition of mid-career nurses is a loss for the profession now and into the future. Research objective: The purpose of the study was (...) to explore relationships of professional values orientation, career development, job satisfaction, and intent to stay in recently hired mid-career and early-career nurses in a large hospital system. Research design: A descriptive correlational study of personal and professional factors on job satisfaction and retention was conducted. Participants and research context: A convenience sample of nurses from a mid-sized hospital in a metropolitan area in the Southwestern United States was recruited via in-house email. Sixty-seven nurses met the eligibility criteria and completed survey documents. Ethical considerations: Institutional Review Board approval was obtained from both the university and hospital system. Findings: Findings indicated a strong correlation between professional values and career development and that both job satisfaction and career development correlated positively with retention. Discussion: Newly hired mid-career nurses scored higher on job satisfaction and planned to remain in their jobs. This is important because their expertise and leadership are necessary to sustain the profession into the future. Conclusion: Nurse managers should be aware that when nurses perceive value conflicts, retention might be adversely affected. The practice environment stimulates nurses to consider whether to remain on the job or look for other opportunities. (shrink)

This paper argues that qualitative research is both useful and necessary, as it provides an essential means of gaining a richer understanding of patients' perceptions, social processes and meanings. In their paper in this edition of Clinical Ethics, Hallowell and Lawton raise many issues relating to the way that qualitative research is treated by RECs in the UK. In this paper I discuss just three key topics stimulated by their paper: the way that methodology relates to ethics, the experience and (...) character of the researcher, and the normative/descriptive distinction. I strongly support Hallowell and Lawton's appeal for greater communication between qualitative researchers and RECs. In other respects, I would argue that they do not go far enough. The recent review of research ethics structures and the review process provides an opportunity to move away from the present 'one size fits all' approach to ethical review. I would argue that this change could only benefit qualitative research and researchers. (shrink)

By measuring the level of CSR communication carried out by hotels located in the Colombian Caribbean region and identifying the main determinant factors influencing this level (including pressure from the different stakeholders), this paper contributes to deepening our understanding of the antecedents of CSR communication in small and medium‐sized enterprises (SMEs) operating in emerging economies and, particularly, in the hotel industry, for which no previous studies on this topic could be uncovered. The results reveal that the level of CSR disclosure (...) is low in the region and that the size of the hotel, the pressure from government agencies, and the age and educational background of the hotel’s top manager have a significant influence on the level of CSR communication. Results indicate a reactive approach to CSR communication confirming the prominent role played by government agencies, thus contributing to gain a richer understanding of institutional influences on CSR in Latin American countries. In terms of practical implications, findings suggest that governments should play a more active role in stimulating CSR communication in emerging countries, particularly in the case of SMEs. (shrink)

Linguistics falls in the gap between arts and science, on the edges of which the most fascinating discoveries and the most important problems are found. Rather than following the conventional organization of many contemporary introductions to the subject, the author of this stimulating guide begins his discussion with the oldest, 'arts' end of the subject and moves chronologically through to the newest research - the 'science' aspects. A series of short thematic chapters look in turn at such areas as the (...) prehistory of languages and their common origins, language and evolution, language in time and space, grammars and dictionaries, and phonetics. Explication of the newest discoveries pertaining to language in the brain completes the coverage of all major aspects of linguistics from a refreshing and insightful angle. ABOUT THE SERIES: The Very Short Introductions series from Oxford University Press contains hundreds of titles in almost every subject area. These pocket-sized books are the perfect way to get ahead in a new subject quickly. Our expert authors combine facts, analysis, perspective, new ideas, and enthusiasm to make interesting and challenging topics highly readable. (shrink)

Our think tank tasked by the Dutch Health Council, consisting of Radboud University Nijmegen Honours Academy students with various backgrounds, investigated the implications of Deep Brain Stimulation for psychiatric patients. During this investigation, a number of methodological, ethical and societal difficulties were identified. We consider these difficulties to be a reflection of a still fragmented field of research that can be overcome with improved organization and communication. To this effect, we suggest that it would be useful to found a centralized (...) DBS organization. Such an organization makes it possible to 1) set up and maintain a repository, 2) facilitate DBS studies with a larger sample size, 3) improve communication amongst researchers, clinicians and ethical committees, and 4) improve communication between DBS experts and the public at large. (shrink)

We analyse the effect of the regulatory T cells (Tregs) in the local control of the immune responses by T cells. We obtain an explicit formula for the level of antigenic stimulation of T cells as a function of the concentration of T cells and the parameters of the model. The relation between the concentration of the T cells and the antigenic stimulation of T cells is an hysteresis, that is unfold for some parameter values. We study the appearance of (...) autoimmunity from cross-reactivity between a pathogen and a self antigen or from bystander proliferation. We also study an asymmetry in the death rates. With this asymmetry we show that the antigenic stimulation of the Tregs is able to control locally the population size of Tregs. Other effects of this asymmetry are a faster immune response and an improvement in the simulations of the bystander proliferation. The rate of variation of the levels of antigenic stimulation determines if the outcome is an immune response or if Tregs are able to maintain control due to the presence of a transcritical bifurcation for some tuning between the antigenic stimuli of T cells and Tregs. This behavior is explained by the presence of a transcritical bifurcation. (shrink)

It is a striking point that, in the general context of the municipal administration's reform, this administration itself is never brought into discredit. When criticisms are formulated, they concern the fact that not all municipalities are able to offer their inhabitants the services which they normally may expect, as well for their immediate human development as for the adapted extension of the material infrastructure and of their vital environment. This normally raises the question of the municipalities' administrative power.The factors which (...) determine that power can be considered in direct or indirect connection with the number of inhabitants.In the first place, the population has to be sufficiently differentiated to enable the conception of a development-policy that comes up to the requirements of the present society. One may assume that in municipalities with 2.000 inhabitants, which perform a centre-function or are located near a town-centre, the possibility exists to elect a properly composed common council. For rural municipalities the numberof inhabitants must undoubtedly be higher. Moreover, the municipality should have the disposal of specialised personnel to help the municipal authorities with the conception and practice of their policy. InBelgium a municipal secretary cannot do bis work properly if the municipality does not count 2.500 to 3.000 inhabitants.In the second place, administrative power is determined by available finances. Calculations have been made per category of municipalities, based on disposable data concerning 196.5 and 1966.As far as the extraordinary accounts are concerned, which essentially refer to investment expenses, it is relevant to note that the average figures per inhabitant are equally high in municipalities with less than1.000 and with 10.000 inhabitants. But, taking into account the cost of planned infrastructure-works, it is a fact that only from 10.000 inhabitants on a municipality has the disposal of sufficient finances to performa development-policy.The figures concerning ordinary accounts, which refer to operation- and administrative costs, show that a municipality with less than 1.000 inhabitants - although offering less services - has to spend more perinhabitant than a municipality with 5.000 to 10.000 inhabitants. lts fiscal charge is also higher than that of a municipality belonging to the latter category.The figures clearly show the disadvantage of smaller municipalities.In that context one should not forget that practically 63 to 70 % of ordinary expenses concern the actual operations and municipal debts. Seen in proportional relations, small municipalities have but little means to take care of policy-tasks.To be complete «municipality with administrative power» also means «municipality with a democratic function». As a matter of fact, administrative power is not exclusively determined by sufficient financialresources or by a minimum of differentiation of the inhabitants. Generally speaking one can assume in this context that the geographical size of the territory does not normally hamper the functioning of alocal democracy. More attention however should be given to the question if that functioning is not rather hindered by the number of inhabitants, when a certain population-maximum is exceeded. lt appearsindeed that local authorities have less appeal in urbanised municipalities or as soon as a population-number of 20.000 to 30.000 inhabitants is reached. For that reason, attempts should be made in bigger municipalities to stimulate the population's participation in policy-matters.Activities with a definitively technical character, need a wider approach. So it seems more advisable to work on the basis of regions, rather than on the basis of large municipalities.Taking into account the big number of small municipalities, one can state as a conclusion that the municipal elections miss a great part of their signification in the majority of Belgian municipalities. Practically two thirds of them have no possibility to perform an adapted policy.Changing the constitution of those who are responsible for that policy cannot give much of a result as there are no material means to realize a modern policy with administrative power. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Maps for the Classical World: Where Do We Go from Here?Richard TalbertThe apa’s classical atlas project was conceived as the means to an end, and rightly so. Good maps were taken to be vital tools for understanding ancient history and culture at any level, and the ones available in the early 1980s were altogether woefully inadequate. The project was designed to fill this void by preparing a comprehensive atlas (...) for publication in the not-too-distant future.To make a definitive claim at this moment that the target of publication by the end of 1999 will be met must still rank as hubris. Without doubt, however, the odds have increasingly shifted over the past few years in favor of timely completion. As everyone knows, the problems of designing, funding, and developing any ambitious collaborative project are immense, and the atlas has been handed its full share of such difficulties and more. Yet gradually the difficulties seem to have been surmounted, and the project—at present, anyway—remains resolutely on schedule, as much to the surprise of its Director as to everyone else.As the odds have shifted, so, too, has my own perception of the project as an end. To be sure, the maps appearing in the atlas volume will offer the intended comprehensive vision of the physical and cultural landscape of classical antiquity that has been so seriously lacking since Carl Müller provided the last one for William Smith’s Atlas of Ancient Geography in the 1870s. Further gains are assured, too. In particular, to accommodate different needs, it should certainly prove practical to issue the maps in a variety of alternative formats—in sets of loose sheets, for example (with or without cultural data marked on the ancient physical landscape), as wall-maps, slides, digitized images, even a reduced-size textbook atlas. One way or another, these maps have the potential to exert a formative influence on our perception of the classical landscape for many decades to come.Even at the current stage, well before publication, the Atlas Project [End Page 323] has already stimulated fresh attention to cartography: this has grown without any special effort on the project’s part. Most notably, colleagues have become aware that there is now for the first time somewhere to which they can turn as they seek out suitable cartographic materials and design for their research or publications or field survey.Classical studies worldwide would benefit immensely if that “somewhere” were to be made a permanent “center,” established around the same time as the publication of the Atlas of the Greek and Roman World. In the creation of the atlas, both materials and expertise have been accumulated, which it would be irresponsible simply to abandon. The materials cover a wide range—from elements for all the aeronautical charts forming the physical bases for the atlas maps, to copies of older rare maps devoted to classical antiquity.Such maps (and whatever text accompanies them) are by no means necessarily all about to be rendered obsolete by the atlas. The French “archaeological atlases” of Algeria and Tunisia, for example, were compiled by the Brigades Topographiques in the late nineteenth and early twentieth centuries at scales as generous as 1 : 50,000, whereas the atlas limits itself to 1 : 500,000 in this region (and the area covered by one map at 1 : 500,000 corresponds to literally dozens at 1 : 50,000). Thus for any study with a close focus on Algeria or Tunisia, these French series remain indispensable, although the Tunisian one, with its two editions, is exceptionally rare and hard to obtain. Typically, the few libraries that hold this material have bound the original loose sheet maps into books (rendering it impossible to use the sheets individually), and for obvious reasons, they are not willing lenders. The Atlas Project, I imagine, has been the first to photograph the printed map sheets onto transparent plastic positives. These are sturdy, dimensionally stable, and immune from the fading and deterioration of paper; in addition, when they are laid on top of other maps, everything underneath remains visible.Examples of further cartographic materials for the classical world which will continue to... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Comments on Margaret Watkins, The Philosophical Progress of Hume’s “Essays”Jacqueline Taylor (bio)After David Hume’s death, Adam Smith wrote a letter to Hume’s publisher, William Strahan, to recount some of the final words and the attitude of “our late excellent friend, Mr. Hume.”1 Despite declining health and increasing weakness, Hume faced his approaching demise “with great cheerfulness” (EMPL xlvi). He had recently been reading Lucian’s Dialogues of the Dead, and (...) although feeling he had every reason “to die contented,” Smith describes the “jocular excuses” Hume might make to Charon to delay his death (EMPL xlv). He first requests more time so that he can see how the public responds to the latest corrections he had been making to his works, but Charon replied that this would only lead Hume to want more time to make further corrections. Hume tries another tack: “Have a little patience, good Charon, I have been endeavouring to open the eyes of the public. If I live a few years longer, I may have the satisfaction of seeing the downfall of some of the prevailing systems of superstition,” to which Charon replies, “You loitering rogue, that will not happen these many hundred years... Get into the boat this instant, you lazy loitering rogue” (EMPL xlvi). This imaginary dialogue makes evident Hume’s self-awareness as an author who cared greatly about both the correctness of his written works and the influence of these works on the public.In her book, Margaret Watkins argues that Hume’s concern to open the eyes of the public goes well beyond attempts to bring about the downfall of systems of superstition.2 She credits him with the broader aim of writing essays for a literate audience that would stimulate both public and individual improvement in various areas of human activity, including government, work, aesthetic experience, and intimate [End Page 155] relationships. The first three chapters of the book examine the case for Hume’s concern with public improvement. Chapter 1 focuses primarily on the political essays, and examines Hume’s account of governing and his criticism of the irrationality apt to arise with divisive political factionalism. Chapter 2 turns to inequalities of power and the circumstances that allow some to exercise to a greater degree the domineering tendency that is part of human nature. Watkins uses Hume’s essay on the population size of ancient and modern societies to reconstruct his view on the ills—to both masters and slaves—of ancient slaveholding. She complicates this discussion by looking at modern slaveholding in the colonies, and Hume’s puzzling lack of attention to this. In the ancient world, slaveholding resulted from war and conquest, and Watkins examines how ancient warfare also led to greater ferocity and anger in fighting and exacerbated cruelty (a trait Hume had deemed the worst vice in the Treatise [T 3.3.3.8]).3 This is another place where Watkins sees Hume taking stock of modern improvements. In the wide-ranging third chapter, entitled “Working,” Watkins considers economic circumstances as moral causes that can shape character, highlighting the importance for Hume of the commercial virtues, especially industry.4 She also shows that in the four essays on happiness, modeled on Hellenistic sects, each type of philosopher regards industry, or at least occupation, as essential to human happiness. Watkins concludes that the need for industry is thus something we are naturally motivated to seek out, and so an integral part of human nature. Chapter 4, on “Composing,” shows Watkins’s talents as a philosophical essayist in her own right, as she relates art and other forms of beauty to the cultivation of calm passions. We find here an insightful discussion of art, whether composing or consuming, as having particularly therapeutic effects on melancholy and other forms of nervous conditions. Chapters 5 and 6 take up, respectively, love for oneself and love for others. The former looks at the importance Hume places on both self-love and pride. Here Watkins draws primarily on Hume’s more morally theoretical works, both the Treatise and EPM, since they have more to say about self-valuing. Chapter 6 shows how we may fruitfully read... (shrink)

“This is a delightful and engaging little book. With its bite-size chapters, lively exposition, and important subject matter, this is the kind of book that can spark an interest in philosophy among those unfamiliar with it. But its appeal is not limited to neophytes; it poses significant new challenges to moral theory that even hardened professional philosophers will find stimulating and provocative”.

In lieu of an abstract, here is a brief excerpt of the content:Introduction:Beyond Nature/Culture Dualism: Let's Try Co-Evolution Instead of "Control"Ronnie Hawkins (bio)In the original call for papers for this special issue, nature/culture dualism was characterized as a way of thinking that holds human culture and nonhuman nature to be radically different ontological spheres, hyperseparated and oppositional, or, as Val Plumwood maintains in her essay, an orientation that assumes "separate casts of characters in separate dramas." In the human sphere, individuals (...) are unique and their lives are precious (at least theoretically), with concerns understood "from the inside," in terms of experience, intention and agency. In the sphere of nature, on the other hand, nonhuman beings are seen "from the outside," at best as replaceable members of species or populations needed for ecosystem functioning and, at worst, as unagentive, thinglike objects open for unbridled human exploitation. With our vast information and communication systems now largely in place, however, our human "noösphere" is rapidly enlarging to place us firmly within the biosphere (which, of course, in the imagery of Venn diagrams, must make up the larger circle on the screen), illuminating "both casts in both dramas," or perhaps joining all actors on the stage in a many-act, multidimensional play, the denoument of which, whether or not the extant lifeforms on this [End Page 1] planet will continue to evolve, remains as yet unwritten. The five essays in this collection speak to these points, and together they develop an alternative vision to our present dualistic impasse, seeing multiple natural agencies engaged with humanity in ongoing co-evolution and, as Freya Mathews suggests, raising the hope for a synergistic restructuring of lifeways that may yet save us from anthropogenic catastrophe.In "The Culture of Nature As Seen Through Mississippian Geographies," Jeff Baldwin shows us the broad scope of interacting agents, human and nonhuman, biological and geological, in what he terms "the nature-culture of the Mississippi River," as highlighted by the recent devastation of human habitation along the Gulf Coast of the United States wrought by Hurricanes Katrina and Rita. By enacting a role in which we "believe [our]selves to rule over a mechanistic world," we humans have, over the last century or so, stemmed the natural flooding of the Mississippi, rerouting the sediments that maintained and extended the delta, funneling them into the sea and thereby bringing about the subsidence and erosion of hundreds of square miles of coastal land. Concomitantly, we have let agricultural runoff from the huge Mississippi drainage basin eject excess nutrients into the Gulf of Mexico, stimulating algal blooms and die-offs, depleting the water of oxygen so as to create a hypoxic "dead zone" that is now the size of Massachusetts, and (though Baldwin does not discuss this aspect of the problem) we have released enough petrochemical pollution in the area to have earned the lower reaches of the River the name "Cancer Alley" decades ago. A failure to grasp the import of these large anthropogenic effects is, sadly, evident in calls for rebuilding the New Orleans area according to the same mechanistic model that has already proven so inadequate. Baldwin observes that the earth changes wrought through human cultural innovation often occur so rapidly, or have their negative feedbacks technologically so displaced through time and space, that their eventual impacts on the larger system may initially go unappreciated. His vision of "the culture of nature," however, is ultimately an optimistic one, since his functional understanding of culture is that it ultimately works toward mutualism, promoting increasingly appropriate relationships among all interacting components, and he finds evidence of a growing effort to establish an "intentional co-evolution," a conscious alignment of human projects with the ongoing projects of a living nature that encompasses them. [End Page 2]If Baldwin's essay helps us see our human activities "from the outside"—not just "from within" prevailing human culture, where they seem taken-for-granted necessities given a certain form of social construction, but as they alternatively appear inside biospherical space, often as inappropriate, exploitative interferences and intrusions—Stacey Sowards' essay, "Identification Through Orangutans: Destabilizing the Nature/Culture Dualism," explores the potential for our connecting with nonhuman life "from the inside," relating... (shrink)

This work is intended to illustrate how gravity is a major factor in shaping life as we know it. It will be argued here that gravity has an influence at all levels, from particles to planets. Moreover, that any change in gravitational acceleration will have a direct and inevitable impact upon the form of any organism. From a fresh perspective some of the mysteries of evolution will be examined in light of gravity and its ubiquity. The creatures of the Earth, (...) past and present, have taken on many forms but why is it that all the terrestrial mega fauna have become extinct? Why is it that reptiles today are only a fraction of the size of their ancestors? Why is it that an insect never reaches the size of a large mammal? What is Tensegrity and how does it influence the structure of the cell, the protein and the larger body of an organism? Many of the considerations here are taken from novel scientific thinkers; these will be outlined and discussed. Many of the ideas may seem controversial and provocative but the author makes no apology for their inclusion. Indeed the purpose here is to stimulate a debate that hopefully leads to a better understanding of life and its evolution. (shrink)

Human resource management (HRM) scholars and practitioners are increasingly interested in how to leverage HRM tools to address pressing environmental issues while balancing an organization’s need for profit. One important theme of this line of research is the use of contingent compensation (i.e., green compensation) to motivate managers to engage in pro-environmental behavior. However, current research on the efficacy of green compensation in promoting managers’ environmental contribution yields two seemingly contradictory views. First, based on agency theory, green compensation is found (...) to be an effective tool to elicit managers’ environmental efforts. On the other hand, from a stewardship theory perspective, green compensation is regarded as ineffective in attempts to stimulate managers’ environmental contributions. In this paper, we propose that this potential conflict could stem from the way green compensation is designed. To address this issue, drawing upon goal-framing theory, we develop a normative theoretical framework toward designing key features of green compensation that could help to promote managers’ pro-environmental behaviors while mitigating potential pitfalls. These key features include explicitly acknowledging managers’ contributions to environmental endeavors, distribution of the compensation by prominent stakeholders with salient pro-environmental values, distribution of the compensation in public ceremonies, ensuring modesty in size of the compensation compared with managers’ non-contingent compensation, monitoring outcome and process performance, and developing group-based in addition to individual-based compensation. We conclude with implications of this design for theory and practice. (shrink)

Martin’s conjecture is an attempt to classify the behavior of all definable functions on the Turing degrees under strong set theoretic hypotheses. Very roughly it says that every such function is either eventually constant, eventually equal to the identity function or eventually equal to a transfinite iterate of the Turing jump. It is typically divided into two parts: the first part states that every function is either eventually constant or eventually above the identity function and the second part states that (...) every function which is above the identity is eventually equal to a transfinite iterate of the jump. If true, it would provide an explanation for the unique role of the Turing jump in computability theory and rule out many types of constructions on the Turing degrees.In this thesis, we will introduce a few tools which we use to prove several cases of Martin’s conjecture. It turns out that both these tools and these results on Martin’s conjecture have some interesting consequences both for Martin’s conjecture and for a few related topics.The main tool that we introduce is a basis theorem for perfect sets, improving a theorem due to Groszek and Slaman. We also introduce a general framework for proving certain special cases of Martin’s conjecture which unifies a few pre-existing proofs. We will use these tools to prove three main results about Martin’s conjecture: that it holds for regressive functions on the hyperarithmetic degrees, that part 1 holds for order preserving functions on the Turing degrees, and that part 1 holds for a class of functions that we introduce, called measure preserving functions.This last result has several interesting consequences for the study of Martin’s conjecture. In particular, it shows that part 1 of Martin’s conjecture is equivalent to a statement about the Rudin-Keisler order on ultrafilters on the Turing degrees. This suggests several possible strategies for working on part 1 of Martin’s conjecture, which we will discuss.The basis theorem that we use to prove these results also has some applications outside of Martin’s conjecture. We will use it to prove a few theorems related to Sacks’ question about whether it is provable in $\mathsf {ZFC}$ that every locally countable partial order of size continuum embeds into the Turing degrees. We will show that in a certain extension of $\mathsf {ZF}$, this holds for all partial orders of height two, but not for all partial orders of height three. Our proof also yields an analogous result for Borel partial orders and Borel embeddings in $\mathsf {ZF}$, which shows that the Borel version of Sacks’ question has a negative answer.We will end the thesis with a list of open questions related to Martin’s conjecture, which we hope will stimulate further research.prepared by Patrick Lutz.E-mail: [email protected]. (shrink)

Sinking organic particles transfer ∼10 gigatonnes of carbon into the deep ocean each year, keeping the atmospheric CO2 concentration significantly lower than would otherwise be the case. The exact size of this effect is strongly influenced by biological activity in the ocean's twilight zone (∼50–1,000 m beneath the surface). Recent work suggests that the resident zooplankton fragment, rather than ingest, the majority of encountered organic particles, thereby stimulating bacterial proliferation and the deep‐ocean microbial food web. Here we speculate that (...) this apparently counterintuitive behaviour is an example of ‘microbial gardening’, a strategy that exploits the enzymatic and biosynthetic capabilities of microorganisms to facilitate the ‘gardener's’ access to a suite of otherwise unavailable compounds that are essential for metazoan life. We demonstrate the potential gains that zooplankton stand to make from microbial gardening using a simple steady state model, and we suggest avenues for future research. (shrink)

Support from grandparents plays a role in mothers’ perinatal mental health. However, previous research on maternal mental health has mainly focused on influences of partner support or general social support and neglected the roles of grandparents. In this narrative review and meta-analysis, the scientific evidence on the association between grandparental support and maternal perinatal mental health is reviewed. Searches in PubMed, EMBASE, MEDLINE, Scopus, and PsycINFO yielded 11 empirical studies on N = 3381 participants, reporting on 35 effect sizes. A (...) multilevel approach to meta-analysis was applied to test the association between grandparental support and maternal mental health. The results showed a small, statistically significant association (r =.16; 95% CI: 0.09–0.25). A moderator test indicated that the association was stronger for studies reporting on support from the maternal grandmother in particular (r =.23; 95% CI: 0.06–0.29). Our findings suggest that involved grandparents, in particular mother’s own mother, constitute a protective factor for the development of maternal postpartum mental health problems. These findings have clear implications for interventions. Future studies should examine whether stimulating high-quality support from grandparents is a fruitful avenue for enhancing maternal postpartum mental health. (shrink)

The purpose of the study is to determine the current state, threats and prospects for the development of Russia's economic security. The scientific novelty lies in the development of key areas for countering threats to Russia's economic security, which are represented by the consequences of the impact of the COVID-19 coronavirus infection. The solution to the key problems that have arisen as a result of the pandemic is to ensure effective protection of the Russian economy. Accordingly, the key direction of (...) public administration should be the solution of strategic issues to stimulate the activity of small and medium-sized businesses, as well as to increase investment flows. As a result, the key risks and threats affecting the economic security of the Russian Federation were identified. In addition, the key problems affecting the level of economic security of the country are identified, which determines the relevance of studying the features of ensuring economic security in the country. In conclusion, recommendations aimed at improving the current system of economic security at the country level are proposed. (shrink)

2. Invariant Sensorimotor Features ("Affordances"). To say this is not to declare oneself a Gibsonian, whatever that means. It is merely to point out that what a sensorimotor system can do is determined by what can be extracted from its motor interactions with its sensory input. If you lack sonar sensors, then your sensorimotor system cannot do what a bat's can do, at least not without the help of instruments. Light stimulation affords color vision for those of us with the (...) right sensory apparatus, but not for those of us who are color-blind. The geometric fact that, when we move, the "shadows" cast on our retina by nearby objects move faster than the shadows of further objects means that, for those of us with normal vision, our visual input affords depth perception. From more complicated facts of projective and solid geometry it follows that a 3-dimensional shape, such as, say, a boomerang, can be recognized as being the same shape Ð and the same size Ð even though the size and shape of its shadow on our retinas changes as we move in relation to it or it moves in relation to us. Its shape is said to be invariant under these sensorimotor transformations, and our visual systems can detect and extract that invariance, and translate it into a visual constancy. So we keep seeing a boomerang of the same shape and size even though the shape and size of its retinal shadows keep changing. (shrink)