Please, don't do it! Fifteen years of progress of non-invasive brain stimulation in action inhibition

open3noThe ability to inhibit prepotent responses is critical for survival. Action inhibition can be investigated using a stop-signal task (SST), designed to provide a reliable measure of the time taken by the brain to suppress motor responses. Here we review the major research advances using the combination of this paradigm with the use of non-invasive brain stimulation techniques in the last fifteen years. We highlight new methodological approaches to understanding and exploiting several processes underlying action control, which is critically impaired in several psychiatric disorders. In this review we present and discuss existing literature demonstrating i) the importance of the use of non-invasive brain stimulation in studying human action inhibition, unveiling the neural network involved ii) the critical role of prefrontal areas, including the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus (IFG), in inhibitory control iii) the neural and behavioral evidence of proactive and reactive action inhibition. As the main result of this review, the specific literature demonstrated the crucial role of pre-SMA and IFG as evidenced from the field of noninvasive brain stimulation studies. Finally, we discuss the critical questions that remain unanswered about how such non-invasive brain stimulation protocols can be translated to therapeutic treatments.embargoed_20210915Borgomaneri S.; Serio G.; Battaglia S.Borgomaneri S.; Serio G.; Battaglia S

Addressing Root Causes: The Need for Ex-Ante Regulation in Business and Human Rights

With the rise of mandatory human rights due diligence (HRDD) laws across various jurisdictions, governments are turning to regulatory tools to tackle the transnational challenges of business and human rights. Yet, the dominant focus on an ex-post standard such as mandatory HRDD may not adequately address the root causes of rights abuses in commercial activities. The individualized ex-post enforcement model which underpins HRDD has limited potential to address the systemic infrastructure of exploitative business practices. The upstream purchasing and contracting practices which lead to human rights violations in supply chains are overlooked, and even reinforced, in such a model. Without dispelling the importance of HRDD in charting a path of progress and corporate accountability, this Article critically evaluates its weaknesses in light of the risk that the status quo of exploitative business models may be preserved even as due diligence laws are ushered forward. To counter this ex-post tendency, this Article examines whether proactive ex-ante mechanisms can fill the gaps where HRDD has fissured and cracked. From both a normative perspective and by drawing upon existing debates between ex-ante and ex-post enforcement (or rules versus standards), this Article makes the case for lawmakers to embrace a smart mix of both and presents some options for implementation. The aim is not to pause the current impetus in legislative efforts—instead, it is to capture this momentum and highlight avenues through which domestic policymakers can take a prophylactic approach for prevention, accountability and remedy in business and human rights

E-Synthesis: A Bayesian Framework for Causal Assessment in Pharmacosurveillance

Background: Evidence suggesting adverse drug reactions often emerges unsystematically and unpredictably in form of anecdotal reports, case series and survey data. Safety trials and observational studies also provide crucial information regarding the (un-)safety of drugs. Hence, integrating multiple types of pharmacovigilance evidence is key to minimising the risks of harm. Methods: In previous work, we began the development of a Bayesian framework for aggregating multiple types of evidence to assess the probability of a putative causal link between drugs and side effects. This framework arose out of a philosophical analysis of the Bradford Hill Guidelines. In this article, we expand the Bayesian framework and add “evidential modulators,” which bear on the assessment of the reliability of incoming study results. The overall framework for evidence synthesis, “E-Synthesis”, is then applied to a case study. Results: Theoretically and computationally, E-Synthesis exploits coherence of partly or fully independent evidence converging towards the hypothesis of interest (or of conflicting evidence with respect to it), in order to update its posterior probability. With respect to other frameworks for evidence synthesis, our Bayesian model has the unique feature of grounding its inferential machinery on a consolidated theory of hypothesis confirmation (Bayesian epistemology), and in allowing any data from heterogeneous sources (cell-data, clinical trials, epidemiological studies), and methods (e.g., frequentist hypothesis testing, Bayesian adaptive trials, etc.) to be quantitatively integrated into the same inferential framework. Conclusions: E-Synthesis is highly flexible concerning the allowed input, while at the same time relying on a consistent computational system, that is philosophically and statistically grounded. Furthermore, by introducing evidential modulators, and thereby breaking up the different dimensions of evidence (strength, relevance, reliability), E-Synthesis allows them to be explicitly tracked in updating causal hypotheses

Calls for Change: Seeing Cancel Culture from a Multi-Level Perspective

Transition Design offers a framework and employs an array of tools to engage with complexity. “Cancel culture” is a complex phenomenon that presents an opportunity for administrators in higher education to draw from the Transition Design approach in framing and responding to this trend.  Transition Design ofrece un marco y emplea una variedad de herramientas para abordar la complejidad. “Cancelar la cultura” es un fenómeno complejo que presenta una oportunidad para que los administradores de la educación superior se basen en el enfoque del Diseño de Transición para enmarcar y responder a esta tendencia. O Transition Design oferece uma estrutura e emprega uma variedade de ferramentas para lidar com a complexidade. A “cultura do cancelamento” é um fenômeno complexo que apresenta uma oportunidade para os administradores do ensino superior se basearem na abordagem do Design de Transição para enquadrar e responder a essa tendência

Investigating the efficacy of dual-site transcranial alternating current stimulation for alleviating age-related declines in response inhibition

Response inhibition, the ability to suppress or cancel a pre-potent motor action, is instrumental in the flexible adaptation of behaviour to an ever-changing external environment. Unfortunately, inhibitory performance deteriorates with ageing, which is detrimental to the functional independence of older adults. The main objective of this thesis was two-fold. Firstly, to ascertain if age-related declines in response inhibition can be ameliorated by transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation. Secondly, to gain mechanistic insight into the neurophysiological underpinnings of response inhibition in healthy older individuals. A narrative review (Chapter 1) was conducted to examine the available research evidence on the neural correlates of inhibitory performance. It was found that effective response inhibition performance is subserved by the functional connectivity between the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA), especially for neural activity at beta frequencies. The extant literature also indicates that dual-site tACS can exert facilitatory effects on the functional connectivity between brain regions. Specifically, in-phase tACS, which entails the delivery of currents at the same oscillatory phase to two target sites, was found to promote inter-regional connectivity. Conversely, anti-phase tACS, whereby the currents to the target sites are delivered at opposite phases, was found to weaken interregional connectivity. Therefore, it was deduced that the application of beta frequency inphase tACS over the rIFG and the preSMA could potentially mitigate age-related deficits in inhibitory performance. To test this hypothesis, a double-blind crossover study involving 18 healthy older adults and 15 younger older adults was carried out to elucidate the effects of in- and anti-phase beta tACS (1 mA; 20 min; applied at rest) on stop-signal task performance (Study 1: Chapters 2 to 5). In-phase tACS led to significant improvements in the action cancellation speeds of younger, but not older, individuals. Moreover, in-phase stimulation resulted in a significant brain-behaviour relationship between cancellation speed and resting-state rIFG-preSMA connectivity for younger participants only. The effects of tACS on inhibitory performance appeared to be contingent upon the endogenous beta-band phase angle difference between rIFG and preSMA during resting-state. Anti-phase tACS was also found to exert differential effects on cortico-cortical gamma-band coupling for older and younger individuals. However, these age-related differences in network connectivity were not reflected in inhibitory performance. tACS-induced changes in response inhibition performance also appeared to be independent of task-related rIFG-preSMA phase connectivity on the scalp- and cortical-level for both older and younger adults. A substantial inter-individual variability in tACS-induced neurophysiological outcomes was also detected, particularly for older participants. This suggests that there may be greater heterogeneity in the dose-response relationship of older adults, in comparison to their younger counterparts. Subsequently, electric field simulation modelling was conducted to explore how the current dosage of the dual-site tACS protocol could be modified to improve the intensity and focality of tACS-induced currents in the brain (Study 2: Chapter 6). It was found that higher field strengths are accompanied by poorer field focality to target sites, and that this strengthfocality trade-off must be considered when deciding on tACS current intensities. The current dosages of the tACS protocol utilised in Study 1 were revised in consideration of the findings of Study 2. A sham-controlled, double-blind, crossover study was conducted to test the efficacy of this modified tACS protocol (1.0 mA for rIFG, 1.6 mA for preSMA; 20 min) on improving the inhibitory performance of seven healthy older adults (Study 3: Chapter 7). The study also investigated if an ‘online’ approach, where tACS was administered during task performance, would be more efficacious than if tACS was applied ‘offline’, i.e., when participants were at rest and in a task-free state. Due to the small sample size, group-level and single-subject analyses were employed. The findings of Study 3 indicated that neither online nor offline tACS significantly improved stop-signal task performance. Furthermore, not only was cancellation speed not associated with beta-band phase-coupling between rIFG and preSMA during resting-state and task performance, their inter-regional phase connectivity was not a significant predictor of stop outcome, i.e., the success or failure of stop attempts. Instead, task-related gamma-band rIFG-preSMA phase-coupling was found to be a significant predictor of stop outcome. Changes in source-reconstructed cortio-cortical networks from pre- to post-sham stimulation were also indicative of potential fatigue-related changes in network connections – this is an important factor that future research will need to account for when studying tACS-induced changes in phase-coupling during task performance. Overall, the findings of this thesis suggest that rIFG-preSMA beta tACS was potentially efficacious in facilitating the inhibitory performance of healthy younger adults. However, its effects in healthy older individuals were subject to considerable heterogeneity. Despite the lack of clear evidence supporting the efficacy of this tACS protocol in alleviating age-related declines in response inhibition, the findings of this thesis have provided important insights into the neural underpinnings of inhibitory performance and contributed to a broader mechanistic understanding of the effects of dual-site tACS on functional connectivity

System Theoretic Safety Analysis of the Sewol-Ho Ferry Accident in South Korea

This paper is to show the application of CAST, Causal Analysis based on STAMP (Systems Theoretic Accident Model and Processes) accident analysis tool to investigate the Sewol‐Ho Ferry Accident at the entire maritime transportation sociotechnological system level and to provide the system level safety improvements to the system safety control structure; to show that CAST is an accident analysis tool to effectively and holistically analyze the entire maritime transportation sociotechnological system level disaster; and to show that CAST can provide preventive solutions in a holistic view of top‐down system safety engineering

Master/worker parallel discrete event simulation

The execution of parallel discrete event simulation across metacomputing infrastructures is examined. A master/worker architecture for parallel discrete event simulation is proposed providing robust executions under a dynamic set of services with system-level support for fault tolerance, semi-automated client-directed load balancing, portability across heterogeneous machines, and the ability to run codes on idle or time-sharing clients without significant interaction by users. Research questions and challenges associated with issues and limitations with the work distribution paradigm, targeted computational domain, performance metrics, and the intended class of applications to be used in this context are analyzed and discussed. A portable web services approach to master/worker parallel discrete event simulation is proposed and evaluated with subsequent optimizations to increase the efficiency of large-scale simulation execution through distributed master service design and intrinsic overhead reduction. New techniques for addressing challenges associated with optimistic parallel discrete event simulation across metacomputing such as rollbacks and message unsending with an inherently different computation paradigm utilizing master services and time windows are proposed and examined. Results indicate that a master/worker approach utilizing loosely coupled resources is a viable means for high throughput parallel discrete event simulation by enhancing existing computational capacity or providing alternate execution capability for less time-critical codes.Ph.D.Committee Chair: Fujimoto, Richard; Committee Member: Bader, David; Committee Member: Perumalla, Kalyan; Committee Member: Riley, George; Committee Member: Vuduc, Richar

Impact of the weather on Swiss railway punctuality

Aquesta tesi investiga l'impacte dels fenòmens meteorològics en els retards dels trens a Suïssa. Concretament, analitza l'efecte de la pluja, la neu, el vent i les temperatures extremes en els trens d'SBB que viatgen entre Berna i Zúric. L'estudi utilitza dades obertes dels darrers cinc anys. Les anàlisis revelen que tots els factors meteorològics contribueixen a augmentar els retards, amb especial atenció a la pluja, que és el fenomen més freqüent. Es proposa un mètode de 'clustering' per identificar els dies de neu, assolellats i plujosos i caracteritzar el seu retard esperat. L'estudi també revela que la meteorologia afecta els retards durant tot l'any, i especialment durant la temporada de tardor, les hores punta i els vespres. Aquest impacte s'observa a totes les estacions, línies i direccions de tren. Els trens directes i els que viatgen cap a l'oest del país són els que pateixen retards més importants. L'anàlisi també demostra que els retards es produeixen entre parades, mentre que els trens recuperen temps a les estacions. L'anàlisi en altres trams ferroviaris de la mateixa línia mostra resultats similars, la qual cosa ofereix un potencial prometedor per aplicar els mateixos mètodes a altres regions i línies suïsses. No hi ha evidència que les cancel·lacions de trens es vegin afectades per les condicions meteorològiques. L'estudi també conclou que predir els retards dels trens és un repte complex, independentment dels predictors, el 'target' o el tipus del model. Tanmateix, les variables meteorològiques poden ajudar a millorar models de predicció més complexos. La quantificació de l'impacte de la meteorologia en els retards ofereix conclusions rellevants per a SBB i qualsevol altre operador ferroviari. Això ajudarà en la formulació d'estratègies per gestionar aquests retards de manera eficaç i, en última instància, millorar l'eficiència, fiabilitat i satisfacció del client del transport públic suís