Institute of Science and Ethics

This paper uses a new data set on budgetary institutions in Europe to examine the impact of fiscal rules and budget procedures in EU countries on public finances. It briefly describes the main pattern of budgetary institutions and their determinants across the EU 15 member states. Empirical evidence for the time period 1985-2004 suggests that the centralisation of budgeting procedures restrains public debt. In countries with one-party governments or coalition governments where parties are closely aligned, this is achieved by the delegation of decisionmaking power to the minister of finance. Fiscal contracts that require countries to set multiyear targets and that reinforce those targets increase fiscal discipline in countries with ideologically dispersed coalitions.

Abstract Inflammation within the CNS is a major component of many neurodegenerative diseases. A characteristic feature is the generation of microglia‐derived factors that play an essential role in the immune response. IL ‐1β is a pro‐inflammatory cytokine released by activated microglia, able to exacerbate injury at elevated levels. In the presence of caspase‐1, pro‐ IL ‐1β is cleaved to the mature cytokine following NOD‐like receptor pyrin domain containing 3 ( NLRP 3) inflammasome activation. Growing evidence suggests that ceramide plays a critical role in NLRP 3 inflammasome assembly, however, the relationship between ceramide and inflammasome activation in microglia remains unknown. Here, we investigated potential mechanistic links between ceramide as a modulator of NLRP 3 inflammasome assembly and the resulting secretion of IL ‐1β using small bioactive enzyme stimulators and inhibitors of ceramide signaling in wild‐type and apoptosis‐associated speck‐like protein containing a CARD knockout ( ASC −/− ) primary microglia. To induce the expression of inflammasome components, microglia were primed prior to experiments. Treatment with sodium palmitate ( PA ) induced de novo ceramide synthesis via modulation of its synthesizing protein serine palmitoyl transferase resulting in increased IL ‐1β secretion in microglia. Exposure of microglia to the serine palmitoyl transferase‐inhibitor l ‐cycloserine significantly prevented PA ‐induced IL ‐1β secretion. Application of the ceramide analogue C2 and the sphingosine‐1‐phosphate‐receptor agonist Fingolimod ( FTY 720) up‐regulated levels of IL ‐1β and cleaved caspase‐1 in wild‐type microglia, whereas ASC −/− microglia were unaffected. HPA ‐12 inhibition of ceramide transport did not affect inflammasome activation. Taken together, our findings reveal a critical role for ceramide as a positive modulator of NLRP 3 inflammasome assembly and the resulting release of IL ‐1β. image

The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

Abstract In this paper, I examine whether the use of artificial intelligence (AI) and automated decision-making (ADM) aggravates issues of discrimination as has been argued by several authors. For this purpose, I first take up the lively philosophical debate on discrimination and present my own definition of the concept. Equipped with this account, I subsequently review some of the recent literature on the use AI/ADM and discrimination. I explain how my account of discrimination helps to understand that the general claim in view of the aggravation of discrimination is unwarranted. Finally, I argue that the use of AI/ADM can, in fact, increase issues of discrimination, but in a different way than most critics assume: it is due to its epistemic opacity that AI/ADM threatens to undermine our moral deliberation which is essential for reaching a common understanding of what should count as discrimination. As a consequence, it turns out that algorithms may actually help to detect hidden forms of discrimination.

This document presents the Bonn PRINTEGER Consensus Statement: Working with Research Integrity—Guidance for research performing organisations. The aim of the statement is to complement existing instruments by focusing specifically on institutional responsibilities for strengthening integrity. It takes into account the daily challenges and organisational contexts of most researchers. The statement intends to make research integrity challenges recognisable from the work-floor perspective, providing concrete advice on organisational measures to strengthen integrity. The statement, which was concluded February 7th 2018, provides guidance on the following key issues:

Computer systems for medical diagnosis based on machine learning are not mere science fiction. Despite undisputed potential benefits, such systems may also raise problems. Two (interconnected) issues are particularly significant from an ethical point of view: The first issue is that epistemic opacity is at odds with a common desire for understanding and potentially undermines information rights. The second (related) issue concerns the assignment of responsibility in cases of failure. The core of the two issues seems to be that understanding and responsibility are concepts that are intrinsically tied to the discursive practice of giving and asking for reasons. The challenge is to find ways to make the outcomes of machine learning algorithms compatible with our discursive practice. This comes down to the claim that we should try to integrate discursive elements into machine learning algorithms. Under the title of "explainable AI" initiatives heading in this direction are already under way. Extensive research in this field is needed for finding adequate solutions.

Critics currently argue that applied ethics approaches to artificial intelligence (AI) are too principles-oriented and entail a theory-practice gap. Several applied ethical approaches try to prevent such a gap by conceptually translating ethical theory into practice. In this article, we explore how the currently most prominent approaches of AI ethics translate ethics into practice. Therefore, we examine three approaches to applied AI ethics: the embedded ethics approach, the ethically aligned approach, and the Value Sensitive Design (VSD) approach. We analyze each of these three approaches by asking how they understand and conceptualize theory and practice. We outline the conceptual strengths as well as their shortcomings: an embedded ethics approach is context-oriented but risks being biased by it; ethically aligned approaches are principles-oriented but lack justification theories to deal with trade-offs between competing principles; and the interdisciplinary Value Sensitive Design approach is based on stakeholder values but needs linkage to political, legal, or social governance aspects. Against this background, we develop a meta-framework for applied AI ethics conceptions with three dimensions. Based on critical theory, we suggest these dimensions as starting points to critically reflect on the conceptualization of theory and practice. We claim, first, that the inclusion of the dimension of affects and emotions in the ethical decision-making process stimulates reflections on vulnerabilities, experiences of disregard, and marginalization already within the AI development process. Second, we derive from our analysis that considering the dimension of justifying normative background theories provides both standards and criteria as well as guidance for prioritizing or evaluating competing principles in cases of conflict. Third, we argue that reflecting the governance dimension in ethical decision-making is an important factor to reveal power structures as well as to realize ethical AI and its application because this dimension seeks to combine social, legal, technical, and political concerns. This meta-framework can thus serve as a reflective tool for understanding, mapping, and assessing the theory-practice conceptualizations within AI ethics approaches to address and overcome their blind spots.

The last comprehensive International Commission on Radiological Protection (ICRP) recommendations have been published in 1991(1). Since that time new data in physics and biology that are relevant for radiological protection have appeared in the scientific literature. Also, the general thinking about safety standards at the workplace as well as for the protection of the public has developed. Thus, a review of the recommendations is needed. However, as the present standards have worked well, these new recommendations should build on the present ones. Only a process of further development should take place allowing for the following key points: The fundamental principles of radiological protection will remain the same as they have been described in ICRP publication 60(1): These documents are: Drafts have been presented on the website of ICRP (www.icrp.org). Many constructive comments have been made which have been evaluated and considered for possible changes. In this publication it is focussed on the chapters with data from physics and biology and only a rough overview of the later parts of the recommendations are given.

Given the UK’s modest 60% consent rate for donation of organs from brain stem dead donors, <b>Sheila Bird</b> and <b>John Harris</b> argue that allowing donation unless the donor has explicitly opted out would substantially increase the number of organs available

Abstract This paper argues that the terms ‘Sustainable artificial intelligence (AI)’ in general and ‘Sustainability of AI’ in particular are overused to the extent that they have lost their meaning. The AI for (social) good movement is a manifestation of this trend in which almost any application used in the context of healthcare or agriculture can be classified as AI for good regardless of whether such applications have been evaluated from a broader perspective. In this paper, we aim to create a common understanding of what the ‘AI for Sustainability’ movement ought to mean. We distinguish between two possible AI for Sustainability applications, namely those that fulfill the necessary conditions and those that fulfill the sufficient conditions. The former are purely predictive systems that serve as information providers. The latter are directly involved in an activity that contributes to a sustainability goal. We argue that taking action is a key element in distinguishing between these two application groups, as inaction is the key bottleneck in effectively tackling climate change. Furthermore, we question how effective the use of AI applications can be for sustainability when the systems themselves are inherently unsustainable. Hence, AI for Sustainability should include both an action that contributes to a sustainable end goal as well as an investigation of the sustainability issues of the AI system itself. Following that, Sustainable AI research can be on a gradient: AI in an application domain, AI towards sustainability, and AI for Sustainability.

Healthy Aims is a 23- million, four-year project, funded under the EU's information society technology sixth framework program to develop intelligent medical implants and diagnostic systems (www.healthyaims.org). The project has 25 partners from 10 countries, including commercial, clinical, and research groups. This consortium represents a combination of disciplines to design and fabricate new medical devices and components as well as to test them in laboratories and subsequent clinical trials. The project focuses on medical implants for nerve stimulation and diagnostic equipment based on strain-gauge technology.

Abstract With the introduction of the concept of Sustainable AI, considerations of the environmental impact of the technology have begun to enter AI ethics discussions. This, Aimee van Wynsberghe suggests, constitutes a new “third wave of AI ethics” which yet needs to be ushered in. In this paper, we ask what is entailed by Sustainable AI that should warrant such special accentuation. Do we find simply run-of-the-mill AI ethics applied to an environmental context? Or does Sustainable AI constitute a true a “game-changer”? We engage in a discussion about what the “waves of AI ethics” ought to mean and the criteria for labelling a wave as such. We argue that the third wave of AI ethics rests on a turn towards a structural approach for uncovering ethical issues on a broader scale, often paired with an analysis of power structures that prevent the uncovering of these issues.

‘Sustainable AI’ sets itself apart from other AI ethics frameworks by its inherent regard for the ecological costs of AI, a concern that has so far been woefully overlooked in the policy space. Recently, two German-based research and advocacy institutions have published a joint report on Sustainability Criteria for Artificial Intelligence. This is, to our knowledge, the first AI ethics document in the policy space that puts sustainability at the center of its considerations. We take this as an opportunity to highlight the foundational problems we see in current debates about AI ethics guidelines. Although we do believe the concept of sustainability has the potential to introduce a paradigm shift, we question whether the suggestions and conceptual grounding found in this report have the strength to usher it in. We show this by presenting this new report as an example of current approaches to AI ethics and identify the problems of this approach, which we will describe as ‘checklist ethics’ and ‘ethics of carefulness’. We argue to opt for an ‘ethics of desirability’ approach. This can be completed, we suggest, by reconceptualizing sustainability as a property of complex systems. Finally, we offer a set of indications for further research.

The availability of embryonic stem (ES) cells isolated from human blastocysts may open novel avenues for medical treatment of otherwise incurable diseases. Yet the generation of human ES cells requires the destruction of early human embryos. This confronts us with the moral problem of whether it is justifiable to sacrifice human life in order to treat other human life. This article outlines the development of the German debate about research with ES cells and explicates the arguments that are central to that debate with respect to the aims and means of research with ES cells. With regard to the means, the isolation of ES cells from human embryos raises the question of the moral status of the human embryo. A restrictive position acknowledges the human dignity of the embryo in its very early stage of development and claims that the embryo's life must be protected accordingly. In contrast, a gradualist position acknowledges human dignity, and therefore the full level of protection, only when the embryo has reached a certain stage of development. In addition, the intentions behind the generation of human embryos, i.e. exclusively for research purposes, and the mode of generating them, i.e. by nuclear transfer technology, have strong ethical relevance in the German debate. Based on these results, the ethical reasoning underlying the draft of a Stem Cell Act recently passed by the German Parliament is outlined.

In the past, several model checking algorithms have been proposed to verify probabilistic reactive systems. The techniques to combat the state-explosion problem have mainly concentrated on symbolic methods with variants of decision diagrams or abstraction methods. In this paper, we show how partial order reduction with a variant of Peled's ample set method can be applied in the context of LTL model checking for probabilistic systems modelled by Markov decision processes.

We performed a whole genome scan in a family with maternally transmitted paraganglioma (PGL3). The family included five patients with histologically proven paraganglioma and one patient with imaging findings consistent with a paraganglioma. In addition, there were 33 clinically unaffected family members. Of these eight could be examined by magnetic resonance imaging. Our investigations indicate that PGL3 is located in 1q21-q23 for several reasons: 1) two-point linkage analysis yielded the highest LOD score of 2.25 at 1q21-q23 (marker D1S2675); 2) haplotype analysis was most consistent for 1q21-q23 markers; and 3) the locus was excluded from more than 97% of the genome using a total of 381 highly polymorphic markers.

Abstract In this paper, we use some elements of the philosophical theories of Wilfrid Sellars and Robert Brandom for examining the interactions between humans and machines. In particular, we adopt the concept of the space of reasons for analyzing the status of artificial intelligent agents (AIAs). One could argue that AIAs, like the widely used recommendation systems, have already entered the space of reasons, since they seem to make knowledge claims that we use as premises for further claims. This, in turn, can lead to a sense of alienation because AIAs do not quite play by the rules of the space of the reason. We, therefore, ask somewhat pointedly whether aliens have entered the space of reasons. A closer look reveals that it is a misconception to consider AIAs as being (already) in the space of reasons. In fact, they should be seen as very sophisticated tools. Since these tools affect our own acting in the space of reasons, special regulations are required for their proper use.

Interferon (IFN) regulatory factors (IRFs) are transcription factors with versatile functions in the regulation of innate and adaptive immune responses. In the current issue of the European Journal of Immunology, Steinhagen et al. [Eur. J. Immunol. 2013. 43: 1896-1906] investigate the regulation of IFN-β and IL-6 induction in human plasmacytoid DCs stimulated with CpG DNA. Using RNA interference studies, the authors identify critical roles for IRF5 and IRF8 as positive and negative regulators, respectively. In contrast, knockdown of IRF7 had no significant effect on IFN-β or IL-6 gene induction. In this Commentary, these findings are discussed in the context of the published literature and recent data regarding IRF5 and IRF8 as susceptibility genes for autoimmunity.

Background: Pet robots are gaining momentum as a technology-based intervention to support the psychosocial wellbeing of people with dementia. Current research suggests that they can reduce agitation, improve mood and social engagement. The implementation of pet robots in care for persons with dementia raises several ethical debates. However, there is a paucity of empirical evidence to uncover care providers' ethical intuitions, defined as individuals' fundamental moral knowledge that are not underpinned by any specific propositions. Objectives: Explore care professionals' and organisational leaders' ethical intuitions before and when implementing pet robots in nursing homes for routine dementia care. Materials and methods: We undertook a secondary qualitative analysis of data generated from in-depth, semi-structured interviews with 22 care professionals and organisational leaders from eight nursing homes in Ireland. Data were analysed using reflexive thematic analysis. Ethical constructs derived from a comprehensive review of argument-based ethics literature were used to guide the deductive coding of concepts. An inductive approach was used to generate open codes not falling within the pre-existing concepts. Findings: Ethical intuitions for implementing pet robots manifested at three levels: an (1) individual-relational, (2) organisational and (3) societal level. At the individual-relational level, ethical intuitions involved supporting the autonomy of residents and care providers, using the robots to alleviate residents' social isolation, and the physical and psychosocial impacts associated with their use. Some care providers had differing sentiments about anthropomorphizing pet robots. At the organisational level, intuitions related to the use of pet robots to relieve care provision, changes to the organisational workflow, and varying extents of openness amongst care providers to use technological innovations. At the societal level, intuitions pertained conceptions of dementia care in nursing homes, and social justice relating to the affordability and availability of pet robots. Discrepancies between participants' ethical intuitions and existing philosophical arguments were uncovered. Conclusion: Care professionals and organisational leaders had different opinions on how pet robots are or should be implemented for residents with dementia. Future research should consider involving care practitioners, people with dementia, and their family members in the ethics dialogue to support the sustainable, ethical use of pet robots in practice.

Inflammasomes are cytosolic multimeric signaling complexes of the innate immune system that induce activation of caspases. The NOD‐like receptor NLRP9 recruits the adaptor protein ASC to form an ASC‐dependent inflammasome to limit rotaviral replication in intestinal epithelial cells, but only little is known about the molecular mechanisms regulating and driving its assembly. Here, we present the crystal structure of the human NLRP9 pyrin domain (PYD). We show that NLRP9 PYD is not able to self‐polymerize nor to nucleate ASC specks in HEK293T cells. A comparison with filament‐forming PYDs revealed that NLRP9 PYD adopts a conformation compatible with filament formation, but several charge inversions of interfacing residues might cause repulsive effects that prohibit self‐oligomerization. These results propose that inflammasome assembly of NLRP9 might differ largely from what we know of other inflammasomes.