Technological Opacity of Machine Learning in Healthcare

Recently, a host of propositions for guidelines for the ethical development and use of artificial intelligence (AI) has been published. This body of work contains timely contributions for sensitizing developers to the ethical and societal implications of their work. However, a sustained embedding of ethics in largely algorithm-based technology development, research and studies requires a precise framing of the origins of the new vulnerabilities created. Recently, scholars have been referring to ethics associated with technology that is in some way “opaque” to at least part of its associated stakeholders. This “opacity” can take several forms which will be discussed in this paper. There are various ways in which such an opacity can create vulnerabilities and, hence, relevant ethical, societal, epistemic and regulatory challenges. This paper provides a non-exhaustive list of examples in healthcare that call for educational resources and consideration in development processes that try to reveal and counter these opacities

Molecular insights into the transport lectin function of ERGIC-53

Secretion of proteins is an essential function of eukaryotic cells. The secretory proteins’ journey along the organelles of the exocytic pathway is initiated by the exit from the endoplasmic reticulum (ER), which defines a major rate-limiting step for protein secretion. ER-exit is subject to tight quality control. Selective, receptor-mediated cargo capture is one of the mechanisms thought to contribute to the elaborate proof-reading system of the ER. The recycling mannose lectin ERGIC-53 operates as an ER-export receptor of a subset of secretory glycoproteins. The required signals for this transport step, however, remain poorly described. Experiments in this thesis show that ERGIC-53 assisted ER-exit of procathepsin Z depends on a novel transport motif that is composed of a high-mannose type oligosaccharide and a peptide β-hairpin loop. Deletion of either determinant compromises ERGIC-53 association and slows procathepsin Z transport. An equivalent carbohydrate/hairpin structure is identified in cathepsin C, another cargo of ERGIC-53, reflecting the general nature of this ER-export signal. Further experiments reveal that the Nglycans of loop-deficient procathepsin Z become efficiently mannose 6-phosphorylated, but undergo increased carbohydrate processing in the Golgi including complex glycosylation. Strikingly, cathepsin Z lacking the peptide loop is not targeted to its normal destination, the lysosome, suggesting that it lacks the correct carbohydrate signal for lysosomal delivery. The presented data describe the first ER-exit signal on a secretory protein and establish an unexpected link between lectin-mediated export from the ER and post-Golgi sorting. This thesis also provides the molecular basis for ERGIC-53/cargo dissociation in the ERGIC. In vitro mannose binding experiments reveal that the lectin only displays its full activity at pH 7.4 – the pH of the ER – but not at slightly lower pH. The acid-sensitivity is modulated by the calcium concentration indicating a molecular link between pH-sensing and calcium complexation. This link is spotted by the identification of His178 that is conserved throughout the family of animal L-type lectins and – in its deprotonated form – binds a calcium ion in the carbohydrate recognition domain (CRD) of ERGIC-53. pH-induced inactivation of ERGIC-53 is also shown in cell culture. Glycoprotein binding is inhibited, if the ER is acidified, and the kinetics of glycoprotein dissociation are slowed, if the ERGIC is neutralized. The results establish the ERGIC as the earliest acid compartment of the secretory pathway and suggest that pH-induced glycoprotein dissociation may be backed by a mechanism that maintains lower levels of free calcium in the ERGIC. The organelles of the secretory pathway operate as intracellular calcium stores. High concentrations of calcium have been measured in the lumen of the ER and the Golgi, but the calcium concentration in the ERGIC is not known. Therefore, a strategy was developed to quantitatively assess the free calcium concentration of the ERGIC in vivo using the green fluorescent protein-based calcium-indicator yellow cameleon. Targeting of the indicator to the ERGIC is achieved by fusing it to an inert variant of the ER-Golgi SNARE Sec22b. The fusion protein dynamically localizes to the ERGIC without disturbing the function of the endogenous SNARE machinery. It will in the future provide a valuable tool for calcium measurements in the ERGIC

Digitally Aided Sovereignty: A Suitable Guide for the E-Government Transformation?

We advocate for the adoption of an integrated strategy aimed at achieving increased participation via effective digital public administration services. We argue that it is urgent to understand the integration of participatory approaches from the field of e-democracy in digitalized public administration, as trendsetting e-government implementations are already underway. We base our arguments on the observation that the approaches in e-democracy and e-government seem to be locked into extremes: In e-democracy, (experimental) platforms have failed to create a participative political culture. E-government, in turn, narrowly perceives citizens as customers. Additionally, efforts to increase digital sovereignty have mostly been educational ones that support citizens' self-determined use of the digital but do not address sovereignty via the digital. As a result, digitalized public administration is not achieving its potential to create opportunities for participation during encounters with the administration. Hence, we argue for the adoption of a digitally aided sovereignty as a normative guide for an e-government transformation that strives to create opportunities for participation via the digital

Teaching ethics through the back door? Employing ideas from assemblage theory to foster a responsible innovation mindset

Adding ethics courses to engineering curricula seeks to equip students with the critical mindset that enables careers committed to serving humanity. Yet, the knowledge of ethical theories is neither a necessary, let alone sufficient condition for being good [1]. There is no automatism that translates ethical knowledge into action, overriding attitudes that were developed during the enculturation of a student. However, we deem teaching assemblage theory a promising means to achieve a sustained commitment to responsible innovation practice. We base our argument on assemblage theory’s (cf. [2, 3]) capacity to conceptualize the interplay of human actors and technological artefacts in terms of dynamic evolutionary systems. The notion of an assemblage as a collection of potentially heterogeneous elements that—despite displaying consistency—remains malleable through reorganization, interconnection and, (re- )attribution forms the ontological basis that guides a conceptual approach to thinking in-between the extremes of technological determinism and social constructivism. Information algorithms, e.g., can be regarded as having the power to facilitate ethical action as part of a larger assemblage [4] and artificial intelligence can arguably only be understood as “trustworthy” within sociotechnological systems in which a shared responsibility realizes both epistemic and moral conditions for trust [5]. Ultimately, we intend engineering students to realize the extent of their influence on the world and, therefore, their responsibility for contributing to a prosperous community. Thus, ethics is not only taught by conveying its classical normative theories but rather explored by discovering the entangledness of technology and society

Course and Outcome of Bacteremia Due to Staphylococcus aureus: Evaluation of Different Clinical Case Definitions

In a retrospective survey of patients hospitalized in the University Hospital of Basel, Switzerland, the course and outcome of 281 cases of true bacteremia due to Staphylococcus aureus over a 7-year period were analyzed. The main purpose was to evaluate different case definitions. In 78% of cases the source of bacteremia was obvious; vascular access sites (27%) and wounds (10%) were the most common sources. Metastasizing foci were more common in cases of primary vs. secondary bacteremia (P < .001). The incidence of endocarditis was higher in cases in which no portal of entry was defined (P < .03). The overall mortality rate was high at 34% partly because of inappropriate initial antibiotic therapy. With the introduction of an infectious disease service at the hospital, the fraction of misjudged results of blood culture diminished 2.5-fold. Among the differently defined cases, the mortality rate was significantly higher for cases of complicated vs. uncomplicated bacteremia (P < .01), for cases of primary vs. secondary bacteremia (P = .05), and for patients with endocarditis or other secondary foci (P < .001). Since only one methicillin-resistant strain was isolated, multiresistant staphylococci were not a problem in the hospital. Different case definitions allowed the detection of patients at increased risk for complications and death. In the treatment of sepsis with no evident focus, initial antimicrobial therapy should include the use of agents with antistaphylococcal activit

From praxis to pragmatism: Junior scholars and policy impact

Drawing on Buckingham’s observation that academic research either has to become public knowledge or its originators must have a high visibility in the public realm before their research can find inclusion into policymaking processes, this article offers a variety of examples of how academics have managed to bridge the gap between media and communication policy scholarship and policymaking. Contrary to the long-standing belief that policy impact is extremely difficult and rare to achieve, we argue that junior scholars have many opportunities to have their work become part of the policymaking process through new forms of conversation, collaboration, coalition-building, changing perceptions of public knowledge, and a more conceptual understanding of impact