Impact of Responsible AI on the Occurrence and Resolution of Ethical Issues: Protocol for a Scoping Review

\ua9 2024 JMIR Publications Inc.. All rights reserved. Background: Responsible artificial intelligence (RAI) emphasizes the use of ethical frameworks implementing accountability, responsibility, and transparency to address concerns in the deployment and use of artificial intelligence (AI) technologies, including privacy, autonomy, self-determination, bias, and transparency. Standards are under development to guide the support and implementation of AI given these considerations. Objective: The purpose of this review is to provide an overview of current research evidence and knowledge gaps regarding the implementation of RAI principles and the occurrence and resolution of ethical issues within AI systems. Methods: A scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines was proposed. PubMed, ERIC, Scopus, IEEE Xplore, EBSCO, Web of Science, ACM Digital Library, and ProQuest (Arts and Humanities) will be systematically searched for articles published since 2013 that examine RAI principles and ethical concerns within AI. Eligibility assessment will be conducted independently and coded data will be analyzed along themes and stratified across discipline-specific literature. Results: The results will be included in the full scoping review, which is expected to start in June 2024 and completed for the submission of publication by the end of 2024. Conclusions: This scoping review will summarize the state of evidence and provide an overview of its impact, as well as strengths, weaknesses, and gaps in research implementing RAI principles. The review may also reveal discipline-specific concerns, priorities, and proposed solutions to the concerns. It will thereby identify priority areas that should be the focus of future regulatory options available, connecting theoretical aspects of ethical requirements for principles with practical solutions

Beam Based Alignment of Interaction Region Magnets

In conventional beam based alignment (BBA) procedures, the relative alignment of a quadrupole to a nearby beam position monitor is determined by finding a beam position in the quadrupole at which the closed orbit does not change when the quadrupole field is varied. The final focus magnets of the interaction regions (IR) of circular colliders often have some specialized properties that make it difficult to perform conventional beam based alignment procedures. At the HERA interaction points, for example, these properties are: (a) The quadrupoles are quite strong and long. Therefore a thin lens approximation is quite imprecise. (b) The effects of angular magnet offsets become significant. (c) The possibilities to steer the beam are limited as long as the alignment is not within specifications. (d) The beam orbit has design offsets and design angles with respect to the axis of the low-beta quadrupoles. (e) Often quadrupoles do not have a beam position monitor in their vicinity. Here we present a beam based alignment procedure that determines the relative offset of the closed orbit from a quadrupole center without requiring large orbit changes or monitors next to the quadrupole. Taking into account the alignment angle allows us to reduce the sensitivity to optical errors by one to two orders of magnitude. We also show how the BBA measurements of all IR quadrupoles can be used to determine the global position of the magnets. The sensitivity to errors of this method is evaluated and its applicability to HERA is shown

High-Resolution Recombination Patterns in a Region of Human Chromosome 21 Measured by Sperm Typing

For decades, classical crossover studies and linkage disequilibrium (LD) analysis of genomic regions suggested that human meiotic crossovers may not be randomly distributed along chromosomes but are focused instead in “hot spots.” Recent sperm typing studies provided data at very high resolution and accuracy that defined the physical limits of a number of hot spots. The data were also used to test whether patterns of LD can predict hot spot locations. These sperm typing studies focused on several small regions of the genome already known or suspected of containing a hot spot based on the presence of LD breakdown or previous experimental evidence of hot spot activity. Comparable data on target regions not specifically chosen using these two criteria is lacking but is needed to make an unbiased test of whether LD data alone can accurately predict active hot spots. We used sperm typing to estimate recombination in 17 almost contiguous ~5 kb intervals spanning 103 kb of human Chromosome 21. We found two intervals that contained new hot spots. The comparison of our data with recombination rates predicted by statistical analyses of LD showed that, overall, the two datasets corresponded well, except for one predicted hot spot that showed little crossing over. This study doubles the experimental data on recombination in men at the highest resolution and accuracy and supports the emerging genome-wide picture that recombination is localized in small regions separated by cold areas. Detailed study of one of the new hot spots revealed a sperm donor with a decrease in recombination intensity at the canonical recombination site but an increase in crossover activity nearby. This unique finding suggests that the position and intensity of hot spots may evolve by means of a concerted mechanism that maintains the overall recombination intensity in the region

Evaluation of the LEP Centre-of-Mass Energy Above the W-Pair Production Threshold

Knowledge of the centre-of-mass energy at LEP2 is of primary importance to set the absolute energy scale for the measurement of the W-boson mass. The beam energy above 80 GeV is derived from continuous measurements of the magnetic bending field by 16 NMR probes situated in a number of the LEP dipoles. The relationship between the fields measured by the probes and the beam energy is calibrated against precise measurements of the average beam energy between 41 and 55 GeV made using the resonant depolarisation technique. The linearity of the relationship is tested by comparing the fields measured by the probes with the total bending field measured by a flux loop. This test results in the largest contribution to the systematic uncertainty. Several further corrections are applied to derive the the centre-of-mass energies at each interaction point. In addition the centre-of-mass energy spread is evaluated. The beam energy has been determined with a precision of 25 MeV for the data taken in 1997, corresponding to a relative precision of 2.7x10^{-4}. This is small in comparison to the present uncertainty on the W mass measurement at LEP. However, the ultimate statistical precision on the W mass with the full LEP2 data sample should be around 25 MeV, and a smaller uncertainty on the beam energy is desirable. Prospects for improvements are outlined.Comment: 24 pages, 10 figures, Latex, epsfig; replaced by version accepted by European Physical Journal

Unmasking features of the auto-epitope essential for β(1)-adrenoceptor activation by autoantibodies in chronic heart failure

AIMS: Chronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and/or second extracellular loops of cardiac β(1)-adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine-map the conformational epitope within the second extracellular loop of the human β(1)-adrenoceptor (β(1) EC(II)) that is targeted by stimulating β(1)-receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto-epitope. METHODS AND RESULTS: Non-conserved amino acids within the β(1) ECII loop (compared with the amino acids constituting the ECII loop of the β(2)-adrenoceptor) were one by one replaced with alanine; potential intra-loop disulfide bridges were probed by cysteine-serine exchanges. Effects on antibody binding and allosteric receptor activation were assessed (i) by (auto)antibody neutralization using cyclopeptides mimicking β(1) ECII ± the above replacements, and (ii) by (auto)antibody stimulation of human β(1)-adrenoceptors bearing corresponding point mutations. With the use of stimulating β(1)-receptor (auto)antibodies raised in mice, rats, or rabbits and isolated from exemplary dilated cardiomyopathy patients, our series of experiments unmasked two features of the β(1) ECII loop essential for (auto)antibody binding and allosteric receptor activation: (i) the NDPK(211-214) motif and (ii) the intra-loop disulfide bond C(209)↔C(215). Of note, aberrant intra-loop disulfide bond C(209)↔C(216) almost fully disrupted the functional auto-epitope in cyclopeptides. CONCLUSIONS: The conformational auto-epitope targeted by cardio-pathogenic β(1)-receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the β(1) EC(II) loop bearing the NDPK(211-214) motif and the C(209)↔C(215) bridge while lacking cysteine C(216). Such molecules provide promising tools for novel diagnostic and therapeutic approaches in β(1)-autoantibody-positive CHF

C-Terminal regions of topoisomerase IIα and IIβ determine isoform-specific functioning of the enzymes in vivo

Topoisomerase II removes supercoils and catenanes generated during DNA metabolic processes such as transcription and replication. Vertebrate cells express two genetically distinct isoforms (α and β) with similar structures and biochemical activities but different biological roles. Topoisomerase IIα is essential for cell proliferation, whereas topoisomerase IIβ is required only for aspects of nerve growth and brain development. To identify the structural features responsible for these differences, we exchanged the divergent C-terminal regions (CTRs) of the two human isoforms (α 1173-1531 and β 1186-1621) and tested the resulting hybrids for complementation of a conditional topoisomerase IIα knockout in human cells. Proliferation was fully supported by all enzymes bearing the α CTR. The α CTR also promoted chromosome binding of both enzyme cores, and was by itself chromosome-bound, suggesting a role in enzyme targeting during mitosis. In contrast, enzymes bearing the β CTR supported proliferation only rarely and when expressed at unusually high levels. A similar analysis of the divergent N-terminal regions (α 1-27 and β 1-43) revealed no role in isoform-specific functions. Our results show that it is the CTRs of human topoisomerase II that determine their isoform-specific functions in proliferating cells. They also indicate persistence of some functional redundancy between the two isoforms

States emerging from hybrid political orders: Pacific experiences The Australian Centre for Peace and Conflict Studies Occasional Papers Series.

This study explores current processes of state formation in the Pacific islands, focusing on Vanuatu, Solomon Islands, Tonga, Bougainville (as an autonomous region of Papua New Guinea), Southern Highlands Province of Papua New Guinea, and East Timor. It challenges the mainstream discourse on fragile states as a framework for analysis of the situation of any of these countries or regions, and argues that it is more appropriate to talk about states emerging from hybrid political orders as a common denominator. Hybrid political orders combine elements of the introduced Western models of governance and elements stemming from local indigenous traditions. In East Timor and the Pacific island countries customary governance, deeply rooted in locality, has significant implications for state capacity and functionality as well as legitimacy. Tonga with its constitutional monarchy is transitioning to more liberal democratic forms of governance. This gradual process is driven by civil society forces that are growing in strength. In the Melanesian cases of Vanuatu, Bougainville and Solomon Islands there is negotiation of the conditions and possibilities of a ‘marriage’ between customary governance and introduced Western forms of governance, based on relatively strong customary spheres and state institutions that struggle with problems of effectiveness and legitimacy. East Timor is engaged in a conventional state-building process (with massive external assistance) focusing on the transfer and strengthening of central government institutions. The process has taken little account of customary institutions and their potential for contributing to governance and order, and has inadvertently marginalised both local culture and rural communities more generally, with considerable negative effects for Timorese state formation. In the Southern Highlands Province of PNG a vacuum of effective and legitimate governance can be found. In all of these countries or regions there is considerable potential for state and non-state actors to play complementary roles in the provision of functions which OECD countries normally assign exclusively to the state. We also found areas of incompatibility and areas of considerable friction between state and customary institutions. These, however, are not due to insurmountable contradictions between customary and liberal democratic principles and could be overcome by processes of mutual adaptation. These findings—large areas of complementarity, at times intense, but surmountable incompatibilities—augur well for constructive interaction between state and customary institutions which might lead to the emergence of networks of resilient governance which are not introduced from the outside, but are embedded in the societal structures on the ground. Keyword(s) state formatio

Accuracy and safety of an autonomous artificial intelligence clinical assistant conducting telemedicine follow-up assessment for cataract surgery

\ua9 2024 The AuthorsBackground: Artificial intelligence deployed to triage patients post-cataract surgery could help to identify and prioritise individuals who need clinical input and to expand clinical capacity. This study investigated the accuracy and safety of an autonomous telemedicine call (Dora, version R1) in detecting cataract surgery patients who need further management and compared its performance against ophthalmic specialists. Methods: 225 participants were recruited from two UK public teaching hospitals after routine cataract surgery between 17 September 2021 and 31 January 2022. Eligible patients received a call from Dora R1 to conduct a follow-up assessment approximately 3 weeks post cataract surgery, which was supervised in real-time by an ophthalmologist. The primary analysis compared decisions made independently by Dora R1 and the supervising ophthalmologist about the clinical significance of five symptoms and whether the patient required further review. Secondary analyses used mixed methods to examine Dora R1\u27s usability and acceptability and to assess cost impact compared to standard care. This study is registered with ClinicalTrials.gov (NCT05213390) and ISRCTN (16038063). Findings: 202 patients were included in the analysis, with data collection completed on 23 March 2022. Dora R1 demonstrated an overall outcome sensitivity of 94% and specificity of 86% and showed moderate to strong agreement (kappa: 0.758–0.970) with clinicians in all parameters. Safety was validated by assessing subsequent outcomes: 11 of the 117 patients (9%) recommended for discharge by Dora R1 had unexpected management changes, but all were also recommended for discharge by the supervising clinician. Four patients were recommended for discharge by Dora R1 but not the clinician; none required further review on callback. Acceptability, from interviews with 20 participants, was generally good in routine circumstances but patients were concerned about the lack of a ‘human element’ in cases with complications. Feasibility was demonstrated by the high proportion of calls completed autonomously (195/202, 96.5%). Staff cost benefits for Dora R1 compared to standard care were \ua335.18 per patient. Interpretation: The composite of mixed methods analysis provides preliminary evidence for the safety, acceptability, feasibility, and cost benefits for clinical adoption of an artificial intelligence conversational agent, Dora R1, to conduct follow-up assessment post-cataract surgery. Further evaluation in real-world implementation should be conducted to provide additional evidence around safety and effectiveness in a larger sample from a more diverse set of Trusts. Funding: This manuscript is independent research funded by the National Institute for Health Research and NHSX (Artificial Intelligence in Health and Care Award, AI_AWARD01852)