Computational modelling for decision-making: where, why, what, who and how

In order to deal with an increasingly complex world, we need ever more sophisticated computational models that can help us make decisions wisely and understand the potential consequences of choices. But creating a model requires far more than just raw data and technical skills: it requires a close collaboration between model commissioners, developers, users and reviewers. Good modelling requires its users and commissioners to understand more about the whole process, including the different kinds of purpose a model can have and the different technical bases. This paper offers a guide to the process of commissioning, developing and deploying models across a wide range of domains from public policy to science and engineering. It provides two checklists to help potential modellers, commissioners and users ensure they have considered the most significant factors that will determine success. We conclude there is a need to reinforce modelling as a discipline, so that misconstruction is less likely; to increase understanding of modelling in all domains, so that the misuse of models is reduced; and to bring commissioners closer to modelling, so that the results are more useful

Towards AI Standards Whitepaper: Thought-leadership in AI legal, ethical and safety specifications through experimentation

With the rapid adoption of algorithms in business and society there is a growing concern to safeguard the public interest. Researchers, policy-makers and industry sharing this view convened to collectively identify future areas of focus in order to advance AI standards - in particular the acute need to ensure standard suggestions are practical and empirically informed. This discussion occurred in the context of the creation of a lab at UCL with these concerns in mind (currently dubbed as UCL The Algorithms Standards and Technology Lab). Via a series of panels, with the main stakeholders, three themes emerged, namely (i) Building public trust, (ii) Accountability and Operationalisation, and (iii) Experimentation. In order to forward the themes, lab activities will fall under three streams - experimentation, community building and communication. The Lab’s mission is to provide thought-leadership in AI standards through experimentation

Towards algorithm auditing: managing legal, ethical and technological risks of AI, ML and associated algorithms

­Business reliance on algorithms is becoming ubiquitous, and companies are increasingly concerned about their algorithms causing major financial or reputational damage. High-profile cases include Google’s AI algorithm for photo classification mistakenly labelling a black couple as gorillas in 2015 (Gebru 2020 In The Oxford handbook of ethics of AI, pp. 251–269), Microsoft’s AI chatbot Tay that spread racist, sexist and antisemitic speech on Twitter (now X) (Wolf et al. 2017 ACM Sigcas Comput. Soc. 47, 54–64 (doi:10.1145/3144592.3144598)), and Amazon’s AI recruiting tool being scrapped after showing bias against women. In response, governments are legislating and imposing bans, regulators fining companies and the judiciary discussing potentially making algorithms artificial ‘persons’ in law. As with financial audits, governments, business and society will require algorithm audits; formal assurance that algorithms are legal, ethical and safe. A new industry is envisaged: Auditing and Assurance of Algorithms (cf. data privacy), with the remit to professionalize and industrialize AI, ML and associated algorithms. The stakeholders range from those working on policy/regulation to industry practitioners and developers. We also anticipate the nature and scope of the auditing levels and framework presented will inform those interested in systems of governance and compliance with regulation/standards. Our goal in this article is to survey the key areas necessary to perform auditing and assurance and instigate the debate in this novel area of research and practice

Inhibition of S/G(2) phase CDK4 reduces mitotic fidelity

Cyclin-dependent kinase 4 (CDK4)/cyclin D has a key role in regulating progression through late G(1) into S phase of the cell cycle. CDK4-cyclin D complexes then persist through the latter phases of the cell cycle, although little is known about their potential roles. We have developed small molecule inhibitors that are highly selective for CDK4 and have used these to define a role for CDK4-cyclin D in G(2) phase. The addition of the CDK4 inhibitor or small interfering RNA knockdown of cyclin D3, the cyclin D partner, delayed progression through G(2) phase and mitosis. The G(2) phase delay was independent of ATM/ATR and p38 MAPK but associated with elevated Wee1. The mitotic delay was because of failure of chromosomes to migrate to the metaphase plate. However, cells eventually exited mitosis, with a resultant increase in cells with multiple or micronuclei. Inhibiting CDK4 delayed the expression of the chromosomal passenger proteins survivin and borealin, although this was unlikely to account for the mitotic phenotype. These data provide evidence for a novel function for CDK4-cyclin D3 activity in S and G(2) phase that is critical for G(2)/M progression and the fidelity of mitosis

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Coherency Maximizing Exploration in the Supermarket

Related information for Riefer, Prior, Blair, Pavey and Love (2017

A UVR-induced G2-phase checkpoint response to ssDNA gaps produced by replication fork bypass of unrepaired lesions is defective in melanoma

UVR is a major environmental risk factor for the development of melanoma. Here we describe a coupled DNAdamage tolerance (DDT) mechanism and G2-phase cell cycle checkpoint induced in response to suberythemal doses of UVR that is commonly defective in melanomas. This coupled response is triggered by a small number of UVR-induced DNA lesions incurred during G1 phase that are not repaired by nucleotide excision repair (NER). These lesions are detected during S phase, but rather than stalling replication, they trigger the DDTdependent formation of single-stranded DNA (ssDNA) gaps. The ssDNA attracts replication protein A (RPA), which initiates ATR–Chk1 (ataxia telangiectasia and Rad3-related/checkpoint kinase 1) G2-phase checkpoint signaling, and colocalizes with components of the RAD18 and RAD51 postreplication repair pathways. We demonstrate that depletion of RAD18 delays both the resolution of RPA foci and exit from the G2-phase arrest, indicating the involvement of RAD18-dependent postreplication repair in ssDNA gap repair during G2 phase. Moreover, the presence of RAD51 and BRCA1 suggests that an error-free mechanism may also contribute to repair. Loss of the UVR-induced G2-phase checkpoint results in increased UVR signature mutations after exposure to suberythemal UVR. We propose that defects in the UVR-induced G2-phase checkpoint and repair mechanism are likely to contribute to melanoma development

Towards algorithm auditing: managing legal, ethical and technological risks of AI, ML and associated algorithms

­Business reliance on algorithms is becoming ubiquitous, and companies are increasingly concerned about their algorithms causing major financial or reputational damage. High-profile cases include Google’s AI algorithm for photo classification mistakenly labelling a black couple as gorillas in 2015 (Gebru 2020 In The Oxford handbook of ethics of AI, pp. 251–269), Microsoft’s AI chatbot Tay that spread racist, sexist and antisemitic speech on Twitter (now X) (Wolf et al. 2017 ACM Sigcas Comput. Soc. 47, 54–64 (doi:10.1145/3144592.3144598)), and Amazon’s AI recruiting tool being scrapped after showing bias against women. In response, governments are legislating and imposing bans, regulators fining companies and the judiciary discussing potentially making algorithms artificial ‘persons’ in law. As with financial audits, governments, business and society will require algorithm audits; formal assurance that algorithms are legal, ethical and safe. A new industry is envisaged: Auditing and Assurance of Algorithms (cf. data privacy), with the remit to professionalize and industrialize AI, ML and associated algorithms. The stakeholders range from those working on policy/regulation to industry practitioners and developers. We also anticipate the nature and scope of the auditing levels and framework presented will inform those interested in systems of governance and compliance with regulation/standards. Our goal in this article is to survey the key areas necessary to perform auditing and assurance and instigate the debate in this novel area of research and practice