Responsible AI Pattern Catalogue: A Collection of Best Practices for AI Governance and Engineering

Responsible AI is widely considered as one of the greatest scientific challenges of our time and is key to increase the adoption of AI. Recently, a number of AI ethics principles frameworks have been published. However, without further guidance on best practices, practitioners are left with nothing much beyond truisms. Also, significant efforts have been placed at algorithm-level rather than system-level, mainly focusing on a subset of mathematics-amenable ethical principles, such as fairness. Nevertheless, ethical issues can arise at any step of the development lifecycle, cutting across many AI and non-AI components of systems beyond AI algorithms and models. To operationalize responsible AI from a system perspective, in this paper, we present a Responsible AI Pattern Catalogue based on the results of a Multivocal Literature Review (MLR). Rather than staying at the principle or algorithm level, we focus on patterns that AI system stakeholders can undertake in practice to ensure that the developed AI systems are responsible throughout the entire governance and engineering lifecycle. The Responsible AI Pattern Catalogue classifies the patterns into three groups: multi-level governance patterns, trustworthy process patterns, and responsible-AI-by-design product patterns. These patterns provide systematic and actionable guidance for stakeholders to implement responsible AI

Neuroprotective activities of Nepalese and Native American traditional medicine in Parkinson\u27s disease models

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease with 5% of the population being affected by age 85. The disease involves a loss of dopaminergic neurons from the substantia nigra in the midbrain, and this loss of neurons is largely responsible for motor symptoms such as the inability to initiate movement, resting tremor, and reduced balance. Molecular phenomena underlying neurodegeneration in PD include oxidative stress, loss of mitochondrial function, aggregation of the pre-synaptic protein alpha-synuclein (aSyn), and neuroinflammation. Current therapeutic strategies for PD only alleviate symptoms and do not reverse the neuronal death. Hence, patients and health care providers are in need of safe and effective neuroprotective therapies that can slow the neurodegenerative process. Traditional medicine is the primary form of healthcare for 80% of the population in developing countries. This form of medicine results from empirical determination of the safest and most efficient plant preparations to achieve desired health-promoting benefits. A number of in vitro and in vivo studies have led to the identification of polyphenols (including isoflavones and anthocyanins (ANC)) as a major class of plant-derived compounds with potential neuroprotective activities. As a result of these observations, we hypothesized that medicinal plants used in Nepalese and Native American traditional medicine to treat symptoms related to PD or other CNS disorders are potential neuroprotective candidates for the development of PD therapies. The studies outlined in this thesis were aimed at identifying traditional herbal medicines used to treat PD and CNS-related disorders in (i) Nepalese communities living in three eco-geographical areas, and (ii) two Native American tribes (the Pikuni-Blackfeet and Lumbee tribes) with different cultural identities and traditional practices. Our ethnopharmacological study yielded insight into the strong influence of the surrounding environment on the practice of traditional medicine. In all three study areas, we observed and reported on the impact of cultural, historical and environmental pressures on the evolution of traditional medicine. Our study led to the identification of medicinal plants across various botanical families with potential neuroprotective activities. We developed a primary screen to test the ability of 23 botanical extracts to activate Nrf2, a transcription factor that acts as a master regulator of the cellular antioxidant response. Extracts that produced the most robust activation of Nrf2 signaling were further studied to determine their neuroprotective effects against toxicity elicited by PD-related insults. The extracts of garlic, juneberry, elderflower, red clover, Mucuna pruriens and Tinospora sinensis alleviated neurodegeneration induced by the pesticide rotenone, the herbicide paraquat, and/or the A53T genetic mutant of aSyn. Following the observation that isoflavones-rich extracts (red clover) and ANC-rich berry extracts (juneberry) are potent neuroprotective agents, we carried out two studies aimed at understanding the beneficial role of isoflavones and ANC in PD models. In these studies we characterized several isoflavone-rich extracts, individual isoflavones, and ANC-rich extracts in terms of their ability to prevent dopaminergic cell loss, activate the Nrf2/ARE response, and alleviate mitochondrial dysfunction. We found that the extracts and compounds alleviated neurodegeneration by modulating different pro-survival pathways. The red clover and ANC-rich extracts, but not the soy extract or individual isoflavones, activated the Nrf2/ARE pathway. Interestingly, Nrf2 activation mediated by ANC-rich extracts was ROS-dependent, whereas activation by the red clover extract was dependent on UPS inhibition. Furthermore, the red clover, soy, and ANC-rich extracts mitigated rotenone-induced mitochondrial impairment, and the amelioration of mitochondrial dysfunction by the red clover extract apparently involved the displacement of rotenone from its complex I binding site. Collectively, our data indicate that ethnopharmacological studies are an effective strategy to identify botanical specimens with neuroprotective activity. Polyphenol-rich herbal extracts achieve neuroprotection via multiple pro-survival mechanisms including activation of the Nrf2/ARE antioxidant response and maintenance of mitochondrial function. Our findings suggest that plant-based extracts with neuroprotective activity could potentially reduce the risk of PD and slow disease progression in patients

PREVALENCE DE L'ENZYME TEM-24 CHEZ LES ENTEROBACTERIES PRODUCTRICES DE BETA-LACTAMASE A SPECTRE ETENDU (DES BIOL. MED.)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Society on social implications of technology (SSIT) Australia response to the Discussion Paper on Artificial Intelligence: Australia’s Ethics Framework

The following submission has been prepared by members of the IEEE Society on Social Implications of Technology (SSIT) in Australia. IEEE is the world’s largest technology professional association, with 420,000 members in 161 countries. Founded in 1972, SSIT is the unit within IEEE which addresses the relationship between technology and society. SSIT Australia was formed in 2005 and has members in all states. SSIT Australia members have actively contributed to the IEEE's Ethically Aligned Design First Edition report (‘IEEE EAD’)1, referred to in the Discussion Paper on Artificial Intelligence: Australia’s Ethics Framework (‘Discussion Paper’).SSIT Australia welcomes this opportunity to participate in the development of Australia’s Ethics Framework. Overall, we see the Discussion Paper as a positive contribution and a useful starting point to stimulate further and wider discussions on the topic. In this submission we highlight a range of concerns with the Discussion Paper and also propose a number of improvements

Towards intellectual freedom in an AI Ethics Global Community

The recent incidents involving Dr. Timnit Gebru, Dr. Margaret Mitchell, and Google have triggered an important discussion emblematic of issues arising from the practice of AI Ethics research. We ofer this paper and its bibliography as a resource to the global community of AI Ethics Researchers who argue for the protection and freedom of this research community. Corpo�rate, as well as academic research settings, involve responsibility, duties, dissent, and conficts of interest. This article is meant to provide a reference point at the beginning of this decade regarding matters of consensus and disagreement on how to enact AI Ethics for the good of our institutions, society, and individuals. We have herein identifed issues that arise at the intersection of information technology, socially encoded behaviors, and biases, and individual researchers’ work and responsibilities. We revisit some of the most pressing problems with AI decision-making and examine the difcult relationships between corporate interests and the early years of AI Ethics research. We propose several possible actions we can take collectively to support researchers throughout the feld of AI Ethics, especially those from marginalized groups who may experience even more bar�riers in speaking out and having their research amplifed. We promote the global community of AI Ethics researchers and the evolution of standards accepted in our profession guiding a technological future that makes life better for all

Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk

WOS:000454834200006International audienceBRCA1 mutations have been identified that increase the risk of developing hereditary breast and ovarian cancers. Genetic screening is now offered to patients with a family history of cancer, to adapt their treatment and the management of their relatives. However, a large number of BRCA1 variants of uncertain significance (VUS) are detected. To better understand the significance of these variants, a high-throughput structural and functional analysis was performed on a large set of BRCA1 VUS. Information on both cellular localization and homology-directed DNA repair (HR) capacity was obtained for 78 BRCT missense variants in the UMD-BRCA1 database and measurement of the structural stability and phosphopeptide-binding capacities was performed for 42 mutated BRCT domains. This extensive and systematic analysis revealed that most characterized causal variants affect BRCT-domain solubility in bacteria and all impair BRCA1 HR activity in cells. Furthermore, binding to a set of 5 different phosphopeptides was tested: all causal variants showed phosphopeptide-binding defects and no neutral variant showed such defects. A classification is presented on the basis of mutated BRCT domain solubility, phosphopeptide-binding properties, and VUS HR capacity. These data suggest that HR-defective variants, which present, in addition, BRCT domains either insoluble in bacteria or defective for phosphopeptide binding, lead to an increased cancer risk. Furthermore, the data suggest that variants with a WT HR activity and whose BRCT domains bind with a WT affinity to the 5 phosphopeptides are neutral. The case of variants with WT HR activity and defective phosphopeptide binding should be further characterized, as this last functional defect might be sufficient per se to lead to tumorigenesis. Implications: The analysis of the current study on BRCA1 structural and functional defects on cancer risk and classification presented may improve clinical interpretation and therapeutic selection

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed