Governance of Autonomous Agents on the Web: Challenges and Opportunities

International audienceThe study of autonomous agents has a long tradition in the Multiagent System and the Semantic Web communities, with applications ranging from automating business processes to personal assistants. More recently, the Web of Things (WoT), which is an extension of the Internet of Things (IoT) with metadata expressed in Web standards, and its community provide further motivation for pushing the autonomous agents research agenda forward. Although representing and reasoning about norms, policies and preferences is crucial to ensuring that autonomous agents act in a manner that satisfies stakeholder requirements, normative concepts, policies and preferences have yet to be considered as first-class abstractions in Web-based multiagent systems. Towards this end, this paper motivates the need for alignment and joint research across the Multiagent Systems, Semantic Web, and WoT communities, introduces a conceptual framework for governance of autonomous agents on the Web, and identifies several research challenges and opportunities

The diagnosis and management of idiosyncratic drug‐induced liver injury

Drug‐induced liver injury (DILI) is an uncommon but important cause of liver disease that can arise after exposure to a multitude of drugs and herbal and dietary supplements. The severity of idiosyncratic DILI varies from mild serum aminotransferase elevations to the development of severe liver injury that can progress to acute liver failure resulting in death or liver transplantation within days of DILI onset. Chronic liver injury that persists for more than 6 months after DILI onset is also becoming increasingly recognized in up to 20% of DILI patients. Host demographic (age, gender, race), clinical and laboratory features at DILI onset have been associated with the severity and outcome of liver injury in DILI patients. In addition to cessation of the suspect drug, other medical interventions including the use of N‐acetylcysteine and corticosteroids in selected patients have shown some clinical benefit, but additional prospective studies are needed. A number of promising diagnostic, prognostic and mechanistic serum and genetic biomarkers may help improve our understanding of the pathogenesis and treatment of idiosyncratic DILI.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147192/1/liv13931.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147192/2/liv13931_am.pd

Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile

BACKGROUND: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. METHODS: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK-Biobank. The Lifelines, and The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. RESULTS: In the UK-Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. CONCLUSIONS: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans

Adaptive and plastic responses of Quercus petraea populations to climate across Europe

How temperate forests will respond to climate change is uncertain; projections range from severe decline to increased growth. We conducted field tests of sessile oak (Quercus petraea), a widespread keystone European forest tree species, including more than 150,000 trees sourced from 116 geographically diverse populations. The tests were planted on 23 field sites in six European countries, in order to expose them to a wide range of climates, including sites reflecting future warmer and drier climates. By assessing tree height and survival, our objectives were twofold: (1) to identify the source of differential population responses to climate (genetic differentiation due to past divergent climatic selection versus plastic responses to ongoing climate change), (2) to explore which climatic variables (temperature or precipitation) trigger the population responses. Tree growth and survival were modeled for contemporary climate and then projected using data from four regional climate models for years 2071-2100, using two greenhouse gas concentration trajectory scenarios each. Overall results indicated a moderate response of tree height and survival to climate variation, with changes in dryness (either annual or during the growing season) explaining the major part of the response. Whilst, on average, populations exhibited local adaptation, there was significant clinal population differentiation for height growth with winter temperature at the site of origin. The most moderate climate model (HIRHAM5-EC; rcp4.5) predicted minor decreases in height and survival, whilst the most extreme model (CCLM4-GEM2-ES; rcp8.5) predicted large decreases in survival and growth for southern and southeastern edge populations. Other non-marginal populations with continental climates were predicted to be severely and negatively affected, while populations at the contemporary northern limit (colder and humid maritime regions) will probably not show large changes in growth and survival in response to climate change

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.Methods and results Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 +/- 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P &lt;0.001).Conclusion Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).</p

'It's Just More Acceptable to Be White or Mixed Race and Gay Than Black and Gay': The Perceptions and Experiences of Homophobia in St. Lucia

Lesbian, gay and bisexual (LGB) individuals come from diverse cultural groups with differing ethnic and racial identities. However, most research on LGB people uses white western samples and studies of Afro-Caribbean diaspora often use Jamaican samples. Thus, the complexity of Afro-Caribbean LGB peoples’ experiences of homophobia is largely unknown. The authors’ analyses explore experiences of homophobia among LGB people in St. Lucia. Findings indicate issues of skin-shade orientated tolerance, regionalized disparities in levels of tolerance towards LGB people and regionalized passing (regionalized sexual identity shifting). Finally, the authors’ findings indicate that skin shade identities and regional location influence the psychological health outcomes of homophobia experienced by LGB people in St. Lucia

Platelet-Activating Factor Induces TLR4 Expression in Intestinal Epithelial Cells: Implication for the Pathogenesis of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in neonatal intensive care units, however its pathogenesis is not completely understood. We have previously shown that platelet activating factor (PAF), bacteria and TLR4 are all important factors in the development of NEC. Given that Toll-like receptors (TLRs) are expressed at low levels in enterocytes of the mature gastrointestinal tract, but were shown to be aberrantly over-expressed in enterocytes in experimental NEC, we examined the regulation of TLR4 expression and signaling by PAF in intestinal epithelial cells using human and mouse in vitro cell lines, and the ex vivo rat intestinal loop model. In intestinal epithelial cell (IEC) lines, PAF stimulation yielded upregulation of both TLR4 mRNA and protein expression and led to increased IL-8 secretion following stimulation with LPS (in an otherwise LPS minimally responsive cell line). PAF stimulation resulted in increased human TLR4 promoter activation in a dose dependent manner. Western blotting and immunohistochemical analysis showed PAF induced STAT3 phosphorylation and nuclear translocation in IEC, and PAF-induced TLR4 expression was inhibited by STAT3 and NFκB Inhibitors. Our findings provide evidence for a mechanism by which PAF augments inflammation in the intestinal epithelium through abnormal TLR4 upregulation, thereby contributing to the intestinal injury of NEC

Probing the nature of black holes: Deep in the mHz gravitational-wave sky

Black holes are unique among astrophysical sources: they are the simplest macroscopic objects in the Universe, and they are extraordinary in terms of their ability to convert energy into electromagnetic and gravitational radiation. Our capacity to probe their nature is limited by the sensitivity of our detectors. The LIGO/Virgo interferometers are the gravitational-wave equivalent of Galileo’s telescope. The first few detections represent the beginning of a long journey of exploration. At the current pace of technological progress, it is reasonable to expect that the gravitational-wave detectors available in the 2035-2050s will be formidable tools to explore these fascinating objects in the cosmos, and space-based detectors with peak sensitivities in the mHz band represent one class of such tools. These detectors have a staggering discovery potential, and they will address fundamental open questions in physics and astronomy. Are astrophysical black holes adequately described by general relativity? Do we have empirical evidence for event horizons? Can black holes provide a glimpse into quantum gravity, or reveal a classical breakdown of Einstein’s gravity? How and when did black holes form, and how do they grow? Are there new long-range interactions or fields in our Universe, potentially related to dark matter and dark energy or a more fundamental description of gravitation? Precision tests of black hole spacetimes with mHz-band gravitational-wave detectors will probe general relativity and fundamental physics in previously inaccessible regimes, and allow us to address some of these fundamental issues in our current understanding of nature