Agence Nationale De La Recherche Research Articles

Humoral signatures of Caspr2-antibody spectrum disorder track with clinical phenotypes and outcomes.

Immunoglobulin (Ig) G4 auto-antibodies (Abs) against contactin-associated protein-like 2 (Caspr2), a transmembrane cell adhesion protein expressed in the central and peripheral nervous system, are found in patients with a broad spectrum of neurological symptoms. While the adoptive transfer of Caspr2-specific IgG induces brain pathology in susceptible rodents, the mechanisms by which Caspr2-Abs mediate neuronal dysfunction and translate into clinical syndromes are incompletely understood. We use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral biosignatures in patients with Caspr2-Ab-associated neurological syndromes. We identify two signatures strongly associated with two major clinical phenotypes, limbic encephalitis (LE) and predominant peripheral nerve hyperexcitability without LE (non-LE). Caspr2-IgG Fc-driven pro-inflammatory features, characterized by increased binding affinities for activating Fcγ receptors (FcγRs) and C1q, along with a higher prevalence of IgG1-class Abs, in addition to IgG4, are strongly associated with LE. Both the occurrence of Caspr2-specific IgG1 and higher serum levels of interleukin (IL)-6 and IL-15, along with increased concentrations of biomarkers reflecting neuronal damage and glial cell activation, are associated with poorer clinical outcomes at 1-year follow-up. The presence of IgG1 isotypes and Fc-mediated effector functions control the pathogenicity of Caspr2-specific Abs to induce LE. Biologics targeting FcR function might potentially restrain Caspr2-Ab-induced pathology and improve clinical outcomes. This study was funded by a German-French joint research program supported by the German Research Foundation (DFG) and the Agence Nationale de la Recherche (ANR) and by the Interdisciplinary Centre for Clinical Research (IZKF) Münster.

Value-Positivity for Matrix Games

Matrix games are the most basic model in game theory, and yet robustness with respect to small perturbations of the matrix entries is not fully understood. In this paper, we introduce value positivity and uniform value positivity, two properties that refine the notion of optimality in the context of polynomially perturbed matrix games. The first concept captures how the value depends on the perturbation parameter, and the second consists of the existence of a fixed strategy that guarantees the value of the unperturbed matrix game for every sufficiently small positive parameter. We provide polynomial-time algorithms to check whether a polynomially perturbed matrix game satisfies these properties. We further provide the functional form for a parameterized optimal strategy and the value function. Finally, we translate our results to linear programming and stochastic games, where value positivity is related to the existence of robust solutions. Funding: This research was supported by Fondation CFM pour la Recherche, the H2020 European Research Council [Grant ERC-CoG-863818 (ForM-SMArt)], the Austrian Science Fund [Grant 10.55776/COE12], ANID Chile [Grant ACT210005], and Agence Nationale de la Recherche [Grant ANR-21-CE40-0020].

Correlated Equilibria in Large Anonymous Bayesian Games

We consider multipopulation Bayesian games with a large number of players. Each player aims at minimizing a cost function that depends on this player’s own action, the distribution of players’ actions in all populations, and an unknown state parameter. We study the nonatomic limit versions of these games and introduce the concept of Bayes correlated Wardrop equilibrium, which extends the concept of Bayes correlated equilibrium to nonatomic games. We prove that Bayes correlated Wardrop equilibria are limits of action flows induced by Bayes correlated equilibria of the game with a large finite set of small players. For nonatomic games with complete information admitting a convex potential, we prove that the set of correlated and of coarse correlated Wardrop equilibria coincide with the set of probability distributions over Wardrop equilibria and that all equilibrium outcomes have the same costs. We get the following consequences. First, all flow distributions of (coarse) correlated equilibria in convex potential games with finitely many players converge to mixtures of Wardrop equilibria when the weight of each player tends to zero. Second, for any sequence of flows satisfying a no-regret property, its empirical distribution converges to the set of distributions over Wardrop equilibria, and the average cost converges to the unique Wardrop cost. Funding: This work was partially supported by European Cooperation in Science and Technology Action 16228 GAMENET. F. Koessler acknowledges the support of the Agence Nationale de la Recherche [Grant StratCom ANR-19-CE26-0010-01]. M. Scarsini acknowledges the support of the Gruppo Nazionale per l’Analisi Matematica, la Probabilità e le loro Applicazioni project [Grant CUP_E53C22001930001], the Ministero dell’Università e della Ricerca Progetti di Rilevante Interesse Nazionale [Grant 2022EKNE5K], and the European Union-Next Generation EU, component M4C2, investment 1.1 (Ministero dell’Università e della Ricerca Progetti di Rilevante Interesse Nazionale Piano Nazionale di Ripresa e Resilienza) [Grant P2022XT8C8]. T. Tomala gratefully acknowledges the support of the HEC foundation and Agence Nationale de la Recherche/Investissements d’Avenir [Grant ANR-11-IDEX-0003/Labex Ecodec/ANR-11-LABX-0047].

Diagnostic and prognostic biomarkers in immune checkpoint inhibitor-related encephalitis: a retrospective cohort study

Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors. This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015-2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade<3at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. Neurofilament light chain (NfL) was measured by enzyme-linked immunosorbent assay. Sixty-seven patients with definite encephalitis were identified (median age, 69 years; 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), while 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24 patients, 92%) and pleocytosis (24/24 patients, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62% versus 8/24, 33%, p=0.025), PNS-related antibodies (36/43, 84% versus 1/24, 4%, p<0.001), and neuroendocrine cancers (22/43, 51% versus 1/24, 4%; p<0.001) than patients with meningoencephalitis. Focal encephalitis patients had a lower rate of irAE treatment response (7/39, 18%) and higher mortality (27/43, 63%) compared to meningoencephalitis patients (12/22, 77% and 5/24, 21%, respectively, p<0.001 each). PNS-related antibodies were associated with less irAE treatment response, independently of age, sex, and baseline severity (adjusted OR 0.05; 95%CI [0.01; 0.19]; p<0.001) as well as higher mortality, independently of age and cancer type (adjusted HR 5.07; 95% CI [2.12; 12.12]; p<0.001). Serum NfL discriminated patients with definite ICI-encephalitis (n=27) from cancer-matched controls (n=16; optimal cut-off >273.5pg/mL, sensitivity 81%, specificity 88%, AUC 0.87, 95% CI [0.76; 0.98]) and irAE treatment responders (n=10) from non-responders (n=17, optimal cut-off >645pg/mL, sensitivity 90%, specificity 65%; AUC 0.75, 95% CI [0.55; 0.94]). ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations. Agence Nationale de la Recherche.

Ex vivo susceptibility to antimalarial drugs and polymorphisms in drug resistance genes of African Plasmodium falciparum, 2016-2023: a genotype-phenotype association study.

Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount. We measured the susceptibility to six antimalarials using ex vivo growth inhibition assays (IC50) for a total of 805 Plasmodium falciparum isolates obtained from travelers returning to France (2016-2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting fourteen drug resistance genes across the parasite genome. Ex vivo susceptibility to several drugs has significantly decreased in 2019-2023 versus 2016-2018 parasite samples: lumefantrine (median IC50: 23·0 nM [IQR: 14·4-35·1] in 2019-2023 versus 13·9 nM [8·42-21·7] in 2016-2018, p<0·0001), monodesethylamodiaquine (35·4 [21·2-51·1] versus 20·3 nM [15·4-33·1], p<0·0001), and marginally piperaquine (20·5 [16·5-26·2] versus 18.0 [14·2-22·4] nM, p<0·0001). Only four isolates carried a validated pfkelch13 mutation. Multiple mutations in pfcrt and one in pfmdr1 (N86Y) were significantly associated with altered susceptibility to multiple drugs. The susceptibility to lumefantrine was altered by pfcrt and pfmdr1 mutations in an additive manner, with the wild-type haplotype (pfcrt K76-pfmdr1 N86) exhibiting the least susceptibility. Our study on P. falciparum isolates from West and Central Africa indicates a low prevalence of molecular markers of artemisinin resistance but a significant decrease in susceptibility to the partner drugs that have been the most widely used since a decade -lumefantrine and amodiaquine. These phenotypic changes likely mark parasite adaptation to sustained drug pressure and call for intensifying the monitoring of antimalarial drug resistance in Africa. This work was supported by the French Ministry of Health (grant to the French National Malaria Reference Center) and by the Agence Nationale de la Recherche (ANR-17-CE15-0013-03 to JC). JAB was supported by NIH R01AI139520. JR postdoctoral fellowship was funded by Institut de Recherche pour le Développement.

On the Convex Formulations of Robust Markov Decision Processes

Robust Markov decision processes (MDPs) are used for applications of dynamic optimization in uncertain environments and have been studied extensively. Many of the main properties and algorithms of MDPs, such as value iteration and policy iteration, extend directly to RMDPs. Surprisingly, there is no known analog of the MDP convex optimization formulation for solving RMDPs. This work describes the first convex optimization formulation of RMDPs under the classical sa-rectangularity and s-rectangularity assumptions. By using entropic regularization and exponential change of variables, we derive a convex formulation with a number of variables and constraints polynomial in the number of states and actions, but with large coefficients in the constraints. We further simplify the formulation for RMDPs with polyhedral, ellipsoidal, or entropy-based uncertainty sets, showing that, in these cases, RMDPs can be reformulated as conic programs based on exponential cones, quadratic cones, and nonnegative orthants. Our work opens a new research direction for RMDPs and can serve as a first step toward obtaining a tractable convex formulation of RMDPs. Funding: The work in the paper was supported, in part, by NSF [Grants 2144601 and 1815275]; and Agence Nationale de la Recherche [Grant 11-LABX-0047].

Aversion to Hiring Algorithms: Transparency, Gender Profiling, and Self-Confidence

We run an online experiment to study the origins of algorithm aversion. Participants are in the role of either workers or managers. Workers perform three real-effort tasks: task 1, task 2, and the job task, which is a combination of tasks 1 and 2. They choose whether the hiring decision between themselves and another worker is made by a participant in the role of a manager or by an algorithm. In a second set of experiments, managers choose whether they want to delegate their hiring decisions to the algorithm. When the algorithm does not use workers’ gender to predict their job-task performance and workers know this, they choose the algorithm more often than in the baseline treatment where gender is employed. Feedback to the managers about their performance in hiring the best workers increases their preference for the algorithm relative to the baseline without feedback, because managers are, on average, overconfident. Finally, providing details on how the algorithm works does not increase the preference for the algorithm for workers or for managers. This paper was accepted by Elena Katok, special issue on the human-algorithm connection. Funding: D. Kübler acknowledges financial support from the Deutsche Forschungsgemeinschaft [CRC TRR 190], R. Hakimov acknowledges financial support from the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [Project 100018_189152], and M.-P. Dargnies acknowledges financial support from the Agence Nationale de la Recherche (ANR JCJC TrustSciTruths). Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.02774 .

Human-Robot Interactions in Investment Decisions

We study the introduction of robo-advising on a large set of employee saving plans. Different from many services that fully automate portfolio decisions, our robo-advisor proposes investment and rebalancing strategies, leaving investors free to follow or ignore them. The resulting human-robot interactions occur both at the time of the subscription and over time, as the robot sends alerts when the investor’s portfolio gets too far from the target allocation. We show that the robo-service is associated with an increase in investors’ attention and trading activities. Following the robot’s alerts, investors change their rebalancing behaviors so as to stay closer to their target allocation, which results in larger portfolio returns. Counterfactual returns induced by automatic rebalancing by the robot would be only slightly higher, suggesting that, on average, the financial cost of letting investors retain control is not large. This paper was accepted by Jean-Edouard Colliard, special issue on the human-algorithm connection. Funding: This work was supported by Observatoire epargne europeenne, as well as LTI@Unito and Agence Nationale de la Recherche [Grant ANR-17-EURE-0010] to M. Bianchi. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.03886 .

Consumption of Values

Consumption decisions are partly influenced by values and ideologies. Consumers care about global warming, child labor, fair trade, etc. We develop an axiomatic model of intrinsic values—those that are carriers of meaning in and of themselves—and argue that they often introduce discontinuities near zero. For example, a vegetarian’s preferences would be discontinuous near zero amount of animal meat. We distinguish intrinsic values from instrumental ones, which are means rather than ends and serve as proxies for intrinsic values. We illustrate the relevance of our value-based model in different contexts, including equity concerns and prosocial behavior. This paper was accepted by Manel Baucells, behavioral economics and decision analysis. Funding: The authors acknowledge support from the Agence Nationale de la Recherche [Grants ANR-11-IDEX-0003 and 11-LABX-0047], the Israel Science Foundation [Grant 1443/20], the AXA Research Fund [Chair for Decision Sciences], the Foerder Institute at Tel-Aviv University, and the Sapir Center for Economic Development (Gilboa). Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2023.01632 .

The Best Decisions Are Not the Best Advice: Making Adherence-Aware Recommendations

Many high-stake decisions follow an expert-in-loop structure in that a human operator receives recommendations from an algorithm but is the ultimate decision maker. Hence, the algorithm’s recommendation may differ from the actual decision implemented in practice. However, most algorithmic recommendations are obtained by solving an optimization problem that assumes recommendations will be perfectly implemented. We propose an adherence-aware optimization framework to capture the dichotomy between the recommended and the implemented policy and analyze the impact of partial adherence on the optimal recommendation. Our framework provides useful tools to analyze the structure and to compute optimal recommendation policies that are naturally immune against such human deviations and are guaranteed to improve upon the baseline policy. This paper was accepted by Nicolas Stier-Moses, special issue on the human-algorithm connection. Funding: J. Grand-Clément was supported by the Agence Nationale de la Recherche [Grant 11-LABX-0047] and Hi! Paris. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.01851 .

Plasmodium ovale spp dhfr mutations associated with reduced susceptibility to pyrimethamine in sub-Saharan Africa: a retrospective genetic epidemiology and functional study

Mutations in the Plasmodium falciparum dhfr gene confer resistance to pyrimethamine, which is widely used for malaria chemoprevention in Africa. We aimed to evaluate the frequency and evolution of dhfr mutations in Plasmodium ovale spp in Africa and their functional consequences, which are incompletely characterised. We analysed dhfr mutations and their frequencies in P ovale spp isolates collected between Feb 1, 2004, and Aug31, 2023, from the French National Malaria Reference Centre collection and from field studies in Benin, Gabon, and Kenya. Genetic patterns of positive selection were investigated. Full-length recombinant wild-type and mutant DHFR enzymes from both P ovale curtisi and P ovale wallikeri were expressed in bacteria to test whether the most common mutations reduced pyrimethamine susceptibility. We included 518 P ovale spp samples (314 P ovale curtisi and 204 P ovale wallikeri). In P ovale curtisi, Ala15Ser-Ser58Arg was the most common dhfr mutation (39%; 124 of 314 samples). In P ovale wallikeri, dhfr mutations were less frequent, with Phe57Leu-Ser58Arg reaching 17% (34 of 204 samples). These two mutants were the most prevalent in central and east Africa and were fixed in Kenyan isolates. We detected six and four other non-synonymous mutations, representing 8% (24 isolates) and 2% (five isolates) of the P ovale curtisi and Povale wallikeri isolates, respectively. Whole-genome sequencing and microsatellite analyses revealed reduced genetic diversity around themutant pocdhfr and powdhfr genes. The mutant DHFR proteins showed structural changes at the pyrimethamine binding site in-silico, confirmed by a 4-times increase in pyrimethamine half-maximal inhibitory concentration in an Escherichia coli growth assay for the Phe57Leu-Ser58Arg mutant and 50-times increase for the Ala15Ser-Ser58Arg mutant, compared with the wild-type counterparts. The widespread use of sulfadoxine-pyrimethamine for malaria chemoprevention might have exerted fortuitous selection pressure for dhfr mutations in P ovale spp. This calls for closer monitoring of dhfr and dhps mutations in P ovale spp. French Ministry of Health, Agence Nationale de la Recherche, and Global Emerging Infections Surveillance branch of the Armed Forces Health Surveillance Division.

Data-Driven Mergers

We study mergers between firms operating in data-connected markets: the data generated as a byproduct of the activity in market A can be used by firms operating in market B. The effects of such a merger depend on whether data trade among independent firms is possible and whether data use benefits consumers or leads to more surplus extraction. When data increases product B’s quality, the merger benefits consumers in both markets if data cannot be traded absent the merger and harms them otherwise. When data are used to extract consumer surplus in market B, the merger increases consumer surplus in market A and reduces it in market B. This paper was accepted by Joshua Gans, business strategy. Funding: This work was supported by Agence Nationale de la Recherche [Grant ANR-17-EURE-0010] (Investissements d’Avenir program) to A. de Cornière; Oxford Internet Institute’s Research Programme on AI, Government, and Policy, funded by the Dieter Schwarz Stiftung gGmbH to G. Taylor; and TSE Digital Center.

Are People Willing to Pay for Reduced Inequality?

Would consumers be willing to pay more for goods for which there is less inequality in wages across those involved in their production? In incentive-compatible behavioral choice studies on representative samples of the English and U.S. populations, we find significantly positive willingness to pay for such inequality reductions in more than 80% of subjects. Although it varies with political leaning and the extent of the inequality reduction, willingness to pay is positive across the political spectrum and for all studied inequality differences. It is higher for more intuitive and informative inequality-reporting formats. Our findings have policy implications for both governments and firms. On the one hand, they suggest the promise of universal provision of product-level inequality information as a tool for moderating income inequality. On the other hand, they highlight the potential relevance of inequality reporting for firms’ marketing strategies. This paper was accepted by Dorothea Kübler, behavioral economics and decision analysis. Funding: This work was supported by the Agence Nationale de la Recherche [LabEx Ecodec/ANR-11-LABX-0047] and the Fondation HEC [Budget F]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.01974 .

Marginal Values of a Stochastic Game

Zero-sum stochastic games are parameterized by payoffs, transitions, and possibly a discount rate. In this article, we study how the main solution concepts, the discounted and undiscounted values, vary when these parameters are perturbed. We focus on the marginal values, introduced by Mills in 1956 in the context of matrix games—that is, the directional derivatives of the value along any fixed perturbation. We provide a formula for the marginal values of a discounted stochastic game. Further, under mild assumptions on the perturbation, we provide a formula for their limit as the discount rate vanishes and for the marginal values of an undiscounted stochastic game. We also show, via an example, that the two latter differ in general. Funding: This work was supported by Fondation CFM pour la Recherche; the European Research Council [Grant ERC-CoG-863818 (ForM-SMArt)]; and Agence Nationale de la Recherche [Grant ANR-21-CE40-0020].

Multiomic analysis in fibroblasts of patients with inborn errors of cobalamin metabolism reveals concordance with clinical and metabolic variability

The high variability in clinical and metabolic presentations of inborn errors of cobalamin (cbl) metabolism (IECM), such as the cblC/epicblC types with combined deficits in methylmalonyl-coA mutase (MUT) and methionine synthase (MS), are not well understood. They could be explained by the impaired expression/activity of enzymes from other metabolic pathways. We performed metabolomic, genomic, proteomic, and post-translational modification (PTM) analyses in fibroblasts from three cblC cases and one epi-cblC case compared with three cblG cases with specific MS deficits and control fibroblasts. CblC patients had metabolic profilings consistent with altered urea cycle, glycine, and energy mitochondrial metabolism. Metabolomic analysis showed partial disruption and increased glutamate/ketoglutarate anaplerotic pathway of the tricarboxylic acid cycle (TCA), in patient fibroblasts. RNA-seq analysis showed decreased expression of MT-TT (mitochondrial tRNA threonine), MT-TP (mitochondrial tRNA proline), OXCT1 (succinyl CoA:3-oxoacid CoA transferase deficiency), and MT-CO1 (cytochrome C oxidase subunit 1). Proteomic changes were observed for key mitochondrial enzymes, including NADH:ubiquinone oxidoreductase subunit A8 (NDUFA8), carnitine palmitoyltransferase 2 (CPT2), and ubiquinol-cytochrome C reductase, complex III subunit X (UQCR10). Propionaldehyde addition in ornithine aminotransferase was the predominant PTM in cblC cells and could be related with the dramatic cellular increase in propionate and methylglyoxalate. It is consistent with the decreased concentration of ornithine reported in 3 cblC cases. Whether the changes detected after multi-omic analyses underlies clinical features in cblC and cblG types of IECM, such as peripheral and central neuropathy, cardiomyopathy, pulmonary hypertension, development delay, remains to be investigated. The omics-related effects of IECM on other enzymes and metabolic pathways are consistent with the diversity and variability of their age-related metabolic and clinical manifestations. PTMs are expected to produce cumulative effects, which could explain the influence of age on neurological manifestations. French Agence Nationale de la Recherche (Projects PREDICTS and EpiGONE) and Inserm.

The Iterates of the Frank–Wolfe Algorithm May Not Converge

The Frank–Wolfe algorithm is a popular method for minimizing a smooth convex function f over a compact convex set [Formula: see text]. Whereas many convergence results have been derived in terms of function values, almost nothing is known about the convergence behavior of the sequence of iterates [Formula: see text]. Under the usual assumptions, we design several counterexamples to the convergence of [Formula: see text], where f is d-time continuously differentiable, [Formula: see text], and [Formula: see text]. Our counterexamples cover the cases of open-loop, closed-loop, and line-search step-size strategies and work for any choice of the linear minimization oracle, thus demonstrating the fundamental pathologies in the convergence behavior of [Formula: see text]. Funding: The authors acknowledge the support of the AI Interdisciplinary Institute ANITI funding through the French “Investments for the Future – PIA3” program under the Agence Nationale de la Recherche (ANR) agreement [Grant ANR-19-PI3A0004], the Air Force Office of Scientific Research, Air Force Material Command, U.S. Air Force [Grants FA866-22-1-7012 and ANR MaSDOL 19-CE23-0017-0], ANR Chess [Grant ANR-17-EURE-0010], ANR Regulia, and Centre Lagrange.

Linear Program-Based Policies for Restless Bandits: Necessary and Sufficient Conditions for (Exponentially Fast) Asymptotic Optimality

We provide a framework to analyze control policies for the restless Markovian bandit model under both finite and infinite time horizons. We show that when the population of arms goes to infinity, the value of the optimal control policy converges to the solution of a linear program (LP). We provide necessary and sufficient conditions for a generic control policy to be (i) asymptotically optimal, (ii) asymptotically optimal with square root convergence rate, and (iii) asymptotically optimal with exponential rate. We then construct the LP-index policy that is asymptotically optimal with square root convergence rate on all models and with exponential rate if the model is nondegenerate in finite horizon and satisfies a uniform global attractor property in infinite horizon. We next define the LP-update policy, which is essentially a repeated LP-index policy that solves a new LP at each decision epoch. We conclude by providing numerical experiments to compare the efficiency of different LP-based policies. Funding: This work was supported by Agence Nationale de la Recherche [Grant ANR-19-CE23-0015].

An Experiment on Gender Representation in Majoritarian Bargaining

Women are underrepresented in business, academic, and political decision-making bodies across the world. To investigate the causal effect of gender representation on multilateral negotiations, we experimentally manipulate the composition of triads in a majoritarian, divide-the-dollar game. We document a robust gender gap in earnings driven largely by the exclusion of women from alliances rather than differential shares within alliances. Experiments with different subject pools show that distinct bargaining dynamics can underlie the same inequitable outcomes; gender-biased outcomes can be caused by outright discrimination, but they can also be driven by more complex dynamics related to differences in bargaining strategies. Although replacing the male with a female majority all but eliminates the gap in one pool, it has minimal effect in the other. These findings show that there is no “one-size-fits-all” solution to the gender gap we uncovered and highlight the importance of studying bargaining dynamics in detail. This paper was accepted by Marie-Claire Villeval, behavioral economics and decision analysis. Funding: A. Baranski recognizes financial support from Tamkeen [under the New York University Abu Dhabi Research Institute; Grant CG005]. J. Tremewan acknowledges funding from the Agence Nationale de la Recherche [Grant ANR-21-CE03-0018 (Project ENDURA)]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.01800 .

Mouse models of diabetes-related ulcers: a systematic review and network meta-analysis

Diabetic foot ulcers (DFUs) are a common complication of diabetes, associated with important morbidity. Appropriate animal models of DFUs may improve drug development, and subsequently the success rate of clinical trials. However, while many models have been proposed, they are extremely heterogeneous, and no standard has emerged. We thus propose a systematic review with a network meta-analysis (NMA) to gather direct and indirect evidence, and compare the different mouse models of diabetes-related ulcers. The systematic search was performed in Pubmed and Embase. The main outcomes were wound size measurement at days 3, 7, 11 and 15 (±1 day). The risk of bias and methodological quality of all included studies was assessed by using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool. Meta-regressions were done on prespecified variables, including mouse strain, type of ulcer, sex, age, and use of a splint. We included 295 studies. Among all models, only db/db, ob/ob, streptozotocin (STZ), and STZ+high fat diet mice showed a significantly delayed wound healing, compared with controls, at each time point. Age, sex and ulcer type had influence on wound healing, although not at all time points. In conclusion, the db/db model is associated with the largest delay in wound healing The STZ model also exhibits significantly decreased wound healing. STZ+high fat diet and ob/ob mice may also be relevant models of diabetes-related ulcers, although the results rely on a more limited number of studies. This work was funded by the Agence Nationale de la Recherche (grant ANR-18-CE17-0017).

The burden of very early dropout in infertility care: a nationwide population-based cohort study.

What is the frequency and the associated factors of very early dropout following unsuccessful clomiphene citrate (CC)/gonadotropin treatment in the context of full coverage of treatment cost. Despite free treatment, almost one in four women had a very early dropout following unsuccessful CC/gonadotropin treatment, with patients below the poverty line being more likely to drop out early. Success of infertility care is tarnished by very high dropout rates. Infertility care dropout has been considered as resulting principally from financial barriers because of the high cost of treatment. Nearly all previous work addressed dropout following IVF/ICSI. Factors associated with dropout following CC/gonadotropins may be different and also need to be investigated. Nationwide population-based cohort study. Using the French national health insurance and hospital databases, we included in the cohort 27 416 women aged 18-49 years unsuccessfully treated with CC/gonadotropins in 2017. The main outcome was very early dropout, defined as discontinuation of all infertility treatment after unsuccessful treatment for 1-3 months. Very early treatment dropout was analysed by multivariate logistic regression. Among women unsuccessfully treated with CC/gonadotropins, 22% dropped out of infertility care within 3 months. In multivariate analysis, higher early dropout following unsuccessful CC/gonadotropin treatment was associated with older and younger ages (≥35 and <25 years), being below the poverty line, being treated with CC prescribed by a general practitioner and lack of infertility tests or monitoring. This study is based on health administrative data that do not include reasons for dropout and record only a limited amount of information. It is thus not possible to analyse the reason for early dropout. Despite full coverage of all infertility treatment, women under the poverty line have a higher risk of very early dropout following unsuccessful CC/gonadotropin treatment. Better understanding is needed of the non-financial barriers and difficulties faced by these patients. To address disparities in infertility treatment, practitioner training could be reinforced to adapt to patients from different social and cultural backgrounds. This work was supported by the ANR StimHo project, grant ANR-17-CE36-0011-01 from the French Agence Nationale de la Recherche. The authors have no conflict of interest to declare. N/A.