Bone Marrow Transplant

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy

Metacognitive ability predicts learning cue-stimulus associations in the absence of external feedback

Abstract Learning how certain cues in our environment predict specific states of nature is an essential ability for survival. However learning typically requires external feedback, which is not always available in everyday life. One potential substitute for external feedback could be to use the confidence we have in our decisions. Under this hypothesis, if no external feedback is available, then the agents’ ability to learn about predictive cues should increase with the quality of their confidence judgments (i.e. metacognitive efficiency). We tested and confirmed this novel prediction in an experimental study using a perceptual decision task. We evaluated in separate sessions the metacognitive abilities of participants (N = 65) and their abilities to learn about predictive cues. As predicted, participants with greater metacognitive abilities learned more about the cues. Knowledge of the cues improved accuracy in the perceptual task. Our results provide strong evidence that confidence plays an active role in improving learning and performance

How Overconfidence Bias Influences Suboptimality in Perceptual Decision Making

International audienceIn perceptual decision making, it is often found that human observers combine sensory information and prior knowledge suboptimally. Typically, in detection tasks, when an alternative is a priori more likely to occur, observers choose it more frequently to account for the unequal base rate but not to the extent they should, a phenomenon referred to as “conservative decision bias” (i.e., observers do not shift their decision criterion enough). One theoretical explanation of this phenomenon is that observers are overconfident in their ability to interpret sensory information, resulting in overweighting the sensory information relative to prior knowledge. Here, we derived formally this candidate model, and we tested it in a visual discrimination task in which we manipulated the prior probabilities of occurrence of the stimuli. We measured confidence in decisions and decision criterion placement in two separate experimental sessions for the same participants (N = 69). Both overconfidence bias and conservative decision bias were found in our data, but critically the link that was predicted between these two quantities was absent. Our data suggested instead that when informed about the a priori probability, overconfident participants put less effort into processing sensory information. These findings offer new perspectives on the role of overconfidence bias to explain suboptimal decisions

How economic success shapes redistribution: The role of self-serving beliefs, in-group bias and justice principles.

International audienceIn the face of economic inequalities, redistribution of wealth is a key debate forsociety, and understanding the reasons why individuals may support moreor less re-distribution can inform this debate. Here we investigate the mechanisms by whichexperiencing success in a task decreases the support for redistribution of the wealthgenerated by the task, such that overachievers favor less redistribution than under-achievers. In a laboratory experiment, we replicate this effect and explore how it thatmay be mediated by an in-group bias, or by changes in individuals’ principlesof redis-tributive justice. Critically, both in-group favoritism and self-serving adjustments ofjustice principles partially accounted for the effect of status on redistribution choices.Our study thus sheds new light on the various ways by which economic experienceaffects support for redistribution

How economic success shapes redistribution

In the face of economic inequalities, redistribution of wealth is a key debate for society, and understanding the reasons why individuals may support more or less redistribution can inform this debate. Here we investigate the mechanisms by which experiencing success in a task decreases the support for redistribution of the wealth generated by the task, such that overachievers favor less redistribution than under-achievers. In a laboratory experiment, we replicate this effect and explore how it that may be mediated by an in-group bias, or by changes in individuals’ principles of redis-tributive justice. Critically, both in-group favoritism and self-serving adjustments of justice principles partially accounted for the effect of status on redistribution choices. Our study thus sheds new light on the various ways by which economic experience affects support for redistribution.</p

Benchmarking analogue models of brittle thrust wedges

We performed a quantitative comparison of brittle thrust wedge experiments to evaluate the variability among analogue models and to appraise the reproducibility and limits of model interpretation. Fifteen analogue modeling laboratories participated in this benchmark initiative. Each laboratory received a shipment of the same type of quartz and corundum sand and all laboratories adhered to a stringent model building protocol and used the same type of foil to cover base and sidewalls of the sandbox. Sieve structure, sifting height, filling rate, and details on off-scraping of excess sand followed prescribed procedures. Our analogue benchmark shows that even for simple plane-strain experiments with prescribed stringent model construction techniques, quantitative model results show variability, most notably for surface slope, thrust spacing and number of forward and backthrusts. One of the sources of the variability in model results is related to slight variations in how sand is deposited in the sandbox. Small changes in sifting height, sifting rate, and scraping will result in slightly heterogeneous material bulk densities, which will affect the mechanical properties of the sand, and will result in lateral and vertical differences in peak and boundary friction angles, as well as cohesion values once the model is constructed. Initial variations in basal friction are inferred to play the most important role in causing model variability. Our comparison shows that the human factor plays a decisive role, and even when one modeler repeats the same experiment, quantitative model results still show variability. Our observations highlight the limits of up-scaling quantitative analogue model results to nature or for making comparisons with numerical models. The frictional behavior of sand is highly sensitive to small variations in material state or experimental set-up, and hence, it will remain difficult to scale quantitative results such as number of thrusts, thrust spacing, and pop-up width from model to nature

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

International audienceIntroduction This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). Methods Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. Results The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. Conclusion This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management

L'eau à découvert

Indispensable à la régulation du climat, au développement de la vie sur Terre, au maintien des écosystèmes, aux populations, au développement de l'agriculture, de l'industrie comme à la production d'énergie, l'eau est un élément vital. Il convient donc, dans un contexte de changement global, d'analyser dans toute sa diversité la place et le rôle de l'eau et de se donner ainsi les moyens de mieux la préserver. Autour de cet enjeu qui engage toute l'humanité, Agathe Euzen, Catherine Jeandel et Rémy Mosseri ont réuni près de cent cinquante contributions, visant à apporter un éclairage sur chacun des domaines et des approches que couvre cette thématique. Quelle est l'origine de l'eau ? Son rapport avec l'apparition de la vie ? Quel rôle a-t-elle joué dans l'histoire de la planète et dans le développement de la vie végétale, animale et humaine ? Quel est son cycle ? Quelles sont ses propriétés chimiques ? Comment les sociétés se sont-elles emparées de cet élément précieux ? Allons-nous manquer d'eau ? L'eau est-elle source de conflits ? Comment l'eau est-elle gérée ? Comment recycle-t-on une eau polluée ? Quels sont les risques pour la santé mondiale ? Quels sont les grands enjeux liés à l'eau au xxie siècle ? Comprendre et proposer des solutions à ces défis majeurs est l'intention de cet ouvrage

Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life

International audienceBackground: Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients' quality of life.Methods: In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed.Results: Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54-4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32-4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97-35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches.Conclusion: Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration