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Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.
(2024) Therriault, Joseph; González Escalante, Armand; Contador, Jose; Puig Pijoan, Albert; Suárez-Calvet, Marc; Rosa-Neto, PedroPolicymaking, trust, and the demand for public services: evidence from a mass sterilization campaign
We study a large-scale family planning intervention in which more than 260,000 Peruvian women were sterilized. Many of these medical procedures are alleged to have been performed without patient consent. The subsequent disclosure of alleged illegal sterilizations caused reductions in the usage of contraceptive methods and prenatal and birth delivery services and, more generally, the demand for medical services in affected areas. As a result, child health worsened. The results persist for at least 17 years after the information disclosure and are driven by disappointed supporters of the implementing government. Learning about the government's malpractices undermined trust in institutions.
(2025) León-Ciliotta, Gianmarco; Zejcirovic, Dijana; Fernández Bazán, FernandoTributação da economia insustentável: o caso das entregas ao domicílio de produtos adquiridos online
As entregas ao domicílio de produtos adquiridos online é uma realidade crescente na sociedade atual. Estes novos modelos de negócio implicam o aumento das emissões de CO2 decorrentes da entrega porta-a-porta de bens ao consumidor e a sobrecarga das infraestruturas urbanas derivada do incremento nos fluxos de trânsito e das necessidades de estacionamento para cargas e descargas. No presente trabalho analisa-se uma forma particular de tributação da economia insustentável. Trata-se de uma taxa implementada na cidade de Barcelona que incide sobre o aproveitamento especial do domínio público para atividades de carga e descarga de bens para posterior distribuição aos consumidores que os adquiriram através de comércio eletrónico.
(2024) Mendonça, Maria Júlia Ildefonso; González-Juliana, ÁlvaroThe ventrolateral pallial (VLp) excitatory neurons in the claustro-amygdalar complex and piriform cortex (PIR; which forms part of the palaeocortex) form reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that results in adaptive behaviours. Early-life disruptions in these circuits are linked to neuropsychiatric disorders, highlighting the importance of understanding their development. Here we reveal that the transcription factors SOX4, SOX11 and TFAP2D have a pivotal role in the development, identity and PFC connectivity of these excitatory neurons. The absence of SOX4 and SOX11 in post-mitotic excitatory neurons results in a marked reduction in the size of the basolateral amygdala complex (BLC), claustrum (CLA) and PIR. These transcription factors control BLC formation through direct regulation of Tfap2d expression. Cross-species analyses, including in humans, identified conserved Tfap2d expression in developing excitatory neurons of BLC, CLA, PIR and the associated transitional areas of the frontal, insular and temporal cortex. Although the loss and haploinsufficiency of Tfap2d yield similar alterations in learned threat-response behaviours, differences emerge in the phenotypes at different Tfap2d dosages, particularly in terms of changes observed in BLC size and BLC-PFC connectivity. This underscores the importance of Tfap2d dosage in orchestrating developmental shifts in BLC-PFC connectivity and behavioural modifications that resemble symptoms of neuropsychiatric disorders. Together, these findings reveal key elements of a conserved gene regulatory network that shapes the development and function of crucial VLp excitatory neurons and their PFC connectivity and offer insights into their evolution and alterations in neuropsychiatric disorders.
(2025) Kaur, Navjot; Martin, Xabier de; Santpere Baró, Gabriel, 1981-; Sestan, NenadWe study promotion incentives in the public sector. In collaboration with Sierra Leone's Ministry of Health, we introduce exogenous variation in the meritocratic nature of promotions from health worker to supervisor positions and in health workers' perceptions of pay progression upon promotion. Ten months later, our findings reveal that meritocracy leads to a 22 percent increase in health workers' productivity. Greater perceived pay progression in a meritocratic system boosts productivity by 23 percent, whereas in a less meritocratic system, it decreases productivity by 27 percent. We show that this reduction is consistent with a negative morale effect.
(2025) Deserranno, Erika; Kastrau, Philipp; León-Ciliotta, Gianmarco