New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Direkte Demokratie, Steuermoral und Steuerhinterziehung: Erfahrungen aus der Schweiz

First it is clarified what„trust”and„tax morale”actually mean and how they are measured. Especially in German-speaking countries, tax morale is often mixed with tax compliance. But the first is a moral conviction while the second denotes actual behaviour, and both do not necessarily need to be congruent. Then it is shown how direct popular rights empower Swiss citizens to influence their tax burden. Finally, we discuss the impact of direct popular rights on tax morale and on tax compliance as well as the impact of the trust between citizens and tax authorities on the latter. It is shown that direct democracy leads to higher tax morale and compliance, even if tax morale is today rather low in Switzerland compared to other countries. Copyright 2007 die Autoren Journal compilation 2007, Verein für Socialpolitik und Blackwell Publishing Ltd.

Uso de indicadores da qualidade para avaliação de prestadores de serviços públicos de odontologia: um estudo de caso

Qualidade é um tema muito discutido, tendo em conta a grande concorrência, a necessidade de conter custos e a maior exigência dos clientes. Exigência esta que se estende a todos os tipos de serviços, inclusive os serviços de saúde. No entanto, não basta apenas dizer que se presta um atendimento de qualidade; é preciso avaliá-la e esta avaliação pode ser realizada pelo uso dos Indicadores da Qualidade, que em saúde são categorizados em três grupos: Estrutura, Processo e Resultado. Desta forma, este trabalho se propôs avaliar um serviço público de odontologia com a utilização de um Indicador da Qualidade de cada categoria. Sendo "horas de treinamento ou cursos fornecidos pela instituição/cirurgião-dentista/ano" o Indicador de Estrutura selecionado, "cuidados com biossegurança" o de Processo e "satisfação do prestador" o de Resultado. Conclui-se que os indicadores aplicados são excelentes instrumentos de avaliação e fonte de dados para planejamento de um serviço de odontologia

Multi-messenger Observations of a Binary Neutron Star Merger

International audienceOn 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim 1.7\,{\rm{s}}$ with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of ${40}_{-8}^{+8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 $\,{M}_{\odot }$. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim 40\,{\rm{Mpc}}$) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position $\sim 9$ and $\sim 16$ days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)