High spatial overlap but diverging age-related trajectories of cortical magnetic resonance imaging markers aiming to represent intracortical myelin and microstructure

ABSTRACT: Statistical effects of cortical metrics derived from standard T1- and T2-weighted magnetic resonance imaging (MRI) images, such as gray–white matter contrast (GWC), boundary sharpness coefficient (BSC), T1-weighted/T2-weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between-marker age-related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo- and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18–81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression-derived cell-type densities, histology-derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between-marker age-related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging

The impact of the Siemens Tim Trio to Prisma upgrade and the addition of volumetric navigators on cortical thickness, structure volume, and 1H-MRS indices: An MRI reliability study with implications for longitudinal study designs

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices (“Prisma Upgrade protocol”) and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence (“vNav protocol”). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia.

Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479Funder: Fonds de Recherche du Québec ‐ SantéFunder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024Funder: NIHR Rare Diseases Translational Research CollaborationFunder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers

Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study

International audiencePurpose: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival.Methods: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression.Results: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality.Conclusion: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality

Coworkers, Makers and Hackers in the city : Reinventing policies, corporate strategies and citizenship ?

The world of work is changing. A century after moving from an agriculture-centered world to an Industrial one, from self-employed workers to salaried employees, our modern economies are slowly transitioning towards a new model: based on simultaneous collaboration and competition, the boundaries of contemporary organizations are blurring; information technologies are allowing individuals and companies to set base away from cities; shared working spaces are triggering new forms of collaborations between individuals and corporations.This White Paper aims at diagnosing key institutional tensions related to new work practices in the city, and putting forward questions and general propositions likely to overcome these tensions. The idea is to analyze how new collaborative communities and collaborative logics (of coworkers, hackers, makers, fabbers, and teleworkers) and more traditional collective activity and modes of decision making (of the city and corporations in the city) can jointly contribute to the co-production of harmonious new ways of life and new ways of working. Reinventing joint public policies, corporate strategies and citizenship appear here as a key stake where usual dichotomies between private-public, collaborative-non-collaborative economy, traditional citizens and hacktivists need to be overcome.We thus identify in this document a set of controversies around four strong political issues both for the city and the field of management, linked to the emergence of collaborative spaces:o Topic 1. Space, territories, and public policy on collaborative communities in the city;o Topic 2. Collaborative communities and their roles in education in the city;o Topic 3. Business models and their communication in the context of collaborative spaces and collaborative communities;o Topic 4. Collaborative spaces and their roles in innovation and entrepreneurial dynamics at the level of the cityBeyond our controversies, we underline three paradoxes which should be at the heart of new questions for policy-makers, hacktivists, actors of collaborative movements, and citizens (distinctions which may become less and less relevant in the years to come):o Social versus economic orientations of both the city and the collaborative communities it can host;o Critical/revolutionary versus more incremental relationships between cities, organizations, societies, collaborative communities, and new work practices;o Local territory (district/proximate area) grounded versus broader city-oriented or connectivity related issues about collaborative movement and new work practices.To balance these tensions, we elaborate seven general areas of questions and propositions for all stakeholders:o The generalization of infra-organization (physical collaborative platforms);o The emergence of “ ‘inclusive lab’ labels” (elaborated and managed by collaborative communities themselves);o A renewed academic presence in the city and in the country-side (with more virtual, distributed and ‘experiential’ logics);o Ephemeral and mobile labs managed jointly by public, collaborative and private stakeholders;o “Open open” innovation in public and semi-public spaces of the city;o Rise of mega-spaces for creativity in the city;o Development of a global infrastructure for coworkers, mobile workers and teleworkers.These are directions we see as particularly promising to manage the tensions, paradoxes and stakes explicated by our controversies.We hope that these questions and propositions will inspire both academics, politicians, hacktivists and entrepreneurs for future collaborations on the study and joint transformation of public policies, corporate strategies, and citizenship

Coworkers, Makers and Hackers in the city : Reinventing policies, corporate strategies and citizenship ?

The world of work is changing. A century after moving from an agriculture-centered world to an Industrial one, from self-employed workers to salaried employees, our modern economies are slowly transitioning towards a new model: based on simultaneous collaboration and competition, the boundaries of contemporary organizations are blurring; information technologies are allowing individuals and companies to set base away from cities; shared working spaces are triggering new forms of collaborations between individuals and corporations.This White Paper aims at diagnosing key institutional tensions related to new work practices in the city, and putting forward questions and general propositions likely to overcome these tensions. The idea is to analyze how new collaborative communities and collaborative logics (of coworkers, hackers, makers, fabbers, and teleworkers) and more traditional collective activity and modes of decision making (of the city and corporations in the city) can jointly contribute to the co-production of harmonious new ways of life and new ways of working. Reinventing joint public policies, corporate strategies and citizenship appear here as a key stake where usual dichotomies between private-public, collaborative-non-collaborative economy, traditional citizens and hacktivists need to be overcome.We thus identify in this document a set of controversies around four strong political issues both for the city and the field of management, linked to the emergence of collaborative spaces:o Topic 1. Space, territories, and public policy on collaborative communities in the city;o Topic 2. Collaborative communities and their roles in education in the city;o Topic 3. Business models and their communication in the context of collaborative spaces and collaborative communities;o Topic 4. Collaborative spaces and their roles in innovation and entrepreneurial dynamics at the level of the cityBeyond our controversies, we underline three paradoxes which should be at the heart of new questions for policy-makers, hacktivists, actors of collaborative movements, and citizens (distinctions which may become less and less relevant in the years to come):o Social versus economic orientations of both the city and the collaborative communities it can host;o Critical/revolutionary versus more incremental relationships between cities, organizations, societies, collaborative communities, and new work practices;o Local territory (district/proximate area) grounded versus broader city-oriented or connectivity related issues about collaborative movement and new work practices.To balance these tensions, we elaborate seven general areas of questions and propositions for all stakeholders:o The generalization of infra-organization (physical collaborative platforms);o The emergence of “ ‘inclusive lab’ labels” (elaborated and managed by collaborative communities themselves);o A renewed academic presence in the city and in the country-side (with more virtual, distributed and ‘experiential’ logics);o Ephemeral and mobile labs managed jointly by public, collaborative and private stakeholders;o “Open open” innovation in public and semi-public spaces of the city;o Rise of mega-spaces for creativity in the city;o Development of a global infrastructure for coworkers, mobile workers and teleworkers.These are directions we see as particularly promising to manage the tensions, paradoxes and stakes explicated by our controversies.We hope that these questions and propositions will inspire both academics, politicians, hacktivists and entrepreneurs for future collaborations on the study and joint transformation of public policies, corporate strategies, and citizenship