Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

La concentration des fonctions à haut contenu en savoir dans le secteur de la production des biens : quel avenir pour les régions non métropolitaines du Québec ?

Les fonctions à haut contenu en savoir jouent un rôle stratégique au sein du secteur de la production des biens. Les régions et les entreprises où se concentrent ces fonctions semblent mieux positionnées que les autres pour assurer leur croissance et leur développement économique. Toutefois, cette réalité suggère de nouvelles disparités économiques à l’échelle régionale. Cet article analyse les tendances de concentration des fonctions à haut contenu en savoir dans les agglomérations du Québec entre 1971 et 2006. L’analyse soulève une concentration métropolitaine qui tend à s’accélérer durant la période. Néanmoins, on constate que certaines régions non métropolitaines ont des niveaux de croissance parfois supérieurs. S’il y a présence de trajectoires distinctes, on ne peut cependant conclure à la présence d’un processus de convergence régionale. Les résultats de l’analyse laissent entendre que la décentralisation de la production des biens a pu en grande partie se limiter aux fonctions de routine et de production.Knowledge-rich functions play a strategic role within the goods producing sector. The regions and businesses where they cluster seem better positioned in terms of future growth and economic development. However, this process suggests new economic disparities at the regional level. Our article examines the concentration of knowledge-rich functions in Quebec urban areas between 1971 and 2006. We find patterns of increasing metropolitan concentration over this period. But higher growth levels can also be found in non-metropolitan areas. While several distinct regional trajectories can be observed, this does not mean we should conclude that a process of regional convergence is developing. Our results suggest that decentralization of production of goods may have largely been limited to routine and production functions.Las funciones a alto contenido de conocimientos juegan un rol estratégico dentro del sector de producción de bienes. Las regiones y empresas donde se concentran esas funciones parecen posicionarse mejor que las otras, asegurando así su crecimiento y desarrollo económico. Sin embargo, esta realidad sugiere nuevas desigualdades económicas a escala regional. Este artículo analiza las tendencias de concentración de esas funciones en las aglomeraciones de la provincia de Quebec entre los años 1971 y 2006. El análisis señala una concentración metropolitana que tiende a acelerarse durante este período. Sin embargo, se constata que ciertas regiones no metropolitanas a veces tienen niveles de crecimiento superiores. Bien que haya trayectorias diferentes, no se puede concluir sobre la presencia de procesos de convergencia regional. Los resultados del análisis dejan entender que le descentralización de la producción de bienes ha podido, en gran parte, limitarse a las funciones de rutina y de producción

Subcentres as Destinations: Job Decentralization, Polycentricity, and the Sustainability of Commuting Patterns in Canadian Metropolitan Areas, 1996–2016

Adopting more sustainable modes of transportation and shorter daily commutes remains a fundamental challenge in the struggle for the sustainable transition of cities. While past studies on the sustainability of commuting behaviours partly focused on the place of residence and how the characteristics of commuters or residential neighbourhoods impact sustainable travel, other studies looked at the place of employment to analyze these dynamics. In this study, we investigate the extent to which the recent phase of the rise of peripheral employment has promoted more sustainable travel behaviour, based on the hypothesis that polycentricity has recently favoured a better job&ndash;housing balance and co-location. We develop a general typology of employment centres, using Census microdata at fine spatial scale over the 1996&ndash;2016 period to observe commuting modes and distances by subcentre types for six major Canadian cities. Our results show that despite recent developments in planning practices&mdash;transit-oriented development, transport infrastructure, and changing travel behaviour, the emergence of peripheral subcentres promoted less sustainable commuting patterns in most Canadian metropolitan areas over the period. However, we find sustainable commuting emerging in subcentres where large public transport infrastructure investments have been made, such as in the case of Vancouver&rsquo;s Millennium and Canada lines. Our study also shows that central business districts (CBDs) and downtown subcentres are becoming relatively more sustainable over the period, which confirms the positive effect of the back-to-the-city movement and changing behaviour toward active transportation in these locations

Accès au très haut débit et développement territorial en période d'incertitude: Note éditoriale

International audienceThe ubiquity of the Internet in our societies raises several questions, many of which have a spatial dimension. An extensive literature exists which focuses, among other topics, on the origin and consequences of the digital divide (e.g., Philip et al., 2017 ; Salemink et al., 2017 ; Szeles, 2018; Thonipara et al., 2020; Whitacre et al., 2015), how the Internet impacts the economic performance of workers, firms, and territories (e.g., Akerman et al., 2015; Bai, 2017; Canzian et al., 2019; DeStefano et al., 2018; Ford, 2018; Haller and Lyons, 2019), on the consequences of the digitization of society on work modes and the residential attractivity of spaces (Conley and Whitacre, 2020; Davies, 2021; Lehtonen, 2020; Mahasuweerachai et al., 2010), or on digital pollution and ways to regulate it (Batmunkh, 2022; Nicolai and Peragin, 2022). More recently, research has also investigated whether more connected economic agents and territories are more resilient in the context of the health crisis (Abidi et al., 2022; Carvalho et al., 2022; Isley and Low, 2022; Pierri and Timmer, 2020). This special issue focuses on two of the most studied topics: the digital divide and the economic impact of the Internet in territories.L’omniprésence d’internet dans nos sociétés pose un grand nombre de questions, dont beaucoup ont une dimension spatiale. Une littérature abondante s’interroge notamment sur l’origine et les conséquences de la fracture numérique (ex.: Philip et al., 2017 ; Salemink et al., 2017 ; Szeles, 2018; Thonipara et al., 2020; Whitacre et al.,2015), l’effet d’internet sur la performance économique des travailleurs, des entreprises, et des territoires (ex.: Akerman et al., 2015; Bai, 2017 ; Canzian et al., 2019; DeStefano et al., 2018; Ford, 2018; Haller et Lyons, 2019), l’impact de la numérisation de la société sur les modes de travail et l’attractivité résidentielle des espaces (Conley et Whitacre, 2020; Davies, 2021; Lehtonen, 2020; Mahasuweerachai et al., 2010), ou encore la pollution numérique et les moyens de la réguler (Batmunkh, 2022; Nicolaï et Peragin, 2022). Plus récemment,les recherches ont également examiné si les agents économiques et les territoires davantage connectés étaient plus résilients dans le contexte de la crise sanitaire (Abidi et al., 2022; Carvalho et al., 2022; Isley et Low, 2022; Pierri et Timmer, 2020). Ce numéro spécial se focalise sur deux des thématiques les plus étudiées : la fracture numérique et les retombées économiques d’internet dans les territoires

Dots to dots : a general methodology to build local indicators using spatial micro-data

Empirical studies in regional science have so far largely relied on discrete conceptualizations of space and aggregated metrics, which do not take into consideration spatial heterogeneity and variability at the micro-level. This paper explores the use of these indicators when dealing with observations at the subregional level, based on micro-data sets that impose the conceptualization of spatial interactions in a continuous and multidirectional space. We propose a general methodology to build local indicators for spatial micro-data sets. Based on distance matrix and matrix calculations, some classical indices of specialization and diversity are extended to their local counterparts to explore the full spatial heterogeneity and variability of space. The methodology is applied to 9,839 establishments covering all economic sectors in the Lower St-Lawrence region (Quebec, Canada). We find that the distribution of the local indicator varies significantly with distance, which suggests that the effects of specialization or diversity are not constant over space. Treating space as continuous may become of prime importance, given that more individual data sets are now available, combined with the fact that the performance of microcomputers is still improving

On the importance of proximity in the faceof exogenous shocks : an analysis of firm survival during the Great Recessionin the peripheral region of the Lower St-Lawrence, Canada

Cet article analyse l’impact des externalités spatiales etde la proximité géographique sur la capacité àrésister aux chocs exogènes à partir d’une étude empirique de la survie d’entreprises individuelles dansla région du Bas-Saint-Laurent (Canada) entre 2006 et 2011. Bien que les externalités traditionnellesoffrent de faibles preuves, nos résultats montrent que la proximité d’une variété d’industries apparentéesde même que la densité locale des liens entre fournisseurs et clients favorisent la survie des entreprises aucours de la période. Ces effets ne sont toutefois pas uniformes dans l’espace–la proximité géographiquemodulant la capacité de résistance aux chocs. Nos résultatsmontrent que répartition spatiale desentreprises, même dans des régions périphériques et à faible densité, structure une variété de lienslocalisés et de relations de proximité, qui jouent un rôle significatif sur la capacité de résistance desentreprises aux chocs économiques.This article analyzes the impacts of spatial externalitiesand geographic proximity on the ability toresist exogenous shocks over time, based on an empirical study of the survival of individual firms in theperipheral Lower-St.-Lawrence region (Canada) between 2006 and 2011. While traditional spatialexternalities offer weak evidence, our results show that the proximity of a variety of related industriesas well as the local density of forward and backward linkagesincrease the survival of firms duringthe period. However, these effects are not uniform across space. Geographic proximity also plays anessential role in the ability to resist shocks. Our results reveal that the spatial distribution of firms,even at small spatial scales and in low-density regions, structures a variety of localized linkages andproximity relations that play a significant role on firms’ capacity to resist economic shocks

The Uneven Economic Diversification of Small and Mid-Sized Canadian Cities, 1971-2016

Economic diversification is a long-standing public policy goal in Canada, driven by concerns about resource dependence and the need to remain innovative and competitive in a complex global economy. While considerable economic diversification of Canada’s urban regions has been noted by a range of observers, the phenomenon remains only partially understood. We propose to study the economic diversification process using an entropy decomposition approach, with industrial composition data compiled from census responses between 1971 and 2016 for 125 small and mid-sized urban regions. We demonstrate that, while industrial concentration indeed declines for almost all regions studied during the study period, trends are highly variable between regions. In about half of regions, diversification was mainly driven by job loss in goods-producing industries rather than job growth in new activities, whereas among the other half of regions, diversification was weaker, but job growth was stronger. This suggests a need for caution in interpreting changes in industrial concentration indices as evidence of economic success stories

L’analyse des trajectoires territoriales de développement : un apport possible des données micro spatiales?

Cet article s’intéresse à l’apport des données micro spatiales dans l’analyse des trajectoires territoriales de développement. Les perspectives émergentes en sciences régionales soulignent le caractère multidimensionnel et multiscalaire des dynamiques territoriales. On constate toutefois que peu de sources de données restent disponibles à des échelles plus fines. L’objectif de cet article est de vérifier s'il existe une possible correspondance entre les bases de données micro spatiales issues d'organismes externes, et les données officielles d'emploi du recensement. Bien que les données d’emploi restent dans l’ensemble comparables entre les bases, ces dernières diffèrent largement quant à leurs distributions spatiales. Ces résultats suggèrent une possible réconciliation entre des approches théoriques qui, a priori, semblent prendre des directions différentes, mais dont les divergences reposent essentiellement sur le niveau de désagrégation des données disponibles. Le développement de nouvelles sources de données micro spatiales offre en outre un potentiel indéniable pour répondre aux thèmes de recherche émergents en sciences régionale

Location Theories and Business Location Decisions : A Micro-Spatial Investigation from Canada

International audienc