Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and ...transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer’s and Parkinson’s disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.
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•Microglia single-cell expression and morphology across 450 million years of evolution•Microglia express a conserved core program, including CNS ligand-receptors pairs•Human microglia show significant heterogeneity in comparison with all mammals•Identification of disease-associated microglia gene expression modules in humans
Single-cell sequencing of microglia across evolutionary timescales leads to definition of a conserved core expression program and identification of heterogeneity in human microglia lacking in other species.
In this paper we analyze the impact of an increase in the local supply of immigrants on firms’ outcomes, allowing for heterogeneous effects across firms. Using micro-level data on French ...manufacturing firms spanning the period 1995–2005, we show that a supply-driven increase in the share of foreign-born workers in a French département (a small geographic area) increased the total factor productivity of firms in that département. We also find this effect to be significantly stronger for firms with low initial productivity and small size. The positive productivity effect of immigrants was also associated with faster growth of capital, larger exports, and higher wages for natives. Highly-skilled natives, in competition with immigrants, moved towards firms hiring fewer immigrants spreading positive productivity effects to those firms too.
•We estimate transition rates of foreign college graduates to US labor markets.•We find transition rates of 0.23 (0.08) for foreign master’s (bachelor’s) graduates.•Estimated transition rates account ...for the endogenous location of foreign students.•This implies significant leakage of human capital of foreign students out of the US.•Transition to labor market was higher for foreign STEM graduates and after the 2008 OPT reform.
While US universities attract millions of international students, we do not know how many of them work in the US after graduating. In this paper we implement an instrumental variable estimation, using quasi-random variations in the tuition charged, and we estimate that between 2003 and 2017 one more international master (or bachelor) student, attracted by a university, increased the US skilled labor supply in the year of graduation by about 0.23 (0.08) employees. Only for STEM students such effect on labor supply was positive and significant, especially after the 2008 Optional Practical Training reform.
•Psychological treatment is the treatment of choice for dissociative seizures (DS).•Psychological treatment providers’ experiences with DS were studied.•People with DS are a heterogeneous group ...thought to require individualized treatment.•Improvement of quality of life seemed more important than reducing seizures.•Working with DS is complex and requires experience with trauma therapy.
Limited research exists exploring the experiences of psychological therapy providers (PTPs) working with people with dissociative seizures (DS). PTPs play a key role in the treatment of DS, yet sit at the end of a long, often ineffective process of diagnosis and waiting before treatment can commence. This qualitative study was undertaken involving 12 PTPs from specialist DS services throughout England and Scotland. Semi-structured interviews were carried out, using thematic analysis to evaluate the data. Four key themes were identified, “neurological to psychological”, “putting the person with DS at the center”, “treatment process”, and “issues and impact of therapy with patients with DS”. The findings showed that an unclear and uncomprehended diagnosis, together with waiting times had a detrimental impact on patients at the starting point of therapy. People with DS were perceived as a heterogeneous group whose treatment needed to be individualized, using the PTPs’ full ‘toolkit’ of modalities and techniques, with a focus on improving quality of life, rather than reducing seizures. The study highlighted the complexity for PTPs of working with major but also accumulated minor traumas, compounded by the impact of DS on both PTPs and treatment. The desire of PTPs to be totally patient-focused meant that individualized treatment was considered essential and meant that participants were doubtful about the possibility of compiling an effective manual for the psychological treatment for DS.
Abstract
We develop a political economy model to study the decision of representative democracies to join a preferential trading agreement, distinguishing between free trade areas and customs unions. ...Our theoretical analysis shows that bilateral trade imbalances and income inequality are important factors determining the formation of preferential trading agreements, whereas the patterns of geographic specialisation explain whether a customs union or a free trade area will emerge. Our empirical analysis—using a comprehensive panel dataset spanning 187 countries over the period 1960–2015—provides strong support for these predictions.
Allergic immunity is orchestrated by group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells prominently arrayed at epithelial- and microbial-rich barriers. However, ILC2s and Th2 cells ...are also present in fibroblast-rich niches within the adventitial layer of larger vessels and similar boundary structures in sterile deep tissues, and it remains unclear whether they undergo dynamic repositioning during immune perturbations. Here, we used thick-section quantitative imaging to show that allergic inflammation drives invasion of lung and liver non-adventitial parenchyma by ILC2s and Th2 cells. However, during concurrent type 1 and type 2 mixed inflammation, IFNγ from broadly distributed type 1 lymphocytes directly blocked both ILC2 parenchymal trafficking and subsequent cell survival. ILC2 and Th2 cell confinement to adventitia limited mortality by the type 1 pathogen Listeria monocytogenes. Our results suggest that the topography of tissue lymphocyte subsets is tightly regulated to promote appropriately timed and balanced immunity.
We estimate the aggregate long-run elasticity of substitution between more educated workers and less educated workers (the slope of the inverse demand curve for more relative to less educated ...workers) at the U.S. state level. Our data come from the (five) 1950-1990 decennial censuses. Our empirical approach allows for state and time fixed effects and relies on time- and state-dependent child labor and compulsory school attendance laws as instruments for (endogenous) changes in the relative supply of more educated workers. We find the aggregate long-run elasticity of substitution between more and less educated workers to be around 1.5.
AbstractThe disposal of fly ash is an environmental challenge globally, and the only viable solution for its mass disposal is its use in the construction industry, especially for brick production. ...Hence, the substantial growth in masonry structures using fly ash bricks in India where coal-based power plants dominate the power sector has been recently seen. However, the safety and strength assessment of structures made of fly ash bricks often require the modeling of the uncertainty of its properties. The present study investigated the variability of compressive strength of fly ash bricks and proposes the most appropriate model for the statistical distribution. Twenty-six probability distributions were considered to conduct the three goodness-of-fit tests, namely, Kolmogorov-Smirnov, Kolmogorov-Smirnov-Lilliefors, and Anderson-Darling tests. The analysis concluded that the Johnson SB distribution is the best suited of the distributions considered for similar cases to model the variability in the compressive strength of fly ash bricks. In addition, the microstructures of these bricks were examined to investigate the cause of such variations.
To make sense of the unprecedented destruction wrought by World War II, Soviet historians have increasingly turned to diaries for insight into how this conflict was experienced and understood by ...individual citizens. This essay explores recent historiographical approaches to Soviet wartime diaries by examining the groundbreaking and diverse methods of Oleg Budnitskii, Jochen Hellbeck, and Jeffrey K. Hass, as well as discussing my own research. Using soldiers’ diaries, Budnitskii has illuminated lesser known and taboo aspects of frontline service, complicating both the celebrated myth of the Great Patriotic War and the assumption that Soviet people did not think outside of the categories of Soviet ideology in the process. Hellbeck has investigated Stalin-era practices of diary writing as a tool for perfecting oneself, purging it of bourgeois individualism, and aligning it with collective. Based on this, he has argued that Soviets had a unique self-concept (or subjectivity), which was distinct from the liberal, western tradition. Donning a historical-sociological approach, Hass has studied diaries from the Leningrad Blockade to discern how extreme starvation put pressure on various norms and behavioral logics at work in the besieged community. Drawing inspiration from all of these researchers, my study – also of wartime Leningrad – attends to the cognitive and narrative strategies that Leningraders employed to come to intellectual grips with the siege. I treat the diary as a sense-making text rather than as a laboratory of self.
Soucieux de mieux comprendre les ravages inouïs causés par la Seconde Guerre mondiale, les historiens de l’Union soviétique ont manifesté un intérêt croissant pour les journaux intimes, afin de saisir la manière dont ce conflit avait été vécu et perçu par les citoyens. Dans cet essai, j’explore les récentes approches historiographiques des journaux de guerre soviétiques, en examinant les méthodes révolutionnaires et néanmoins différentes d’Oleg Budnitskii, Jochen Hellbeck et Jeffrey K. Hass, avant de développer ma propre recherche. Budnitskii s’est appuyé sur des journaux personnels de soldats pour mettre en lumière certains aspects méconnus, voire tabous, du service au front, compliquant de la sorte à la fois l’illustre mythe de la Grande Guerre patriotique et l’idée selon laquelle, en écrivant, les diaristes de l’URSS restaient prisonniers du cadre de l’idéologie soviétique. Analysant la pratique du journal intime à l’époque stalinienne, Hellbeck y a vu un outil d’autoperfectionnement, utilisé par le diariste pour purger en soi l’individualisme bourgeois et aligner sa conscience sur le collectif ; il en a déduit l’existence d’un concept de soi (ou d’une subjectivité) soviétique unique, distinct de la subjectivité libérale occidentale. Privilégiant une approche historico-sociologique, Hass s’est penché sur les journaux personnels du siège de Leningrad afin de déterminer dans quelle mesure une situation de famine avait pesé sur certaines normes et logiques comportementales au sein de la communauté assiégée. Inspirée de l’ensemble de ces chercheurs, ma propre recherche – également centrée sur la ville de Leningrad en temps de guerre – porte sur les stratégies cognitives et narratives déployées par les Léningradois pour appréhender l’état de siège. Ce faisant, je traite le journal comme un texte producteur de sens plutôt que comme un laboratoire du soi.
Om betekenis te geven aan de vernietiging zonder voorgaande die de Tweede Wereldoorlog met zich meebracht, hebben historici uit de Sovjet-Unie zich in toenemende mate tot dagboeken gewend om inzicht te krijgen in hoe het conflict ervaren en begrepen werd door individuele burgers. Dit artikel verkent recente historische benaderingen van dagboeken uit de Sovjet-Unie van tijdens de oorlog en doet dat door de baanbrekende en van elkaar verschillende benaderingen van Oleg Budnitskii, Jochen Hellbeck en Jeffrey K. Hass onder de loep te nemen, en vervolgens ook mijn eigen onderzoek voor te stellen. Door dagboeken van soldaten te gebruiken heeft Budnitskii minder bekende en taboe-aspecten van de militaire dienst aan het front belicht, waarbij hij zowel de illustere mythe van de Grote Patriottische Oorlog als de veronderstelling problematiseerde dat de Sovjetbevolking toen niet buiten de lijntjes van de Sovjetideologie kleurde. Hellbeck heeft in de praktijk van het dagboekschrijven tijdens de Stalin-periode een middel tot zelfvervolmaking gezien, die het ik zuiverde van bourgeois individualisme en op één lijn bracht met het collectief. Hij heeft daaruit een uniek zelfbegrip (of subjectiviteit) afgeleid dat verschillend was van de liberale, westerse traditie. Vanuit een historisch-sociologisch perspectief heeft Hass dagboeken van het Beleg van Leningrad bestudeerd om te bepalen hoe extreme hongersnood bepaalde normen onder druk zet en ook de gedragslogica verandert die in een belegerde gemeenschap heerst. Geïnspireerd door al deze onderzoekers richt mijn eigen onderzoek zich – ook van het Leningrad in oorlogstijd – op de cognitieve en verhalende strategieën van de inwoners van Leningrad om intellectueel grip te krijgen op de belegering. Ik behandel het dagboek als een tekst die betekenis moet geven eerder dan als een laboratorium van het ik.
The identification of aggregate human-capital externalities is still not fully understood. The existing (Mincerian) approach confounds positive externalities with wage changes due to a downward ...sloping demand curve for human capital. As a result, the Mincerian approach yields positive externalities even when wages equal marginal social products. We propose an approach that identifies human-capital externalities, whether or not aggregate demand for human capital slopes downward. Another advantage of our approach is that it does not require estimates of the individual return to human capital. Applications to U.S. cities and states between 1970 and 1990 yield no evidence of significant average-schooling externalities.
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