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We use two-round survey data from 62 elections in 10 countries since 1952 to study the formation of vote choice, beliefs, and policy preferences and assess how televised debates contribute to this process. Our data include 253,000 observations. We compare the consistency between vote intention and vote choice of respondents surveyed at different points before, and then again after, the election, and show that 17% to 29% of voters make up their mind during the final two months of campaigns. Changes in vote choice are concomitant to shifts in issues voters find most important and in beliefs about candidates, and they generate sizable swings in vote shares. In contrast, policy preferences remain remarkably stable throughout the campaign. Finally, we use an event study to estimate the impact of TV debates, in which candidates themselves communicate with voters, and of shocks such as natural and technological disasters which, by contrast, occur independently from the campaign. We do not find any effect of either type of event on vote choice formation, suggesting that information received throughout the campaign from other sources such as the media, political activists, and other citizens is more impactful.

Conflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain. Next, we showed that cuprizone-fed mice, which is an MS model, tended to have increased melatonin levels. While we used different approaches to alter the circadian rhythm of melatonin and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. Therefore, melatonin should not be considered a universal remedy, as is currently claimed. Our data emphasize the importance of monitoring melatonin/cortisol oscillations in each MS patient by considering diet and lifestyle to avoid melatonin overdose.

Alzheimer disease (AD) is the first progressive neurodegenerative disease worldwide, and the disease is characterized by an accumulation of amyloid in the brain and neurovasculature that triggers cognitive decline and neuroinflammation. The innate immune system has a preponderant role in AD. The last decade, scientists focused their efforts on therapies aiming to modulate innate immunity. The latter is of great interest, since they participate to the inflammation and phagocytose the amyloid in the brain and blood vessels. We and others have developed pharmacological approaches to stimulate these cells using various ligands. These include toll-like receptor 4, macrophage colony stimulating factor, and more recently nucleotide-binding oligomerization domain-containing 2 receptors. This review will discuss the great potential to take advantage of the innate immune system to fight naturally against amyloid

In a large-scale randomised experiment implemented with Kenya’s Electoral Commission, text messages intended to mobilise voters boosted electoral participation. However, the messages also decreased trust in electoral institutions after the election. This decrease was stronger for individuals on the losing side and in areas that experienced election-related violence. We hypothesise that the mobilisation campaign backfired because the Electoral Commission promised a transparent and orderly electoral process but failed to deliver on these expectations. Several potential mechanisms account for the intervention’s unexpected effects, including a simple model where signalling capacity via mobilisation messages can negatively affect beliefs about election fairness.

Rooftops cover a large percentage of land area in urban areas, which can potentially be used for stormwater purposes. Seeking adaptation strategies, there is an increasing interest in utilising green roofs for stormwater management. However, the impact of extreme rainfall on the hydrological performance of green roofs and their design implications remain challenging to quantify. In this study, a method was developed to assess the detention performance of a detention-based green roof (underlaid with 100 mm of expanded clay) for current and future climate conditions under extreme precipitation using an artificial rainfall generator. The green roof runoff was found to be more sensitive to the initial water content than the hyetograph shape. The green roof outperformed the black roof in terms of all performance indicators (time of concentration, centroid delay, T50 or peak attenuation). While the time of concentration for the reference black roof was within 5 minutes independently of rainfall intensity, for the green roof was extrapolated between 30 and 90 minutes with intensity from 0.8 to 2.5 mm/min. Adding a layer of expanded clay under the green roof substrate provided a significant improvement to the detention performance under extreme precipitation in current and future climate conditions. © 2020 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits copying, adaptation and redistribution, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/).

Despite large take-up rates in most OECD countries, millions of people still refuse COVID-19 vaccination. The large number of unvaccinated individuals raises major concerns about the diffusion of the virus. Anti-vax individuals are often very vocal about their choice and use social media to convince undecided individuals not to get vaccinated. Using original data from two surveys in nine OECD countries, we show that half of the individuals, who expressed anti-vax intentions in December 2020, were vaccinated by summer 2021. We find that information plays a key role. Vaccinations were more likely among individuals aged 50+, more informed on traditional media, trusting scientists, exposed to COVID-19, compliant with public restrictions, and less concerned about vaccines’ side effects. We also run a survey experiment with informational messages in the first wave. A striking result is that these informational treatments affected not only immediate vaccination intentions, but also actual vaccination rates recorded six months later – even among individuals, who had initially expressed anti-vax intentions. Altruistic messages, about protecting health or the economy, had the largest effect. Important differences in the relative impact of our different treatments across countries indicate that successful information campaigns should be tailored to the context.

Alzheimer’s disease (AD) constitutes a major cause of dementia, affecting more women than men. It is characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles (NFTs) formation, associated with a progressive cognitive decline. Evidence indicates that AD onset increases the prevalence of cerebral microinfarcts caused by vascular pathologies, which occur in approximately in half of AD patients. In this project, we postulated that multifocal cerebral microinfarcts decisively influence early AD-like pathology progression in a sex dependent manner in young APP/PS1 mice. For this purpose, we used a novel approach to model multifocal microinfarcts in APP/PS1 mice via the sporadic occlusions of the microvasculature. Our findings indicate that microinfarcts reduced Aβ deposits without affecting soluble Aβ levels in the brain of male and female APP/PS1 mice, while causing rapid and prolonged cognitive deficits in males, and a mild and transient cognitive decline in females. In male APP/PS1 mice, microinfarcts triggered an acute hypoperfusion followed by a chronic hyperperfusion. Whereas in female APP/PS1 mice, microinfarcts caused an acute hypoperfusion, which was recovered in the chronic phase. Microinfarcts triggered a robust microglial activation and recruitment of peripheral monocytes to the lesion sites and Aβ plaques more potently in female APP/PS1 mice, possibly accounting for the reduced Aβ deposition. Finally, expression of Dickkopf-1 (DKK1), which plays a key role in mediating synaptic and neuronal dysfunction in AD, was strongly induced at the lesion sites of male APP/PS1 mice, while its expression was reduced in females. Our findings suggest that multifocal microinfarcts accelerate AD pathology more potently in young males compared to young females independently upon Aβ pathology via modulation of neurovascular coupling, inflammatory response, and DKK1 expression. Our results suggest that the effects of microinfarcts should be taken into consideration in AD diagnosis, prognosis, and therapies.

Controls on the deformation pattern (shortening mode and tectonic style) of orogenic forelands during tectonic shortening remain poorly understood. Here, we use high-resolution 2D thermomechanical ...

Alzheimer’s disease (AD) is the most common form of dementia in the world. The prevalence is steadily increasing due to an aging population and the lack of effective treatments. However, modulation of innate immune cells is a new therapeutic avenue, which is quite effective at delaying disease onset and improving cognitive decline. Methods: We studied the effect of the NOD2 receptor ligand muramyl dipeptide (MDP) on the modulation of the innate immune cells, namely patrolling monocytes and microglia. We administrated MDP once a week for 3 months in an APPswe/PS1 mouse model in both sexes. We started the treatment at 3 months before plaque formation and evaluated its effects at 6 months. Results: We showed that the MDP injections delay cognitive decline in both sexes via different mechanisms and protect the blood brain barrier (BBB). In males, MDP triggers the sink effect from the BBB, leading to a diminution in the amyloid load in the brain. This phenomenon is underlined by the increased expression of phagocytosis markers such as TREM2, CD68, and LAMP2 and a higher expression of ABCB1 and LRP1 at the BBB level. The beneficial effect seems more restricted to the brain in females treated with MDP, where microglia surround amyloid plaques and prevent the spreading of amyloid peptides. This phenomenon is also associated with an increase in TREM2 expression. Interestingly, both treated groups showed an increase in Arg-1 expression compared to controls, suggesting that MDP modulates the inflammatory response. Conclusion: These results indicate that stimulation of the NOD2 receptor in innate immune cells is a promising therapeutic avenue with potential different mechanisms between males and females.

SummaryWomen die less than men of COVID-19, but have been more concerned about its health consequences and more compliant with the public health rules imposed during the pandemic. Since return to normal life depends on vaccination, but delays in acceptance or outright refusals of vaccination are already evident, we investigate gender differences in attitudes and expected behaviors regarding COVID-19 vaccination. Using original data from a survey conducted in December 2020 in ten developed countries (N=13,326), we discover aCOVID-19 Vaccine’s gender paradox. Being more concerned about COVID-19 and more likely to believe to be infected and consequently to become seriously ill, women could be expected to be more supportive of vaccination than men. Instead, our findings show that women agree less than men to be vaccinated and to make vaccination compulsory. Our evidence suggests that their vaccine hesitance is partly due skepticism, since women are less likely to believe that vaccination is the only solution to COVID-19 and more likely to believe that COVID-19 was created by large corporations. Using a survey experiment performed in these ten countries, we show that information provision on the role of vaccination to become immune to COVID-19 is effective in reducing vaccine hesitance.

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS, their proliferation, activation and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods: Here we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system, the knock-out (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knock-out at 3-month-old, before plaque formation and evaluated both 6 and 8-month-old groups of mice. Results: Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate controls groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology is associated with a decrease in plaque volume in cortex and hippocampus area. A compensating system seems to take place following the knock-out, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions: Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

We measure the overall influence of contextual versus individual factors (e.g., voting rules and media as opposed to race and education) on voter behavior, and explore underlying mechanisms. Using a U.S.-wide voter-level panel, 2008–18, we examine voters who relocate across state and county lines, tracking changes in registration, turnout, and party affiliation to estimate location and individual fixed effects in a value-added model. Location explains 37 percent of the cross-state variation in turnout (to 63 percent for individual characteristics) and an only slightly smaller share of variation in party affiliation. Place effects are larger for young and White voters.

Microglia are the brain resident immune cells; they can produce a large variety of growth factors (GFs) to prevent neuronal damages and promote recovery. In neurodegenerative diseases, microglia can play both benefic and deleterious roles, depending on different factors and disease context. In multiple sclerosis, microglia are involved in both demyelination (DM) and remyelination (RM) processes. Recent studies suggest a beneficial role of microglia in regenerative processes. These include the regenerative development of myelin after DM. This review gives an overlook of how microglia and GFs can influence the RM properties.

Using original data from two waves of a survey conducted in March and April 2020 in eight OECD countries (N = 21,649), we show that women are more likely to see COVID-19 as a very serious health problem, to agree with restraining public policy measures adopted in response to it, and to comply with them. Gender differences in attitudes and behavior are substantial in all countries, robust to controlling for a large set of sociodemographic, employment, psychological, and behavioral factors, and only partially mitigated for individuals who cohabit or have direct exposure to COVID-19. The results are not driven by differential social desirability bias. They carry important implications for the spread of the pandemic and may contribute to explain gender differences in vulnerability to it.

We test whether politicians can use direct contact to reconnect with citizens, increase turnout, and win votes. During the 2014 Italian municipal elections, we randomly assigned 26,000 voters to receive visits from city council candidates, canvassers supporting the candidates' list, or to a control group. While canvassers' visits increased turnout by 1.8 percentage points, candidates' had no impact on participation. Candidates increased their own vote share in the precincts they canvassed, but only at the expense of other candidates on the list. This suggests that their failure to mobilize non‐voters resulted from focusing on securing the preferences of active voters.

Microglia are the innate immune cells of the CNS and their proliferation, activation, and survival have previously been shown to be highly dependent on macrophage colony-stimulating factor receptor (CSF1R). Here we investigated the impact of the receptor in such processes using two different models of nerve injuries, namely hypoglossal axotomy and cuprizone-induced demyelination. Both models are associated with a robust microgliosis. The role of CSF1R was investigated using the gene deletion Cre/Lox system, which allows the conditional knock-out following tamoxifen administration. We found that after 5 weeks of cuprizone diet that CSF1R suppression caused a significant impairment of microglia function. A reduced microgliosis was detected in the corpus collosum of CSF1R knock-out mice compared to controls. In contrast to cuprizone model, the overall number of Iba1 cells was unchanged at all the times evaluated following hypoglossal axotomy in WT and cKO conditions. After nerve lesion, a tremendous proliferation was noticed in the ipsilateral hypoglossal nucleus to a similar level in both knock-out and wild-type groups. We also observed infiltration of bone-marrow derived cells specifically in CSF1R-deficient mice, these cells tend to compensate the CSF1R signaling pathway suppression in resident microglia. Taking together our results suggest a different role of CSF1R in microglia depending on the model. In the pathologic context of cuprizone-induced demyelination CSF1R signaling pathway is essential to trigger proliferation and survival of microglia, while this is not the case in a model of systemic nerve injury. M-CSF/CSF1R is consequently not the unique system involved in microgliosis following nerve damages.

Using multi-country data from 62 elections since 1952, we show that 17% to 29% of voters make up their mind during the final two months of campaigns, generating sizeable swings in candidates’ vote shares. We obtain these results by measuring the consistency between vote intention and vote choice of respondents surveyed at different points before, and then again after, the election. Changes in vote choice are concomitant to shifts in salient issues and beliefs about candidates, while policy preferences remain remarkably stable. Televised debates do not affect vote choice formation, suggesting that information continuously received by voters is more impactful.

This paper provides the first estimate of the effect of door-to-door canvassing on actual electoral outcomes, via a countrywide experiment embedded in François Hollande's campaign in the 2012 French presidential election. While existing experiments randomized door-to-door visits at the individual level, the scale of this campaign (five million doors knocked) enabled randomization by precinct, the level at which vote shares are recorded administratively. Visits did not affect turnout, but increased Hollande's vote share in the first round and accounted for one-fourth of his victory margin in the second. Visits' impact persisted in later elections, suggesting a lasting persuasion effect. (JEL C93, D7, D83)

In French parliamentary and local elections, candidates ranked first and second in the first round automatically qualify for the second round, while a third candidate qualifies only when selected by more than 12.5 percent of registered citizens. Using a fuzzy RDD around this threshold, we find that the third candidate's presence substantially increases the share of registered citizens who vote for any candidate and reduces the vote share of the top two candidates. It disproportionately harms the candidate ideologically closest to the third and causes her defeat in one fifth of the races. Additional evidence suggests that these results are driven by voters who value voting expressively over voting strategically for the top‐two candidate they dislike the least to ensure her victory; and by third candidates who, absent party‐level agreements leading to their dropping out, value the benefits associated with competing in the second round more than influencing its outcome.

U.S. states increasingly require identification to vote – an ostensive attempt to deter fraud that prompts complaints of selective disenfranchisement. Using a difference-in-differences design on a 1.6-billion-observations panel dataset, 2008–2018, we find that the laws have no negative effect on registration or turnout, overall or for any group defined by race, gender, age, or party affiliation. These results hold through a large number of specifications and cannot be attributed to voters’ reaction against the laws, measured by campaign contributions and self-reported political engagement. However, the likelihood that non-white voters were contacted by a campaign increases by 5.4 percentage points, suggesting that parties’ mobilization might have offset modest effects of the laws on the participation of ethnic minorities. Finally, strict ID requirements have no effect on fraud – actual or perceived. Overall, our findings suggest that efforts to improve elections may be better directed at other reforms.

We present the results from a field experiment on team diversity. Individuals working as door-to-door canvassers for a non-profit organization were randomly assigned a teammate, a supervisor, and a list of individuals to canvass. This created random variation within teams in the degree of horizontal diversity (between teammates), vertical diversity (between teammates and their supervisor) and external diversity (between teams and the individuals they canvassed). We observe team-level measures of performance and find that horizontal ethnic diversity decreases performance, while vertical diversity often improves performance, and external diversity has no effect. The data on time use suggests that horizontally homogeneous teams organized tasks in a more efficient way, while vertically homogeneous teams exerted lower effort.

Background Multiple sclerosis is a neurodegenerative disorder characterized by myelin loss in the brain parenchyma. To mimic the disease, mice are fed a cuprizone-supplemented diet for 5 weeks, which leads to demyelination of white and grey matter regions, with the corpus callosum being the most susceptible to cuprizone intoxication. Although this model is highly exploited, classical behavioural tests showed inconsistent results. Objective In our study, we aimed to use the automated system Intellicage to phenotype the behaviour of cuprizone-fed mice. Methods Mice were continuously monitored during the 5 weeks of intoxication in their home cages, with minimal interference from the experimenter. Mice were assessed for spontaneous activity, fine movements, and impulsivity. Results Consistently, cuprizone-fed mice showed reduced activity and impulsivity throughout the test period. These behavioral results were confirmed by repeating the battery of behavioral tests in a second cohort of cuprizone-fed mice. Our results suggest that the behavioural phenotyping of cuprizone-fed mice using Intellicage is reproducible and sensitive enough to detect changes normally missed in standard behavioral test batteries. Conclusion Using a reproducible and standardized method to assess behavioral changes in mice intoxicated with cuprizone is crucial to better understand the disease as well as the functional outcome of treatments.

The purinergic receptor P2Y6 is expressed in immune cells, including the microglia that are implicated in neurological disorders. Its ligand, UDP, is a signaling molecule that can serve as an “find-me” signal when released in significant quantities by damaged/dying cells. The binding of UDP by P2Y6R leads to the activation of different biochemical pathways, depending on the disease context and the pathological environment. Generally, P2Y6R stimulates phagocytosis. However, whether or not phagocytosis coincides with cell activation or the secretion of pro-inflammatory cytokines needs further investigation. The current review aims to discuss the various functions of P2Y6R in some CNS disorders. We present evidence that P2Y6R may have a detrimental or beneficial role in the nervous system, in the context of neurological pathologies, such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, radiation-induced brain injury, and neuropathic pain.

Background Improving patients’ tuberculosis (TB) knowledge is a salient component of TB control strategies. Patient knowledge of TB may encourage infection prevention behaviors and improve treatment adherence. The purpose of this study is to examine how TB knowledge and infection prevention behaviors change over the course of treatment. Methods A matched patient-health worker dataset (n = 6,031) of publicly treated TB patients with NGO-provided treatment support health workers was compiled in nine Indian cities from March 2013 to September 2014. At the beginning and end of TB treatment, patients were asked about their knowledge of TB symptoms, transmission, and treatment and infection prevention behaviors. Results Patients beginning TB treatment (n = 3,424) demonstrated moderate knowledge of TB; 52.5% (50.8%, 54.2%) knew that cough was a symptom of TB and 67.2% (65.6%, 68.7%) knew that TB was communicable. Overall patient knowledge was significantly associated with literacy, education, and income, and was higher at the end of treatment than at the beginning (3.7%, CI: 3.02%, 4.47%). Infection prevention behaviors like covering a cough (63.4%, CI: 61.2%, 65.0%) and sleeping separately (19.3%, CI: 18.0%, 20.7%) were less prevalent. The age difference between patient and health worker as well as a shared language significantly predicted patient knowledge and adherence to infection prevention behaviors. Conclusions Social proximity between health worker and patients predicted greater knowledge and adherence to infection prevention behaviors but the latter rate remains undesirably low.

We study the demand for household water connections in urban Morocco, and the effect of such connections on household welfare. In the northern city of Tangiers, among homeowners without a private connection to the city's water grid, a random subset was offered a simplified procedure to purchase a household connection on credit (at a zero percent interest rate). Take-up was high, at 69%. Because all households in our sample had access to the water grid through free public taps (often located fairly close to their homes), household connections did not lead to any improvement in the quality of the water households consumed; and despite significant increase in the quantity of water consumed, we find no change in the incidence of waterborne illnesses. Nevertheless, we find that households are willing to pay a substantial amount of money to have a private tap at home. Being connected generates important time gains, which are used for leisure and social activities, rather than productive activities. Because water is often a source of tension between households, household connections improve social integration and reduce conflict. Overall, within 6 months, self-reported well-being improved substantially among households in the treatment group, despite the financial cost of the connection. Our results suggest that facilitating access to credit for households to finance lump sum quality-of-life investments can significantly increase welfare, even if those investments do not result in income or health gains.