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Tuition levels in the US have been rising at an above-the-inflation pace, leading to spiraling student debt levels and negative effects on students' well-being. While student outcomes of rising tuition are well known, the political reasons behind the decisions of policy makers to contain tuition increases or not remain poorly understood. In this article, we focus on electoral accountability that policy makers face for rising tuition by examining voters' reactions. Using a survey experiment with a sample of US adults (N = 1040), we show that clarity of responsibility is an important factor affecting reactions to rising tuition levels. When voters are informed about the role of the government in tuition setting, they are more likely to vote out policy makers responsible for cuts in funding. We show a similar relationship in observational data using a nationally representative survey from Cooperative Congressional Election Study. State governors' approval is lower in states where tuition levels increased recently, and the relationship is moderated by the visibility of government in tuition-setting. By demonstrating that policy makers face repercussions for rising tuition but are able to avoid blame in certain conditions, we contribute to scholarly understanding of preferences of policy makers in higher education.

Abstract Introduction The purpose of this study is to assess the real-life efficacy and tolerance of a new preservative-free, surfactant-free latanoprost (PFSF-LAT) formulation. Methods Retrospective, multicentre, non-comparative, observational study in patients with ocular hypertension or open angle glaucoma, naïve or non-naïve to previous intraocular pressure (IOP)-lowering treatment, and treated for at least 3 months with the study eye drop. IOP for worse eye, ocular signs and symptoms, and concomitant use of artificial tears were collected at study drug initiation and at last visit under treatment. Reasons for discontinuing the study eye drop (if relevant) and investigators’ satisfaction were also assessed. Results In the per protocol population (103 eyes; 63 naïve, 39 switched, 1 not classified because of missing data), IOP decreased significantly (p

How do voters respond to a co-partisan political candidate after hearing about a serious scandal? We apply qualitative content analysis to open-ended text responses collected from survey respondents, focusing on 159 respondents who remain willing to vote for a hypothetical male candidate after learning that allegations of sexual harassment against him were settled out of court. We uncover two main strategies by which respondents explained and justified their willingness to look past the misconduct allegations. The dominant strategy was to extend moral licence to the candidate based on his prior good deeds; a second prominent strategy was to disbelieve and reject the allegations. Our findings offer new insights on why some political candidates and careers appear untroubled by even serious allegations of misconduct, and frames new research avenues on which voters might be more likely to extend moral licence and in what circumstances.

Abstract Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood–brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis. Sex hormonal dysregulation in early development has been implicated in neurodevelopmental disorders with highly sexually dimorphic features, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Both disorders show higher prevalence in men, with varying symptoms between sexes, with boys exhibiting more externalizing behaviors, such as aggressivity or hyperactivity, and girls displaying higher internalizing behaviors, including anxiety, depression, or attention disorders. Indeed, ASD and ADHD are linked to high prenatal testosterone exposure and reduced aromatase expression, potentially explaining sex differences in prevalence and symptomatology. In line with this, high estrogen levels seem to attenuate ADHD symptoms. At the cerebrovascular level, sex- and region-specific variations of cerebral blood flow perfusion have been reported in both conditions, indicating an impact of gonadal hormones on the brain vascular system, disrupting its ability to respond to neuronal demands. This review aims to provide an overview of the existing knowledge concerning the impact of sex hormones on cerebrovascular formation and maturation, as well as the onset of neurodevelopmental disorders. Here, we explore the concept of gonadal hormone interactions with brain vascular and BBB development to function, with a particular focus on the modulation of VEGF and Wnt signaling. We outline how these pathways may be involved in the underpinnings of ASD and ADHD. Outstanding questions and potential avenues for future research are highlighted, as uncovering sex-specific physiological and pathological aspects of brain vascular development might lead to innovative therapeutic approaches in the context of ASD, ADHD and beyond.

In previous studies, the mean geothermal gradient of the Tlemcen region has been estimated as low (3.7°C/100m). The existing boreholes in the Remchi plain (North of the Tlemcen Mountains) reveal thermal waters (26-48°C) and a remarkable artesianism. To understand the hydrodynamics and origin of thermalism of this groundwater, we merged geophysical and physical-chemical data. Geophysical data allowed us to improve the resolution of the fault network, to estimate the thickness of various sandstone beds connected with the thermal reservoir and to delimit the productive aquifer. Chemical characteristics of waters have been used for a statistical analysis, which displayed two independent water clusters resulting from two hydrodynamic patterns throughout the aquifer. The hydrothermal analysis identifies the depth reached by water and the relationship between water circulation and the fault network. Comparison with previous studies allowed us to build a schematic geological model, which explains hydrodynamics, origin and role of this structure in the groundwater flow.

Objectives: The aim of this study was to demonstrate the performance and added value of rapid glucose determination in cerebrospinal fluid using a connected glucometer. Design and Methods: Intra-assay and inter-assay accuracies were calculated using residual clinical samples. Accuracies were measured by comparing the results obtained with the glucometer to those from the central laboratory on a large routine chemistry platform. Results: The intra-assay coefficients of variation were between 6.1% and 6.2% for low values (18 mg/dL) and between 5.6% and 6.8% for high values (58 mg/dL). The inter-assay coefficients of variation were between 9.4% and 16.3% for the low values (18 mg/dL) and between 5.7% and 8.7% for the high values (pool; ±75 mg/dL). The regression equation by comparison to the central laboratory was y = 4.08 + 0.82 x, with a coefficient of determination (r2) of 0.95. Conclusions: The measurement of glycorrhachia with a connected glucometer before the analysis in the central laboratory allows a rapid orientation in the deferential diagnosis of a meningitis of viral vs bacterial origin. The response time is fast (6 s) and requires only a small amount of fluid (1.2 μL), which is important in infants, especially since lumbar puncture is an integral part of the investigation of the origin of a fever in this population.

Abstract Quinones are electrochemical probes which are used for a large range of applications including bioenergetics. One electrochemical feature of quinones is their possible slow electron transfer kinetics. In this article we compared several quinones towards electron transfer kinetics and the ability of anodic pretreatment to increase electron transfer rate constant. Rotating disk electrode and chronoamperometry measurements were used to revisit their electrochemical behavior. Additionally, the number of electrons exchanged as a function of the characteristic time was used as a proxy to investigate kinetic limitations. A model was suggested to rationalize our results. Beyond a classification of quinones regarding the kinetic and thermodynamic ability of the hydroquinone form to be re‐oxidized, some intrinsic physicochemical properties were identified from our model (such as a time dependency of the exchanged number of electrons) to characterize such important redox mediators.

Abstract The Minamata Convention, a global and legally binding treaty that entered into force in 2017, aims to protect human health and the environment from harmful mercury (Hg) effects by reducing anthropogenic Hg emissions and environmental levels. The Conference of the Parties is to periodically evaluate the Convention’s effectiveness, starting in 2023, using existing monitoring data and observed trends. Monitoring atmospheric Hg levels has been proposed as a key indicator. However, data gaps exist, especially in the Southern Hemisphere. Here, we present over a decade of atmospheric Hg monitoring data at Amsterdam Island (37.80°S, 77.55°E), in the remote southern Indian Ocean. Datasets include gaseous elemental and oxidised Hg species ambient air concentrations from either active/continuous or passive/discrete acquisition methods, and annual total Hg wet deposition fluxes. These datasets are made available to the community to support policy-making and further scientific advancements.

Abstract The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

Lentiviral vectors (LVVs) play a critical role in gene delivery for ex vivo gene-modified cell therapies. However, the lack of scalable LVV production methods and the high cost associated with them may limit their use. In this work, we demonstrate the optimization and development of a scalable, chemically defined, animal component-free LVV production process using adherent human embryonic kidney 293T cells in a fixed-bed bioreactor. The initial studies focused on the optimization of the culture process in 2D static cultures. Process changes such as decreasing cell seeding density on day 0 from 2.5 × 104 to 5 × 103 cells/cm2, delaying the transient transfection from 24 to 120 h post-seeding, reducing plasmid DNA to 167 ng/cm2, and adding 5 mM sodium butyrate 6 h post-transfection improved functional LVV titers by 26.9-fold. The optimized animal component-free production process was then transferred to the iCELLis Nano bioreactor, a fixed-bed bioreactor, where titers of 1.2 × 106 TU/cm2 were achieved when it was operated in perfusion. In this work, comparable functional LVV titers were obtained with FreeStyle 293 Expression medium and the conventional Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum both at small and large scale.

In recent years, the global economy has been hit by a sequence of severe shocks that affected the two largest economies, the USA and the Euro Area, severely. Uncertainties about the future abound. While the challenges are similar for both economies and the policy tools resemble each other, they apply to different economic landscapes. What can they learn from each other? This paper looks at the basic structural facts, the nature of uncertainty shocks, and the efficiency of policy tools in the two economies. The key to understanding recent developments is uncertainty. This paper argues that the channel through which uncertainty influences inflation, wage cost, and unemployment is the markup firms charge to cover their cost of capital. While the measurements of uncertainty are uncertain, adding a proxy for uncertainty can improve the estimates of the basic New Keynesian model. The Federal Reserve Bank has been more successful because it operates in a more integrated capital market. In the Euro Area, uncertainty is higher than in the US and this could make disinflation in Europe more painful in terms of unemployment.

Introduction: Postoperative spinal epidural hematoma (SEH) is a potentially devastating complication for patients and caregivers, and a leading cause for litigation in spine surgery. This article provides a literature review and the consensus statement of the Belgian Society of Neurosurgery (BSN) on the management of postoperative SEH. Research question: Can we implement current evidence to establish a framework on the management of postoperative SEH? Material and methods: Based on a Pubmed search, abstracts were screened for topics covering incidence, pathophysiology, risk factors, surveillance, diagnosis, treatment, and outcome. Relevant topics are presented in a narrative review format, followed by a consensus statement of the BSN with emphasis on rapid diagnosis and treatment. Results: Symptomatic SEH is rare (0.3–1%) and can have an insidious onset with rapid progression to neurological deficits. Recurring risk factors are coagulation deficiencies and multilevel surgery. The protective effect of a postoperative drainage system is uncertain, and early thrombo-embolic prophylaxis does not increase the risk of SEH. Prognosis is dependent on residual neurological function and critically, on the time to reintervention. There is a need for structured neurological observation formats after spine surgery. Discussion and conclusion: Symptomatic SEH after surgery is an unpredictable and severe complication requiring rapid action to maximize outcomes. The BSN proposes three nuclear terms central to SEH management, converging on a triple ‘S’: 1) high level of suspicion 2) speed of diagnosis and 3) immediate surgery. All spine centers can benefit from an institutional protocol in which SEH should be treated as an emergency.

The permeabilization of liposomes by melittin, an antimicrobial peptide (AMP), has been studied by an electrochemiluminescence (ECL) imaging strategy. The methodology consisted first of encapsulating ECL reagents in sealed giant asymmetrical liposomes (100 μm in diameter) made of DOPG/DOPC phospholipids (i.e., 1,2-dioleoyl-sn-glycerol-3-phospho-(1′-rac-glycerol) sodium salt/1,2-dioleolyl-sn-glycero-3-phosphocholine). Then liposomes were placed on an indium tin oxide electrode coated with poly-l-lysine to avoid any membrane poration/permeabilization through polarization of the electrode surface. Finally, the addition of melittin (from 10 μM to 100 nM in concentration) enabled the permeabilization of the lipid membrane followed by the liposome content release and subsequent light generation through the ECL reagents oxidation processes. Interestingly, at a melittin concentration of 10 μM, two successive leakages occurring on the same liposome could be imaged. Combination of ECL and photoluminescence imaging allowed comprehensive monitoring of the permeabilization and content release of a single liposome. This ECL imaging approach opens interesting perspectives to characterize the instant release of vesicle content upon permeabilization by AMPs or other membrane-active species.

The emerging heteropathotype shigatoxigenic (STEC) and extra-intestinal pathogenic Escherichia coli (ExPEC) O80:H2 has been the second leading cause of pediatric HUS in France since the mid-2010s. In contrast with other highly pathogenic STEC serotypes, for which ruminants have clearly been identified as the main human infection source, this heteropathotype’s reservoir remains unknown. In this context, we describe for the first time the isolation of seven STEC O80:H2 strains from healthy cattle on a single cattle farm in France. This study aimed at (i) characterizing the genome and (ii) investigating the phylogenetic positions of these O80:H2 STEC strains. The virulomes, resistomes, and phylogenetic positions of the seven bovine isolates were investigated using in silico typing tools, antimicrobial susceptibility testing and cgMLST analysis after short-read whole genome sequencing (WGS). One representative isolate (A13P112V1) was also subjected to long-read sequencing. The seven isolates possessed ExPEC-related virulence genes on a pR444_A-like mosaic plasmid, previously described in strain RDEx444 and known to confer multi-drug resistance. All isolates were clonally related and clustered with human clinical strains from France and Switzerland with a range of locus differences of only one to five. In conclusion, our findings suggest that healthy cattle in France could potentially act as a reservoir of the STEC-ExPEC O80:H2 pathotype.

The ongoing African swine fever (ASF) pandemic continues to have a major impact on global pork production and trade. Since ASF cannot be distinguished from other swine hemorrhagic fevers clinically, ASF-specific laboratory diagnosis is critical. Thus ASF virus (ASFV)-specific monoclonal antibodies (mAbs) are critical for the development of laboratory diagnostics. In this study, we report one ASFV-specific mAb, F88ASF-55, that was generated and characterized. This mAb recognizes the ASFV A137R-encoded protein (pA137R). Epitope mapping results revealed a highly conserved linear epitope recognized by this mAb, corresponding to amino acids 111–125 of pA137R. We explored the potential use of this mAb in diagnostic applications. Using F88ASF-55 as the detection antibody, six ASFV strains were detected in an enzyme-linked immunosorbent assay (ELISA) with low background. In immunohistochemistry (IHC) assays, this mAb specifically recognized ASFV antigens in the submandibular lymph nodes of animals experimentally infected with different ASFV strains. Although not all ASFV genotypes were tested in this study, based on the conserved ASFV epitope targeted by F88ASF-55, it has the potential to detect multiple ASFV genotypes. In conclusion, this newly generated ASFV pA137R-specific mAb has potential value in ASF diagnostic tool development. It can be used in ELISA, IHC, and possibly-immunochromatographic strip assays for ASFV detection. It also suggests that pA137R may be a good target for diagnostic assays to detect ASFV infection.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

The design of advanced experimental nuclear reactors consists in integrating safety and operational requirements as well as reaching targets in terms of thermal power and neutron spectrum. In order to meet theses constraints, slender structures with little supports and crossing the entire reactor vessel are implemented in the reactor and are subjected to an axial flow that generates flow-induced vibration (FIV). From the industrial point of view, the mastering of the occurrence of FIV and its associated wear in case of contacts is requested. The stationary fluid forces applying on slender tubular structure in response to its motion are of primary interest since they can significantly affect the vibration amplitudes and even the stability of the system, especially in case of confined axial flow with high velocities (typically higher than 10 m/s). In this study it proposed to compare two approaches to estimate the vibration induced by turbulent excitation of an industrial device encountered in a research nuclear reactor. The control-rod guide-tube mock-up of the Jules Horowitz Reactor, previously tested in an hydraulic channel at the Technical Center from Le Creusot in France, is retained for this benchmark. Two models are proposed, one based on derivation of leakage flow theory and the other one was based on potential flow theory with adjusted coefficients given by CFD simulations. The flow induced vibration amplitude is consistent with the experimental data. Also, the calculation and experiment provide similar trends when the boundary conditions are changed.

Development is often assumed to be hardwired in the genome, but several lines of evidence indicate that it is susceptible to environmental modulation with potential long-term consequences, including in mammals1,2. The embryonic germline is of particular interest because of the potential for intergenerational epigenetic effects. The mammalian germline undergoes extensive DNA demethylation3-7 that occurs in large part by passive dilution of methylation over successive cell divisions, accompanied by active DNA demethylation by TET enzymes3,8-10. TET activity has been shown to be modulated by nutrients and metabolites, such as vitamin C11-15. Here we show that maternal vitamin C is required for proper DNA demethylation and the development of female fetal germ cells in a mouse model. Maternal vitamin C deficiency does not affect overall embryonic development but leads to reduced numbers of germ cells, delayed meiosis and reduced fecundity in adult offspring. The transcriptome of germ cells from vitamin-C-deficient embryos is remarkably similar to that of embryos carrying a null mutation in Tet1. Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in vitamin C during gestation partially recapitulates loss of TET1, and provide a potential intergenerational mechanism for adjusting fecundity to environmental conditions.