Deriving Niger’s Demographic and Education Future to 2062 with Stakeholders: Which Results?

Niger has the fastest population growth in the world while being among the least developed countries. With an average fertility above seven children per woman in the last decades, rapid population growth will continue in the medium to long term representing a planning challenge for Niger's development whose actual population is likely to double within the next two decades. At the same time, socio-economic variables whether in terms of health, wealth, and education levels are lagging behind, also relatively to many countries in sub-Saharan Africa. While both demographic and education variables occupy a central position in the government strategy, they are not necessarily linked. However, the future of Niger will largely be a reflection of its ability to meet both challenges. Within a project piloted by the Ministry of Planning and funded by the United Nations Children’s Fund, we have derived together with local experts and stakeholders narratives about the possible future of Niger. These were further translated into five scenarios with assumptions about different future paths of demographic and educational development for Niger that were used to project the population, also at sub-national level, using multi-state population projection models with the aim to inform policy. This article reports some projection results related to educational and demographic developments

American political affiliation, 2003–43: a cohort component projection

The recent rise and stability in American party identification has focused interest on the long-term dynamics of party bases. Liberal commentators cite immigration and youth as forces which will produce a natural Democratic advantage in the future while conservative writers highlight the importance of high Republican fertility in securing Republican growth. These concerns foreground the neglect of demography within political science. This paper addresses this omission by conducting the first ever cohort component projection of American partisan populations to 2043 based on survey and census data. A number of scenarios are modeled, but, on current trends, we predict that American partisanship will shift much less than the nation’s ethnic composition because the parties’ age structures are similar. Still, our projections find that the Democrats gain two to three percentage points from the Republicans by 2043, mainly through immigration, though Republican fertility may redress the balance in the very long term

Restriction of HIV-1 Replication in Monocytes Is Abolished by Vpx of SIVsmmPBj

Background: Human primary monocytes are refractory to infection with the human immunodeficiency virus 1 (HIV-1) or transduction with HIV-1-derived vectors. In contrast, efficient single round transduction of monocytes is mediated by vectors derived from simian immunodeficiency virus of sooty mangabeys (SIVsmmPBj), depending on the presence of the viral accessory protein Vpx. Methods and Findings: Here we analyzed whether Vpx of SIVsmmPBj is sufficient for transduction of primary monocytes by HIV-1-derived vectors. To enable incorporation of PBj Vpx into HIV-1 vector particles, a HA-Vpr/Vpx fusion protein was generated. Supplementation of HIV-1 vector particles with this fusion protein was not sufficient to facilitate transduction of human monocytes. However, monocyte transduction with HIV-1-derived vectors was significantly enhanced after delivery of Vpx proteins by virus-like particles (VLPs) derived from SIVsmmPBj. Moreover, pre-incubation with Vpx-containing VLPs restored replication capacity of infectious HIV-1 in human monocytes. In monocytes of non-human primates, single-round transduction with HIV-1 vectors was enabled. Conclusion: Vpx enhances transduction of primary human and even non-human monocytes with HIV-1-derived vectors, only if delivered in the background of SIVsmmPBj-derived virus-like particles. Thus, for accurate Vpx function the presence of SIVsmmPBj capsid proteins might be required. Vpx is essential to overcome a block of early infection steps in primary monocytes

Hepatitis C virus infection among transmission-prone medical personnel

Hepatitis C virus (HCV)-infected physicians have been reported to infect some of their patients during exposure-prone procedures (EPPs). There is no European consensus on the policy for the prevention of this transmission. To help define an appropriate preventive policy, we determined the prevalence of HCV infection among EPP-performing medical personnel in the Academic Medical Center in Amsterdam, the Netherlands. The prevalence of HCV infection was studied among 729 EPP-performing health care workers. Serum samples, stored after post-hepatitis B virus (HBV) vaccination testing in the years 2000–2009, were tested for HCV antibodies. Repeat reactive samples were confirmed by immunoblot assay and the detection of HCV RNA. The average age of the 729 health care workers was 39 years (range 18–66), suggesting a considerable cumulative occupational exposure to the blood. Nevertheless, only one of the 729 workers (0.14%; 95% confidence interval [CI]: <0.01% to 0.85%) was tested and confirmed to be positive for anti-HCV and positive for HCV RNA, which is comparable to the prevalence of HCV among Amsterdam citizens. Against this background, for the protection of personnel and patients, careful follow-up after needlestick injuries may be sufficient. If a zero-risk approach is desirable and costs are less relevant, the recurrent screening of EPP-performing personnel for HCV is superior to the follow-up of reported occupational exposures

Updating the Shared Socioeconomic Pathways (SSPs) Global Population and Human Capital Projections

The first set of population projections following the Shared Socioeconomic Pathways (SSPs) was developed in 2013. These projections have found widespread use within the environmental and climate change community, among others. In 2018, an SSPs update was generated but not integrated into the SSP database. In 2021, the SSP community requested an update of the human core of the SSPs, which is detailed in this report. This updated version is based on 2020 as the reference year, with adjustments to certain short-term assumptions extending to 2030. Consequently, the assumptions' trend component is grounded in recent observed changes. The modeling approaches for fertility, mortality, and educational attainment have been revised. Notably, there are updates to education-specific fertility rates with new estimates. Education-specific mortality has been made specific to countries and regions. Additionally, this version introduces explicit education-specific migration differentials. The paper presents a comparison between the methodology used for developing the global population and education projections under the five SSPs and the previous method. Furthermore, a brief analysis is conducted on the primary results regarding population size and composition, with comparisons made to earlier projections and other organizations, including the United Nations Population Division

SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Goutières Syndrome Are Highly Susceptible to HIV-1 Infection

Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 degradation rendered primary monocytes highly susceptible to HIV-1 infection; Vpx with a T17A mutation, defective for SAMHD1 binding and degradation, did not show this activity. Several single nucleotide polymorphisms in the SAMHD1 gene have been associated with Aicardi-Goutières syndrome (AGS), a very rare and severe autoimmune disease. Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation. Our results indicate that within PBMC from AGS patients, CD14+ cells were the subpopulation susceptible to HIV-1 infection, whereas cells from healthy donors did not support infection. The monocytic lineage of the infected SAMHD1 -/- cells, in conjunction with mostly undetectable levels of cytokines, chemokines and type I interferon measured prior to infection, indicate that aberrant cellular activation is not the cause for the observed phenotype. Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor

Interferon-Alpha Mediates Restriction of Human Immunodeficiency Virus Type-1 Replication in Primary Human Macrophages at an Early Stage of Replication

Type I interferons (IFNα and β) are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα

Thresholds of ENDOGLIN expression in endothelial cells explains vascular etiology in Hereditary Hemorrhagic Telangiectasia type 1

Hereditary Hemorrhagic Telangiectasia type 1 (HHT1) is an autosomal dominant inherited disease characterized by arteriovenous malformations and hemorrhage. HHT1 is caused by mutations in ENDOGLIN, which encodes an ancillary receptor for Transforming Growth Factor-beta/Bone Morphogenetic Protein-9 expressed in all vascular endothelial cells. Haploinsufficiency is widely accepted as the underlying mechanism for HHT1. However, it remains intriguing that only some, but not all, vascular beds are affected, as these causal gene mutations are present in vasculature throughout the body. Here, we have examined the endoglin expression levels in the blood vessels of multiple organs in mice and in humans. We found a positive correlation between low basal levels of endoglin and the general prevalence of clinical manifestations in selected organs. Endoglin was found to be particularly low in the skin, the earliest site of vascular lesions in HHT1, and even undetectable in the arteries and capillaries of heterozygous endoglin mice. Endoglin levels did not appear to be associated with organ-specific vascular functions. Instead, our data revealed a critical endoglin threshold compatible with the haploinsufficiency model, below which endothelial cells independent of their tissue of origin exhibited abnormal responses to Vascular Endothelial Growth Factor. Our results support the development of drugs promoting endoglin expression as potentially protective.Stem cells & developmental biolog

The influence of localised size reorganisation on short-duration bidispersed granular flows

We investigate experimentally the runout resulting from the collapse of a granular column containing two particle species that differ in size only. The experimental configuration is strictly twodimensional (only one particle per width of the experimental tank) and we explore both the role of the initial arrangement and proportion of the two particle sizes in the column, using high-speed videography, and by determining the centres of mass of the big and small particles in the initial column and the final deposit. The duration of the experiment is sufficiently short that large-scale segregation does not occur, however, we find a clear dependence of runout on both initial mixture arrangement and proportion for all conditions. We investigated this observation through detailed analysis of the flow front motion, and identify a characteristic "stopping" phase when dissipation dominates, and we apply a shallow layer model at the flow front to show how the initial mixture arrangement and proportion influence the effective coefficient of friction during emplacement. We find that a bidispersed mixture can induce a larger friction on emplacement than a monodispersed mixture, and the highest coefficient of friction was found for a well-mixed initial arrangement of particles at the proportion that shows maximum horizontal spreading of the flow. These observations suggest that downwards percolation of fine particles takes place at the front of the collapsing column, and so localised size segregation processes at the flow front can control flow mobility. This effect is likely to be important in controlling the mobility of large geophysical flows that occur on finite time scales, and whose deposits typically show granular segregation at the front and edges but not throughout the entire deposit