Scenarios of Delayed First Births and Associated Cohort Fertility Levels.

Fertility rates among individuals in their 20s have fallen sharply across Europe over the past 50 years. The implications of delayed first births for fertility levels in modern family regimes remain little understood. Using microsimulation models of childbearing and partnership for the 1970-1979 birth cohorts in Italy, Great Britain, Sweden, and Norway, we implement fictive scenarios that reduce the risk of having a first child before age 30 and examine fertility recovery mechanisms for aggregate fertility indicators (the proportion of women with at least one, two, three, or four children; cohort completed fertility rate). Exposure to a first birth increases systematically in the ages following the simulated reduction in first-birth risks, leading to a structural recovery in childbearing that varies across countries according to their fertility and partnership regimes. Full recovery requires an increase in late first-birth risks, with greater increases in countries where late family formation is uncommon and average family sizes are larger: in scenarios where early fertility declines substantially (a linear decline from 50% at age 15 to 0% at age 30), first-birth risks above age 30 would have to increase by 54% in Great Britain, 40% in Norway and Sweden, and 20% in Italy to keep completed fertility constant.

CORESIDENCE: National and subnational data on household size and composition around the world, 1964-2021.

The CORESIDENCE Database (CoDB) represents a significant advancement in the field of family studies, addressing existing data gaps and facilitating comprehensive analysis of households' composition and living arrangements at the national and subnational levels. This article introduces the CoDB, developed for the ERC project Intergenerational Coresidence in Global Perspective: Dimensions of Change. The database draws on global-scale individual microdata from four main repositories and national household surveys, encompassing over 150 million individual records representing more than 98% of the world's population. The CoDB provides datasets at the national, subnational, and subnational-harmonized levels, covering 156 countries, 3950 regions, and 1511 harmonized regions for the period 1964-2021. It includes 146 indicators on household composition and family arrangements, allowing researchers to explore intergenerational co-residence patterns, gender dynamics within households, and longitudinal trends in living arrangements. The CoDB fills an important gap in comparative household studies, enabling researchers to undertake ground breaking research at both macro and micro levels, ultimately fostering a deeper understanding of the complex dynamics of family structures and living arrangements.

Pathogenic T cell responses against aquaporin 4.

Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4.

T cell-activation in neuromyelitis optica lesions plays a role in their formation.

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS), which is characterized by the presence of pathogenic serum autoantibodies against aquaporin 4 (AQP4) in the vast majority of patients. The contribution of T cells to the formation of astrocyte destructive lesions is currently unclear. However, active human NMO lesions contain CD4+ T-lymphocytes expressing the activation marker Ox40, and the expression is more profound compared to that seen in MS lesions of comparable activity. Therefore, we analyzed the role of T-cell activation within the CNS in the initiation of NMO lesions in an experimental model of co-transfer of different encephalitogenic T-cells and human AQP4 antibody containing NMO immunoglobulin (NMO IgG). We further studied the expression of the T-cell activation marker Ox40 in NMO and multiple sclerosis lesions in different stages of activity. RESULTS: All encephalitogenic T-cell lines used in our experiments induced brain inflammation with a comparable extent of blood brain barrier damage, allowing human NMO IgG to penetrate into the brain and spinal cord tissue. However, astrocyte destructive NMO lesions were only seen with T-cells, which showed signs of activation in the lesions. T-cell activation was reflected by the expression of the activation marker Ox40 and pronounced production of γ-IFN, which was able to increase the production of complement proteins and of the Fc gamma III receptor (Fcgr3) and decreased production of complement inhibitory protein Factor H in microglia. CONCLUSIONS: Our data indicate that local activation of T-cells provide an inflammatory environment in the CNS, which allows AQP4 auto-antibodies to induce astrocyte destructive NMO-like lesions.