Early, late or never? When does parental education impact child outcomes?

We study the intergenerational effects of parents’ education on their children’s educational outcomes. The endogeneity of parental education is addressed by exploiting the exogenous shift in education levels induced by the 1972 Raising of the School Leaving Age (RoSLA) from age 15 to 16 in England and Wales. Using data from the Avon Longitudinal Study of Parents and Children – a rich cohort dataset of children born in the early 1990s in Avon, England – allows us to examine the timing of impacts throughout the child’s life, from pre-school assessments through the school years to the final exams at the end of the compulsory schooling period. We also determine whether there are differential effects for literacy and numeracy. We find that increasing parental education has a positive causal effect on children’s outcomes that is evident at age 4 and continues to be visible up to and including the high stakes exams taken at age 16. Children of parents affected by the reform gain results just under 0.1 standard deviations higher than those whose parents were not impacted. The effect is focused on the lower educated parents where we would expect there to be more of an impact: children of these parents gaining results approximately 0.2 standard deviations higher. The effects appear to be broadly equal across numeracy and literacy test scores

Basic mechanisms of DNA-raised antibody responses to intramuscular and gene gun immunizations

DNA-raised antibody (Ab) responses have been compared for the dependence on CD4+ and CD8+ cells, the longevity of functional antigen (Ag) expression, and the nature of the Ag-presenting cell after intramuscular (i.m.) and gene gun inoculations. A plasmid expressing the hemagglutinin (HA) glycoprotein of influenza virus was used for immunizations of BALB/c mice. Intramuscular and gene gun-raised Abs had similar dependencies on CD4+ and CD8+ cells but different temporal patterns of functional Ag expression. The two methods of DNA immunization also appeared to have different frequencies or types of Ag-presenting cells in the draining lymph nodes and spleen. For both methods of DNA delivery, Ab was independent of CD8+ cells but dependent on CD4+ cells. The CD4 dependence occurred at priming but not booster immunizations and resulted in a 1-month delay in the Ab response. Temporal T-cell transfers from TCR+/+ mice into immunized TCR-/- mice revealed the persistence of DNA-expressed Ag for up to 1 month after both i.m. and gene gun inoculations. For gene gun, but not i.m. immunizations, approximately 90% of the functional Ag expression was lost by 1 week, consistent with the sloughing of the epidermal target site. Despite similar titers of raised Ab, Ag-presenting dendritic cells could be detected in the draining lymph nodes and spleen of gene gun- but not i.m. DNA-immunized mice. In the gene gun-immunized mice, Ag-presenting dendritic cells appeared in the draining lymph nodes before the spleen

Use of DNAs Expressing HIV-1 Env and Noninfectious HIV-1 Particles to Raise Antibody Responses in Mice

AbstractTwo DNA constructs encoding portions of the human immunodeficiency virus type-1 (HIV-1) genome have been used to raise antibody responses in BABL/c mice. One DNA (pNL4-3.env) expresses the natural form of the envelope glycoprotein (Env) of HIV-1-NL4-3 (NL4-3). The second (pNL4-3.dpol) produces noninfectious NL4-3 particles. These two DNAs (alone or in combination) raised only transient titers of anti-Env IgG. In the same group in which pNL4-3.dpol DNA raised only transient antibody responses to Env, this DNA raised persistent antibody responses to the p24 virion capsid protein (CA). Antibody responses to Env and CA also showed different abilities to be boosted. The final boosts of pNL4-3.dpol DNA increased titers of anti-CA antibody, but failed to boost the falling titers of anti-Env antibody. At peak titers of anti-Env activity, sera with relatively low ELISA titers of anti-Env IgG (end points of 1:6250) had good titers of neutralizing antibody (∼ 1:3800 for 50 TCID50 of NL4-3). At the end of the experiment (a time when anti-Env antibodies had fallen to near background levels), in vitro-restimulated splenocytes from both pNL4-3.env and pNL4-3.dpol DNA vaccine groups exhibited similar cytotoxic activity

Age-related macular degeneration: choroidal ischaemia?

Aim: Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods: Digitized 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results: In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions: Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion

Taxonbridge: an R package to create custom taxonomies based on the NCBI and GBIF taxonomies

Biological taxonomies establish conventions by which researchers can catalogue and systematically compare their work using nomenclature such as species binomial names and reference identifiers. The ideal taxonomy is unambiguous and exhaustive; however, no such single taxonomy exists, partly due to continuous changes and contributions made to existing taxonomies. The degree to which a taxonomy is useful furthermore depends on context provided by such variables as the taxonomic neighbourhood of a species (e.g., selecting arthropod or vertebrate species) or the geological time frame of the study (e.g., selecting extinct versus extant species). Collating the most relevant taxonomic information from multiple taxonomies is hampered by arbitrarily defined identifiers, ambiguity in scientific names, as well as duplicated and erroneous entries. The goal of taxonbridge is to provide tools for merging the Global Biodiversity Information Facility (GBIF) Backbone Taxonomy and the United States National Center for Biotechnology Information (NCBI) Taxonomy in order to create consistent, deduplicated and disambiguated custom taxonomies that reference both extant and extinct species

Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus

DNA vaccines offer promising strategies for immunization against infections. However, their clinical use requires improvements in immunogenicity. We explored the efficacy of Toll-like receptor (TLR) ligands (TLR-Ls) on augmenting the immunogenicity of a DNA prime–modified vaccinia virus Ankara (MVA) boost vaccine against SIV. Rhesus macaques were injected with Fms-like tyrosine kinase 3 (Flt3)–ligand (FL) to expand dendritic cells (DCs) and were primed with a DNA vaccine encoding immunodeficiency virus antigens mixed with ligands for TLR9 or TLR7/8. Subsequently, the animals were boosted with DNA and twice with recombinant MVA expressing the same antigens. TLR9-L (CpG DNA) mediated activation of DCs in vivo and enhanced the magnitude of antigen-specific CD8+ interferon (IFN) γ+ T cells and polyfunctional CD8+ T cells producing IFN-γ, tumor necrosis factor α, and interleukin 2. Although this trial was designed primarily as an immunogenicity study, we challenged the animals with pathogenic SIVmac251 and observed a reduction in peak viremia and cumulative viral loads in the TLR9-L plus FL-adjuvanted group relative to the unvaccinated group; however, the study design precluded comparisons between the adjuvanted groups and the group vaccinated with DNA/MVA alone. Viral loads were inversely correlated with the magnitude and quality of the immune response. Thus, the immunogenicity of DNA vaccines can be augmented with TLR9-L plus FL

Enhanced Avidity Maturation of Antibody to Human Immunodeficiency Virus Envelope: DNA Vaccination with gp120-C3d Fusion Proteins

DNA vaccination can elicit both humoral and cellular immune responses and can confer protection against several pathogens. However, DNA vaccines expressing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at generating high titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, we report that fusion of Env and the complement component, C3d, in a DNA vaccine, enhances the titers of antibody to Env. Plasmids were generated that expressed a secreted form of Env (sgp120) from three isolates of HIV and these same forms fused to three tandem copies of the murine homologue of C3d (sgp120-3C3d). Analyses of titers and avidity maturation of the raised antibody indicated that immunizations with each of the sgp120-3C3d-expressing DNAs accelerated both the onset and the avidity maturation of antibody to Env. Originally published AIDS Research and Human Retroviruses, Vol. 17, No. 9, June 200

Examining evidence for behavioural mimicry of parental eating by adolescent females.:An observational study

Behavioural mimicry is a potential mechanism explaining why adolescents appear to be influenced by their parents' eating behaviour. In the current study we examined whether there is evidence that adolescent females mimic their parents when eating. Videos of thirty-eight parent and female adolescent dyads eating a lunchtime meal together were examined. We tested whether a parent placing a food item into their mouth was associated with an increased likelihood that their adolescent child would place any food item (non-specific mimicry) or the same item (specific mimicry) in their mouth at three different time frames, namely, during the same second or within the next fifteen seconds (+15), five seconds (+5) or two second (+2) period. Parents and adolescents' overall food intake was positively correlated, whereby a parent eating a larger amount of food was associated with the adolescent eating a larger meal. Across all of the three time frames adolescents were more likely to place a food item in their mouth if their parent had recently placed that same food item in their mouth (specific food item mimicry); however, there was no evidence of non-specific mimicry. This observational study suggests that when eating in a social context there is evidence that adolescent females may mimic their parental eating behaviour, selecting and eating more of a food item if their parent has just started to eat that food

GM-CSF DNA: An adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine

AbstractSingle intradermal or intramuscular inoculations of GM-CSF DNA with the DNA prime for a simian–human immunodeficiency virus (SHIV)-89.6 vaccine, which consists of DNA priming followed by modified vaccinia Ankara (MVA) boosting, increased protection of both the blood and intestines against the acute phase of an intrarectal SHIV-89.6P challenge. GM-CSF appeared to contribute to protection by enhancing two antibody responses: the avidity maturation of anti-Env IgG in blood (p=<0.01) and the presence of long lasting anti-viral IgA in rectal secretions (p<0.01). The avidity of anti-Env IgG showed strong correlations with protection both pre and post challenge. Animals with the highest avidity anti-Env Ab had 1000-fold reductions in peak viremia over those with the lowest avidity anti-Env Ab. The enhanced IgA response was associated with the best protection, but did not achieve significance

Application of a new multi-locus variable number tandem repeat analysis (MLVA) scheme for the seasonal investigation of Cryptosporidium parvum cases in Wales and the northwest of England, spring 2022

The protozoan Cryptosporidium parvum is an important cause of gastroenteritis in humans and livestock, and cryptosporidiosis outbreaks are common. However, a multi-locus genotyping scheme is not widely adopted. We describe the further development and application of a seven-locus multi-locus variable number of tandem repeats analysis (MLVA) scheme. From 28th March to 31st July 2022, confirmed C. parvum stools (n = 213) from cryptosporidiosis patients (cases) in Wales (n = 95) and the north west of England (n = 118) were tested by MLVA. Typability (defined as alleles identified at all seven loci in a sample) was 81.2% and discriminatory power estimated by Hunter Gaston Discriminatory Index was 0.99. A MLVA profile was constructed from the alleles, expressed in chromosomal order. Profiles were defined as simple (single allele at each locus) or mixed (more than one allele at any locus). A total of 161 MLVA profiles were identified; 13 were mixed, an additional 38 simple profiles contained null records, and 110 were complete simple profiles. A minimum spanning tree was constructed of simple MLVA profiles and those identical at all seven loci defined genetic clusters of cases (here, null records were considered as an allele); 77 cases formed 25 clusters, ranging from two to nine (mode = two) cases. The largest cluster, following epidemiological investigation, signalled a newly-identified outbreak. Two other cases with mixed profiles that contained the outbreak alleles were included in the outbreak investigation. In another epidemiologically-identified outbreak of six initial cases, MLVA detected two additional cases. In a third, small outbreak of three cases, identical MLVA profiles strengthened the microbiological evidence. Review of the performance characteristics of the individual loci and of the seven-locus scheme suggested that two loci might be candidates for review, but a larger dataset over a wider geographical area and longer timeframe will help inform decision-making about the scheme by user laboratories and stakeholders (such as public health agencies). This MLVA scheme is straightforward in use, fast and cheap compared to sequence-based methods, identifies mixed infections, provides an important tool for C. parvum surveillance, and can enhance outbreak investigations and public health action