Is the onset of disabling chronic conditions in later childhood associated with exposure to social disadvantage in earlier childhood? A prospective cohort study using the ONS Longitudinal Study for England and Wales

Background: The aetiology of disabling chronic conditions in childhood in high income countries is not fully understood, particularly the association with socio-economic status (SES). Very few studies have used longitudinal datasets to examine whether exposure to social disadvantage in early childhood increases the risk of developing chronic conditions in later childhood. Here we examine this association, and its temporal ordering, with onset of all-cause disabling chronic later childhood in children reported as free from disability in early childhood. Methods: The study comprised a prospective cohort study, using data from the Office for National Statistics Longitudinal Study (ONSLS) for England and Wales. The study sample included 52,839 children with complete data born between 1981–1991 with no disabling chronic condition/s in 1991. Index cases were children with disability recorded in 2001. Comparison cases were children with no recorded disability in 1991. A socio-economic disadvantage index (SDI) was constructed from data on social class, housing tenure and car/van access. Associations were explored with logistic regression modelling controlling sequentially for potentially confounding factors; age, gender, ethnicity and lone parenthood. Results: By 2001, 2049 (4%) had at least one disability. Socio-economic disadvantage, age, gender and lone parenthood but not ethnicity were significantly associated with onset of disabling chronic conditions. The SDI showed a finely graded association with onset of disabling chronic conditions in the index group (most disadvantaged OR 2·11 [CI 1·76 to 2·53]; disadvantaged in two domains OR 1·45 [CI 1·20 to 1·75]; disadvantaged in one domain OR 1·14 [CI 0·93 to 1·39] that was unaffected by age, gender and ethnicity and slightly attenuated by lone parenthood. Conclusion: To our knowledge, this is the first study to identify socio-economic disadvantage in earlier childhood as a predisposing factor for onset of all-cause disabling chronic conditions in later childhood. Temporal ordering and gradation of the response indicate socio-economic disadvantage may play a causal role. This suggests that targeting preventative efforts to reduce socio-economic disadvantage in early childhood is likely to be an important public health strategy to decease health inequalities in later childhood and early adulthood

Issues of gender, reflexivity and positionality in the field of disability : researching visual impairment in an Arab society

This article examines how the social and cultural context influence the way in which field research methods are utilized. Research methods need to be modified to meet the sensibilities and sensitivities of particular social groups and settings. Through a reflexive analysis of a research study on the lives of visually impaired young people and adults in Bahrain, this article discusses how gender, religion and culture need to be taken account of. It also discusses how the research process needed to take account of the participants’ disabilities. It examines the issues of research access, informed consent, researcher’s dress, confidentiality, research location, and time. It highlights how the gender of the researcher was constraining in some gender segregated educational settings in a Muslim society. The article engages with the researcher’s positionality through reflexive discussion

Effect of strategies to reduce exposure of infants to environmental tobacco smoke in the home : cross sectional survey

Objective To examine parents' reported knowledge and use of harm reduction strategies to protect their infants from exposure to tobacco smoke in the home, and the relation between reported use of strategies and urinary cotinine to creatinine ratios in the infants. Design Cross sectional survey. Settings Coventry and Birmingham. Main outcome measures Parents’ reported knowledge and use of harm reduction strategies and urinary cotinine to creatinine ratios in their infants. Participants 314 smoking households with infants. Results 86% of parents (264/307) believed that environmental tobacco smoke is harmful, 90% (281/314) believed that infants can be protected from it in the home, and 10% (32/314) were either unaware of measures or reported using none. 65% of parents (205/314) reported using two or more measures, but only 18% (58/314) reported not allowing smoking in the home. No difference was found in mean log e transformed urinary cotinine to creatinine ratio in infants from households that used no measures compared with households that used less strict measures. Mean log cotinine to creatinine ratios were significantly different in households banning smoking in the home compared with those using less strict or no measures. Banning smoking in the home was independently associated with a significant reduction in urinary cotinine to creatinine ratio by a factor of 2.6 (1.6 to 4.2) after adjustment for average household cigarette consumption, tenure, and overcrowding. Conclusions Less than a fifth of parents in smoking households ban smoking in the home. Banning smoking was associated with a small but significant reduction in urinary cotinine to creatinine ratio in infants, whereas less strict measures compared with no measures had no effect on the infants’ exposure to environmental tobacco smoke

Disabling chronic conditions in childhood and socioeconomic disadvantage : a systematic review and meta-analyses of observational studies

Objective To determine the association of socioeconomic disadvantage with the prevalence of childhood disabling chronic conditions in high-income countries. Study design Systematic review and meta-analyses. Data sources 6 electronic databases, relevant websites, reference lists and experts in the field. Study selection 160 observational studies conducted in high-income countries with data on socioeconomic status and disabling chronic conditions in childhood, published between 1 January 1991 and 31 December 2013. Data extraction and synthesis Abstracts were reviewed, full papers obtained, and papers identified for inclusion by 2 independent reviewers. Inclusion decisions were checked by a third reviewer. Where reported, ORs were extracted for low versus high socioeconomic status. For studies reporting raw data but not ORs, ORs were calculated. Narrative analysis was undertaken for studies without data suitable for meta-analysis. Results 126 studies had data suitable for meta-analysis. ORs for risk estimates were: all-cause disabling chronic conditions 1.72 (95% CI 1.48 to 2.01); psychological disorders 1.88 (95% CI 1.68 to 2.10); intellectual disability 2.41 (95% CI 2.03 to 2.86); activity-limiting asthma 2.20 (95% CI 1.87 to 2.85); cerebral palsy 1.42 (95% CI 1.26 to 1.61); congenital abnormalities 1.41 (95% CI 1.24 to 1.61); epilepsy 1.38 (95% CI 1.20 to 1.59); sensory impairment 1.70 (95% CI 1.39 to 2.07). Heterogeneity was high across most estimates (I2>75%). Of the 34 studies without data suitable for meta-analysis, 26 reported results consistent with increased risk associated with low socioeconomic status. Conclusions The findings indicate that, in high-income countries, childhood disabling chronic conditions are associated with social disadvantage. Although evidence of an association is consistent across different countries, the review provides limited evidence to explain the association; future research, using longitudinal data, will be required to distinguish low socioeconomic status as the cause or consequence of childhood disabling chronic conditions and the aetiological pathways and mechanisms

Monitoring the Sustainable Intensification of Arable Agriculture:the Potential Role of Earth Observation

Sustainable intensification (SI) has been proposed as a possible solution to the conflicting problems of meeting projected increases in food demand and preserving environmental quality. SI would provide necessary production increases while simultaneously reducing or eliminating environmental degradation, without taking land from competing demands. An important component of achieving these aims is the development of suitable methods for assessing the temporal variability of both the intensification and sustainability of agriculture. Current assessments rely on traditional data collection methods that produce data of limited spatial and temporal resolution. Earth Observation (EO) provides a readily accessible, long-term dataset with global coverage at various spatial and temporal resolutions. In this paper we demonstrate how EO could significantly contribute to SI assessments, providing opportunities to quantify agricultural intensity and environmental sustainability. We review an extensive body of research on EO-based methods to assess multiple indicators of both agricultural intensity and environmental sustainability. To date these techniques have not been combined to assess SI; here we identify the opportunities and initial steps required to achieve this. In this context, we propose the development of a set of essential sustainable intensification variables (ESIVs) that could be derived from EO data

Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function

BACKGROUND: Parasites exploit sophisticated strategies to evade host immunity that require both adaptation of existing genes and evolution of new gene families. We have addressed this question by testing the immunological function of novel genes from helminth parasites, in which conventional transgenesis is not yet possible. We investigated two such novel genes from Brugia malayi termed abundant larval transcript (alt), expression of which reaches ~5% of total transcript at the time parasites enter the human host. RESULTS: To test the hypothesis that ALT proteins modulate host immunity, we adopted an alternative transfection strategy to express these products in the protozoan parasite Leishmania mexicana. We then followed the course of infection in vitro in macrophages and in vivo in mice. Expression of ALT proteins, but not a truncated mutant, conferred greater infectivity of macrophages in vitro, reaching 3-fold higher parasite densities. alt-transfected parasites also caused accelerated disease in vivo, and fewer mice were able to clear infection of organisms expressing ALT. alt-transfected parasites were more resistant to IFN-γ-induced killing by macrophages. Expression profiling of macrophages infected with transgenic L. mexicana revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, both associated with the Th2-type response observed in in vivo filarial infection. CONCLUSION: Leishmania transfection is a tractable and informative approach to determining immunological functions of single genes from heterologous organisms. In the case of the filarial ALT proteins, our data suggest that they may participate in the Th2 bias observed in the response to parasite infection by modulating cytokine-induced signalling within immune system cells

Real-time imaging of Leishmania mexicana-infected early phagosomes: a study using primary macrophages generated from green fluorescent protein-Rab5 transgenic mice

The small GTPase Rab5 is a key regulator of endosome/phagosome maturation and in intravesicular infections marks a phagosome stage at which decisions over pathogen replication or destruction are integrated. It is currently unclear whether Leishmania-infected phagosomes uniformly pass through a Rab5+ stage on their intracellular path to compartments with late endosomal/early lysosomal characteristics. Differences in routes and final compartments could have consequences for accessibility to antileishmanial drugs. Here, we generated a unique gfp-rab5 transgenic mouse model to visualize Rab5 recruitment to early parasite-containing phagosomes in primary host cells. Using real-time fluorescence imaging of phagosomes carrying Leishmania mexicana, we determined that parasite-infested phagosomes follow a uniform sequence of transient Rab5 recruitment. Residence in Rab5+ compartments was much shorter compared with phagosomes harboring latex beads. Furthermore, a comparative analysis of parasite life-cycle stages and mutants deficient in lpg1, the gene encoding the enzyme required for synthesis of the dominant surface lipophosphoglycan, indicated that parasite surface ligands and host cell receptors modulate pathogen residence times in Rab5+ phagosomes, but, as far as tested, had no significant effect on intracellular L. mexicana survival or replication.—Lippuner, C., Paape, D., Paterou, A., Brand, J., Richardson, M., Smith, A. J., Hoffmann, K., Brinkmann, V., Blackburn, C., Aebischer, T. Real-time imaging of Leishmania mexicana-infected early phagosomes: a study using primary macrophages generated from green fluorescent protein-Rab5 transgenic mice

Developing a new paradigm for Thymus organogenesis

The mature thymic epithelium is complex, with two major compartments — the cortex and the medulla — each containing several functionally distinct epithelial-cell types. There is considerable debate as to the embryonic origins of these different thymic epithelial-cell subpopulations. The textbook view is a dual origin, with cortical thymic epithelium arising from the ectoderm and medullary thymic epithelium originating in the endoderm. However, the literature has been divided on this issue since it was first considered. In this review, we discuss recent embryological, functional, genetic and molecular data that collectively support a new model of thymus organogenesis and patterning