Addressing diversity and inclusion in the early years in conflict-affected societies: A case study of the Media Initiative for Children – Northern Ireland

This article reports on the development and systematic evaluation of an innovative early years programme aimed at encouraging young children to respect differences within a deeply-divided society that is emerging out of a prolonged period of violent conflict. The programme, the Media Initiative for Children – Northern Ireland, has been the product of a partnership between an US-based organisation (the Peace Initiatives Institute) and NIPPA – The Early Years Organisation and has been supported by academic research and the efforts of a range of voluntary and statutory organisations. It has attempted to encourage young children to value diversity and be more inclusive of those who are different to themselves through the use of short cartoons designed for and broadcast on television as well as specially-prepared curricular materials for use in pre-school settings. To date the programme has been delivered through 200 settings to approximately 3,500 pre-school children across Northern Ireland. This article describes how the programme was developed and implemented as well as the rigorous approach taken to evaluating its effects on young children’s attitudes and awareness. Key lessons from this are identified and discussed in relation to future work in this area.

Early target cells of measles virus after aerosol infection of non-human primates

Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMV(KS)EGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n?=?3 per time point) and infected (EGFP(+)) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP(+) cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia.

Developmental care for high-risk newborns:Emerging science, clinical application, and continuity from newborn intensive care unit to community

Neonatology has optimized medical outcomes for high-risk newborns yet neurodevelopmental outcomes continue to be a concern. Basic science, clinical research, and environmental design perspectives have shown the impact of the caregiving environment on the developing brain and the role of professional caregivers in providing supportive intervention to both infants and their families. This recognition has prompted a focus on early developmentally supportive care (DSC) for high-risk newborns both in the hospital and in community follow up. DSC has emerged as a recognized standard of care in most neonatal intensive care units. Still, many questions remain and much integrative research is needed.

GENOTYPE-PHENOTYPE ASSOCIATIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE:To examine associations between recognized genetic susceptibility loci and angiographic subphenotypes of the neovascular variant of age-related macular degeneration (nvAMD).METHODS:Participants (247 nvAMD, 52 early age-related macular degeneration [AMD], and 103 controls) were genotyped (complement factor H and ARMS2/HTRA1). nvAMD participants were assigned to one of two subcategories: mainly classic or mainly occult (based on the proportions of classic and occult choroidal neovascularization). nvAMD and early AMD were reassigned to two groups based on the extent and severity of drusen (retinal pigment epithelium dysfunction or not). Univariate and multivariate analysis were used to examine for associations between participant characteristics and genetic loci after adjusting for age, smoking status, and history of cardiovascular disease.RESULTS:Univariate analysis confirmed the known significant associations between AMD stage and age, hypertension, and a history of cardiovascular disease. Those with retinal pigment epithelium dysfunction (F = 5.46; P = 0.02) or a positive smoking history (F = 3.89; P = 0.05) were more likely to have been classified as having mainly an occult rather than a mainly classic lesion. Multivariate analysis showed that significant associations were noted with the number of ARMS2/HTRA1 risk alleles (P

Attention Engagement in Early Infancy

We report a longitudinal study investigating developmental changes in the structure of attention engagement during early infancy. Forty-three infants were observed monthly from 2 to 4 months. Attention engagement was assessed from play interactions with parents, using a coding system developed by Bakeman and Adamson (1984). The results indicated a developmental transition in attention engagement at 3 months: after this age infants engaged for longer periods and in a wider variety of states. Most infants displayed person engagement at 2 months, passive joint engagement at 3 months, and object engagement at 4 months. To address whether emerging abilities of attention engagement allow infants to follow the attention of social partners, we compared attention engagement to performance on an experimental measure of attention control (reported by Perra & Gattis, 2010). Analyses revealed a positive relation between passive joint engagement and checking back, suggesting that changes in passive joint engagement reflect the development in attention control.

ARMS2 Increases the Risk of Early and Late Age-Related Macular Degeneration in the European Eye Study

OBJECTIVE:
To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2.
DESIGN:
Population-based, cross-sectional European Eye Study in 7 countries in Europe.
PARTICIPANTS:
Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.
METHODS:
Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression.
MAIN OUTCOME MEASURES:
Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
RESULTS:
Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD).
CONCLUSIONS:
A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a significant gene-environment interaction with cigarette smoking was confirmed.

Lipoproteins and diabetic microvascular complications

Risk factors for the microvascular complications (nephropathy and retinopathy) of Type 1 and Type 2 diabetes mellitus and the associated accelerated atherosclerosis include: age, diabetes duration, genetic factors, hyperglycaemia, hypertension, smoking, inflammation, glycation and oxidative stress and dyslipoproteinaemia. Hypertriglyceridaemia, low HDL and small dense LDL are common features of Type 2 diabetes and Type 1 diabetes with poor glycaemic control or renal complications. With the expansion of knowledge and of clinical and research laboratory tools, a broader definition of 'lipid' abnormalities in diabetes is appropriate. Dyslipoproteinaemia encompasses alterations in lipid levels, lipoprotein subclass distribution, composition (including modifications such as non-enzymatic glycation and oxidative damage), lipoprotein-related enzymes, and receptor interactions and subsequent cell signaling. Alterations occur in all lipoprotein classes; chylomicrons, VLDL, LDL, HDL, and Lp(a). There is also emerging evidence implicating lipoprotein related genotypes in the development of diabetic nephropathy and retinopathy. Lipoprotein related mechanisms associated with damage to the cardiovascular system may also be relevant to damage to the renal and ocular microvasculature. Adverse tissue effects are mediated by both alterations in lipoprotein function and adverse cellular responses. Recognition and treatment of lipoprotein-related risk factors, supported by an increasing array of assays and therapeutic agents, may facilitate early recognition and treatment of high complication risk diabetic patients. Further clinical and basic research, including intervention trials, is warranted to guide clinical practice. Optimal lipoprotein management, as part of a multi-faceted approach to diabetes care, may reduce the excessive personal and economic burden of microvascular complications and the related accelerated atherosclerosis.

Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age

Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm =32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-?B, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm. © 2013 Grunau et al.

Burkholderia pseudomallei:another emerging pathogen in cystic fibrosis

BACKGROUND: Burkholderia pseudomallei is an important cause of acute fulminant pneumonia and septicaemia in tropical regions of northern Australia and south east Asia. Subacute and chronic forms of the disease also occur. There have been three recent reports of adults with cystic fibrosis (CF) who presumably acquired B pseudomallei infection during extended vacations or residence in either Thailand or northern Australia.

METHODS: The clinical course, molecular characteristics, serology and response to treatment are described in four adult CF patients infected with B pseudomallei. Polymerase chain reaction (PCR) based methods were used to confirm B pseudomallei and exclude B cepacia complex. Genotyping was performed using randomly amplified polymorphic DNA (RAPD) PCR and pulsed field gel electrophoresis (PFGE).

RESULTS: Four patients are described with a mean duration of infection of 32 months. All but one patient lived in tropical Queensland. Two patients (with the longest duration of infection) deteriorated clinically and one subsequently died of respiratory failure. Both responded to intravenous treatment specifically targeting B pseudomallei. Another patient suffered two severe episodes of acute bronchopneumonia following acquisition of B pseudomallei. Eradication of the organism was not possible in any of the cases. PFGE of a sample isolate from each patient revealed the strains to be unique and RAPD analysis showed retention of the same strain within an individual over time.

CONCLUSIONS: These findings support a potential pathogenic role for B pseudomallei in CF lung disease, producing both chronic infection and possibly acute bronchopneumonia. Identical isolates are retained over time and are unique, consistent with likely environmental acquisition and not person to person spread. B pseudomallei is emerging as a significant pathogen for patients with CF residing and holidaying in the tropics.

Young People’s Early Offending: The Context of Strained Leisure Careers

Criminology has witnessed a growth of interest in the later stages of criminal careers with less attention given to providing an understanding of the onset of offending which goes beyond identifying the precipitative or ‘risk’ factors. Drawing on findings from a study of young people’s offending careers in Ireland, this article provides a contextualized understanding of the onset of crime located in young people’s biographical experiences and transition through youth more specifically. It focuses on one particular dimension of this process, suggesting that early offending can be understood as emerging in the context of strained leisure careers. The findings also highlight the close interaction between the development of young people’s leisure careers and their experiences of the local neighbourhood and social networks. It argues that responses to the early stages of youth offending must widen their focus from the individual to incorporate an understanding of broader socio-economic and cultural contexts.

The emerging roles of DNA methylation in the clinical management of prostate cancer

Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor beta2 (RARbeta2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer.