Melanopsin mediated post-illumination pupil response in early age-related macular degeneration

Purpose To determine whether melanopsin expressing intrinsically photosensitive Retinal Ganglion Cell (ipRGC) inputs to the pupil light reflex (PLR) are affected in early age-related macular degeneration (AMD). Methods The PLR was measured in 40 participants (20 early AMD and 20 age-matched controls) using a custom-built Maxwellian-view pupillometer. Sinusoidal stimuli (0.5 Hz, 11.9 s duration, 35.6° diameter) were presented to the study eye and the consensual pupil response was measured for stimuli with high melanopsin excitation (464nm; blue) and with low melanopsin excitation (638 nm; red) that biased activation to the outer retina. Two melanopsin PLR metrics were quantified: the Phase Amplitude Percentage (PAP) during the sinusoidal stimulus presentation and the Post-Illumination Pupil Response (PIPR). The PLR during stimulus presentation was analyzed using latency to constriction, transient pupil response and maximum pupil constriction metrics. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. Results The blue PIPR was significantly less sustained in the early AMD group (p<0.001). The red PIPR was not significantly different between groups (p>0.05). The PAP and blue stimulus constriction amplitude were significantly lower in the early AMD group (p < 0.05). There was no significant difference between groups in the latency or transient amplitude for both stimuli (p>0.05). ROC analysis showed excellent diagnostic accuracy for the blue PIPR metrics (AUC>0.9). Conclusions This is the initial report that the melanopsin controlled PIPR is dysfunctional in early AMD. The non-invasive, objective measurement of the ipRGC controlled PIPR has excellent diagnostic accuracy for early AMD.

Melanopsin ganglion cell function in early age-related macular degeneration

Purpose Melanopsin-expressing retinal ganglion cells (mRGCs) have non-image forming functions including mediation of the pupil light reflex (PLR). There is limited knowledge about mRGC function in retinal disease. Initial retinal changes in age-related macular degeneration (AMD) occur in the paracentral region where mRGCs have their highest density, making them vulnerable during disease onset. In this cross-sectional clinical study, we measured the PLR to determine if mRGC function is altered in early stages of macular degeneration. Methods Pupil responses were measured in 8 early AMD patients (AREDS 2001 classification; mean age 72.6 ± 7.2 years, 5M, and 3F) and 12 healthy control participants (mean age 66.6 ± 6.1 years, 8M and 4F) using a custom-built Maxwellian-view pupillometer. Stimuli were 0.5 Hz sinewaves (10 s duration, 35.6° diameter) of short wavelength light (464nm, blue; retinal irradiance = 14.5 log quanta.cm-2.s-1) to produce high melanopsin excitation and of long wavelength light (638nm, red; retinal irradiance = 14.9 log quanta.cm-2.s-1), to bias activation to outer retina and provide a control. Baseline pupil diameter was determined during a 10 s pre-stimulus period. The post illumination pupil response (PIPR) was recorded for 40 s. The 6 s PIPR and maximum pupil constriction were expressed as percentage baseline (M ± SD). Results The blue PIPR was significantly less sustained (p<0.01) in the early AMD group (75.49 ± 7.88%) than the control group (58.28 ± 9.05%). The red PIPR was not significantly different (p>0.05) between the early AMD (84.79 ± 4.03%) and control groups (82.01 ± 5.86%). Maximum constriction amplitude in the early AMD group for blue (43.67 ± 6.35%) and red (48.64 ± 6.49%) stimuli were not significantly different to the control group for blue (39.94 ± 3.66%) and red (44.98 ± 3.15%) stimuli (p>0.05). Conclusions These results are suggestive of inner retinal mRGC deficits in early AMD. This non-invasive, objective measure of pupil responses may provide a new method for quantifying mRGC function and monitoring AMD progression.

A randomized trial of fellowships for early career researchers finds a high reliability in funding decisions

Objectives Funding for early career researchers in Australia's largest medical research funding scheme is determined by a competitive peer-review process using a panel of four reviewers. The purpose of this experiment was to appraise the reliability of funding by duplicating applications that were considered by separate grant review panels. Study Design and Methods Sixty duplicate applications were considered by two independent grant review panels that were awarding funding for Australia's National Health and Medical Research Council. Panel members were blinded to which applications were included in the experiment and to whether it was the original or duplicate application. Scores were compared across panels using Bland–Altman plots to determine measures of agreement, including whether agreement would have impacted on actual funding. Results Twenty-three percent of the applicants were funded by both panels and 60 percent were not funded by both, giving an overall agreement of 83 percent [95% confidence interval (CI): 73%, 92%]. The chance-adjusted agreement was 0.75 (95% CI: 0.58, 0.92). Conclusion There was a comparatively high level of agreement when compared with other types of funding schemes. Further experimental research could be used to determine if this higher agreement is due to nature of the application, the composition of the assessment panel, or the characteristics of the applicants.

Submission to Queensland Law Reform Commission WP 73 Review of Child Protection Mandatory Reporting Laws for the Early Childhood Education and Care Sector

In 2015 the QLRC is conducting an inquiry into whether to extend legislative mandatory reporting duties for physical abuse and sexual abuse to early childhood education and care practitioners. The current legislation does not require these practitioners to report suspected cases of significant harm from physical or sexual absue to child welfare agencies. Based on the literature, and a multidisciplinary analysis, our overall recommendation is that we endorse the extension to selected early childhood education and care practitioners of Queensland’s current mandatory reporting duty in the Child Protection Act 1999 s 13E.

Early life stress, nicotinic acetylcholine receptors and alcohol use disorders

Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Oxygen transport in a three-dimensional microvascular network incorporated with early tumour growth and preexisting vessel cooption: Numerical simulation study

We propose a dynamic mathematical model of tissue oxygen transport by a preexisting three-dimensional microvascular network which provides nutrients for an in situ cancer at the very early stage of primary microtumour growth. The expanding tumour consumes oxygen during its invasion to the surrounding tissues and cooption of host vessels. The preexisting vessel cooption, remodelling and collapse are modelled by the changes of haemodynamic conditions due to the growing tumour. A detailed computational model of oxygen transport in tumour tissue is developed by considering (a) the time-varying oxygen advection diffusion equation within the microvessel segments, (b) the oxygen flux across the vessel walls, and (c) the oxygen diffusion and consumption with in the tumour and surrounding healthy tissue. The results show the oxygen concentration distribution at different time points of early tumour growth. In addition, the influence of preexisting vessel density on the oxygen transport has been discussed. The proposed model not only provides a quantitative approach for investigating the interactions between tumour growth and oxygen delivery, but also is extendable to model other molecules or chemotherapeutic drug transport in the future study.

What parents want: Parent preference regarding sleep for their preschool child when attending Early Care and Education

Background While most children cease napping between the ages of 2 and 5 years, across a range of international settings the allocation of a mandatory naptime is a common feature of the daily routine in Early Care and Education (ECE) programs for children of this age. Evidence regarding the developmental effects of napping is limited but, beyond age 2, is consistently associated with delayed night sleep onset and increased number of awakenings. Objectives The present study examined parent preferences towards napping in ECE. Methods Participants were 750 parents of preschool-aged children attending a representative sample of Australian ECE programs across metropolitan, regional and rural sites in 2011. We analysed quantitative and open-ended questionnaire data from a large, longitudinal study of the effectiveness of Australian early education programs (E4Kids). Statistical analyses examined prevalence of parent preference for sleep and demographic correlates. Thematic analyses were employed to identify parents' rationale for this preference. Results The majority of parents (78.7%) preferred that their children did not regularly sleep while attending ECE. The dominant explanation provided by parents was that regular naps were no longer appropriate and adversely impacted their children's health and development. Parents of younger children were more likely to support regular naps. Conclusions The results highlight a disjuncture between parent preferences and current sleep policy and practices in ECE. Further research is needed to establish evidence-based guidelines to support healthy sleep-rest practices in ECE. Such evidence will guide appropriate practice and support parent-educator communication regarding sleep and rest.

Early stopping by using stochastic curtailment in a three-arm sequential trial

Summary. Interim analysis is important in a large clinical trial for ethical and cost considerations. Sometimes, an interim analysis needs to be performed at an earlier than planned time point. In that case, methods using stochastic curtailment are useful in examining the data for early stopping while controlling the inflation of type I and type II errors. We consider a three-arm randomized study of treatments to reduce perioperative blood loss following major surgery. Owing to slow accrual, an unplanned interim analysis was required by the study team to determine whether the study should be continued. We distinguish two different cases: when all treatments are under direct comparison and when one of the treatments is a control. We used simulations to study the operating characteristics of five different stochastic curtailment methods. We also considered the influence of timing of the interim analyses on the type I error and power of the test. We found that the type I error and power between the different methods can be quite different. The analysis for the perioperative blood loss trial was carried out at approximately a quarter of the planned sample size. We found that there is little evidence that the active treatments are better than a placebo and recommended closure of the trial.

Depositional model for the early Miocene turbidite sequence, the Whakataki Formation, NZ

This research examined the influence of tectonic activity on submarine sedimentation processes, through a deposit-based analysis of turbidites in outcrop. A comprehensive field study of the Miocene Whakataki Formation yielded significant data that was analysed using methods of process-sedimentology, stratigraphy, and ichnology. Signatures of the tectonically active depositional environment were identifiable at very high resolution, from grain composition and texture to trace-fossil assemblages, as well as on a broader-scale in stratigraphic stacking patterns and structural deformation. From these results and environmental interpretations, an original facies characterisation and conceptual depositional model have been established.

Breastmilk-saliva interactions boost innate immunity by regulating the oral microbiome in early infancy

Introduction Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined. Results Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 μM). Fresh breastmilk contained 27.3±12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2–449) compared to adults (620 U/L, 48–1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns. Discussion and Conclusion During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral–and hence gut–microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.

The SAGE Handbook of Early Childhood Research

Recent decades have seen an upsurge of research with and about young children, their families and communities. The Handbook of Early Childhood Research will provide a landmark overview of the field of early childhood research and will set an agenda for early childhood research into the future. It includes 31 chapters provided by internationally recognized experts in early childhood research. The team of international contributors apply their expertise to conceptual and methodological issues in research and to relevant fields of practice and policy. The Handbook recognizes the main contexts of early childhood research: home and family contexts; out-of-home contexts such as services for young children and their families; and broader societal contexts of that evoke risk for young children.

The effects of psychosocial factors on the mother's emotional well-being during early parenthood: A cross-cultural study of Britain and Greece

The effect of psychosocial factors on the emotional well-being of mothers following childbirth were examined within the cultural contexts of Britain and Greece. These mothers had already completed questionnaires during pregnancy and were contacted a second time in the postpartum period. At 4–6 weeks postpartum a sample of 165 Greek mothers and 101 British mothers and their partners completed the Edinburgh Postnatal Depression Scale. The relationship between mothers' EPDS scores and measures of emotional well-being in pregnancy (CCEI), social support, life events, fathers' EPDS score, and father's perception of change in partner was examined in each culture. No difference in the distribution of EPDS scores in each culture was found. Social support and life events were found to predict postnatal depression in both cultures. Additionally, in Greece, emotional well-being in pregnancy made a separate contribution to prediction. The major difference between the two cultures was in the relationship between mothers and their partners. Greek fathers were more emotionally and physically distanced from their partners during pregnancy, birth and early parenthood and perceived their partners as being more changed by the transition to parenthood. These differences were not reflected in differences in emotional well-being possibly because they accord with social expectation in each culture.

How to develop an online community for pre-service and early career teachers

This paper contributes a number of design principles for developing large-scale online communities of pre-service and early career teachers (PS&ECTs). It presents the paradigms of connected learning, networked learning and communities of practice and contrasts them. It describes the potential for online communities to meet the needs of PS&ECTs and it identifies gaps that exist within certain types of existing online communities that currently support PS&ECTs. The paper proposes design principles for a new type of online community for PS&ECTs. These principles are drawn from the literature and from the preliminary outcomes of a pilot study.

Key ideas, research and challenges in early childhood education and care

The Australian government has recognised the importance of early childhood education and care (ECEC) in recent years. With over one million Australian children accessing early childhood education provision every day (Productivity Commission, 2014), today’s children are a generation who spend a large part of their early years in some form of out-of-home child care. Early chapters in this text have discussed a range of people, theories and approaches that inform the development of ECEC. Early childhood pedagogical practice is an eclectic mix of these ideas. This chapter begins with an overview of the ways young children learn in early childhood education, highlighting play-based learning as a pedagogical response to our understandings about children. Next the chapter outlines areas that have more recently influenced ECEC including international models of early childhood education, neuroscience, studies of young children, economic research and social justice principles. Drawing on the reflections of educators working in various ECEC contexts, the chapter then presents four topics encountered by educators as part of their everyday work with diverse communities. These topics include: • the educational program for children in the early years • relationships and partnerships with diverse families • professional accountabilities, and • changing constructions of childhood.