New migrants' access to primary healthcare services in Aotearoa New Zealand.

AIM: To explore new migrants' access to primary healthcare services in the first 10 years after arrival in Aotearoa New Zealand. METHODS: Data come from three New Zealand Health Surveys (2014/2015, 2015/2016 and 2016/2017), which each sampled around 13,500 people, aged 15+ years, who were usual residents of Aotearoa New Zealand. Respondents who said they were born overseas were asked the first year they had come to Aotearoa New Zealand. Those who had arrived in the 10 years before their survey was completed were considered new migrants. The survey data were pooled and around 3,700 respondents were estimated to fit this category. Log-linear models, with adjustments for age, sex, ethnicity and New Zealand Deprivation Index, were used to look at last year use of primary healthcare. RESULTS: Overall, new migrants used primary healthcare similarly to other New Zealanders. They were more likely to have comprehensive health insurance and paid more for GP visits upon arrival but acted similarly to other New Zealanders after 4 years. CONCLUSION: Generally, new migrants-after adjusting for covariates-appear to be accessing primary healthcare services in a similar manner to other New Zealanders, on average, soon after arrival.

Do Infants With Down Syndrome Show an Early Receptive Language Advantage?

Purpose The study explored longitudinally the course of vocabulary and general language development in a group of infants with Down syndrome (DS) compared to a group of typically developing (TD) infants matched on nonverbal mental ability (NVMA). Method We compared the vocabulary and general language trajectories of the two groups in two ways: (a) at three time points during a 12-month period and (b) at two time points when the groups had made equal progress in NVMA (a period of 6 months for the TD infants vs. 12 months for the infants with DS). Results The TD group had overtaken the DS group on all general language and vocabulary measures by the end of the 12-month period. However, expressive communication and expressive vocabulary were developing at the same rate and level in the two groups when examined over a period in which the two groups were matched in gains in NVMA. Furthermore, the infants with DS showed a receptive language advantage over the TD group; this group's auditory comprehension and receptive vocabulary scores were superior to those of the TD group at both time points when NVMA was accounted for. Conclusion The results shed light on the widely reported discrepancy between expressive and receptive language in individuals with DS. Although infants with DS appear to be developing language skills more slowly than chronological age TD peers, when NVMA is taken into account, infants with DS do not have expressive language delays, and they seem to show a receptive language advantage.

Longitudinal predictors of early language in infants with Down syndrome: A preliminary study.

PURPOSE: Children with Down syndrome (DS) typically have marked delays in language development relative to their general cognitive development, with particular difficulties in expressive compared to receptive language. Although early social communication skills, including gestures and joint attention, have been shown to be related to later language outcomes in DS, knowledge is limited as to whether these factors exclusively predict outcomes, or whether other factors (e.g. perceptual and non-verbal skills) are involved. This study addressed this question. METHOD: Longitudinal data for a group of infants with DS (n = 14) and a group of typically-developing (TD) infants (n = 35) were collected on measures that have been shown to predict language in TD infants and/or those with developmental delays. These included: non-verbal mental ability, speech segmentation skills, and early social communication skills (initiating and responding to joint attention, initiating behavioural requests). RESULTS: Linear regression analyses showed that speech segmentation and initiating joint attention were the strongest predictors of later language in the TD group, whereas non-verbal mental ability and responding to joint attention were the strongest predictors of later language for infants with DS. CONCLUSIONS: Speech segmentation ability may not determine language outcomes in DS, and language acquisition may be more constrained by social communication and general cognitive skills.

Facebook study: a little bit unethical but worth it?

Human research involving the use social media raises many of the same issues as medical research. The publication of a paper in June 2014 investigating "emotional contagion" received extensive publicity recently because of the methods used. The approach involved manipulating the "News Feeds" of Facebook users, but the participants were not informed of their involvement in the research and had no opportunity to consent or opt out. Some commentators have argued that although it would have been preferable to obtain informed consent, it was not strictly required because the research was unlikely to cause significant harm and was important. This paper argues that the research was unethical because (i) it should have been overseen by an independent ethics committee or review board and (ii) informed consent could and should have been obtained. Regardless of the importance of any research and irrespective of its likelihood to cause harm, the ethical principles that have evolved since the 1940s should be followed in all instances when experimental research is being carried out on human participants.

Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary fibrosis via CCL2 modulation in bronchoalveolar lavage.

The potential for amniotic fluid stem cell (AFSC) treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF), is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0) or chronic (day 14) intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL), but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.

Computerized memory training leads to sustained improvement in visuospatial short-term memory skills in children with Down syndrome.

This study evaluated the impact of a computerized visuospatial memory training intervention on the memory and behavioral skills of children with Down syndrome. Teaching assistants were trained to support the delivery of a computerized intervention program to individual children over a 10-16 week period in school. Twenty-one children aged 7-12 years with Down syndrome were randomly allocated to either an intervention or waiting list control group. Following training, performance on trained and non-trained visuospatial short-term memory tasks was significantly enhanced for children in the intervention group. This improvement was sustained four months later. These results suggest that computerized visuospatial memory training in a school setting is both feasible and effective for children with Down syndrome.

Modulating the alveolar milieu to enhance resolution of fibrotic lung injury.

Fibrotic lung injury is often attributed to a myriad of factors, including environmental exposure, age, genetic predisposition, epigenetics, coexisting conditions, acute lung injury, and viral infection. No effective therapies, other than lung transplantation, have proven effective against lung fibrosis. Loss of cellular homeostasis mechanisms in alveolar epithelial type I cells and any inability of type II progenitor cells to resist and repair epithelial injury are indicators that impaired response to injury and regeneration is a critical component of this disorder. The alveolar epithelium has a limited repertoire of responses to injury, which are dictated by the alveolar milieu, a repository of cytokines and growth factors that affect recruitment of other cells to the site of injury, or the proliferation of resident cells at the site of injury. The identification and characterization of the cytokines, growth factors, and other biomarkers that dictate the response to disease is key to understanding, diagnosing, treating, and determining the trajectory of various lung disorders. Corrective therapy of the alveolar milieu may therefore prove to be beneficial in many presently serious and incurable lung diseases that likely begin and progress with injury to the alveolar epithelium.

Molecular mechanisms of MMP9 overexpression and its role in emphysema pathogenesis of Smad3-deficient mice.

Previous studies have found that inappropriate elevation of matrix metalloproteinase-9 (MMP9) expression and activity is coincident with early onset of emphysema in Smad3-null mice. Herein, we further investigated the role of increased MMP9 in emphysema pathogenesis and the related molecular regulatory mechanisms of elevated MMP9 in Smad3-null lung. Genetic blockade of MMP9 in Smad3-null mice significantly attenuated emphysema pathology but not hypoalveolarization during early postnatal lung development. Furthermore, Smad3 was found to be a transcription factor to positively regulate a protein deacetylase sirtuin 1 (SIRT1) by binding to an AP-1 site of SIRT1 promoter. A synergistic regulatory effect on SIRT1 expression was also detected between Smad3 and c-Jun. Consistently, Smad3 knockout lung at P28 had reduced SIRT1 expression, which in turn resulted in increased acetylation of histone H3 at the transcription factor activator protein 1 (AP-1), NF-κB, and Pea3 binding sites of MMP9 promoter and increased acetylation of NF-κB. In addition, increased Pea3 expression and nuclear accumulation was also detected in Smad3-null lungs at P28. Consistently, bindings of acetylated NF-κB and Pea3 to the MMP9 promoter were elevated in Smad3-null lung. We thus propose that deficiency of Smad3 causes downregulation of SIRT1 and increased Pea3 expression/nuclear accumulation, respectively. Decreased SIRT1 activity resulted in increased acetylation of histone H3 and NF-κB. Subsequently, increased bindings of transcription factors including NF-κB and Pea3 to MMP9 promoter significantly upregulate MMP9 transcription, contributing to emphysema pathogenesis.

Efficacy of a reading and language intervention for children with Down syndrome: a randomized controlled trial.

BACKGROUND: This study evaluates the effects of a language and literacy intervention for children with Down syndrome. METHODS: Teaching assistants (TAs) were trained to deliver a reading and language intervention to children in individual daily 40-min sessions. We used a waiting list control design, in which half the sample received the intervention immediately, whereas the remaining children received the treatment after a 20-week delay. Fifty-seven children with Down syndrome in mainstream primary schools in two U.K. locations (Yorkshire and Hampshire) were randomly allocated to intervention (40 weeks of intervention) and waiting control (20 weeks of intervention) groups. Assessments were conducted at three time points: pre-intervention, after 20 weeks of intervention, and after 40 weeks of intervention. RESULTS: After 20 weeks of intervention, the intervention group showed significantly greater progress than the waiting control group on measures of single word reading, letter-sound knowledge, phoneme blending and taught expressive vocabulary. Effects did not transfer to other skills (nonword reading, spelling, standardised expressive and receptive vocabulary, expressive information and grammar). After 40 weeks of intervention, the intervention group remained numerically ahead of the control group on most key outcome measures; but these differences were not significant. Children who were younger, attended more intervention sessions, and had better initial receptive language skills made greater progress during the course of the intervention. CONCLUSIONS: A TA-delivered intervention produced improvements in the reading and language skills of children with Down syndrome. Gains were largest in skills directly taught with little evidence of generalization to skills not directly taught in the intervention.

Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium.

Cell polarity, mitotic spindle orientation and asymmetric division play a crucial role in the self-renewal/differentiation of epithelial cells, yet little is known about these processes and the molecular programs that control them in embryonic lung distal epithelium. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized with characteristic perpendicular cell divisions. Consistent with these findings, spindle orientation-regulatory proteins Insc, LGN (Gpsm2) and NuMA, and the cell fate determinant Numb are asymmetrically localized in embryonic lung distal epithelium. Interfering with the function of these proteins in vitro randomizes spindle orientation and changes cell fate. We further show that Eya1 protein regulates cell polarity, spindle orientation and the localization of Numb, which inhibits Notch signaling. Hence, Eya1 promotes both perpendicular division as well as Numb asymmetric segregation to one daughter in mitotic distal lung epithelium, probably by controlling aPKCζ phosphorylation. Thus, epithelial cell polarity and mitotic spindle orientation are defective after interfering with Eya1 function in vivo or in vitro. In addition, in Eya1(-/-) lungs, perpendicular division is not maintained and Numb is segregated to both daughter cells in mitotic epithelial cells, leading to inactivation of Notch signaling. As Notch signaling promotes progenitor cell identity at the expense of differentiated cell phenotypes, we test whether genetic activation of Notch could rescue the Eya1(-/-) lung phenotype, which is characterized by loss of epithelial progenitors, increased epithelial differentiation but reduced branching. Indeed, genetic activation of Notch partially rescues Eya1(-/-) lung epithelial defects. These findings uncover novel functions for Eya1 as a crucial regulator of the complex behavior of distal embryonic lung epithelium.

"Healthy Eating - Healthy Action": evaluating New Zealand's obesity prevention strategy.

BACKGROUND: New Zealand rates of obesity and overweight have increased since the 1980s, particularly among indigenous Maori people, Pacific people and those living in areas of high deprivation. New Zealand's response to the obesity epidemic has been The Healthy Eating-Healthy Action: Oranga Kai - Oranga Pumau (HEHA) Strategy ('the Strategy'), launched in 2003. Because the HEHA Strategy explicitly recognises the importance of evaluation and the need to create an evidence base to support future initiatives, the Ministry of Health has commissioned a Consortium of researchers to evaluate the Strategy as a whole. METHODS: This paper discusses the Consortium's approach to evaluating the HEHA Strategy. It includes an outline of the conceptual framework underpinning the evaluation, and describes the critical components of the evaluation which are: judging to what extent stakeholders were engaged in the process of the strategy implementation and to what extent their feedback was incorporated in to future iterations of the Strategy (continuous improvement), to what extent the programmes, policies, and initiatives implemented span the target populations and priority areas, whether there have been any population changes in nutrition and/or physical activity outcomes or behaviours relating to those outcomes, and to what extent HEHA Strategy and spending can be considered value for money. DISCUSSION: This paper outlines our approach to evaluating a complex national health promotion strategy. Not only does the Evaluation have the potential to identify interventions that could be adopted internationally, but also the development of the Evaluation design can inform other complex evaluations.

The power of behavioural approaches - we need a revival.

Behavioural approaches can be used very effectively to teach new skills and to change behaviours that are challenging and not socially adaptive. They have gone out of fashion but should be revived, as the studies discussed here indicate.

It is time to take memory training seriously.

It has been known for a long while that children with Down syndrome have specific impairments in verbal shortterm memory. Research now indicates that memory training activities may be effective.

Ten years of achievement in Russia.

The Moscow charity Downside Up is celebrating its 10th Anniversary this year. In Russia, on average only 15% of children with Down syndrome live with their families. In Moscow, thanks to the work of Downside Up, some 45% of new babies are now being taken home. Downside Up is working to ensure children with Down syndrome receive high quality services from birth to 7 years.

Teaching numeracy.

Understanding number concepts and basic mathematical skills is important for many everyday activities in modern societies. Little is understood about the numeracy abilities of people with Down syndrome. At present, it appears that numeracy is an area of relative difficulty and that progress with more complex mathematical understanding is slow. However, some teaching approaches that seek to utilise certain relative strengths to communicate number concepts seem to be useful in practice. Further research is needed to define the precise difficulties experienced by children with Down syndrome and to evaluate teaching strategies.