Changing parental high risk behaviour in the reduction of SIDS : the imperative of translational research

Objectives To investigate the factors associated with sudden infant death syndrome (SIDS) from birth to age 2 years, whether recent advice has been followed, whether any new risk factors have emerged, and the specific circumstances in which SIDS occurs while cosleeping (infant sharing the same bed or sofa with an adult or child). Design Four year population based case-control study. Parents were interviewed shortly after the death or after the reference sleep (within 24 hours) of the two control groups. Setting South west region of England (population 4.9 million, 184 800 births). Participants 80 SIDS infants and two control groups weighted for age and time of reference sleep: 87 randomly selected controls and 82 controls at high risk of SIDS (young, socially deprived, multiparous mothers who smoked). Results The median age at death (66 days) was more than three weeks less than in a study in the same region a decade earlier. Of the SIDS infants, 54% died while cosleeping compared with 20% among both control groups. Much of this excess may be explained by a significant multivariable interaction between cosleeping and recent parental use of alcohol or drugs (31% v 3% random controls) and the increased proportion of SIDS infants who had coslept on a sofa (17% v 1%). One fifth of SIDS infants used a pillow for the last sleep (21% v 3%) and one quarter were swaddled (24% v 6%). More mothers of SIDS infants than random control infants smoked during pregnancy (60% v 14%), whereas one quarter of the SIDS infants were preterm (26% v 5%) or were in fair or poor health for the last sleep (28% v 6%). All of these differences were significant in the multivariable analysis regardless of which control group was used for comparison. The significance of covering the infant’s head, postnatal exposure to tobacco smoke, dummy use, and sleeping in the side position has diminished although a significant proportion of SIDS infants were still found prone (29% v 10%). Conclusions Many of the SIDS infants had coslept in a hazardous environment. The major influences on risk, regardless of markers for socioeconomic deprivation, are amenable to change and specific advice needs to be given, particularly on use of alcohol or drugs before cosleeping and cosleeping on a sofa.

Expression and prognostic influence of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer

Background Matrix metalloproteinases (MMPs) are a family of endopeptidases that digest the extracellular matrix (ECM). Overexpression of different MMPs has been shown to promote tumour cell invasion in vitro. Tissue inhibitors of matrix metalloproteinases (TIMPs) are specific inhibitors of MMPs that also possess growth-promoting properties. Aims To analyse the expression profile of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer (NSCLC) and to assess the impact of expression on survival. Methods This is a retrospective study of patients who underwent resection for stage I-IIIa NSCLC with a post-operative survival >60 days. Patient follow up was a minimum of 2 years. Standard ABC immunohistochemistry was performed on 4μm paraffin-embedded sections from the tumour periphery using monoclonal antibodies to MMP-2, MMP-9 and TIMP-2. Results The results of the immunohistochemistry are set out below. marker tumour expression log-rank survival stromal expression log-rank survival MMP-2 9/72 (13%) p=0.10 34/72 (47%) p=0.34 MMP-9 79/152 (52%) p=0.04* 69/152 (45%) p=0.84 TIMP-2 28/90 (31%) p=0.04* 66/90 (73%) p=0.90 Two or more 16/59 (27%) p=0.007* There were no associations between expression and clinicopathological findings for any tumour marker. There was co-expression of MMP-2 and MMP-9 in tumour cells (p=0.01). Conclusions MMP-2, MMP-9 and TIMP-2 are expressed in NSCLC. MMP-9 and TIMP-2 tumour expression correlate with a poor outcome (both p=0.04) and are potential prognostic markers for NSCLC. Cumulative expression of two or more MMPs/TIMPs may also have increased prognostic significance. Proteases and their inhibitors are novel targets for therapeutic intervention and should be evaluated in NSCLC.

Potential role of bcl-2 as a suppressor of tumour angiogenesis in non- small-cell lung cancer

It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The relationship between bcl-2, p53 and tumour vascularization and epidermal-growth-factor- receptor(EGFR) and c-erbB-2 expression was also studied. Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl-2, p53, EGFR and c-erbB-2 expression. bcl-2 expression was found in 20/107 (19%) cases and was associated with squamous-cell histology (p = 0.03). A strong inverse relationship was found between bcl-2 expression and vascular grade (p = 0.005). All c-erbB-2-positive cases were negative for bcl-2 expression (p = 0.01). Overall no association was found between c-erbB-2 expression and vascular grade. However, in bcl-2-negative cases positive c-erbB-2 expression correlated with low angiogenesis (p = 0.05). No relationship was found between p53 and EGFR expression and bcl-2, c-erbB-2 or vascular grade. The improved prognosis reported in bcl-2-positive NSCLC may be related to low tumour vascularization. The results suggest that the anti-apoptotic gene bcl- 2 plays a role in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl-2, a sequence of tumour progression involving loss of bcl-2, then activation of c-erbB-2 or increase in tumour vascularization is proposed.

Back to basics: Informing the public of co-morbid physical health problems in those with mental illness

Abstract OBJECTIVE: Those with mental illness are at increased risk of physical health problems. The current study aimed to examine the information available online to the Australian public about the increased risk and consequences of physical illness in those with mental health problems and the services available to address these co-morbidities. METHODS: A structured online search was conducted with the search engine Google Australia (www.google.com.au) using generic search terms 'mental health information Australia', 'mental illness information Australia', 'depression', 'anxiety', and 'psychosis'. The direct content of websites was examined for information on the physical co-morbidities of mental illness. All external links on high-profile websites [the first five websites retrieved under each search term (n = 25)] were examined for information pertaining to physical health. RESULTS: Only 4.2% of websites informing the public about mental health contained direct content information about the increased risk of physical co-morbidities. The Australian Government's Department of Health and Ageing site did not contain any information. Of the high-profile websites, 62% had external links to resources about physical health and 55% had recommendations or resources for physical health. Most recommendations were generic. CONCLUSIONS: Relative to the seriousness of this problem, there is a paucity of information available to the public about the increased physical health risks associated with mental illness. Improved public awareness is the starting point of addressing this health inequity.

The art of co-creative media : an Australian survey

This article describes how - in the processes of responding to participatory storytelling practices - community, public service, and to a lesser extent, commercial media institutions are themselves negotiated and changed. Although there are significant variations in the conditions, durability, extent, motivations and quality of these developments and their impacts, they nonetheless increase the possibilities and pathways of participatory media culture. This description first frames digital storytelling as a ‘co-creative’ media practice. It then discusses the role of community arts and cultural development (CACD) practitioners and networks as co-creative media intermediaries, and then considers their influence in Australian broadcast and Internet media. It looks at how participatory storytelling methods are evolving in the Australian context and explores some of the implications for cultural inclusion arising from a shared interest in ‘co-creative’ media methods and approaches.

Prediction of CO concentrations based on a hybrid Partial Least Square and Support Vector Machine model

Due to the health impacts caused by exposures to air pollutants in urban areas, monitoring and forecasting of air quality parameters have become popular as an important topic in atmospheric and environmental research today. The knowledge on the dynamics and complexity of air pollutants behavior has made artificial intelligence models as a useful tool for a more accurate pollutant concentration prediction. This paper focuses on an innovative method of daily air pollution prediction using combination of Support Vector Machine (SVM) as predictor and Partial Least Square (PLS) as a data selection tool based on the measured values of CO concentrations. The CO concentrations of Rey monitoring station in the south of Tehran, from Jan. 2007 to Feb. 2011, have been used to test the effectiveness of this method. The hourly CO concentrations have been predicted using the SVM and the hybrid PLS–SVM models. Similarly, daily CO concentrations have been predicted based on the aforementioned four years measured data. Results demonstrated that both models have good prediction ability; however the hybrid PLS–SVM has better accuracy. In the analysis presented in this paper, statistic estimators including relative mean errors, root mean squared errors and the mean absolute relative error have been employed to compare performances of the models. It has been concluded that the errors decrease after size reduction and coefficients of determination increase from 56 to 81% for SVM model to 65–85% for hybrid PLS–SVM model respectively. Also it was found that the hybrid PLS–SVM model required lower computational time than SVM model as expected, hence supporting the more accurate and faster prediction ability of hybrid PLS–SVM model.

Accurate placement of a pelvic binder improves reduction of unstable fractures of the pelvic ring

The aim of this study was to assess the accuracy of placement of pelvic binders and to determine whether circumferential compression at the level of the greater trochanters is the best method of reducing a symphyseal diastasis. Patients were identified by a retrospective review of all pelvic radiographs performed at a military hospital over a period of 30 months. We analysed any pelvic radiograph on which the buckle of the pelvic binder was clearly visible. The patients were divided into groups according to the position of the buckle in relation to the greater trochanters: high, trochanteric or low. Reduction of the symphyseal diastasis was measured in a subgroup of patients with an open-book fracture, which consisted of an injury to the symphysis and disruption of the posterior pelvic arch (AO/OTA 61-B/C). We identified 172 radiographs with a visible pelvic binder. Five cases were excluded due to inadequate radiographs. In 83 (50%) the binder was positioned at the level of the greater trochanters. A high position was the most common site of inaccurate placement, occurring in 65 (39%). Seventeen patients were identified as a subgroup to assess the effect of the position of the binder on reduction of the diastasis. The mean gap was 2.8 times greater (mean difference 22 mm) in the high group compared with the trochanteric group (p < 0.01). Application of a pelvic binder above the level of the greater trochanters is common and is an inadequate method of reducing pelvic fractures and is likely to delay cardiovascular recovery in these seriously injured patients.

Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

Background Transcription factors (TFs) co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1) leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA, it does provide a tool to characterise cis-regulatory sequences that are necessary for transcription activation in a complex list of co-ordinately regulated genes.

The loss of CO from the ortho, meta and para forms of deprotonated methyl benzoate in the gas phase

The ortho, meta and para anions of methyl benzoate may be made in the source of a mass spectrometer by the S(N)2(Si) reactions between HO- and methyl (o-, m-, and p-trimethylsilyl)benzoate respectively. All three anions lose CO upon collisional activation to form the ortho anion of anisole in the ratio ortho>>meta > para. The rearrangement process is charge directed through the ortho anion. Theoretical calculations at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory indicate that the conversion of the meta and para anions to the ortho anion prior to loss of CO involve 1,2-H transfer(s), rather than carbon scrambling of the methoxycarbonylphenyl anion. There are two mechanisms which can account for this rearrangement, viz. (A) cyclisation of the ortho anion centre to the carbonyl group of the ester to give a cyclic carbonyl system in which the incipient methoxide anion substitutes at one of the two equivalent ring carbons of the three membered ring to yield an intermediate which loses CO to give the ortho anion of anisole, and (B) an elimination reaction to give an intermediate benzyne-methoxycarbonyl anion complex in which the MeOCO- species acts as a MeO- donor, which then adds to benzyne to yield the ortho anion of anisole. Calculations at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory indicate that (i) the barrier in the first step (the rate determining step) of process A is 87 kJ mol(-1) less than that for the synchronous benzyne process B, and (ii) there are more low frequency vibrations in the transition state for benzyne process B than for the corresponding transition state for process A. Stepwise process A has the lower barrier for the rate determining step, and the lower Arrhenius factor: we cannot differentiate between these two mechanisms on available evidence.

Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels

Although tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to be not only an inhibitor of matrix metalloproteinases (MMP) but also a cofactor for membrane-type 1 MMP (MT1-MMP)-mediated MMP-2 activation, it is still unclear how TIMP-2 regulates MMP-2 activation and cleavage of substrates by MT1-MMP. In the present study we examined the levels of cell-surface MT1-MMP, MMP-2 activation and cleavage of MT1-MMP substrates in 293T cells transfected with the MT1-MMP and TIMP-2 genes. Co-expression of TIMP-2 at an appropriate level increased the level of cell-surface MT1-MMP, both the TIMP-2-bound and free forms, and generated processed MMP-2 with gelatin-degrading activity. In contrast, MT1-MMP substrates testican-1 and syndecan-1 were cleaved by the cells expressing MT1-MMP, which was inhibited by TIMP-2 even at levels that stimulate MMP-2 activation. These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.

Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage

Purpose: The therapeutic ratio for ionising radiation treatment of tumour is a trade-off between normal tissue side-effects and tumour control. Application of a radioprotector to normal tissue can reduce side-effects. Here we study the effects of a new radioprotector on the cellular response to radiation. Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA. To substantiate this hypothesis, we studied protection by methylproamine at both clonogenic survival and radiation-induced DNA damage, assessed by γH2AX (histone 2AX phosphorylation at serine 139) focus formation endpoints. Materials and methods: The human keratinocyte cell line FEP1811 was used to study clonogenic survival and yield of γH2AX foci following irradiation (137Cs γ-rays) of cells exposed to various concentrations of methylproamine. Uptake of methylproamine into cell nuclei was measured in parallel. Results: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM. Conclusions: These results are consistent with the hypothesis that radioprotection by methylproamine is mediated by attenuation of the extent of initial DNA damage.

Community uses of co-creative media. Digital storytelling and Co-creative Media : The role of community arts and media in propagating and coordinating population-wide creative practice

This report describes a dynamic ‘Co-creative Media System’ that is emerging in the social space bounded by the following institutional pillars: • major cultural institutions (including screen culture agencies, libraries, museums, galleries and public service broadcasters) • the Community Arts and Cultural Development sector (historically supported through various programs of the Australia Council for the Arts) • the community broadcasting sector • the Indigenous media sector, and • the higher education sector. It illustrates how this system activates the immense creative potential of the Australian population through the ongoing development and application of participatory storytelling methods and media.

The exhaustive reduction of formylporphyrins to methylporphyrins using dimethylformamide/water as reductant under microwave irradiation

The reduction of meso-formyl derivatives of 5,15-diaryl- and 5,10,15-triphenylporphyrin (and their nickel(II) complexes) to the corresponding meso-methyl porphyrins is achieved in high yield by microwave heating of the substrate in dimethylformamide (DMF) in the presence of acids such as trifluoroacetic acid, or even just with added water. The reactions are complete in less than 30 min at 250 °C. The reaction is strongly suppressed in very dry DMF in the absence of added acid. The meso-hydroxymethyl porphyrins are also reduced to the methyl derivatives, suggesting the primary alcohols may be intermediates in the exhaustive reduction. UV-visible spectra taken at intervals during reaction at 240 °C indicated that at least one other intermediate is present, but it was not identified. In d7-DMF, the methylporphyrin isolated was mainly Por-CD2H, showing that both of the added hydrogens arise from the solvent, and not from the added water or acid.

Community uses of co-creative media digital storytelling and co-creative Media: The role of community arts and media in propagating and coordinating population-wide creative practice

How is creative expression and communication extended among whole populations? What is the social and cultural value of this activity? What roles do formal agencies, community-based organisations and content producer networks play? Specifically, how do participatory media and arts projects and networks contribute to building this capacity in the contemporary communications environment? The latest issue of CSJ article in a special issue on “Broadening Digital Storytelling Horizons” edited by Burcu Simsek.