Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

BACKGROUND: The increased production of nanomaterials has caused a corresponding increase in concern about human exposures in consumer and occupational settings. Studies in rodents have evaluated dose–response relationships following respiratory tract (RT) delivery of nanoparticles (NPs) in order to identify potential hazards. However, these studies often use bolus methods that deliver NPs at high dose rates that do not reflect real world exposures and do not measure the actual deposited dose of NPs. We hypothesize that the delivered dose rate is a key determinant of the inflammatory response in the RT when the deposited dose is constant. METHODS: F-344 rats were exposed to the same deposited doses of titanium dioxide (TiO(2)) NPs by single or repeated high dose rate intratracheal instillation or low dose rate whole body aerosol inhalation. Controls were exposed to saline or filtered air. Bronchoalveolar lavage fluid (BALF) neutrophils, biochemical parameters and inflammatory mediator release were quantified 4, 8, and 24 hr and 7 days after exposure. RESULTS: Although the initial lung burdens of TiO(2) were the same between the two methods, instillation resulted in greater short term retention than inhalation. There was a statistically significant increase in BALF neutrophils at 4, 8 and 24 hr after the single high dose TiO(2) instillation compared to saline controls and to TiO(2) inhalation, whereas TiO(2) inhalation resulted in a modest, yet significant, increase in BALF neutrophils 24 hr after exposure. The acute inflammatory response following instillation was driven primarily by monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, mainly within the lung. Increases in heme oxygenase-1 in the lung were also higher following instillation than inhalation. TiO(2) inhalation resulted in few time dependent changes in the inflammatory mediator release. The single low dose and repeated exposure scenarios had similar BALF cellular and mediator response trends, although the responses for single exposures were more robust. CONCLUSIONS: High dose rate NP delivery elicits significantly greater inflammation compared to low dose rate delivery. Although high dose rate methods can be used for quantitative ranking of NP hazards, these data caution against their use for quantitative risk assessment

Open Access

Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammatio

SROI in the art gallery: valuing social impact

This article considers a project that used the Social Return on Investment (SROI) methodology to describe and measure the social impact of Turner Contemporary art gallery in Margate, a coastal town in the South East of England. The article details the reasons why the methodology was chosen by the gallery, setting this in the context of the wider debate around evaluation and social impact reporting. A section of the research and analysis, which was carried out by COaST, a consultancy and research centre based within Canterbury Christ Church University, is described in detail, allowing the reader to understand the processes involved in this type of project and the kinds of outcomes that can be delivered using this method. Finally, an account is given of the impact the work had on the management of the gallery, and the ways in which the final report was used

Conditions for parents' participation in the care of their child in neonatal intensive care – a field study

<p>Abstract</p> <p>Background</p> <p>To promote participation by parents in the care of their child in neonatal intensive care units (NICU), health professionals need better understanding of what facilitates and what obstructs participation. The aim was to elucidate conditions for parents' participation in the care of their child in NICUs.</p> <p>Methods</p> <p>A field study with a hermeneutic lifeworld approach was used and data were collected at two NICUs through participative observations and interviews with representatives of management, staff and parents.</p> <p>Results</p> <p>The results point to a number of contradictions in the way parents were offered the opportunity to participate in neonatal intensive care. Management and staff both had good ambitions to develop ideal care that promoted parent participation. However, the care including the conditions for parental participation was driven by the terms of the staff, routines focusing on the medical-technical care and environment, and budgetary constraints.</p> <p>Conclusion</p> <p>The result shows that tangible strategies need to be developed in NICUs aimed at optimising conditions for parents to be present and involved in the care of their child.</p

Teaching strategies and gender in higher education instrumental studios

This study investigates instrumental music teaching strategies in higher education settings, in order to identify those employed and their frequency and context of use. An instrument- and gender-balanced sample of 24 lessons from five institutions was analysed using a researcher-designed observational instrument. The results reveal the predominance of teacher demonstration, general directives and praise as most frequent teaching strategies employed in lessons. Gender differences emerged in the teaching approaches: the male teachers gave more general directives and explanations and the female teachers offered more answers and practice discussions; the male students received the most specific teacher criticism despite uniform use of praise. The findings provide new evidence of teaching practices in advanced instrumental studios and raise questions regarding gender issues in music teaching

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Database for mRNA Half-Life of 19 977 Genes Obtained by DNA Microarray Analysis of Pluripotent and Differentiating Mouse Embryonic Stem Cells

Degradation of mRNA is one of the key processes that control the steady-state level of gene expression. However, the rate of mRNA decay for the majority of genes is not known. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. Median estimated half-life was 7.1 h and only <100 genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 3′-untranslated region (UTR) and CpG di-nucleotides in the 5′-UTR. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells

Maternal distress and perceptions of infant development following extracorporeal membrane oxygenation and conventional ventilation for persistent pulmonary hypertension

Neurodevelopmental outcome and concurrent maternal distress were examined for infants who suffered persistent pulmonary hypertension at birth and were treated with either extracorporeal membrane oxygenation (ECMO) ( n = 19) or conventional ventilation (CV) ( n = 15). Mothers were asked to complete inventories assessing their infant's (mean age 8.74 months) developmental growth as well as their own psychological health. Relevant sociodemographic and treatment parameters were also entered into the analysis. The results indicated that ECMO and CV infants did not differ on developmental indices and impairment rates were 15–23% respectively, similar to previous reports, in addition, ECMO and CV mothers did not differ in their reports of psychological distress. Correlational analyses revealed that length of treatment for ECMO but not CV infants significantly predicted developmental delay and maternal distress. For CV mothers, maternal distress was associated with the perception of delayed language. The results are discussed in terms of the limited morbidity associated with ECMO and CV interventions and the possible role of a ‘vulnerable child syndrome’ in understanding the maternal-infant relationship following ECMO therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73367/1/j.1365-2214.1995.tb00410.x.pd