Rat mammary carcinogenesis following neutron- or X-radiation

Female 61 to 63 - day - old Sprague-Dawley rats were exposed once to a single dose of either 0.43 - MeV neutrons or 250 - kVX - rays . For neutrons 23 rats were exposed in plastic tubes rotated around and 31 c m from a water-cooled tritium impregnated target bombarded with 2.45 - MeV protons from a V a n de Graaff generator. The mean kerma was measured at the rat location by integrating the response of a rat - sized homogeneous tissue equivalent ionization chamber of minimum mass. The ratio between absorbed dose and kerma is under investigation and is anticipated to be approximately 0.7. A compensated GM gamma-ray dosimeter indicated that the gamma - ray doses were 3.5% of the total dose. All rats were examined weekly for the presence of breast tumours and these were removed, fixed, stained and verified histologically as mammary neoplasms. At 10 months after exposure 98<7ο of the rats were a live . The neutron kerma, the per cent of rats with mammary neoplasia, and the number of rats were, respectively: 0.125 rads, 8.2°}o, 182; 0.5 rads, 9.0^0, 89; 2 rads, 20. 6,68; and 8 rads, 31.1%, 45. The X - ray results were: 30 R, 1.4% 95; 60 R, 27. l°Io, 48; and 90 R, 35.4%, 48. A 3. O^o incidence was found in 167 control rats. At 10 months after exposure the mammary neoplastic response after 8 rads of neutrons corresponds approximately to that after 60 - 90 R of X - rays . Similarly, the response after 2 rads of neutrons was intermediate between 30 and 60 R of X - rays and the response after 0 . 125 and 0.5 rads of neutrons was similar to that after 30 R of X - rays . This demonstrates that the RBE for 0.43 - MeV neutrons is much lower at high doses than at low doses. Determination of the confidence limits for the dose-RBE dependence and dose-incidence relationship will be determined as additional data are collected

Phagocytes and the Lung

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72927/1/j.1749-6632.1997.tb46258.x.pd

Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing

The regulation of mitochondrial turnover under conditions of stress occurs partly through the AMPK-NAD+-PGC1α-SIRT1 signalling pathway. This pathway can be affected by both genomic instability and chronic inflammation since these will result in an increased rate of NAD+ degradation through PARP1 and CD38 respectively. In this work we develop a computational model of this signalling pathway, calibrating and validating it against experimental data. The computational model is used to study mitochondrial turnover under conditions of stress and how it is affected by genomic instability, chronic inflammation and biological ageing in general. We report that the AMPK-NAD+-PGC1α-SIRT1 signalling pathway becomes less responsive with age and that this can prime for the accumulation of dysfunctional mitochondria

Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones

ACKNOWLEDGMENTS This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003).Peer reviewedPublisher PD

High‐Frequency Dissolved Organic Carbon and Nitrate Measurements Reveal Differences in Storm Hysteresis and Loading in Relation to Land Cover and Seasonality

Storm events dominate riverine loads of dissolved organic carbon (DOC) and nitrate and are expected to increase in frequency and intensity in many regions due to climate change. We deployed three high‐frequency (15 min) in situ absorbance spectrophotometers to monitor DOC and nitrate concentration for 126 storms in three watersheds with agricultural, urban, and forested land use/land cover. We examined intrastorm hysteresis and the influences of seasonality, storm size, and dominant land use/land cover on storm DOC and nitrate loads. DOC hysteresis was generally anticlockwise at all sites, indicating distal and plentiful sources for all three streams despite varied DOC character and sources. Nitrate hysteresis was generally clockwise for urban and forested sites, but anticlockwise for the agricultural site, indicating an exhaustible, proximal source of nitrate in the urban and forested sites, and more distal and plentiful sources of nitrate in the agricultural site. The agricultural site had significantly higher storm nitrate yield per water yield and higher storm DOC yield per water yield than the urban or forested sites. Seasonal effects were important for storm nitrate yield in all three watersheds and farm management practices likely caused complex interactions with seasonality at the agricultural site. Hysteresis indices did not improve predictions of storm nitrate yields at any site. We discuss key lessons from using high‐frequency in situ optical sensors

Improving inpatient postnatal services: midwives views and perspectives of engagement in a quality improvement initiative

Background: despite major policy initiatives in the United Kingdom to enhance women's experiences of maternity care, improving in-patient postnatal care remains a low priority, although it is an aspect of care consistently rated as poor by women. As part of a systems and process approach to improving care at one maternity unit in the South of England, the views and perspectives of midwives responsible for implementing change were sought. Methods: a Continuous Quality Improvement (CQI) approach was adopted to support a systems and process change to in-patient care and care on transfer home in a large district general hospital with around 6000 births a year. The CQI approach included an initial assessment to identify where revisions to routine systems and processes were required, developing, implementing and evaluating revisions to the content and documentation of care in hospital and on transfer home, and training workshops for midwives and other maternity staff responsible for implementing changes. To assess midwifery views of the quality improvement process and their engagement with this, questionnaires were sent to those who had participated at the outset. Results: questionnaires were received from 68 (46%) of the estimated 149 midwives eligible to complete the questionnaire. All midwives were aware of the revisions introduced, and two-thirds felt these were more appropriate to meet the women's physical and emotional health, information and support needs. Some midwives considered that the introduction of new maternal postnatal records increased their workload, mainly as a consequence of colleagues not completing documentation as required. Conclusions: this was the first UK study to undertake a review of in-patient postnatal services. Involvement of midwives at the outset was essential to the success of the initiative. Midwives play a lead role in the planning and organisation of in-patient postnatal care and it was important to obtain their feedback on whether revisions were pragmatic and achieved anticipated improvements in care quality. Their initial involvement ensured priority areas for change were identified and implemented. Their subsequent feedback highlighted further important areas to address as part of CQI to ensure best quality care continues to be implemented. Our findings could support other maternity service organisations to optimise in-patient postnatal services

TimiRGeN: R/Bioconductor package for time series microRNA-mRNA integration and analysis

Motivation: The analysis of longitudinal datasets and construction of gene regulatory networks (GRNs) provide a valuable means to disentangle the complexity of microRNA (miRNA)-mRNA interactions. However, there are no computational tools that can integrate, conduct functional analysis and generate detailed networks from longitudinal miRNA-mRNA datasets. Results: We present TimiRGeN, an R package that uses time point-based differential expression results to identify miRNA-mRNA interactions influencing signaling pathways of interest. miRNA-mRNA interactions can be visualized in R or exported to PathVisio or Cytoscape. The output can be used for hypothesis generation and directing in vitro or further in silico work such as GRN construction

Cytokine and Adhesion Molecule Requirements for Lung Injury Induced by Anti-Glomerular Basement Membrane Antibody

Acute hemorrhagic lung injury occurs in humans with anti-GBM antibody (Goodpasture's syndrome), however, the mechanism of this injury is still largely unknown. To date, treatment has been confined to steroids and plasmaphoresis. Infusion of anti-GBM antibody into rats caused lung injury with intra-alveolar hemorrhage and intrapulmonary accumulation of neutrophils. Lung injury was dependent on the presence of neutrophils and complement and required both TNFα and IL-1. Experiments employing blocking antibodies to adhesion molecules demonstrated requirements for the β 1 integrin VLA-4, β 2 integrins LFA-1 and Mac-1, and L-selectin. The endothelial cell adhesion molecules, E-selectin and ICAM-1, were also required for the full development of lung injury. Inhibition of TNFα or IL-1 or adhesion molecules reduced both lung injury and tissue neutrophil accumulation. Thus, this study underscores cytokine and adhesion molecule requirements for neutrophil mediated injury in lung and kidney caused by anti-GBM, suggesting potential targets for the treatment of Goodpasture's syndrome in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44520/1/10753_2004_Article_416573.pd

Rat mammary carcinogenesis following neutron- or x-radiation

From effects of neutron irradiation upon cell function; Neuherberg, F. R. Germany (20 Oct 1973). Sprague-Dawley female rats, 61 to 63 days of age, were given a single dose of either 0.10, 0.40, 1.6, or 6.4 rads of 0.43-MeV neutrons, or 28, 56, or 85 rads of 250-kVp x rays, or no radiation in a single experiment. The interim results, either in terms of percent of rats with mammary neoplasia or mean number of mammary neoplasms per rat, at the end of 14 months after irradiation, indicate that 0.10 to 0.40 neutron rads was followed by a mammary neoplastic response much like that following 28 xray rads. The mammary neoplastic response to either 6.4 neutron rads or 56 to 85 x-ray rads was similar. Thus the RBE for neutrons for the induction of mammary neoplasia in the SpragueDawley rat is much larger at low neutron doses than at high doses. (auth