Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

NSAM-derived total surface area vs. SMPS-derived "mobility equivalent" surface area for different environmentally relevant aerosols

The surface area of inhaled particles deposited in the alveolar region, as reported by the TSI nanoparticle surface area monitor (NSAM), was compared with the corresponding value estimated by a TSI scanning mobility particle sizer (SMPS) for a range of environmentally relevant aerosols, including petrol emissions, ETS, laser printer emissions, cooking emissions and ambient aerosols. The SMPS values were based on a mobility size distribution assuming spherical particles using the appropriate size-dependent alveolar-deposition factors provided by the ICRP. In most cases, the two instruments showed good linear agreement. With petrol emissions and ETS, the linearity extended to over 103 μm2 cm-3. With printer emissions, there was good linearity up to about 300 μm2 cm-3 while the NSAM increasingly overestimated the surface area at higher concentrations. The presence of a nucleation event in ambient air caused the NSAM to over-estimate the surface area by a factor of 2. We summarize these results and conclude that the maximum number concentration up to which the NSAM is accurate clearly depends on the type of aerosol being sampled and provide guidance for the use of the instrument.

Phosphorus as a limiting factor on sustainable greywater irrigation

Water reuse through greywater irrigation has been adopted worldwide and has been proposed as a potential sustainable solution to increased water demands. Despite widespread adoption there is limited domestic knowledge of greywater reuse, there is no pressure to produce lowlevel phosphorus products and current guidelines and legislation, such as those in Australia, may be inadequate due to the lack of long-term data to provide a sound scientific basis. Research has clearly identified phosphorus as a potential environmental risk to waterways from many forms of irrigation. To assess the sustainability of greywater irrigation, this study compared four residential lots that had been irrigated with greywater for four years and adjacent non-irrigated lots that acted as controls. Each lot was monitored for the volume of greywater applied and selected physic-chemical water quality parameters and soil chemistry profiles were analysed. The non-irrigated soil profiles showed low levels of phosphorus and were used as controls. The Mechlich3 Phosphorus ratio (M3PSR) and Phosphate Environmental Risk Index (PERI) were used to determine the environmental risk of phosphorus leaching from the irrigated soils. Soil phosphorus concentrations were compared to theoretical greywater irrigation loadings. The measured phosphorus soil concentrations and the estimated greywater loadings were of similar magnitude. Sustainable greywater reuse is possible; however incorrect use and/or a lack of understanding of how household products affect greywater can result in phosphorus posing a significant risk to the environment.

Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men

BACKGROUND/OBJECTIVES: Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. RESULTS: No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). CONCLUSIONS: No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

Testing the psychometric properties of the Brisbane Practice Environment Measure using Exploratory Factor Analysis and Confirmatory Factor Analysis in an Australian registered nurse population

A cross-sectional survey was conducted, and the construct validity and reliability of the Brisbane Practice Environment Measure in an Australian sample of registered nurses were examined. Nurses were randomly selected from the database of an Australian nursing organization. The original 33 items of the Brisbane Practice Environment Measure were utilized to inform the psychometric properties using confirmatory factor analysis. The Cronbach's alpha was 0.938 for the total scale and ranged 0.657–0.887 for the subscales. A five-factor structure of the measure was confirmed, χ2 = 944.622, (P < 0.01), χ2/d.f. ratio = 2.845, Tucker Lewis Index 0.929, Root Mean Square Error = 0.061 and Comparative Fit Index = 0.906. The selected 28 items of the measure proved reliable and valid in measuring effects of the practice environment upon Australian nurses. The implications are that regular measurement of the practice environment using these 28 items might assist in the development of strategies which might improve job satisfaction and retention of registered nurses in Australia.

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

An R2R3 MYB transcription factor determines red petal colour in an Actinidia (kiwifruit) hybrid population

Background Red colour in kiwifruit results from the presence of anthocyanin pigments. Their expression, however, is complex, and varies among genotypes, species, tissues and environments. An understanding of the biosynthesis, physiology and genetics of the anthocyanins involved, and the control of their expression in different tissues, is required. A complex, the MBW complex, consisting of R2R3-MYB and bHLH transcription factors together with a WD-repeat protein, activates anthocyanin 3-O-galactosyltransferase (F3GT1) to produce anthocyanins. We examined the expression and genetic control of anthocyanins in flowers of Actinidia hybrid families segregating for red and white petal colour. Results Four inter-related backcross families between Actinidia chinensis Planch. var. chinensis and Actinidia eriantha Benth. were identified that segregated 1:1 for red or white petal colour. Flower pigments consisted of five known anthocyanins (two delphinidin-based and three cyanidin-based) and three unknowns. Intensity and hue differed in red petals from pale pink to deep magenta, and while intensity of colour increased with total concentration of anthocyanin, no association was found between any particular anthocyanin data and hue. Real time qPCR demonstrated that an R2R3 MYB, MYB110a, was expressed at significant levels in red-petalled progeny, but not in individuals with white petals. A microsatellite marker was developed that identified alleles that segregated with red petal colour, but not with ovary, stamen filament, or fruit flesh colour in these families. The marker mapped to chromosome 10 in Actinidia. The white petal phenotype was complemented by syringing Agrobacterium tumefaciens carrying Actinidia 35S::MYB110a into the petal tissue. Red pigments developed in white petals both with, and without, co-transformation with Actinidia bHLH partners. MYB110a was shown to directly activate Actinidia F3GT1 in transient assays. Conclusions The transcription factor, MYB110a, regulates anthocyanin production in petals in this hybrid population, but not in other flower tissues or mature fruit. The identification of delphinidin-based anthocyanins in these flowers provides candidates for colour enhancement in novel fruits.

Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer : NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry. irNGAL was not present in normal ovaries and the NGAL expression was weak to moderate in benign tissues. Both borderline and grade 1 tumors displayed the highest amount of NGAL expression with moderate to strong staining, whereas in grade 2 and 3 tumors, the extent of staining was significantly less (p < 0.01) and staining intensity was weak to moderate. Staining in all cases was confined to the epithelium. NGAL expression was analyzed by ELISA in 62 serum specimens from normal and different grades of cancer patients. Compared to control samples, the NGAL concentration was 2 and 2.6-fold higher in the serum of patients with benign tumors and cancer patients with grade 1 tumors (p < 0.05) and that result was consistent with the expression of NGAL performed by Western blot. NGAL expression was evaluated by Western blot in an immortalized normal ovarian cell line (IOSE29) as well as ovarian cancer cell lines. Moderate to strong expression of NGAL was observed in epithelial ovarian cancer cell lines SKOV3 and OVCA433 while no expression of NGAL was evident in normal IOSE29 and mesenchyme-like OVHS1, PEO.36 and HEY cell lines. NGAL expression was downregulated in ovarian cancer cell lines undergoing epithelio-mesenchymal transition (EMT) induced by epidermal growth factor (EGF). Down-regulation of NGAL expression correlated with the upregulation of vimentin expression, enhanced cell dispersion and downregulation of E-cadherin expression, some of the hallmarks of EMT. EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. These data indicate that NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies.

Measuring Productivity Gains from Deregulation of the Japanese Urban Gas Industry

The Japanese government initiated a series of regulatory reforms in the mid-1990s. The Japanese urban gas industry consists of various sized private and non-private firms. Numerous previous studies find that deregulation leads to productivity improvements. We extend the literature by analyzing deregulation, privatization, and other aspects of a regulated industry using unique firm level data. This study measures productivity to evaluate the effect of the deregulation reform. Using data from 205 firms from 1993 to 2004, we find that the deregulation effect differs depending on firm size. Competitive pressure contributes to advanced productivity. The deregulation of gas sales to commercial customers is the most important factor for advancing productivity. Copyright © 2013 by the IAEE. All rights reserved.

Productivity change of Nigerian insurance companies : 1994-2005

The aim of this paper is to estimate the productivity change of Nigerian insurance companies and to rank the companies analysed in the sample according to their productivity score. This benchmark exercise provides the companies analysed with a view of how their relative productivity can be upgraded. For this purpose, the non-parametric Luenberger productivity model is used. For comparative purposes, the non-parametric Luenberger-Hicks-Moorsteen productivity indicator is also used. The companies are ranked according to their total productivity for the period 1994-2005, using both models, which produce variations in the respective results. Economic implications arising from the study are derived.

Diverse urban plantings managed with sufficient resource availability can increase plant productivity and arthropod diversity

Buildings structures and surfaces are explicitly being used to grow plants, and these “urban plantings” are generally designed for aesthetic value. Urban plantings also have the potential to contribute significant “ecological values” by increasing urban habitat for animals such as arthropods and by increasing plant productivity. In this study, we evaluated how the provision of these additional ecological values is affected by plant species richness; the availability of essential resources for plants, such as water, light, space; and soil characteristics. We sampled 33 plantings located on the exterior of three buildings in the urban center of Brisbane, Australia (subtropical climatic region) over 2, 6 week sampling periods characterized by different temperature and rainfall conditions. Plant cover was estimated as a surrogate for productivity as destructive sampling of biomass was not possible. We measured weekly light levels (photosynthetically active radiation), plant CO2 assimilation, soil CO2 efflux, and arthropod diversity. Differences in plant cover were best explained by a three-way interaction of plant species richness, management water regime and sampling period. As the richness of plant species increased in a planter, productivity and total arthropod richness also increased significantly—likely due to greater habitat heterogeneity and quality. Overall we found urban plantings can provide additional ecological values if essential resources are maintained within a planter such as water, light and soil temperature. Diverse urban plantings that are managed with these principles in mind can contribute to the attraction of diverse arthropod communities, and lead to increased plant productivity within a dense urban context.

Transit route occupancy load factor and passenger average travel time for quality of service assessment

This paper investigates quality of service (QoS) and resource productivity implications of transit route passenger loading and travel time. It highlights the value of occupancy load factor as a direct passenger comfort QoS measure. Automatic Fare Collection data for a premium radial bus route in Brisbane, Australia, is used to investigate time series correlation between occupancy load factor and passenger average travel time. Correlation is strong across the entire span of service in both directions. Passengers tend to be making longer, peak direction commuter trips under significantly less comfortable conditions than off-peak. The Transit Capacity and Quality of Service Manual uses segment based load factor as a measure of onboard loading comfort QoS. This paper provides additional insight into QoS by relating the two route based dimensions of occupancy load factor and passenger average travel time together in a two dimensional format, both from the passenger’s and operator’s perspectives. Future research will apply Value of Time to QoS measurement, reflecting perceived passenger comfort through crowding and average time spent onboard. This would also assist in transit service quality econometric modeling. The methodology can be readily applied in a practical setting where AFC data for fixed scheduled routes is available. The study outcomes also provide valuable research and development directions.

Transit route occupancy load factor and passenger average travel time for quality of service assessment

This presentation investigates quality of service (QoS) and resource productivity implications of transit route passenger loading and travel time. It highlights the value of occupancy load factor as a direct passenger comfort QoS measure. Automatic Fare Collection data for a premium radial bus route in Brisbane, Australia, is used to investigate time series correlation between occupancy load factor and passenger average travel time. Correlation is strong across the entire span of service in both directions. Passengers tend to be making longer, peak direction commuter trips under significantly less comfortable conditions than off-peak. The Transit Capacity and Quality of Service Manual uses segment based load factor as a measure of onboard loading comfort QoS. This paper provides additional insight into QoS by relating the two route based dimensions of occupancy load factor and passenger average travel time together in a two dimensional format, both from the passenger’s and operator’s perspectives. Future research will apply Value of Time to QoS measurement, reflecting perceived passenger comfort through crowding and average time spent onboard. This would also assist in transit service quality econometric modeling. The methodology can be readily applied in a practical setting where AFC data for fixed scheduled routes is available. The study outcomes also provide valuable research and development directions.

Interpersonal violence : an important risk factor for disease and injury in South Africa

Background Burden of disease estimates for South Africa have highlighted the particularly high rates of injuries related to interpersonal violence compared with other regions of the world, but these figures tell only part of the story. In addition to direct physical injury, violence survivors are at an increased risk of a wide range of psychological and behavioral problems. This study aimed to comprehensively quantify the excess disease burden attributable to exposure to interpersonal violence as a risk factor for disease and injury in South Africa. Methods The World Health Organization framework of interpersonal violence was adapted. Physical injury mortality and disability were categorically attributed to interpersonal violence. In addition, exposure to child sexual abuse and intimate partner violence, subcategories of interpersonal violence, were treated as risk factors for disease and injury using counterfactual estimation and comparative risk assessment methods. Adjustments were made to account for the combined exposure state of having experienced both child sexual abuse and intimate partner violence. Results Of the 17 risk factors included in the South African Comparative Risk Assessment study, interpersonal violence was the second leading cause of healthy years of life lost, after unsafe sex, accounting for 1.7 million disability-adjusted life years (DALYs) or 10.5% of all DALYs (95% uncertainty interval: 8.5%-12.5%) in 2000. In women, intimate partner violence accounted for 50% and child sexual abuse for 32% of the total attributable DALYs. Conclusions The implications of our findings are that estimates that include only the direct injury burden seriously underrepresent the full health impact of interpersonal violence. Violence is an important direct and indirect cause of health loss and should be recognized as a priority health problem as well as a human rights and social issue. This study highlights the difficulties in measuring the disease burden from interpersonal violence as a risk factor and the need to improve the epidemiological data on the prevalence and risks for the different forms of interpersonal violence to complete the picture. Given the extent of the burden, it is essential that innovative research be supported to identify social policy and other interventions that address both the individual and societal aspects of violence.

Clinical use of diodes and micro-chambers to obtain accurate small field output factor measurements

There have been substantial advances in small field dosimetry techniques and technologies, over the last decade, which have dramatically improved the achievable accuracy of small field dose measurements. This educational note aims to help radiation oncology medical physicists to apply some of these advances in clinical practice. The evaluation of a set of small field output factors (total scatter factors) is used to exemplify a detailed measurement and simulation procedure and as a basis for discussing the possible effects of simplifying that procedure. Field output factors were measured with an unshielded diode and a micro-ionisation chamber, at the centre of a set of square fields defined by a micro-multileaf collimator. Nominal field sizes investigated ranged from 6×6 to 98×98 mm2. Diode measurements in fields smaller than 30 mm across were corrected using response factors calculated using Monte Carlo simulations of the full diode geometry and daisy-chained to match micro-chamber measurements at intermediate field sizes. Diode measurements in fields smaller than 15 mm across were repeated twelve times over three separate measurement sessions, to evaluate the to evaluate the reproducibility of the radiation field size and its correspondence with the nominal field size. The five readings that contributed to each measurement on each day varied by up to 0.26%, for the “very small” fields smaller than 15 mm, and 0.18% for the fields larger than 15 mm. The diode response factors calculated for the unshielded diode agreed with previously published results, within 1.6%. The measured dimensions of the very small fields differed by up to 0.3 mm, across the different measurement sessions, contributing an uncertainty of up to 1.2% to the very small field output factors. The overall uncertainties in the field output factors were 1.8% for the very small fields and 1.1% for the fields larger than 15 mm across. Recommended steps for acquiring small field output factor measurements for use in radiotherapy treatment planning system beam configuration data are provided.