Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells

Obesity and type 2 diabetes lead to dramatically increased risks of atherosclerosis and CHD. Multiple mechanisms converge to promote atherosclerosis by increasing endothelial oxidative stress and up-regulating expression of pro-inflammatory molecules. Microvesicles (MV) are small ( < 1 μm) circulating particles that transport proteins and genetic material, through which they are able to mediate cell–cell communication and influence gene expression. Since MV are increased in plasma of obese, insulin-resistant and diabetic individuals, who often exhibit chronic vascular inflammation, and long-term feeding of a high-fat diet (HFD) to rats is a well-described model of obesity and insulin resistance, we hypothesised that this may be a useful model to study the impact of MV on endothelial inflammation. The number and cellular origin of MV from HFD-fed obese rats were characterised by flow cytometry. Total MV were significantly increased after feeding HFD compared to feeding chow (P< 0·001), with significantly elevated numbers of MV derived from leucocyte, endothelial and platelet compartments (P< 0·01 for each cell type). MV were isolated from plasma and their ability to induce reactive oxygen species (ROS) formation and vascular cell adhesion molecule (VCAM)-1 expression was measured in primary rat cardiac endothelial cells in vitro. MV from HFD-fed rats induced significant ROS (P< 0·001) and VCAM-1 expression (P= 0·0275), indicative of a pro-inflammatory MV phenotype in this model of obesity. These findings confirm that this is a useful model to further study the mechanisms by which diet can influence MV release and subsequent effects on cardio-metabolic health

Nitrosourea-misonidazole combination chemotherapy: effect on KHT sarcomas, marrow stem cells and gut.

C3H/HeJ mice bearing i.m. transplanted KHT sarcomas were treated with varying doses of either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin; CHLZ) as single agents or in combination with 1 mg/g of the chemical radiosensitizer, misonidazole (MISO). Using an in vivo-in vitro tumour-excision assay, the administration of MISO simultaneously with or 3 h after low doses of BCNU (less than 20 mg/kg) was found to give a dose-modification factor (DMF) of approximately 1.65 relative to BCNU alone. At higher doses of BCNU, there was less enhancement of cell kill. The DMF for tumour growth delay was likewise dependent on BCNU dose, continuously decreasing with increasing BCNU dose. In contrast, the anti-tumour activity of CHLZ, assessed by both clonogenic cell survival and tumour-growth delay, was not significantly enhanced by the addition of MISO. The enhancement of gastrointestinal toxicity and haematotoxicity by BCNU-MISO combinations was assessed by LD50/7 and CFU-S assays, respectively. MISO enhanced BCNU marrow toxicity by a factor of 1.2-1.3, whilst gut toxicity was enhanced by a factor of approximately 1.2

From Mothering Without a Net to Mothering on the Net: The Impact of an Online Social Networking Site on Experiences of Postpartum Depression

This research speaks to the desire expressed by women, health care professionals, and researchers alike, for an alternative, non-pharmacological or therapy-related intervention for postpartum depression (PPD). Interviews with twenty-two mothers and members of Momstown.ca—a social networking site focused on connecting mothers online and face-to-face—demonstrated new mothers are increasingly isolated and without community. However, mothers reported becoming members of Momstown allowed them to build a social network providing them company, camaraderie, and community, resulting in improved mental health. We conclude services like Momstown could be viable, alternative interventions for women with ppd, enabling mothers to survive and thrive postpartum

In vivo response of KHT sarcomas to combination chemotherapy with radiosensitizers and BCNU.

Female C3H/HeJ mice bearing intramuscularly transplanted KHT sarcomas were treated with a single dose of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, 30 mg/kg, i.p.) alone or in combination with a single dose of misonidazole (MISO, 1.0 mg/g, i.p.) or its desmethylated metabolite Ro-05-9963 (2.0 mg/g, i.p.). The effectiveness of drug therapy was assessed by a tumour growth-delay assay (i.e. measuring the median time required for tumours to grow to treatment size x 4). The relative efficacy of administering the nitroimidazoles in various schedules ranging from 12 h before to 12 h after BCNU administration also was evaluated. Untreated control KHT tumours grew to the initial size x 4 in a median time of 4 days. No significant growth delay was seen in mice treated with either nitroimidazole alone, whilst treatment with BCNU alone produced a median growth delay of 7 days. Combination chemotherapy with 9963 administration 3 h after BCNU significantly increased the median tumour growth delay to 9 days. However, no significant growth delay was produced in any of the other combinations of these agents. The median growth delay was significantly reduced to 5 days when MISO was administered 3 h before BCNU, whereas MISO administered simultaneously 3,6, or 12 h after BCNU significantly enhanced delays ( 9 days). These results indicate that both MISO and 0063 may be combined with conventional therapeutic agents, in this particular case a nitrosourea, to produce an enhanced tumour response. The production of such a response appears to be nitroimidazole as well as schedule dependent

Radio haloes in nearby galaxies modelled with 1D cosmic-ray transport using SPINNAKER

We present radio continuum maps of 12 nearby ($D\leq 27~\rm Mpc$), edge-on ($i\geq 76^{\circ}$), late-type spiral galaxies mostly at $1.4$ and 5 GHz, observed with the Australia Telescope Compact Array, Very Large Array, Westerbork Synthesis Radio Telescope, Effelsberg 100-m and Parkes 64-m telescopes. All galaxies show clear evidence of radio haloes, including the first detection in the Magellanic-type galaxy NGC 55. In 11 galaxies, we find a thin and a thick disc that can be better fitted by exponential rather than Gaussian functions. We fit our SPINNAKER (SPectral INdex Numerical Analysis of K(c)osmic-ray Electron Radio-emission) 1D cosmic-ray transport models to the vertical model profiles of the non-thermal intensity and to the non-thermal radio spectral index in the halo. We simultaneously fit for the advection speed (or diffusion coefficient) and magnetic field scale height. In the thick disc, the magnetic field scale heights range from 2 to 8 kpc with an average across the sample of $3.0\pm 1.7~\rm kpc$; they show no correlation with either star-formation rate (SFR), SFR surface density ($\Sigma_{\rm SFR}$) or rotation speed ($V_{\rm rot}$). The advection speeds range from 100 to $700~\rm km\,s^{-1}$ and display correlations of $V\propto \rm SFR^{0.36\pm 0.06}$ and $V\propto \Sigma_{\rm SFR}^{0.39\pm 0.09}$; they agree remarkably well with the escape velocities ($0.5\leq V/V_{\rm esc}\leq 2$), which can be explained by cosmic-ray driven winds. Radio haloes show the presence of disc winds in galaxies with $\Sigma_{\rm SFR} > 10^{-3}~\rm M_{\odot}\,yr^{-1}\,kpc^{-2}$ that extend over several kpc and are driven by processes related to the distributed star formation in the disc.Comment: 39 pages, 20 colour figures, 10 tables. Accepted by MNRA

The PULSE@Parkes project: A new observing technique for long-term pulsar monitoring

The PULSE@Parkes project has been designed to monitor the rotation of radio pulsars over time spans of days to years. The observations are obtained using the Parkes 64-m and 12-m radio telescopes by Australian and international high school students. These students learn the basis of radio astronomy and undertake small projects with their observations. The data are fully calibrated and obtained with the state-of-the-art pulsar hardware available at Parkes. The final data sets are archived and are currently being used to carry out studies of 1) pulsar glitches, 2) timing noise, 3) pulse profile stability over long time scales and 4) the extreme nulling phenomenon. The data are also included in other projects such as gamma-ray observatory support and for the Parkes Pulsar Timing Array project. In this paper we describe the current status of the project and present the first scientific results from the Parkes 12-m radio telescope. We emphasise that this project offers a straightforward means to enthuse high school students and the general public about radio astronomy while obtaining scientifically valuable data sets.Comment: accepted for publication by PAS

Analysis of climate variability and change in observational groundwater quality data

This report details Task 1 (“Evaluation of historical observational groundwater quality data”) of Phase 2 of the Environment Agency-BGS collaborative project “climate and land use change impacts on groundwater quality”. The objective of this task is to evaluate historical observational groundwater quality data held by the Environment Agency (EA) to determine the following: (1) the suitability of existing monitoring for future monitoring of long-term impacts of climate and land use change and (2) whether there is evidence for climate variability, and if possible, impacts of historical climate change in the observations. It was agreed in an EA-BGS kickoff meeting that this task would investigate climate variability and change in nitrate and groundwater temperature data. This task focusses on southeast England as a case study. Analysis of groundwater nitrate data held by the Environment Agency in WIMS has shown that a small number of sites meet the required time series length requirement for climate change impact monitoring in southeast England (30 years). The recent natural variability in climate combined with short record length means that any climate change impacts cannot be observed in the data provided. Cluster analysis has revealed different modes of temporal fluctuations in nitrate concentrations. The depth of groundwater flow system intercepted by the boreholes appears to control the long-term direction of change in groundwater nitrate concentrations. Non-linear and seasonal behaviour associated with climate variability are present in two clusters, which are weakly spatially coherent across the North and South Downs. Cross-correlation of nitrate time series with both raw and standardised indices of groundwater level and precipitation show that the extent of nitrate fluctuation appears to be controlled by precipitation and groundwater level fluctuation. This may be due to a combination of piston flow and changing groundwater flow paths. Under future climate change, nitrate fluctuations may change associated with the changing intersection of the water table and the legacy nitrate peak in the unsaturated zone. The timescales for land use change impacts on nitrate at the water table will vary substantially depending on the dominant process controlling nitrate fluctuations. Processes which represent a transfer of mass (bypass flow) will impact concentrations much more rapidly than processes representing a transfer of energy (piston flow). Analysis of groundwater temperature data for 20 boreholes has shown that, for 8 of 17 shallow boreholes with temperature data over 2012-2022, groundwater temperature trends are broadly consistent with current air temperature trends. 7 of these sites show increasing trends, with a mean trend of 0.66 °C/decade. Three deep interfluve sites show increases, with a mean trend if 0.38 °C/decade. It is likely that these trends are controlled by current and historical near-decadal trends in local air temperature for shallow and deep sites respectively. The remaining 8 shallow sites show inconsistent trends in comparison with local air temperature trends. For these sites it likely that in addition to air temperature trends, additional heat fluxes into the subsurface are occurring superimposed on changes in groundwater flow to the boreholes. The shallow sites show seasonal temperature fluctuations associated with propagation of air temperature signals, with seasonal range in groundwater temperature significantly negatively correlated with borehole depth. Three very shallow sites show diurnal fluctuations, although these fluctuations are below the accuracy of the sensors. The increases in groundwater temperature observed have some implications for other components of groundwater quality (e.g. biogeochemical cycles, stygofauna, pollutant (N, pesticide, LNAPL) degradation and for the role that groundwater discharges to surface water play in providing cold-water hydro-refugia to cold-water species during summer

In the Interests of clients or commerce? Legal aid, supply, demand, and 'ethical indeterminacy' in criminal defence work

As a professional, a lawyer's first duty is to serve the client's best interests, before simple monetary gain. In criminal defence work, this duty has been questioned in the debate about the causes of growth in legal aid spending: is it driven by lawyers (suppliers) inducing unnecessary demand for their services or are they merely responding to increased demand? Research reported here found clear evidence of a change in the handling of cases in response to new payment structures, though in ways unexpected by the policy's proponents. The paper develops the concept of 'ethical indeterminacy' as a way of understanding how defence lawyers seek to reconcile the interests of commerce and clients. Ethical indeterminacy suggests that where different courses of action could each be said to benefit the client, the lawyer will tend to advise the client to decide in the lawyer's own interests. Ethical indeterminacy is mediated by a range of competing conceptions of 'quality' and 'need'. The paper goes on to question the very distinction between 'supply' and 'demand' in the provision of legal services