Artificial weathering of some soil clays

An artificial weathering experiment was set up to test for reversibility within the system. 2:1 – 2:2 Al-intergrade vermiculture montmorillonite. Strongly chelating (0.20M and 0.02M citrate) and weakly chelating (0.02M acetate) solutions buffered at pH 3.5, 4.5 and 5.5, were leached for varying periods of time up to 6 monhts, through B2 horizon. Craigieburn silt loam. X-Ray diffraction of the leached soil clay fraction showed that the period of leaching was too short to cause a clay transformation from the initial 2:1 – 2:2 Al-intergrade into a 2:1 layer silicate. However, X-Ray and electron microscopy studies showed removal of some surface coatings and interlayer hydroxy Al. Analyses leachates showed that the citrate (chelating) buffers were more effective at removing Al and Fe from the solid phases than acetate (non-chelating) buffers. Quantities removed and rates of solution of Al and Fe increase with decreasing pH. Rapid initial loss of Al and Fe probably involved disordered gels and surface coatings. Increasing the citrate concentration above a certain limit did not increase the ability of the solution to remove Al and Fe. Leaching with 1.5M AlCl3 solution at pH’s 3.5, 4.5 and 5.5 caused rapid fixation of Al in the A2 horizon of the Katrine silt loam. A vermiculite-montmorillonite intergrade was rapidly transformed into a 2:1 – 2:2 Al-intergrade, suggesting that an increase in pH leading to build up in Al species in the soil would result in montmorillonite being transformed into 2:1 – 2:2 Al-intergrade. It was concluded that leaching for longer periods, using a lower concentration of chelating solution, that would more closely simulate the natural system should be attempted. Developments of the method are suggested

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Seasonal analysis of submicron aerosol in Old Delhi using high-resolution aerosol mass spectrometry: chemical characterisation, source apportionment and new marker identification

We present the first real-time composition of submicron particulate matter (PM1) in Old Delhi using high-resolution aerosol mass spectrometry (HR-AMS). Old Delhi is one of the most polluted locations in the world, and PM1 concentrations reached ∼ 750 µg m−3 during the most polluted period, the post-monsoon period, where PM1 increased by 188 % over the pre-monsoon period. Sulfate contributes the largest inorganic PM1 mass fraction during the pre-monsoon (24 %) and monsoon (24 %) periods, with nitrate contributing most during the post-monsoon period (8 %). The organics dominate the mass fraction (54 %–68 %) throughout the three periods, and, using positive matrix factorisation (PMF) to perform source apportionment analysis of organic mass, two burning-related factors were found to contribute the most (35 %) to the post-monsoon increase. The first PMF factor, semi-volatility biomass burning organic aerosol (SVBBOA), shows a high correlation with Earth observation fire counts in surrounding states, which links its origin to crop residue burning. The second is a solid fuel OA (SFOA) factor with links to local open burning due to its high composition of polyaromatic hydrocarbons (PAHs) and novel AMS-measured marker species for polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Two traffic factors were resolved: one hydrocarbon-like OA (HOA) factor and another nitrogen-rich HOA (NHOA) factor. The N compounds within NHOA were mainly nitrile species which have not previously been identified within AMS measurements. Their PAH composition suggests that NHOA is linked to diesel and HOA to compressed natural gas and petrol. These factors combined make the largest relative contribution to primary PM1 mass during the pre-monsoon and monsoon periods while contributing the second highest in the post-monsoon period. A cooking OA (COA) factor shows strong links to the secondary factor, semi-volatility oxygenated OA (SVOOA). Correlations with co-located volatile organic compound (VOC) measurements and AMS-measured organic nitrogen oxides (OrgNO) suggest SVOOA is formed from aged COA. It is also found that a significant increase in chloride concentrations (522 %) from pre-monsoon to post-monsoon correlates well with SVBBOA and SFOA, suggesting that crop residue burning and open waste burning are responsible. A reduction in traffic emissions would effectively reduce concentrations across most of the year. In order to reduce the post-monsoon peak, sources such as funeral pyres, solid waste burning and crop residue burning should be considered when developing new air quality policy

Avoiding the danger that stop smoking services may exacerbate health inequalities: building equity into performance assessment

<p>Abstract</p> <p>Background</p> <p>The UK is the only developed country to have established a nation-wide stop smoking treatment service. Apart from addressing tobacco dependence, which is the leading preventable cause of ill health and premature death, smoking cessation has been identified by the UK department of health as a service priority for reducing gaps in health between disadvantaged groups and the country as a whole. However smoking cessation tends to be more successful among affluent than disadvantaged groups. This means that for stop smoking services there is a trade-off to be had in terms of maximising the number of quitters and reducing socioeconomic inequalities in smoking prevalence. Current performance targets for the national stop smoking services in the UK are set only in terms of numbers of quitters, which does not encourage the adoption of strategies to reduce socioeconomic inequalities in smoking prevalence.</p> <p>Discussion</p> <p>This paper proposes an assessment framework, which allows the two dimensions of overall reduction in smoking prevalence and reductions of inequalities in smoking prevalence to be assessed together. The framework is used to assess the performance over time of a stop smoking service in Derwentside, a former Primary Care Trust in the North East of England, both in terms of meeting targets for the overall number of quitters and in terms of reducing socioeconomic inequalities in smoking prevalence.</p> <p>The example demonstrates how the proposed assessment framework can be applied in practice given existing records kept by stop smoking services in England and the available information on smoking prevalence at small area level. For Derwentside it is shown that although service expansion was successful in increasing the overall number of quitters, the service continued to exacerbate inequality in smoking prevalence between deprived and affluent wards.</p> <p>Summary</p> <p>The Secretary of State for Health in the UK has warned about the dangers of health promotion services and messages being taken up more readily by the better-off, thus exacerbating health inequalities. Because smokers from affluent backgrounds are more successful at quitting than those living in deprived circumstances, it is important to build an equity element into the monitoring of individual stop smoking services. Otherwise the danger highlighted by the Secretary of State for Health will go undetected and unaddressed.</p

The ACCESS study a Zelen randomised controlled trial of a treatment package including problem solving therapy compared to treatment as usual in people who present to hospital after self-harm: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>People who present to hospital after intentionally harming themselves pose a common and important problem. Previous reviews of interventions have been inconclusive as existing trials have been under powered and done on unrepresentative populations. These reviews have however indicated that problem solving therapy and regular written communications after the self-harm attempt may be an effective treatment. This protocol describes a large pragmatic trial of a package of measures which include problem solving therapy, regular written communication, patient support, cultural assessment, improved access to primary care and a risk management strategy in people who present to hospital after self-harm using a novel design.</p> <p>Methods</p> <p>We propose to use a double consent Zelen design where participants are randomised prior to giving consent to enrol a large representative cohort of patients. The main outcome will be hospital attendance following repetition of self-harm, in the 12 months after recruitment with secondary outcomes of self reported self-harm, hopelessness, anxiety, depression, quality of life, social function and hospital use at three months and one year.</p> <p>Discussion</p> <p>A strength of the study is that it is a pragmatic trial which aims to recruit large numbers and does not exclude people if English is not their first language. A potential limitation is the analysis of the results which is complex and may underestimate any effect if a large number of people refuse their consent in the group randomised to problem solving therapy as they will effectively cross over to the treatment as usual group. However the primary analysis is a true intention to treat analysis of everyone randomised which includes both those who consent and do not consent to participate in the study. This provides information about how the intervention will work in practice in a representative population which is a major advance in this study compared to what has been done before.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000641291.aspx">ACTRN12609000641291</a></p

Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment

BACKGROUND: Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. METHOD: An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naïve to abacavir and non-nucleoside reverse transcriptase inhibitors. RESULTS: At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm(3 )in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments. CONCLUSION: In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm(3), substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Introduction to Special Issue - In-depth study of air pollution sources and processes within Beijing and its surrounding region (APHH-2 Beijing)

Abstract. The Atmospheric Pollution and Human Health in a Chinese Megacity (APHH-Beijing) programme is an international collaborative project focusing on understanding the sources, processes and health effects of air pollution in the Beijing megacity. APHH-Beijing brings together leading China and UK research groups, state-of-the-art infrastructure and air quality models to work on four research themes: (1) sources and emissions of air pollutants; (2) atmospheric processes affecting urban air pollution; (3) air pollution exposure and health impacts; and (4) interventions and solutions. Themes 1 and 2 are closely integrated and support Theme 3, while Themes 1-3 provide scientific data for Theme 4 to develop cost-effective air pollution mitigation solutions. This paper provides an introduction to (i) the rationale of the APHH-Beijing programme, and (ii) the measurement and modelling activities performed as part of it. In addition, this paper introduces the meteorology and air quality conditions during two joint intensive field campaigns - a core integration activity in APHH-Beijing. The coordinated campaigns provided observations of the atmospheric chemistry and physics at two sites: (i) the Institute of Atmospheric Physics in central Beijing, and (ii) Pinggu in rural Beijing during 10 November – 10 December 2016 (winter) and 21 May- 22 June 2017 (summer). The campaigns were complemented by numerical modelling and automatic air quality and low-cost sensor observations in the Beijing megacity. In summary, the paper provides background information on the APHH-Beijing programme, and sets the scene for more focussed papers addressing specific aspects, processes and effects of air pollution in Beijing

The role of horizontal resolution in simulating drivers of the global hydrological cycle

The role of atmospheric general circulation model (AGCM) horizontal resolution in representing the global energy budget and hydrological cycle is assessed, with the aim of improving the understanding of model uncertainties in simulating the hydrological cycle. We use two AGCMs from the UK Met Office Hadley Centre: HadGEM1-A at resolutions ranging from 270 to 60 km, and HadGEM3-A ranging from 135 to 25 km. The models exhibit a stable hydrological cycle, although too intense compared to reanalyses and observations. This over-intensity is explained by excess surface shortwave radiation, a common error in general circulation models (GCMs). This result is insensitive to resolution. However, as resolution is increased, precipitation decreases over the ocean and increases over the land. This is associated with an increase in atmospheric moisture transport from ocean to land, which changes the partitioning of moisture fluxes that contribute to precipitation over land from less local to more non-local moisture sources. The results start to converge at 60-km resolution, which underlines the excessive reliance of the mean hydrological cycle on physical parametrization (local unresolved processes) versus model dynamics (large-scale resolved processes) in coarser HadGEM1 and HadGEM3 GCMs. This finding may be valid for other GCMs, showing the necessity to analyze other chains of GCMs that may become available in the future with such a range of horizontal resolutions. Our finding supports the hypothesis that heterogeneity in model parametrization is one of the underlying causes of model disagreement in the Coupled Model Intercomparison Project (CMIP) exercises