In situ mixing of organic matter decreases hydraulic conductivity of denitrification walls in sand aquifers

In a previous study, a denitrification wall was constructed in a sand aquifer using sawdust as the carbon substrate. Ground water bypassed around this sawdust wall due to reduced hydraulic conductivity. We investigated potential reasons for this by testing two new walls and conducting laboratory studies. The first wall was constructed by mixing aquifer material in situ without substrate addition to investigate the effects of the construction technique (mixed wall). A second, biochip wall, was constructed using coarse wood chips to determine the effect of size of the particles in the amendment on hydraulic conductivity. The aquifer hydraulic conductivity was 35.4 m/d, while in the mixed wall it was 2.8 m/d and in the biochip wall 3.4 m/d. This indicated that the mixing of the aquifer sands below the water table allowed the particles to re-sort themselves into a matrix with a significantly lower hydraulic conductivity than the process that originally formed the aquifer. The addition of a coarser substrate in the biochip wall significantly increased total porosity and decreased bulk density, but hydraulic conductivity remained low compared to the aquifer. Laboratory cores of aquifer sand mixed under dry and wet conditions mimicked the reduction in hydraulic conductivity observed in the field within the mixed wall. The addition of sawdust to the laboratory cores resulted in a significantly higher hydraulic conductivity when mixed dry compared to cores mixed wet. This reduction in the hydraulic conductivity of the sand/sawdust cores mixed under saturated conditions repeated what occurred in the field in the original sawdust wall. This indicated that laboratory investigations can be a useful tool to highlight potential reductions in field hydraulic conductivities that may occur when differing materials are mixed under field conditions

Finite temperature behaviour of the ISS-uplifted KKLT model

We study the static phase structure of the ISS-KKLT model for moduli stabilisation and uplifting to a zero cosmological constant. Since the supersymmetry breaking sector and the moduli sector are only gravitationally coupled, we expect negligible quantum effects of the modulus upon the ISS sector, and the other way around. Under this assumption, we show that the ISS fields end up in the metastable vacua. The reason is not only that it is thermally favoured (second order phase transition) compared to the phase transition towards the supersymmetric vacua, but rather that the metastable vacua form before the supersymmetric ones. This nice feature is exclusively due to the presence of the KKLT sector. We also show that supergravity effects are negligible around the origin of the field space. Finally, we turn to the modulus sector and show that there is no destabilisation effect coming from the ISS sector.Comment: 23 pages, 3 figures, mistake corrected, one plot updated, physical conclusions unchange

Long QT Syndrome Type 2: Emerging Strategies for Correcting Class 2 \u3cem\u3eKCNH2 (hERG)\u3c/em\u3e Mutations and Identifying New Patients

Significant advances in our understanding of the molecular mechanisms that cause congenital long QT syndrome (LQTS) have been made. A wide variety of experimental approaches, including heterologous expression of mutant ion channel proteins and the use of inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LQTS patients offer insights into etiology and new therapeutic strategies. This review briefly discusses the major molecular mechanisms underlying LQTS type 2 (LQT2), which is caused by loss-of-function (LOF) mutations in the KCNH2 gene (also known as the human ether-à-go-go-related gene or hERG). Almost half of suspected LQT2-causing mutations are missense mutations, and functional studies suggest that about 90% of these mutations disrupt the intracellular transport, or trafficking, of the KCNH2-encoded Kv11.1 channel protein to the cell surface membrane. In this review, we discuss emerging strategies that improve the trafficking and functional expression of trafficking-deficient LQT2 Kv11.1 channel proteins to the cell surface membrane and how new insights into the structure of the Kv11.1 channel protein will lead to computational approaches that identify which KCNH2 missense variants confer a high-risk for LQT2

Elevated DNA Oxidation and DNA Repair Enzyme Expression in Brain White Matter in Major Depressive Disorder

Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood. Methods:Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8). Results:DNA oxidation in BA10 white matter was robustly elevated in MDD as compared to control donors, with a smaller elevation occurring in schizophrenia donors. DNA oxidation levels in psychiatrically affected donors that died by suicide did not significantly differ from DNA oxidation levels in psychiatrically affected donors dying by other causes (non-suicide). Gene expression levels of two base excision repair enzymes, PARP1 and OGG1, were robustly elevated in oligodendrocytes laser captured from BA10 and amygdala white matter of MDD donors, with smaller but significant elevations of these gene expressions in astrocytes. In rats, repeated stress-induced anhedonia, as measured by a reduction in sucrose preference, was associated with increased DNA oxidation in white, but not gray, matter. Conclusions:Cellular residents of brain white matter demonstrate markers of oxidative damage in MDD. Medications that interfere with oxidative damage or pathways activated by oxidative damage have potential to improve treatment for MDD

Transition pathways to a low carbon economy: Linking governance patterns and assessment methodologies

This paper describes work being undertaken as part of an interdisciplinary project on transition pathways to a low carbon economy, bringing together insights from engineers, social scientists and policy analysts. The project is examining the plausibility of different transition pathways for a low carbon energy system in the UK, under different governance patterns, in relation to both centralised and decentralised systems for meeting energy service demands. It uses a conceptual and analytical framework combining the multi-level transitions perspective of landscape, regime and niche levels, with more detailed analysis of the technological feasibility and social acceptability of the pathways. The research uses an interpretative frame based on an „action space‟ of governance patterns relating to the mix and balance of actions led by three sets of actors in central government, in liberalized markets and in civil society. In order to evaluate these pathways, the project team is employing a „toolkit‟ of techniques to explore and evaluate specific implications of the selected transition pathways to a highly electric, low carbon economy. These aim: to provide a transparent sustainability appraisal framework (economic, social, environmental and technical benefits) for the transition pathways; to explore and evaluate the „whole system‟ implications of the selected transition pathways. This paper highlights how these assessment tools will be used to explore the implications of different governance patterns in relation to the transition pathways

Knowledge exchange and research capacity building in urban Aboriginal health

The Centre for Research Excellence (CRE) on urban Aboriginal Child Health is linked to this unique base of information on 1600 children and their parents/ caregivers. The Centre is designed to: (a) increase the translation of knowledge arising from the SEARCH program and additional data collection undertaken as part of the CRE; (b) to enable ACCHSs to effectively use the information emerging from SEARCH to improve the quality of primary care, and; (c) enhance research capacity in primary health care within ACCHSs by increasing their capacity to undertake multidisciplinary research and knowledge translation in primary care. This work will provide evidence to support sustainable and transferable improvements in Aboriginal primary health care and, ultimately, health outcomes.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Color & Weak triplet scalars, the dimuon asymmetry in BsB_s decay, the top forward-backward asymmetry, and the CDF dijet excess

The new physics required to explain the anomalies recently reported by the D0 and CDF collaborations, namely the top forward-backward asymmetry (FBA), the like-sign dimuon charge asymmetry in semileptonic b decay, and the CDF dijet excess, has to feature an amount of flavor symmetry in order to satisfy the severe constrains arising from flavor violation. In this paper we show that, once baryon number conservation is imposed, color & weak triplet scalars with hypercharge $Y=1/3$ can feature the required flavor structure as a consequence of standard model gauge invariance. The color & weak triplet model can simultaneously explain the top FBA and the dimuon charge asymmetry or the dimuon charge asymmetry and the CDF dijet excess. However, the CDF dijet excess appears to be incompatible with the top FBA in the minimal framework. Our model for the dimuon asymmetry predicts the observed pattern $h_d\ll h_s$ in the region of parameter space required to explain the top FBA, whereas our model for the CDF dijet anomaly is characterized by the absence of beyond the SM b-quark jets in the excess region. Compatibility of the color & weak triplet with the electroweak constraints is also discussed. We show that a Higgs boson mass exceeding the LEP bound is typically favored in this scenario, and that both Higgs production and decay can be significantly altered by the triplet. The most promising collider signature is found if the splitting among the components of the triplet is of weak scale magnitude.Comment: references added, published versio

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

Development of a cDNA microarray for the measurement of gene expression in the sheep scab mite Psoroptes ovis

Background: Sheep scab is caused by the ectoparasitic mite Psoroptes ovis which initiates a profound cutaneous inflammatory response, leading to the development of the skin lesions which are characteristic of the disease. Existing control strategies rely upon injectable endectocides and acaricidal dips but concerns over residues, eco-toxicity and the development of acaricide resistance limit the sustainability of this approach. In order to identify alternative means of disease control, a deeper understanding of both the parasite and its interaction with the host are required. Methods: Herein we describe the development and utilisation of an annotated P. ovis cDNA microarray containing 3,456 elements for the measurement of gene expression in this economically important ectoparasite. The array consists of 981 P. ovis EST sequences printed in triplicate along with 513 control elements. Array performance was validated through the analysis of gene expression differences between fed and starved P. ovis mites. Results: Sequences represented on the array include homologues of major house dust mite allergens and tick salivary proteins, along with factors potentially involved in mite reproduction and xenobiotic metabolism. In order to validate the performance of this unique resource under biological conditions we used the array to analyse gene expression differences between fed and starved P. ovis mites. These analyses identified a number of house dust mite allergen homologues up-regulated in fed mites and P. ovis transcripts involved in stress responses, autophagy and chemosensory perception up-regulated in starved mites. Conclusion: The P. ovis cDNA microarray described here has been shown to be both robust and reproducible and will enable future studies to analyse gene expression in this important ectoparasite