Australia had reserves of over 258,888 petajoules or 6.65 trillion cubic metres of unconventional Coal Seam Gas (CSG) at the end of 2014. The exploration for this rich source of energy requires ...proponent firms to negotiate access and compensation with landholders under the relevant state policies and regulations. In this study, a summative payment and benefits model is proposed and built using inputs to a dual pass governmental review into compensation for landholders hosting CSG energy projects in New South Wales, Australia. This theoretical model exposed that landholder compensation and production payments policies and regulations are inadequate and require expedited improvements and revisions. Specifically, the potential long term impacts of CSG extraction; landholder injurious affections in relation to personal health, loss of amenity, and diminution of current and future land use; and further consideration of neighbour compensation and compulsory land acquisition options are policy prescriptions that require deeper governmental consideration and analysis. In addition, the replacement of monetary compensation with long term production benefits may offer landholders increased sources of ongoing compensatory income, and thus requires more policy and regulatory exactitude.
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•Highlights 6.65 trillion cubic metres of Coal Seam Gas (CSG) reserves in Australia.•Describes a theoretical summative compensation and benefits sharing model.•Shows typical rates of landholder compensation of A$30,000–50,000 per annum.•Exposes the lack of compensation mechanisms for long term CSG extraction impacts.•Outlines CSG policy and regulations deficiencies and proposed improvements.
Patient specific models of ventricular mechanics require the optimization of their many parameters under the uncertainties associated with imaging of cardiac function. We present a strategy to reduce ...the complexity of parametric searches for 3-D FE models of left ventricular contraction. The study employs automatic image segmentation and analysis of an image database to gain geometric features for several classes of patients. Statistical distributions of geometric parameters are then used to design parametric studies investigating the effects of: (1) passive material properties during ventricular filling, and (2) infarct geometry on ventricular contraction in patients after a heart attack. Gaussian Process regression is used in both cases to build statistical models trained on the results of biophysical FEM simulations. The first statistical model estimates unloaded configurations based on either the intraventricular pressure or the end-diastolic fiber strain. The technique provides an alternative to the standard fixed-point iteration algorithm, which is more computationally expensive when used to unload more than 10 ventricles. The second statistical model captures the effects of varying infarct geometries on cardiac output. For training, we designed high resolution models of non-transmural infarcts including refinements of the border zone around the lesion. This study is a first effort in developing a platform combining HPC models and machine learning to investigate cardiac function in heart failure patients with the goal of assisting clinical diagnostics.
In a vast majority of cases, seepage barriers increase the reliability of dams. However, it is important to recognize that seepage barriers often drastically increase hydraulic gradients around the ...boundaries of the barrier, and through any windows or defects in the barrier. The result is increased water pressures and hydraulic gradients behind and around the barrier. These increased pressures and gradients have potential to provide the catalyst for initiation of several modes of internal erosion that were either unlikely or less likely without the seepage barrier. As a consequence, seepage barriers give rise to the potential for additional mechanisms of internal erosion and piping in the dam and the foundation. A compendium of 30 case histories of dams that have had seepage barriers in place for over 10 years has been assembled, and observations and insights garnered from these case studies were compiled. Finite-element seepage and deformation analyses have been performed to provide better understanding of the performance of seepage barriers and the mechanisms that affect their performance. This paper presents a summary of our findings from the case histories and the analyses performed.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated ...with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance.
•Exome sequencing were performed on 6 bipolar cases from a four-generation pedigree.•A suggestive linkage peak region was identified on 10q23.1-10q23.33.•5 candidate genes including DYDC2, GHITM, CDHR1, GRID1 and MINPP1 were identified.
Most cases of multidrug-resistant (MDR) tuberculosis (TB) are never diagnosed (328,300 of the ∼490,000 cases in 2016 were missed). The Xpert MTB/RIF assay detects resistance only to rifampin, despite ...∼20% of rifampin-resistant cases being susceptible to isoniazid (a critical first-line drug). Consequently, many countries require further testing with the GenoType MTBDR
assay. However, MTBDR
is not recommended for use on smear-negative specimens, and thus, many specimens require culture-based drug susceptibility testing. Furthermore, MTBDR
requires specialized expertise, lengthy hands-on time, and significant laboratory infrastructure and interpretation is not automated. To address these gaps, we evaluated the accuracy of the FluoroType MTBDR (FluoroType) assay. Sputa from 244 smear-positive and 204 smear-negative patients with presumptive TB (Xpert MTB positive,
= 343) were tested. Culture and MTBDR
on isolates served as reference standards (for active TB and MDR-TB, respectively). Sanger sequencing and MTBDR
, both of which were performed on sputa, were used to resolve discrepancies. The sensitivity of FluoroType for the detection of
complex was 98% (95% confidence interval CI, 95 to 99%) and 92% (95% CI, 84 to 96%) for smear-positive and smear-negative specimens, respectively (232/237 versus 90/98 specimens;
< 0.009). The sensitivity and specificity for smear-negative specimens were 100% and 97%, respectively, for rifampin resistance; 100% and 98%, respectively, for isoniazid resistance; and 100% and 100%, respectively, for MDR-TB. FluoroType identified 98%, 97%, and 97% of the
,
, and
promoter mutations, respectively. FluoroType has excellent sensitivity with sputa equivalent to that of MTBDR
with the isolates and can provide rapid drug susceptibility testing for rifampin and isoniazid. In addition, the capacity of FluoroType to simultaneously identify virtually all mutations in the
,
, and
promoter may be useful for individualized treatment regimens.
Protein kinases phosphorylate proteins for functional changes and are involved in nearly all cellular processes, thereby regulating almost all aspects of plant growth and development, and responses ...to biotic and abiotic stresses. We generated two independent co‐expression networks of soybean genes using control and stress response gene expression data and identified 392 differentially highly interconnected kinase hub genes among the two networks. Of these 392 kinases, 90 genes were identified as “syncytium highly connected hubs”, potentially essential for activating kinase signalling pathways in the nematode feeding site. Overexpression of wild‐type coding sequences of five syncytium highly connected kinase hub genes using transgenic soybean hairy roots enhanced plant susceptibility to soybean cyst nematode (SCN; Heterodera glycines) Hg Type 0 (race 3). In contrast, overexpression of kinase‐dead variants of these five syncytium kinase hub genes significantly enhanced soybean resistance to SCN. Additionally, three of the five tested kinase hub genes enhanced soybean resistance to SCN Hg Type 1.2.5.7 (race 2), highlighting the potential of the kinase‐dead approach to generate effective and durable resistance against a wide range of SCN Hg types. Subcellular localization analysis revealed that kinase‐dead mutations do not alter protein cellular localization, confirming the structure–function of the kinase‐inactive variants in producing loss‐of‐function phenotypes causing significant decrease in nematode susceptibility. Because many protein kinases are highly conserved and are involved in plant responses to various biotic and abiotic stresses, our approach of identifying kinase hub genes and their inactivation using kinase‐dead mutation could be translated for biotic and abiotic stress tolerance.
Overexpression of kinase‐dead variants of syncytium kinase hub genes significantly increased soybean resistance to soybean cyst nematode (Heterodera glycines) Hg Type 0 (race 3) and Hg Type 1.2.5.7 (race 2).
The efficacy of corticosteroids in patients with psoriatic arthritis (PsA) and inflammatory back pain has not been studied to date. In this controlled trial, we aimed to investigate the comparative ...performance of corticosteroids in patients with active axial-PsA (AxPsA) versus those with active ankylosing spondylitis (AS).
Patients with AxPsA and AS (naïve to biologic therapies), who not only had clinically active disease, but also had bone marrow oedema on magnetic resonance imaging of the sacroiliac joints, were recruited. Clinically active disease was defined as inflammatory back pain (fulfilling Assessment of Spondyloarthritis International Society (ASAS) expert criteria), with spinal pain score (numerical rating scale 0-10) ≥4 and Bath AS Disease Activity Index (BASDAI) score ≥4 despite taking nonsteroidal anti-inflammatory drugs. Moreover, we recruited a control group of patients with non-inflammatory lower back pain. All patients received a single, intra-muscular dose of depot corticosteroid injection (triamcinolone acetonide 80 mg) at baseline. The intra-muscular corticosteroid option was used to overcome any drug compliance issues. Clinical outcome assessments were made at the following time points: baseline, week 2, and week 4. The primary efficacy end point was mean change in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 2. Key secondary outcomes were mean change in the BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Quality of Life (ASQoL) at weeks 2 and 4.
In total, 40 patients were recruited (15 with AxPsA, 15 with AS, and 10 controls). At week 2 following corticosteroid treatment, patients with AxPsA had significantly greater improvement in the mean ASDAS compared to patients with AS (1.43 ± 0.39 vs. 1.03 ± 0.30, p = 0.004), and also when compared to controls (p < 0.001). At week-4, similar significant trend of ASDAS improvement was seen among AxPsA patients compared to AS patients (1.09 ± 0.32 vs. 0.77 ± 0.27, p = 0.007) and controls (p < 0.001). Similarly, the mean BASDAI, visual analogue scale spinal pain score, ASQoL and BASFI improved significantly among patients with AxPsA compared to patients with AS and controls at week 2 (p < 0.05), with this trend also largely maintained at week 4.
Axial inflammation in patients with PsA responds significantly better to corticosteroids than in patients with AS. This furthers the argument and adds to the growing evidence that AxPsA and AS are distinct entities.
Abstract
Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week ...(DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces
SPI1
mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies
MAPT
as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.
AbstractGeomorphic features in the soil layers underlying a structure often have a significant effect on the underseepage behavior and the potential for initiating internal erosion. Based on the ...assumption that the preponderance of the underseepage risk to a levee reach is due to the geomorphic features along that reach, methodology has been developed to perform a stochastic assessment of the properties of the seepage regime with the intention of assessing the probability of internal erosion initiation. The methodology consists of a response surface-Monte Carlo analysis that takes into account the uncertainty in the subsurface geometry and soil properties in assessing the seepage regime associated with the feature. Three-dimensional finite-element seepage analyses are used to develop the response surface to take into account the inherent three-dimensional aspects of the feature. As a result of the analysis, probability distribution functions with respect to hydraulic gradient and factor of safety against heave are developed. The methodology can be adapted to any type of geomorphic feature and, as an example, a crevasse splay deposit is presented.
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