Adapting a Markov Monte Carlo simulation model for forecasting the number of Coronary Artery Revascularisation Procedures in an era of rapidly changing technology and policy

<p>Abstract</p> <p>Background</p> <p>Treatments for coronary heart disease (CHD) have evolved rapidly over the last 15 years with considerable change in the number and effectiveness of both medical and surgical treatments. This period has seen the rapid development and uptake of statin drugs and coronary artery revascularization procedures (CARPs) that include Coronary Artery Bypass Graft procedures (CABGs) and Percutaneous Coronary Interventions (PCIs). It is difficult in an era of such rapid change to accurately forecast requirements for treatment services such as CARPs. In a previous paper we have described and outlined the use of a Markov Monte Carlo simulation model for analyzing and predicting the requirements for CARPs for the population of Western Australia (Mannan et al, 2007). In this paper, we expand on the use of this model for forecasting CARPs in Western Australia with a focus on the lack of adequate performance of the (standard) model for forecasting CARPs in a period during the mid 1990s when there were considerable changes to CARP technology and implementation policy and an exploration and demonstration of how the standard model may be adapted to achieve better performance.</p> <p>Methods</p> <p>Selected key CARP event model probabilities are modified based on information relating to changes in the effectiveness of CARPs from clinical trial evidence and an awareness of trends in policy and practice of CARPs. These modified model probabilities and the ones obtained by standard methods are used as inputs in our Markov simulation model.</p> <p>Results</p> <p>The projected numbers of CARPs in the population of Western Australia over 1995–99 only improve marginally when modifications to model probabilities are made to incorporate an increase in effectiveness of PCI procedures. However, the projected numbers improve substantially when, in addition, further modifications are incorporated that relate to the increased probability of a PCI procedure and the reduced probability of a CABG procedure stemming from changed CARP preference following the introduction of PCI operations involving stents.</p> <p>Conclusion</p> <p>There is often knowledge and sometimes quantitative evidence of the expected impacts of changes in surgical practice and procedure effectiveness and these may be used to improve forecasts of future requirements for CARPs in a population.</p

Identifying sources, pathways and risk drivers in ecosystems of Japanese Encephalitis in an epidemic-prone north Indian district

Japanese Encephalitis (JE) has caused repeated outbreaks in endemic pockets of India. This study was conducted in Kushinagar, a highly endemic district, to understand the human-animal-ecosystem interactions, and the drivers that influence disease transmission. Utilizing the ecosystems approach, a cross-sectional, descriptive study, employing mixed methods design was employed. Four villages (two with pig-rearing and two without) were randomly selected from a high, a medium and a low burden (based on case counts) block of Kushinagar. Children, pigs and vectors were sampled from these villages. A qualitative arm was incorporated to explain the findings from the quantitative surveys. All human serum samples were screened for JE-specific IgM using MAC ELISA and negative samples for JE RNA by rRT-PCR in peripheral blood mononuclear cells. In pigs, IgG ELISA and rRT-PCR for viral RNA were used. Of the 242 children tested, 24 tested positive by either rRT-PCR or MAC ELISA; in pigs, 38 out of the 51 pigs were positive. Of the known vectors, Culex vishnui was most commonly isolated across all biotopes. Analysis of 15 blood meals revealed human blood in 10 samples. Univariable analysis showed that gender, religion, lack of indoor residual spraying of insecticides in the past year, indoor vector density (all species), and not being vaccinated against JE in children were significantly associated with JE positivity. In multivariate analysis, only male gender remained as a significant risk factor. Based on previous estimates of symptomatic: asymptomatic cases of JE, we estimate that there should have been 618 cases from Kushinagar, although only 139 were reported. Vaccination of children and vector control measures emerged as major control activities; they had very poor coverage in the studied villages. In addition, lack of awareness about the cause of JE, lack of faith in the conventional medical healthcare system and multiple referral levels causing delay in diagnosis and treatment emerged as factors likely to result in adverse clinical outcomes

Using a Markov simulation model to assess the impact of changing trends in coronary heart disease incidence on requirements for coronary artery revascularization procedures in Western Australia

<p>Abstract</p> <p>Background</p> <p>The population incidence of coronary heart disease (CHD) has been declining in Australia and many other countries. This decline has been due to reduced population levels of risk factors for CHD and improved medical care for those at higher risk of CHD. However, there are signs that there may be a slowing down or even reversal in the decline of CHD incidence due to the 'obesity epidemic' and other factors and this will have implications for the requirements for surgical treatments for those with CHD.</p> <p>Methods</p> <p>Using a validated Markov simulation model applied to the population of Western Australia, different CHD incidence trend scenarios were developed to explore the effect of changing CHD incidence on requirements for coronary artery bypass graft (CABG) and percutaneous coronary interventions (PCI), together known as coronary artery revascularization procedures (CARPs).</p> <p>Results</p> <p>The most dominant component of CHD incidence is the risk of CHD hospital admission for those with no history of CHD and if this risk leveled off and the trends in all other risks continued unchanged, then the projected numbers of CABGs and PCIs are only minimally changed. Further, the changes in the projected numbers remained small even when this risk was increased by 20 percent (although it is an unlikely scenario). However, when the other CHD incidence components that had also been declining, namely, the risk of CABG and that of CHD death for those with no history of CHD, were also projected to level off as these were declining in 1998-2000 and the risk of PCI for those with no history of CHD (which was already increasing) was projected to further increase by 5 percent, it had a substantial effect on the projected numbers of CARPs.</p> <p>Conclusion</p> <p>There needs to be dramatic changes to several CHD incidence components before it has a substantial impact on the projected requirements for CARPs. Continued monitoring of CHD incidence and also the mix of initial presentation of CHD incidence is required in order to understand changes to future CARP requirements.</p

Evaluation of Spatially Targeted Strategies to Control Non-Domiciliated Triatoma dimidiata Vector of Chagas Disease

Chagas disease is one of the most important parasitic diseases in Latin America. Since the 1980's, many national and international initiatives have contributed to eliminate vectors developing inside human domiciles. Today's challenge is to control vectors that are non-adapted to the human domicile, but still able to transmit the parasite through regular short stay in the houses. Here, we assess the potential of different control strategies applied in specific spatial patterns using a mathematical model that reproduces the dynamic of dispersion of such ‘non-domiciliated’ vectors within a village of the Yucatan Peninsula, Mexico. We show that no single strategy applied in the periphery of the village, where the insects are more abundant, provides satisfying protection to the whole village. However, combining the use of insect screens in houses at the periphery of the village (to simultaneously fight insects dispersing from the garden and the forest), and the cleaning of the peri-domicile areas of the centre of the village (where sylvatic insects are absent), would provide a cost-effective control. This type of spatially mixed strategy offers a promising way to reduce the cost associated with the repeated interventions required to control non-domiciliated vectors that permanently attempt to infest houses

Expression of tung tree diacylglycerol acyltransferase 1 in E. coli

<p>Abstract</p> <p>Background</p> <p>Diacylglycerol acyltransferases (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Database search has identified at least 59 DGAT1 sequences from 48 organisms, but the expression of any DGAT1 as a full-length protein in <it>E. coli </it>had not been reported because DGAT1s are integral membrane proteins and difficult to express and purify. The objective of this study was to establish a procedure for expressing full-length DGAT1 in <it>E. coli</it>.</p> <p>Results</p> <p>An expression plasmid containing the open reading frame for tung tree (<it>Vernicia fordii</it>) DGAT1 fused to maltose binding protein and poly-histidine affinity tags was constructed and expressed in <it>E. coli </it>BL21(DE3). Immunoblotting showed that the recombinant DGAT1 (rDGAT1) was expressed, but mostly targeted to the membranes and insoluble fractions. Extensive degradation also occurred. Nonetheless, the fusion protein was partially purified from the soluble fraction by Ni-NTA and amylose resin affinity chromatography. Multiple proteins co-purified with DGAT1 fusion protein. These fractions appeared yellow in color and contained fatty acids. The rDGAT1 was solubilized from the insoluble fraction by seven detergents and urea, with SDS and Triton X-100 being the most effective detergents. The solubilized rDGAT1 was partially purified by Ni-NTA affinity chromatography. PreScission protease digestion confirmed the identity of rDGAT1 and showed extensive precipitation following Ni-NTA affinity purification.</p> <p>Conclusions</p> <p>This study reports the first procedure for expressing full-length DGAT1 from any species using a bacterial expression system. The results suggest that recombinant DGAT1 is degraded extensively from the carboxyl terminus and associated with other proteins, lipids, and membranes.</p

Characterization of the Dispersal of Non-Domiciliated Triatoma dimidiata through the Selection of Spatially Explicit Models

Chagas disease is one of the most important neglected diseases in Latin America. Although insecticides have been successfully sprayed to control domiciliated vector populations, this strategy has proven to be ineffective in areas where non-domiciliated vectors immigrating from peridomestic or sylvatic ecotopes can (re-)infest houses. The development of strategies for the control of non-domiciliated vectors has thus been identified by the World Health Organization as a major challenge. Such development primarily requires a description of the spatio-temporal dynamics of infestation by these vectors, and a good understanding of their dispersal. We combined for the first time extensive spatio-temporal data sets describing house infestation dynamics by Triatoma dimidiata inside one village, and spatially explicit population dynamics models. The models fitted and predicted remarkably the observed infestation dynamics. They thus provided both key insights into the dispersal of T. dimidiata in this area, and a suitable mathematical background to evaluate the efficacy of various control strategies. Interestingly, the observed and modelled patterns of infestation suggest that interventions could focus on the periphery of the village, where there is the highest risk of transmission. Such spatial optimization may allow for reducing the cost of control, compensating for repeated interventions necessary for non-domiciliated vectors

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Gastric cancer is associated with NOS2 -954G/C polymorphism and environmental factors in a Brazilian population

<p>Abstract</p> <p>Background</p> <p>Gastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from <it>Helicobacter pylori </it>infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (<it>NOS2</it>), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of <it>NOS2 </it>polymorphisms Ser⁶⁰⁸Leu (rs2297518) in exon 16, -954G/C and -1173C/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and <it>H. pylori </it>infection.</p> <p>Methods</p> <p>We conducted a population-based case-control study in 474 Southeast Brazilian individuals (150 with gastric cancer, 160 with chronic gastritis, and 164 healthy individuals), in which we performed <it>NOS2 </it>genotyping by PCR-RFLP.</p> <p>Results</p> <p>SNP Ser⁶⁰⁸Leu was not associated with risk of chronic gastritis or gastric cancer. The polymorphic allele -1173T was not found in the studied population. However, the frequency of -954GC+CC genotypes was significantly higher (p < 0.01) in the cancer group (48.7%) than in both the gastritis (28.1%) and the control (29.9%) groups. Multivariate logistic regression showed that the <it>NOS2 </it>SNP -954G/C was associated with higher risk of gastric cancer (OR = 1.87; 95% CI = 1.12-3.13). We also observed an association with risk factors such as smoking and alcohol intake in both the gastric cancer (OR = 2.68; 95% CI = 1.58-4.53; OR = 3.60; 95% CI = 2.05-6.32, respectively) and the chronic gastritis (OR = 1.93; 95% CI = 1.19-3.13; OR = 2.79; 95% CI = 1.55-5.02, respectively) groups. This is the first report of increased risk of gastric cancer in association with the -954G/C polymorphism. These findings show that several polymorphisms in the promoter region of the <it>NOS2 </it>gene may contribute to the susceptibility to gastric cancer.</p> <p>Conclusions</p> <p>Polymorphism <it>NOS2 </it>-954 G/C, along with alcohol intake and tobacco smoking, is associated with gastric cancer. However, the <it>NOS2 </it>Ser⁶⁰⁸Leu polymorphism was not associated with gastric carcinogenesis. The <it>NOS2 </it>-1173C/T polymorphism was absent in the studied population.</p

Adaptation and conservation insights from the koala genome

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as ‘vulnerable’ due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala’s ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala’s survival in the wild

Multiple Reflection Symmetry Detection via Linear-Directional Kernel Density Estimation

Symmetry is an important composition feature by investigating similar sides inside an image plane. It has a crucial effect to recognize man-made or nature objects within the universe. Recent symmetry detection approaches used a smoothing kernel over different voting maps in the polar coordinate system to detect symmetry peaks, which split the regions of symmetry axis candidates in inefficient way. We propose a reliable voting representation based on weighted linear-directional kernel density estimation, to detect multiple symmetries over challenging real-world and synthetic images. Experimental evaluation on two public datasets demonstrates the superior performance of the proposed algorithm to detect global symmetry axes respect to the major image shapes