Promoter methylation analysis of WNT/β-catenin pathway regulators and its association with expression of DNMT1 enzyme in colorectal cancer

Background: Aberrant DNA methylation as the most important reason making epigenetic silencing of genes is a main mechanism of gene inactivation in patients with colorectal cancer. In this study, we decided to identify promoter methylation status of ten genes encoding WNT negative regulators, and measure the expression of DNMT1 enzyme in colorectal cancer samples. Results: Aberrant methylation of APC gene was statistically significant associated with age over 50 (p = 0.017), DDK3 with male (p < 0.0001), SFRP4, WIF1, and WNT5a with increasing tumor stage (p = 0.004, p = 0.029, and p = 0.004), SFRP4 and WIF1 with tumor differentiation (p = 0.009 and p = 0.031) and SFRP2 and SFRP5 with histological type (p = 0.001 and p = 0.025). The increasing number of methylated genes correlated with the expression levels of the DNMT1 mRNA. Conclusions: The rate of gene promoter methylation of WNT pathway regulators is high in colorectal cancer cells. Hyper-methylation is associated with increased expression of the DNMT1 enzyme. © 2014 Mansour Samaei et al.; licensee BioMed Central

A semismooth newton method for the nearest Euclidean distance matrix problem

The Nearest Euclidean distance matrix problem (NEDM) is a fundamentalcomputational problem in applications such asmultidimensional scaling and molecularconformation from nuclear magnetic resonance data in computational chemistry.Especially in the latter application, the problem is often large scale with the number ofatoms ranging from a few hundreds to a few thousands.In this paper, we introduce asemismooth Newton method that solves the dual problem of (NEDM). We prove that themethod is quadratically convergent.We then present an application of the Newton method to NEDM with $H$-weights.We demonstrate the superior performance of the Newton method over existing methodsincluding the latest quadratic semi-definite programming solver.This research also opens a new avenue towards efficient solution methods for the molecularembedding problem

Effect of solute content and temperature on the deformation mechanisms and critical resolved shear stress in Mg-Al and Mg-Zn alloys

The influence of solute atoms (Al and Zn) on the deformation mechanisms and the critical resolved shear stress for basal slip in Mg alloys at 298 K and 373 K was ascertained by micropillar compression tests in combination with high-throughput processing techniques based on the diffusion couples. It was found that the presence of solute atoms enhances the size effect at 298 K as well as the localization of deformation in slip bands, which is associated with large strain bursts in the resolved shear stress ($\tau_{RSS}$)-strain ($\epsilon$) curves. Deformation in pure Mg and Mg alloys was more homogeneous at 373 K and the influence of the micropillar size on the critical resolved shear stress was much smaller. In this latter case, it was possible to determine the effect of solute content on the critical resolved shear stress for basal slip in Mg-Al and Mg-Zn alloys

A regime switching approach for hedging tanker shipping freight rates

Tanker shipping is the primary means for the transportation of petroleum and petroleum products around the world and thus plays a crucial role in the energy supply chain. However, the high volatility of tanker freight rates has been a major concern for market participants and led to the development of the tanker freight derivatives in the form of forward freight agreements (FFAs). The aim of this paper is to investigate the performance of these instruments in managing tanker freight rate risk. Using a data set for six major tanker routes covering the period between 2005 and 2013, we examine the effectiveness of alternative hedging methods, including a bivariate Markov Regime Switching GARCH model, in hedging tanker freight rates. The regime switching GARCH specification links the concept of equilibrium freight rate determination underlying different market conditions and the dynamics of the conditional second moments across high and low volatility regimes. Overall, we find evidence supporting the argument that the tanker freight market is characterized by different regimes. However, while the use of a regime switching model allows for a significant improvement in the performance of the hedge in-sample, out-of-sample results are mixed

Superplasticity of a nano-grained Mg-Gd-Y-Zr alloy processed by high-pressure torsion

While most of the reports on Mg-Gd-Y-Zr alloys report superplasticity after extrusion or friction stir processing, it is important to investigate superplasticity in these alloys after other severe plastic deformation processes having greater grain refinement capability. Accordingly, superplasticity was studied in an Mg–9Gd–4Y–0.4Zr (GW94) alloy after different high-pressure torsion (HPT) conditions. The HPT was performed at room temperature under an applied pressure of 6.0 GPa for up to 16 turns. TEM microstructural characterization revealed that the grain size was reduced from an initial value of ?8.6 ?m in the extruded condition to ?95±10 and ?85±10 nm after 8 and 16 turns, respectively. A shear punch testing method was used for evaluation of superplasticity at 573, 623, 673 and 723 K. Maximum strain rate sensitivities of ?0.51±0.05 and ?0.48±0.05 were obtained at 623 K for the material processed through 16 and 8 turns, respectively. This strain rate sensitivity and an activation energy of ?100±5 kJ mol–1 suggests the occurrence of grain boundary sliding in the superplastic regio

Optimal quantum detectors for unambiguous detection of mixed states

We consider the problem of designing an optimal quantum detector that distinguishes unambiguously between a collection of mixed quantum states. Using arguments of duality in vector space optimization, we derive necessary and sufficient conditions for an optimal measurement that maximizes the probability of correct detection. We show that the previous optimal measurements that were derived for certain special cases satisfy these optimality conditions. We then consider state sets with strong symmetry properties, and show that the optimal measurement operators for distinguishing between these states share the same symmetries, and can be computed very efficiently by solving a reduced size semidefinite program.Comment: Submitted to Phys. Rev.

How can patient journey in surgical wards of a referral hospital be improved?

Background: We studied the patient journey in surgical wards in order to find an effective and efficient way of scheduling in surgical wards.Methods: We applied Root cause analysis (RCA) model within three months in a referral hospital. After understanding root causes of the events occurred through a focus discussion group, required interventions were proposed according to literatures, experiences, and preference of the stakeholders. Possible interventions were also analyzed based on its ability to reduce contributing factors in the events and the belief of process-owner that if interventions can be implemented.Results: The results were provided for five main steps: 1) the most important root cause was “not prioritizing patients and pre-scheduling the number of surgical procedures in the days before”. 2) Constraints indicated that workforce weren't allocated proportionally to the number of surgical operations in varying shift lengths, increased numbers of on-calls physicians increased related costs, the admission of patients in VIP wards have been getting a high priority, and surgeon compensation based on fee for service method was challenging. 3) The current situation of allocating three rooms on average for each physician can be changed depending on numbers of surgeries. 4) Proposed interventions are establishing a computer registration system, reforming payment methods, setting up an electronic waiting list, development of scheduling guidelines, and Applying MIP model.Conclusions: Implementing of scheduling reforms requires a comprehensive action plan system and predefined functional indicators. These should be achieved with considering comments of all clinical and technical groups to ensure the feasibility of an operating room schedule.Keywords: patient journey, surgery, scheduling, Root cause analysis (RCA), patient transfe

A rare presentation of late right coronary artery spasm following aortic valve replacement

BACKGROUND: Coronary artery spasm (CAS) is defined as a reversible, sudden epicardial coronary artery stenosis that causes vessel occlusion or near occlusion. CASE REPORT: In this article, we present a clinical case of CAS in a 48-year-old woman undergoing elective aortic valve replacement surgery for aortic stenosis. On the 3rd post-operative day, the patient suffered from chest pain and dyspnea. Emergent coronary angiography demonstrated a significant spasm of the ostium portion of the right coronary artery. CONCLUSION: This case shows that delayed coronary spasm should be considered as a cause of hemodynamic instability after valvular surgery. © 2015, Isfahan University of Medical Sciences(IUMS). All rights reserved

Impact of Age and Biological Sex on Cerebrovascular Reactivity in Adult Moderate/Severe Traumatic Brain Injury: An Exploratory Analysis

Age and biological sex are two potential important modifiers of cerebrovascular reactivity post-traumatic brain injury (TBI) requiring close evaluation for potential subgroup responses. The goal of this study was to provide a preliminary exploratory analysis of the impact of age and biological sex on measures of cerebrovascular function in moderate/severe TBI. Forty-nine patients from the prospectively maintained TBI database at the University of Manitoba with archived high-frequency digital cerebral physiology were evaluated. Cerebrovascular reactivity indices were derived as follows: PRx (correlation between intracranial pressure [ICP] and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and RAC (correlation between AMP and cerebral perfusion pressure [CPP]). Time above clinically significant thresholds for each index was calculated over different periods of the acute intensive care unit stay. The association between PRx, PAx, and RAC measures with age was assessed using linear regression, and an age trichotomization scheme (60) using Kruskal-Wallis testing. Similarly, association with biological sex was tested using Mann-Whitney U testing. Biological sex did not demonstrate an impact on any measures of cerebrovascular reactivity. Linear regression between age and PAx and RAC demonstrated a statistically significant positive linear relationship. Median PAx and RAC measures between trichotomized age categories demonstrated statistically significant increases with advancing age. The PRx failed to demonstrate any statistically significant relationship with age in this cohort, suggesting that in elderly patients with controlled ICP, PAx and RAC may be better metrics for detecting impaired cerebrovascular reactivity. Biological sex appears to not be associated with differences in cerebrovascular reactivity in this cohort. The PRx performed the worst in detecting impaired cerebrovascular reactivity in those with advanced age, where PAx and RAC appear to have excelled. Future work is required to validate these findings and explore the utility of different cerebrovascular reactivity indices

Continuous Time-Domain Cerebrovascular Reactivity Metrics and Discriminate Capacity for the Upper and Lower Limits of Autoregulation: A Scoping Review of the Animal Literature.

Over a wide range of systemic arterial pressures, cerebral blood flow (CBF) is regulated fairly constantly by the cerebral vessels in a process termed cerebral autoregulation (CA), which is depicted by the Lassen autoregulatory curve. After traumatic brain injury (TBI), CA can get impaired and these impairments manifest in changes of the Lassen autoregulatory curve. Continuous surrogate metrics of pressure-based CA, termed cerebrovascular reactivity (CVR) metrics, evaluate the relationship between slow vasogenic fluctuations in a driving pressure for cerebral blood flow, and the most commonly studied and utilized measures are based in the time domain and have been increasingly applied in bedside TBI care and have sparked the investigation of individualized cerebral perfusion pressure targets. However, not all CVR metrics have been validated as true measures of autoregulation in the pre-clinical setting. We reviewed all available pre-clinical animal literature that assessed the association between continuous time-domain metrics of CVR and some aspect of the Lassen autoregulatory curve. All 15 articles found associated the evaluated continuous metrics to the lower limit of autoregulation curve whereas none looked at the upper limit. Most of the evaluated metrics showed the ability to discriminate the lower limit of autoregulation with various methods of perturbation. Further work is required to evaluate the utility of such surrogate measures against the upper limit of autoregulation, while also providing validation to the existing literature supporting specific indices and their ability to discriminate the lower limit