Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries

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Ultra-fast Microwave Synthesis of ZnO Nanowires and their Dynamic Response Toward Hydrogen Gas

Ultra-fast and large-quantity (grams) synthesis of one-dimensional ZnO nanowires has been carried out by a novel microwave-assisted method. High purity Zinc (Zn) metal was used as source material and placed on microwave absorber. The evaporation/oxidation process occurs under exposure to microwave in less than 100 s. Field effect scanning electron microscopy analysis reveals the formation of high aspect-ratio and high density ZnO nanowires with diameter ranging from 70 to 80 nm. Comprehensive structural analysis showed that these ZnO nanowires are single crystal in nature with excellent crystal quality. The gas sensor made of these ZnO nanowires exhibited excellent sensitivity, fast response, and good reproducibility. Furthermore, the method can be extended for the synthesis of other oxide nanowires that will be the building block of future nanoscale devices

Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF)

BACKGROUND: Health related quality of life (HRQOL) is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC) receiving either a standard or an experimental treatment. METHODS: Seventy-one patients have been treated in Cancer Institute (Tehran, Iran) with docetaxel, cisplatin, 5 FU (TCF) or epirubicin, cisplatin, 5-FU (ECF) and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy. RESULTS: The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001). Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups. CONCLUSION: Docetaxel based treatment (TCF) showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF). However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients

Normal-State Spin Dynamics and Temperature-Dependent Spin Resonance Energy in an Optimally Doped Iron Arsenide Superconductor

The proximity of superconductivity and antiferromagnetism in the phase diagram of iron arsenides, the apparently weak electron-phonon coupling and the "resonance peak" in the superconducting spin excitation spectrum have fostered the hypothesis of magnetically mediated Cooper pairing. However, since most theories of superconductivity are based on a pairing boson of sufficient spectral weight in the normal state, detailed knowledge of the spin excitation spectrum above the superconducting transition temperature Tc is required to assess the viability of this hypothesis. Using inelastic neutron scattering we have studied the spin excitations in optimally doped BaFe1.85Co0.15As2 (Tc = 25 K) over a wide range of temperatures and energies. We present the results in absolute units and find that the normal state spectrum carries a weight comparable to underdoped cuprates. In contrast to cuprates, however, the spectrum agrees well with predictions of the theory of nearly antiferromagnetic metals, without complications arising from a pseudogap or competing incommensurate spin-modulated phases. We also show that the temperature evolution of the resonance energy follows the superconducting energy gap, as expected from conventional Fermi-liquid approaches. Our observations point to a surprisingly simple theoretical description of the spin dynamics in the iron arsenides and provide a solid foundation for models of magnetically mediated superconductivity.Comment: 8 pages, 4 figures, and an animatio

Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds

Quantitative Understanding of Probabilistic Behavior of Living Cells Operated by Vibrant Intracellular Networks

For quantitative understanding of probabilistic behaviors of living cells, it is essential to construct a correct mathematical description of intracellular networks interacting with complex cell environments, which has been a formidable task. Here, we present a novel model and stochastic kinetics for an intracellular network interacting with hidden cell environments, employing a complete description of cell state dynamics and its coupling to the system network. Our analysis reveals that various environmental effects on the product number fluctuation of intracellular reaction networks can be collectively characterized by Laplace transform of the time-correlation function of the product creation rate fluctuation with the Laplace variable being the product decay rate. On the basis of the latter result, we propose an efficient method for quantitative analysis of the chemical fluctuation produced by intracellular networks coupled to hidden cell environments. By applying the present approach to the gene expression network, we obtain simple analytic results for the gene expression variability and the environment-induced correlations between the expression levels of mutually noninteracting genes. The theoretical results compose a unified framework for quantitative understanding of various gene expression statistics observed across a number of different systems with a small number of adjustable parameters with clear physical meanings.open1143sciescopu

A general reaction-diffusion model of acidity in cancer invasion

We model the metabolism and behaviour of a developing cancer tumour in the context of its microenvironment, with the aim of elucidating the consequences of altered energy metabolism. Of particular interest is the Warburg Effect, a widespread preference in tumours for cytosolic glycolysis rather than oxidative phosphorylation for glucose breakdown, as yet incompletely understood. We examine a candidate explanation for the prevalence of the Warburg Effect in tumours, the acid-mediated invasion hypothesis, by generalising a canonical non-linear reaction–diffusion model of acid-mediated tumour invasion to consider additional biological features of potential importance. We apply both numerical methods and a non-standard asymptotic analysis in a travelling wave framework to obtain an explicit understanding of the range of tumour behaviours produced by the model and how fundamental parameters govern the speed and shape of invading tumour waves. Comparison with conclusions drawn under the original system—a special case of our generalised system—allows us to comment on the structural stability and predictive power of the modelling framework

The Na(+)–H(+ )exchanger-1 induces cytoskeletal changes involving reciprocal RhoA and Rac1 signaling, resulting in motility and invasion in MDA-MB-435 cells

INTRODUCTION: An increasing body of evidence shows that the tumour microenvironment is essential in driving neoplastic progression. The low serum component of this microenvironment stimulates motility/invasion in human breast cancer cells via activation of the Na(+)–H(+ )exchanger (NHE) isoform 1, but the signal transduction systems that underlie this process are still poorly understood. We undertook the present study to elucidate the role and pattern of regulation by the Rho GTPases of this serum deprivation-dependent activation of both NHE1 and subsequent invasive characteristics, such as pseudopodia and invadiopodia protrusion, directed cell motility and penetration of normal tissues. METHODS: The present study was performed in a well characterized human mammary epithelial cell line representing late stage metastatic progression, MDA-MB-435. The activity of RhoA and Rac1 was modified using their dominant negative and constitutively active mutants and the activity of NHE1, cell motility/invasion, F-actin content and cell shape were measured. RESULTS: We show for the first time that serum deprivation induces NHE1-dependent morphological and cytoskeletal changes in metastatic cells via a reciprocal interaction of RhoA and Rac1, resulting in increased chemotaxis and invasion. Deprivation changed cell shape by reducing the amount of F-actin and inducing the formation of leading edge pseudopodia. Serum deprivation inhibited RhoA activity and stimulated Rac1 activity. Rac1 and RhoA were antagonistic regulators of both basal and stimulated tumour cell NHE1 activity. The regulation of NHE1 activity by RhoA and Rac1 in both conditions was mediated by an alteration in intracellular proton affinity of the exchanger. Interestingly, the role of each of these G-proteins was reversed during serum deprivation; basal NHE1 activity was regulated positively by RhoA and negatively by Rac1, whereas RhoA negatively and Rac1 positively directed the stimulation of NHE1 during serum deprivation. Importantly, the same pattern of RhoA and Rac1 regulation found for NHE1 activity was observed in both basal and serum deprivation dependent increases in motility, invasion and actin cytoskeletal organization. CONCLUSION: Our findings suggest that the reported antagonistic roles of RhoA and Rac1 in cell motility/invasion and cytoskeletal organization may be due, in part, to their concerted action on NHE1 activity as a convergence point

Quantum Criticality in Heavy Fermion Metals

Quantum criticality describes the collective fluctuations of matter undergoing a second-order phase transition at zero temperature. Heavy fermion metals have in recent years emerged as prototypical systems to study quantum critical points. There have been considerable efforts, both experimental and theoretical, which use these magnetic systems to address problems that are central to the broad understanding of strongly correlated quantum matter. Here, we summarize some of the basic issues, including i) the extent to which the quantum criticality in heavy fermion metals goes beyond the standard theory of order-parameter fluctuations, ii) the nature of the Kondo effect in the quantum critical regime, iii) the non-Fermi liquid phenomena that accompany quantum criticality, and iv) the interplay between quantum criticality and unconventional superconductivity.Comment: (v2) 39 pages, 8 figures; shortened per the editorial mandate; to appear in Nature Physics. (v1) 43 pages, 8 figures; Non-technical review article, intended for general readers; the discussion part contains more specialized topic