Pharmacogenomic Approaches to Asthma Treatment

Major classes of medication in asthma management include bronchodilating β2-agonists, anti-inflammatory inhaled corticosteroids, leukotriene modifiers and theophyllines. However, all asthmatics do not respond to the same extent to a given medication. Available data suggest that a substantial range of individual variability, as much as 70%, may be due to genetic characteristics of each patient. Pharmacogenomics offers the potential to optimize medications for individual asthmatics by using genetic information to improve efficacy or avoid adverse effects. The best-studied case of the potential contribution of pharmacogenomics to treatment response in asthma comes from studies on human β2 adrenergic receptors. In addition, genetic variation in β2-adrenergic receptor (Arg16Gly) may predict response to anticholinergics for the treatment of asthma. In case of inhaled corticosteroids, a recent investigation using a traditional SNP-based approach identified a gene for corticotropin releasing hormone receptor 1 as a potential marker of response. Another major pathway that has been investigated is the pathway underlying response to cysteinyl leukotriene receptor antagonist. It is likely that in the near future, pharmacogenomic approaches based on individual genetic information will be introduced into an asthma treatment guideline and this guideline will allow us to identify those who have the best chance to respond to a specific medication

Solution and Asymptotic Behavior for a Nonlocal Coupled System of Reaction-Diffusion

This paper concerns with existence, uniqueness and asymptotic behavior of the solutions for a nonlocal coupled system of reaction-diffusion. We prove the existence and uniqueness of weak solutions by the Faedo-Galerkin method and exponential decay of solutions by the classic energy method. We improve the results obtained by Chipot-Lovato and Menezes for coupled systems. A numerical scheme is presented

Particulate blood analogues reproducing the erythrocytes cell-free layer in a microfluidic device containing a hyperbolic contraction

The interest in the development of blood analogues has been increasing recently as a consequence of the increment in the number of experimental hemodynamic studies and the difficulties associated with the manipulation of real blood in vitro because of ethical, economical or hazardous issues. Although one-phase Newtonian and non-Newtonian blood analogues can be found in the literature, there are very few studies related to the use of particulate solutions in which the particles mimic the behaviour of the red blood cells (RBCs) or erythrocytes. One of the most relevant effects related with the behaviour of the erythrocytes is a cell-free layer (CFL) formation, which consists in the migration of the RBCs towards the center of the vessel forming a cell depleted plasma region near the vessel walls, which is known to happen in in vitro microcirculatory environments. Recent studies have shown that the CFL enhancement is possible with an insertion of contraction and expansion region in a straight microchannel. These effects are useful for cell manipulation or sorting in lab-on-chip studies. In this experimental study we present particulate Newtonian and non-Newtonian solutions which resulted in a rheological blood analogue able to form a CFL, downstream of a microfluidic hyperbolic contraction, in a similar way of the one formed by healthy RBCs.The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT), COMPETE and FEDER through projects PTDC/SAU-BEB/105650/2008, PTDC/SAU-ENB/116929/2010, PTDC/EQU-FTT/118716/2010, EXPL/EMS-SIS/2215/2013, EXPL/EMS-TRA/2306/2013, fellowships SFRH/BD/89077/2012, SFRH/BPD/69663/2010 and SFRH/BPD/69664/2010 and grants IF/00148/2013 and IF/00190/2013.info:eu-repo/semantics/publishedVersio

A transformative route to nanoporous manganese oxides of controlled oxidation states with identical textural properties

Nanoporous nanocrystalline metal oxides with tunable oxidation states are crucial for controlling their catalytic, electronic, and optical properties. However, previous approaches to modulate oxidation states in nanoporous metal oxides commonly lead to the breakdown of the nanoporous structure as well as involve concomitant changes in their morphology, pore size, surface area, and nanocrystalline size. Herein, we present a transformative route to nanoporous metal oxides with various oxidation states using manganese oxides as model systems. Thermal conversion of Mn-based metal-organic frameworks (Mn-MOFs) at controlled temperature and atmosphere yielded a series of nanoporous manganese oxides with continuously tuned oxidation states: MnO, Mn3O 4, Mn5O8, and Mn2O3. This transformation enabled the preparation of low-oxidation phase MnO and metastable intermediate phase Mn5O8 with nanoporous architectures, which were previously rarely accessible. Significantly, nanoporous MnO, Mn3O4, and Mn5O8 had a very similar morphology, surface area, and crystalline size. We investigated the electrocatalytic activity of nanoporous manganese oxides for oxygen reduction reaction (ORR) to identify the role of oxidation states, and observed oxidation state-dependent activity and kinetics for the ORR.close5

Collapse of Turbulent Cores and Reconnection Diffusion

For a molecular cloud clump to form stars some transport of magnetic flux is required from the denser, inner regions to the outer regions of the cloud, otherwise this can prevent the collapse. Fast magnetic reconnection which takes place in the presence of turbulence can induce a process of reconnection diffusion (RD). Extending earlier numerical studies of reconnection diffusion in cylindrical clouds, we consider more realistic clouds with spherical gravitational potentials and also account for the effects of the gas self-gravity. We demonstrate that within our setup RD is efficient. We have also identified the conditions under which RD becomes strong enough to make an initially subcritical cloud clump supercritical and induce its collapse. Our results indicate that the formation of a supercritical core is regulated by a complex interplay between gravity, self-gravity, the magnetic field strength and nearly transonic and trans-Alfv\'enic turbulence, confirming that RD is able to remove magnetic flux from collapsing clumps, but only a few of them become nearly critical or supercritical, sub-Alfv\'enic cores, which is consistent with the observations. Besides, we have found that the supercritical cores built up in our simulations develop a predominantly helical magnetic field geometry which is also consistent with observations. Finally, we have evaluated the effective values of the turbulent reconnection diffusion coefficient and found that they are much larger than the numerical diffusion, especially for initially trans-Alfv\'enic clouds, ensuring that the detected magnetic flux removal is due to to the action of the RD rather than to numerical diffusivity.Comment: 24 pages, 18 figures, accepted for publication in the Ap

Magnetization of cloud cores and envelopes and other observational consequences of reconnection diffusion

Recent observational results for magnetic fields in molecular clouds reviewed by Crutcher (2012) seem to be inconsistent with the predictions of the ambipolar diffusion theory of star formation. These include the measured decrease in mass to flux ratio between envelopes and cores, the failure to detect any self-gravitating magnetically subcritical clouds, the determination of the flat PDF of the total magnetic field strengths implying that there are many clouds with very weak magnetic fields, and the observed scaling $B \propto \rho^{2/3}$ that implies gravitational contraction with weak magnetic fields. We consider the problem of magnetic field evolution in turbulent molecular clouds and discuss the process of magnetic field diffusion mediated by magnetic reconnection. For this process that we termed "reconnection diffusion" we provide a simple physical model and explain that this process is inevitable in view of the present day understanding of MHD turbulence. We address the issue of the expected magnetization of cores and envelopes in the process of star formation and show that reconnection diffusion provides an efficient removal of magnetic flux that depends only on the properties of MHD turbulence in the core and the envelope. As a result, the magnetic flux trapped during the collapse in the envelope is being released faster than the flux trapped in the core, resulting in much weaker fields in envelopes than in cores, as observed. We provide simple semi-analytical model calculations which support this conclusion and qualitatively agree with the observational results. We argue that magnetic reconnection provides a solution to the magnetic flux problem of star formation that agrees better with observations than the long-standing ambipolar diffusion paradigm.Comment: 22 pages, 11 figures, submitted to ApJ, revised version. arXiv admin note: substantial text overlap with arXiv:1111.069

Theory and Applications of Non-Relativistic and Relativistic Turbulent Reconnection

Realistic astrophysical environments are turbulent due to the extremely high Reynolds numbers. Therefore, the theories of reconnection intended for describing astrophysical reconnection should not ignore the effects of turbulence on magnetic reconnection. Turbulence is known to change the nature of many physical processes dramatically and in this review we claim that magnetic reconnection is not an exception. We stress that not only astrophysical turbulence is ubiquitous, but also magnetic reconnection itself induces turbulence. Thus turbulence must be accounted for in any realistic astrophysical reconnection setup. We argue that due to the similarities of MHD turbulence in relativistic and non-relativistic cases the theory of magnetic reconnection developed for the non-relativistic case can be extended to the relativistic case and we provide numerical simulations that support this conjecture. We also provide quantitative comparisons of the theoretical predictions and results of numerical experiments, including the situations when turbulent reconnection is self-driven, i.e. the turbulence in the system is generated by the reconnection process itself. We show how turbulent reconnection entails the violation of magnetic flux freezing, the conclusion that has really far reaching consequences for many realistically turbulent astrophysical environments. In addition, we consider observational testing of turbulent reconnection as well as numerous implications of the theory. The former includes the Sun and solar wind reconnection, while the latter include the process of reconnection diffusion induced by turbulent reconnection, the acceleration of energetic particles, bursts of turbulent reconnection related to black hole sources as well as gamma ray bursts. Finally, we explain why turbulent reconnection cannot be explained by turbulent resistivity or derived through the mean field approach.Comment: 66 pages, 24 figures, a chapter of the book "Magnetic Reconnection - Concepts and Applications", editors W. Gonzalez, E. N. Parke

Impact of obesity on surgical outcomes following laminectomy for spinal metastases

To determine the effect of obesity (body mass index >30 kg/m(2)) on perioperative morbidity and mortality after surgical decompression of spinal metastases. Methods: The American College of Surgeons National Surgical Quality Improvement Program database is a large multicenter clinical registry that collects preoperative risk factors, intraoperative variables, and 30-day postoperative morbidity and mortality outcomes from hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent decompression with laminectomy for treatment of metastatic spinal lesions between 2010 and 2014. Patients were separated into 2 cohorts based on the presence of absence of obesity. Univariate analysis and multivariate logistic regression analysis were used to analyze the effect of obesity on perioperative morbidity and mortality. Results: There was a significantly higher rate of venous thromboembolism (VTE; obese 6.6% vs nonobese 4.2%; P = .01) and pulmonary complications (obese 2.6% vs nonobese 2.2%; P = .046) in the obese group compared with the nonobese group. The nonobese group had prolonged hospitalization (obese 62.0% vs nonobese 69.0%; P = .001) and a higher incidence of blood transfusions (obese 26.8% vs nonobese 34.2%; P < .001). On multivariate analysis, obesity was found to be an independent risk factor for VTE (odds ratio = 1.75, confidence interval = 1.17-2.63, P = .007). Conclusions: Obese patients were predisposed to an elevated risk of VTE following laminectomy for spinal metastases. Early postoperative mobilization and a low threshold to evaluate for perioperative VTE are important in these patients in order to appropriately diagnose and treat these complications and minimize morbidity93254259sem informaçãosem informaçã

Hypoalbuminemia as an independent risk factor for perioperative complications following surgical decompression of spinal metastases

Malnutrition has been shown to be a risk factor for poor perioperative outcomes in multiple surgical subspecialties, but few studies have specifically investigated the effect of hypoalbuminemia in patients undergoing operative treatment of metastatic spinal tumors. The aim of this study was to assess the role of hypoalbuminemia as an independent risk factor for 30-day perioperative mortality and morbidity after surgical decompression of metastatic spinal tumors using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2011 to 2014. We identified 1498 adult patients in the ACS-NSQIP database who underwent laminectomy and excision of metastatic extradural spinal tumors. Patients were categorized into normoalbuminemic and hypoalbuminemic (ie, albumin level <3.5 g/dL) groups. Univariate and multivariate regression analyses were performed to examine the association between preoperative hypoalbuminemia and 30-day perioperative mortality and morbidity. Subgroup analysis was performed in the hypoalbuminemic group to assess the dose-dependent effect of albumin depletion. Hypoalbuminemia was associated with increased risk of perioperative mortality, any complication, sepsis, intra- or postoperative transfusion, prolonged hospitalization, and non-home discharge. However, albumin depletion was also associated with decreased risk of readmission. There was an albumin level–dependent effect of increasing mortality and complication rates with worsening albumin depletion. Hypoalbuminemia is an independent risk factor for perioperative mortality and morbidity following surgical decompression of metastatic spinal tumors with a dose-dependent effect on mortality and complication rates. Therefore, it is important to address malnutrition and optimize nutritional status prior to surgery9332133

Integration of first-principles methods and crystallographic database searches for new ferroelectrics: Strategies and explorations

In this concept paper, the development of strategies for the integration of first-principles methods with crystallographic database mining for the discovery and design of novel ferroelectric materials is discussed, drawing on the results and experience derived from exploratory investigations on three different systems: (1) the double perovskite Sr(Sb$_{1/2}$Mn$_{1/2}$)O$_3$ as a candidate semiconducting ferroelectric; (2) polar derivatives of schafarzikite $M$Sb$_2$O$_4$; and (3) ferroelectric semiconductors with formula $M_2$P$_2$(S,Se)$_6$. A variety of avenues for further research and investigation are suggested, including automated structure type classification, low-symmetry improper ferroelectrics, and high-throughput first-principles searches for additional representatives of structural families with desirable functional properties.Comment: 13 pages, 5 figures, 4 table