Progression of diffuse gliomas - from the first diagnosis to recurrence

Gliomas are the most frequent primary brain tumours. The cardinal features of gliomas are infiltrative growth pattern and progression from low-grade tumours to a more malignant phenotype. These features of gliomas generally prevent their complete surgical excision and cause their inherent tendency to recur after initial treatment and lead to poor long-term prognosis. Increasing knowledge about the molecular biology of gliomas has produced new markers that supplement histopathological diagnostics. Molecular markers are also used to evaluate the prognosis and predict therapeutic response. The purpose of this thesis is to study molecular events involved in the malignant progression of gliomas. Gliomas are highly vascularised tumours. Contrast enhancement in magnetic resonance imaging (MRI) reflects a disrupted blood-brain barrier and is often seen in malignant gliomas. In this thesis, 62 astrocytomas, oligodendrogliomas and oligoastrocytomas were studied by MRI and immunohistochemistry. Contrast enhancement in preoperative MRI was associated with angiogenesis, tumour cell proliferation and histological grade of gliomas. Activation of oncogenes by gene amplification is a common genetic aberration in gliomas. EGFR amplification on chromosome 7p12 occurs in 30-40% of glioblastomas. PDGFRA, KIT and VEGFR2 are receptor tyrosine kinase genes located on chromosome 4q12. Amplification of these genes was studied using in situ hybridisation in the primary and recurrent astrocytomas, oligodendrogliomas and oligoastrocytomas of 87 patients. PDGFRA, KIT or VEGFR2 amplification was found in 22% of primary tumours and 36% of recurrent tumours including low-grade and malignant gliomas. The most frequent aberration was KIT amplification, which occurred in 10% of primary tumours and in 27% of recurrent tumours. The expression of ezrin, cyclooxygenase 2 (COX-2) and HuR was studied immunohistochemically in a series of primary and recurrent gliomas of 113 patients. Ezrin is a cell membrane-cytoskeleton linking-protein involved in the migration of glioma cells. The COX-2 enzyme is implicated in the carcinogenesis of epithelial neoplasms and is overexpressed in gliomas. HuR is an RNA-stabilising protein, which regulates the expression of several proteins including COX-2. Ezrin, COX-2 and HuR were associated with histological grade and the overall survival of glioma patients. However, in multivariate analysis they were not independent prognostic factors. In conclusion, these results suggest that contrast enhancement in MRI can be used as a surrogate marker for the proliferative and angiogenic potential of gliomas. Aberrations of PDGFRA, KIT and VEGFR2 genes, as well as the dysregulated expression of ezrin, COX-2 and HuR proteins, are linked to the progression of gliomas.

Pain measurement and management in elderly patients : Clinical studies in long term hospital care and after cardiac surgery

The proportion of patients over 75 years of age, receiving all different types of healthcare, is constantly increasing. The elderly undergo surgery and anaesthetic procedures more often than middle-aged patients. Poor pain management in the elderly is still an issue. Although the elderly consumes the greatest proportion of prescribed medicines in Western Europe, most clinical pharmacological studies have been performed in healthy volunteers or middle-aged patients. The aim of this study was to investigate pain measurement and management in cognitively impaired patients in long term hospital care and in cognitively normal elderly patients after cardiac surgery. This thesis incorporated 366 patients, including 86 home-dwelling or hospitalized elderly with chronic pain and 280 patients undergoing cardiac surgery with acute pain. The mean age of patients was 77 (SD ± 8) years and approximately 8400 pain measurements were performed with four pain scales: Verbal Rating Scale (VRS), the Visual Analogue Scale (VAS), the Red Wedge Scale (RWS), and the Facial Pain Scale (FPS). Cognitive function, depression, functional ability in daily life, postoperative sedation and postoperative confusion were assessed with MMSE, GDS, Barthel Index, RASS, and CAM-ICU, respectively. The effects and plasma concentrations of fentanyl and oxycodone were measured in elderly (≥ 75 years) and middle-aged patients (≤ 60 years) and the opioid-sparing effect of pregabalin was studied after cardiac surgery. The VRS pain scores after movement correlated with the Barthel Index. The VRS was most successful in the groups of demented patients (MMSE 17-23, 11-16 and ≤ 10) and in elderly patients on the first day after cardiac surgery. The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients. The plasma concentrations of oxycodone were comparable between the groups. Pain intensity on the VRS was lower and the sedation scores were higher in the elderly. Total oxycodone consumption during five postoperative days was reduced by 48% and the CAM-ICU scores were higher on the first postoperative day in the pregabalin group. The incidence of postoperative pain during movement was lower in the pregabalin group three months after surgery. This investigation demonstrates that chronic pain did not seem to impair daily activities in home-dwelling Finnish elderly. The VRS appeared to be applicable for elderly patients with clear cognitive dysfunction (MMSE ≤17) and it was the most feasible pain scale for the early postoperative period after cardiac surgery. After cardiac surgery, plasma concentrations of fentanyl in elderly were elevated, although oxycodone concentrations were at similar level compared to middle-aged patients. The elderly had less pain and were more sedated after doses of oxycodone. Therefore, particular attention must be given to individual dosing of the opioids in elderly surgical patients, who often need a smaller amount for adequate analgesia than middle-aged patients. The administration of pregabalin reduced postoperative oxycodone consumption after cardiac surgery. Pregabalin-treated patients had less confusion, and additionally to less postoperative pain on the first postoperative day and during movement at three months post-surgery. Pregabalin might be a new alternative as analgesic for acute postoperative and chronic pain management in the elderly. Its clinical role and safety remains to be verified in large-scale randomized and controlled studies. In the future, many clinical trials in the older category of patients will be needed to facilitate improvements in health care methods.

Interest in university studies : Its role and relation to other motivational variables

This dissertation empirically explored interest as a motivational force in university studies, including the role it currently plays and possible ways of enhancing this role as a student motivator. The general research questions were as follows: 1) What role does interest play in university studies? 2) What explains academic success if studying is not based on interest? 3) How do different learning environments support or impede interest-based studying? Four empirical studies addressed these questions. Study 1 (n=536) compared first-year students explanations of their disciplinary choices in three fields: veterinary medicine, humanities and law. Study 2 (n=28) focused on the role of individual interest in the humanities and veterinary medicine, fields which are very different from each other as regards their nature of studying. Study 3 (n=52) explored veterinary students motivation and study practices in relation to their study success. Study 4 (n=16) explored veterinary students interest experience in individual lectures on a daily basis. By comparing different fields and focusing on one study field in more detail, it was possible to obtain a many-sided picture of the role of interest in different learning environments. Questionnaires and quantitative methods have often been used to measure interest in academic learning. The present work is based mostly on qualitative data, and qualitative methods were applied to add to the previous research. Study 1 explored students open-ended answers, and these provided a basis for the interviews in Study 2. Study 3 explored veterinary students portfolios in a longitudinal setting. For Study 4, a diary including both qualitative and quantitative measures was designed to capture veterinary students interest experience. Qualitative content analysis was applied in all four studies, but quantitative analyses were also added. The thesis showed that university students often explain their disciplinary choices in terms of interest. Because interest is related to high-quality learning, the students seemed to have a good foundation for successful studies. However, the learning environments did not always support interest-based studying; Time-management and coping skills were found to be more important than interest in terms of study success. The results also indicated that interest is not the only motivational variable behind university studies. For example, future goals are needed in order to complete a degree. Even so, the results clearly indicated that it would be worth supporting interest-based studying both in professionally and generally oriented study fields. This support is important not only to promote high-quality learning but also meaningful studying, student well-being, and life-long learning.

Carbon Dioxide emissions from an Acacia plantation on peatland in Sumatra, Indonesia

Abstract. Peat surface CO2 emission, groundwater table depth and peat temperature were monitored for two years along transects in an Acacia plantation on thick tropical peat (>4 m) in Sumatra, Indonesia. A total of 2300 emission measurements were taken at 144 locations. The autotrophic root respiration component of the CO2 emission was separated from heterotrophic emissions caused by peat oxidation in three ways: (i) by comparing CO2 emissions within and beyond the tree rooting zone, (ii) by comparing CO2 emissions with and without peat trenching (i.e. cutting any roots remaining in the peat beyond the tree rooting zone), and (iii) by comparing CO2 emissions before and after Acacia tree harvesting. On average, the contribution of root respiration to daytime CO2 emission is 21 % along transects in mature tree stands. At locations 0.5 m from trees this is up to 80 % of the total emissions, but it is negligible at locations more than 1.3 m away. This means that CO2 emission measurements well away from trees are free of any root respiration contribution and thus represent only peat oxidation emission. We find daytime mean annual CO2 emission from peat oxidation alone of 94 t ha−1 yr−1 at a mean water table depth of 0.8 m, and a minimum emission value of 80 t ha−1 yr−1 after correction for the effect of diurnal temperature fluctuations, which resulted in a 14.5 % reduction of the daytime emission. There is a positive correlation between mean long-term water table depths and peat oxidation CO2 emission. However, no such relation is found for instantaneous emission/water table depth within transects and it is clear that factors other than water table depth also affect peat oxidation and total CO2 emissions. The increase in the temperature of the surface peat due to plantation development may explain over 50 % of peat oxidation emissions.

Strongly magnetized cold degenerate electron gas: Mass-radius relation of the magnetized white dwarf

We consider a relativistic, degenerate electron gas at zero temperature under the influence of a strong, uniform, static magnetic field, neglecting any form of interactions. Since the density of states for the electrons changes due to the presence of the magnetic field (which gives rise to Landau quantization), the corresponding equation of state also gets modified. In order to investigate the effect of very strong magnetic field, we focus only on systems in which a maximum of either one, two, or three Landau level(s) is/are occupied. This is important since, if a very large number of Landau levels are filled, it implies a very low magnetic field strength which yields back Chandrasekhar's celebrated nonmagnetic results. The maximum number of occupied Landau levels is fixed by the correct choice of two parameters, namely, the magnetic field strength and the maximum Fermi energy of the system. We study the equations of state of these one-level, two-level, and three-level systems and compare them by taking three different maximum Fermi energies. We also find the effect of the strong magnetic field on the mass-radius relation of the underlying star composed of the gas stated above. We obtain an exciting result that it is possible to have an electron-degenerate static star, namely, magnetized white dwarfs, with a mass significantly greater than the Chandrasekhar limit in the range 2.3-2.6M(circle dot), provided it has an appropriate magnetic field strength and central density. In fact, recent observations of peculiar type Ia supernovae-SN 2006gz, SN 2007if, SN 2009dc, SN 2003fg-seem to suggest super-Chandrasekhar-mass white dwarfs with masses up to 2.4-2.8M(circle dot) as their most likely progenitors. Interestingly, our results seem to lie within these observational limits.

On the recurrence of great subduction zone earthquakes

The last decade has witnessed two unusually large tsunamigenic earthquakes. The devastation from the 2004 Sumatra Andaman and the 2011 Tohoku-Oki earthquakes (both of moment magnitude >= 9.0) and their ensuing tsunamis comes as a harsh reminder on the need to assess and mitigate coastal hazards due to earthquakes and tsunamis worldwide. Along any given subduction zone, megathrust tsunamigenic earthquakes occur over intervals considerably longer than their documented histories and thus, 2004-type events may appear totally `out of the blue'. In order to understand and assess the risk from tsunamis, we need to know their long-term frequency and magnitude, going beyond documented history, to recent geological records. The ability to do this depends on our knowledge of the processes that govern subduction zones, their responses to interseismic and coseismic deformation, and on our expertise to identify and relate tsunami deposits to earthquake sources. In this article, we review the current state of understanding on the recurrence of great thrust earthquakes along global subduction zones.

Pristine and graphitized-MWCNTs as durable cathode-catalyst supports for PEFCs

Long-term deterioration in the performance of PEFCs is attributed largely to reduction in active area of the platinum catalyst at cathode, usually caused by carbon-support corrosion. Multi-walled carbon-nanotubes (MWCNTs) as cathode-catalyst support are found to enhance long-term stability of platinum catalyst (Pt) in relation to non-graphitic carbon. In addition, highly graphitic MWCNTs (G-MWCNTs) are found to be electrochemically more stable than pristine MWCNTs. This is because graphitic-carbon-supported-Pt (Pt/MWCNTs) cathodes exhibit higher resistance to carbon corrosion in-relation to non-graphitic-carbon-supported-Pt (Pt/C) cathodes in PEFCs during accelerated stress-test (AST) as evidenced by chronoamperometry and carbon dioxide studies. The corresponding change in electrochemical surface area (ESA), cell performance, and charge-transfer resistance are monitored through cyclic voltammetry, cell polarization, and impedance measurements, respectively. The extent of crystallinity, namely amorphous or graphitic nature of the three supports, is examined by Raman spectroscopy. X-ray diffraction and transmission electron microscopy studies both prior and after AST suggest lesser deformation in catalyst layer and catalyst particles for Pt/G-MWCNTs and Pt/MWCNTs cathodes in relation to Pt/C cathodes, reflecting that graphitic carbon-support resists carbon corrosion and helps mitigating aggregation of Pt particles. It is also found that with increasing degree of graphitization, the electrochemical stability for MWCNTs increases due to the lesser surface defects.

Spinning strings and minimal surfaces in AdS(3) with mixed 3-form fluxes

Motivated by the recent proposal for the S-matrix in AdS(3) x S-3 with mixed three form fluxes, we study classical folded string spinning in AdS(3) with both Ramond and Neveu-Schwarz three form fluxes. We solve the equations of motion of these strings and obtain their dispersion relation to the leading order in the Neveu-Schwarz flux b. We show that dispersion relation for the spinning strings with large spin S acquires a term given by -root lambda/2 pi b(2) log(2) S in addition to the usual root lambda/pi log S term where root lambda is proportional to the square of the radius of AdS(3). Using SO(2, 2) transformations and re-parmetrizations we show that these spinning strings can be related to light like Wilson loops in AdS(3) with Neveu-Schwarz flux b. We observe that the logarithmic divergence in the area of the light like Wilson loop is also deformed by precisely the same coefficient of the b(2) log(2) S term in the dispersion relation of the spinning string. This result indicates that the coefficient of b(2) log(2) S has a property similar to the coefficient of the log S term, known as cusp-anomalous dimension, and can possibly be determined to all orders in the coupling lambda using the recent proposal for the S-matrix.

Spectrum of the three-dimensional fuzzy well

We develop the formalism of quantum mechanics on three-dimensional fuzzy space and solve the Schrodinger equation for the free particle, finite and infinite fuzzy wells. We show that all results reduce to the appropriate commutative limits. A high energy cut-off is found for the free particle spectrum, which also results in the modification of the high energy dispersion relation. An ultra-violet/infra-red duality is manifest in the free particle spectrum. The finite well also has an upper bound on the possible energy eigenvalues. The phase shifts due to scattering around the finite fuzzy potential well are calculated.

Dielectric elastomers: Asymptotically-correct three-dimensional displacement field

Asymptotically-accurate dimensional reduction from three to two dimensions and recovery of 3-D displacement field of non-prestretched dielectric hyperelastic membranes are carried out using the Variational Asymptotic Method (VAM) with moderate strains and very small ratio of the membrane thickness to its shortest wavelength of the deformation along the plate reference surface chosen as the small parameters for asymptotic expansion. Present work incorporates large deformations (displacements and rotations), material nonlinearity (hyperelasticity), and electrical effects. It begins with 3-D nonlinear electroelastic energy and mathematically splits the analysis into a one-dimensional (1-D) through-the-thickness analysis and a 2-D nonlinear plate analysis. Major contribution of this paper is a comprehensive nonlinear through-the-thickness analysis which provides a 2-D energy asymptotically equivalent of the 3-D energy, a 2-D constitutive relation between the 2-D generalized strain and stress tensors for the plate analysis and a set of recovery relations to express the 3-D displacement field. Analytical expressions are derived for warping functions and stiffness coefficients. This is the first attempt to integrate an analytical work on asymptotically-accurate nonlinear electro-elastic constitutive relation for compressible dielectric hyperelastic model with a generalized finite element analysis of plates to provide 3-D displacement fields using VAM. A unified software package `VAMNLM' (Variational Asymptotic Method applied to Non-Linear Material models) was developed to carry out 1-D non-linear analysis (analytical), 2-D non-linear finite element analysis and 3-D recovery analysis. The applicability of the current theory is demonstrated through an actuation test case, for which distribution of 3-D displacements are provided. (C) 2014 Elsevier Ltd. All rights reserved.

Long-Term Sustained Release of Salicylic Acid from Cross-Linked Biodegradable Polyester Induces a Reduced Foreign Body Response in Mice

There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 x 10(-4) h(-1) over similar to 1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-alpha and IL-1 beta), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

Impact of compost, vermicompost and biochar on soil fertility, maize yield and soil erosion in Northern Vietnam: A three year mesocosm experiment

Compost, vermicompost and biochar amendments are thought to improve soil quality and plant yield. However, little is known about their long-term impact on crop yield and the environment in tropical agro-ecosystems. In this study we investigated the effect of organic amendments (buffalo manure, compost and verrnicompost) and biochar (applied alone or with vermicompost) on plant yield, soil fertility, soil erosion and water dynamics in a degraded Acrisol in Vietnam. Maize growth and yield, as well as weed growth, were examined for three years in terrestrial mesocosms under natural rainfall. Maize yield and growth showed high inter-annual variability depending on the organic amendment. Vermicompost improved maize growth and yield but its effect was rather small and was only significant when water availability was limited (year 2). This suggests that vermicompost could be a promising substrate for improving the resistance of agrosystems to water stress. When the vermicompost biochar mixture was applied, further growth and yield improvements were recorded in some cases. When applied alone, biochar had a positive influence on maize yield and growth, thus confirming its interest for improving long-term soil productivity. All organic amendments reduced water runoff, soil detachment and NH4+ and NO3- transfer to water. These effects were more significant with vermicompost than with buffalo manure and compost, highlighting that the beneficial influence of vermicompost is not limited to its influence on plant yield. In addition, this study showed for the first time that the combination of vermicompost and biochar may not only improve plant productivity but also reduce the negative impact of agriculture on water quality. (C) 2015 Elsevier B.V. All rights reserved.

NMR relaxation studies in doped poly-3-methylthiophene

NMR relaxation rates (1/T-1), magnetic susceptibility, and electrical conductivity studies in doped poly-3-methylthiophene are reported in this paper. The magnetic susceptibility data show the contributions from both Pauli and Curie spins, with the size of the Pauli term depending strongly on the doping level. Proton and fluorine NMR relaxation rates have been studied as a function of temperature (3-300 K) and field (for protons at 0.9, 9.0, 16.4, and 23.4 T, and for fluorine at 9.0 T). The temperature dependence of T-1 is classified into three regimes: (a) For T < (g mu(B) B/2k(B)), the relaxation mechanism follows a modified Korringa relation due to electron-electron interactions and disorder. H-1-T-1 is due to the electron-nuclear dipolar interaction in addition to the contact term. (b) For the intermediate temperature range (g mu(B) B/2k(B)) < T < T-BPP (the temperature where the contribution from the reorientation motion to the T-1 is insignificant) the relaxation mechanism is via spin diffusion to the paramagnetic centers. (c) In the high-temperature regime and at low Larmor frequency the relaxation follows the modified Bloembergen, Purcell, and Pound model. T-1 data analysis has been carried out in light of these models depending upon the temperature and frequency range of study. Fluorine relaxation data have been analyzed and attributed to the PF6 reorientation. The cross relaxation among the H-1 and F-19 nuclei has been observed in the entire temperature range suggesting the role of magnetic dipolar interaction modulated by the reorientation of the symmetric molecular subgroups. The data analysis shows that the enhancement in the Korringa ratio is greater in a less conducting sample. Intra-and interchain hopping of charge carriers is found to be a dominant relaxation mechanism at low temperature. Frequency dependence of T-1(-1) on temperature shows that at low temperature T < (g mu(B) B/2k(B))] the system shows three dimensions and changes to quasi one dimension at high temperature. Moreover, a good correlation between electrical conductivity, magnetic susceptibility, and NMR T-1 data has been observed.

Stalagmite growth perturbations from the Kumaun Himalaya as potential earthquake recorders

The central part of the Himalaya (Kumaun and Garhwal Provinces of India) is noted for its prolonged seismic quiescence, and therefore, developing a longer-term time series of past earthquakes to understand their recurrence pattern in this segment assumes importance. In addition to direct observations of offsets in stratigraphic exposures or other proxies like paleoliquefaction, deformation preserved within stalagmites (speleothems) in karst system can be analyzed to obtain continuous millennial scale time series of earthquakes. The Central Indian Himalaya hosts natural caves between major active thrusts forming potential storehouses for paleoseismological records. Here, we present results from the limestone caves in the Kumaun Himalaya and discuss the implications of growth perturbations identified in the stalagmites as possible earthquake recorders. This article focuses on three stalagmites from the Dharamjali Cave located in the eastern Kumaun Himalaya, although two other caves, one of them located in the foothills, were also examined for their suitability. The growth anomalies in stalagmites include abrupt tilting or rotation of growth axes, growth termination, and breakage followed by regrowth. The U-Th age data from three specimens allow us to constrain the intervals of growth anomalies, and these were dated at 4273 +/- 410 years BP (2673-1853 BC), 2782 +/- 79 years BP (851-693 BC), 2498 +/- 117 years BP (605-371 BC), 1503 +/- 245 years BP (262-752 AD), 1346 +/- 101 years BP (563-765 AD), and 687 +/- 147 years BP (1176-1470 AD). The dates may correspond to the timings of major/great earthquakes in the region and the youngest event (1176-1470 AD) shows chronological correspondence with either one of the great medieval earthquakes (1050-1250 and 1259-1433 AD) evident from trench excavations across the Himalayan Frontal Thrust.

The Displacement and Strain Field of Three-Dimensional Rheologic Model of Earthquake Preparation

Based on the three-dimensional elastic inclusion model proposed by Dobrovolskii, we developed a rheological inclusion model to study earthquake preparation processes. By using the Corresponding Principle in the theory of rheologic mechanics, we derived the analytic expressions of viscoelastic displacement U(r, t) , V(r, t) and W(r, t), normal strains epsilon(xx) (r, t), epsilon(yy) (r, t) and epsilon(zz) (r, t) and the bulk strain theta (r, t) at an arbitrary point (x, y, z) in three directions of X axis, Y axis and Z axis produced by a three-dimensional inclusion in the semi-infinite rheologic medium defined by the standard linear rheologic model. Subsequent to the spatial-temporal variation of bulk strain being computed on the ground produced by such a spherical rheologic inclusion, interesting results are obtained, suggesting that the bulk strain produced by a hard inclusion change with time according to three stages (alpha, beta, gamma) with different characteristics, similar to that of geodetic deformation observations, but different with the results of a soft inclusion. These theoretical results can be used to explain the characteristics of spatial-temporal evolution, patterns, quadrant-distribution of earthquake precursors, the changeability, spontaneity and complexity of short-term and imminent-term precursors. It offers a theoretical base to build physical models for earthquake precursors and to predict the earthquakes.