Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population

Background: Renal transplant recipients were noted to appear cushingoid while on low doses of steroid as part of a triple therapy immunosuppression of cyclosporin A (CsA), prednisolone, and azathioprine. Methods: The study group comprised adult renal transplant recipients with stable graft function who had received their renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control group was healthy nontransplant subjects [median dose 10 mg (10-30)]. Prednisolone bioavailability was measured using a limited 6-hour area under the curve (AUC), with prednisolone measured using specific HPLC assay. Results: The median prednisolone AUC/mg dose for all transplant recipients was significantly greater than the control group by approximately 50% (316 nmol(.)h/L/mg prednisolone versus 218). AUC was significantly higher in female recipients (median 415 versus 297 for men) and in recipients receiving cyclospotin (348 versus 285). The highest AUC was in women on estrogen supplements who were receiving cyclosporin (median 595). A significantly higher proportion of patients on triple therapy had steroid side effects compared with those on steroid and azathioprine (17/27 versus 4/15), more women than men had side effects (14/16 versus 7/22), and the AUC/mg prednisone was greater in those with side effects than without (median 377 versus 288 nmol-h/L/mg). Discussion: The results are consistent with the hypothesis that CsA increases the bioavailability of prednisolone, most likely through inhibition of beta-glycoprotein. The increased exposure to steroid increased the side-effect profile of steroids in the majority of patients. Because the major contributor to AUC is the maximum postdose concentration, it may be possible to use single-point monitoring (2 hours postdose) for routine clinical studies.

Adaptive responses of wild mungbean (Vigna radiata ssp sublobata) to photo-thermal environment. II. Growth, biomass, and seed yield

The leaf growth, dry matter production, and seed yield of 11 wild mungbean ( Vigna radiata ssp. sublobata) accessions of diverse geographic origin were observed under natural and artificial photoperiod temperature conditions, to determine the extent to which genotypic differences could be attributed to adaptive responses to photo-thermal environment. Environments included serial sowings in the field in SE Queensland, complemented by artificial photoperiod extension and controlled-environment growth rooms. Photo-thermal environment influenced leaf growth, total dry matter production ( TDM), and seed yield directly, through effects of ( mainly cool) temperature on growth, and indirectly, through effects on phenology. In terms of direct effects, leaf production, leaf expansion, and leaf area were all sensitive to temperature, with implied base temperatures higher than usually observed in cultivated mungbean ( V. radiata ssp. radiata). Genotypic sensitivity to temperature varied systematically with accession provenance and appeared to be of adaptive significance. In terms of the indirect effects of photo-thermal environment, genotypic and environmental effects on TDM were positively related to changes in total growth duration, and harvest index was negatively related to the period from sowing to flowering, similar to cultivated mungbean. However, seed yield was positively related to the duration of reproductive growth, reflecting the indeterminate growth habit of the wild accessions. As a consequence, the wild accessions are more responsive to favourable environments than typically observed in cultivated mungbean, which is determinate in habit. It is suggested that the introduction of the indeterminate trait into mungbean from the wild subspecies would increase the responsiveness of mungbean to favourable environments, analogous to that of black gram ( V. mungo). Although the wild subspecies appeared more sensitive to cool temperature than cultivated mungbean, it may provide a source of tolerance to the warmer temperatures experienced during the wet season in the tropics.

Resonant cavity Fibre Bragg grating sensor interrogation

This thesis presents a novel high-performance approach to time-division-multiplexing (TDM) fibre Bragg grating (FBG) optical sensors, known as the resonant cavity architecture. A background theory of FBG optical sensing includes several techniques for multiplexing sensors. The limitations of current wavelength-division-multiplexing (WDM) schemes are contrasted against the technological and commercial advantage of TDM. The author’s hypothesis that ‘it should be possible to achieve TDM FBG sensor interrogation using an electrically switched semiconductor optical amplifier (SOA)’ is then explained. Research and development of a commercially viable optical sensor interrogator based on the resonant cavity architecture forms the remainder of this thesis. A fully programmable SOA drive system allows interrogation of sensor arrays 10km long with a spatial resolution of 8cm and a variable gain system provides dynamic compensation for fluctuating system losses. Ratiometric filter- and diffractive-element spectrometer-based wavelength measurement systems are developed and analysed for different commercial applications. The ratiometric design provides a low-cost solution that has picometre resolution and low noise using 4% reflective sensors, but is less tolerant to variation in system loss. The spectrometer design is more expensive, but delivers exceptional performance with picometre resolution, low noise and tolerance to 13dB system loss variation. Finally, this thesis details the interrogator’s peripheral components, its compliance for operation in harsh industrial environments and several examples of commercial applications where it has been deployed. Applications include laboratory instruments, temperature monitoring systems for oil production, dynamic control for wind-energy and battery powered, self-contained sub-sea strain monitoring.

Time-division-multiplexing using pulse position locking for 100 Gb/s applications

Recently, there is a great interest in pushing communication technologies to 100 Gb/s. However, there are still many challenges to perform high speed (> 40 Gb/s) clock and data recovery, and data time-division-multiplexing (TDM). Here, we propose and numerically analyze an asynchronous optical packet retimer using parabolic or sinusoidal phase modulation and linear dispersion. This scheme is named pulse position locking (PPL). Numerical simulation shows that this scheme can effectively resynchronize input signals with arbitrary delays to the local clock, and reduce input jitter. The scheme can also be applied to TDM 10 Gb/s and 40 Gb/s signals to over 100 Gb/s.

Optical interconnection of core and metro networks

A network concept is introduced that exploits transparent optical grooming of traffic between an access network and a metro core ring network. This network is enabled by an optical router that allows bufferless aggregation of metro network traffic into higher-capacity data streams for core network transmission. A key functionality of the router is WDM to time-division multiplexing (TDM) transmultiplexing.

Resonant cavity time-division-multiplexed fiber Bragg grating sensor interrogator

The first resonant-cavity time-division-multiplexed (TDM) fiber Bragg grating sensor interrogation system is reported. This novel design uses a pulsed semiconductor optical amplifier in a cyclic manner to function as the optical source, amplifier, and modulator. Compatible with a range of standard wavelength detection techniques, this optically gated TDM system allows interrogation of low reflectivity "commodity" sensors spaced just 2 m apart, using a single active component. Results demonstrate an exceptional optical signal-to-noise ratio of 36 dB, a peak signal power of over +7 dBm, and no measurable crosstalk between sensors. Temperature tuning shows that the system is fully stable with a highly linear response. © 2004 IEEE.

High speed and high resolution demodulation system for hybrid WDM/FDM based fiber microstructure sensor network by using Fabry-Perot filter

Hybrid WDM/TDM enabled microstructure based optical fiber sensor network with large capacity is proposed. Assisted by Fabry-Perot filter, the demodulation system with high speed of 500Hz and high wavelength resolution less than 4.91pm is realized. © OSA 2015.

Estudo da correlação das características clínico-patológicas do câncer colorretal com a expressão imunohistoquímica de proteínas da progressão tumoral

Except the non-melanoma skin tumors, colorectal cancer is the second most common in the Southeastern Region of Brazil, the third most common in the Southern and Central Regions. It is also the forth most common in the Northern Region and it is the fifth one in the Northeastern. To assess pathological and clinical variables of colorectal Cancer is crucial to know the possible conclusions for the survival of patients and point out the characteristics in the progress of tumor, such as the profile of tumor invasion and its angiogenesis. This work focuses on analyzing clinically and pathologically some settings in colorectal cancer patients (CRC) in the city of Natal and its countryside through those variables as parameters of prognosis and determine the level of protein expression, for instance: E-cadherin (E-cad), beta- -catenin (β-cat), galectin-3 (gal-3), matrix metalloproteinases (MMP) 2 and 9 and vascular-endothelial growth factor alpha (α VEGF) in the tumor tissues. A retrospective study was done in colorectal cancer cases in the regions of Rio Grande do Norte state from 1995 to 2005, specifically in Natal city/RN/Brazil. The pathological and clinical variables, such as: age, gender, ethnicity, lifestyle, family history, the location of the primary tumor, level of differentiation, TDM staging, modified Dukes’, treatment and survival were analyzed. The pathological and clinical data were collected from medical records through a specific form and were filed on Excel. A total of 534 patients were selected from the Pathology Department file in this institution, however, 176 patients were excluded. 358 patients were included for Epidemiological analysis and its clinical and pathological correlations were selected. 180 patients were also selected for histological and immunohistochemical studies. The tumor progression of these selected proteins mentioned before were analyzed. The Paraffin blocks of these samples were treated by Microarray Tissue technique and its blades subjected to immunohistochemistry to test the intensity of these proteins in tumor tissues. The results of this analysis were correlated with clinicopathologic variables of patients. Statistical analysis using the chi-frame Pearson test and analysis of midlife by Kaplan-Meier curve was also utilized. P values < 0.05 were considered statistically significant. The average age of our sample was 58.8 years and 51.7 % were female. Alcohol consumption has increased by 1.71 time the risk of death by CCR (p = 0.034) and tobacco consumption increased 2.7 times the chance of developing tumors of high TNM stage (p = 0.001). Cancer patients had a family history of 3,833 times the chance of developing the CCR (p = 0.002). The expression of MMP-2 showed a significant association with tumors of high TNM stage (p <0.046) and mortality (p = 0.041). The α VEGF expression had statistically significant correlation with high TNM stage (p <0.009), degree of cell indifferentiation (p <0.025) and mortality (p <0.035). Expressions of E-cadherin and beta-catetina demonstrated tumor linked to high TNM stage (p = 0.0001) and Dukes› modified (p = 0.05), lesions in the rectum (p = 0.03 and p = 0.007, respectively), smoking (p = 0.05) and indifferentiation (p = 0.001). The expression of Gal-3 showed statistical significance with high TNM stage of patients (p = 0.01), smokers (p = 0.01), alcohol drinking (p = 0.03), indifferentiation (p = 0.0001) and mortality (p = 0.0001). Based on the results, therefore, we could realize that lifestyle and family history had correlation in the CCR prognosis, as well as MMP-2 expression, MMP-9, VEGF alpha, E-cadherin, Beta-catenin and Galectin-3 were important prognostic markers in tumor progression in colorectal cancer.

Petrologia e geocronologia U-Pb do plúton granítico Serra da Rajada, porção central do domínio Rio Piranhas - Seridó, Província Borborema, NE do Brasil

The ediacaran plutonic activity related to the Brasilian/Pan-African orogeny is one of the most important geological features in the Borborema Province, represented along its extension by numerous batholiths, stocks, and dikes.The object of this study, the Serra Rajada Granitic Pluton (SRGP), located in the central portion of the Piranhas-Seridó River Domain is an example of this activity. This pluton has been the subject of cartographic, petrographic, geochronological and lithogeochemical studies and its rocks were characterized by two facies. First, the granitic facies were described as monzogranites consisting of K-feldspar, plagioclase (oligoclase - An23-24%), quartz and biotite (main mafic) and opaque minerals such as titanite, allanite, apatite, and zircon as accessories. Alteration minerals are chlorite, white mica and carbonate. Second, the dioritic facies consist of rocks formed by quartz diorite containing plagioclase (dominant mineral phase), quartz and K-feldspar. Biotite and amphibole are the dominant mafic minerals; and titanite, opaque minerals, allanite, zircon and apatite are the accessories. However, previous geological mapping work in the region also identified the presence of other lithostratigraphic units. These were described as gneisses and migmatites with undifferentiated amphibolite lenses related to the Caicó Complex (Paleoproterozoic) and metasedimentary rocks of the Seridó Group (Neoproterozoic) composed of paragneiss with calc-silicate lenses, muscovite quartzite and biotite schist (respectively, the Jucurutu formations, Equador and Seridó), the host rocks for the SRGP rocks. Leucomicrogranite and pegmatite dikes have also been identified, both related to the end of the Ediacaran magmatism and colluvial- eluvial and alluvial deposits related to Neogene and Quaternary, respectively. Lithogeochemical data on the SRGP granite facies, highlighted quite evolved rocks (SiO2 69% to 75%), rich in alkalis (Na2O+K2O ≥ 8.0%), depleted of MgO (≤ 0.45%), CaO (≤ 1.42%) and TiO2 (≤ 0.36%) and moderate levels of Fe2O3t (2.16 to 3.53%). They display transitional nature between metaluminous and peraluminous (predominance of the latter) with sub-alkaline/monzonitic (High K calcium-alkali) affinity. Harker diagrams show negative correlations for Fe2O3t, MgO, and CaO, indicating mafic and plagioclase fractionation. REE spectrum shows enrichment of LREE relative to heavy REE (LaN/YbN = 23.70 to 10.13), with negative anomaly in the Eu (Eu/Eu* = 0.70 to 0.23), suggesting fractionation or accumulation in the feldspars source (plagioclase). Data integration allows to correlate the SRGP rocks with those described as Calcium-Alkaline Suite of equigranular High K. The crystallization conditions of the SRGP rocks were determined from the integration of petrographic and lithogeochemical data. These data indicated intermediate to high conditions of ƒO2 (mineral paragenesis titanite + magnetite + quartz), parent magma saturated in H2O (early biotite crystallization), tardi-magmatic processes of fluids rich in ƒCO2, H2O and O2 causing part of the mineral assembly to change (plagioclase carbonation and saussuritization, biotite chloritization and opaques Sphenitization). Thermobarometrical conditions were estimated based on geochemical parameters (Zr and P2O5) and CIPW normative minerals, with results showing the liquidus minimum temperature of about800°C and the solidus temperature of approximately 700°C. The final/minimum crystallization pressure are suggested to be between 3 and 5 Kbar. The presence of zoned minerals (plagioclase and allanite) associated with lithogeochemical data in bi-log diagrams for Rb vs. Ba and Rb vs. Sr suggest the role of fractional crystallization as the dominant process in the magmatic evolution of SRGP. U-Pb Geochronological and Sm-Nd isotope studies indicated, respectively, the crystallization age of biotite monzogranite as 557 ± 13 Ma, with TDM model age of 2.36 Ga, and εNd value of -20.10 to the crystallization age, allowing to infer paleoproterozoic crustal source for the magma.

Petrologia e geocronologia U-Pb do plúton granítico Serra da Rajada, porção central do domínio Rio Piranhas - Seridó, Província Borborema, NE do Brasil

The ediacaran plutonic activity related to the Brasilian/Pan-African orogeny is one of the most important geological features in the Borborema Province, represented along its extension by numerous batholiths, stocks, and dikes.The object of this study, the Serra Rajada Granitic Pluton (SRGP), located in the central portion of the Piranhas-Seridó River Domain is an example of this activity. This pluton has been the subject of cartographic, petrographic, geochronological and lithogeochemical studies and its rocks were characterized by two facies. First, the granitic facies were described as monzogranites consisting of K-feldspar, plagioclase (oligoclase - An23-24%), quartz and biotite (main mafic) and opaque minerals such as titanite, allanite, apatite, and zircon as accessories. Alteration minerals are chlorite, white mica and carbonate. Second, the dioritic facies consist of rocks formed by quartz diorite containing plagioclase (dominant mineral phase), quartz and K-feldspar. Biotite and amphibole are the dominant mafic minerals; and titanite, opaque minerals, allanite, zircon and apatite are the accessories. However, previous geological mapping work in the region also identified the presence of other lithostratigraphic units. These were described as gneisses and migmatites with undifferentiated amphibolite lenses related to the Caicó Complex (Paleoproterozoic) and metasedimentary rocks of the Seridó Group (Neoproterozoic) composed of paragneiss with calc-silicate lenses, muscovite quartzite and biotite schist (respectively, the Jucurutu formations, Equador and Seridó), the host rocks for the SRGP rocks. Leucomicrogranite and pegmatite dikes have also been identified, both related to the end of the Ediacaran magmatism and colluvial- eluvial and alluvial deposits related to Neogene and Quaternary, respectively. Lithogeochemical data on the SRGP granite facies, highlighted quite evolved rocks (SiO2 69% to 75%), rich in alkalis (Na2O+K2O ≥ 8.0%), depleted of MgO (≤ 0.45%), CaO (≤ 1.42%) and TiO2 (≤ 0.36%) and moderate levels of Fe2O3t (2.16 to 3.53%). They display transitional nature between metaluminous and peraluminous (predominance of the latter) with sub-alkaline/monzonitic (High K calcium-alkali) affinity. Harker diagrams show negative correlations for Fe2O3t, MgO, and CaO, indicating mafic and plagioclase fractionation. REE spectrum shows enrichment of LREE relative to heavy REE (LaN/YbN = 23.70 to 10.13), with negative anomaly in the Eu (Eu/Eu* = 0.70 to 0.23), suggesting fractionation or accumulation in the feldspars source (plagioclase). Data integration allows to correlate the SRGP rocks with those described as Calcium-Alkaline Suite of equigranular High K. The crystallization conditions of the SRGP rocks were determined from the integration of petrographic and lithogeochemical data. These data indicated intermediate to high conditions of ƒO2 (mineral paragenesis titanite + magnetite + quartz), parent magma saturated in H2O (early biotite crystallization), tardi-magmatic processes of fluids rich in ƒCO2, H2O and O2 causing part of the mineral assembly to change (plagioclase carbonation and saussuritization, biotite chloritization and opaques Sphenitization). Thermobarometrical conditions were estimated based on geochemical parameters (Zr and P2O5) and CIPW normative minerals, with results showing the liquidus minimum temperature of about800°C and the solidus temperature of approximately 700°C. The final/minimum crystallization pressure are suggested to be between 3 and 5 Kbar. The presence of zoned minerals (plagioclase and allanite) associated with lithogeochemical data in bi-log diagrams for Rb vs. Ba and Rb vs. Sr suggest the role of fractional crystallization as the dominant process in the magmatic evolution of SRGP. U-Pb Geochronological and Sm-Nd isotope studies indicated, respectively, the crystallization age of biotite monzogranite as 557 ± 13 Ma, with TDM model age of 2.36 Ga, and εNd value of -20.10 to the crystallization age, allowing to infer paleoproterozoic crustal source for the magma.

SDN enabled dynamically reconfigurable high capacity optical access architecture for converged services

Dynamically reconfigurable time-division multiplexing (TDM) dense wavelength division multiplexing (DWDM) long-reach passive optical networks (PONs) can support the reduction of nodes and network interfaces by enabling a fully meshed flat optical core. In this paper we demonstrate the flexibility of the TDM-DWDM PON architecture, which can enable the convergence of multiple service types on a single physical layer. Heterogeneous services and modulation formats, i.e. residential 10G PON channels, business 100G dedicated channel and wireless fronthaul, are demonstrated co-existing on the same long reach TDM-DWDM PON system, with up to 100km reach, 512 users and emulated system load of 40 channels, employing amplifier nodes with either erbium doped fiber amplifiers (EDFAs) or semiconductor optical amplifiers (SOAs). For the first time end-to-end software defined networking (SDN) management of the access and core network elements is also implemented and integrated with the PON physical layer in order to demonstrate two service use cases: a fast protection mechanism with end-to-end service restoration in the case of a primary link failure; and dynamic wavelength allocation (DWA) in response to an increased traffic demand.

Strontium and neodymium concentrations and isotopic compositions of Arctic marine sediments

Sr and Nd isotopic compositions of Arctic marine sediments characterize changes of sediment source regions and trace shelf-ocean particle pathways during glacial-interglacial transitions in the eastern Arctic Ocean. In the 140-ka sedimentary record of a marine core from Yermak Plateau, north of Svalbard, 87Sr/86Sr ratios and epsion-Nd values vary between 0.717 and 0.740 and 39.3 and 314.9, respectively. Sr and Nd isotopic composition both change characteristically during glacial-interglacial cycles and are correlated with the extension of the Svalbard/Barents Sea ice sheet (SBIS). The downcore variation in Sr and Nd isotopic composition indicates climatically induced changes in sediment provenance from two isotopically distinct end-members: (1) Eurasian shelf sediments as a distal source; and (2) Svalbard bedrock as a proximal source that coincide with a change in transport mechanism from sea ice to glacial ice. During glacier advance from Svalbard and intensified glacial bedrock erosion, epsion-Nd values decrease gradually to a minimum value of 314.9 due to increased input of crystalline Svalbard bedrock material. During glacial maxima, the SBIS covered the entire Barents Sea shelf and supplied increasing amounts of Eurasian shelf material to the Arctic Ocean as ice rafted detritus (IRD). Epsion-Nd values in glacial sediments reach maximum values that are comparable to the average value of modern Eurasian shelf and sea ice sediments (epsion-Nd = 310.3). This confirms ice rafting as a major sediment transport mechanism for Eurasian shelf sediments into the Arctic Ocean and trace a sediment origin from the Kara Sea/Laptev Sea shelf area. After the decay of the shelf-based SBIS, the glacial shelf sediment spikes during glacial terminations I (epsion-Nd = 310.6) and II (epsion-Nd = 310.1) epsion-Nd values rapidly decrease to values of 312.5 typical for interglacial averages. The downcore Sr isotopic composition is anticorrelated to the Nd isotopic composition, but may be also influenced by grain-size effects. In contrast, the Nd isotopic composition in clay- to silt-size fractions of one bulk sediment sample is similar to within 0.3-0.8 epsion-Nd units and seems to be a grain-size independent provenance tracer.

Radionuclides of bulk and terrigenous surface sediments in the Southern Ocean

Sr and Nd isotopic compositions of Late Quaternary surface sediment and sediment cores from the south Atlantic and southeast Pacific sectors of the Southern Ocean are used to constrain the provenance and transport mechanisms of their terrigenous component. We report isotopic and mineralogical data for core samples from three localities, the Mid-Atlantic Ridge at 41°S and the northern and southern Scotia Sea. In addition, data for surface sediment samples from the south Atlantic and southeast Pacific sectors of the Southern Ocean are presented. The variations of Sr and Nd isotopic compositions of the bulk sediment samples in all cores were correlated with the magnetic susceptibility of the sediment and with the inferred glacial-interglacial stages. The isotopic data indicate that, during glacial periods, sediment was delivered from continental crust with a shorter residence time than that supplying material during interglacial periods. At the core site near the Mid-Atlantic Ridge, Nd isotopic, combined with mineralogical evidence indicates interglacial period deposition of a relatively high amount of kaolinite and silt with low epsilon-Nd values < -8. The material was probably supplied by North Atlantic Deep Water from low latitudes. For glacial periods, a high contribution of silt and clay with epsilon-Nd > -4.5, probably derived from southern South America, was indicated. The glacial-interglacial shift in sources may be due to either a decreasing influence of North Atlantic Deep Water during glacial times or by a larger contribution of glaciogenic detritus from southern South America. At the core site in the northern Scotia Sea, sediment of interglacial periods is dominated by smectite with epsilon-Nd < - 6 and silt with epsilon-Nd > -4. We suggest that smectite was derived from the Falkland shelf and silt was derived from the Argentinian shelf. During glacial periods, the Argentinian shelf was an important source for silt and chlorite with epsilon-Nd > -4. The contribution from the Falkland shelf seems to have remained similar during glacial and interglacial periods. Hydrographic transport by bottom currents and turbidites could account for the high glacial detrital flux. An evaluation of the significance of an aeolian contribution to deep sea sediment suggests that it plays only a minor role. In the southern Scotia Sea, the Antarctic Peninsula is considered an important source for young material with epsilon-Nd > -4, in particular during glacial periods. During interglacial periods, sediment supply from the Antarctic Peninsula was lower than during glacial times, resulting in a relatively high contribution of old material (epsilon-Nd < -8) from East Antarctica. Deep water currents and icebergs could account for the transport of the old component to the southern Scotia Sea. The accumulation rates of material from the various source regions for glacial times are in agreement with an increase in the strength of the Antarctic Circumpolar Current. The production rate and the circulation pattern of bottom water in the Weddell Sea appear to have remained similar over most of the last 150 kyr.

A proveniência dos sedimentos e cinzas vulcânicas dos sedimentos permianos da bacia do Paraná : implicações para a história geológica do sul-sudoeste de Gondwana

Tese (doutorado)—Universidade de Brasília, Instituto de Geociências, Programa de Pós-Graduação em Geologia, 2016.

Dispositivos intraorais em atletas praticantes de râguebi: sua ação nos sinais e sintomas associadas à DTM

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz