DX Level Research Articles

79 Flexible Support Materials Maintain Disc Height and Support the Formation of Hydrated Tissue Engineered Intervertebral Discs in Vivo

OBJECTIVES/GOALS: We evaluated the long-term success of tissue engineered intervertebral discs (TE-IVDs) cultured in flexible (FPLA) or stiff (PLA) support materials, hypothesizing that FPLA would maintain disc height and tissue hydration in the minipig spine. METHODS/STUDY POPULATION: TE-IVD: NP cells were encapsulated in alginate and NP plugs were placed in the center of FPLA cages. AF cells were encapsulated in type I collagen and pipetted around NP plugs. Implantation: Empty FPLA cages (n=4), and TE-IVDs cultured in FPLA (n=4) were implanted at C3-4 or C5-6 following complete discectomy (DX) in skeletally mature minipigs (n=4). Imaging and Quantification: Terminal disc height indices (DHI) were calculated from weekly x-rays using a previously described method, and results were compared to the PLA pilot study. T2 MRI scans were taken of levels treated with TE-IVDs to quantify disc hydration as previously described. RESULTS/ANTICIPATED RESULTS: FPLA cages restored DHIs to native levels until endpoint. In contrast, PLA cages fractured, and terminal DHIs were statistically similar to DX levels. Of the four levels treated with TE-IVDs, 2 were displaced from the disc space. Stabilized levels yielded DHIs which were statistically similar to native IVD and greater than displaced and DX levels. Displaced levels yielded DHIs which were significantly lower than native and stabilized levels, but greater than DX levels (P<0.05). T2 MRIs of stabilized TEIVDs revealed that levels treated with a construct maintained tissue hydration which was significantly greater than levels treated with an empty cage or DX levels (P<0.0001), but which was about half the hydration of native disc tissue. DISCUSSION/SIGNIFICANCE: Implanting TE-IVDs with FPLA support cages leads to disc height maintenance and the stabilization of hydrated tissues in the spine, enhancing the long term success of TE-IVD implants and providing a basis for clinical translation.

Changes in health-related quality of life (HRQL) after bladder cancer (BC) diagnosis (DX): A longitudinal population-based study.

317 Background: Few studies have examined longitudinal changes in HRQL among BC patients. To our knowledge, this is the largest prospective population-based study to quantify HRQL changes from before to after BC DX and to compare their HRQL with a non-cancer cohort. Methods: Our sample included 179 BC patients (≥ age 65) and 376,986 non-cancer subjects within the SEER-Medicare Health Outcomes Survey database (1998-2007). We assessed HRQL as measured by physical (PCS) and mental (MCS) component summary scores of the veterans RAND 12-item health survey. An analysis of covariance model was used to estimate changes in HRQL scores for patients after BC DX relative to control subjects with adjustment for baseline HRQL scores and covariates. Results: 84.4% (N=151) of BC patients had non-muscle invasive BC (NMIBC) and 15.6% (N=28) had muscle invasive BC (MIBC). 49.2% and 39.1% of BC patients had ≥2 comorbid conditions and ≥1 activities of daily living (ADL) deficit, respectively. Compared to the control subjects, more BC patients were men (67.0% vs 38.5%; P<0.01), current or former smokers (58.7% vs 37.3%; P<0.01), and had income ≥ $50,000(15.1% vs 8.8%; P=0.02). Other baseline demographic and socioeconomic characteristics were similar (P>0.05). After DX, BC patients reported a significant decline in PCS (1.9; 95% CI 0.1, 3.7) score compared to non-cancer controls whereas the decrease in MCS score (1.4; 95% CI -0.1, 3.0) was not statistically significant. For those with NMIBC, HRQL was not significantly different than that of the non-cancer cohort (P>0.05) after DX. However, the PCS and MCS scores of MIBC patients decreased by 5.3 (95% CI 0.9, 9.8) and 3.8 points (95% CI -0.1, 7.7) after DX, respectively. Older age at BC DX, lower educational and income levels, smoking history, and higher numbers of comorbid conditions and ADL deficits were significantly associated with inferior PCS and MCS scores after BC DX (P<0.01). Conclusions: Treatment-related side effects and/or symptoms due to BC adversely affect HRQL of BC patients, especially in those with MIBC, and should be consistently assessed by health care providers. Future research that examines interventions to improve HRQL is critical to improve BC care.

Predicting the Oncotype DX score: An inexpensive guesstimation.

557 Background: Oncotype DX Recurrence Score [RS] is used to predict the benefits of chemotherapy added to adjuvant hormone therapy in ER positive early stage breast cancer. It is also prognostic. However, its expense may be a concern in some health care systems and communities. In addition, it is labor intensive, requiring shipment of tissue samples to a single laboratory with an average 10-14 day turnaround time (in the US). A reliable and inexpensive estimator of the Oncotype DX risk score using readily available pathologic variables from tumor specimens could be useful. Methods: We reviewed our prospective database of patients with Oncotype DX results obtained over 2.5 years (1155 specimens with Oncotype DX scores, September 2008 – March 2011) and identified 766 invasive ductal carcinomas with known ER status, PR status, histologic grade, and nuclear grade. Through linear regression analysis, we predicted recurrence score for each tumor using these four parameters. After categorizing according to the same risk classification as in Oncotype DX (low risk: RS<18, intermediate risk: RS 18-30, or high risk: RS>30) we compared our predicted recurrence score to actual Oncotype DX recurrence score. Results: Overall 69.7% of specimens were assigned the same risk category as with the Oncotype DX level. In the predicted low risk group, 1.7% of patients were actually high risk. None of the predicted high risk patients had a low score. Conclusions: We found a strong correlation between scores estimated using our model and actual reported Recurrence Scores. If validated, our model could provide a clinically useful estimation of risk at lower cost. [Table: see text]

Desenvolvimento de um radioimunoensaio de dexametasona no soro como subsídio para o diagnóstico da síndrome de Cushing

INTRODUÇÃO: O teste de supressão com 1 mg de dexametasona (TSDx) é amplamente empregado no rastreamento da síndrome de Cushing (SC) dada sua elevada acurácia diagnóstica. A SC é um distúrbio endocrinometabólico resultante do hipercortisolismo crônico com característica de ausência de supressão do cortisol no TSDx. OBJETIVO: Desenvolver um radioimunoensaio (RIE) para a dosagem de dexametasona (Dx) no soro para complementar o TSDx. MÉTODOS: Foram imunizados três coelhos com o conjugado dexametasona-21-hemissuccinato-BSA para escolha do melhor anticorpo e o RIE foi desenvolvido de acordo com as recomendações da RE 899/2003 da Agência Nacional de Vigilância Sanitária (ANVISA). Analisamos 96 voluntários, sendo 67 submetidos ao TSDx e 29 não, e 12 pacientes com SC, estudados na Universidade Federal de São Paulo (UNIFESP) e na Santa Casa de Misericórdia de São Paulo. RESULTADOS: O anticorpo contra Dx selecionado mostrou boa especificidade, coeficiente de variação (CV%) intra e interensaio < 20%, exatidão de 93,8% e dose mínima detectada de 19,5 ng/dl. A concentração de Dx no soro foi semelhante nos voluntários e pacientes com SC (ausência/supressão do cortisol): 205 a 703 ng/dl e 174 a 661 ng/dl (intervalo de confiança [IC] 95%), respectivamente; os valores foram indetectáveis naqueles que não se submeteram ao teste. DISCUSSÃO: O anticorpo empregado apresenta boa afinidade e especificidade para quantificar a Dx no soro. O RIE mostrou reprodutibilidade e eficiência na determinação dos níveis séricos de Dx durante o TSDx. CONCLUSÃO: O presente RIE para a dosagem de Dx no soro é acurado e confiável, permitindo estabelecer uma faixa de referência de valores para subsidiar a interpretação do TSDx.

Time-resolved photoluminescence of delta-doped AlGaAs/GaAs heterostructures

The photoluminescence (PL) at low temperature of three delta-doped AlGaAs/GaAs heterostructures is investigated under continuous and pulsed excitations. The PL under continuous excitations allows the identification of the trapping centres and probes the carrier's transfer to the GaAs channel. The time-resolved photoluminescence (TRPL) inquires about carrier dynamics and gives radiative lifetimes of different levels. The DX level shows two time constants of the intensity decay relating the splitting of the valence band under impurity strains which reduce the crystal symmetry. The two time constants evolve with temperature and exhibit an increase near T=50 K.

Determination of Absorption Coefficients and Thermal Diffusivity of Modulated Doped GaAlAs/GaAs Heterostructure by Photothermal Deflection Spectroscopy

We report in this study theoretical and experimental studies of photothermal deflection spectroscopy (PDS) for planar doped heterostructures AlGaAs/GaAs. The PDS spectra at T=300K are recorded by varying the wavelength of the excited radiation for different modulation frequencies. They show two different regions related to the fundamental electronic transitions from GaAs and Si doped AlGaAs. The DX levels have been observed approximately at 0.150 eV below the conduction band edge of Si doped Al0.33Ga0.67As (Eg=1.835 eV at 300 K). We give in this study a method of measuring the absorption coefficient of AlGaAs/GaAs heterostructures from the amplitude measurement of PDS signal. The optical absorption coefficient found was between 10 and 105 cm-1 in the energy range 1-2.5eV for samples. The PDS data are compared with those given by conventional transmission technique. The evolution of PDS amplitude spectra by varying the modulation frequency from 5 to 100 Hz (usually called depth profile analysis) and using He-Ne laser probe beam shows that the PDS signal amplitude increases with decreasing the modulated frequency. A numerical procedure is applied to fit the measured amplitude of the PDS signal. The value of thermal diffusivity (Ds=0. 27cm2s-1) shows a very good agreement with results given by spectroscopic ellipsometry.

Pharmacokinetic interaction with digoxin and glucocorticoids in rats detected by radio-immunoassay using a novel specific antiserum

We previously prepared a more specific antiserum (Antiserum-I) to digoxin (Dx) compared with commercially available anti-Dx antiserum (Antiserum-II), clinically used in the therapeutic drug monitoring of Dx. The aims of this study are to compare Dx disposition kinetics by radio-immunoassay (RIA) using Antiserum-I and Antiserum-II, and evaluate the drug-drug interaction with Dx and glucocorticoids in rats. When Dx metabolites were added to rat serum containing Dx, the recovery ratios using Antiserum-I showed 100 to 110% and were remarkably lower than those using Antiserum-II. In rats, serum concentration-time courses of Dx after a single i.v. or p.o. administration of Dx (0.017 mg/kg) by RIA using Antiserum-I were much lower than those using Antiserum-II. The area under the concentration-time course of Dx was significantly lower than that using Antiserum-II and the total body clearance values were significantly higher, while an obvious change of bioavailability was not observed. When using Antiserum-I, rats twice and six times pretreated with dexamethasone (75 mg/kg/day, i.p.) and prednisolone (69 mg/kg/day, i.p.), respectively, showed significant change of the pharmacokinetic parameters of Dx compared with the control rats. In contrast, using Antiserum-II, it took three and nine times of pretreatment with dexamethasone and prednisolone, respectively, to significantly change the parameters of Dx. In conclusion, these results demonstrate that Antiserum-I is very useful not only to more precisely monitor serum Dx levels, but also to determine earlier the drug-drug interaction with glucocorticoids than Antiserum-II.

Transition of the near-surface δ layer in an Al/δ(Si)-GaAs tunnel structure to the insulating state under pressure

The tunnel and lateral conductivities of an Al/GaAs tunnel structure with a surface Si δ-doped layer are measured at liquid-helium temperatures under a hydrostatic pressure of up to 3 GPa. Transition of the δ layer to the insulating state at a pressure of about 2 GPa is revealed. During this transition, the tunnel resistance increases steadily (on a logarithmic scale) and the zero-bias anomaly in the tunnel resistance exhibits a sharp peak. These results are interpreted in terms of representations of the effect of pressure on the energy-band structure and behavior of DX levels.

Evidence of three DX centers in Al0.28Ga0.72As:Si from Hall experiments

In this article, we report the effect of cooling conditions on transport data in Si-doped AlxGa1−xAs. We show that a rapid cooling induces a freezing out of electrons similar to that observed after photoionization of the sample at low temperatures. By diving the sample in liquid nitrogen, we have evidenced a multicomponent structure with three resolved peaks on transport curves for a relatively low aluminum composition x=0.28. These peaks were assigned to the nonresonant 3 Al–, 2 Al—, and 1 Al–DX levels.

Determination of the occupancy level of the DX center resonant with the conduction band in Te-doped AlGaSb

The analysis of the amplitude of the deep level transient spectroscopy signal due to DX centers is exploited to determine the EDX occupancy level of the DX center in Te-doped AlxGa1−xSb in the range of low values of x where EDX is resonant with the conduction band. We take advantage of a small but still detectable change in the occupancy factor of the DX level induced by the filling pulse. It is shown that EDX is very close to the L conduction band edge for x⩽0.20. This behavior is different from the one at x⩾0.30 where EDX lies in the forbidden energy gap and exhibits an x dependence similar to the X edge. These results are discussed at the light of different atomic configuration for DX centers at an anion-substitutional impurity.

Deep levels in GaAs due to Si δ doping

δ(Si)-doped GaAs samples grown by metalorganic vapor phase epitaxy are studied by capacitance–voltage and deep level transient spectroscopy (DLTS) techniques. A detailed analysis of the DLTS signal (including spatial profiles) is performed. DLTS spectra exhibit a clear development depending on the sheet dopant concentration ranging from 5×1014 to 2×1016 m−2. Two observed peaks do not change its activation energy with the doping level while their amplitude increases rapidly when the doping rises. We assign them to defects generated by high silicon concentration, probably related to gallium vacancy. Another peak in the most densely doped sample seems to correspond to the DX level which is occupied near the δ layer. Peculiar features of the EL2 level are observed in δ-doped GaAs and explained by the band bending due to the dopant sheet. No indication of the emission from the quantum confinement states is found in DLTS spectra taken at temperatures 80–400 K.

DX CENTERS IN AlGaN

In this letter, recent theoretical and experimental investigations of DX centers in Al x Ga 1-x N are reviewed. Due to the technological importance of III–V nitride semiconductors, studies of deep-level defects in AlGaN have attracted a great deal of interest. Oxygen impurities form DX centers in GaN under hydrostatic pressure and in Al x Ga 1-x N alloys. For GaN under pressures greater than 20 GPa, the DX level emerges from the conduction band, leading to a decrease in the free-electron concentration. The localization of free carriers leads to a decrease in the far-infrared absorption and an increase in the LO Raman peak intensity. In Al x Ga 1-x N alloys, Hall effect and persistent photoconductivity measurements indicate that the DX state is energetically favorable for x&gt;0.3. The experimental data for oxygen DX centers are in excellent agreement with first-principles calculations. Experiments have shown that silicon remains a shallow donor up to at least x=0.5 and theory indicates that it may remain shallow up to x=1.

Pharmacokinetic interactions of paclitaxel, docetaxel and their vehicles with doxorubicin

The combination of doxorubicin (Dx) with paclitaxel or docetaxel is clinically effective but there are concerns regarding the higher incidence of cardiotoxicity of the combination compared with Dx alone. The mechanism of the increased toxicity is still unclear. To assess whether there is a pharmacokinetic interaction between paclitaxel, docetaxel or their vehicles and Dx in mice. CDF1 male mice were treated with Dx either alone (10 mg/kg i.v.) or in combination with paclitaxel (25 mg/kg) or docetaxel (25 mg/kg) or their vehicles, i.e., cremophor-ethanol-glucose (cremophor) or polysorbate80-ethanol-glucose (polysorbate). Four mice were killed 4, 8 or 24 hours after Dx in each experimental group and Dx was assayed in serum and in heart, liver, kidney and spleen by HPLC. Four hours after treatment the concentrations of Dx in heart, liver and kidney were much higher in mice concomitantly treated with paclitaxel, docetaxel (dissolved in either cremophor or polysorbate) and cremophor. At subsequent times the differences were modest and only reached statistical significance in a few cases. Dx metabolites were modified by concomitant treatment with taxanes or their vehicles. In particular, the levels of Dx aglycone in liver and kidney were significantly lower in mice treated with the combination than in mice given Dx alone. Paclitaxel, docetaxel and cremophor when given together with Dx modify its distribution and metabolism, increasing Dx levels in many tissues including the heart. This might have some bearing on the toxicity of regimens in which Dx is combined with taxanes.

Occupancy level of the DX center in Te-doped AlxGa1−xSb

Hall effect measurements were performed in Te-doped AlxGa1−xSb layers grown by molecular beam epitaxy to investigate the composition dependence of the DX center occupancy level. The investigated samples have AlSb molar fractions in the 0.25⩽x⩽0.50 range and n-type doping of about 1018 cm−3. A family of x≈0.40 samples of different doping (5×1015–1018 cm−3) were also studied. The Hall electron density data versus temperature were analyzed at high temperatures (T⩾150 K) where the DX center is at equilibrium, by assuming the negative-U model for the DX level and by taking into account the multivalley conduction effects. The DX level, degenerate in energy with the conduction band at low x values, enters the forbidden gap at x≈0.25 and then it becomes deeper with increasing x. In lightly doped samples, the introduction of a second level of the same Te impurity is required to fit the data; such level can be identified with the nonmetastable level which controls the low temperature electrical properties of the material. A critical discussion on the choice of the conduction band parameters for the fitting is reported.

The DX Center in GaAsP Alloys

Using Deep Level Transient Spectroscopy (DLTS), we have investigated the properties of the DX center in GaAsP for the whole range of alloy composition x. We have determined the variation of the defect characteristics (thermal ionization energy E i , barrier for electron capture B, and energy level location E DX ) versus x. From the relationship that exists between E i , B and E DX , and between B and Δ, the energy difference between the L band and the bottom of the conduction band, we deduce that electron emission and capture occur from and to the DX center via the L band in the same fashion as in GaAlAs alloys. A good fit of the variation of E i and B versus x is obtained in a model where the DX level is a donor state associated with the L band which is 200 meV deep, like in GaAlAs, as a result of intervalley mixing.

Hydrostatic pressure studies of GaAs tunnel diodes

GaAs (doped with Zn and Sn in the p and n parts, respectively) tunnel diode I–V characteristics were studied under hydrostatic pressure. The decrease in peak and valley current was explained using the band-gap pressure dependence and the fact that the Fermi energy is pinned by the DX level at normal pressure for heavy Sn doping. These findings are verified by calculating theoretical normalized peak and valley currents, which substantially agree with the experimental results.

Metastability of Oxygen Donors in AlGaN

Experimental and theoretical evidence is presented for the metastability of oxygen donors in AlxGa12xN. As the aluminum content increases, Hall effect measurements reveal an increase in the electron activation energy, consistent with the emergence of a deep DX level from the conduction band. Persistent photoconductivity is observed in Al0.39Ga0.61N:O at temperatures below 150 K after exposure to light, with an optical threshold energy of 1.3 eV. A configuration coordinate diagram is obtained from first-principles calculations and yields values for the capture barrier, emission barrier, and optical threshold which are in good agreement with the experimental results. [S0031-9007(98)05950-X]

Evidence for Oxygen DX Centers in AlGaN

ABSTRACTExperimental and theoretical evidence is presented for oxygen DX centers in AlxGa1−xN. As the aluminum content increases, Hall effect measurements reveal an increase in the electron activation energy, consistent with the emergence of a deep DX level from the conduction band. Persistent photoconductivity is observed in Al0 39Ga0. 61N:O at temperatures below 150 K after exposure to light, with an optical threshold energy of 1.3 eV, in excellent agreement with first-principles calculations. Unlike oxygen, silicon does not exhibit DX-like behavior, in agreement with previous theoretical predictions.

Electrical properties of silicon and beryllium doped (AlyGa1−y)0.52In0.48P

The electrical properties of silicon and beryllium doped (AlyGa1−y)0.52In0.48P grown by gas source molecular beam epitaxy were studied. Unintentionally doped (GaIn)P has a n-type background concentration of 5.1×1014 cm−3 and a free-carrier mobility of ∼3500 cm2/V s at room temperature. Hall measurements of n-(GaIn)P give a linear increase in the free-carrier concentration for values up to 4.0×1018 cm−3. Silicon doping of (GaIn)P and (Al0.7Ga0.3)0.52In0.48P reveals a linear increase in the impurity carrier concentration for values up to 8.0×1018 cm−3 by capacitance–voltage measurements. In contrast, the free electron concentration saturates at a value of 4.8×1017 cm−3 in (Al0.7Ga0.3)0.52In0.48P, due to Fermi-level pinning at the DX level. Beryllium doping of (GaIn)P reveals a linear increase in the Hall free-hole concentration for values up to 1.4×1019 cm−3 with a room-temperature mobility of ∼34 cm2/V s.

Detailed electrical characterization of DX centers in Se-doped AlxGa1−xAs

DX centers in selenium doped AlxGa1−xAs with two values of the aluminum content, x=0.34 and 0.48, are carefully analyzed by three different techniques: deep level transient spectroscopy (DLTS), admittance spectroscopy, and the capacitance voltage transient technique (CVTT). We use conceptual differences between these techniques to extract important information about the nature of the DX centers. Good agreement is found between the capacitance transients recorded during the DLTS measurements and those obtained by CVTT at every point in the space charge region. From that, we conclude that is the very nature of the DX centers the solely responsible for the anomalies found in DLTS results. The main cause for these anomalies is the thermal dependence of the electron capture rate of these centers. CVTT curves also reveal that no electric field enhanced emission processes take place for these centers. For our analysis of the shape of the DLTS and admittance spectroscopy curves we conclude that several DX levels exist, according to the alloy broadening theory. Finally, some simulations of the DLTS spectra were made. These calculations reveal the important effect of experimental parameters such as the filling pulse duration, the velocity of the temperature scan, and the initial conditions of the occupation factor of the deep levels on the DLTS curves.