An NTCP Analysis of Urethral Complications from Low Doserate Mono- and Bi-Radionuclide Brachytherapy.

PubMed

Nuttens, V E; Nahum, A E; Lucas, S

2011-01-01

Urethral NTCP has been determined for three prostates implanted with seeds based on (125)I (145 Gy), (103)Pd (125 Gy), (131)Cs (115 Gy), (103)Pd-(125)I (145 Gy), or (103)Pd-(131)Cs (115 Gy or 130 Gy). First, DU(20), meaning that 20% of the urhral volume receive a dose of at least DU(20), is converted into an I-125 LDR equivalent DU(20) in order to use the urethral NTCP model. Second, the propagation of uncertainties through the steps in the NTCP calculation was assessed in order to identify the parameters responsible for large data uncertainties. Two sets of radiobiological parameters were studied. The NTCP results all fall in the 19%-23% range and are associated with large uncertainties, making the comparison difficult. Depending on the dataset chosen, the ranking of NTCP values among the six seed implants studied changes. Moreover, the large uncertainties on the fitting parameters of the urethral NTCP model result in large uncertainty on the NTCP value. In conclusion, the use of NTCP model for permanent brachytherapy is feasible but it is essential that the uncertainties on the parameters in the model be reduced.

Early detection of probable idiopathic Parkinson's disease: I. development of a diagnostic test battery.

PubMed

Montgomery, Erwin B; Koller, William C; LaMantia, Theodora J K; Newman, Mary C; Swanson-Hyland, Elizabeth; Kaszniak, Alfred W; Lyons, Kelly

2000-05-01

We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87. Copyright © 2000 Movement Disorder Society.

Excitation Functions of Helion-Induced Nuclear Reactions for the Production of the Medical Radioisotope 103Pd

NASA Astrophysics Data System (ADS)

Skakun, Ye.; Qaim, S. M.

2005-05-01

Excitation functions were measured by the stacked-foil technique for the reactions 100Ru(α,n)103Pd, 101Ru(α,2n)103Pd, 101Ru(3He,n)103Pd, and 102Ru(3He,2n)103Pd for incident energies up to 25 and 34 MeV for α-particles and 3He ions, respectively. The integral thick target yields of the product radionuclide 103Pd calculated from the excitation functions of the above-named four reactions amount to 960, 1050, 50, and 725 KBq/μAh, respectively, at the maximum energy of the incident particle. The data are compared with the results of statistical model calculations and other charged particle induced reaction investigations.

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

NASA Astrophysics Data System (ADS)

Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

2003-09-01

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

Brachytherapy dosimetry of 125I and 103Pd sources using an updated cross section library for the MCNP Monte Carlo transport code.

PubMed

Bohm, Tim D; DeLuca, Paul M; DeWerd, Larry A

2003-04-01

Permanent implantation of low energy (20-40 keV) photon emitting radioactive seeds to treat prostate cancer is an important treatment option for patients. In order to produce accurate implant brachytherapy treatment plans, the dosimetry of a single source must be well characterized. Monte Carlo based transport calculations can be used for source characterization, but must have up to date cross section libraries to produce accurate dosimetry results. This work benchmarks the MCNP code and its photon cross section library for low energy photon brachytherapy applications. In particular, we calculate the emitted photon spectrum, air kerma, depth dose in water, and radial dose function for both 125I and 103Pd based seeds and compare to other published results. Our results show that MCNP's cross section library differs from recent data primarily in the photoelectric cross section for low energies and low atomic number materials. In water, differences as large as 10% in the photoelectric cross section and 6% in the total cross section occur at 125I and 103Pd photon energies. This leads to differences in the dose rate constant of 3% and 5%, and differences as large as 18% and 20% in the radial dose function for the 125I and 103Pd based seeds, respectively. Using a partially updated photon library, calculations of the dose rate constant and radial dose function agree with other published results. Further, the use of the updated photon library allows us to verify air kerma and depth dose in water calculations performed using MCNP's perturbation feature to simulate updated cross sections. We conclude that in order to most effectively use MCNP for low energy photon brachytherapy applications, we must update its cross section library. Following this update, the MCNP code system will be a very effective tool for low energy photon brachytherapy dosimetry applications.

Single-Crystal Bismuth Iodide Gamma-Ray Spectrometers

DTIC Science & Technology

2012-02-01

the density of the crystal (g/cm\\ M is the molecular weight of the vapor (g/mole), and R is the gas constant (cai/(K·mole)). Equation (6) indicates...along the vertical axis with a fixed rate. This simulated the downward movement of the ampoule in the conventional vertical Bridgman method. The...3cl512 1.03 4512 4.6 961 Pd Pd3d 336.5 Pd 3d512 1.03 6796 4.6 1477 Pdb N3d 340.3 Pd 3d3J2 1.03 2978 4.6 647 Pd Pd3d 341.7 Pd 3d3J2 1.03 4486 4.6 975

Prostate implant nomograms for the North American scientific {sup 103}Pd seed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jay J.; Stevens, Ritchie N

Palladium-103-({sup 103}Pd) seed has been increasingly used in prostate implantation as either definitive or boost therapy because of its shorter half-life and higher initial dose rate. Because a growing number of radiation oncologists prefer real-time implantation in the operating room, it will be helpful if the total activity of the seeds can be determined based on the gland size before the patient is taken to the operating room. Based on our clinic data, nomograms have therefore been developed for one of the widely used {sup 103}Pd seeds, the MED3633 seed, which is produced by North American Scientific, Inc. (NASI). Themore » total activities for implant volume ranging from 15 cc to 55 cc are provided for both seed 'monotherapy' and seed boost.« less

On determining dose rate constants spectroscopically.

PubMed

Rodriguez, M; Rogers, D W O

2013-01-01

To investigate several aspects of the Chen and Nath spectroscopic method of determining the dose rate constants of (125)I and (103)Pd seeds [Z. Chen and R. Nath, Phys. Med. Biol. 55, 6089-6104 (2010)] including the accuracy of using a line or dual-point source approximation as done in their method, and the accuracy of ignoring the effects of the scattered photons in the spectra. Additionally, the authors investigate the accuracy of the literature's many different spectra for bare, i.e., unencapsulated (125)I and (103)Pd sources. Spectra generated by 14 (125)I and 6 (103)Pd seeds were calculated in vacuo at 10 cm from the source in a 2.7 × 2.7 × 0.05 cm(3) voxel using the EGSnrc BrachyDose Monte Carlo code. Calculated spectra used the initial photon spectra recommended by AAPM's TG-43U1 and NCRP (National Council of Radiation Protection and Measurements) Report 58 for the (125)I seeds, or TG-43U1 and NNDC(2000) (National Nuclear Data Center, 2000) for (103)Pd seeds. The emitted spectra were treated as coming from a line or dual-point source in a Monte Carlo simulation to calculate the dose rate constant. The TG-43U1 definition of the dose rate constant was used. These calculations were performed using the full spectrum including scattered photons or using only the main peaks in the spectrum as done experimentally. Statistical uncertainties on the air kerma/history and the dose rate/history were ≤0.2%. The dose rate constants were also calculated using Monte Carlo simulations of the full seed model. The ratio of the intensity of the 31 keV line relative to that of the main peak in (125)I spectra is, on average, 6.8% higher when calculated with the NCRP Report 58 initial spectrum vs that calculated with TG-43U1 initial spectrum. The (103)Pd spectra exhibit an average 6.2% decrease in the 22.9 keV line relative to the main peak when calculated with the TG-43U1 rather than the NNDC(2000) initial spectrum. The measured values from three different investigations are in much better agreement with the calculations using the NCRP Report 58 and NNDC(2000) initial spectra with average discrepancies of 0.9% and 1.7% for the (125)I and (103)Pd seeds, respectively. However, there are no differences in the calculated TG-43U1 brachytherapy parameters using either initial spectrum in both cases. Similarly, there were no differences outside the statistical uncertainties of 0.1% or 0.2%, in the average energy, air kerma/history, dose rate/history, and dose rate constant when calculated using either the full photon spectrum or the main-peaks-only spectrum. Our calculated dose rate constants based on using the calculated on-axis spectrum and a line or dual-point source model are in excellent agreement (0.5% on average) with the values of Chen and Nath, verifying the accuracy of their more approximate method of going from the spectrum to the dose rate constant. However, the dose rate constants based on full seed models differ by between +4.6% and -1.5% from those based on the line or dual-point source approximations. These results suggest that the main value of spectroscopic measurements is to verify full Monte Carlo models of the seeds by comparison to the calculated spectra.

SU-F-T-44: A Comparison of the Pre-Plan, Intra-Operative Plan, and Post-Implant Dosimetry for a Prostate Implant Case Using Prefabricated Linear Polymer-Encapsulated Pd-103

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheu, R; Powers, A; McGee, H

Purpose: To investigate the reproducibility and limitations of Pd-103 prostate brachytherapy using fixed length linear sources (CivaString). Methods: An LDR prostate brachytherapy case which was preplanned on MR images with prefabricated linear polymer-encapsulated Pd-103 sources (CivaString) was studied and compared with ultrasound based intra-operative planning and CT based post-implant dosimetry. We evaluated the following parameters among the three studies: prostate geometry (volume and cross sectional area), needle position and alignment deviations, and dosimetry parameters (D90). Results: The prostate volumes and axial cross sectional areas at center of prostate were measured as 41.8, 39.3 and 36.8 cc, and 14.9, 14.3, andmore » 11.3 respectively on pre-plan MR, inter-op US, and post-implant CT studies. The deviation of prostate volumes and axial cross sectional areas measured on pre-planning MR and intra-operative US were within 5%. 17 out of 19 pre-planned needles were positioned within 5mm (the template grid size). One needle location was adjusted intra-operatively and another needle was removed due to proximity to urethra. The needle pathways were not always parallel to the trans-rectal probe due to the flexibility of CivaString. The angle of deviation was up to 10 degrees. Two pairs of needles were exchanged to better fit the length of prostate at the time of implant. This resulted in a prostate D90 of 153.8 Gy (124%) and 131.4 Gy (106.7%) for intra-op and PID respectively. Conclusion: Preplanning is a necessary part of implants performed with prefabricated linear polymer sources. However, as is often the case, there were real-time deviations from the pre-plan. Intra-op planning provides the ability conform to anatomy at the time of implant. Therefore, we propose to develop a systematic way to order extra strings of different length to provide the flexibility to perform intra-operative planning with fixed length strands.« less

Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

PubMed Central

Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-01-01

Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer. PMID:21772076

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

NASA Astrophysics Data System (ADS)

(Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-08-01

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the α/β ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer.

SU-F-19A-05: Experimental and Monte Carlo Characterization of the 1 Cm CivaString 103Pd Brachytherapy Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, J; Micka, J; Culberson, W

Purpose: To determine the in-air azimuthal anisotropy and in-water dose distribution for the 1 cm length of the CivaString {sup 103}Pd brachytherapy source through measurements and Monte Carlo (MC) simulations. American Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry parameters were also determined for this source. Methods: The in-air azimuthal anisotropy of the source was measured with a NaI scintillation detector and simulated with the MCNP5 radiation transport code. Measured and simulated results were normalized to their respective mean values and compared. The TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function for this sourcemore » were determined from LiF:Mg,Ti thermoluminescent dosimeter (TLD) measurements and MC simulations. The impact of {sup 103}Pd well-loading variability on the in-water dose distribution was investigated using MC simulations by comparing the dose distribution for a source model with four wells of equal strength to that for a source model with strengths increased by 1% for two of the four wells. Results: NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy showed that ≥95% of the normalized data were within 1.2% of the mean value. TLD measurements and MC simulations of the TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function agreed to within the experimental TLD uncertainties (k=2). MC simulations showed that a 1% variability in {sup 103}Pd well-loading resulted in changes of <0.1%, <0.1%, and <0.3% in the TG-43 dose-rate constant, radial dose distribution, and polar dose distribution, respectively. Conclusion: The CivaString source has a high degree of azimuthal symmetry as indicated by the NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy. TG-43 dosimetry parameters for this source were determined from TLD measurements and MC simulations. {sup 103}Pd well-loading variability results in minimal variations in the in-water dose distribution according to MC simulations. This work was partially supported by CivaTech Oncology, Inc. through an educational grant for Joshua Reed, John Micka, Wesley Culberson, and Larry DeWerd and through research support for Mark Rivard.« less

CD103+CD8+ T lymphocytes in non-small cell lung cancer are phenotypically and functionally primed to respond to PD-1 blockade.

PubMed

Wang, Peiliang; Huang, Bing; Gao, Yi; Yang, Jianjian; Liang, Zhihui; Zhang, Ni; Fu, Xiangning; Li, Lequn

2018-03-01

CD103 + CD8 + tumor infiltrating lymphocytes (TILs) have been linked to prolonged survival in various types of cancer including non-small cell lung cancer (NSCLC). However, the factors associated with the retention of CD103 + CD8 + TILs in lung cancer tissues remain largely unknown. Additionally, the contribution of CD103 + CD8 + TILs to effective PD-1 based immunotherapy has not been fully elucidated. In this study, we identified that the expression levels of E-cadherin and TGF-β were significantly correlated with the distribution and the density of CD103 + TILs in lung cancer tumor tissues. Unexpectedly, we observed that CD103 + CD8 + TILs that expressed higher levels of PD-1 co-express Ki-67. Moreover, CD103 + CD8 + TILs expressed an increased level of T-bet compared to their counterparts, indicating these cells may be better armed for immunotherapy. Lastly, PD-1 pathway blockade led to a significantly increased production of IFN-γ by CD103 + CD8 + TILs, suggesting CD103 + CD8 + TILs could serve as a predictive biomarker for PD-1 based immunotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

SU-F-19A-06: Experimental Investigation of the Energy Dependence of TLD Sensitivity in Low-Energy Photon Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Z; Nath, R

Purpose: To measure the energy dependence of TLD sensitivity in lowenergy photon beams with equivalent mono-energetic energy matching those of 103Pd, 125I and 131Cs brachytherapy sources. Methods: A Pantek DXT 300 x-ray unit (Precision X-ray, Branford, CT), with stable digital voltage control down to 20 kV, was used to establish three lowenergy photon beams with narrow energy spread and equivalent monoenergetic energies matching those of 103Pd, 125I and 131Cs brachytherapy sources. The low-energy x-ray beams and a reference 6 MV photon beam were calibrated according to the AAPM TG-61 and TG-51 protocols, respectively, using a parallel-plate low-energy chamber and amore » Farmer cylindrical chamber with NIST traceable calibration factors. The dose response of model TLD-100 micro-cubes (1×1×1 mm{sup 3}) in each beam was measured for five different batches of TLDs (each contained approximately 100 TLDs) that have different histories of irradiation and usage. Relative absorbed dose sensitivity was determined as the quotient of the slope of dose response for a beam-of-interest to that of the reference beam. Results: Equivalent mono-energetic photon energies of the low-energy beams established for 103Pd, 125I and 131Cs sources were 20.5, 27.5, and 30.1 keV, respectively. Each beam exhibited narrow spectral spread with energyhomogeneity index close to 90%. The relative absorbed-dose sensitivity was found to vary between different batches of TLD with maximum differences of up to 8%. The mean and standard deviation determined from the five TLD batches was 1.453 ± 0.026, 1.541 ± 0.035 and 1.529 ± 0.051 for the simulated 103P, 125I and 131Cs beams, respectively. Conclusion: Our measured relative absorbed-dose sensitivities are greater than the historically measured value of 1.41. We find that the relative absorbed-dose sensitivity of TLD in the 103P beam is approximately 5% lower than that of 125I and 131Cs beams. Comparison of our results with other studies will be presented.« less

1-[2-(4-Benzyloxyphenoxy)Ethyl]Imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent models of Parkinson's disease.

PubMed

Chung, Jin Yong; Lee, Ji Won; Ryu, Choon Ho; Min, Hye Kyung; Yoon, Yeo Jin; Lim, Mi Jung; Park, Cheol Hyoung

2015-08-01

Monoamine oxidase B (MAO-B) is well known as a therapeutic target for Parkinson's disease (PD). MAO-B inhibitors retain antiparkinsonism abilities to improve motor function and prevent neuronal loss by decreasing dopamine metabolism and oxidative stress in the brain. From the study to find novel antiparkinsonism drugs that can inhibit MAO-B activity, neuronal loss, and behavioral deficits in the mouse model of PD, we identified that 1-[2-(4-benzyloxyphenoxy)ethyl]imidazole (BPEI) or safinamide strongly and selectively inhibited MAO-B activities in a dose-dependent manner (IC50 of BPEI and safinamide for MAO-B were 0.016 and 0.0021 µM and for MAO-A were 70.0 and 370 µM, respectively). In ex vivo studies after an administration (30 mg/kg, i.p.) of BPEI or safinamide to normal mice, the MAO-B activity in the brain was reduced by up to 90.6% or 82.4% at 1.0 hr. BPEI (20 mg/kg, i.p.) or safinamide (20 mg/kg, i.p.) significantly reversed the behavioral impairments, dopamine levels in the striatum, and neuronal loss in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared with the MPTP-alone-treated group. In the 6-hydroxydopamine-induced PD rat model, behavioral improvement by levodopa sparing activity was observed in the BPEI- or safinamide-treated (20 mg/kg, i.p.) rats. Moreover, BPEI revealed additional curative activities for nonmotor symptoms of PD such as pain, anxiety, epilepsy, and depression in rodent disease models. Therefore, BPEI has broad therapeutic potential for treating motor symptoms via strong and selective inhibitory effects on MAO-B, with additional benefits for comorbid symptoms in PD. © 2015 Wiley Periodicals, Inc.

On determining dose rate constants spectroscopically

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez, M.; Rogers, D. W. O.

2013-01-15

Purpose: To investigate several aspects of the Chen and Nath spectroscopic method of determining the dose rate constants of {sup 125}I and {sup 103}Pd seeds [Z. Chen and R. Nath, Phys. Med. Biol. 55, 6089-6104 (2010)] including the accuracy of using a line or dual-point source approximation as done in their method, and the accuracy of ignoring the effects of the scattered photons in the spectra. Additionally, the authors investigate the accuracy of the literature's many different spectra for bare, i.e., unencapsulated {sup 125}I and {sup 103}Pd sources. Methods: Spectra generated by 14 {sup 125}I and 6 {sup 103}Pd seedsmore » were calculated in vacuo at 10 cm from the source in a 2.7 Multiplication-Sign 2.7 Multiplication-Sign 0.05 cm{sup 3} voxel using the EGSnrc BrachyDose Monte Carlo code. Calculated spectra used the initial photon spectra recommended by AAPM's TG-43U1 and NCRP (National Council of Radiation Protection and Measurements) Report 58 for the {sup 125}I seeds, or TG-43U1 and NNDC(2000) (National Nuclear Data Center, 2000) for {sup 103}Pd seeds. The emitted spectra were treated as coming from a line or dual-point source in a Monte Carlo simulation to calculate the dose rate constant. The TG-43U1 definition of the dose rate constant was used. These calculations were performed using the full spectrum including scattered photons or using only the main peaks in the spectrum as done experimentally. Statistical uncertainties on the air kerma/history and the dose rate/history were Less-Than-Or-Slanted-Equal-To 0.2%. The dose rate constants were also calculated using Monte Carlo simulations of the full seed model. Results: The ratio of the intensity of the 31 keV line relative to that of the main peak in {sup 125}I spectra is, on average, 6.8% higher when calculated with the NCRP Report 58 initial spectrum vs that calculated with TG-43U1 initial spectrum. The {sup 103}Pd spectra exhibit an average 6.2% decrease in the 22.9 keV line relative to the main peak when calculated with the TG-43U1 rather than the NNDC(2000) initial spectrum. The measured values from three different investigations are in much better agreement with the calculations using the NCRP Report 58 and NNDC(2000) initial spectra with average discrepancies of 0.9% and 1.7% for the {sup 125}I and {sup 103}Pd seeds, respectively. However, there are no differences in the calculated TG-43U1 brachytherapy parameters using either initial spectrum in both cases. Similarly, there were no differences outside the statistical uncertainties of 0.1% or 0.2%, in the average energy, air kerma/history, dose rate/history, and dose rate constant when calculated using either the full photon spectrum or the main-peaks-only spectrum. Conclusions: Our calculated dose rate constants based on using the calculated on-axis spectrum and a line or dual-point source model are in excellent agreement (0.5% on average) with the values of Chen and Nath, verifying the accuracy of their more approximate method of going from the spectrum to the dose rate constant. However, the dose rate constants based on full seed models differ by between +4.6% and -1.5% from those based on the line or dual-point source approximations. These results suggest that the main value of spectroscopic measurements is to verify full Monte Carlo models of the seeds by comparison to the calculated spectra.« less

An Introduction to Structural Reliability Theory

DTIC Science & Technology

1989-01-01

Test Samples psi COV Distribution Remarks Yield stress 66 (XX 0.09 assumed lognormal mill test I containment vesel SA537 GrB Yield stress 󈧗 6W8...straightened shape Tension :32 57.909 0.089 cold straightened shape Tension 9 84.039 0.1124 annealed , alloy steel Tension 9 124,9 0.1796 . quenched...alloys, annealed and quenched, and drawn samples Tension 22 29.50 X 103 0.0072 .. structural steel Compression 22 29.49 X 103 0.0146 ... structural

Measurement of excitation functions of helion-induced reactions on enriched Ru targets for production of medically important 103Pd and 101mRh and some other radionuclides.

PubMed

Skakun, Ye; Qaim, S M

2008-05-01

Excitation functions were determined by the stacked-foil and induced radioactivity measurement technique for the reactions (100)Ru(alpha,n)(103)Pd, (101)Ru(alpha,2n)(103)Pd, (101)Ru((3)He,n)(103)Pd, and (102)Ru((3)He,2n)(103)Pd, producing the therapeutic radionuclide (103)Pd, and for the reactions (101)Ru((3)He,x)(101 m)Rh(Cum) and (102)Ru((3)He,x)(101 m)Rh(Cum), producing the medically interesting radionuclide (101 m)Rh. Data were also measured for the reactions (101)Ru((3)He,pn+d)(102 m,g)Rh, (102)Ru((3)He,p2n+dn+t)(102 m,g)Rh, (101)Ru((3)He,x)(101 g)Rh(Cum), (102)Ru((3)He,x)(101 g)Rh(Cum), (101)Ru((3)He,3n)(101)Pd, (102)Ru((3)He,4n)(101)Pd, (101)Ru((3)He,4n)(100)Pd, and (101)Ru((3)He,p3n+d2n+tn)(100)Rh, producing other palladium and rhodium isotopes/isomers. The energy ranges covered were up to 25 MeV for alpha-particles and up to 34 MeV for (3)He ions. The radioactivity of the radionuclide (103)Pd induced in thin metallic foils of the enriched ruthenium isotopes was measured by high-resolution X-ray spectrometry and the radioactivities of other radionuclides by gamma-ray spectrometry. The integral thick target yields of the radionuclide (103)Pd calculated from the excitation functions of the first four of the above-named reactions amount to 960, 1050, 50, and 725 kBq/microAh, respectively, at the maximum investigated energies of the incident particles. The integral thick target yields of the radionuclide (101 m)Rh amount to 16.1 and 2.9 MBq/microAh for (101)Ru and (102)Ru targets, respectively, at 34 MeV energy of incident (3)He ions. The integral yields of the other observed radionuclides were also deduced from the excitation functions of the above-mentioned respective nuclear reactions. The excitation functions and integral yields of some rare reaction products were also determined. The experimental excitation functions of some reactions are compared with the predictions of nuclear model calculations. In general, good agreement was obtained.

Comparison of TG-43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes.

PubMed

Zaker, Neda; Zehtabian, Mehdi; Sina, Sedigheh; Koontz, Craig; Meigooni, Ali S

2016-03-08

Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross-sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross-sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in 125I and 103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code - MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low-energy sources such as 125I and 103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for 103Pd and 10 cm for 125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for 192Ir and less than 1.2% for 137Cs between the three codes.

α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease.

PubMed

Kang, Seong Su; Ahn, Eun Hee; Zhang, Zhentao; Liu, Xia; Manfredsson, Fredric P; Sandoval, Ivette M; Dhakal, Susov; Iuvone, P Michael; Cao, Xuebing; Ye, Keqiang

2018-06-15

Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration. Interestingly, the dopamine metabolite, DOPAL, strongly activates AEP, and the N103 fragment of α-Syn binds and activates MAO-B. Accordingly, overexpression of AEP in SNCA transgenic mice elicits α-Syn N103 cleavage and accelerates PD pathogenesis, and inhibition of MAO-B by Rasagiline diminishes α-Syn-mediated PD pathology and motor dysfunction. Moreover, virally mediated expression of α-Syn N103 induces PD pathogenesis in wild-type, but not MAO-B-null mice. Our findings thus support that AEP-mediated cleavage of α-Syn at N103 is required for the association and activation of MAO-B, mediating PD pathogenesis. © 2018 The Authors.

A Physical Model of Human Skin and Its Application for Search and Rescue

DTIC Science & Technology

2009-12-01

allow iv for the development of skin detection algorithms with a high probability of detection (PD) and a low probability of false alarm ( PFA ). The...various skin colors were collected. The skin detection algorithm developed in this work had a PD as high as 0.95 with a PFA of 0.006. Skin...threshold 0 < γ < 1. . . . . . . . . . . . . 103 63. Top: Detection Image with NDSI threshold γ = 0.314 with PD = 0.95 and corresponding PFA = 0.0156

MO-FG-BRA-03: A Monte-Carlo Study of Cellular Dosimetry of Radioactive Gold-Palladium Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Y; Michaud, F; Fortin, M

Purpose: Radioactive gold-palladium nanoparticles ({sup 103}Pd:Pd@Au NPs) are being developed for prostate cancer brachytherapy. Photons emitted by the radioisotope palladium (photon energy: 20.1 and 23.0 keV), interacting with gold-coating of NPs, lead to enhanced energy distribution in nucleus. Here, a simple cellular model was studied using detailed track-structure method. Methods: Geant4-DNA was used with auger electrons enabled. Biological cell was modeled as a sphere of radius r=5 µm that were immersed in a fluid containing large number of NPs at different concentrations (S=1, 2.15, 5.1, 17.2 mg-Au/g-H2O). Nucleus was modeled as a concentric sphere (r=3µm). Thickness of gold-coating on {supmore » 103}Pd core was 15nm, 20nm and 25nm, respectively. A scenario of NP diffusion was investigated, where S=5.1 mg-Au/g-H2O outside cell and S=1 mg-Au/g-H2O in cytoplasm. 10{sup 10} {sup 103}Pd decays were simulated for each combination of NP concentration and gold-coating. Results: A uniform increase in energy deposition (Edep) is observed in cell nucleus and the energy enhancement ratio (EER) is 1.16, 1.22 and 1.3 for 15nm, 20nm and 25nm of gold -coatings, respectively. Edep at the center of nucleus is increased by a factor of 1.47, 2.51 and 5.54 when the NP concentration in the cytoplasm increases from 1 mg-Au/g-H2O to 2.15, 5.10 and 17.2 mg-Au/g-H2O, respectively. When NPs diffuse into cytoplasm, the mean value of Edep in nucleus increases from 0.42 to 1.13 MeV per 10{sup 9} decays (GBq-Second) of {sup 103}Pd and the maximum value increases from 0.54 to 2.5 MeV per GBq-Second. Conclusion: These results suggest that {sup 103}Pd:Pd@Au NPs constitute a promising nanotherapeutic agent. Ongoing studies use transmission electron microscopy (TEM) images of prostate cancer.« less

Simulating Rule-Based Systems

DTIC Science & Technology

1988-12-01

the number of facts. NFIRE : location of the rule status flag. NLVL: the number of levels. NRULE: the number of rules. 116 NRUN: the number of runs. PD...C-INITIALIZE THE RULE MATRIX 124 C NFIRE -4 +MAXL+MAXR NFAC-0 IL-MAXL-MINL+l IR-MAXR-MINR+ 1 DO 10 I-1,NRULE MR(I,1)=I NR( I, 2)-MINL+INT(RAN( II) *IL...NR( I, 3)-MINR+INT(RAN(II)*IR) NR( I, NFIRE )-0 10 CONTINUE-A C C-STORE THE RANDOM-ASSERTION SET IN A MATRIX C READ(8,* )NRUN, lASS DO 120 I-1,NRTJN

Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd, 125I, 192Ir, 137Cs, and 60Co.

PubMed

Villegas, Fernanda; Tilly, Nina; Bäckström, Gloria; Ahnesjö, Anders

2014-09-21

Analysing the pattern of energy depositions may help elucidate differences in the severity of radiation-induced DNA strand breakage for different radiation qualities. It is often claimed that energy deposition (ED) sites from photon radiation form a uniform random pattern, but there is indication of differences in RBE values among different photon sources used in brachytherapy. The aim of this work is to analyse the spatial patterns of EDs from 103Pd, 125I, 192Ir, 137Cs sources commonly used in brachytherapy and a 60Co source as a reference radiation. The results suggest that there is both a non-uniform and a uniform random component to the frequency distribution of distances to the nearest neighbour ED. The closest neighbouring EDs show high spatial correlation for all investigated radiation qualities, whilst the uniform random component dominates for neighbours with longer distances for the three higher mean photon energy sources (192Ir, 137Cs, and 60Co). The two lower energy photon emitters (103Pd and 125I) present a very small uniform random component. The ratio of frequencies of clusters with respect to 60Co differs up to 15% for the lower energy sources and less than 2% for the higher energy sources when the maximum distance between each pair of EDs is 2 nm. At distances relevant to DNA damage, cluster patterns can be differentiated between the lower and higher energy sources. This may be part of the explanation to the reported difference in RBE values with initial DSB yields as an endpoint for these brachytherapy sources.

Comparison of TG‐43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes

PubMed Central

Zaker, Neda; Sina, Sedigheh; Koontz, Craig; Meigooni1, Ali S.

2016-01-01

Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross‐sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross‐sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in  125I and  103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code — MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low‐energy sources such as  125I and  103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for  103Pd and 10 cm for  125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for  192Ir and less than 1.2% for  137Cs between the three codes. PACS number(s): 87.56.bg PMID:27074460

Modified COMS Plaques for {sup 125}I and {sup 103}Pd Iris Melanoma Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomson, Rowan M., E-mail: rthomson@physics.carleton.c; Furutani, Keith M.; Pulido, Jose S.

2010-11-15

Purpose: Novel plaques are used to treat iris melanoma at the Mayo Clinic Rochester. The plaques are a modification of the Collaborative Ocular Melanoma Study (COMS) 22 mm plaque design with a gold alloy backing, outer lip, and silicone polymer insert. An inner lip surrounds a 10 mm diameter cutout region at the plaque center. Plaques span 360{sup o}, 270{sup o}, and 180{sup o} arcs. This article describes dosimetry for these plaques and others used in the treatment of anterior eye melanomas. Methods and Materials: The EGSnrc user-code BrachyDose is used to perform Monte Carlo simulations. Plaques and seeds aremore » fully modeled. Three-dimensional dose distributions for different plaque models, TG-43 calculations, and {sup 125}I (model 6711) and {sup 103}Pd (model 200) seeds are compared via depth-dose curves, tabulation of doses at points of interest, and isodose contours. Results: Doses at points of interest differ by up to 70% from TG-43 calculations. The inner lip reduces corneal doses. Matching plaque arc length to tumor extent reduces doses to eye regions outside the treatment area. Maintaining the same prescription dose, {sup 103}Pd offers lower doses to critical structures than {sup 125}I, with the exception of the sclera adjacent to the plaque. Conclusion: The Mayo Clinic plaques offer several advantages for anterior eye tumor treatments. Doses to regions outside the treatment area are significantly reduced. Doses differ considerably from TG-43 predictions, illustrating the importance of complete Monte Carlo simulations. Calculations take a few minutes on a single CPU, making BrachyDose sufficiently fast for routine clinical treatment planning.« less

Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd, 125I, 192Ir, 137Cs, and 60Co

NASA Astrophysics Data System (ADS)

Villegas, Fernanda; Tilly, Nina; Bäckström, Gloria; Ahnesjö, Anders

2014-09-01

Analysing the pattern of energy depositions may help elucidate differences in the severity of radiation-induced DNA strand breakage for different radiation qualities. It is often claimed that energy deposition (ED) sites from photon radiation form a uniform random pattern, but there is indication of differences in RBE values among different photon sources used in brachytherapy. The aim of this work is to analyse the spatial patterns of EDs from 103Pd, 125I, 192Ir, 137Cs sources commonly used in brachytherapy and a 60Co source as a reference radiation. The results suggest that there is both a non-uniform and a uniform random component to the frequency distribution of distances to the nearest neighbour ED. The closest neighbouring EDs show high spatial correlation for all investigated radiation qualities, whilst the uniform random component dominates for neighbours with longer distances for the three higher mean photon energy sources (192Ir, 137Cs, and 60Co). The two lower energy photon emitters (103Pd and 125I) present a very small uniform random component. The ratio of frequencies of clusters with respect to 60Co differs up to 15% for the lower energy sources and less than 2% for the higher energy sources when the maximum distance between each pair of EDs is 2 nm. At distances relevant to DNA damage, cluster patterns can be differentiated between the lower and higher energy sources. This may be part of the explanation to the reported difference in RBE values with initial DSB yields as an endpoint for these brachytherapy sources.

Comparative NMR studies of diffusional water permeability of red blood cells from different species: XV. Agile wallaby (Macropus agilis), red-necked wallaby (Macropus rufogriseus) and Goodfellow's tree kangaroo (Dendrolagus goodfellowi).

PubMed

Benga, Gheorghe; Chapman, Bogdan E; Kuchel, Philip W

2009-09-01

The water diffusional permeability (P(d)) of red blood cells (RBC) from agile wallaby (Macropus agilis), red-necked wallaby (Macropus rufogriseus) and Goodfellow's tree kangaroo (Dendrolagus goodfellowi) was monitored using an Mn(2+)-doping (1)H nuclear magnetic resonance (NMR) technique at 400 MHz. The P(d) (cm s(-1)) values of agile wallaby RBCs were 7.5 x 10(-3) at 25 degrees C, 9 x 10(-3) at 30 degrees C, 11 x 10(-3) at 37 degrees C, and 13 x 10(-3) at 42 degrees C. The inhibitory effect of a mercury-containing sulfhydryl (SH)-modifying reagent p-chloromercuribenzoate (PCMB) on agile wallaby RBCs was investigated. The maximal inhibition was reached in 90 min at 37 degrees C with 2 mmol L(-1) PCMB. The value of maximal inhibition was approximately 63% when measured at 25 degrees C, approximately 52% at 37 degrees C and approximately 45% at 42 degrees C. The lowest value of P(d) (corresponding to the basal permeability to water) was approximately 3 x 10(-3) cm s(-1) at 25 degrees C. For the RBCs from red-necked wallaby (M. rufogriseus) the values of P(d) (cm s(-1)) were 7 x 10(-3) at 25 degrees C, 8 x 10(-3) at 30 degrees C, 10 x 10(-3) at 37 degrees C, and 12 x 10(-3) at 42 degrees C. Higher values of P(d) (cm s(-1)) were found for the RBCs from Goodfellow's tree kangaroo (D. goodfellowi): 8.5 x 10(-3) at 25 degrees C, 10 x 10(-3) at 30 degrees C, 13 x 10(-3) at 37 degrees C, and 15 x 10(-3) at 42 degrees C. The mean values of the activation energy of water diffusion (E(a,d)) were approximately 25 kJ mol(-1) for RBCs from the agile wallaby and tree kangaroo, respectively, and approximately 23 kJ mol(-1) for RBCs from red-necked wallaby. The values of E(a,d) increased after exposure of agile wallaby RBCs to PCMB, reaching a value of approximately 43-46 kJ mol(-1) when the maximal inhibition of P(d) was achieved.

Etude microdosimetrique de l'influence des materiaux sur l'efficacite biologique d'une source d'iode-125

NASA Astrophysics Data System (ADS)

Taschereau, Richard

Cette these concerne les implants permanents pour la prostate. Les isotopes employes, le 103Pd et l'125I, semblent produire les memes resultats cliniques: le premier a cause d'une radiation plus efficace et le second a cause de sa demi-vie plus longue. La recherche utilise le cadre theorique de la microdosimetrie et des simulations Monte Carlo. Elle propose d'employer le spectre d'ejection dans le calcul de l'efficacite; ce changement fait passer l'efficacite relative du 103Pd de 10% a 5%. Elle montre ensuite qu'il est possible d'ameliorer l'efficacite de la radiation de 125I par l'exploitation des rayons X caracteristiques de la capsule. Une source amelioree faite de molybdene et d'yttrium est donnee en exemple. Elle procure une radiation de 5--7% plus efficace, ce qui surclasse les deux sources existantes. Les applications ne se limitent pas au traitement de la prostate; le traitement du melanome oculaire et la curietherapie endovasculaire pourraient en beneficier.

All Prime Contract Awards by State or Country, Place, and Contractor. Part 14 (Akron, New York-Wilson, North Carolina)

DTIC Science & Technology

1990-01-01

i4 i-N( 000U or- L-4ɘ 0-4 0- ɘin L-- )CO 1-00 V) 11 034 Was00 Mtn0 40 00 (90 NO inO -400 -100 ,-411 I.1 . : I Iz o I of 103 - 110 nin I -4 -I 0 in w...4 U- 103 (0< If 0 0 0000 00000000 0 00 00000000 0 : ID ::O4I 00 00 000400 000000000 00 0. ~0 000000000o 0M If M (40 < I-4 4 14 44 .. ൴ -4-4 -i1--i -4...xzz xzzzzzzz MO) :: ax ZZ OZZZZ* a) z o z Q)Zzzz* 4)z O)zz* wzzzzzzz I moo it Z z z Z z I z z z 4D I moo 11 0) QC>00 11 cn a a) PD In In ",4 *4D-qamr-m

Air-kerma strength determination of a new directional (103)Pd source.

PubMed

Aima, Manik; Reed, Joshua L; DeWerd, Larry A; Culberson, Wesley S

2015-12-01

A new directional (103)Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing (103)Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active (103)Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normally used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (S(K)) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring S(K) to a well-type ionization chamber. S(K) measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity S(K) from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the MCNP 6 Monte Carlo code in order to determine S(K) with the presence of gold fluorescent energy lines. In addition to S(K) measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating S(K) values for a directional source within a cylindrically symmetric measurement volume. The UW VAFAC was successfully used to measure the S(K) of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an S(K)-based calibration to a clinical user. S(K) per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the S(K) measurement approach. This characterization of a new (103)Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield.

Air-kerma strength determination of a new directional 103Pd source

PubMed Central

Reed, Joshua L.; DeWerd, Larry A.; Culberson, Wesley S.

2015-01-01

Purpose: A new directional 103Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing 103Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active 103Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normally used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (SK) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring SK to a well-type ionization chamber. Methods: SK measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity SK from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the mcnp 6 Monte Carlo code in order to determine SK with the presence of gold fluorescent energy lines. In addition to SK measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating SK values for a directional source within a cylindrically symmetric measurement volume. Results: The UW VAFAC was successfully used to measure the SK of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an SK-based calibration to a clinical user. SK per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the SK measurement approach. Conclusions: This characterization of a new 103Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield. PMID:26632069

Periodontal disease and breast cancer: Prospective cohort study of postmenopausal women

PubMed Central

Freudenheim, Jo L; Genco, Robert J; LaMonte, Michael J; Millen, Amy E; Hovey, Kathleen M; Mai, Xiaodan; Nwizu, Ngozi; Andrews, Christopher A; Wactawski-Wende, Jean

2015-01-01

Background Periodontal disease (PD) has been consistently associated with chronic disease; there are no large studies of breast cancer although oral-associated microbes are present in breast tumors. Methods In the Women’s Health Initiative Observational Study, a prospective cohort of postmenopausal women, 73,737 women without previous breast cancer were followed. Incident, primary, invasive breast tumors were verified by physician adjudication. PD was by self-report. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards, adjusted for breast cancer risk factors. Because the oral microbiome of those with PD differs with smoking status, we examined associations stratified by smoking. Results 2,124 incident, invasive breast cancer cases were identified after mean follow-up of 6.7 years. PD, reported by 26.1% of women, was associated with increased breast cancer risk (HR 1.14, 95% CI 1.03 to 1.26), particularly among former smokers who quit within 20 years (HR 1.36; 95% CI 1.05 to 1.77). Among current smokers, the trend was similar (HR 1.32; 95% CI 0.83 to 2.11); there were few cases (n=74) and the CI included the null. The population attributable fraction was 12.06% (95% CI 1.12 to 21.79) and 10.90% (95% CI 10.31 to 28.94) for PD among former smokers quitting within 20 years and current smokers, respectively. Conclusion PD, a common chronic inflammatory disorder, was associated with increased risk of postmenopausal breast cancer, particularly among former smokers who quit in the past 20 years. Impact Understanding a possible role of the oral microbiome in breast carcinogenesis could impact prevention. PMID:26689418

Life Path as a Predictor of Performance in the Navy: A Longitudinal Study.

DTIC Science & Technology

1980-04-01

learning came easy to me. Q103. Write letters. o Reading Q 36. I spent a lot of time in the library . Q 45. I was a good reader when I was in high school...Q 50. I could read when I entered first grade. Q 81. I spent a lot of my time reading. Q102. Go to libraries . Q104 . Read newspapers. Q115. Read...Bought my first car Personal Competence V37 Time in library V46 Good reader V51 Read when entered first grade(- V105 Went boating (-) V124 Read

40 CFR 33.202 - How does an entity qualify as an MBE or WBE under EPA's 8% statute?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Indian tribes and Alaska Native Corporations; 13 CFR 124.110 for special rules applicable to Native... 124.103; see also 13 CFR 124.109 for special rules applicable to Indian tribes and Alaska Native... regulations (13 CFR 124.104). (See also 13 CFR 124.109 for special rules applicable to Indian tribes and...

A systematic evaluation of the dose-rate constant determined by photon spectrometry for 21 different models of low-energy photon-emitting brachytherapy sources.

PubMed

Chen, Zhe Jay; Nath, Ravinder

2010-10-21

The aim of this study was to perform a systematic comparison of the dose-rate constant (Λ) determined by the photon spectrometry technique (PST) with the consensus value ((CON)Λ) recommended by the American Association of Physicists in Medicine (AAPM) for 21 low-energy photon-emitting interstitial brachytherapy sources. A total of 63 interstitial brachytherapy sources (21 different models with 3 sources per model) containing either (125)I (14 models), (103)Pd (6 models) or (131)Cs (1 model) were included in this study. A PST described by Chen and Nath (2007 Med. Phys. 34 1412-30) was used to determine the dose-rate constant ((PST)Λ) for each source model. Source-dependent variations in (PST)Λ were analyzed systematically against the spectral characteristics of the emitted photons and the consensus values recommended by the AAPM brachytherapy subcommittee. The values of (PST)Λ for the encapsulated sources of (103)Pd, (125)I and (131)Cs varied from 0.661 to 0.678 cGyh(-1) U(-1), 0.959 to 1.024 cGyh(-1)U(-1) and 1.066 to 1.073 cGyh(-1)U(-1), respectively. The relative variation in (PST)Λ among the six (103)Pd source models, caused by variations in photon attenuation and in spatial distributions of radioactivity among the source models, was less than 3%. Greater variations in (PST)Λ were observed among the 14 (125)I source models; the maximum relative difference was over 6%. These variations were caused primarily by the presence of silver in some (125)I source models and, to a lesser degree, by the variations in photon attenuation and in spatial distribution of radioactivity among the source models. The presence of silver generates additional fluorescent x-rays with lower photon energies which caused the (PST)Λ value to vary from 0.959 to 1.019 cGyh(-1)U(-1) depending on the amount of silver used by a given source model. For those (125)I sources that contain no silver, their (PST)Λ was less variable and had values within 1% of 1.024 cGyh(-1)U(-1). For the 16 source models that currently have an AAPM recommended (CON)Λ value, the agreement between (PST)Λ and (CON)Λ was less than 2% for 15 models and was 2.6% for 1 (103)Pd source model. Excellent agreement between (PST)Λ and (CON)Λ was observed for all source models that currently have an AAPM recommended consensus dose-rate constant value. These results demonstrate that the PST is an accurate and robust technique for the determination of the dose-rate constant for low-energy brachytherapy sources.

Keeping an eye on the ring: COMS plaque loading optimization for improved dose conformity and homogeneity.

PubMed

Gagne, Nolan L; Cutright, Daniel R; Rivard, Mark J

2012-09-01

To improve tumor dose conformity and homogeneity for COMS plaque brachytherapy by investigating the dosimetric effects of varying component source ring radionuclides and source strengths. The MCNP5 Monte Carlo (MC) radiation transport code was used to simulate plaque heterogeneity-corrected dose distributions for individually-activated source rings of 14, 16 and 18 mm diameter COMS plaques, populated with (103)Pd, (125)I and (131)Cs sources. Ellipsoidal tumors were contoured for each plaque size and MATLAB programming was developed to generate tumor dose distributions for all possible ring weighting and radionuclide permutations for a given plaque size and source strength resolution, assuming a 75 Gy apical prescription dose. These dose distributions were analyzed for conformity and homogeneity and compared to reference dose distributions from uniformly-loaded (125)I plaques. The most conformal and homogeneous dose distributions were reproduced within a reference eye environment to assess organ-at-risk (OAR) doses in the Pinnacle(3) treatment planning system (TPS). The gamma-index analysis method was used to quantitatively compare MC and TPS-generated dose distributions. Concentrating > 97% of the total source strength in a single or pair of central (103)Pd seeds produced the most conformal dose distributions, with tumor basal doses a factor of 2-3 higher and OAR doses a factor of 2-3 lower than those of corresponding uniformly-loaded (125)I plaques. Concentrating 82-86% of the total source strength in peripherally-loaded (131)Cs seeds produced the most homogeneous dose distributions, with tumor basal doses 17-25% lower and OAR doses typically 20% higher than those of corresponding uniformly-loaded (125)I plaques. Gamma-index analysis found > 99% agreement between MC and TPS dose distributions. A method was developed to select intra-plaque ring radionuclide compositions and source strengths to deliver more conformal and homogeneous tumor dose distributions than uniformly-loaded (125)I plaques. This method may support coordinated investigations of an appropriate clinical target for eye plaque brachytherapy.

Investigation of the Dynamics of Low-Tension Cables

DTIC Science & Technology

1992-06-01

chapter 3. An implicit time domain routine is nec- essary as the high propagation speed of elastic waves would require prohibitively small time-step...singularities by ensuring smooth curvature. However, sustained boundary layers are found to develop, demonstrating the importance of the underlying physical...chain and elastic chain, EA* = 4.0 x 103 ............... 124 3.10 Mode shape for tension variation due to elastic waves , using EA* - 4.0 x 103.125 6.11

Recoil distance lifetime measurements in 122,124Xe

NASA Astrophysics Data System (ADS)

Govil, I. M.; Kumar, A.; Iyer, H.; Li, H.; Garg, U.; Ghugre, S. S.; Johnson, T.; Kaczarowski, R.; Kharraja, B.; Naguleswaran, S.; Walpe, J. C.

1998-02-01

Lifetimes of the lower-excited states in 122,124Xe are measured using the recoil-distance Doppler-shift technique. The reactions 110Pd(16O,4n)122Xe and 110Pd(18O,4n)124Xe at a beam energy of 66 MeV were used for this experiment. The lifetimes of the 2+, 4+, 6+, and 8+ states of the ground state band were extracted using the computer code LIFETIME including the corrections due to the side feeding and the nuclear deorientation effects. The lifetime of the 2+ state in 122Xe agrees with the recoil distance method (RDM) measurements but for the 124Xe it does not agree with the RDM measurements but agrees with the Coulomb-excitation experiment. The measured B(E2) values for both the nuclei are compared with the standard algebraic and the multishell models.

Air-kerma strength determination of a new directional {sup 103}Pd source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aima, Manik, E-mail: aima@wisc.edu; Reed, Joshua L.; DeWerd, Larry A.

2015-12-15

Purpose: A new directional {sup 103}Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing {sup 103}Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active {sup 103}Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normallymore » used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (S{sub K}) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring S{sub K} to a well-type ionization chamber. Methods: S{sub K} measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity S{sub K} from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the MCNP 6 Monte Carlo code in order to determine S{sub K} with the presence of gold fluorescent energy lines. In addition to S{sub K} measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating S{sub K} values for a directional source within a cylindrically symmetric measurement volume. Results: The UW VAFAC was successfully used to measure the S{sub K} of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an S{sub K}-based calibration to a clinical user. S{sub K} per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the S{sub K} measurement approach. Conclusions: This characterization of a new {sup 103}Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield.« less

Low Energy Electron Diffraction (LEED)-Auger-Thin-Layer Electrochemical Studies of the Underpotential Deposition of Lead onto Gold Single Crystals.

DTIC Science & Technology

1979-12-15

i’attcns for Clean Au. SinlY \\’ td Fim aroid 107. f-set ting: Q.’ fxposurL INC t ir...12, 1975, pp. 107-124 IFF -169- 103. G. E. Rhead, J. Phys. F:- Metal Phys., 3, L53 (1973). 104. C. S. McKee, M. W. Robaerts and M. L. Williams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gagne, Nolan L.; Leonard, Kara L.; Rivard, Mark J.

Purpose: Clinical optimization of Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy is currently limited to tumor coverage, consensus prescription dosage, and dose calculations to ocular structures. The biologically effective dose (BED) of temporary brachytherapy treatments is a function of both chosen radionuclide R and implant duration T. This study endeavored to evaluate BED delivered to the tumor volume and surrounding ocular structures as a function of plaque position P, prescription dose, R, and T. Methods: Plaque-heterogeneity-corrected dose distributions were generated with MCNP5 for the range of currently available COMS plaques loaded with sources using three available low-energy radionuclides. Thesemore » physical dose distributions were imported into the PINNACLE{sup 3} treatment planning system using the TG-43 hybrid technique and used to generate dose volume histograms for a T = 7 day implant within a reference eye geometry including the ciliary body, cornea, eyelid, foveola, lacrimal gland, lens, optic disc, optic nerve, retina, and tumor at eight standard treatment positions. The equation of Dale and Jones was employed to create biologically effective dose volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs. Isobiologically effective prescription doses were calculated for T = 5 days down to 0.01 days, with BEDVHs subsequently generated for all ROIs using correspondingly reduced prescription doses. Objective functions were created to evaluate the BEDVHs as a function of R and T. These objective functions are mathematically accessible and sufficiently general to be applied to temporary or permanent brachytherapy implants for a variety of disease sites. Results: Reducing T from 7 to 0.01 days for a 10 mm plaque produced an average BED benefit of 26%, 20%, and 17% for {sup 103}Pd, {sup 125}I, and {sup 131}Cs, respectively, for all P; 16 and 22 mm plaque results were more position-dependent. {sup 103}Pd produced a 16%-35% BED benefit over {sup 125}I, whereas {sup 131}Cs produced a 3%-7% BED detriment, independent of P, T, and plaque size. Additionally, corresponding organ at risk physical doses were lowest using {sup 103}Pd in all circumstances. Conclusions: The results suggest that shorter implant durations may correlate with more favorable outcomes compared to 7 day implants when treating small or medium intraocular lesions. The data also indicate that implant duration may be safely reduced if the prescription physical dose is likewise diminished and that {sup 103}Pd offers a substantial radiobiological benefit over {sup 125}I and {sup 131}Cs irrespective of plaque position, implant duration, and tumor size.« less

Synthesis, characterization of Ag(I), Pd(II) and Pt(II) complexes of a triazine-3-thione and their interactions with bovine serum albumin

NASA Astrophysics Data System (ADS)

Zhang, Xiuying; Li, Shuyan; Yang, Lin; Fan, Changqing

2007-11-01

Ag(I), Pd(II) and Pt(II) complexes of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (LH 2OCH 3) have been synthesized and characterized by elemental analysis, molar conductance, 1H NMR, IR spectra, UV spectra and thermal analysis (TG-DTA). The components of the three complexes are [Ag(C 15H 10N 3S)] 6, Pd(C 15H 10N 3S) 2 and Pt(C 15H 10N 3S) 2·C 3H 6O·2H 2O, respectively. All the complexes are nonelectrolyte and have high thermodynamic stability. The ligand may act as bidentate NS donor for Pd(II) and Pt(II) complexes, while it seems to be bidentate NS bridging via sulphur atom for Ag(I) complex. A planar quadrangular structure is proposed for Pd(II) and Pt(II) complexes and Ag(I) complex may be a hexanuclear cluster. Their interactions with bovine serum albumin (BSA) are investigated using steady state fluorescence technology. It is observed that all of them can quench the intrinsic fluorescence of BSA through static quenching procedure. The binding constants ( KA) at different temperatures, thermodynamic parameters enthalpy changes (Δ H) and entropy changes (Δ S) between BSA and the compounds are calculated. Based on the values of Δ H and Δ S, it is judged that the main acting force of PtL 2·C 3H 6O·2H 2O with BSA may be electrostatic interaction, and for the LH 2OCH 3, Ag 6L 6 and PdL 2, hydrophobic and electrostatic interactions may be involved in their binding processes.

TU-F-CAMPUS-T-05: Dose Escalation to Biological Tumor Volumes of Prostate Cancer Patients Using Gold Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jermoumi, M; Ngwa, W; Department of Radiation Oncology, Dana Farber Cancer Insitute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA

2015-06-15

Purpose: Studies have shown that radiation boosting could help reduce prostate cancer (PCa) recurrence. Biological tumor volumes (BTV) are a high priority for such radiation boosting. The purpose of this study is to investigate the potential of radiation boosting of real patient BTVs using gold nanoparticles (GNP) released from gold-loaded brachytherapy spacers (GBS) during brachytherapy. Methods: The BTVs of 12 patients having prostate adenocarcinoma identified with positron emission tomography (PET) and CT scanner using C-11 labeled tracer [11C]acetate were investigated. The initial GNP concentration and time to achieve a dose enhancement effect (DEF) of 2 was simulated using the freelymore » downloadable software RAID APP. The investigations were carried out for low dose rate (LDR) brachytherapy sources (BTS) described in AAPM Task Group report 43: Cs-131, I-125, and Pd-103. In first case, we used 7 mg/g and 18 mg/g of GNP initial concentrations to estimate the time needed for released GNP to achieve a DEF of 2 for the different BTS, and compare with clinically relevant treatment times. In second case, we calculated the initial concentration of GNPs needed to achieve a DEF of 2 during the time the BTS would typically deliver 50%, 70% and 90% of the total dose. Results: For an initial concentration of 18 mg/g, when using Cs-131, and Pd-103, a DEF of 2 could only be achieved for BTV of 3.3 cm3 and 1 cm3 respectively. Meanwhile a DEF of 2 could be achieved for all 12 BTVs when using I-125. To achieve a DEF of 2 for all patients using Cs-131 and Pd-103, much higher initial concentrations would have to be used than have been typically employed in pre-clinical studies. Conclusion: The I-125 is the most viable BTS that can be employed with GBS to guide dose painting treatment planning for localized PCa.« less

The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis.

PubMed

Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Singh, Amar; Lokensgard, James R

2017-04-13

Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bT RM ) following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8 + T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bT RMs . In wild-type (WT) animals, we observed a switch in the phenotype of brain-infiltrating CD8 + T cell populations from KLRG1 + CD127 - (SLEC) to KLRG1 - CD127 + (MPEC) during transition from acute through chronic phases of infection. At 14 and 30 dpi, the majority of CD8 + T cells expressed CD127, a marker of memory cells. In contrast, fewer CD8 + T cells expressed CD127 within brains of infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of CD8 + T cells was phenotyped as CD103 + CD69 + , markers of bT RM , and differences were observed in the numbers of these cells when compared to PD-L1 KOs. Immunohistochemical studies revealed that brain-resident CD103 + bT RM cells were localized to the parenchyma. Higher frequencies of CXCR3 were also observed among WT animals in contrast to PD-L1 KOs. Taken together, our results indicate that bT RMs are present within the CNS following viral infection and the PD-1: PD-L1 pathway plays a role in the generation of this brain-resident population.

Influence of source batch S{sub K} dispersion on dosimetry for prostate cancer treatment with permanent implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuñez-Cumplido, E., E-mail: ejnc-mccg@hotmail.com; Hernandez-Armas, J.; Perez-Calatayud, J.

2015-08-15

Purpose: In clinical practice, specific air kerma strength (S{sub K}) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with {sup 125}I and {sup 103}Pd sources; in fact, commercial TPS provide only one S{sub K} input value for all implanted sources and the certified shipment average is typically used. However, the value for S{sub K} is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their S{sub K} values. The purpose of this work is tomore » examine the impact of S{sub K} dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). Methods: The authors have developed a new algorithm to compute dose distributions with different S{sub K} values for each source. Three different prostate volumes (20, 30, and 40 cm{sup 3}) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for {sup 125}I sources; for the palladium, typical implants were simulated. To assess the many different possible S{sub K} values for each source belonging to a class, the authors assigned an S{sub K} value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform S{sub K} value for all the implanted sources. The authors analyzed several dose coverage (V{sub 100} and D{sub 90}) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum. Results: The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and prostate V{sub 100} and D{sub 90} variations ranged between 0.2% and 1.78% for both sources. Variations for the overdosage parameters V{sub 150} and V{sub 200} compared to dose coverage parameters were observed and, in general, variations were larger for parameters related to {sup 125}I sources than {sup 103}Pd sources. For OAR dosimetry, variations with respect to the reference D{sub 0.1cm{sup 3}} were observed for rectum values, ranging from 2% to 3%, compared with urethra values, which ranged from 1% to 2%. Conclusions: Dose coverage for prostate and PTV was practically unaffected by S{sub K} dispersion, as was the maximum dose deposited in the urethra due to the implant technique geometry. However, the authors observed larger variations for the PTV V{sub 150}, rectum V{sub 100}, and rectum D{sub 0.1cm{sup 3}} values. The variations in rectum parameters were caused by the specific location of sources with S{sub K} value that differed from the average in the vicinity. Finally, on comparing the two sources, variations were larger for {sup 125}I than for {sup 103}Pd. This is because for {sup 103}Pd, a greater number of sources were used to obtain a valid dose distribution than for {sup 125}I, resulting in a lower variation for each S{sub K} value for each source (because the variations become averaged out statistically speaking)« less

Gold-nanoparticle-based theranostic agents for radiotherapy of malignant solid tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina

Radiation therapy is one of the three major methods of cancer treatment. The fundamental goal of radiotherapy is to deliver high radiation doses to targets while simultaneously minimizing doses to critical structures and healthy normal tissues. The aim of this study is to develop a general, practical, and facile method to prepare nanoscale theranostic agents for more efficacious radiation therapy with less adverse side effects. First, a novel type of gold nanoparticle, hollow Au nanoparticles (HAuNPs) which was synthesized using the unique bubble template synthesis method developed in our lab, are studied in vitro and in vivo to investigate their effect as radiosensitizing agents to enhance the radiation dose during external radiotherapy. The results showed the promising potential of using HAuNPs as radiosensitization agents for efficacious treatment of breast cancer. Second, a novel radiolabeling method is developed to incorporate medical radioisotopes to gold nanoparticles. We incorporate palladium-103 (103Pd), a radioisotope currently in clinical brachytherapy, into a hollow gold nanoparticle. The resulting 103Pd Au nanoparticles in the form of a colloidal suspension can be administered by direct injection into tumors, serving as internal radiation sources (nanoseeds) for radiation therapy. The size of the nanoseed, 150nm in diameter, is large enough to prevent nanoseeds from diffusing into other areas while still small enough to allow them to homogeneously distribute inside the tumor. The therapeutic efficacy of 103Pd Au nanoseeds have been tested when intratumorally injected into a prostate cancer xenograft model. The findings showed that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors. Finally, to make real clinical application more plausible, multi-functional magnetic nanoseeds nanoparticles for imaging-guided radiotherapy are synthesized and characterized.

Developing A Directional High-Dose Rate (d-HDR) Brachytherapy Source

NASA Astrophysics Data System (ADS)

Heredia, Athena Yvonne

Conventional sources used in brachytherapy provide nearly isotropic or radially symmetric dose distributions. Optimizations of dose distributions have been limited to varied dwell times at specified locations within a given treatment volume, or manipulations in source position for seed implantation techniques. In years past, intensity modulated brachytherapy (IMBT) has been used to reduce the amount of radiation to surrounding sensitive structures in select intracavitary cases by adding space or partial shields. Previous work done by Lin et al., at the University of Wisconsin-Madison, has shown potential improvements in conformality for brachytherapy treatments using a directionally shielded low dose rate (LDR) source for treatments in breast and prostate. Directional brachytherapy sources irradiate approximately half of the radial angles around the source, and adequately shield a quarter of the radial angles on the opposite side, with sharp gradient zones between the treated half and shielded quarter. With internally shielded sources, the radiation can be preferentially emitted in such a way as to reduce toxicities in surrounding critical organs. The objective of this work is to present findings obtained in the development of a new directional high dose rate (d-HDR) source. To this goal, 103Pd (Z = 46) is reintroduced as a potential radionuclide for use in HDR brachytherapy. 103Pd has a low average photon energy (21 keV) and relatively short half -life (17 days), which is why it has historically been used in low dose rate applications and implantation techniques. Pd-103 has a carrier-free specific activity of 75000 Ci/g. Using cyclotron produced 103Pd, near carrier-free specific activities can be achieved, providing suitability for high dose rate applications. The evolution of the d-HDR source using Monte Carlo simulations is presented, along with dosimetric parameters used to fully characterize the source. In addition, a discussion on how to obtain elemental palladium, Pd(0), will be discussed in detail. Directional HDR has the potential to improve upon current treatments, providing better dose conformality to the target volume, while maintaining the benefits of HDR applications.

Genomic, Proteomic and Morphological Characterization of Two Novel Broad Host Lytic Bacteriophages ΦPD10.3 and ΦPD23.1 Infecting Pectinolytic Pectobacterium spp. and Dickeya spp.

PubMed Central

Czajkowski, Robert; Ozymko, Zofia; de Jager, Victor; Siwinska, Joanna; Smolarska, Anna; Ossowicki, Adam; Narajczyk, Magdalena; Lojkowska, Ewa

2015-01-01

Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc), P. wasabiae (Pwa) and Dickeya solani (Dso) with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Pulsed-field gel electrophoresis (PFGE), genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed. PMID:25803051

Enhanced J-protein interaction and compromised protein stability of mtHsp70 variants lead to mitochondrial dysfunction in Parkinson's disease.

PubMed

Goswami, Arvind Vittal; Samaddar, Madhuja; Sinha, Devanjan; Purushotham, Jaya; D'Silva, Patrick

2012-08-01

Parkinson's disease (PD) is the second most prevalent progressive neurological disorder commonly associated with impaired mitochondrial function in dopaminergic neurons. Although familial PD is multifactorial in nature, a recent genetic screen involving PD patients identified two mitochondrial Hsp70 variants (P509S and R126W) that are suggested in PD pathogenesis. However, molecular mechanisms underlying how mtHsp70 PD variants are centrally involved in PD progression is totally elusive. In this article, we provide mechanistic insights into the mitochondrial dysfunction associated with human mtHsp70 PD variants. Biochemically, the R126W variant showed severely compromised protein stability and was found highly susceptible to aggregation at physiological conditions. Strikingly, on the other hand, the P509S variant exhibits significantly enhanced interaction with J-protein cochaperones involved in folding and import machinery, thus altering the overall regulation of chaperone-mediated folding cycle and protein homeostasis. To assess the impact of mtHsp70 PD mutations at the cellular level, we developed yeast as a model system by making analogous mutations in Ssc1 ortholog. Interestingly, PD mutations in yeast (R103W and P486S) exhibit multiple in vivo phenotypes, which are associated with 'mitochondrial dysfunction', including compromised growth, impairment in protein translocation, reduced functional mitochondrial mass, mitochondrial DNA loss, respiratory incompetency and increased susceptibility to oxidative stress. In addition to that, R103W protein is prone to aggregate in vivo due to reduced stability, whereas P486S showed enhanced interaction with J-proteins, thus remarkably recapitulating the cellular defects that are observed in human PD variants. Taken together, our findings provide evidence in favor of direct involvement of mtHsp70 as a susceptibility factor in PD.

Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent gamma-rays.

PubMed

He, Gui-jin; Sun, Dan-dan; Ji, Da-wei; Sui, Dong-ming; Yu, Fa-qiang; Gao, Qin-yi; Dai, Xian-wei; Gao, Hong; Jiang, Tao; Dai, Chao-liu

2008-06-05

In recent years, interventional tumor therapy, involving implantation of intra-cholangial metal stents through percutaneous trans-hepatic punctures, has provided a new method for treating cholangiocarcinoma. (103)Pd cholangial radioactive stents can concentrate high radioactive dosages into the malignant tumors and kill tumor cells effectively, in order to prevent re-stenosis of the lumen caused by a relapsed tumor. The aim of the present study was to investigate the efficacy of gamma-rays released by the (103)Pd biliary duct radioactive stent in treating cholangiocarcinoma via induction of biliary cholangiocarcinoma cell apoptosis. A group of biliary duct cancer cells was collectively treated with a dose of gamma-rays. Cells were then examined by the 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl terazolium-bromide (MTT) technique for determining the inhibition rate of the biliary duct cancer cells, as well as with other methods including electron microscopy, DNA agarose gel electrophoresis, and flow cytometry were applied for the evaluation of their morphological and biochemical characteristics. The growth curve and the growth inhibition rate of the cells were determined, and the changes in the ultrastructure of the cholangiocarcinoma cells and the DNA electrophoresis bands were examined under a UV-lamp. The gamma-ray released by (103)Pd inhibited cholangiocarcinoma cell growth, as demonstrated when the growth rate of the cells was stunned by a gamma-ray with a dosage larger than 197.321 MBq. Typical features of cholangiocarcinoma cell apoptosis were observed in the 197.321 MBq dosage group, while cell necrosis was observed when irradiated by a dosage above 245.865 MBq. DNA agarose gel electrophoresis results were different between the 197.321 MBq irradiation dosage group, the 245.865 MBq irradiation dosage group, and the control group. (103)Pd radioactive stents which provide a radioactive dosage of 197.321 MBq are effective in the treatment of cholangiocarcinoma; (103)Pd radioactive stents should be useful for the clinical treatment of cholangiocarcinoma.

Factors associated with peritoneal dialysis catheter complications in children.

PubMed

Stewart, Camille L; Acker, Shannon N; Pyle, Laura L; Kulungowski, Ann; Cadnapaphornchai, Melissa; Bruny, Jennifer L; Karrer, Frederick

2016-01-01

Peritoneal dialysis (PD) is a common method of renal replacement therapy for children. However, placement of PD catheters has risk, and some are never used. We conducted a retrospective chart review of children with a PD catheter placed between 2000 and 2014. Logistic regression analyses were used to identify covariates associated with complications. We identified 175 children with PD catheters. 110 complications developed in 80 children (45.7%). Complications including unexpected return to the operating room and peritonitis increased as the length of time a catheter was in place increased. Children who weighed <12.4 kg had 3.2 times greater odds of developing a leak (95% CI 1.21-8.63, p=0.02). Twelve children never used their PD catheters, 9 with acute kidney injury (AKI) who recovered from their disease more quickly than expected. No covariate was associated with nonuse. Complications with PD catheters are common and increase the longer catheters are in place. Lower weight children are at greater risk of PD catheter leak. Decreased initial volumes of dialysate in smaller children may mitigate this risk. Nonuse may be reduced if dialysis is permitted the day of placement for children with AKI. Copyright © 2016 Elsevier Inc. All rights reserved.

Measurement of activation cross-section of long-lived products in deuteron induced nuclear reactions on palladium in the 30-50MeV energy range.

PubMed

Ditrói, F; Tárkányi, F; Takács, S; Hermanne, A; Ignatyuk, A V

2017-10-01

Excitation functions were measured in the 31-49.2MeV energy range for the nat Pd(d,xn) 111,110m,106m,105,104g,103 Ag, nat Pd(d,x) 111m,109,101,100 Pd, nat Pd(d,x), 105,102m,102g,101m,101g,100,99m,99g Rh and nat Pd(d,x) 103,97 Ru nuclear reactions by using the stacked foil irradiation technique. The experimental results are compared with our previous results and with the theoretical predictions calculated with the ALICE-D, EMPIRE-D and TALYS (TENDL libraries) codes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monte Carlo calculated doses to treatment volumes and organs at risk for permanent implant lung brachytherapy

NASA Astrophysics Data System (ADS)

Sutherland, J. G. H.; Furutani, K. M.; Thomson, R. M.

2013-10-01

Iodine-125 (125I) and Caesium-131 (131Cs) brachytherapy have been used with sublobar resection to treat stage I non-small cell lung cancer and other radionuclides, 169Yb and 103Pd, are considered for these treatments. This work investigates the dosimetry of permanent implant lung brachytherapy for a range of source energies and various implant sites in the lung. Monte Carlo calculated doses are calculated in a patient CT-derived computational phantom using the EGsnrc user-code BrachyDose. Calculations are performed for 103Pd, 125I, 131Cs seeds and 50 and 100 keV point sources for 17 implant positions. Doses to treatment volumes, ipsilateral lung, aorta, and heart are determined and compared to those determined using the TG-43 approach. Considerable variation with source energy and differences between model-based and TG-43 doses are found for both treatment volumes and organs. Doses to the heart and aorta generally increase with increasing source energy. TG-43 underestimates the dose to the heart and aorta for all implants except those nearest to these organs where the dose is overestimated. Results suggest that model-based dose calculations are crucial for selecting prescription doses, comparing clinical endpoints, and studying radiobiological effects for permanent implant lung brachytherapy.

Bounding Analysis of Effects of Fractionation of Radionuclides inFallout on Estimation of Doses to Atomic Veterans

DTIC Science & Technology

2007-05-04

140 Sm-156 Y-91m Rh - 103m Cd-115 Te-129 La-141 Eu-156 Y-91 Ru-105 In-115m I-130 Ce-141 Eu-157 Sr-92 Rh -105m Sn-121 Te-131m Ce-143 Gd-159 Y-92 Rh ...Tc-99m 6.02 h R 1.09E+00n (0.886) Ru-103 39.35 d V 2.04E-07 9.65E-01 6.81E-12 Rh - 103m 56.119 m V 1.00E+00n (0.997) 1.00E+00 Ru-105 4.44 h...08 1.24E-08 9.09E-09 Rh - 103m 6.36E-09 1.34E-08 1.23E-08 9.07E-09 Ru-105 1.20E-02 5.36E-02 4.05E-02 3.22E-02 2.90E-10 1.30E-09 9.79E-10 7.78E-10

Study of the structure of yrast bands of neutron-rich 114-124Pd isotopes

NASA Astrophysics Data System (ADS)

Chaudhary, Ritu; Devi, Rani; Khosa, S. K.

2018-02-01

The projected shell model calculations have been carried out in the neutron-rich 114-124Pd isotopic mass chain. The results have been obtained for the deformation systematics of E(2+1) and E(4+1)/E({2}+1) values, BCS subshell occupation numbers, yrast spectra, backbending phenomena, B( E2) transition probabilities and g-factors in these nuclei. The observed systematics of E(2+1) values and R_{42} ratios in the 114-124Pd isotopic mass chain indicate that there is a decrease of collectivity as the neutron number increases from 68 to 78. The occurrence of backbending in these nuclei as well as the changes in the calculated B( E2) transition probabilities and g -factors predict that there are changes in the structure of yrast bands in these nuclei. These changes occur at the spin where there is crossing of g-band by 2-qp bands. The predicted backbendings and predicted values of B( E2)s and g-factors in some of the isotopes need to be confirmed experimentally.

High-affinity PD-1 molecules deliver improved interaction with PD-L1 and PD-L2.

PubMed

Li, Yanyan; Liang, Zhaoduan; Tian, Ye; Cai, Wenxuan; Weng, Zhiming; Chen, Lin; Zhang, Huanling; Bao, Yifeng; Zheng, Hongjun; Zeng, Sihai; Bei, Chunhua; Li, Yi

2018-06-11

The inhibitory checkpoint molecule programmed death (PD)-1 plays a vital role in maintaining immune homeostasis upon binding to its ligands, PD-L1 and PD-L2. Several recent studies have demonstrated that soluble PD-1 (sPD-1) can block the interaction between membrane PD-1 and PD-L1 to enhance the anti-tumor capability of T cells. However, the affinity of natural sPD-1 binding to PD-L1 is too low to permit therapeutic applications. Here a PD-1 variant with ~3,000-fold and ~70-fold affinity increase to bind PD-L1 and PD-L2, respectively, was generated through directed molecular evolution and phage display technology. Structural analysis showed that mutations at amino acid positions 124 and 132 of PD-1 played major roles in enhancing the affinity of PD-1 binding to its ligands. The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells or dendritic cells (DCs), and it could enhance the proliferation and IFN-γ release of activated lymphocytes. These features potentially qualify the high-affinity PD-1 variant as a unique candidate for the development of a new class of PD-1 immune checkpoint blockade therapeutics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-{sup 124}I-iodobenzoate in rat myocardial infarction model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Min Hwan; School of Life Sciences and Biotechnology, Korea University, Seoul; Woo, Sang-Keun

Highlights: • We developed a safe, simple and appropriate stem cell labeling method with {sup 124}I-HIB. • ADSC survival can be monitored with PET in MI model via direct labeling. • Tracking of ADSC labeled with {sup 124}I-HIB was possible for 3 days in MI model using PET. • ADSC viability and differentiation were not affected by {sup 124}I-HIB labeling. • Survival of ADSC in living bodies can be longitudinally tracked with PET imaging. - Abstract: This study aims to monitor how the change of cell survival of transplanted adipose-derived stem cells (ADSCs) responds to myocardial infarction (MI) via themore » hexadecyl-4-{sup 124}I-iodobenzoate ({sup 124}I-HIB) mediated direct labeling method in vivo. Stem cells have shown the potential to improve cardiac function after MI. However, monitoring of the fate of transplanted stem cells at target sites is still unclear. Rat ADSCs were labeled with {sup 124}I-HIB, and radiolabeled ADSCs were transplanted into the myocardium of normal and MI model. In the group of {sup 124}I-HIB-labeled ADSC transplantation, in vivo imaging was performed using small-animal positron emission tomography (PET)/computed tomography (CT) for 9 days. Twenty-one days post-transplantation, histopathological analysis and apoptosis assay were performed. ADSC viability and differentiation were not affected by {sup 124}I-HIB labeling. In vivo tracking of the {sup 124}I-HIB-labeled ADSCs was possible for 9 and 3 days in normal and MI model, respectively. Apoptosis of transplanted cells increased in the MI model compared than that in normal model. We developed a direct labeling agent, {sup 124}I-HIB, and first tried to longitudinally monitor transplanted stem cell to MI. This approach may provide new insights on the roles of stem cell monitoring in living bodies for stem cell therapy from pre-clinical studies to clinical trials.« less

A photon spectrometric dose-rate constant determination for the Advantage Pd-103 brachytherapy source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Zhe Jay; Bongiorni, Paul; Nath, Ravinder

Purpose: Although several dosimetric characterizations using Monte Carlo simulation and thermoluminescent dosimetry (TLD) have been reported for the new Advantage Pd-103 source (IsoAid, LLC, Port Richey, FL), no AAPM consensus value has been established for the dosimetric parameters of the source. The aim of this work was to perform an additional dose-rate constant ({Lambda}) determination using a recently established photon spectrometry technique (PST) that is independent of the published TLD and Monte Carlo techniques. Methods: Three Model IAPD-103A Advantage Pd-103 sources were used in this study. The relative photon energy spectrum emitted by each source along the transverse axis wasmore » measured using a high-resolution germanium spectrometer designed for low-energy photons. For each source, the dose-rate constant was determined from its emitted energy spectrum. The PST-determined dose-rate constant ({sub PST}{Lambda}) was then compared to those determined by TLD ({sub TLD}{Lambda}) and Monte Carlo ({sub MC}{Lambda}) techniques. A likely consensus {Lambda} value was estimated as the arithmetic mean of the average {Lambda} values determined by each of three different techniques. Results: The average {sub PST}{Lambda} value for the three Advantage sources was found to be (0.676{+-}0.026) cGyh{sup -1} U{sup -1}. Intersource variation in {sub PST}{Lambda} was less than 0.01%. The {sub PST}{Lambda} was within 2% of the reported {sub MC}{Lambda} values determined by PTRAN, EGSnrc, and MCNP5 codes. It was 3.4% lower than the reported {sub TLD}{Lambda}. A likely consensus {Lambda} value was estimated to be (0.688{+-}0.026) cGyh{sup -1} U{sup -1}, similar to the AAPM consensus values recommended currently for the Theragenics (Buford, GA) Model 200 (0.686{+-}0.033) cGyh{sup -1} U{sup -1}, the NASI (Chatsworth, CA) Model MED3633 (0.688{+-}0.033) cGyh{sup -1} U{sup -1}, and the Best Medical (Springfield, VA) Model 2335 (0.685{+-}0.033) cGyh{sup -1} U{sup -1} {sup 103}Pd sources. Conclusions: An independent {Lambda} determination has been performed for the Advantage Pd-103 source. The {sub PST}{Lambda} obtained in this work provides additional information needed for establishing a more accurate consensus {Lambda} value for the Advantage Pd-103 source.« less

Comparative NMR studies of diffusional water permeability of red blood cells from different species: XVIII platypus (Ornithorhynchus anatinus) and saltwater crocodile (Crocodylus porosus).

PubMed

Benga, Gheorghe; Chapman, Bogdan E; Cox, Guy C; Kuchel, Philip W

2010-07-01

As part of a programme of comparative measurements of Pd (diffusional water permeability) the RBCs (red blood cells) from an aquatic monotreme, platypus (Ornithorhynchus anatinus), and an aquatic reptile, saltwater crocodile (Crocodylus porosus) were studied. The mean diameter of platypus RBCs was estimated by light microscopy and found to be approximately 6.3 microm. Pd was measured by using an Mn2+-doping 1H NMR (nuclear magnetic resonance) technique. The Pd (cm/s) values were relatively low: approximately 2.1 x 10(-3) at 25 degrees C, 2.5 x 10(-3) at 30 degrees C, 3.4 x 10(-3) at 37 degrees C and 4.5 at 42 degrees C for the platypus RBCs and approximately 2.8 x 10(-3) at 25 degrees C, 3.2 x 10(-3) at 30 degrees C, 4.5 x 10(-3) at 37 degrees C and 5.7 x 10(-3) at 42 degrees C for the crocodile RBCs. In parallel with the low water permeability, the Ea,d (activation energy of water diffusion) was relatively high, approximately 35 kJ/mol. These results suggest that "conventional" WCPs (water channel proteins), or AQPs (aquaporins), are probably absent from the plasma membranes of RBCs from both the platypus and the saltwater crocodile.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aryal, P; Molloy, JA; Rivard, MJ

Purpose: To investigate the effect of plaque design and radionuclides on eye plaque dosimetry. Methods: The Monte Carlo N-particle Code version 6 (MCNP6) was used for radiation transport simulations. The 14 mm and 16 mm diameter COMS plaques and the model EP917 plaque were simulated using brachytherapy seeds containing I-125, Pd-103, and Cs-131 radionuclides. The origin was placed at the scleral inner surface. The central axis (CAX) doses of both COMS plaques at −1 mm, 0 mm, 1 mm, 2 mm, 5 mm, 10 mm, 15 mm, 20 mm, and 22.6 mm were compared to the model EP917 plaque. Dosemore » volume histograms (DVHs) were also created for both COMS plaques for the tumor and outer sclera then compared to results for the model EP917 plaque. Results: For all radionuclides, the EP917 plaque delivered higher dose (max 343%) compared to the COMS plaques, except for the 14 mm COMS plaque with Cs-131 at 1 mm and 2 mm depths from outer sclera surface. This could be due to source design. For all radionuclides, the 14 mm COMS plaque delivered higher doses compared to the 16 mm COMS plaque for the depths up to 5 mm. Dose differences were not significant beyond depths of 10 mm due to ocular lateral scatter for the different plaque designs. Tumor DVHs for the 16 mm COMS plaque with Cs-131 provided better dose homogeneity and conformity compared to other COMS plaques with I-125 and Pd-103. Using Pd-103, DVHs for the 16 mm COMS plaque delivered less dose to outer sclera compared to other plaques. Conclusion: This study identified improved tumor homogeneity upon considering radionuclides and plaque designs, and found that scleral dose with the model EP917 plaque was higher than for the 16 mm COMS plaque for all the radionuclides studied.« less

Evaluation of water-mimicking solid phantom materials for use in HDR and LDR brachytherapy dosimetry

NASA Astrophysics Data System (ADS)

Schoenfeld, Andreas A.; Thieben, Maike; Harder, Dietrich; Poppe, Björn; Chofor, Ndimofor

2017-12-01

In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose profiles generated in water or a water-equivalent phantom have to be available in the interest of patient safety. However, the commercially available brachytherapy photon sources cover a wide range of photon emission spectra, and the range of the in-phantom photon spectrum is further widened by Compton scattering, so that the achievement of water-mimicking properties of such phantoms involves high requirements on their atomic composition. In order to classify the degree of water equivalence of the numerous commercially available solid water-mimicking phantom materials and the energy ranges of their applicability, the radial profiles of the absorbed dose to water, D w, have been calculated using Monte Carlo simulations in these materials and in water phantoms of the same dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co-60 HDR (60Co), Eckert und Ziegler BEBIG GmbH CSM-11 (137Cs), Implant Sciences Corporation HDR Yb-169 Source 4140 (169Yb) as well as the LDR therapy sources IsoRay Inc. Proxcelan CS-1 (131Cs), IsoAid Advantage I-125 IAI-125A (125I), and IsoAid Advantage Pd-103 IAPd-103A (103Pd). Thereby our previous comparison between phantom materials and water surrounding a Varian GammaMed Plus HDR therapy 192Ir source (Schoenfeld et al 2015) has been complemented. Simulations were performed in cylindrical phantoms consisting of either water or the materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT, Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue Water, polyethylene, polystyrene and PMMA. While for 192Ir, 137Cs and 60Co most phantom materials can be regarded as water equivalent, for 169Yb the materials Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the low-energy sources 106Pd, 131Cs and 125I, only Plastic Water LR can be classified as water equivalent.

Evaluation of water-mimicking solid phantom materials for use in HDR and LDR brachytherapy dosimetry.

PubMed

Schoenfeld, Andreas A; Thieben, Maike; Harder, Dietrich; Poppe, Björn; Chofor, Ndimofor

2017-11-21

In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose profiles generated in water or a water-equivalent phantom have to be available in the interest of patient safety. However, the commercially available brachytherapy photon sources cover a wide range of photon emission spectra, and the range of the in-phantom photon spectrum is further widened by Compton scattering, so that the achievement of water-mimicking properties of such phantoms involves high requirements on their atomic composition. In order to classify the degree of water equivalence of the numerous commercially available solid water-mimicking phantom materials and the energy ranges of their applicability, the radial profiles of the absorbed dose to water, D w , have been calculated using Monte Carlo simulations in these materials and in water phantoms of the same dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co-60 HDR ( 60 Co), Eckert und Ziegler BEBIG GmbH CSM-11 ( 137 Cs), Implant Sciences Corporation HDR Yb-169 Source 4140 ( 169 Yb) as well as the LDR therapy sources IsoRay Inc. Proxcelan CS-1 ( 131 Cs), IsoAid Advantage I-125 IAI-125A ( 125 I), and IsoAid Advantage Pd-103 IAPd-103A ( 103 Pd). Thereby our previous comparison between phantom materials and water surrounding a Varian GammaMed Plus HDR therapy 192 Ir source (Schoenfeld et al 2015) has been complemented. Simulations were performed in cylindrical phantoms consisting of either water or the materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT, Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue Water, polyethylene, polystyrene and PMMA. While for 192 Ir, 137 Cs and 60 Co most phantom materials can be regarded as water equivalent, for 169 Yb the materials Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the low-energy sources 106 Pd, 131 Cs and 125 I, only Plastic Water LR can be classified as water equivalent.

SU-E-T-123: Anomalous Altitude Effect in Permanent Implant Brachytherapy Seeds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watt, E; Spencer, DP; Meyer, T

Purpose: Permanent seed implant brachytherapy procedures require the measurement of the air kerma strength of seeds prior to implant. This is typically accomplished using a well-type ionization chamber. Previous measurements (Griffin et al., 2005; Bohm et al., 2005) of several low-energy seeds using the air-communicating HDR 1000 Plus chamber have demonstrated that the standard temperature-pressure correction factor, P{sub TP}, may overcompensate for air density changes induced by altitude variations by up to 18%. The purpose of this work is to present empirical correction factors for two clinically-used seeds (IsoAid ADVANTAGE™ {sup 103}Pd and Nucletron selectSeed {sup 125}I) for which empiricalmore » altitude correction factors do not yet exist in the literature when measured with the HDR 1000 Plus chamber. Methods: An in-house constructed pressure vessel containing the HDR 1000 Plus well chamber and a digital barometer/thermometer was pumped or evacuated, as appropriate, to a variety of pressures from 725 to 1075 mbar. Current measurements, corrected with P{sub TP}, were acquired for each seed at these pressures and normalized to the reading at ‘standard’ pressure (1013.25 mbar). Results: Measurements in this study have shown that utilization of P{sub TP} can overcompensate in the corrected current reading by up to 20% and 17% for the IsoAid Pd-103 and the Nucletron I-125 seed respectively. Compared to literature correction factors for other seed models, the correction factors in this study diverge by up to 2.6% and 3.0% for iodine (with silver) and palladium respectively, indicating the need for seed-specific factors. Conclusion: The use of seed specific altitude correction factors can reduce uncertainty in the determination of air kerma strength. The empirical correction factors determined in this work can be applied in clinical quality assurance measurements of air kerma strength for two previously unpublished seed designs (IsoAid ADVANTAGE™ {sup 103}Pd and Nucletron selectSeed {sup 125}I) with the HDR 1000 Plus well chamber.« less

Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.

PubMed

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2012-01-01

Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5-1 μm, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.

(124)I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of (131)I-L19-SIP radioimmunotherapy.

PubMed

Tijink, Bernard M; Perk, Lars R; Budde, Marianne; Stigter-van Walsum, Marijke; Visser, Gerard W M; Kloet, Reina W; Dinkelborg, Ludger M; Leemans, C René; Neri, Dario; van Dongen, Guus A M S

2009-08-01

The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with (131)I-L19-SIP was recently started. In the present study, after GMP production of (124)I and efficient production of (124)I-L19-SIP, we aimed to demonstrate the suitability of (124)I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical (131)I-L19-SIP RIT. (124)I was produced in a GMP compliant way via (124)Te(p,n)(124)I reaction and using a TERIMO module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected (124)I- and (131)I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while (124)I PET images were obtained from mice with tumours of <50 to approximately 700 mm(3). (124)I was produced highly pure with an average yield of 15.4 +/- 0.5 MBq/microAh, while separation yield was approximately 90% efficient with <0.5% loss of TeO(2). Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for (124)I-L19-SIP: approximately 80 , 99.9 and >90%, respectively. Tumour uptake was 7.3 +/- 2.1, 10.8 +/- 1.5, 7.8 +/- 1.4, 5.3 +/- 0.6 and 3.1 +/- 0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribution results were obtained with (124)I- and (131)I-L19-SIP. Immuno-PET with (124)I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm(3) and no adverse uptake in other organs. (124)I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with (124)I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting (131)I-L19-SIP biodistribution.

THERMODYNAMIC PROPERTIES OF Zr AND Hf HALIDES (in Rumanian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lungu, S.N.

1962-01-01

The following standard heats of formation were found: ZrCl/sub 3/, 178.6 plus or minus 3.2; ZrCl/sub 2/, 124.3 plus or minus 3; ZrBr/sub 3/, 151 plus or minus 7; Zr Br/sbu 2/, 100 plus or minus 6; ZrI/sub 3/, 103 plus or minus 6; ZrI/sub 2/, 68 plus or minus 4; and HfCl/sub 4/, 239.4 plus or minus 5.5; HfCl/sub 3/, 186.6; HfCl/sub 2/, 130; HfBr/sub 4/, 200; HfBr/sub 3/, 157; HfBr / sub 2/, 108; HfI/sub 4/, 140; HfI/sub 3/, 113; and HfI/sub 2/, 72 kcal/mole. (R.V.J.)

SU-E-T-212: Comparison of TG-43 Dosimetric Parameters of Low and High Energy Brachytherapy Sources Obtained by MCNP Code Versions of 4C, X and 5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zehtabian, M; Zaker, N; Sina, S

2015-06-15

Purpose: Different versions of MCNP code are widely used for dosimetry purposes. The purpose of this study is to compare different versions of the MCNP codes in dosimetric evaluation of different brachytherapy sources. Methods: The TG-43 parameters such as dose rate constant, radial dose function, and anisotropy function of different brachytherapy sources, i.e. Pd-103, I-125, Ir-192, and Cs-137 were calculated in water phantom. The results obtained by three versions of Monte Carlo codes (MCNP4C, MCNPX, MCNP5) were compared for low and high energy brachytherapy sources. Then the cross section library of MCNP4C code was changed to ENDF/B-VI release 8 whichmore » is used in MCNP5 and MCNPX codes. Finally, the TG-43 parameters obtained using the MCNP4C-revised code, were compared with other codes. Results: The results of these investigations indicate that for high energy sources, the differences in TG-43 parameters between the codes are less than 1% for Ir-192 and less than 0.5% for Cs-137. However for low energy sources like I-125 and Pd-103, large discrepancies are observed in the g(r) values obtained by MCNP4C and the two other codes. The differences between g(r) values calculated using MCNP4C and MCNP5 at the distance of 6cm were found to be about 17% and 28% for I-125 and Pd-103 respectively. The results obtained with MCNP4C-revised and MCNPX were similar. However, the maximum difference between the results obtained with the MCNP5 and MCNP4C-revised codes was 2% at 6cm. Conclusion: The results indicate that using MCNP4C code for dosimetry of low energy brachytherapy sources can cause large errors in the results. Therefore it is recommended not to use this code for low energy sources, unless its cross section library is changed. Since the results obtained with MCNP4C-revised and MCNPX were similar, it is concluded that the difference between MCNP4C and MCNPX is their cross section libraries.« less

Driving safety in Parkinson's disease.

PubMed

Zesiewicz, T A; Cimino, C R; Malek, A R; Gardner, N; Leaverton, P L; Dunne, P B; Hauser, R A

2002-12-10

In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = -3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (chi(2) = 12.4, p = 0.006) and correlated with Unified Parkinson's Disease Rating Scale score (r = 0.5, p < 0.01).

Walking economy in people with Parkinson's disease.

PubMed

Christiansen, Cory L; Schenkman, Margaret L; McFann, Kim; Wolfe, Pamela; Kohrt, Wendy M

2009-07-30

Gait dysfunction is an early problem identified by patients with Parkinson's disease (PD). Alterations in gait may result in an increase in the energy cost of walking (i.e., walking economy). The purpose of this study was to determine whether walking economy is atypical in patients with PD when compared with healthy controls. A secondary purpose was to evaluate the associations of age, sex, and level of disease severity with walking economy in patients with PD. The rate of oxygen consumption (VO(2)) and other responses to treadmill walking were compared in 90 patients (64.4 +/- 10.3 years) and 44 controls (64.6 +/- 7.3 years) at several walking speeds. Pearson correlation coefficients (r) were calculated to determine relationships of age, sex, and disease state with walking economy in PD patients. Walking economy was significantly worse in PD patients than in controls at all speeds above 1.0 mph. Across all speeds, VO(2) was 6 to 10% higher in PD patients. Heart rate, minute ventilation, respiratory exchange ratio, and rating of perceived exertion were correspondingly elevated. No significant relationship of age, sex, or UPDRS score with VO(2) was found for patients with PD. The findings suggest that the physiologic stress of daily physical activities is increased in patients with early to mid-stage PD, and this may contribute to the elevated level of fatigue that is characteristic of PD. Copyright 2009 Movement Disorder Society.

Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.

PubMed

Okiyama, Naoko; Katz, Stephen I

2014-09-01

Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases. Published by Elsevier Ltd.

Dye-induced aggregation of single stranded RNA: a mechanistic approach.

PubMed

Biver, Tarita; Ciatto, Carlo; Secco, Fernando; Venturini, Marcella

2006-08-15

The binding of proflavine (D) to single stranded poly(A) (P) was investigated at pH 7.0 and 25 degrees C using T-jump, stopped-flow and spectrophotometric methods. Equilibrium measurements show that an external complex PD(I) and an internal complex PD(II) form upon reaction between P and D and that their concentrations depend on the polymer/dye concentration ratio (C(P)/C(D)). For C(P)/C(D)<2.5, cooperative formation of stacks external to polymer strands prevails (PD(I)). Equilibria and T-jump experiments, performed at I=0.1M and analyzed according to the Schwarz theory for cooperative binding, provide the values of site size (g=1), equilibrium constant for the nucleation step (K( *)=(1.4+/-0.6)x10(3)M(-1)), equilibrium constant for the growth step (K=(1.2+/-0.6)x10(5)M(-1)), cooperativity parameter (q=85) and rate constants for the growth step (k(r)=1.2x10(7)M(-1)s(-1), k(d)=1.1 x 10(2)s(-1)). Stopped-flow experiments, performed at low ionic strength (I=0.01 M), indicate that aggregation of stacked poly(A) strands do occur provided that C(P)/C(D)<2.5.

Comparison of primary position measurements and abduction deficit between type 1 Duane syndrome and sixth cranial nerve palsy.

PubMed

Batra, Noopur Nikki; Arnoldi, Kyle; Reynolds, James D; Strominger, Mitchell B

2011-06-01

Unilateral Duane retraction syndrome type 1 (DRS-I) and unilateral sixth nerve palsy (6NP) present with limitation of abduction, incomitant esotropia, and frequently, a compensatory head turn. The purpose of this study was to compare the mean primary position measurement and to correlate this with the abduction deficit to determine if these measurements may be used to differentiate between the 2 conditions when other clinical signs of DRS-I (globe retraction, changes in lid fissure height, and upshoots/downshoots) are subtle. A database search of patients examined over a 5-year period revealed 69 cases of DRS-I and 62 cases of unilateral 6NP. Primary position measurements both at distance and near and limitation of abduction on version testing were recorded and compared. Mean abduction deficit was -3.5 ± 0.1 for DRS-I and -2.6 ± 0.2 for 6NP (P = 0.0004). Mean esotropia at near was 8.4 ± 1.1 prism diopters (PD) for DRS-I and 27.2 ± 2.4 PD for 6NP (P < 0.0001). Mean esotropia at distance was 10.3 ± 1.3 PD for DRS-I and 36.4 ± 2.4 PD for 6NP (P < 0.0001). The mean distance-near disparity for DRS-I was 1.94 ± 0.62 PD and 9.19 ± 1.28 PD for 6NP (P < 0.0001). The age-group of ≤2 years consisted of 23 DRS-I and only 2 6NP cases. The age-group between >2 years and <18 years had 41 DRS-I and 16 6NP cases, respectively. Finally, the age-group of ≥18 years had only 5 DRS-I and 44 6NP cases (P < 0.0001). Patients with DRS-I showed greater abduction deficit yet significantly less esotropia in primary position than those with 6NP. Patients with 6NP were more likely to have a significant distance-near disparity. In addition, patients with DRS-I tended to be younger than those with 6NP. This report documents that DRS-I and 6NP can be differentiated based on magnitude of primary position esotropia, comparison of primary position esotropia with severity of abduction deficit, distance-near disparity, and patient age.

Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach.

PubMed

Südmeyer, Martin; Antke, Christina; Zizek, Tanja; Beu, Markus; Nikolaus, Susanne; Wojtecki, Lars; Schnitzler, Alfons; Müller, Hans-Wilhelm

2011-05-01

In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG scintigraphy is likely to significantly increase TA in differentiating PD from APD. The differential diagnosis of degenerative parkinsonism may thus be facilitated.

Microsoft Kinect can distinguish differences in over-ground gait between older persons with and without Parkinson's disease.

PubMed

Eltoukhy, Moataz; Kuenze, Christopher; Oh, Jeonghoon; Jacopetti, Marco; Wooten, Savannah; Signorile, Joseph

2017-06-01

Gait patterns differ between healthy elders and those with Parkinson's disease (PD). A simple, low-cost clinical tool that can evaluate kinematic differences between these populations would be invaluable diagnostically; since gait analysis in a clinical setting is impractical due to cost and technical expertise. This study investigated the between group differences between the Kinect and a 3D movement analysis system (BTS) and reported validity and reliability of the Kinect v2 sensor for gait analysis. Nineteen subjects participated, eleven without (C) and eight with PD (PD). Outcome measures included spatiotemporal parameters and kinematics. Ankle range of motion for C was significantly less during ankle swing compared to PD (p=0.04) for the Kinect. Both systems showed significant differences for stride length (BTS (C 1.24±0.16, PD=1.01±0.17, p=0.009), Kinect (C=1.24±0.17, PD=1.00±0.18, p=0.009)), gait velocity (BTS (C=1.06±0.14, PD=0.83±0.15, p=0.01), Kinect (C=1.06±0.15, PD=0.83±0.16, p=0.01)), and swing velocity (BTS (C=2.50±0.27, PD=2.12±0.36, p=0.02), Kinect (C=2.32±0.25, PD=1.95±0.31, p=0.01)) between groups. Agreement (Range ICC =0.93-0.99) and consistency (Range ICC =0.94-0.99) were excellent between systems for stride length, stance duration, swing duration, gait velocity, and swing velocity. The Kinect v2 can was sensitive enough to detect between group differences and consistently produced results similar to the BTS system. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Macronutrients intake and risk of Parkinson's disease: A meta-analysis.

PubMed

Wang, Aimin; Lin, Yan; Wu, Yili; Zhang, Dongfeng

2015-05-01

We carried out a meta-analysis to summarize the evidence from published studies on macronutrients intake and risk of Parkinson's disease (PD). Pertinent studies were identified by a search of PubMed and Embase. Study-specific effect was combined with the random-effect model. The dose-response relationship was assessed by the restricted cubic spline. For highest versus lowest level of intake, the relative risk (RR) of PD was 1.13 (95% CI 0.88-1.44) for protein (7 articles including 1570 PD cases among 357,827 subjects), RR 1.24 (95% CI 1.05-1.48) for carbohydrate (8 articles including 1482 PD cases among 232,869 subjects), RR 0.88 (95% CI 0.74-1.06) for fat (12 articles including 2936 PD cases among 374,124 subjects), RR 0.97 (95% CI 0.75-1.26) for cholesterol (6 articles including 1713 PD cases among 170,058 subjects) and 1.39 (95% CI 1.01-1.92) for energy (8 articles including 1553 PD cases among 170,317 subjects), respectively. Among prospective studies adjusting for smoking and coffee/caffeine, no associations were found between PD risk and intake of protein (RR 1.02, 95% CI 0.80-1.30), carbohydrate (RR 1.11, 95% CI 0.86-1.43), fat (RR 0.90, 95% CI 0.70-1.16), cholesterol (RR 0.89, 95% CI 0.74-1.09) and energy (RR 0.97, 95% CI 0.93-1.02); however, polyunsaturated fatty acid (RR 0.78, 95% CI 0.64-0.96) was inversely associated with PD risk. Limited data showed a linear dose-response relationship between the aforementioned macronutrients and PD risk. Dietary intake of protein, carbohydrate, cholesterol and energy might be not independently associated with PD risk. Higher intake of polyunsaturated fatty acid might be inversely associated with PD risk. Confounding by smoking and coffee/caffeine should be considered regarding the association between fat intake and PD risk in further studies. © 2014 Japan Geriatrics Society.

Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort.

PubMed

Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y; Chou, Shaun; Carlino, Matteo S; Kefford, Richard; Fernandez-Penas, Pablo

2016-03-01

Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these patients. We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Dosimetric effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chibani, Omar; Williamson, Jeffrey F.; Todor, Dorin

2005-08-15

A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKSmore » versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For {sup 103}Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of {sup 125}I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D{sub 90} by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V{sub 150} and V{sub 200} are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yazhen; Musser, Sarah K.; Saleh, Sam

1,N{sup 2}-Propanodeoxyguanosine (PdG) is a stable structural analogue for the 3-(2'-deoxy-{beta}-d-erythro-pentofuranosyl)pyrimido[1,2-?]purin-10(3H)-one (M{sub 1}dG) adduct derived from exposure of DNA to base propenals and to malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for three template-primer DNA sequences were determined, with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4), at resolutions between 2.4 and 2.7 {angstrom}. Three template 18-mer-primer 13-mer sequences, 5'-d(TCACXAAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTT)-3' (template I), 5'-d(TCACXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template II), and 5'-d(TCATXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template III), where X is PdG, were analyzed. With templates I and II, diffracting ternary complexes including dGTP were obtained. The dGTP did not pair with PdG, but instead with the 5'-neighboring templatemore » dC, utilizing Watson-Crick geometry. Replication bypass experiments with the template-primer 5?-TCACXAAATCCTTACGAGCATCGCCCCC-3'{center_dot}5'-GGGGGCGATGCTCGTAAGGATTT-3', where X is PdG, which includes PdG in the 5'-CXA-3' template sequence as in template I, showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the PdG adduct. For template III, in which the template sequence was 5'-TXG-3', a diffracting ternary complex including dATP was obtained. The dATP did not pair with PdG, but instead with the 5'-neighboring T, utilizing Watson-Crick geometry. Thus, all three ternary complexes were of the 'type II' structure described for ternary complexes with native DNA [Ling, H., Boudsocq, F., Woodgate, R., and Yang, W. (2001) Cell 107, 91--102]. The PdG adduct remained in the anti conformation about the glycosyl bond in each of these threee ternary complexes. These results provide insight into how -1 frameshift mutations might be generated for the PdG adduct, a structural model for the exocylic M{sub 1}dG adduct formed by malondialdehyde.« less

24 CFR 103.10 - What can I do if I believe someone is discriminating against me in the sale, rental, finance, or...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false What can I do if I believe someone is discriminating against me in the sale, rental, finance, or advertisement of housing? 103.10 Section 103.10 Housing and Urban Development Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY,...

Predictors of baseline peritoneal transport status in Australian and New Zealand peritoneal dialysis patients.

PubMed

Rumpsfeld, Markus; McDonald, Stephen P; Purdie, David M; Collins, John; Johnson, David W

2004-03-01

Factors that predict peritoneal transport status in peritoneal dialysis (PD) patients are poorly understood. The aim of the present study is to determine these factors in Australian and New Zealand incident PD patients. The study included all patients on the Australian and New Zealand Dialysis and Transplant Registry who started PD therapy between April 1, 1991, and March 31, 2002, and underwent a peritoneal equilibration test (PET) within the first 6 months. Predictors of peritoneal transport category and dialysate-plasma creatinine ratio at 4 hours (D-P Cr 4h) were assessed by multivariate ordinal logistic regression and multiple linear regression, respectively. A total of 3,188 patients were studied. Mean D-P Cr 4h was 0.69 +/- 0.13. High transport status was associated with older age (adjusted odds ratio [OR], 1.08 for each 10 years; 95% confidence interval [CI], 1.03 to 1.13), Maori and Pacific Islander racial origin (OR, 1.48; 95% CI, 1.13 to 1.94), and normal body mass index (BMI; < 18.5 kg/m2: OR, 0.90; 95% CI, 0.65 to 1.24; BMI of 18.5 to 25 kg/m2: OR, 1 [reference]; BMI of 25 to 30 kg/m2: OR, 0.81; 95% CI, 0.70 to 0.95; BMI > 30 kg/m2: OR, 0.71; 95% CI, 0.58 to 0.86), but was not independently predicted by sex, diabetes, other comorbid diseases, smoking, previous hemodialysis therapy or transplantation, or residual renal function. Similar results were found when peritoneal permeability was modeled as a continuous variable (D-P Cr 4h). In Australian and New Zealand PD patients, higher peritoneal transport status is independently associated with racial origin, older age, and lower BMI. The diversity of peritoneal transport characteristics in different ethnic populations suggests that additional validation of PET measurements in various racial groups and study of their relationship to patient outcomes are warranted.

Preface

DTIC Science & Technology

2016-09-13

lems arising, for example, after discretization of optimal control problems. Lucien developed a general framework for quantifying near-optimality...Polak, E., Da Cunha, N.O.: Constrainedminimization under vector valued-criteria in finite dimensional spaces. J. Math . Anal. Appl. 19(1), 103–124...1969) 12. Pironneau, O., Polak, E.: On the rate of convergence of certain methods of centers. Math . Program. 2(2), 230–258 (1972) 13. Polak, E., Sargent

Development and validation of an SPME-GC method for a degradation kinetics study of propiconazole I, propiconazole II and tebuconazole in blueberries in Concordia, the main production area of Argentina.

PubMed

Munitz, Martín S; Medina, María B; Montti, María I T

2017-05-01

An analytical method for the simultaneous determination of propiconazole isomers and tebuconazole residues in blueberries was developed using solid-phase microextraction (SPME) coupled to gas chromatography. Confirmation was performed by gas chromatography-mass spectrometry in selected-ion monitoring mode. The SPME fibre coating selected was CWX-DVB, and the pH was adjusted to 7 with NaOH. The method is selective with adequate precision and high accuracy and sensitivity. Recoveries ranged between 97.4% and 98.9% for all compounds; and detection and quantification limits were respectively 0.21 and 0.49 μg kg -1 for propiconazole I; 0.16 and 0.22 μg kg -1 for propiconazole II; and 0.16 and 0.48 μg kg -1 for tebuconazole. The degradation of these fungicides in blueberries followed first-order rate kinetics. The half-life times for flowering and fruit set applications were respectively 4.0 and 10.3 days for propiconazole I, 4.0 and 11.4 days for propiconazole II, and 3.5 and 12.4 days for tebuconazole.

Late-life Hemoglobin and the Incidence of Parkinson’s Disease

PubMed Central

Abbott, Robert D.; Ross, G. Webster; Tanner, Caroline M.; Andersen, Julie K.; Masaki, Kamal H.; Rodriguez, Beatriz L.; White, Lon R.; Petrovitch, Helen

2010-01-01

Background Brain iron promotes neurodegeneration in Parkinson’s disease (PD). While hemoglobin (Hb) is the most abundant source of peripheral iron in humans, its relationship with PD is uncertain. This report examines the association between Hb in late-life and PD incidence. Methods From 1991-1993, Hb was measured in 3,507 men in the Honolulu-Asia Aging Study. Men were aged 71-93 years and without PD. Participants were followed until 2001 for incident PD. Results Hb levels declined markedly with age. For men aged 71-75 years, 14.8% had levels <14 g/dL versus 53.6% in those aged 86 and older (p<0.001). During follow-up, 47 men developed PD (19.8/10,000 person-years). After age-adjustment, PD incidence rose significantly from 10.3 to 34.9/10,000 person-years as Hb increased from <14 to ≥16 g/dL (p=0.024, relative hazard 3.2, 95% CI 1.2-8.9). Associations persisted after accounting for early mortality and adjustments for concomitant risk factors. Conclusions While Hb declines with advancing age, evidence suggests that Hb that remains high in elderly men is associated with an increased risk of PD. PMID:20709430

Palladium-103 plaque radiation therapy for ciliary body melanoma through a functioning glaucoma filtering bleb.

PubMed

Pathan, Arif H K; Barash, Alexander; Tena, Lawrence B; Finger, Paul T

2018-01-01

To provide a clinical description of the long-term outcome of a 103 Pd plaque-irradiated ciliary body melanoma with extrascleral extension while attempting to preserve a subadjacent glaucoma filtering bleb. A 75-year-old woman with pseudoexfoliative glaucoma for 17 years, 16 years status post argon laser trabeculoplasty, and 15 years status post trabeculectomy in the left eye, was diagnosed with an ipsilateral ciliary body melanoma with visible extrascleral extension. Treatment involved insertion of a 103 Pd radioactive plaque over the functioning trabeculectomy, with removal 7 days later. At plaque insertion, amniotic membrane grafts were used to cover the plaque and protect the filtering site. The tumor was successfully treated without clinical evidence of harm to the filtering bleb, with resultant stable intraocular pressure. However, the patient developed blebitis 1.5 years later. Though it resolved with topical antibiotic therapy, the bleb became less succulent. Two years postoperatively, she developed a spontaneous hyphema that resolved after one injection of transscleral bevacizumab 1.25 mg. Her tumor continually regressed in thickness. Without additional glaucoma surgery, her intraocular pressure remained well-controlled on topical medications for 6 years. Ciliary body melanoma with minimal extrascleral extension beneath a functioning filtering bleb can be treated using radioactive plaque therapy. In this case, we were able to achieve both tumor regression and glaucoma control by covering the plaque with an amniotic membrane graft.

Lack of Radiation Maculopathy After Palladium-103 Plaque Radiotherapy for Iris Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yousef, Yacoub A.; Finger, Paul T., E-mail: pfinger@eyecancer.com

2012-07-15

Purpose: To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by {sup 103}Pd plaque radiotherapy. Methods and Materials: This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. Results: Thirty patients were followed for a median 36 months (range, 12-90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extendingmore » into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75-100 Gy), lens dose 43.5 Gy (range, 17.8-60 Gy), fovea dose 1.8 Gy (range, 1.3-5 Gy), and central optic disc dose 1.7 Gy (range, 1.3-4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was {>=}20/25 in 28 patients (93%) at a median 36 months' follow-up. Conclusion: Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after {sup 103}Pd treatment of iris and iridociliary melanomas.« less

Moving Toward Focal Therapy in Prostate Cancer: Dual-Isotope Permanent Seed Implants as a Possible Solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todor, Dorin A., E-mail: dtodor@mcvh-vcu.edu; Barani, Igor J.; Lin, Peck-Sun

2011-09-01

Purpose: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Methods and Materials: Nine plans, using {sup 125}I, {sup 103}Pd, and {sup 131}Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTV{sub i}) were delineated along with PTV (prostate + 5 mm), rectum, and urethra. Single-isotope implants,more » prescribed to conventional doses, were generated to achieve good PTV coverage. The PTV{sub i} were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. Results: The EUBED of PTV{sub i} in the setting of primary {sup 125}I implant increased 20-66% when {sup 103}Pd and {sup 131}Cs were used compared with {sup 125}I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTV{sub i} (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. Conclusions: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland.« less

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

The production of radionuclides for nuclear medicine from a compact, low-energy accelerator system.

PubMed

Webster, William D; Parks, Geoffrey T; Titov, Dmitry; Beasley, Paul

2014-05-01

The field of nuclear medicine is reliant on radionuclides for medical imaging procedures and radioimmunotherapy (RIT). The recent shut-downs of key radionuclide producers have highlighted the fragility of the current radionuclide supply network, however. To ensure that nuclear medicine can continue to grow, adding new diagnostic and therapy options to healthcare, novel and reliable production methods are required. Siemens are developing a low-energy, high-current - up to 10 MeV and 1 mA respectively - accelerator. The capability of this low-cost, compact system for radionuclide production, for use in nuclear medicine procedures, has been considered. The production of three medically important radionuclides - (89)Zr, (64)Cu, and (103)Pd - has been considered, via the (89)Y(p,n), (64)Ni(p,n) and (103)Rh(p,n) reactions, respectively. Theoretical cross-sections were generated using TALYS and compared to experimental data available from EXFOR. Stopping power values generated by SRIM have been used, with the TALYS-generated excitation functions, to calculate potential yields and isotopic purity in different irradiation regimes. The TALYS excitation functions were found to have a good agreement with the experimental data available from the EXFOR database. It was found that both (89)Zr and (64)Cu could be produced with high isotopic purity (over 99%), with activity yields suitable for medical diagnostics and therapy, at a proton energy of 10MeV. At 10MeV, the irradiation of (103)Rh produced appreciable quantities of (102)Pd, reducing the isotopic purity. A reduction in beam energy to 9.5MeV increased the radioisotopic purity to 99% with only a small reduction in activity yield. This work demonstrates that the low-energy, compact accelerator system under development by Siemens would be capable of providing sufficient quantities of (89)Zr, (64)Cu, and (103)Pd for use in medical diagnostics and therapy. It is suggested that the system could be used to produce many other isotopes currently useful to nuclear medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship Between Gender, Age, and Weight and the Serum Ionized Calcium Variations in Dog Periodontal Disease Evolution.

PubMed

Carreira, L Miguel; Dias, Daniela; Azevedo, Pedro

2015-06-01

To analyze the relationships between gender, age, weight, and variations in the levels of serum ionized calcium ([iCa(2+)]) during periodontal disease (PD) evolution. In this study, dogs (n = 50) were divided into 5 groups according to the stage of PD: G0 (no PD), G1 (gingivitis), G2 (initial periodontitis), G3 (moderate periodontitis), and G4 (severe periodontitis). Statistically significant correlations were observed between age, [iCa(2+)] levels, and PD stage. Older dogs had lower [iCa(2+)] levels and more advanced PD stages (high positive correlation), and their body weight decreased as PD developed (negative correlation). Lower [iCa(2+)] values were associated with more severe PD. Copyright © 2015 Elsevier Inc. All rights reserved.

New concepts for HgI2 scintillator gamma ray spectroscopy

NASA Technical Reports Server (NTRS)

Iwanczyk, Jan S.

1994-01-01

The primary goals of this project are development of the technology for HgI2 photodetectors (PD's), development of a HgI2/scintillator gamma detector, development of electronics, and development of a prototype gamma spectrometer. Work on the HgI2 PD's involved HgI2 purification and crystal growth, detector surface and electrical contact studies, PD structure optimization, encapsulation and packaging, and testing. Work on the HgI2/scintillator gamma detector involved a study of the optical - mechanical coupling for the optimization of CsI(Tl)/HgI2 gamma ray detectors and determination of the relationship between resolution versus scintillator type and size. The development of the electronics focused on low noise amplification circuits using different preamp input FET's and the use of a coincidence technique to maximize the signal, minimize the noise contribution in the gamma spectra, and improve the overall system resolution.

Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas.

PubMed

Kim, Jennifer E; Patel, Mira A; Mangraviti, Antonella; Kim, Eileen S; Theodros, Debebe; Velarde, Esteban; Liu, Ann; Sankey, Eric W; Tam, Ada; Xu, Haiying; Mathios, Dimitrios; Jackson, Christopher M; Harris-Bookman, Sarah; Garzon-Muvdi, Tomas; Sheu, Mary; Martin, Allison M; Tyler, Betty M; Tran, Phuoc T; Ye, Xiaobu; Olivi, Alessandro; Taube, Janis M; Burger, Peter C; Drake, Charles G; Brem, Henry; Pardoll, Drew M; Lim, Michael

2017-01-01

Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS. C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed. Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples. This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124-36. ©2016 AACR. ©2016 American Association for Cancer Research.

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

PubMed Central

Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

2011-01-01

Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson’s disease (PD) and incidental Parkinson’s disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders. PMID:21717034

Development of personality and the remission and onset of personality pathology.

PubMed

Wright, Aidan G C; Pincus, Aaron L; Lenzenweger, Mark F

2011-12-01

The current study used the Longitudinal Study of Personality Disorders data set (Lenzenweger, 1999) to examine the development of personality traits in the context of the remission and onset of personality disorder (PD) symptoms. Despite high levels of stability, past research on the development of basic personality traits has also found a mean trend toward increased maturity and that individuals vary in their trajectories of trait development. Research on PD change has shown a similar pattern. We employed individual growth curve modeling to examine the relationship between personality trait development and PD symptom course. We found that both are indeed related and that remission in PD symptoms is associated with patterns of trait development associated with more rapid maturity. In contrast, deviating from the mean of trait development either through no change (i.e., stagnation) or change in the opposite direction (i.e., regression) was associated with developing PD symptoms over the course of the study.

Photodemethylation of Methylmercury in Eastern Canadian Arctic Thaw Pond and Lake Ecosystems.

PubMed

Girard, Catherine; Leclerc, Maxime; Amyot, Marc

2016-04-05

Permafrost thaw ponds of the warming Eastern Canadian Arctic are major landscape constituents and often display high levels of methylmercury (MeHg). We examined photodegradation potentials in high-dissolved organic matter (DOC) thaw ponds on Bylot Island (BYL) and a low-DOC oligotrophic lake on Cornwallis Island (Char Lake). In BYL, the ambient MeHg photodemethylation (PD) rate over 48 h of solar exposure was 6.1 × 10(-3) m(2) E(-1), and the rate in MeHg amended samples was 9.3 × 10(-3) m(2) E(-1). In contrast, in low-DOC Char Lake, PD was only observed in the first 12 h, which suggests that PD may not be an important loss process in polar desert lakes. Thioglycolic acid addition slowed PD, while glutathione and chlorides did not impact northern PD rates. During an ecosystem-wide experiment conducted in a covered BYL pond, there was neither net MeHg increase in the dark nor loss attributable to PD following re-exposure to sunlight. We propose that high-DOC Arctic thaw ponds are more prone to MeHg PD than nearby oligotrophic lakes, likely through photoproduction of reactive species rather than via thiol complexation. However, at the ecosystem level, these ponds, which are widespread through the Arctic, remain likely sources of MeHg for neighboring systems.

Thermodynamics of Palladium (Pd) and Tantalum (Ta) Relevant to Secondary Copper Smelting

NASA Astrophysics Data System (ADS)

Shuva, M. A. H.; Rhamdhani, M. A.; Brooks, G. A.; Masood, S. H.; Reuter, M. A.

2017-02-01

The slag-to-metal distribution ratios of palladium (Pd), L_{{Pd}}^{s/m} , in the range of oxygen partial pressure ( pO2) from 10-10 to 10-7 atm at 1473 K to 1623 K (1200 °C to 1350 °C); distribution ratios of tantalum (Ta), L_{{Ta}}^{s/m} , in the range of pO2 from 10-16 to 10-12 atm at 1673 K and 1873 K (1400 °C and 1600 °C), have been determined in this study. The L_{{Pd}}^{s/m} in FeO x -CaO-SiO2-MgO and copper at 1573 K (1300 °C) and pO2 = 10-8 atm is dependant strongly on basicity of slag, i.e. (CaO + MgO)/SiO2 or optical basicity. The current results suggest that Pd presents in the FeO x -CaO-SiO2-MgO slag predominantly as Pd2+. The activity coefficient of PdO in the slag at 1573 K (1300 °C) and pO2 = 10-8 atm was calculated to be in the range of 3.89 × 10-3 to 2.63 × 10-2. The L_{{Pd}}^{s/m} was also found to increase with increasing of pO2 and with decreasing of temperature. It was observed that Ta mostly partition to slag phase and very small amount of Ta was found in liquid copper at the high temperature and reduced condition studied. It can be suggested that to promote recovery of palladium from Pd-containing e-waste, a slag with lower silica content and basic flux based, high temperature with reducing atmosphere, is highly desired particularly in secondary copper smelting.

"We Always Want to Get Better": Teachers' Voices on Professional Development

ERIC Educational Resources Information Center

Parise, Leigh M.; Finkelstein, Carla; Alterman, Emma

2015-01-01

Through the Innovative Professional Development (iPD) Challenge, the Bill & Melinda Gates Foundation has invested in helping school districts and networks redesign their professional development systems to serve educators better and improve student performance. MDRC's evaluation of the iPD Challenge involves case studies and multiple rounds of…

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

NASA Astrophysics Data System (ADS)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2010-11-01

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g-1, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to brachytherapy, with lower energy sources. Such ablative magnitude dose enhancement in a relatively small endothelial volume may rapidly disrupt or cause severe biological damage to tumor endothelial cells, without increased toxicity to healthy tissues not containing AuNPs. The findings provide significant impetus for considering the application of AuNPs as VDAs during brachytherapy.

Panic disorder and perceived parental rearing behavior investigated by the Japanese version of the EMBU scale.

PubMed

Someya, T; Kitamura, H; Uehara, T; Sakado, K; Kaiya, H; Tang, S W; Takahashi, S

2000-01-01

Although recent studies have found dysfunctional parental rearing behaviour is associated with certain aspects of psychopathology of panic disorder (PD), the results are not in complete agreement. By using a translated Japanese version of the EMBU (Egna Minnen Beträffande Uppfostran), we investigated the parental rearing behavior perceived by 103 normal subjects, 71 PD patients with agoraphobia, and 32 PD patients without agoraphobia. The PD patients scored both parents as more rejecting and overprotective than did the controls. However, subgroup analysis showed that the patients with agoraphobia reported significantly more rejection from both parents and less emotional warmth from mothers, while the patients without agoraphobia, by contrast, reported more overprotection from both parents and more favouring subject from fathers than did the controls. Interestingly, these results were consistent with those documented in the Western literature, which reported "affectionless control" as a parenting style in PD, and, furthermore, indicated a cross-cultural similarity of parental rearing factor. In addition, it was suggested that a lack of care might be associated with the development of agoraphobia in Japan.

Professional Development in a Reform Context: Understanding the Design and Enactment of Learning Experiences Created by Teacher Leaders for Science Educators

NASA Astrophysics Data System (ADS)

Shafer, Laura

Teacher in-service learning about education reforms like NGSS often begin with professional development (PD) as a foundational component (Supovitz & Turner, 2000). Teacher Leaders, who are early implementers of education reform, are positioned to play a contributing role to the design of PD. As early implementers of reforms, Teacher Leaders are responsible for interpreting the purposes of reform, enacting reforms with fidelity to meet those intended goals, and are positioned to share their expertise with others. However, Teacher Leader knowledge is rarely accessed as a resource for the design of professional development programs. This study is unique in that I analyze the knowledge Teacher Leaders, who are positioned as developers of PD, bring to the design of PD around science education reform. I use the extended interconnected model of professional growth (Clarke & Hollingsworth, 2002; Coenders & Terlouw, 2015) to analyze the knowledge pathways Teacher Leaders' access as PD developers. I found that Teacher Leaders accessed knowledge pathways that cycled through their personal domain, domain of practice and domain of consequence. Additionally the findings indicated when Teacher Leaders did not have access to these knowledge domains they were unwilling to continue with PD design. These findings point to how Teacher Leaders prioritize their classroom experience to ground PD design and use their perceptions of student learning outcomes as an indicator of the success of the reform. Because professional development (PD) is viewed as an important resource for influencing teachers' knowledge and beliefs around the implementation of education reform efforts (Garet, et al., 2001; Suppovitz & Turner, 2000), I offer that Teacher Leaders, who are early implementers of reform measures, can contribute to the professional development system. The second part of this dissertation documents the instantiation of the knowledge of Teacher Leaders, who are positioned as designers and facilitators of PD. I examine the extent to which Teacher Leader knowledge is instantiated into specific resources and tasks during PD specifically for the Next Generation Science Standards (NGSS). The findings indicate that Teacher Leaders' knowledge is instantiated in tasks that promote and facilitate alignment of Teacher Leader goals for NGSS science practices-based instruction, which are framed around student learning outcomes. I offer a number of ways in which these findings can help educators and PD developers to better structure activities that present an alternative vision for science education that also provides the needed resources to shape how classroom tasks are designed and managed in ways that attend to and build on the practical knowledge of Teacher Leaders. The third part of this dissertation addresses the role Teacher Leaders play in this reform context with respect to their contributions to the professional development system. Based on the analyses of the Teacher Leaders in this study, I claim Teacher Leaders are essential contributors to the professional development system that extends beyond their typical role of participant. I argue that Teacher Leaders bring special expertise to the role of designers and facilitators of PD programs, and to the role of ambassadors for professional learning communities in a reform context. Because Teacher Leaders have a broader influence on the professional development system as pictured here, the Teacher Leaders in this study represent an essential piece of the reform puzzle.

Employment as a welder and Parkinson disease among heavy equipment manufacturing workers.

PubMed

Marsh, Gary M; Gula, Mary Jean

2006-10-01

We investigated whether employment as a welder with potential exposure to manganese and other substances is associated with Parkinson disease (PD), parkinsonism or related neurological disorders, or accelerates the age of onset of PD. We selected cases and controls from 12,595 persons ever employed at three Caterpillar Inc. (CAT) plants between 1976 and 2004 with potential to make a medical insurance claim between 1998 and 2004. Cases had filed a claim for 1) PD, 2) "secondary parkinsonism", 3) "other degenerative diseases of the basal ganglia" or 4) "essential and other specific forms of tremor". Cases were grouped by claims: Group 1-claims 1 and 2 and Group 2-claims 1 to 4, and as study period incident (SPI) or prevalent. Each case was matched to two series of 10 controls each on date of case's first claim, year of birth, race and sex. Series I was also matched on plant. Odds ratios (OR) and 95% confidence intervals (CI) for the variable, "ever welder in any CAT plant" were: Group 1-SPI Cases: Series I (OR = .76, CI = .26-2.19), Series II (OR = .81, CI = .29-2.25); Group 1- Prevalent Cases: Series I (OR = .82, CI = .36-1.86), Series II (OR = .97, CI = .42-2.23); Group 2- SPI Cases: Series I (OR = 1.03, CI = .57-1.87), Series II (OR = 1.21, CI = .67-2.20) Group 2-Prevalent Cases: Series I (OR = 1.02, CI = .62-1.71), Series II (OR = .86, CI = .51-1.43). Our finding of no statistically significant associations for welding employment was maintained following adjustment for potential confounding and evaluation of possible effect modification. Employment as a welder did not accelerate the age of onset of PD. Our study supported the conclusion that employment as a welder is not associated with Parkinson disease, parkinsonism or a related neurological disorder.

24 CFR 103.40 - Can I change my complaint after it is filed?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Can I change my complaint after it is filed? 103.40 Section 103.40 Housing and Urban Development Regulations Relating to Housing and... it is filed? (a) Yes, you may change your fair housing complaint: (1) At any time to add or remove...

PET imaging of β-glucuronidase activity by an activity-based 124I-trapping probe for the personalized glucuronide prodrug targeted therapy.

PubMed

Su, Yu-Cheng; Cheng, Ta-Chun; Leu, Yu-Ling; Roffler, Steve R; Wang, Jaw-Yuan; Chuang, Chih-Hung; Kao, Chien-Han; Chen, Kai-Chuan; Wang, Hsin-Ell; Cheng, Tian-Lu

2014-12-01

Beta-glucuronidase (βG) is a potential biomarker for cancer diagnosis and prodrug therapy. The ability to image βG activity in patients would assist in personalized glucuronide prodrug cancer therapy. However, whole-body imaging of βG activity for medical usage is not yet available. Here, we developed a radioactive βG activity-based trapping probe for positron emission tomography (PET). We generated a (124)I-tyramine-conjugated difluoromethylphenol beta-glucuronide probe (TrapG) to form (124)I-TrapG that could be selectively activated by βG for subsequent attachment of (124)I-tyramine to nucleophilic moieties near βG-expressing sites. We estimated the specificity of a fluorescent FITC-TrapG, the cytotoxicity of tyramine-TrapG, and the serum half-life of (124)I-TrapG. βG targeting of (124)I-TrapG in vivo was examined by micro-PET. The biodistribution of (131)I-TrapG was investigated in different organs. Finally, we imaged the endogenous βG activity and assessed its correlation with therapeutic efficacy of 9-aminocamptothecin glucuronide (9ACG) prodrug in native tumors. FITC-TrapG showed specific trapping at βG-expressing CT26 (CT26/mβG) cells but not in CT26 cells. The native TrapG probe possessed low cytotoxicity. (124)I-TrapG preferentially accumulated in CT26/mβG but not CT26 cells. Meanwhile, micro-PET and whole-body autoradiography results demonstrated that (124)I-TrapG signals in CT26/mβG tumors were 141.4-fold greater than in CT26 tumors. Importantly, Colo205 xenografts in nude mice that express elevated endogenous βG can be monitored by using infrared glucuronide trapping probes (NIR-TrapG) and suppressed by 9ACG prodrug treatment. (124)I-TrapG exhibited low cytotoxicity allowing long-term monitoring of βG activity in vivo to aid in the optimization of prodrug targeted therapy. ©2014 American Association for Cancer Research.

Development of Personality and the Remission and Onset of Personality Pathology

PubMed Central

Wright, Aidan G. C.; Pincus, Aaron L.; Lenzenweger, Mark F.

2011-01-01

The current study uses the Longitudinal Study of Personality Disorders dataset (Lenzenweger, 1999) to examine the development of personality traits in the context of the remission and onset of personality disorder (PD) symptoms. Despite high levels of stability, past research that has examined the development of basic personality traits has also found a mean trend towards increased maturity, and that individuals vary in their trajectories of trait development. Research on PD change has shown a similar pattern. We employ individual growth curve modeling to examine the relationship between personality trait development and PD symptom course. We found that the two are indeed related, and that remission in PD symptoms is associated with patterns of trait development associated with more rapid maturity. In contrast, deviating from the mean of trait development either through no change (i.e., stagnation) or change in the opposite direction (i.e., regression) was associated with developing PD symptoms over the course of the study. PMID:21967009

PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Gevensleben, Heidrun; Holmes, Emily Eva; Goltz, Diane; Dietrich, Jörn; Sailer, Verena; Ellinger, Jörg; Dietrich, Dimo; Kristiansen, Glen

2016-11-29

The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa). In the training cohort, normal tissue showed significantly lower levels of mPD-L1 compared to tumor tissue. High mPD-L1 in PCa was associated with biochemical recurrence (BCR) in univariate Cox proportional hazards (hazard ratio (HR)=2.60 [95%CI: 1.50-4.51], p=0.001) and Kaplan-Meier analyses (p<0.001). These results were corroborated in an independent validation cohort in univariate Cox (HR=1.24 [95%CI: 1.08-1.43], p=0.002) and Kaplan-Meier analyses (p=0.029). Although mPD-L1 and PD-L1 protein expression did not correlate in the validation cohort, both parameters added significant prognostic information in bivariate Cox analysis (HR=1.22 [95%CI: 1.05-1.42], p=0.008 for mPD-L1 and HR=2.58 [95%CI: 1.43-4.63], p=0.002 for PD-L1 protein expression). mPD-L1 was analyzed in a training cohort from The Cancer Genome Atlas (n=498) and was subsequently measured in an independent validation cohort (n=299) by quantitative methylation-specific real-time PCR. All patients had undergone radical prostatectomy. mPD-L1 is a promising biomarker for the risk stratification of PCa patients and might offer additional relevant prognostic information to the implemented clinical parameters, particularly in the setting of immune checkpoint inhibition.

Endotherapy is effective for pancreatic ductal disruption: A dual center experience.

PubMed

Das, Rohit; Papachristou, Georgios I; Slivka, Adam; Easler, Jeffrey J; Chennat, Jennifer; Malin, Jessica; Herman, Justin B; Laique, Sobia N; Hayat, Umar; Ooi, Yinn Shaung; Rabinovitz, Mordechai; Yadav, Dhiraj; Siddiqui, Ali A

2016-01-01

Pancreatic duct (PD) disruptions occur as a result of different etiologies and can be managed medically, endoscopically, or surgically. The aim of this study was to provide an evaluation on the efficacy of endotherapy for treatment of PD disruption in a large cohort of patients and identify factors that predict successful treatment outcome. We retrospectively evaluated consecutive patients who underwent endoscopic retrograde pancreatography (ERP) for transpapillary pancreatic stent placement for PD disruption from 2008 to 2013 at two tertiary referral institutions. PD disruption was defined as extravasation of contrast from the pancreatic duct as seen on ERP. Therapeutic success was defined by resolution of PD leak on ERP, clinical, and/or imaging evaluation. We evaluated 107 patients (58% male, mean age 53 years) with PD disruption. Etiologies of PD disruption were acute pancreatitis (36%), post-operative (31%), chronic pancreatitis (29%), and trauma (4%). PD disruption was successfully bridged by a stent in 45 (44%) patients. Two patients developed post-sphincterotomy bleeding, two had stent migration, and two patients died as a result of post-ERP related complications. Placement of a PD stent was successful in 103/107 (96%) patients. Therapeutic success was achieved in 80/107 (75%) patients. Non-acute pancreatitis etiologies and absence of complete duct disruption were independent predictors of therapeutic success. Endoscopic therapy using a transpapillary stent for PD disruption is safe and effective. Absence of complete duct disruption and non-AP etiologies determine a favorable endoscopic outcome. Published by Elsevier India Pvt Ltd.

Impact of glucose-6-phosphate dehydrogenase deficiency on sickle cell anaemia expression in infancy and early childhood: a prospective study.

PubMed

Benkerrou, Malika; Alberti, Corinne; Couque, Nathalie; Haouari, Zinedine; Ba, Aissatou; Missud, Florence; Boizeau, Priscilla; Holvoet, Laurent; Ithier, Ghislaine; Elion, Jacques; Baruchel, André; Ducrocq, Rolande

2013-12-01

In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal screening, including 27 G6PD-deficient patients, who were matched on sex, age and parents' geographic origin to 81 randomly selected patients with normal G6PD activity. In the G6PD-deficient group, steady-state haemoglobin was lower (-6·2 g/l, 95% confidence interval (CI), [-10·1; -2·3]) and reticulocyte count higher (247 × 10(9) /l, 95%CI, [97; 397]). The acute anaemic event rate was 3 times higher in the G6PD-deficient group (P < 10(-3) ). A higher proportion of G6PD-deficient patients required blood transfusion (20/27 [74%] vs. 37/81 [46%], P < 10(-3) ), for acute anaemic events, and also vaso-occlusive and infectious events. No significant between-group differences were found regarding the rates of vaso-occlusive, infectious, or cerebrovascular events. G6PD deficiency in babies with SCA worsens anaemia and increases blood transfusion requirements in the first years of life. These effects decrease after 2 years of age, presumably as the decline in fetal haemoglobin levels leads to increased sickle cell haemolysis and younger red blood cells with higher G6PD activity. © 2013 John Wiley & Sons Ltd.

KSC-08pd1271

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- Two of the crewmembers for the STS-124 mission, Pilot Ken Ham and Mission Specialist Akihiko Hoshide, depart NASA's Kennedy Space Center in a T-38 training jet after a successful launch dress rehearsal called the terminal countdown demonstration test. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

KSC-08pd1270

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The crew for the STS-124 mission departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Mission Specialist Akihiko Hoshide climbs into the T-38 training jet for he flight back to Houston. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

KSC-08pd1268

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- Two of the crewmembers for the STS-124 mission, Mission Specialists Ron Garan and Karen Nyberg, depart NASA's Kennedy Space Center in a T-38 training jet after a successful launch dress rehearsal called the terminal countdown demonstration test. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

Comparison of linear–stochastic and nonlinear–deterministic algorithms in the analysis of 15-minute clinical ECGs to predict risk of arrhythmic death

PubMed Central

Skinner, James E; Meyer, Michael; Nester, Brian A; Geary, Una; Taggart, Pamela; Mangione, Antoinette; Ramalanjaona, George; Terregino, Carol; Dalsey, William C

2009-01-01

Objective: Comparative algorithmic evaluation of heartbeat series in low-to-high risk cardiac patients for the prospective prediction of risk of arrhythmic death (AD). Background: Heartbeat variation reflects cardiac autonomic function and risk of AD. Indices based on linear stochastic models are independent risk factors for AD in post-myocardial infarction (post-MI) cohorts. Indices based on nonlinear deterministic models have superior predictability in retrospective data. Methods: Patients were enrolled (N = 397) in three emergency departments upon presenting with chest pain and were determined to be at low-to-high risk of acute MI (>7%). Brief ECGs were recorded (15 min) and R-R intervals assessed by three nonlinear algorithms (PD2i, DFA, and ApEn) and four conventional linear-stochastic measures (SDNN, MNN, 1/f-Slope, LF/HF). Out-of-hospital AD was determined by modified Hinkle–Thaler criteria. Results: All-cause mortality at one-year follow-up was 10.3%, with 7.7% adjudicated to be AD. The sensitivity and relative risk for predicting AD was highest at all time-points for the nonlinear PD2i algorithm (p ≤0.001). The sensitivity at 30 days was 100%, specificity 58%, and relative risk >100 (p ≤0.001); sensitivity at 360 days was 95%, specificity 58%, and relative risk >11.4 (p ≤0.001). Conclusions: Heartbeat analysis by the time-dependent nonlinear PD2i algorithm is comparatively the superior test. PMID:19707283

Kinetics and inhibition of cyclomaltodextrinase from alkalophilic Bacillus sp. I-5.

PubMed

Kim, M J; Park, W S; Lee, H S; Kim, T J; Shin, J H; Yoo, S H; Cheong, T K; Ryu, S; Kim, J C; Kim, J W; Moon, T W; Robyt, J F; Park, K H

2000-01-01

The cyclomaltodextrinase from alkalophilic Bacillus sp. I-5 (CDase I-5) was expressed in Escherichia coli and the purified enzyme was used for characterization of the enzyme action. The hydrolysis products were monitored by both HPLC and high-performance ion chromatography analysis that enable the kinetic analysis of the cyclomaltodextrin (CD)-degrading reaction. Analysis of the kinetics of cyclomaltodextrin hydrolysis by CDase I-5 indicated that ring-opening of the cyclomaltodextrin was the major limiting step and that CDase I-5 preferentially degraded the linear maltodextrin chain by removing the maltose unit. The substrate binding affinity of the enzyme was almost same for those of cyclomaltodextrins while the rate of ring-opening was the fastest for cyclomaltoheptaose. Acarbose and methyl 6-amino-6-deoxy-alpha-d-glucopyranoside were relatively strong competitive inhibitors with K(i) values of 1.24 x 10(-3) and 8.44 x 10(-1) mM, respectively. Both inhibitors are likely to inhibit the ring-opening step of the CD degradation reaction. Copyright 2000 Academic Press.

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

PubMed

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

2016-06-15

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. © 2016 American Academy of Sleep Medicine.

New National Air-Kerma-Strength Standards for 125I and 103Pd Brachytherapy Seeds

PubMed Central

Seltzer, Stephen M.; Lamperti, Paul J.; Loevinger, Robert; Mitch, Michael G.; Weaver, James T.; Coursey, Bert M.

2003-01-01

The new U.S. measurement standard for the air-kerma strength from low-energy photon-emitting brachytherapy seed sources is formally described in detail. This instrument-based standard was implemented on 1 January 1999, with its salient features and the implications of differences with the previous standard given only through a series of informal communications. The Wide-Angle Free-Air Chamber (WAFAC) is specially designed to realize air kerma from a single-seed source emitting photons with energies up to about 40 keV, and is now used to measure the wide variety of seeds used in prostate-cancer therapy that has appeared in the last few years. For the two 125I seed models that have been subject to both the old and new standards, the new standard reduces the air-kerma strength by 10.3 %. This change is mainly due to the removal of the influence on the measurement of the Ti K x rays produced in the source encapsulation, a component with no clinical significance. PMID:27413614

Assessment of Minimum 124I Activity Required in Uptake Measurements Before Radioiodine Therapy for Benign Thyroid Diseases.

PubMed

Gabler, Anja S; Kühnel, Christian; Winkens, Thomas; Freesmeyer, Martin

2016-08-01

This study aimed to assess a hypothetical minimum administered activity of (124)I required to achieve comparability between pretherapeutic radioiodine uptake (RAIU) measurements by (124)I PET/CT and by (131)I RAIU probe, the clinical standard. In addition, the impact of different reconstruction algorithms on (124)I RAIU and the evaluation of pixel noise as a parameter for image quality were investigated. Different scan durations were simulated by different reconstruction intervals of 600-s list-mode PET datasets (including 15 intervals up to 600 s and 5 different reconstruction algorithms: filtered-backprojection and 4 iterative techniques) acquired 30 h after administration of 1 MBq of (124)I. The Bland-Altman method was used to compare mean (124)I RAIU levels versus mean 3-MBq (131)I RAIU levels (clinical standard). The data of 37 patients with benign thyroid diseases were assessed. The impact of different reconstruction lengths on pixel noise was investigated for all 5 of the (124)I PET reconstruction algorithms. A hypothetical minimum activity was sought by means of a proportion equation, considering that the length of a reconstruction interval equates to a hypothetical activity. Mean (124)I RAIU and (131)I RAIU already showed high levels of agreement for reconstruction intervals of as short as 10 s, corresponding to a hypothetical minimum activity of 0.017 MBq of (124)I. The iterative algorithms proved generally superior to the filtered-backprojection algorithm. (124)I RAIU showed a trend toward higher levels than (131)I RAIU if the influence of retrosternal tissue was not considered, which was proven to be the cause of a slight overestimation by (124)I RAIU measurement. A hypothetical minimum activity of 0.5 MBq of (124)I obtained with iterative reconstruction appeared sufficient both visually and with regard to pixel noise. This study confirms the potential of (124)I RAIU measurement as an alternative method for (131)I RAIU measurement in benign thyroid disease and suggests that reducing the administered activity is an option. CT information is particularly important in cases of retrosternal expansion. The results are relevant because (124)I PET/CT allows additional diagnostic means, that is, the possibility of performing fusion imaging with ultrasound. (124)I PET/CT might be an alternative, especially when hybrid (123)I SPECT/CT is not available. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Impaired frontal lobe functions in patients with Parkinson's disease and psychosis.

PubMed

Thota, Naveen; Lenka, Abhishek; George, Lija; Hegde, Shantala; Arumugham, Shyam Sundar; Prasad, Shweta; Stezin, Albert; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

2017-12-01

Patients with Parkinson's disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinson's disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-E-T-378: Evaluation of An Analytical Model for the Inter-Seed Attenuation Effect in 103-Pd Multi-Seed Implant Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safigholi, H; Soliman, A; Song, W

Purpose: Brachytherapy treatment planning systems based on TG-43 protocol calculate the dose in water and neglects the heterogeneity effect of seeds in multi-seed implant brachytherapy. In this research, the accuracy of a novel analytical model that we propose for the inter-seed attenuation effect (ISA) for 103-Pd seed model is evaluated. Methods: In the analytical model, dose perturbation due to the ISA effect for each seed in an LDR multi-seed implant for 103-Pd is calculated by assuming that the seed of interest is active and the other surrounding seeds are inactive. The cumulative dosimetric effect of all seeds is then summedmore » using the superposition principle. The model is based on pre Monte Carlo (MC) simulated 3D kernels of the dose perturbations caused by the ISA effect. The cumulative ISA effect due to multiple surrounding seeds is obtained by a simple multiplication of the individual ISA effect by each seed, the effect of which is determined by the distance from the seed of interest. This novel algorithm is then compared with full MC water-based simulations (FMCW). Results: The results show that the dose perturbation model we propose is in excellent agreement with the FMCW values for a case with three seeds separated by 1 cm. The average difference of the model and the FMCW simulations was less than 8%±2%. Conclusion: Using the proposed novel analytical ISA effect model, one could expedite the corrections due to the ISA dose perturbation effects during permanent seed 103-Pd brachytherapy planning with minimal increase in time since the model is based on multiplications and superposition. This model can be applied, in principle, to any other brachytherapy seeds. Further work is necessary to validate this model on a more complicated geometry as well.« less

PET/CT imaging of clear cell renal cell carcinoma with 124I labeled chimeric antibody

PubMed Central

Bahnson, Eamonn E.; Murrey, Douglas A.; Mojzisik, Cathy M.; Hall, Nathan C.; Martinez-Suarez, Humberto J.; Knopp, Michael V.; Martin, Edward W.; Povoski, Stephen P.; Bahnson, Robert R.

2009-01-01

Clear cell renal cell carcinoma (ccRCC) presents problems for urologists in diagnosis, treatment selection, intraoperative surgical margin analysis, and long term monitoring. In this paper we describe the development of a radiolabeled antibody specific to ccRCC (124I-cG250) and its potential to help urologists manage each of these problems. We believe 124I-cG250, in conjunction with perioperative Positron emission tomography/computed tomography imaging and intraoperative handheld gamma probe use, has the potential to diagnose ccRCC, aid in determining a proper course of treatment (operative or otherwise), confirm complete resection of malignant tissue in real time, and monitor patients post-operatively. PMID:21789055

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

PubMed Central

Yamaguchi, Rin; Nishimura, Reiki; Osako, Tomofumi; Arima, Nobuyuki; Okumura, Yasuhiro; Okido, Masayuki; Yamada, Mai; Kai, Masaya; Kishimoto, Junji; Oda, Yoshinao; Nakamura, Masafumi

2017-01-01

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies. PMID:28107186

[Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124].

PubMed

Zhu, H; Wang, F; Guo, X Y; Li, L Q; Duan, D B; Liu, Z B; Yang, Z

2018-04-18

To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application. 124 Te (p,n) 124 I nuclide reaction was used for the 124 I production. Firstly, the target material, 124 TeO 2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124 I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124 I.After 740 kBq 124 I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124 I's metabolism in the mice. It was been successfully applied for 200 mg 124 TeO 2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124 Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 μA current on HM-20 cyclotron. Then 370-1 110 MBq 124 I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification. 124 I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124 I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124 I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge, it was the first production of 124 I report in China. In this study, the preparation of 124 TeO 2 solid target was successfully carried out by using the tablet device. After irradiation of the 124 TeO 2 solid target and radio-chemical purification, we successfully produced 370-740 MBq high specific activity 124 I by a cyclotron for biomedical application, and micro-PET imaging of 124 I in normal mice exhibited the thyroid accumulations. Also, slight uptake in stomach were also monitored with almost nonuptake in other organs in the micro-PET imaging. The production of 124 I is expected to provide a new solid target radionuclide for the scientific research and potential clinical application of our country.

A survey of physics and dosimetry practice of permanent prostate brachytherapy in the United States.

PubMed

Prete, J J; Prestidge, B R; Bice, W S; Friedland, J L; Stock, R G; Grimm, P D

1998-03-01

To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.

Professional development for primary science teaching in Thailand: Knowledge, orientations, and practices of professional developers and professional development participants

NASA Astrophysics Data System (ADS)

Musikul, Kusalin

The purpose of this study was to examine an entire PD project as a case to understand the dynamic nature of science PD in a holistic manner. I used a pedagogical content knowledge model by Magnusson, Krajcik, and Borko (1999) as my theoretical framework in examining the professional developers' and teacher participants' knowledge, orientation, and practice for professional development and elementary science teaching. The case study is my research tradition; I used grounded theory for data analysis. The primary data sources were interview, card sort activity, and observation field notes collected during the PD and subsequently in teacher participants' classrooms. Secondary data sources were documents and artifacts that I collected from the professional developers and teachers. An analysis of the data led me to interpret the following findings: (a) the professional developers displayed multiple orientations. These orientations included activity-driven, didactic, discovery, and pedagogy-driven orientations. The orientations that were found among the professional developers deviated from the reformed Thai Science Education Standards; (b) the professional developers had limited PCK for PD, which were knowledge of teachers' learning, knowledge of PD strategies, knowledge of PD curriculum, and knowledge of assessment.; (c) the professional developers' knowledge and orientations influenced their decisions in selecting PD activities and teaching approaches; (d) their orientations and PCK as well as the time factor influenced the design and implementation of the professional development; (e) the elementary teachers displayed didactic, activity-driven, and academic rigor orientations. The orientations that the teachers displayed deviated from the reformed Thai Science Education Standards; and (f) the elementary teachers exhibited limited PCK. It is evident that the limitation of one type of knowledge resulted in an ineffective use of other components of PCK. This study demonstrates the nature of PD in the context of Thailand in a holistic view to understand knowledge, orientation, and implementation of professional developers and professional development participants. Furthermore, the findings have implications for professional development and professional developers in Thailand and include worldwide with respect to promoting sustain and intensive professional development and developing professional developers.

Hydrogen bonding in the mechanism of GDP-mannose mannosyl hydrolase

NASA Astrophysics Data System (ADS)

Mildvan, A. S.; Xia, Z.; Azurmendi, H. F.; Legler, P. M.; Balfour, M. R.; Lairson, L. L.; Withers, S. G.; Gabelli, S. B.; Bianchet, M. A.; Amzel, L. M.

2006-06-01

GDP-mannose mannosyl hydrolase (GDPMH) from E. coli catalyzes the hydrolysis of GDP-α- D-sugars to GDP and β- D-sugars by nucleophilic substitution with inversion at the anomeric C1 of the sugar, with general base catalysis by His-124. The 1.3 Å X-ray structure of the GDPMH-Mg 2+-GDP complex was used to model the complete substrate, GDP-mannose into the active site. The substrate is linked to the enzyme by 12 hydrogen bonds, as well as by the essential Mg 2+. In addition, His-124 was found to participate in a hydrogen bonded triad: His-124-NδH⋯Tyr-127-OH⋯Pro-120(C dbnd6 O). The contributions of these hydrogen bonds to substrate binding and to catalysis were investigated by site-directed mutagenesis. The hydrogen bonded triad detected in the X-ray structure was found to contribute little to catalysis since the Y127F mutation of the central residue shows only 2-fold decreases in both kcat and Km. The GDP leaving group is activated by the essential Mg 2+ which contributes at least 10 5-fold to kcat, and by nine hydrogen bonds, including those from Tyr-103, Arg-37, Arg-52, and Arg-65 (via an intervening water), each of which contribute factors to kcat ranging from 24- to 309-fold. Both Arg-37 and Tyr-103 bind the β-phosphate of the leaving GDP and are only 5.0 Å apart. Accordingly, the R37Q/Y103F double mutant shows partially additive effects of the two single mutants on kcat, indicating cooperativity of Arg-37 and Tyr-103 in promoting catalysis. The extensive activation of the GDP leaving group suggests a mechanism with dissociative character with a cationic oxocarbenium-like transition state and a half-chair conformation of the sugar ring, as found with glycosidase enzymes. Accordingly, Asp-22 which contributes 10 2.1- to 10 2.6-fold to kcat, is positioned to both stabilize a developing cationic center at C1 and to accept a hydrogen bond from the C2-OH of the mannosyl group, and His-88, which contributes 10 2.3-fold to kcat, is positioned to accept a hydrogen bond from the C3-OH of the mannose facilitating its distortion to a half-chair conformation. Also, the fluorinated substrate GDP-2-fluoro-α- D-mannose, for which the oxocarbenium ion-like transition state centered at C1 would be destabilized by electron withdrawal, shows a 16-fold lower kcat and a 2.5-fold greater Km than does GDP-α- D-mannose. The product of the contributions to catalysis of Arg-37 and Tyr-103 (taking their cooperativity into account), Arg-52, Arg-65, Mg 2+, Asp-22, His-124, and His-88 is ≥10 19, which exceeds the 10 12-fold rate acceleration produced by GDPMH by a factor ≥10 7. Hence, additional pairs or groups of catalytic residues must act cooperatively to promote catalysis.

Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease.

PubMed

Zhang, Zhentao; Kang, Seong Su; Liu, Xia; Ahn, Eun Hee; Zhang, Zhaohui; He, Li; Iuvone, P Michael; Duong, Duc M; Seyfried, Nicholas T; Benskey, Matthew J; Manfredsson, Fredric P; Jin, Lingjing; Sun, Yi E; Wang, Jian-Zhi; Ye, Keqiang

2017-08-01

Aggregated forms of α-synuclein play a crucial role in the pathogenesis of synucleinopathies such as Parkinson's disease (PD). However, the molecular mechanisms underlying the pathogenic effects of α-synuclein are not completely understood. Here we show that asparagine endopeptidase (AEP) cleaves human α-synuclein, triggers its aggregation and escalates its neurotoxicity, thus leading to dopaminergic neuronal loss and motor impairments in a mouse model. AEP is activated and cleaves human α-synuclein at N103 in an age-dependent manner. AEP is highly activated in human brains with PD, and it fragments α-synuclein, which is found aggregated in Lewy bodies. Overexpression of the AEP-cleaved α-synuclein 1-103 fragment in the substantia nigra induces both dopaminergic neuronal loss and movement defects in mice. In contrast, inhibition of AEP-mediated cleavage of α-synuclein (wild type and A53T mutant) diminishes α-synuclein's pathologic effects. Together, these findings support AEP's role as a key mediator of α-synuclein-related etiopathological effects in PD.

1,2,4-Tribromobenzene

Integrated Risk Information System (IRIS)

1,2,4 - Tribromobenzene ; CASRN 615 - 54 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcin

1,2,4-Trichlorobenzene

Integrated Risk Information System (IRIS)

1,2,4 - Trichlorobenzene ; CASRN 120 - 82 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarci

A Dual Reporter Iodinated Labeling Reagent for Cancer Positron Emission Tomography Imaging and Fluorescence-Guided Surgery

PubMed Central

2018-01-01

The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92 ± 5% (n = 4) determined by HPLC with an improved one-pot three-component radioiodination reaction. The A5B7 carcinoembryonic antigen (CEA)-specific antibody was conjugated to 124I-Green. High tumor uptake of the dual-labeled A5B7 of 20.21 ± 2.70, 13.31 ± 0.73, and 10.64 ± 1.86%ID/g was observed in CEA-expressing SW1222 xenograft mouse model (n = 3) at 24, 48, and 72 h post intravenous injection, respectively. The xenografts were clearly visualized by both PET/CT and ex vivo fluorescence imaging. These encouraging results warrant the further translational development of 124I-Green for cancer PET imaging and fluorescence-guided surgery. PMID:29388770

Effect of photon energy spectrum on dosimetric parameters of brachytherapy sources.

PubMed

Ghorbani, Mahdi; Mehrpouyan, Mohammad; Davenport, David; Ahmadi Moghaddas, Toktam

2016-06-01

The aim of this study is to quantify the influence of the photon energy spectrum of brachytherapy sources on task group No. 43 (TG-43) dosimetric parameters. Different photon spectra are used for a specific radionuclide in Monte Carlo simulations of brachytherapy sources. MCNPX code was used to simulate 125I, 103Pd, 169Yb, and 192Ir brachytherapy sources. Air kerma strength per activity, dose rate constant, radial dose function, and two dimensional (2D) anisotropy functions were calculated and isodose curves were plotted for three different photon energy spectra. The references for photon energy spectra were: published papers, Lawrence Berkeley National Laboratory (LBNL), and National Nuclear Data Center (NNDC). The data calculated by these photon energy spectra were compared. Dose rate constant values showed a maximum difference of 24.07% for 103Pd source with different photon energy spectra. Radial dose function values based on different spectra were relatively the same. 2D anisotropy function values showed minor differences in most of distances and angles. There was not any detectable difference between the isodose contours. Dosimetric parameters obtained with different photon spectra were relatively the same, however it is suggested that more accurate and updated photon energy spectra be used in Monte Carlo simulations. This would allow for calculation of reliable dosimetric data for source modeling and calculation in brachytherapy treatment planning systems.

Effect of photon energy spectrum on dosimetric parameters of brachytherapy sources

PubMed Central

Ghorbani, Mahdi; Davenport, David

2016-01-01

Abstract Aim The aim of this study is to quantify the influence of the photon energy spectrum of brachytherapy sources on task group No. 43 (TG-43) dosimetric parameters. Background Different photon spectra are used for a specific radionuclide in Monte Carlo simulations of brachytherapy sources. Materials and methods MCNPX code was used to simulate 125I, 103Pd, 169Yb, and 192Ir brachytherapy sources. Air kerma strength per activity, dose rate constant, radial dose function, and two dimensional (2D) anisotropy functions were calculated and isodose curves were plotted for three different photon energy spectra. The references for photon energy spectra were: published papers, Lawrence Berkeley National Laboratory (LBNL), and National Nuclear Data Center (NNDC). The data calculated by these photon energy spectra were compared. Results Dose rate constant values showed a maximum difference of 24.07% for 103Pd source with different photon energy spectra. Radial dose function values based on different spectra were relatively the same. 2D anisotropy function values showed minor differences in most of distances and angles. There was not any detectable difference between the isodose contours. Conclusions Dosimetric parameters obtained with different photon spectra were relatively the same, however it is suggested that more accurate and updated photon energy spectra be used in Monte Carlo simulations. This would allow for calculation of reliable dosimetric data for source modeling and calculation in brachytherapy treatment planning systems. PMID:27247558

Reliability assessment of MVP-BURN and JENDL-4.0 related to nuclear transmutation of light platinum group elements

NASA Astrophysics Data System (ADS)

Terashima, Atsunori; Nilsson, Mikael; Ozawa, Masaki; Chiba, Satoshi

2017-09-01

The Aprés ORIENT research program, as a concept of advanced nuclear fuel cycle, was initiated in FY2011 aiming at creating stable, highly-valuable elements by nuclear transmutation from ↓ssion products. In order to simulate creation of such elements by (n, γ) reaction succeeded by β- decay in reactors, a continuous-energy Monte Carlo burnup calculation code MVP-BURN was employed. Then, it is one of the most important tasks to con↓rm the reliability of MVP-BURN code and evaluated neutron cross section library. In this study, both an experiment of neutron activation analysis in TRIGA Mark I reactor at University of California, Irvine and the corresponding burnup calculation using MVP-BURN code were performed for validation of the simulation on transmutation of light platinum group elements. Especially, some neutron capture reactions such as 102Ru(n, γ)103Ru, 104Ru(n, γ)105Ru, and 108Pd(n, γ)109Pd were dealt with in this study. From a comparison between the calculation (C) and the experiment (E) about 102Ru(n, γ)103Ru, the deviation (C/E-1) was signi↓cantly large. Then, it is strongly suspected that not MVP-BURN code but the neutron capture cross section of 102Ru belonging to JENDL-4.0 used in this simulation have made the big di↑erence as (C/E-1) >20%.

KSC-08pd1269

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The STS-124 crew departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Seated in the T-38 training jet, Mission Specialist Mike Fossum is ready to put on his helmet for the flight back to Houston. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

KSC-08pd1266

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The crew for the STS-124 mission departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Seen here are Commander Mark Kelly and Mission Specialist Greg Chamitoff heading for the T-38 training jets for their flight back to Houston. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

KSC-08pd1265

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The crew for the STS-124 mission departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Seen here are Mission Specialists Ron Garan and Karen Nyberg heading for the T-38 training jets for their flight back to Houston. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1987. Part 8. General Fire Extinguisher Del.-Hawthorne of Missouri, Incorporated.

DTIC Science & Technology

1987-01-01

0-4 .4n~(D r-4.4.4.--00-4N -4O4N4N Q 103 (n 0 l 0 I I toN (n oC 00 0 000000c000 o 0000 00 4i 0000000000000000000000000 00000000 -0 1I00007mo 00...Ij 0 0 00 0000 0 o 7Ŕ CA 00O Io L) ’- I- 4n (oWI W rh - 4 -4 - "oi Io DO Io .- D 01 4NCA 00 01 n0) 0) 0) z0 NI -4 coo N I3 OO I y)W( -4 -0 -4 4 4 0 0...4 00 00 C’) C) 0D 0-4 000 In 0 0 0- 00030 00000 蓐 M40) 1 Co W- Inco COW(D’ CO I CIDr CO r-Cr--- 0 pC-- pD (-pW r--r.-ow0 -4) ow ow 0000 COCOCO

USSR Report, Space Biology and Aerospace Medicine, Vol. 18, No. 3, May-June 1984

DTIC Science & Technology

1984-07-03

high altitude. In the Khan Tengri expedition (6996 m), the climbers took 3-4 ordinary multiple vitamin lozenges per day during the stay in the... Tengri , only 2 of the 20 climbers who reached the top presented distinct signs of mountain sickness (apathy, muscular weakness, impaired...min/kg 4,5±0,2 3,9±0,3 (3,6—4,9) (2,96-4,8) % ECFV/min 1,34±0,I1 1,18±0,14* (1,09—1,59) (0,8—1,5) BPS 124±6 167±5* (103— 137 ) (153—187) BPd 81 ±4

PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors

PubMed Central

Hall, Lance T; Titz, Benjamin; Robins, H Ian; Bednarz, Bryan P; Perlman, Scott B; Weichert, Jamey P; Kuo, John S

2017-01-01

CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with 124I for PET imaging, 131I for targeted radiotherapy and/or SPECT imaging, or 125I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of 124I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of 124I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. 124I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of 124I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. 124I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. 124I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has potential clinical relevance. Expansion of these studies is required to determine the clinical significance of the 124I-CLR1404 PET findings. PMID:28913154

Effect of tissue composition on dose distribution in brachytherapy with various photon emitting sources

PubMed Central

Ghorbani, Mahdi; Salahshour, Fateme; Haghparast, Abbas; Knaup, Courtney

2014-01-01

Purpose The aim of this study is to compare the dose in various soft tissues in brachytherapy with photon emitting sources. Material and methods 103Pd, 125I, 169Yb, 192Ir brachytherapy sources were simulated with MCNPX Monte Carlo code, and their dose rate constant and radial dose function were compared with the published data. A spherical phantom with 50 cm radius was simulated and the dose at various radial distances in adipose tissue, breast tissue, 4-component soft tissue, brain (grey/white matter), muscle (skeletal), lung tissue, blood (whole), 9-component soft tissue, and water were calculated. The absolute dose and relative dose difference with respect to 9-component soft tissue was obtained for various materials, sources, and distances. Results There was good agreement between the dosimetric parameters of the sources and the published data. Adipose tissue, breast tissue, 4-component soft tissue, and water showed the greatest difference in dose relative to the dose to the 9-component soft tissue. The other soft tissues showed lower dose differences. The dose difference was also higher for 103Pd source than for 125I, 169Yb, and 192Ir sources. Furthermore, greater distances from the source had higher relative dose differences and the effect can be justified due to the change in photon spectrum (softening or hardening) as photons traverse the phantom material. Conclusions The ignorance of soft tissue characteristics (density, composition, etc.) by treatment planning systems incorporates a significant error in dose delivery to the patient in brachytherapy with photon sources. The error depends on the type of soft tissue, brachytherapy source, as well as the distance from the source. PMID:24790623

Quality of life and gender identity in Parkinson's disease.

PubMed

Moore, O; Kreitler, S; Ehrenfeld, M; Giladi, N

2005-11-01

We examined the correlation between gender identity (perception of masculinity or femininity) and quality of life (QoL) of 124 Parkinson's disease (PD) patients without dementia (69 men, 55 women, mean age 65.8+/-10.2 years, mean disease duration 8.5+/-5.8 years, mean Hoehn and Yahr [H&Y] stage 2.7+/-0.8). All patients underwent clinical examinations and completed the PDQ-39 and the quality of sexual life questionnaire. Their masculine or feminine stereotypes were determined by the Bem Sex Role Inventory (BSRI) modified by Dior. QoL was significantly correlated with disease duration (r=0.262, p<0.01), H&Y staging (r=0.330, p<0.001) and disease severity (UPDRS) (r=0.432, p<0.001). The QoL of androgynous men and women (i.e., with strong feminine and masculine characteristics) was significantly (p<0.05) better than the other gender groups. A significant interaction was found between the sexes to gender identity (p<0.05). Androgynous PD patients cope better with their disease in terms of QoL parameters, especially androgynous women.

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

2014-02-15

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

The sorafenib anti-relapse effect after alloHSCT is associated with heightened alloreactivity and accumulation of CD8+PD-1+ (CD279+) lymphocytes in marrow

PubMed Central

Lange, Janusz; Dworacki, Grzegorz; Nowak, Dorota; Simiczyjew, Aleksandra; Mordak-Domagala, Monika; Sedzimirska, Mariola

2018-01-01

We studied three FLT3 ITD acute myeloid leukemia (AML) patients who relapsed after allogeneic haematopoietic stem cell transplantation (alloHSCT) and received multikinase inhibitor (MKI) sorafenib as part of salvage therapy. MKI was given to block the effect of FLT3 ITD mutation which powers proliferation of blast cells. However, the known facts that sorafenib is more effective in patents post alloHSCT suggested that this MKI can augment the immune system surveillance on leukaemia. In the present study, we investigated in depth the effect of sorafenib on the alloreactivity seen post-transplant including that on leukaemia. The patients (i) responded to the treatment with cessation of blasts which lasted 1, 17 and 42+ months, (ii) developed skin lesions with CD3+ cell invasion of the epidermis, (iii) had marrow infiltrated with CD8+ lymphocytes which co-expressed PD-1 (programmed cell death protein 1 receptor, CD279) in higher proportions than those in the blood (163±32 x103 cells/μl vs 38±8 x103 cells/μl, p<0.001). The Lymphoprep fraction of marrow cells investigated for the expression of genes involved in lymphocyte activation showed in the patients with long lasting complete remission (CR) a similar pattern characterized by (i) a low expression of nitric oxide synthase 2 (NOS2) and colony stimulating factor 2 (CSF2) as well as that of angiopoietin-like 4 (ANGPTL4) (supporting the immune response and anti-angiogenic) genes, and (ii) higher expression of fibroblast growth factor 1 (FGF1) and collagen type IV alpha 3 chain (COL4A3) as well as toll like receptor 9 (TLR9) and interleukin-12 (IL-12) (pro-inflammatory expression profile) genes as compared with the normal individual. The positive effect in one patient hardly justified the presence of unwanted effects (progressive chronic graft-versus-host disease (cGvHD) and avascular necrosis of the femur), which were in contrast negligible in the other patient. The anti-leukemic and unwanted effects of sorafenib do not rely on each other. PMID:29304116

Cognitive decline and quality of life in incident Parkinson's disease: The role of attention.

PubMed

Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Breen, David P; Khoo, Tien K; Williams-Gray, Caroline H; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J

2016-06-01

Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort. Recently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition. Baseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = -2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = -0.4, p < 0.01). PD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of high 131I-activities on quantitative 124I-PET

NASA Astrophysics Data System (ADS)

Braad, P. E. N.; Hansen, S. B.; Høilund-Carlsen, P. F.

2015-07-01

Peri-therapeutic 124 I-PET/CT is of interest as guidance for radioiodine therapy. Unfortunately, image quality is complicated by dead time effects and increased random coincidence rates from high 131 I-activities. A series of phantom experiments with clinically relevant 124 I/131 I-activities were performed on a clinical PET/CT-system. Noise equivalent count rate (NECR) curves and quantitation accuracy were determined from repeated scans performed over several weeks on a decaying NEMA NU-2 1994 cylinder phantom initially filled with 25 MBq 124 I and 1250 MBq 131 I. Six spherical inserts with diameters 10-37 mm were filled with 124 I (0.45 MBq ml-1 ) and 131 I (22 MBq ml-1 ) and placed inside the background of the NEMA/IEC torso phantom. Contrast recovery, background variability and the accuracy of scatter and attenuation corrections were assessed at sphere-to-background activity ratios of 20, 10 and 5. Results were compared to pure 124 I-acquisitions. The quality of 124 I-PET images in the presence of high 131 I-activities was good and image quantification unaffected except at very high count rates. Quantitation accuracy and contrast recovery were uninfluenced at 131 I-activities below 1000 MBq, whereas image noise was slightly increased. The NECR peaked at 550 MBq of 131 I, where it was 2.8 times lower than without 131 I in the phantom. Quantitative peri-therapeutic 124 I-PET is feasible.

Palladium(II) complexes with highly basic imidazolin-2-imines and their reactivity toward small bio-molecules.

PubMed

Bogojeski, Jovana; Volbeda, Jeroen; Freytag, Matthias; Tamm, Matthias; Bugarčić, Živadin D

2015-10-21

A series of novel Pd(ii) complexes with chelating mono(imidazolin-2-imine) and bis(imidazolin-2-imine) ligands were synthesized. The crystal structures of [Pd(DMEAIm(iPr))Cl2] and [Pd(DPENIm(iPr))Cl2] were determined by X-ray diffraction analysis. The reactivity of the six Pd(ii) complexes, namely, [Pd(en)Cl2], [Pd(EAIm(iPr))Cl2], [Pd(DMEAIm(iPr))Cl2], [Pd(DPENIm(iPr))Cl2], [Pd(BL(iPr))Cl2] and [Pd(DACH(Im(iPr))2)Cl2], were investigated. Spectrophotometric acid-base titrations were performed to determine the pKa values of the coordinated water molecules in [Pd(en)(H2O)2](2+), [Pd(EAIm(iPr))(H2O)2](2+), [Pd(DMEAIm(iPr))(H2O)2](2+), [Pd(DPENIm(iPr))(H2O)2](2+), [Pd(BL(iPr))(H2O)2](2+) and [Pd(DACH(Im(iPr))2)(H2O)2](2+). The substitution of the chloride ligands in these complexes by TU, l-Met, l-His and Gly was studied under pseudo-first-order conditions as a function of the nucleophile concentration and temperature using stopped-flow techniques; the sulfur-donor nucleophiles have shown better reactivity than nitrogen-donor nucleophiles. The obtained results indicate that there is a clear correlation between the nature of the imidazolin-2-imine ligands and the acid-base characteristics and reactivity of the resulting Pd(ii) complexes; the order of reactivity of the investigated Pd(ii) complexes is: [Pd(en)Cl2] > [Pd(EAIm(iPr))Cl2] > [Pd(DMEAIm(iPr))Cl2] > [Pd(DPENIm(iPr))Cl2] > [Pd(BL(iPr))Cl2] > [Pd(DACH(Im(iPr))2)Cl2]. The solubility measurements revealed good solubility of the studied imidazolin-2-imine complexes in water, despite the fact that these Pd(ii) complexes are neutral complexes. Based on the performed studies, three unusual features of the novel imidazolin-2-imine Pd(ii) complexes are observed, that is, good solubility in water, very low reactivity and high pKa values. The coordination geometries around the palladium atoms are distorted square-planar; the [Pd(DMEAIm(iPr))Cl2] complex displays Pd-N distances of 2.013(2) and 2.076(2) Å, while the [Pd(DPENIm(iPr))Cl2] complex displays similar Pd-N distances of 2.034(4) and 2.038(3) Å. The studied systems are of interest because little is known about the substitution behavior of imidazolin-2-imine Pd(ii) complexes with bio-molecules under physiological conditions.

Teaching Argumentative Writing to Teachers and Students: Effects of Professional Development

ERIC Educational Resources Information Center

Howell, Emily; Hunt-Barron, Sarah; Kaminski, Rebecca; Sanders, Rachel

2018-01-01

This multiple-case study design with embedded units of analysis examined a two-year professional development (PD) program in which two rural districts received at least 90 hours of PD. This PD was provided through an Investing in Innovation (i3) grant that the United States Department of Education awarded to the National Writing Project. Two of…

Regression Patterns of Iris Melanoma after Palladium-103 (103Pd) Plaque Brachytherapy.

PubMed

Chaugule, Sonal S; Finger, Paul T

2017-07-01

To evaluate the patterns of regression of iris melanoma after treatment with palladium-103 ( 103 Pd) plaque brachytherapy. Retrospective, nonrandomized, interventional case series. Fifty patients with primary malignant melanoma of the iris. Palladium-103 plaque brachytherapy. Changes in tumor size, pigmentation, and vascularity; incidence of iris neovascularization; and radiation-related complications. The mean age in the case series was 61.2±14.9 years. The mean tumor thickness was 1.4±0.6 mm. According to the American Joint Committee on Cancer, eighth edition, staging criteria for iris melanoma, 21 tumors (42%) were T1a, 5 tumors (10%) were T1b, and 24 tumors (48%) were T2a. The tumor was melanotic in 37 cases (74%) and amelanotic in 13 cases (26%); of these, 13 tumors (26%) showed variable pigmentation. After brachytherapy, mean tumor thickness decreased to 0.9±0.2 mm. Pigmentation increased in 32 tumors (64%), decreased in 11 tumors (22%), and was unchanged in 6 tumors (12%). For intrinsic vascularity (n = 19), 12 tumors (63%) showed decrease and 7 tumors (37%) showed complete resolution. Appearance of ectropion uveae showed diminution in 15 tumors (43%); newly present corectopia was observed in 6 patients (12%). On high-frequency ultrasound imaging, of the 42 tumors (84%) with low to moderate internal reflectivity, 30 tumors (60%) showed an increase in internal reflectivity on regression. Iris stromal atrophy was noted in 26 patients (52%), progression or new-onset cataract was noted in 22 patients (44%), neovascular glaucoma was noted in 1 patient (2%), and there were no cases of corneal opacity. There was no clinical evidence (0%) of radiation-induced retinopathy, maculopathy, or optic neuropathy. Mean follow-up in this series was 5.2 years (range, 0.5-17 years). The most common findings related to iris melanoma regression after 103 Pd plaque brachytherapy included decreased intrinsic tumor vascularity, increased tumor pigmentation, and decreased tumor thickness with synchronous increase in internal ultrasonographic reflectivity. No irreversible sight-limiting complications were noted. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Classification of iRBD and Parkinson's disease patients based on eye movements during sleep.

PubMed

Christensen, Julie A E; Koch, Henriette; Frandsen, Rune; Kempfner, Jacob; Arvastson, Lars; Christensen, Soren R; Sorensen, Helge B D; Jennum, Poul

2013-01-01

Patients suffering from the sleep disorder idiopathic rapid-eye-movement sleep behavior disorder (iRBD) have been observed to be in high risk of developing Parkinson's disease (PD). This makes it essential to analyze them in the search for PD biomarkers. This study aims at classifying patients suffering from iRBD or PD based on features reflecting eye movements (EMs) during sleep. A Latent Dirichlet Allocation (LDA) topic model was developed based on features extracted from two electrooculographic (EOG) signals measured as parts in full night polysomnographic (PSG) recordings from ten control subjects. The trained model was tested on ten other control subjects, ten iRBD patients and ten PD patients, obtaining a EM topic mixture diagram for each subject in the test dataset. Three features were extracted from the topic mixture diagrams, reflecting "certainty", "fragmentation" and "stability" in the timely distribution of the EM topics. Using a Naive Bayes (NB) classifier and the features "certainty" and "stability" yielded the best classification result and the subjects were classified with a sensitivity of 95 %, a specificity of 80% and an accuracy of 90 %. This study demonstrates in a data-driven approach, that iRBD and PD patients may exhibit abnorm form and/or timely distribution of EMs during sleep.

Multi-modal Brain MRI in Subjects with PD and iRBD.

PubMed

Mangia, Silvia; Svatkova, Alena; Mascali, Daniele; Nissi, Mikko J; Burton, Philip C; Bednarik, Petr; Auerbach, Edward J; Giove, Federico; Eberly, Lynn E; Howell, Michael J; Nestrasil, Igor; Tuite, Paul J; Michaeli, Shalom

2017-01-01

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a condition that often evolves into Parkinson's disease (PD). Therefore, by monitoring iRBD it is possible to track the neurodegeneration of individuals who may progress to PD. Here we aimed at piloting the characterization of brain tissue properties in mid-brain subcortical regions of 10 healthy subjects, 8 iRBD, and 9 early-diagnosed PD. We used a battery of magnetic resonance imaging (MRI) contrasts at 3 T, including adiabatic and non-adiabatic rotating frame techniques developed by our group, along with diffusion tensor imaging (DTI) and resting-state fMRI. Adiabatic T 1ρ and T 2ρ , and non-adiabatic RAFF4 (Relaxation Along a Fictitious Field in the rotating frame of rank 4) were found to have lower coefficient of variations and higher sensitivity to detect group differences as compared to DTI parameters such as fractional anisotropy and mean diffusivity. Significantly longer T 1ρ were observed in the amygdala of PD subjects vs. controls, along with a trend of lower functional connectivity as measured by regional homogeneity, thereby supporting the notion that amygdalar dysfunction occurs in PD. Significant abnormalities in reward networks occurred in iRBD subjects, who manifested lower network strength of the accumbens. In agreement with previous studies, significantly longer T 1ρ occurred in the substantia nigra compacta of PD vs. controls, indicative of neuronal degeneration, while regional homogeneity was lower in the substantia nigra reticulata. Finally, other trend-level findings were observed, i.e., lower RAFF4 and T 2ρ in the midbrain of iRBD subjects vs. controls, possibly indicating changes in non-motor features as opposed to motor function in the iRBD group. We conclude that rotating frame relaxation methods along with functional connectivity measures are valuable to characterize iRBD and PD subjects, and with proper validation in larger cohorts may provide pathological signatures of iRBD and PD.

The relative contribution of physical and cognitive fall risk factors in people with Parkinson's disease: a large prospective cohort study.

PubMed

Paul, Serene S; Sherrington, Catherine; Canning, Colleen G; Fung, Victor S C; Close, Jacqueline C T; Lord, Stephen R

2014-01-01

In order to develop multifaceted fall prevention strategies for people with Parkinson's disease (PD), greater understanding of the impact of physical and cognitive performance on falls is required. We aimed to identify the relative contribution of a comprehensive range of physical and cognitive risk factors to prospectively-measured falls in a large sample of people with PD and develop an explanatory multivariate fall risk model in this group. METHODS MEASURES: of PD signs and symptoms, freezing of gait, balance, mobility, proprioception, leg muscle strength, and cognition were collected on 205 community-dwelling people with PD. Falls were monitored prospectively for 6 months using falls diaries. A total of 120 participants (59%) fell during follow-up. Freezing of gait (P < .001), dyskinesia (P = .02), impaired anticipatory and reactive balance (P < .001), impaired cognition (P = .002), reduced leg muscle strength (P = .006), and reduced proprioception (P = .04) were significantly associated with future falls in univariate analyses. Freezing of gait (risk ratio [RR] = 1.03, 95% confidence interval [CI] = 1.00-1.05, P = .02), impaired anticipatory (RR = 1.01, 95% CI = 1.00-1.02, P = .03) and reactive (RR = 1.26, 95% CI = 1.01-1.58, P = .04) balance, and impaired orientation (RR = 1.28, 95% CI = 1.01-1.62, P = .04) maintained significant associations with falls in multivariate analysis. The study findings elucidate important physical and cognitive determinants of falls in people with PD and may assist in developing efficacious fall prevention strategies for this high-risk group.

Moving toward focal therapy in prostate cancer: dual-isotope permanent seed implants as a possible solution.

PubMed

Todor, Dorin A; Barani, Igor J; Lin, Peck-Sun; Anscher, Mitchell S

2011-09-01

To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Ocular Motor and Sensory Function in Parkinson Disease

PubMed Central

Almer, Zina; Klein, Kathyrn S.; Marsh, Laura; Gerstenhaber, Melissa; Repka, Michael X.

2011-01-01

Purpose To evaluate the effect of dopaminergic medication and deep brain stimulation on ocular function in Parkinson disease (PD) and to measure vision-related quality of life in subjects with PD. Design Prospective comparative case series. Participants and Controls Twenty-seven PD and 16 control subjects were recruited. Methods We measured visual acuity, ocular motor function, convergence, and vision-related quality of life using the Visual Function Questionnaire–25 (VFQ-25). Visual sensory and motor measurements were made during the “on” and “off” states of PD dopaminergic treatment. Main Outcome Measures Convergence ability and vision related quality of life. Results The PD subjects had a mean age of 58.8 years; 30% were female. Their mean duration of PD was 10.9 ± 6.8 years. The control subjects had a mean age of 61.6 years; 56% were female. There was no difference in visual acuity, contrast sensitivity or color vision of the PD subjects in their “on” state compared with controls. Convergence amplitudes measured with base-out prism were significantly poorer in PD subjects compared with controls (24.1 ± 8 Δ vs 14.8 ±10.3 Δ; P=0.003). The mean composite VFQ-25 score was significantly worse in the PD subjects compared with the controls (87.1 ± 8.69 vs 96.6 ± 3.05; P=0.0001). Comparing the PD subjects in their “on” with their “off” states, there was no difference in distance exodeviation, near exodeviation or ocular ductions. Mean convergence amplitudes and near point of convergence were better in the “on” state compared with the “off” state, 14.8±10.3 Δ vs 10.7±9.0 Δ, (P=0.0006), and 13.1±9.1 cm vs 18.1±12.2, (P=0.002), respectively. Conclusions Convergence ability is significantly poorer in PD subjects in both their “on” and “off” states compared with controls, but significantly improves with systemic dopaminergic treatment. Ocular motor function in PD subjects fluctuates in response to treatment, which complicates ophthalmic management. PD subjects have a significant reduction in vision-related quality of life, especially near activities, that is not associated with visual acuity. PMID:21959370

Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients.

PubMed

Kotepui, Manas; Uthaisar, Kwuntida; PhunPhuech, Bhukdee; Phiwklam, Nuoil

2016-04-25

This study aimed to evaluate the prevalence and alteration of hematological parameters in malaria patients with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, in the western region of Thailand, an endemic region for malaria. Data about patients with malaria hospitalized between 2013 and 2015 were collected. Clinical and sociodemographic characteristics such as age and gender, diagnosis on admission, and parasitological results were mined from medical records of the laboratory unit of the Phop Phra Hospital in Tak Province, Thailand. Venous blood samples were collected at the time of admission to hospital to determine G6PD deficiency by fluorescence spot test and detect malaria parasites by thick and thin film examination. Other data such as complete blood count and parasite density were also collected and analyzed. Among the 245 malaria cases, 28 (11.4 %) were diagnosed as Plasmodium falciparum infections and 217 cases (88.6 %) were diagnosed as P. vivax infections. Seventeen (6.9 %) patients had a G6PD deficiency and 228 (93.1 %) patients did not have a G6PD deficiency. Prevalence of male patients with G6PD deficiency was higher than that of female patients (P < 0.05, OR = 5.167). Among the patients with a G6PD deficiency, two (11.8 %) were infected with P. falciparum, while the remaining were infected with P. vivax. Malaria patients with a G6PD deficiency have higher monocyte counts (0.6 × 10(3)/μL) than those without a G6PD deficiency (0.33 × 10(3)/μL) (P < 0.05, OR = 5.167). Univariate and multivariate analyses also confirmed that malaria patients with a G6PD deficiency have high monocyte counts. The association between G6PD status and monocyte counts was independent of age, gender, nationality, Plasmodium species, and parasite density (P < 0.005). This study showed a prevalence of G6PD deficiency in a malaria-endemic area. This study also supported the assertion that patients with G6PD-deficient red blood cells had no protection against the P. falciparum infection. In addition, malaria patients with a G6PD deficiency had higher monocyte counts than those without a G6PD deficiency. These findings will help to recognize and diagnose malaria patients with a G6PD deficiency, as well as to identify the risks and protective factors against malaria in endemic areas.

Cellular glucose-6-phosphate dehydrogenase (G6PD) status modulates the effects of nitric oxide (NO) on human foreskin fibroblasts.

PubMed

Cheng, M L; Ho, H Y; Liang, C M; Chou, Y H; Stern, A; Lu, F J; Chiu, D T

2000-06-23

Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in cellular redox homeostasis, which is crucial for cell survival. In the present study, we found that G6PD status determines the response of cells exposed to nitric oxide (NO) donor. Treatment with NO donor, sodium nitroprusside (SNP), caused apoptosis in G6PD-deficient human foreskin fibroblasts (HFF1), whereas it was growth stimulatory in the normal counterpart (HFF3). Such effects were abolished by NO scavengers like hemoglobin. Ectopic expression of G6PD in HFF1 cells switched the cellular response to NO from apoptosis to growth stimulation. Experiments with 1H-¿1,2,4ŏxadiazolo¿4, 3-aquinoxalin-1-one and 8-bromo-cGMP showed that the effects of NO on HFF1 and HFF3 cells were independent of cGMP signalling pathway. Intriguingly, trolox prevented the SNP-induced apoptosis in HFF1 cells. These data demonstrate that G6PD plays a critical role in regulation of cell growth and survival.

(124)I-iodopyridopyrimidinone for PET of Abl kinase-expressing tumors in vivo.

PubMed

Doubrovin, Mikhail; Kochetkova, Tatiana; Santos, Elmer; Veach, Darren R; Smith-Jones, Peter; Pillarsetty, Nagavarakishore; Balatoni, Julius; Bornmann, William; Gelovani, Juri; Larson, Steven M

2010-01-01

Because of the recent development of an iodopyridopyrimidinone Abl protein kinase inhibitor (PKI), (124)I-SKI-212230 ((124)I-SKI230), we investigated the feasibility of a PET-based molecular imaging method for the direct visualization of Abl kinase expression and PKI treatment. In vitro pharmacokinetic properties, including specific and nonspecific binding of (124)I-SKI230 to its Abl kinase target and interaction with other PKIs, were assessed in cell-free medium and chronic myelogenous leukemia (CML) cells overexpressing BCR-Abl (K562), in comparison with BT-474 cells that are low in Abl expression. In a xenograft tumor model, we assessed the in vivo pharmacokinetics of (124)I-SKI230 using PET and postmortem tissue sampling. We also tested a paradigm of (124)I-SKI230 PET after treatment of the animal with a dose of Abl-specific PKI for the monitoring of the tumor response. In vitro studies confirmed that SKI230 binds to Abl kinase with nanomolar affinity, that selective uptake occurs in cell lines known to express Abl kinase, that RNAi knock-down supports specificity of cellular uptake due to Abl kinase, and that imatinib, an archetype Abl PKI, completely displaces SKI230. With SKI230, we obtained successful in vivo PET of Abl-expressing human tumors in a nude rat. We were also able to demonstrate evidence of substrate inhibition of in vivo radiotracer uptake in the xenograft tumor after treatment of the animal as a model of PKI treatment monitoring. These results support the hypothesis that molecular imaging using PET will be useful for the study of in vivo pharmacodynamics of Abl PKI molecular therapy in humans.

KSC-08pd1267

NASA Image and Video Library

2008-05-09

CAPE CANAVERAL, Fla. -- The crew for the STS-124 mission departs NASA's Kennedy Space Center after a successful launch dress rehearsal called the terminal countdown demonstration test. Commander Mark Kelly (right) waits his turn to climb into the cockpit of the T-38 training jet for the flight back to Houston. Mission Specialist Greg Chamitoff is already seated. The crew is expected to return in late May for the May 31 launch of space shuttle Discovery. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

KSC-08pd1174

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Akihiko Hoshide takes his place in the M113 armored personnel carrier, to practice driving as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1171

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Ron Garan is pleased with his driving practice in the M113 armored personnel carrier, part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1182

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Commander Mark Kelly is ready to practice driving the M113 armored personnel carrier as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1180

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Mike Fossum stands ready to practice driving the M113 armored personnel carrier as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1178

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Greg Chamitoff stands ready to practice driving the M113 armored personnel carrier as part of emergency training. He and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1166

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Karen Nyberg waits to begin training on the M113 armored personnel carrier on Launch Pad 39B. She and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1455

NASA Image and Video Library

2008-05-28

CAPE CANAVERAL, Fla. -- After their arrival on the Shuttle Landing Facility at NASA's Kennedy Space Center, the crew members of space shuttle Discovery's STS-124 mission pose for a group photo. From left are Mission Specialists Gregory Chamitoff and Akihiko Hoshide, Pilot Ken Ham, Mission Specialists Karen Nyberg and Mike Fossum, Commander Mark Kelly and Mission Specialist Ron Garan. Launch of Discovery is scheduled for 5:02 p.m. May 31. On the STS-124 mission, the crew of seven will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Photo credit: NASA/Kim Shiflett

Facile synthesis of palladium nanoparticle doped polyaniline nanowires in soft templates for catalytic applications

NASA Astrophysics Data System (ADS)

Kshirasagar, Krushna J.; Markad, Uddhav S.; Saha, Abhijit; Sharma, Kiran Kumar K.; Sharma, Geeta K.

2017-02-01

Palladium nanoparticles doped polyaniline (Pd-PANI) nanocomposite (NCs) is synthesized in surfactant based liquid crystalline mesophase by chemical oxidation followed by radiolysis. The confinement of the liquid crystalline mesophase facilitates polymerization of aniline monomers and their 1D growth into polyaniline (PANI) nanowires by using ammonium persulfate. The PANI nanowires have an average diameter of 30-40 nm. The in situ radiolytic reduction of palladium ions ensures uniform size distribution of the palladium (Pd) nanoparticles on the surface of the PANI nanowires. The synthesized Pd-PANI nanocomposites show wire like structures of PANI (diameter ~30-40 nm) on which Pd nanoparticles of the size 10 nm are decorated. The identical average diameter of the PANI nanowires before and post gamma irradiation suggest high stability of the PANI nanowires in liquid crystalline mesophase. Surface characterization of the NCs were carried out using BET and XPS. The catalytic activity of Pd-PANI NCs are investigated in the reduction of methylene blue (MB) and 4-nitro phenol (4-NP) by sodium borohydride (NaBH4). The kinetics of the Pd-PANI NCs catalysed reactions are analysed using the Langmuir-Hinshelwood model. The apparent rate constant (k app) for the MB and 4-NP reduction reactions is 29  ×  10-3 s-1 and 20  ×  10-3 s-1 respectively with an actual Pd catalyst loading of 2.665  ×  10-4 ppm. Further, the recyclability of the Pd-PANI NCs catalyst in both the reduction reactions shows the stability of the catalyst up to four reaction cycles tested in this investigation and the multifunctional nature of the catalyst. The study provides a new approach for the directional synthesis of conducting polymer-metal nanocomposites and their possible application as a nanocatalyst in environmental remediation.

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell.

PubMed

Berendse, H W; Booij, J; Francot, C M; Bergmans, P L; Hijman, R; Stoof, J C; Wolters, E C

2001-07-01

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]beta-CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, two of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]beta-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Evaluation of excitation functions of proton and deuteron induced reactions on enriched tellurium isotopes with special relevance to the production of iodine-124.

PubMed

Aslam, M N; Sudár, S; Hussain, M; Malik, A A; Shah, H A; Qaim, S M

2010-09-01

Cross-section data for the production of medically important radionuclide (124)I via five proton and deuteron induced reactions on enriched tellurium isotopes were evaluated. The nuclear model codes, STAPRE, EMPIRE and TALYS, were used for consistency checks of the experimental data. Recommended excitation functions were derived using a well-defined statistical procedure. Therefrom integral yields were calculated. The various production routes of (124)I were compared. Presently the (124)Te(p,n)(124)I reaction is the method of choice; however, the (125)Te(p,2n)(124)I reaction also appears to have great potential.

Diffusion-weighted MR imaging in thymic epithelial tumors: correlation with World Health Organization classification and clinical staging.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Khairy, Mohamed; Nada, Nadia

2014-10-01

To assess thymic epithelial tumors with diffusion-weighted magnetic resonance (MR) imaging. Informed consent from patients and institutional review board approval were obtained. Prospective study was conducted on 30 consecutive patients (21 men and nine women; age range, 35-71 years) with thymic epithelial tumors. They underwent true fast imaging with steady-state precession and single-shot echo-planar diffusion-weighted MR imaging of the mediastinum with b values of 0, 400, and 800 sec/mm(2). Apparent diffusion coefficient (ADC) of the thymic epithelial tumors was calculated by the same observer at two settings and was correlated with World Health Organization classification and clinical staging. There was significant difference in longest diameter (P = .001) and necrotic part of the tumor (P = .014) between low-risk thymoma, high-risk thymoma, and thymic carcinoma. Mean ADC value of both readings of thymic epithelial tumors (n = 30) was 1.24 × 10(-3) mm(2)/sec and 1.22 × 10(-3) mm(2)/sec, with good intraobserver agreement (κ = 0.732). There was significant difference in both readings (P = .01 and .20) of low-risk thymoma (1.30 × 10(-3) mm(2)/sec and 1.29 × 10(-3) mm(2)/sec), high-risk thymoma (1.16 × 10(-3) mm(2)/sec and 1.14 × 10(-3) mm(2)/sec), and thymic carcinoma (1.18 × 10(-3) mm(2)/sec and 1.06 × 10(-3) mm(2)/sec). Cutoff ADC values of both readings used to differentiate low-risk thymoma from high-risk thymoma and thymic carcinoma were 1.25 and 1.22 × 10(-3) mm(2)/sec with area under the curve of 0.804 and 0.851, respectively. There was significant difference in both readings of ADC value of early (stage I, II) and advanced stages (stage III, IV) of thymic epithelial tumors (P = .006 and .005, respectively). ADC value is a noninvasive, reliable, and reproducible imaging parameter that may help to assess and characterize thymic epithelial tumors. © RSNA, 2014.

13 CFR 124.103 - Who is socially disadvantaged?

Code of Federal Regulations, 2010 CFR

2010-01-01

... denial of equal access to institutions of higher education, exclusion from social and professional association with students or teachers, denial of educational honors rightfully earned, and social patterns or... prejudice or cultural bias within American society because of their identities as members of groups and...

40 CFR 124.203 - How may I switch from my individual RCRA permit to a standardized permit?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true How may I switch from my individual RCRA permit to a standardized permit? 124.203 Section 124.203 Protection of Environment ENVIRONMENTAL... Permit Applying for A Standardized Permit § 124.203 How may I switch from my individual RCRA permit to a...

40 CFR 124.203 - How may I switch from my individual RCRA permit to a standardized permit?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false How may I switch from my individual RCRA permit to a standardized permit? 124.203 Section 124.203 Protection of Environment ENVIRONMENTAL... Permit Applying for A Standardized Permit § 124.203 How may I switch from my individual RCRA permit to a...

40 CFR 124.203 - How may I switch from my individual RCRA permit to a standardized permit?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false How may I switch from my individual RCRA permit to a standardized permit? 124.203 Section 124.203 Protection of Environment ENVIRONMENTAL... Permit Applying for A Standardized Permit § 124.203 How may I switch from my individual RCRA permit to a...

40 CFR 124.203 - How may I switch from my individual RCRA permit to a standardized permit?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false How may I switch from my individual RCRA permit to a standardized permit? 124.203 Section 124.203 Protection of Environment ENVIRONMENTAL... Permit Applying for A Standardized Permit § 124.203 How may I switch from my individual RCRA permit to a...

40 CFR 124.203 - How may I switch from my individual RCRA permit to a standardized permit?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false How may I switch from my individual RCRA permit to a standardized permit? 124.203 Section 124.203 Protection of Environment ENVIRONMENTAL... Permit Applying for A Standardized Permit § 124.203 How may I switch from my individual RCRA permit to a...

Two-Temperature Vapor Lock and High-Temperature Driveability Performance of 1982 Passenger Vehicles.

DTIC Science & Technology

1984-12-01

Wigd Starting -.*- - Air TcA TcB Air TcA TcB AirT ------- sec RSt# 1 498. 106 144 114 106 169 114 1060 SNP 2 453 99 134 112 99 172 111 990 SNN 0 3 ...sec RSt# 1 500 81 115 101 83 159 88 820 SNP 1 2 39 82 124 104 93 163 90 825 SN 2 3 2 68 102 76 68 112 66 680 SC 1 0 .L i 0 0 0 -- -- KEY-OFF...83 121 99 85 142 99 840 SNP 2 91 85 131 103 86 161 101 855 SN 3 405 66 101 73 68 123 72 680 SC 0 0 0 , ......------ IDLE SOAK ACCELERATIONS

Relational Dynamics in Teacher Professional Development

ERIC Educational Resources Information Center

Finkelstein, Carla

2013-01-01

Teacher professional development (PD) is considered essential to improving student achievement toward high standards. I argue that while current notions of high quality PD foreground cognitive aspects of learning, they undertheorize the influence of relational dynamics in teacher learning interactions. That is, current conceptions of high quality…

[(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection.

PubMed

Zhang, Xiaoyan M; Zhang, Halle H; McLeroth, Patrick; Berkowitz, Richard D; Mont, Michael A; Stabin, Michael G; Siegel, Barry A; Alavi, Abass; Barnett, T Marc; Gelb, Jeffrey; Petit, Chantal; Spaltro, John; Cho, Steve Y; Pomper, Martin G; Conklin, James J; Bettegowda, Chetan; Saha, Saurabh

2016-05-01

Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Body Awareness in Children with Mental Retardation

ERIC Educational Resources Information Center

Simons, Johan; Dedroog, Inge

2009-01-01

The body awareness of 124 toddlers with mental retardation and of 124 children developing normally matched to them on age and gender was examined. Twenty-nine of the children with mental retardation were diagnosed as Down syndrome (DS). The "Pointing and Naming" Test of Berges and Lezine [Berges, J., & Lezine, I. (1978). "Test d'imitation de…

Analysis of results of radiation therapy for stage IB carcinoma of the cervix.

PubMed

Montana, G S; Fowler, W C; Varia, M A; Walton, L A; Mack, Y

1987-11-01

From April of 1969 through December of 1980, 197 patients with Stage IB, invasive, epidermoid carcinoma of the cervix received radical radiation therapy. The treatment consisted of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 5000 to 5500 rad to the pelvic lymph nodes. The 2-, 5-, and 10-year, disease-free survival rates were 87%, 83%, and 81%, respectively. Thirty-six patients developed recurrent and/or metastatic disease. The sites that failed to remain disease-free were: locoregional in five patients (3%), locoregional with distant metastases in 15 patients (8%), and distant metastases only in 14 patients (7%). In addition, there were two patients (1%) who are considered to have died of disease but the site or sites of recurrence could not be determined. Thirty-nine patients developed complications. The complications were mild and self-limiting--Grade I--in 24 patients (12%) and of moderate severity--Grade II--in eight patients (4%). Seven patients (4%) developed severe--Grade III--complications. A correlation was found between the dose to Point A, the bladder, and the rectum and the complications. The mean dose to Point A for patients without and with complications were 7453 rad (SE +/- 91) and 7737 (SE +/- 124), respectively, with a P value of .05. The mean dose to the bladder for patients without and with urinary complications was 5590 rad (SE +/- 103) and 6335 rad (SE +/- 411), respectively, with a P value of 0.14. The mean dose to the rectum for patients without and with intestinal complications was 5837 rad (SE +/- 103) and 6810 rad (SE +/- 236), respectively, with a P value of 0.001. No correlation was found between the dose to Point A and locoregional recurrences.

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

PubMed

Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

2018-02-01

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is the Image Quality of I-124-PET Impaired by an Automatic Correction of Prompt Gammas?

PubMed Central

Preylowski, Veronika; Schlögl, Susanne; Schoenahl, Frédéric; Jörg, Gerhard; Samnick, Samuel; Buck, Andreas K.; Lassmann, Michael

2013-01-01

Objectives The aim of this study is to evaluate the quality of I-124 PET images with and without prompt gamma compensation (PGC) by comparing the recovery coefficients (RC), the signal to noise ratios (SNR) and the contrast to F-18 and Ga-68. Furthermore, the influence of the PGC on the quantification and image quality is evaluated. Methods For measuring the image quality the NEMA NU2-2001 PET/SPECT-Phantom was used containing 6 spheres with a diameter between 10 mm and 37 mm placed in water with different levels of background activity. Each sphere was filled with the same activity concentration measured by an independently cross-calibrated dose calibrator. The “hot” sources were acquired with a full 3D PET/CT (Biograph mCT®, Siemens Medical USA). Acquisition times were 2 min for F-18 and Ga-68, and 10 min for I-124. For reconstruction an OSEM algorithm was applied. For I-124 the images were reconstructed with and without PGC. For the calculation of the RCs the activity concentrations in each sphere were determined; in addition, the influence of the background correction was studied. Results The RCs of Ga-68 are the smallest (79%). I-124 reaches similar RCs (87% with PGC, 84% without PGC) as F-18 (84%). showing that the quantification of I-124 images is similar to F-18 and slightly better than Ga-68. With background activity the contrast of the I-124 PGC images is similar to Ga-68 and F-18 scans. There was lower background activity in the I-124 images without PGC, which probably originates from an overcorrection of the scatter contribution. Consequently, the contrast without PGC was much higher than with PGC. As a consequence PGC should be used for I-124. Conclusions For I-124 there is only a slight influence on the quantification depending on the use of the PGC. However, there are considerable differences with respect to I-124 image quality. PMID:24014105

Reactive Oxygen Species and Inhibitors of Inflammatory Enzymes, NADPH Oxidase, and iNOS in Experimental Models of Parkinson's Disease

PubMed Central

Koppula, Sushruta; Kumar, Hemant; Kim, In Su; Choi, Dong-Kug

2012-01-01

Reactive oxygen species (ROSs) are emerging as important players in the etiology of neurodegenerative disorders including Parkinson's disease (PD). Out of several ROS-generating systems, the inflammatory enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase (iNOS) were believed to play major roles. Mounting evidence suggests that activation of NADPH oxidase and the expression of iNOS are directly linked to the generation of highly reactive ROS which affects various cellular components and preferentially damage midbrain dopaminergic neurons in PD. Therefore, appropriate management or inhibition of ROS generated by these enzymes may represent a therapeutic target to reduce neuronal degeneration seen in PD. Here, we have summarized recently developed agents and patents claimed as inhibitors of NADPH oxidase and iNOS enzymes in experimental models of PD. PMID:22577256

Development of sustainable Palladium-based catalysts for removal of persistent contaminants from drinking water

NASA Astrophysics Data System (ADS)

Shuai, Danmeng

Pd-based catalytic reduction has emerged as an advanced treatment technology for drinking water decontamination, and a suite of persistent contaminants including oxyanions, N-nitrosoamines, and halogenated compounds are amenable to catalytic reduction. The primary goal of this study is to develop novel Pd-based catalysts with enhanced performance (i.e., activity, selectivity, and sustainability) to remove contaminants from drinking water. The effects of water quality (i.e., co-contaminants in water matrix), catalyst support, and catalyst metal were explored, and they provide insights for preparing catalysts with faster kinetics, higher selectivity, and extended lifetime. Azo dyes are wide-spread contaminants, and they are potentially co-exisiting with target contaminants amenable for catalytic removal. The probe azo dye methyl orange (MO) enhanced catalytic reduction kinetics of a suite of oxyanions (i.e., nitrate, nitrite, bromate, chlorate, and perchlorate) and diatrizoate significantly but not N-nitrosodimethylamine (NDMA) with a variety of Pd-based catalysts. Nitrate was selected as a probe contaminant, and several different azo dyes (i.e., (methyl orange, methyl red, fast yellow AB, metanil yellow, acid orange 7, congo red, eriochrome black T, acid red 27, acid yellow 11, and acid yellow 17) were evaluated for their ability to enhance reduction. A hydrogen atom shuttling mechanism was proposed and a kinetic model was proposed based on Bronsted-Evans-Polanyi (BEP) theory, and they suggest sorbed azo dyes and reduced hydrazo dyes shuttle hydrogen atoms to oxyanions or diatrizoate to enhance their reduction kinetics. Next, vapor-grown carbon nanofiber (CNF) supports were used to explore the effects of Pd nanoparticle size and interior versus exterior loading on nitrite reduction activity and selectivity (i.e., dinitrogen over ammonia production). In order to evaluate the amount of interior versus exterior loading of Pd nanoparticles, a fast and accurate geometric model was developed based on two-dimensional transmission electron microscopy (2D TEM). Results from my method agree adequately with 3D scanning transmission electron microscopy (3D TEM), which is recognized as a convincing method to evaluate interior versus exterior loading. By using Pd CNF catalysts for nitrite reduction, results show that both activity and selectivity are not significantly impacted by Pd interior versus exterior loading. Turnover frequencies (TOFs) among all CNF catalysts are consistent, suggesting faster kinetics are achieved on catalysts with smaller Pd nanoparticles, and suggesting nitrite reduction is neither sensitive to Pd location on CNFs nor Pd structure. However selectivity to dinitrogen is more favorable on larger Pd nanoparticles. Therefore, an optimum Pd nanoparticle size on CNFs balances high reduction kinetics and selectivity to dinitrogen. CNF Pd catalysts perform better than conventional activated or alumina supported Pd catalysts in term of kinetics and selectivity for nitrite reduction, and they maintain consistent activity during multiple reduction cycles. Lastly, the structure-sensitivity of catalytic activity and selectivity for contaminant nitrite, NDMA, and diatrizoate removal were investigated on shape- and size-controlled Pd nanoparticles. Results show that TOFs for nitrite, NDMA, and diatrizoate are dependent on coordination numbers of surface Pd sites at low contaminant concentration, but TOFs for nitrite at high concentration are consistent. Selectivity to ammonia for nitrite reduction decreases with increasing surface Pd sites, i.e., decreasing Pd nanoparticle size irrespective of nitrite concentration, but NDMA reduction is neither shape- nor size-specific, and it exclusively proceeds to ammonia and dimethylamine. Diatrizoate reduction selectivity is also likely to be nonspecific to shape and size, and a series of deiodinated intermediates, 3,5-diacetamidobenzoic acid, and iodide are the produced. Hence, this study suggests that contaminant reduction kinetics and selectivity are Pd shape and size dependent, and the dependence varies by contaminant type and concentration. In summary, Pd-based catalysts can be tailored for enhanced activity, selectivity, and longevity, and catalytic treatment holds the promise for advanced drinking water treatment.

76 FR 4696 - Ocean Transportation Intermediary License Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

...: New NVO License. Makro Logistics Group, LLC (NVO & OFF), 2229 NW. 79 Avenue, Doral, FL 33122. Officers.... SAPIA Logistics, Inc. (NVO & OFF), 1331 Gemini Street, Suite 103, Houston, TX 77058. Officers: Vernon... License. Seagull Global Logistics USA Limited Liability Company (OFF), 124 Jackson Avenue, Princeton, NJ...

13 CFR 124.103 - Who is socially disadvantaged?

Code of Federal Regulations, 2014 CFR

2014-01-01

... prejudice or cultural bias within American society because of their identities as members of groups and... institutions of higher education, exclusion from social and professional association with students or teachers... bias because of their identity as group members and without regard to their individual qualities, SBA...

13 CFR 124.103 - Who is socially disadvantaged?

Code of Federal Regulations, 2013 CFR

2013-01-01

... prejudice or cultural bias within American society because of their identities as members of groups and... institutions of higher education, exclusion from social and professional association with students or teachers... bias because of their identity as group members and without regard to their individual qualities, SBA...

13 CFR 124.103 - Who is socially disadvantaged?

Code of Federal Regulations, 2012 CFR

2012-01-01

... prejudice or cultural bias within American society because of their identities as members of groups and... institutions of higher education, exclusion from social and professional association with students or teachers... bias because of their identity as group members and without regard to their individual qualities, SBA...

Is there a one-way street from essential tremor to Parkinson's disease? Possible biological ramifications.

PubMed

Louis, E D; Ottman, R

2013-11-01

There is considerable evidence for an association between essential tremor (ET) and Parkinson's disease (PD), although the topic remains somewhat controversial. An important issue, not previously addressed, is what seems to be the unidirectional nature of the relationship (ET→ET + PD and not PD→PD + ET). The aims of this review are (i) to discuss the evidence for and against a unidirectional relationship and (ii) to discuss the implications of such a unidirectional relationship, if it exists, for disease mechanisms. Evidence 'for' a unidirectional relationship includes (i) abundant clinical anecdotal observation and (ii) clinical and epidemiological studies. Evidence 'against' is theoretical rather than empirical. Overall, the evidence 'for' is stronger, although additional studies are needed in order to be certain; for the time being, it might be best to leave this as an open question. The biological ramifications/extensions of such a unidirectional relationship include (i) that the association is causal (i.e., some aspect of ET pathophysiology predisposes an individual to develop PD) and (ii) that some ET cases may have a circumscribed form of Lewy body disease, and the secondary development of PD may represent a spread of those Lewy bodies in the brainstem. The presence and nature of the links between ET and PD are controversial. Further primary data (epidemiological and pathological) are needed to improve understanding of the relationship and its implications for the pathogenesis of both disorders. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

TU-AB-BRC-08: Egs-brachy, a Fast and Versatile Monte Carlo Code for Brachytherapy Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chamberland, M; Taylor, R; Rogers, D

2016-06-15

Purpose: To introduce egs-brachy, a new, fast, and versatile Monte Carlo code for brachytherapy applications. Methods: egs-brachy is an EGSnrc user-code based on the EGSnrc C++ class library (egs++). Complex phantom, applicator, and source model geometries are built using the egs++ geometry module. egs-brachy uses a tracklength estimator to score collision kerma in voxels. Interaction, spectrum, energy fluence, and phase space scoring are also implemented. Phase space sources and particle recycling may be used to improve simulation efficiency. HDR treatments (e.g. stepping source through dwell positions) can be simulated. Standard brachytherapy seeds, as well as electron and miniature x-ray tubemore » sources are fully modelled. Variance reduction techniques for electron source simulations are implemented (Bremsstrahlung cross section enhancement, uniform Bremsstrahlung splitting, and Russian Roulette). TG-43 parameters of seeds are computed and compared to published values. Example simulations of various treatments are carried out on a single 2.5 GHz Intel Xeon E5-2680 v3 processor core. Results: TG-43 parameters calculated with egs-brachy show excellent agreement with published values. Using a phase space source, 2% average statistical uncertainty in the PTV ((2mm){sup 3} voxels) can be achieved in 10 s for 100 {sup 125}I or {sup 103}Pd seeds in a 36.2 cm{sup 3} prostate PTV, 31 s for 64 {sup 103}Pd seeds in a 64 cm{sup 3} breast PTV, and 56 s for a miniature x-ray tube in a 27 cm{sup 3} breast PTV. Comparable uncertainty is reached in 12 s in a (1 mm){sup 3} water voxel 5 mm away from a COMS 16mm eye plaque with 13 {sup 103}Pd seeds. Conclusion: The accuracy of egs-brachy has been demonstrated through benchmarking calculations. Calculation times are sufficiently fast to allow full MC simulations for routine treatment planning for diverse brachytherapy treatments (LDR, HDR, miniature x-ray tube). egs-brachy will be available as free and open-source software to the medical physics research community. This work is partially funded by the Canada Research Chairs program, the Natural Sciences and Engineering Research Council of Canada, and the Ontario Ministry of Research and Innovation (Ontario Early Researcher Award).« less

Characterization of Low-Energy Photon-Emitting Brachytherapy Sources with Modified Strengths for Applications in Focal Therapy

NASA Astrophysics Data System (ADS)

Reed, Joshua L.

Permanent implants of low-energy photon-emitting brachytherapy sources are used to treat a variety of cancers. Individual source models must be separately characterized due to their unique geometry, materials, and radionuclides, which all influence their dose distributions. Thermoluminescent dosimeters (TLDs) are often used for dose measurements around low-energy photon-emitting brachytherapy sources. TLDs are typically calibrated with higher energy sources such as 60Co, which requires a correction for the change in the response of the TLDs as a function of photon energy. These corrections have historically been based on TLD response to x ray bremsstrahlung spectra instead of to brachytherapy sources themselves. This work determined the TLD intrinsic energy dependence for 125I and 103Pd sources relative to 60Co, which allows for correction of TLD measurements of brachytherapy sources with factors specific to their energy spectra. Traditional brachytherapy sources contain mobile internal components and large amounts of high-Z material such as radio-opaque markers and titanium encapsulations. These all contribute to perturbations and uncertainties in the dose distribution around the source. The CivaString is a new elongated 103Pd brachytherapy source with a fixed internal geometry, polymer encapsulation, and lengths ranging from 1 to 6 cm, which offers advantages over traditional source designs. This work characterized the CivaString source and the results facilitated the formal approval of this source for use in clinical treatments. Additionally, the accuracy of a superposition technique for dose calculation around the sources with lengths >1 cm was verified. Advances in diagnostic techniques are paving the way for focal brachytherapy in which the dose is intentionally modulated throughout the target volume to focus on subvolumes that contain cancer cells. Brachytherapy sources with variable longitudinal strength (VLS) are a promising candidate for use in focal brachytherapy treatments given their customizable activity distributions, although they are not yet commercially available. This work characterized five prototype VLS sources, developed methods for clinical calibration and verification of these sources, and developed an analytical dose calculation algorithm that scales with both source length and VLS.

High Level of Agreement Between Pretherapeutic 124I PET and Intratherapeutic 131I Imaging in Detecting Iodine-Positive Thyroid Cancer Metastases.

PubMed

Ruhlmann, Marcus; Jentzen, Walter; Ruhlmann, Verena; Pettinato, Cinzia; Rossi, Gloria; Binse, Ina; Bockisch, Andreas; Rosenbaum-Krumme, Sandra

2016-09-01

The aim of this retrospective study was to assess the level of agreement between PET and scintigraphy using diagnostic amounts of (124)I and therapeutic amounts of (131)I, respectively, in detecting iodine-positive metastases in patients with differentiated thyroid carcinoma. The study included patients who underwent PET /: CT 24 and 120 h after administration of approximately 25 MBq of (124)I and subsequently underwent imaging 5-10 d after administration of 1-10 GBq of (131)I. For each patient, the intratherapeutic (131)I imaging comprised a whole-body scintigraphy scan and a SPECT/CT scan of the neck to distinguish between metastatic and thyroid remnant tissues. Iodine uptake was rated as a metastatic focus if located outside the thyroid bed. Lesion- and patient-based analyses were performed. The study included 137 patients with 227 metastases iodine-positive on both functional imaging modalities. In the lesion-based analysis, (124)I PET and (131)I imaging detected 98% (223/227) and 99% (225/227) of the iodine-positive metastases, respectively; the level of agreement between (124)I PET and (131)I imaging was 97% (221/227). Four metastases (3 lymph node and 1 bone) in 4 patients were (124)I-negative but (131)I-positive, and 2 lymph node metastases in 2 patients were (131)I-negative but (124)I-positive. In the patient-based analysis, 61 of the 137 patients presented with iodine-positive metastases. (124)I PET and (131)I imaging detected at least one iodine-positive metastasis in 97% (59/61) and 98% (60/61) of the patients, respectively. The level of agreement was 95% (58/61). Both imaging modalities concordantly identified 76 of 137 patients without pathologic iodine uptake. Because of the high level of agreement, pretherapeutic (124)I PET/CT is an adequate methodology in the detection of iodine-positive metastases and can be used as a reliable tool for staging of thyroid cancer patients and individualized treatment planning. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

TRAV7-2*02 Expressing CD8⁺ T Cells Are Responsible for Palladium Allergy.

PubMed

Takeda, Yuri; Suto, Yoshiko; Ito, Koyu; Hashimoto, Wataru; Nishiya, Tadashi; Ueda, Kyosuke; Narushima, Takayuki; Takahashi, Tetsu; Ogasawara, Kouetsu

2017-05-31

While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8⁺ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8⁺ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8⁺ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy.

TRAV7-2*02 Expressing CD8+ T Cells Are Responsible for Palladium Allergy

PubMed Central

Takeda, Yuri; Suto, Yoshiko; Ito, Koyu; Hashimoto, Wataru; Nishiya, Tadashi; Ueda, Kyosuke; Narushima, Takayuki; Takahashi, Tetsu; Ogasawara, Kouetsu

2017-01-01

While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8+ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8+ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8+ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy. PMID:28561797

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

PubMed

Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

2017-01-12

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

DOE PAGES

Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; ...

2015-02-05

The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

40 CFR 124.213 - What procedures must I follow to make routine changes with prior approval?

Code of Federal Regulations, 2014 CFR

2014-07-01

... routine changes with prior approval? 124.213 Section 124.213 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Procedures for RCRA Standardized Permit Maintaining A Standardized Permit § 124.213 What procedures must I follow to make routine changes...

40 CFR 124.213 - What procedures must I follow to make routine changes with prior approval?

Code of Federal Regulations, 2011 CFR

2011-07-01

... routine changes with prior approval? 124.213 Section 124.213 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Procedures for RCRA Standardized Permit Maintaining A Standardized Permit § 124.213 What procedures must I follow to make routine changes...

40 CFR 124.212 - What procedures must I follow to make routine changes?

Code of Federal Regulations, 2014 CFR

2014-07-01

... routine changes? 124.212 Section 124.212 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Procedures for RCRA Standardized Permit Maintaining A Standardized Permit § 124.212 What procedures must I follow to make routine changes? (a) You can...

40 CFR 124.213 - What procedures must I follow to make routine changes with prior approval?

Code of Federal Regulations, 2013 CFR

2013-07-01

... routine changes with prior approval? 124.213 Section 124.213 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Procedures for RCRA Standardized Permit Maintaining A Standardized Permit § 124.213 What procedures must I follow to make routine changes...

[Effects of testosterone and cortisol in sports fatigued organism by Chinese material medica of shixiang yaofa].

PubMed

Lu, He-qi; Wei, Bing; Chao, Zhi-mao; Deng, Yun-long; Cheng, Yu-biao; Wang, Ke-lin; Zhou, Yan-hua; Yang, Kun-jie; Zhang, Hai-zhong; Cheng, Zhao-huan

2007-08-01

To study the endogenous hormone of testosterone and cortisol that secretes volume and rhythm in sports fatigued human bodies and animals. To determine secretory volume and rhythm in sports fatigued human bodies and animals when Shixiang yaofa's drug are used. Radio-immunity method was used to determine secretory volume and rhythm in sports fatigued human bodies and animals and to analyze secretory volume and rhythm. According to the secretory volume and rhythm of testosterone and cortisol, the Shixiang Yaofa's drugs were used. Doses: wenyang jihuo bead 10 g/sack 2 sack, ziyin xiuyang capsule 0.5 g/pill 8 pill pd in human bodies for 28 days. Wenyang jihuo bead 10 g x kg(-1) of crude drug, ziyin xiuyang capsule 4 g x kg(-1) of crude drug pd for hight doses in animals. Other groups for low doses 5 g x kg(-1) and 2 g x kg(-1) of crude drug pd for 15 days. The blood samples were collected for determination. (1) In human bodies the peak value of testosterone was appeared in 8:00 and valley value was appeared in 18:00, ranges: 176.93-281.73 x 10(-5) mg x L(-1). The peak value of cortisol was appeared in 8:00 and valley value was appeared in 22:00, ranges: 1.31-16.13 x 10(-3) mg x L(-1). In the same condition, the mouse peak value of testosterone was appeared in 20:00 and valley value was appeared in 0:00, ranges: (0.56 x 10(-5) - 124.0 x 10(-5)) mg x L(-1). The rhythm in animals was compatible with human bodies, howerer, the peak value was delayed for 12 hours. (2) The testosterone was step up and the cortisol was cut down in sports fatigued human bodies and animals when shixiang yaofa's drug were used (P < 0.05, P < 0.01). The secretion of testosterone and cortisol in sports fatigued human bodies and animals are existed conclusive biologic rhythm. The secretory volume can be available accommodation by shixiang yaofa's drugs.

"I Learned More at Lunchtime": Guideposts for Reimagining Professional Development

ERIC Educational Resources Information Center

Patton, Kevin; Parker, Melissa

2015-01-01

While professional development (PD) initiatives for practicing teachers are not new, an increasing body of research has contributed to a growing understanding of what constitutes effective practice in physical education. Findings indicate an enhanced recognition of the importance of providing teachers with PD opportunities where learning is…

KSC-08pd1041

NASA Image and Video Library

2008-04-26

CAPE CANAVERAL, Fla. -- In the Vehicle Assembly Building at NASA's Kennedy Space Center, space shuttle Discovery, looking like a giant bat, hangs suspended above the transfer aisle. The crane holding it will lift Discovery to the upper levels and lower it into high bay 3. In the bay, Discovery will be mated to the external tank and solid rocket boosters for launch on the upcoming STS-124 mission to the International Space Station. On the mission, the STS-124 crew will transport the Japanese Experiment Module - Pressurized Module and the Japanese Remote Manipulator System to the space station. Launch of Discovery is targeted for May 31 Photo credit: NASA/Jim Grossmann

KSC-08pd1167

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialists Greg Chamitoff (left) and Akihiko Hoshide (center) and Commander Mark Kelly take part in M113 training on Launch Pad 39A. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1172

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Karen Nyberg is ready to begin driving practice in the M113 armored personnel carrier, part of emergency training. Behind her is Pilot Ken Ham. She and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1176

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Pilot Ken Ham stands ready to practice driving the M113 armored personnel carrier as part of emergency training. Behind him is Mission Specialist Karen Nyberg. Ham and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1169

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Ron Garan is ready to drive the M113 armored personnel carrier as part of emergency training. Behind him is Pilot Ken Ham. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1179

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Greg Chamitoff drives the M113 armored personnel carrier as part of emergency training. Behind him Commander Mark Kelly. At center is Battalion Chief George Hoggard providing supervision. Chamitoff and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

Mitochondrial alterations in Parkinson's disease: new clues.

PubMed

Vila, Miquel; Ramonet, David; Perier, Celine

2008-10-01

Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). In particular, complex I impairment and subsequent oxidative stress have been widely demonstrated in experimental models of PD and in post-mortem PD samples. A recent wave of new studies is providing novel clues to the potential involvement of mitochondria in PD. In particular, (i) mitochondria-dependent programmed cell death pathways have been shown to be critical to PD-related dopaminergic neurodegeneration, (ii) many disease-causing proteins associated with familial forms of PD have been demonstrated to interact either directly or indirectly with mitochondria, (iii) aging-related mitochondrial changes, such as alterations in mitochondrial DNA, are increasingly being associated with PD, and (iv) anomalies in mitochondrial dynamics and intra-neuronal distribution are emerging as critical participants in the pathogenesis of PD. These new findings are revitalizing the field and reinforcing the potential role of mitochondria in the pathogenesis of PD. Whether a primary or secondary event, or part of a multi-factorial pathogenic process, mitochondrial dysfunction remains at the forefront of PD research and holds the promise as a potential molecular target for the development of new therapeutic strategies for this devastating, currently incurable, disease.

24 CFR 103.10 - What can I do if I believe someone is discriminating against me in the sale, rental, finance, or...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false What can I do if I believe someone is discriminating against me in the sale, rental, finance, or advertisement of housing? 103.10... discriminating against me in the sale, rental, finance, or advertisement of housing? You can notify HUD if you...

24 CFR 103.10 - What can I do if I believe someone is discriminating against me in the sale, rental, finance, or...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false What can I do if I believe someone is discriminating against me in the sale, rental, finance, or advertisement of housing? 103.10... discriminating against me in the sale, rental, finance, or advertisement of housing? You can notify HUD if you...

24 CFR 103.10 - What can I do if I believe someone is discriminating against me in the sale, rental, finance, or...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false What can I do if I believe someone is discriminating against me in the sale, rental, finance, or advertisement of housing? 103.10... discriminating against me in the sale, rental, finance, or advertisement of housing? You can notify HUD if you...

24 CFR 103.10 - What can I do if I believe someone is discriminating against me in the sale, rental, finance, or...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false What can I do if I believe someone is discriminating against me in the sale, rental, finance, or advertisement of housing? 103.10... discriminating against me in the sale, rental, finance, or advertisement of housing? You can notify HUD if you...

Urinary morbidity following ultrasound-guided transperineal prostate seed implantation.

PubMed

Gelblum, D Y; Potters, L; Ashley, R; Waldbaum, R; Wang, X H; Leibel, S

1999-08-01

To assess the urinary morbidity experienced by patients undergoing ultrasound-guided, permanent transperineal seed implantation for adenocarcinoma of the prostate. Between September 1992 and September 1997, 693 consecutive patients presented with a diagnosis of clinically localized adenocarcinoma of the prostate, and were treated with ultrasound-guided transperineal interstitial permanent brachytherapy (TPIPB). Ninety-three patients are excluded from this review, having received neoadjuvant antiandrogen therapy. TPIPB was performed with 125I in 165 patients and with 103Pd in 435 patients. Patients treated with implant alone received 160 Gy with 125I (pre TG43) or 120 Gy with 103Pd. One hundred two patients received preimplant, pelvic external beam radiation (XRT) to a dose of either 41.4 or 45 Gy because of high-risk features including PSA > or = 10 and/or Gleason score > or = 7. Combined modality patients received 120 Gy and 90 Gy, respectively for 125I or 103Pd. All patients underwent postimplant cystoscopy and placement of an indwelling Foley catheter for 24-48 h. Follow-up was at 5 weeks after implant, every 3 months for the first 2 years, and then every 6 months for subsequent years. Patients completed AUA urinary symptom scoring questionnaires at initial consultation and at each follow-up visit. Urinary toxicity was classified by the RTOG toxicity scale with the following adaptations; grade 1 urinary toxicity was symptomatic nocturia or frequency requiring none or minimal medical intervention such as phenazopyridine; grade 2 urinary toxicity was early obstructive symptomatology requiring alpha-blocker therapy; and grade 3 toxicity was considered that requiring indwelling catheters or posttreatment transurethral resection of the prostate for symptom relief. Log-rank analysis and Chi-square testing was performed to assess AUA score, prostate size, isotope selection, and the addition of XRT as possible prognosticators of postimplant urinary toxicity. The prostate volume receiving 150% of the prescribed dose (V150) was studied in patients to assess its correlation with urinary toxicity. Median follow-up was 37 months (range 6-68). Within the first 60 days, 37.3% of the patients reported grade 1 urinary toxicity, 41% had grade 2, and 2.2% had grade 3 urinary toxicity. By 6 months, 21.4% still reported grade 1 urinary toxicity, whereas 12.8% and 3% complained of grade 2 and 3 urinary difficulties, respectively. Patients with a preimplant AUA score < or = 7 had significantly less grade II toxicity at 60 days compared to those with an AUA score of >7 (32% vs. 59.2%, respectively, p = 0.001). Similarly, prostatic volumes < or = 35 cc had a significantly lower incidence of grade II urinary toxicity (p = 0.001). There was no difference in toxicity regarding the isotope used (p = 0.138 at 60 days, p = 0.45 at 6 months) or the addition of preimplant XRT (p = 0.069 at 60 days, p = 0.84 at 6 months). Twenty-eight patients (4.7%) underwent TURP after 3 isotope half-lives for protracted obstructive symptoms. Five of these men (17%) developed stress incontinence following TURP, but all patients experienced relief of their obstructive symptoms without morbidity at last follow-up. The percent of the prostate receiving 150% of the prescribed dose (V150) did not predict urinary toxicity. TPIPB is well tolerated but associated with mild to moderate urinary morbidity. Pretreatment prostatic volume and AUA scoring were shown to significantly predict for grade 2 toxicity while the use of preimplant, pelvic XRT and isotope selection did not. Patients undergoing TURP for protracted symptoms following TPIPB did well with a 17% risk of developing stress incontinence. V150 did not help identify patients at risk for urinary morbidity. As transperineal prostate implantation is used more frequently the associated toxicities and the definition of possible pretreatment prognostic factors is necessary to

13 CFR 124.103 - Who is socially disadvantaged?

Code of Federal Regulations, 2011 CFR

2011-01-01

... prejudice or cultural bias within American society because of their identities as members of groups and... association with students or teachers, denial of educational honors rightfully earned, and social patterns or... prejudice or cultural bias because of their identity as group members and without regard to their individual...

Side of symptom onset affects motor dysfunction in Parkinson's disease.

PubMed

Haaxma, C A; Helmich, R C G; Borm, G F; Kappelle, A C; Horstink, M W I M; Bloem, B R

2010-11-10

The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic denervation in Parkinson's disease (PD). Using the pegboard dexterity test, we compared motor performance of both hands between healthy subjects (n=48), PD patients with predominantly right-hemispheric dopamine depletion (PD-RIGHT; n=83) and PD patients with more severe left-hemispheric dopamine depletion (PD-LEFT; n=103). All subjects were right-handed. After adjusting for hand-dominance effects, we found that PD-RIGHT patients exhibited a 55% larger difference between right and left dexterity scores than PD-LEFT patients. This effect could be attributed to greater motor dysfunction of the more-affected hand in PD-RIGHT patients, while the less-affected hand performed similarly in both groups. We conclude that the side of symptom onset affects motor dysfunction in PD, and suggest that the non-dominant right hemisphere may be more susceptible to dopaminergic denervation than the dominant left hemisphere. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Procedures for establishing and maintaining consistent air-kerma strength standards for low-energy, photon-emitting brachytherapy sources: recommendations of the Calibration Laboratory Accreditation Subcommittee of the American Association of Physicists in Medicine.

PubMed

DeWerd, Larry A; Huq, M Saiful; Das, Indra J; Ibbott, Geoffrey S; Hanson, William F; Slowey, Thomas W; Williamson, Jeffrey F; Coursey, Bert M

2004-03-01

Low dose rate brachytherapy is being used extensively for the treatment of prostate cancer. As of September 2003, there are a total of thirteen 125I and seven 103Pd sources that have calibrations from the National Institute of Standards and Technology (NIST) and the Accredited Dosimetry Calibration Laboratories (ADCLs) of the American Association of Physicists in Medicine (AAPM). The dosimetry standards for these sources are traceable to the NIST wide-angle free-air chamber. Procedures have been developed by the AAPM Calibration Laboratory Accreditation Subcommittee to standardize quality assurance and calibration, and to maintain the dosimetric traceability of these sources to ensure accurate clinical dosimetry. A description of these procedures is provided to the clinical users for traceability purposes as well as to provide guidance to the manufacturers of brachytherapy sources and ADCLs with regard to these procedures.

Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

PubMed

Tine, Roger C; Sylla, Khadime; Faye, Babacar T; Poirot, Eugenie; Fall, Fatou B; Sow, Doudou; Wang, Duolao; Ndiaye, Magatte; Ndiaye, Jean Louis; Faye, Babacar; Greenwood, Brian; Gaye, Oumar; Milligan, Paul

2017-08-15

More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia. PACTR201411000937373 (www.pactr.org). © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Evidence for hydrodynamic electron flow in PdCoO₂.

PubMed

Moll, Philip J W; Kushwaha, Pallavi; Nandi, Nabhanila; Schmidt, Burkhard; Mackenzie, Andrew P

2016-03-04

Electron transport is conventionally determined by the momentum-relaxing scattering of electrons by the host solid and its excitations. Hydrodynamic fluid flow through channels, in contrast, is determined partly by the viscosity of the fluid, which is governed by momentum-conserving internal collisions. A long-standing question in the physics of solids has been whether the viscosity of the electron fluid plays an observable role in determining the resistance. We report experimental evidence that the resistance of restricted channels of the ultrapure two-dimensional metal palladium cobaltate (PdCoO2) has a large viscous contribution. Comparison with theory allows an estimate of the electronic viscosity in the range between 6 × 10(-3) kg m(-1) s(-1) and 3 × 10(-4) kg m(-1) s(-1), versus 1 × 10(-3) kg m(-1) s(-1) for water at room temperature. Copyright © 2016, American Association for the Advancement of Science.

HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo.

PubMed

Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dent, Paul

2017-10-27

Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles. Combined exposure of cells to [neratinib + HDAC inhibitors] caused inactivation of mTORC1 and mTORC2, enhanced autophagosome and subsequently autolysosome formation, and caused an additive to greater than additive induction of cell death. Knock down of Beclin1 or ATG5 prevented HDAC inhibitors or neratinib from reducing ERBB1/3/4 and K-/N-RAS expression and reduced [neratinib + HDAC inhibitor] lethality. Neratinib and HDAC inhibitors reduced the expression of multiple HDAC proteins via autophagy that was causal in the reduced expression of PD-L1, PD-L2 and ornithine decarboxylase, and increased expression of Class I MHCA. In vivo , neratinib and HDAC inhibitors interacted to suppress the growth of 4T1 mammary tumors, an effect that was enhanced by an anti-PD-1 antibody. Our data support the premises that neratinib lethality can be enhanced by HDAC inhibitors, that neratinib may be a useful therapeutic tool in afatinib resistant NSCLC, and that [neratinib + HDAC inhibitor] exposure facilitates anti-tumor immune responses.

HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo

PubMed Central

Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Avogadri-Connors, Francesca; Cutler, Richard E.; Lalani, Alshad S.; Dent, Paul

2017-01-01

Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles. Combined exposure of cells to [neratinib + HDAC inhibitors] caused inactivation of mTORC1 and mTORC2, enhanced autophagosome and subsequently autolysosome formation, and caused an additive to greater than additive induction of cell death. Knock down of Beclin1 or ATG5 prevented HDAC inhibitors or neratinib from reducing ERBB1/3/4 and K-/N-RAS expression and reduced [neratinib + HDAC inhibitor] lethality. Neratinib and HDAC inhibitors reduced the expression of multiple HDAC proteins via autophagy that was causal in the reduced expression of PD-L1, PD-L2 and ornithine decarboxylase, and increased expression of Class I MHCA. In vivo, neratinib and HDAC inhibitors interacted to suppress the growth of 4T1 mammary tumors, an effect that was enhanced by an anti-PD-1 antibody. Our data support the premises that neratinib lethality can be enhanced by HDAC inhibitors, that neratinib may be a useful therapeutic tool in afatinib resistant NSCLC, and that [neratinib + HDAC inhibitor] exposure facilitates anti-tumor immune responses. PMID:29163826

26 CFR 1.103-10 - Exemption for certain small issues of industrial development bonds.

Code of Federal Regulations, 2014 CFR

2014-04-01

... refunding issues of $1 million or less. (2) $10 million or less. (i) Under section 103(b)(6)(D), the issuing... less, in lieu of the $1 million exemption otherwise provided for in section 103(b)(6)(A), with respect... section 103(b)(6)(A), the outstanding face amount of prior $1 million or $10 million exempt small issues...

26 CFR 1.103-10 - Exemption for certain small issues of industrial development bonds.

Code of Federal Regulations, 2012 CFR

2012-04-01

... refunding issues of $1 million or less. (2) $10 million or less. (i) Under section 103(b)(6)(D), the issuing... less, in lieu of the $1 million exemption otherwise provided for in section 103(b)(6)(A), with respect... section 103(b)(6)(A), the outstanding face amount of prior $1 million or $10 million exempt small issues...

26 CFR 1.103-10 - Exemption for certain small issues of industrial development bonds.

Code of Federal Regulations, 2013 CFR

2013-04-01

... refunding issues of $1 million or less. (2) $10 million or less. (i) Under section 103(b)(6)(D), the issuing... less, in lieu of the $1 million exemption otherwise provided for in section 103(b)(6)(A), with respect... section 103(b)(6)(A), the outstanding face amount of prior $1 million or $10 million exempt small issues...

Modeling the spatio-temporal dynamics of porcine reproductive & respiratory syndrome cases at farm level using geographical distance and pig trade network matrices.

PubMed

Amirpour Haredasht, Sara; Polson, Dale; Main, Rodger; Lee, Kyuyoung; Holtkamp, Derald; Martínez-López, Beatriz

2017-06-07

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases for the swine industry. A better understanding of the disease dynamics and the transmission pathways under diverse epidemiological scenarios is a key for the successful PRRS control and elimination in endemic settings. In this paper we used a two step parameter-driven (PD) Bayesian approach to model the spatio-temporal dynamics of PRRS and predict the PRRS status on farm in subsequent time periods in an endemic setting in the US. For such purpose we used information from a production system with 124 pig sites that reported 237 PRRS cases from 2012 to 2015 and from which the pig trade network and geographical location of farms (i.e., distance was used as a proxy of airborne transmission) was available. We estimated five PD models with different weights namely: (i) geographical distance weight which contains the inverse distance between each pair of farms in kilometers, (ii) pig trade weight (PT ji ) which contains the absolute number of pig movements between each pair of farms, (iii) the product between the distance weight and the standardized relative pig trade weight, (iv) the product between the standardized distance weight and the standardized relative pig trade weight, and (v) the product of the distance weight and the pig trade weight. The model that included the pig trade weight matrix provided the best fit to model the dynamics of PRRS cases on a 6-month basis from 2012 to 2015 and was able to predict PRRS outbreaks in the subsequent time period with an area under the ROC curve (AUC) of 0.88 and the accuracy of 85% (105/124). The result of this study reinforces the importance of pig trade in PRRS transmission in the US. Methods and results of this study may be easily adapted to any production system to characterize the PRRS dynamics under diverse epidemic settings to more timely support decision-making.

KSC-08pd2114

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – At Launch Pad 39A at NASA's Kennedy Space Center, workers spray a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2119

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – At Launch Pad 39A at NASA's Kennedy Space Center, workers spray a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2117

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – At Launch Pad 39A at NASA's Kennedy Space Center, workers spray a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2115

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – At Launch Pad 39A at NASA's Kennedy Space Center, workers on a platform spray a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2118

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – At Launch Pad 39A at NASA's Kennedy Space Center, workers pack a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2111

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – This elevated view of Launch Pad 39A at NASA's Kennedy Space Center shows workers preparing to fill steel grid structures, welded to the wall of the flame trench, with a heat-resistant concrete called Fondue Fyre, developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2112

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – This elevated view of Launch Pad 39A at NASA's Kennedy Space Center shows the steel grid structures, welded to the wall of the flame trench, which workers will be filling with a heat-resistant concrete called Fondue Fyre, developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2113

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – This elevated view of Launch Pad 39A at NASA's Kennedy Space Center shows workers filling steel grid structures, welded to the wall of the flame trench, with a heat-resistant concrete called Fondue Fyre, developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2110

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – This elevated view of Launch Pad 39A at NASA's Kennedy Space Center shows workers preparing to fill steel grid structures, welded to the wall of the flame trench, with a heat-resistant concrete called Fondue Fyre, developed during NASA's Apollo lunar program. Damage to the trench occurred during the May 31 launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

High-level coproduction, purification and characterisation of laccase and exopolysaccharides by Coriolus versicolor.

PubMed

Que, Youxiong; Sun, Shujing; Xu, Liping; Zhang, Yuye; Zhu, Hu

2014-09-15

In this study, a two-stage pH-shift fermentation process was developed for the coproduction of laccase and exopolysaccharides (EPS) by Coriolus versicolor. At the same time, laccase and EPS were purified and characterised in detail. The results showed that the highest laccase and EPS production reached 7680 U l(-1) and 8.2 g l(-1). Furthermore, the flow behaviour of fermentation broth was Newtonian and the maximum μ(ap) was 2.7×10(-3) Pa s. The MW of laccase was 64 kDa and it showed a pI value of 4.2. The CD analysis showed that laccase had a high α-helical content (68%). The MW of the purified EPS was determined to be 1.8×10(6) Da, consisting of carbohydrates (87.6%) and proteins (12.4%). The EPS consisted of 17 amino acids, mainly serine (11.3%), glutamic acid (12.60%), leucine (13.3%) and phenylalanine (9.4%) in protein moiety, and three monosaccharides (galactose, mannose and xylose). Copyright © 2014 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jans, H-S; Dept. of Oncology, University of Alberta, Edmonton, AB; Stypinski, D

Purpose: To compare the radiation dose to normal organs from the radio-iodinated, hypoxia-binding radiosensitizer iodoazomycin arabinoside (IAZA) for three different isotopes of iodine. Methods: Dosimety studies with normal volunteers had been carried out with [{sup 123}I]IAZA, a drug binding selectively to hypoxic sites. Two other isotopes of iodine, {sup 131}I and {sup 124}I, offer the opportunity to use IAZA as an agent for radioisotope therapy and as an imaging tracer for Positron Emission Tomography. Radioisotope dosimetry for {sup 131}I and {sup 124}I was performed by first deriving from the [{sup 123}I]IAZA studies biological uptake and excretion data. The cumulated activitiesmore » for {sup 131}I or {sup 124}I where obtained by including their half-lives when integrating the biological data and then extrapolating to infinite time points considering a) physical decay only or b) physical and biological excretion. Doses were calculated using the Medical Internal Radiation Dose (MIRD) schema (OLINDA1.1 code, Vanderbilt 2007). Results: Compared to {sup 123}I, organ doses were elevated on average by a factor 6 and 9 for {sup 131}I and {sup 124}I, respectively, if both physical decay and biological excretion were modeled. If only physical decay is considered, doses increase by a factor 18 ({sup 131}I) and 19 ({sup 124}I). Highest organ doses were observed in intestinal walls, urinary bladder and thyroid. Effective doses increased by a factor 11 and 14 for {sup 131}I and {sup 124}I, respectively, if biological and physical decay are present. Purely physical decay yields a 23-fold increase over {sup 123}I for both, {sup 131}I and {sup 124}I. Conclusion: Owing to the significant dose increase, caused by their longer half life and the approximately 10 times larger electronic dose deposited in tissue per nuclear decay, normal tissue doses of IAZA labeled with {sup 131}I and {sup 124}I need to be carefully considered when designing imaging and therapy protocols for clinical trials. Effective blocking of iodine uptake in the thyroid is essential. Alberta Innovates - Health Solutions (AIHS) and Canadian Institutes of Health Research (CIHR)« less

An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody protects mice from morbidity without interfering with the development of protective immunity to subsequent homologous challenge.

PubMed

Wilson, Jason R; Belser, Jessica A; DaSilva, Juliana; Guo, Zhu; Sun, Xiangjie; Gansebom, Shane; Bai, Yaohui; Stark, Thomas J; Chang, Jessie; Carney, Paul; Levine, Min Z; Barnes, John; Stevens, James; Maines, Taronna R; Tumpey, Terrence M; York, Ian A

2017-11-01

The emergence of A(H7N9) virus strains with resistance to neuraminidase (NA) inhibitors highlights a critical need to discover new countermeasures for treatment of A(H7N9) virus-infected patients. We previously described an anti-NA mAb (3c10-3) that has prophylactic and therapeutic efficacy in mice lethally challenged with A(H7N9) virus when delivered intraperitoneally (i.p.). Here we show that intrananasal (i.n.) administration of 3c10-3 protects 100% of mice from mortality when treated 24h post-challenge and further characterize the protective efficacy of 3c10-3 using a nonlethal A(H7N9) challenge model. Administration of 3c10-3 i.p. 24h prior to challenge resulted in a significant decrease in viral lung titers and deep sequencing analysis indicated that treatment did not consistently select for viral variants in NA. Furthermore, prophylactic administration of 3c10-3 did not inhibit the development of protective immunity to subsequent homologous virus re-challenge. Taken together, 3c10-3 highlights the potential use of anti-NA mAb to mitigate influenza virus infection. Published by Elsevier Inc.

Empirically supported treatments for panic disorder with agoraphobia in a Spanish psychology clinic.

PubMed

Ballesteros, Francisco; Labrador, Francisco J

2014-10-27

The aim of this work is to study the sociodemographic and clinical characteristics of patients diagnosed with Panic Disorder with Agoraphobia (PD/Ag), as well as the characteristics of the treatment and its results and cost in a University Psychology Clinic. Fifty patients demanded psychological assistance for PD/Ag; 80% were women, with an average age of 29.22 years (SD = 9.03). Mean number of evaluation sessions was 3.26 (SD = 1.03), and of treatment sessions, 13.39 (SD = 9.237). Of the patients, 83.33% were discharged (that is, questionnaire scores were below the cut-off point indicated by the authors, and no PD/Ag was observed at readministration of the semistructured interview), 5.5% refused treatment, and 11% were dropouts. The average number of treatment sessions of patients who achieved therapeutic success was 15.13 (SD = 8.98). Effect sizes (d) greater than 1 were obtained in all the scales. Changes in all scales were significant (p < .05). The estimated cost of treatment for patients who achieved therapeutic success was 945.12€. The treatment results are at least similar to those of studies of efficacy and effectiveness for PD/Ag. The utility of generalizing treatments developed in research settings to a welfare clinic is discussed.

Synthesis, spectral and theoretical studies of Ni(II), Pd(II) and Pt(II) complexes of 5-mercapto-1,2,4-triazole-3-imine-2‧-hydroxynaphyhaline

NASA Astrophysics Data System (ADS)

Gaber, Mohamed; El-Ghamry, Hoda; Atlam, Faten; Fathalla, Shaimaa

2015-02-01

Ni(II), Pd(II) and Pt(II) complexes of 5-mercapto-1,2,4-triazole-3-imine-2‧-hydroxynaphthaline have been isolated and characterized by elemental analysis, IR, 1H NMR, EI-mass, UV-vis, molar conductance, magnetic moment measurements and thermogravimetric analysis. The molar conductance values indicated that the complexes are non-electrolytes. The magnetic moment values of the complexes displayed diamagnetic behavior for Pd(II) and Pt(II) complexes and tetrahedral geometrical structure for Ni(II) complex. From the bioinorganic applications point of view, the interaction of the ligand and its metal complexes with CT-DNA was investigated using absorption and viscosity titration techniques. The Schiff-base ligand and its metal complexes have also been screened for their antimicrobial and antitumor activities. Also, theoretical investigation of molecular and electronic structures of the studied ligand and its metal complexes has been carried out. Molecular orbital calculations were performed using DFT (density functional theory) at B3LYP level with standard 6-31G(d,p) and LANL2DZ basis sets to access reliable results to the experimental values. The calculations were performed to obtain the optimized molecular geometry, charge density distribution, extent of distortion from regular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), Mulliken atomic charges, reactivity index (ΔE), dipole moment (D), global hardness (η), softness (σ), electrophilicity index (ω), chemical potential and Mulliken electronegativity (χ).

Hydrolysis mechanisms for the organopalladium complex [Pd(CNN)P(OMe)3]BF4 in sulfuric acid.

PubMed

García, Begoña; Hoyuelos, Francisco J; Ibeas, Saturnino; Muñoz, María S; Peñacoba, Indalecio; Leal, José M

2009-08-13

The acid-catalyzed hydrolysis of the organopalladium complex [Pd(CNN)P(OMe)3]BF4 species was monitored spectrophotometrically at different sulfuric acid concentrations (3.9 and 11.0 M) in 10% v:v ethanol-water over the 25-45 degrees C temperature range and in 30% and 50% (v/v) ethanol-water at 25 degrees C. Two acidity regions (I and II) could be differentiated. In each of the two regions the kinetic data pairs yielded two different rate constants, k(1obs) and k(2obs), the former being faster. These constants were fitted by an Excess Acidity analysis to different hydrolyses mechanisms: A-1, A-2, and A-SE2. In region I ([H2SO4] < 7.0 M), the k(1obs) values remained constant k(1obs)(av) = 1.6 x 10(-3) s(-1) and the set of k(2obs) values nicely matched an A-SE2 mechanism, yielding a rate-determining constant k(0,ASE2) = 2.4 x 10(-7) M(-1) s(-1). In region II ([H2SO4] > 7.0 M), a switchover was observed from an A-1 mechanism (k(0,A1) = 1.3 x 10(-4) s(-1)) to an A-2 mechanism (k(0,A2) = 3.6 x 10(-3) M(-1) s(-1)). The temperature effect on the rate constants in 10% (v/v) ethanol-water yielded positive DeltaH and negative DeltaS values, except for the A-1 mechanism, where DeltaS adopted positive values throughout. The solvent permittivity effect, epsilonr, revealed that k(1obs)(av) and k(0,A2) dropped with a fall in epsilonr, whereas the k(0,ASE2) value remained unaffected. The set of results deduced is in line with the schemes put forward.

SU-E-T-333: Towards Customizable Radiotherapy Enhancement (CuRE) for Prostate Cancer Using Cisplatin Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinha, N; Cifter, G; Sajo, E

2014-06-01

Purpose: Replacing routinely used brachytherapy spacers with multifunctional ones loaded with cisplatin nanoparticles (CNP), which can be released into the tumor after implantation, could enable customizable radiation boosting to the prostate tumor in addition to chemotherapy effect. This study investigates the feasibility of customizing the intra-tumor biodistribution and corresponding dose enhancement (DEF) over time for the released CNP as a function of nanoparticle size. Methods: Dose enhancement factors (DEF) due to photon-induced emission of photo-/Auger electrons from CNPs were calculated as a function of concentration using previously published analytical calculation method. An experimentally determined diffusion coefficient (D) for 10 nmmore » nanoparticles in mouse tumor model was employed to estimate D for other sizes using the Stoke- Einstein equation. The error function diffusion model in the experimental study was applied to generate the intra-tumor concentration profile for a burst release of CNPs from the spacer over time. The corresponding DEF profiles were then determined for brachytherapy using Pd-103 and I-125 sources. Results: As expected, the generated profiles showed greater DEF over time for smaller CNP sizes at sample distances from the spacer. For example, for a centrally located spacer, clinically significant DEF (> 20%) could be achieved near the tumor periphery (ca. 0.85 cm distance from the spacer for average PCa tumor size) after 20, and 100 days, respectively for CNPs sizes of 2 nm, and 10 nm, using I-125. Meanwhile for Pd-103, clinically significant DEF could be achieved at the same position after 22 and 108 days, respectively, for same size particles. Conclusion: Our preliminary results demonstrate the feasibility of customizing dose enhancement to prostate tumors as a function of spacer location, brachytherapy source type or size of CNPs released from multifunctional spacers. Such an approach could enable customizable radiation boosting to tumor sub-volumes, while minimizing dose to healthy tissues.« less

[Personality disorders in adolescent patients with anorexia and bulimia nervosa].

PubMed

Bottin, Julia; Salbach-Andrae, Harriet; Schneider, Nora; Pfeiffer, Ernst; Lenz, Klaus; Lehmkuhl, Ulrike

2010-09-01

The present study aimed to ascertain the occurrence of personality disorders (PD) in adolescent patients with anorexia (AN) and bulimia nervosa (BN) by means of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). 99 female adolescent patients (57 AN - restrictive type, 17 AN - binge-purging type, 25 BN; M(age) = 16.3 +/- 1.6) were consecutively assessed by means of SCID-II. Furthermore, the influence of age, axis-I-comorbidities, and type of treatment according to PD were examined. 30.3% of the patients met the criteria for PD according to SCID-II. AN patients of the binge-purging type showed higher prevalences of PD and higher dimensional scores than the other eating disorder groups. Moreover, our findings indicate that age and axis-I-comorbidities are associated with the development of PD. Significant differences in the occurrence of PD in the three eating disorder groups were found. Patients of the AN binge-purging type are more often affected than restricting AN or BN patients are. This, and also the influence of age and axis-I-comorbidities, should be taken into account in the treatment of patients with eating disorders.

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

PubMed Central

2010-01-01

Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaCH2), radiolabeled with iodine-124 (124I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging. Methods HuCC49deltaCH2 was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of 18F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection. Results At approximately 1 hour after i.v. injection, 124I-HuCC49deltaCH2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, 18F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder. Conclusions On microPET imaging, 124I-HuCC49deltaCH2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while 18F-FDG failed to demonstrate this. The antigen-directed and cancer-specific 124I-radiolabled anti-TAG-72 monoclonal antibody conjugate, 124I-HuCC49deltaCH2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms. PMID:20691066

KSC-08pd1170

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Ron Garan practices driving the M113 armored personnel carrier as part of emergency training. At center is the Battalion Chief George Hoggard, providing instruction. Behind Garan is Pilot Ken Ham. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1175

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Akihiko Hoshide drives the M113 armored personnel carrier as part of emergency training. Battalion Chief George Hoggard provides supervision. Behind them are Mission Specialist Ron Garan and Pilot Ken Ham. Hoshide and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1181

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 Mission Specialist Mike Fossum drives the M113 armored personnel carrier as part of emergency training. Behind him at left is Mission Specialist Greg Chamitoff. At center is Battalion Chief George Hoggard providing supervision. Fossum and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1539

NASA Image and Video Library

2008-05-31

CAPE CANAVERAL, Fla. -- At the Banana River viewing site, guests applaud the picture-perfect launch of space shuttle Discovery as it leaps from the clouds of smoke below on its STS-124 mission to the International Space Station. Launch was on time at 5:02 p.m. EDT. Discovery is making its 35th flight. The STS-124 mission is the 26th in the assembly of the space station. It is the second of three flights launching components to complete the Japan Aerospace Exploration Agency's Kibo laboratory. The shuttle crew will install Kibo's large Japanese Pressurized Module and its remote manipulator system, or RMS. The 14-day flight includes three spacewalks. Photo credit: NASA/Sam Fat

Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus.

PubMed

Kimoto, Tetsuya; Ishii, Hirotaka; Higo, Shimpei; Hojo, Yasushi; Kawato, Suguru

2010-12-01

Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.

Preparing Future College Instructors: The Role of Graduate Student Teaching Assistants (GTAs) in Successful College Calculus Programs

NASA Astrophysics Data System (ADS)

Ellis, Jessica Fabricant

Graduate student Teaching Assistants (GTAs) contribute to calculus instruction in two ways: as the primary teacher and as recitation leaders. GTAs can also be viewed as the next generation of mathematics instructors. Thus, in addition to their immediate contribution to the landscape of Calculus 1 instruction, GTAs will contribute significantly to the long-term state of calculus in their future occupations. However, their preparation for these roles varies widely and is often minimal. In this study, I first compare the mathematical beliefs, instructional practices, and student success of GTAs to other Calculus 1 instructors. I then provide rich descriptions for three GTA professional development (PD) programs that prepare graduate students as course instructors, as recitation leaders, and as future faculty. I then investigate the instructional practices and mathematical beliefs of graduate students coming from these three PD programs. I conclude this work with a description of a framework for GTA-PD programs. To accomplish this work, I conducted a mixed-method analysis on national survey data and case study data from four doctoral granting institutions. These four institutions were chosen because of their higher-than-expected student success in Calculus 1. The results of these analyses indicate that graduate students teach in more innovative ways than other instructors, though their students were less successful. Among the four case study institutions, I identified three models of GTA-PD, each of which appeared successful in accomplishing their goals. These goals included transitioning graduate students into the role of instructor, preparing graduate students to implement an innovative approach to Calculus 1, and supporting graduate students as recitation leaders. These analyses also led to the development of a framework to be used to characterize, evaluate, and consider the implementation of graduate student professional development programs. This GTA-PD framework is thus one of the major contributions put forth by this dissertation.

A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease

PubMed Central

McDermott, M.P.; Kurlan, R.; Lyness, J.M.; Como, P.G.; Pearson, N.; Factor, S.A.; Juncos, J.; Serrano Ramos, C.; Brodsky, M.; Manning, C.; Marsh, L.; Shulman, L.; Fernandez, H.H.; Black, K.J.; Panisset, M.; Christine, C.W.; Jiang, W.; Singer, C.; Horn, S.; Pfeiffer, R.; Rottenberg, D.; Slevin, J.; Elmer, L.; Press, D.; Hyson, H.C.; McDonald, W.; Richard, Irene; McDonald, William; McDermott, Michael; Como, Peter G.; Kurlan, Roger; Lyness, Jeffrey M.; Pearson, Nancy; Sommerfeld, Barbara; Deeley, Cheryl; de la Torre, Tania; Barnard, Michele; Wilson, April; Lincoln, Maryann; Damgaard, Paula; Gerstenhaber, Melissa; Dustin, Kelly; Zappala, Nancy; Swartz, Camille; Creech, Mary; Shipley, Elda; Blankenship, Samantha; Beland, Monica; Roth, Jessie; Burnette, Heather; Foxworth, Tamara; Quesada, Monica; Lloyd, Mary; Pfeiffer, Brenda; Hansen, Joy; Folie, Joy; Wagner, Renee; Spears, Julia; Taylor, Colleen; Brown, Rachel; Iguchi, Lisa; Lim, Chen; LaDonna, Kori; Megens, Julie; Menza, Matthew; Cummings, Jeffrey; Hamer, Robert; Shannon, Kathleen; Odenkirchen, Joanne; Conwit, Robin; Beck, Christopher; LaDonna, Donna; Bausch, Jan; Kim, Scott; Chismar, Ron; Quinn, Sinead; Bean, Steve; Daigneault, Susan; Lindsay, Patricia; Ross, Tori; Kompoliti, Katie

2012-01-01

Objective: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). Methods: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored >12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. Results: Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. Conclusions: Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. Classification of Evidence: This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD. PMID:22496199

Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

PubMed Central

Aldhous, Marian C.; Reynolds, Rebecca M.; Campbell, Archie; Linksted, Pamela; Lindsay, Robert S.; Smith, Blair H.; Seckl, Jonathan R.; Porteous, David J.; Norman, Jane E.

2015-01-01

Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects’ own diabetes medical records. From F0-parents, we identified F1-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F1-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03–3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13–1.30) and age (OR = 1.03, CI 1.01–1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09–1.29) and percent body-fat (OR = 1.12, CI 1.05–1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved. PMID:26308734

Effect of filters and reconstruction algorithms on I-124 PET in Siemens Inveon PET scanner

NASA Astrophysics Data System (ADS)

Ram Yu, A.; Kim, Jin Su

2015-10-01

Purpose: To assess the effects of filtering and reconstruction on Siemens I-124 PET data. Methods: A Siemens Inveon PET was used. Spatial resolution of I-124 was measured to a transverse offset of 50 mm from the center FBP, 2D ordered subset expectation maximization (OSEM2D), 3D re-projection algorithm (3DRP), and maximum a posteriori (MAP) methods were tested. Non-uniformity (NU), recovery coefficient (RC), and spillover ratio (SOR) parameterized image quality. Mini deluxe phantom data of I-124 was also assessed. Results: Volumetric resolution was 7.3 mm3 from the transverse FOV center when FBP reconstruction algorithms with ramp filter was used. MAP yielded minimal NU with β =1.5. OSEM2D yielded maximal RC. SOR was below 4% for FBP with ramp, Hamming, Hanning, or Shepp-Logan filters. Based on the mini deluxe phantom results, an FBP with Hanning or Parzen filters, or a 3DRP with Hanning filter yielded feasible I-124 PET data.Conclusions: Reconstruction algorithms and filters were compared. FBP with Hanning or Parzen filters, or 3DRP with Hanning filter yielded feasible data for quantifying I-124 PET.

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation.

PubMed

Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan; Xu, Jie

2017-01-01

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668-4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78-28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells.

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation

PubMed Central

Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan

2017-01-01

ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668–4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78–28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells. PMID:28811964

Improved search for two-neutrino double electron capture on 124Xe and 126Xe using particle identification in XMASS-I

NASA Astrophysics Data System (ADS)

Xmass Collaboration; Abe, K.; Hiraide, K.; Ichimura, K.; Kishimoto, Y.; Kobayashi, K.; Kobayashi, M.; Moriyama, S.; Nakahata, M.; Norita, T.; Ogawa, H.; Sato, K.; Sekiya, H.; Takachio, O.; Takeda, A.; Tasaka, S.; Yamashita, M.; Yang, B. S.; Kim, N. Y.; Kim, Y. D.; Itow, Y.; Kanzawa, K.; Kegasa, R.; Masuda, K.; Takiya, H.; Fushimi, K.; Kanzaki, G.; Martens, K.; Suzuki, Y.; Xu, B. D.; Fujita, R.; Hosokawa, K.; Miuchi, K.; Oka, N.; Takeuchi, Y.; Kim, Y. H.; Lee, K. B.; Lee, M. K.; Fukuda, Y.; Miyasaka, M.; Nishijima, K.; Nakamura, S.

2018-05-01

We conducted an improved search for the simultaneous capture of two K-shell electrons on the ^{124}Xe and ^{126}Xe nuclei with emission of two neutrinos using 800.0 days of data from the XMASS-I detector. A novel method to discriminate γ-ray/X-ray or double electron capture signals from β-ray background using scintillation time profiles was developed for this search. No significant signal was found when fitting the observed energy spectra with the expected signal and background. Therefore, we set the most stringent lower limits on the half-lives at 2.1 × 10^{22} and 1.9 × 10^{22} years for ^{124}Xe and ^{126}Xe, respectively, with 90% confidence level. These limits improve upon previously reported values by a factor of 4.5.

"Tiny Talks" between Colleagues: Brief Narratives as Mediation in Teacher Development

ERIC Educational Resources Information Center

Zoshak, Rebecca

2016-01-01

During my third semester as a student pursuing a Masters in Teaching English as a Second Language (TESL)--which was also my second semester as an ESL teacher--I was encouraged by a professor of a graduate seminar to think outside the box about professional development (PD). After all, inquiry-based approaches to PD and teacher education emphasize…

Activation of neurotensin receptor type 1 attenuates locomotor activity.

PubMed

Vadnie, Chelsea A; Hinton, David J; Choi, Sun; Choi, YuBin; Ruby, Christina L; Oliveros, Alfredo; Prieto, Miguel L; Park, Jun Hyun; Choi, Doo-Sup

2014-10-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

SNCA 3'UTR genetic variants in patients with Parkinson's disease and REM sleep behavior disorder.

PubMed

Toffoli, M; Dreussi, E; Cecchin, E; Valente, M; Sanvilli, N; Montico, M; Gagno, S; Garziera, M; Polano, M; Savarese, M; Calandra-Buonaura, G; Placidi, F; Terzaghi, M; Toffoli, G; Gigli, G L

2017-07-01

REM sleep behavior disorder (RBD) is an early marker of Parkinson's disease (PD); however, it is still unclear which patients with RBD will eventually develop PD. Single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of alpha-synuclein (SNCA) have been associated with PD, but at present, no data is available about RBD. The 3'UTR hosts regulatory regions involved in gene expression control, such as microRNA binding sites. The aim of this study was to determine RBD specific genetic features associated to an increased risk of progression to PD, by sequencing of the SNCA-3'UTR in patients with "idiopathic" RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients). Sequencing of SNCA-3'UTR was performed on genomic DNA extracted from peripheral blood samples. Bioinformatic analyses were carried out to predict the potential effect of the identified genetic variants on microRNA binding. We found three SNCA-3'UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four new or previously reported but not annotated specific genetic variants (KP876057, KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the RBD population. The in silico approach highlighted that these variants could affect microRNA-mediated gene expression control. Our data show specific SNPs in the SNCA-3'UTR that may bear a risk for RBD to be associated with PD. Moreover, new genetic variants were identified in patients with iRBD.

Activation of Neurotensin Receptor Type 1 Attenuates Locomotor Activity

PubMed Central

Vadnie, Chelsea A.; Hinton, David J.; Choi, Sun; Choi, YuBin; Ruby, Christina L.; Oliveros, Alfredo; Prieto, Miguel L.; Park, Jun Hyun; Choi, Doo-Sup

2014-01-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. PMID:24929110

[Effects of non-motor symptoms on health-related quality of life in Parkinson's disease].

PubMed

Dong, Hongli; Liu, Chunfeng; Hu, Xiaowei

2014-03-25

To explore the effects of non-motor symptoms (NMS) on health-related quality of life (HRQOL) in Parkinson's disease (PD) patients. By convenient sampling, 128 PD patients were recruited. NMS was assessed by the non-motor symptoms scale for PD (NMSS) and HRQOL by the 39-item PD Questionnaire (PDQ39). All PD patients (100%) had NMS with a general score of (124 ± 48) . Among these NMS, constipation was ranked the highest and the general level of NMS was significantly positively associated with age (r = 0.226, P < 0.05), Hoehn-Yahr staging (r = 0.442, P < 0.05) and disease course (r = 0.223, P < 0.05). However there was no correlation with gender (r = 0.085, P < 0.05). For PD patients, HRQOL became impaired with a general score of (44 ± 16) . Activities of daily living (60 ± 15), mobility (49 ± 21), emotional well-being (49 ± 28) and stigma (48 ± 46) were the most seriously affected. Females (χ² = -1.821 P < 0.05) and senile bereaved patients (χ² = -1.512, P < 0.05) had significantly lower HRQOL than that of others. For PD patients, the general level of HRQOL was significantly positively associated with disease course (r = 0.260, P < 0.05) and severity (r = 0.259, P < 0.05). The general level of HRQOL was significantly positively associated with the general level of NMS (r = 0.686, P < 0.01). Non-motor symptoms (NMS) are quite common in PD patients. For PD patients, NMS has a more negative impact on HRQOL than other symptoms.

Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease

PubMed Central

Sánchez-Danés, Adriana; Richaud-Patin, Yvonne; Carballo-Carbajal, Iria; Jiménez-Delgado, Senda; Caig, Carles; Mora, Sergio; Di Guglielmo, Claudia; Ezquerra, Mario; Patel, Bindiben; Giralt, Albert; Canals, Josep M; Memo, Maurizio; Alberch, Jordi; López-Barneo, José; Vila, Miquel; Cuervo, Ana Maria; Tolosa, Eduard; Consiglio, Antonella; Raya, Angel

2012-01-01

Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model human disease in relevant cell types, but it is unclear whether they could successfully model age-related diseases such as Parkinson's disease (PD). Here, we generated iPSC lines from seven patients with idiopathic PD (ID-PD), four patients with familial PD associated to the G2019S mutation in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene (LRRK2-PD) and four age- and sex-matched healthy individuals (Ctrl). Over long-time culture, dopaminergic neurons (DAn) differentiated from either ID-PD- or LRRK2-PD-iPSC showed morphological alterations, including reduced numbers of neurites and neurite arborization, as well as accumulation of autophagic vacuoles, which were not evident in DAn differentiated from Ctrl-iPSC. Further induction of autophagy and/or inhibition of lysosomal proteolysis greatly exacerbated the DAn morphological alterations, indicating autophagic compromise in DAn from ID-PD- and LRRK2-PD-iPSC, which we demonstrate occurs at the level of autophagosome clearance. Our study provides an iPSC-based in vitro model that captures the patients' genetic complexity and allows investigation of the pathogenesis of both sporadic and familial PD cases in a disease-relevant cell type. PMID:22407749

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

PubMed

Darr, Andreas M; Opfermann, Thomas; Niksch, Tobias; Driesch, Dominik; Marlowe, Robert J; Freesmeyer, Martin

2013-10-01

The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. 124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.

The production of [124I]iodine and [86Y]yttrium.

PubMed

Schmitz, Jochen

2011-05-01

The use of paired tracers such as (124)I/(131)I and (86)Y/(90)Y allows pretherapy PET imaging with positron emitting radioisotopes of the same element as used for therapy. Whereas nowadays most therapy nuclides are produced by reactors or generators, the production of the corresponding PET isotopes requires the irradiation of adequate targets using particle accelerators such as cyclotrons. This paper describes the production routes for (124)I and (86)Y.

Ultrasound-accelerated synthesis of biphenyl compounds using novel Pd(0) nanoparticles immobilized on bio-composite.

PubMed

Baran, Talat

2018-07-01

This study describes (i) an eco-friendly approach for design of Pd(0) nanoparticles on a natural composite, which is composed of carboxymethyl cellulose/agar polysaccharides (CMC/AG), without using any toxic reducing agents and (ii) development of ultrasound assisted simple protocol for synthesis of biphenyl compounds. Chemical characterization studies of Pd(0) nanoparticles (Pd NPs@CMC/AG) revealed that size of the particles were in the range of 37-55 nm. Catalytic performance of Pd NPs@CMC/AG was evaluated in synthesis of various biphenyl compounds by using the ultrasound-assisted method that was developed in this study. Pd NPs@CMC/AG exhibited excellent catalytic performance by producing high reaction yields. In addition, Pd NPs@CMC/AG was successfully used up to six reaction cycles without losing its catalytic activity, indicating high reproducibility of Pd NPs@CMC/AG. Additionally, compared to conventional the methods, new ultrasound-assisted synthesis technique that was followed in this study exhibited some advantages such as shorter reaction time, greener reaction conditions, higher yields and easier work-up. Copyright © 2018 Elsevier B.V. All rights reserved.

World Military Expenditures and Arms Transfers 1996.

DTIC Science & Technology

1997-07-01

rmamuif Aqihv^< Preceding Page Blank Library of Congress Numbers: JX 1974.A1U52 78-645925 ISSN 0897-4667 Released July 1997 For sale by the...d 1985 821 1125 124 20450 28020 9831 12.1 4.0 11.4 93 10.3 2322 1986 771 1030 127 22590 30150 9430 12.3 3.4 10.9 84 10.3 2459 1987 1040 E 1346 E...10 6307 6969 2335 .7 7.0 20.9 705 14.4 10040 1992 NA NA 10 7083 7618 2491 .7 NA NA NA 14.1 10770 1993 262 275 NA 7383 7740 2521 .7 3.6 10.9 382 NA

Comparison of in situ versus in vitro methods of fiber digestion at 120 and 288 hours to quantify the indigestible neutral detergent fiber fraction of corn silage samples.

PubMed

Bender, R W; Cook, D E; Combs, D K

2016-07-01

Ruminal digestion of neutral detergent fiber (NDF) is affected in part by the proportion of NDF that is indigestible (iNDF), and the rate at which the potentially digestible NDF (pdNDF) is digested. Indigestible NDF in forages is commonly determined as the NDF residue remaining after long-term in situ or in vitro incubations. Rate of pdNDF digestion can be determined by measuring the degradation of NDF in ruminal in vitro or in situ incubations at multiple time points, and fitting the change in residual pdNDF by time with log-transformed linear first order or nonlinear mathematical treatments. The estimate of indigestible fiber is important because it sets the pool size of potentially digestible fiber, which in turn affects the estimate of the proportion of potentially digestible fiber remaining in the time series analysis. Our objective was to compare estimates of iNDF based on in vitro (IV) and in situ (IS) measurements at 2 fermentation end points (120 and 288h). Further objectives were to compare the subsequent rate, lag, and estimated total-tract NDF digestibility (TTNDFD) when iNDF from each method was used with a 7 time point in vitro incubation of NDF to model fiber digestion. Thirteen corn silage samples were dried and ground through a 1-mm screen in a Wiley mill. A 2×2 factorial trial was conducted to determine the effect of time of incubation and method of iNDF analysis on iNDF concentration; the 2 factors were method of iNDF analysis (IS vs. IV) and incubation time (120 vs. 288h). Four sample replicates were used, and approximately 0.5g/sample was weighed into each Ankom F 0285 bag (Ankom Technology, Macedon, NY; pore size=25 µm) for all techniques. The IV-120 had a higher estimate of iNDF (37.8% of NDF) than IS-120 (32.1% of NDF), IV-288 (31.2% of NDF), or IS-288 technique (25.7% of NDF). Each of the estimates of iNDF was then used to calculate the rate of degradation of pdNDF from a 7 time point in vitro incubation. When the IV-120 NDF residue was used, the subsequent rates of pdNDF digestion were fastest (2.8% h(-1)) but the estimate of lag was longest (10.3h), compared with when iNDF was based on the IS-120 or IV-288 NDF residues (rates of 2.3%h(-1) and 2.4%h(-1); lag times of 9.7 and 9.8 h, respectively). Rate of pdNDF degradation was slowest (2.1% h(-1)) when IS-288 NDF residue was used as the estimate of iNDF. The estimate of lag based on IS-288 (9.4h) was similar to lag estimates calculated when IS-120 or IV-288 were used as the estimate of iNDF. The TTNDFD estimates did not differ between treatments (35.5%), however, because differences in estimated pools of iNDF resulted in subsequent changes in rates and lag times of fiber digestion that tended to cancel out. Estimates of fiber digestion kinetic parameters and TTNDFD were similar when fit to either the linear or nonlinear fiber degradation models. All techniques also yielded estimates of iNDF that were higher than predicted iNDF based on the commonly used ratio of 2.4 × lignin. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparative NMR studies of diffusional water permeability of red blood cells from different species: XVI Dingo (Canis familiaris dingo) and dog (Canis familiaris).

PubMed

Benga, Gheorghe; Chapman, Bogdan E; Matei, Horea; Cox, Guy C; Romeo, Tony; Mironescu, Eugen; Kuchel, Philip W

2010-03-08

As part of a programme of comparative measurements of Pd (diffusional water permeability) the RBCs (red blood cells) from dingo (Canis familiaris dingo) and greyhound dog (Canis familiaris) were studied. The morphologies of the dingo and greyhound RBCs [examined by light and SEM (scanning electron microscopy)] were found to be very similar, with regard to aspect ratio and size; the mean diameters were estimated to be the same (approximately 7.2 microm) for both dingo and greyhound RBCs. The water diffusional permeability was monitored by using an Mn2+-doping 1H NMR technique at 400 MHz. The Pd (cm/s) values of dingo and greyhound RBCs were similar: 6.5 x 10(-3) at 25 degrees C, 7.5 x 10(-3) at 30 degrees C, 10 x 10(-3) at 37 degrees C and 11.5 x 10(-3) at 42 degrees C. The inhibitory effect of a mercury-containing SH (sulfhydryl)-modifying reagent PCMBS (p-chloromercuribenzene sulfonate) was investigated. The maximal inhibition of dingo and greyhound RBCs was reached in 15-30 min at 37 degrees C with 2 mmol/l PCMBS. The values of maximal inhibition were in the range 72-74% when measured at 25 degrees C and 30 degrees C, and approximately 66% at 37 degrees C. The lowest value of Pd (corresponding to the basal permeability to water) was approximately 2-3 x 10(-3) cm/s in the temperature range 25-37 degrees C. The Ea,d (activation energy of water diffusion) was 25 kJ/mol for dingo RBC and 23 kJ/mol for greyhound RBCs. After incubation with PCMBS, the values of Ea,d increased, reaching 46-48 kJ/mol in the condition of maximal inhibition of water exchange. The electrophoretograms of membrane polypeptides of the dingo and greyhound RBCs were compared and seen to be very similar. We postulate that the RBC parameters reported in the present study are characteristic of all canine species and, in particular in the two cases presented here, these parameters have not been changed by the peculiar Australian habitat over the millennia (as in the case of the dingo) or over shorter time periods, decades or centuries (as in the case of the domestic greyhound).

KSC-08pd2377

NASA Image and Video Library

2008-08-12

CAPE CANAVERAL, Fla. – A view from above of repairs made to the walls of the Launch Pad 39A flame trench at NASA's Kennedy Space Center. Workers sprayed a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the launch of space shuttle Discovery on the STS-124 mission. A 75-foot by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs being completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Dimitri Gerondidakis

KSC-08pd2375

NASA Image and Video Library

2008-08-12

CAPE CANAVERAL, Fla. – An inspector stands in the Launch Pad 39A flame trench at NASA's Kennedy Space Center after tests of the repairs on the wall. Workers sprayed a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the launch of space shuttle Discovery on the STS-124 mission. A 75-foot by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs being completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Dimitri Gerondidakis

KSC-08pd2373

NASA Image and Video Library

2008-08-12

CAPE CANAVERAL, Fla. – A closeup of the wall in the Launch Pad 39A flame trench at NASA's Kennedy Space Center after repairs were made. Workers sprayed a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the launch of space shuttle Discovery on the STS-124 mission. A 75-foot by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs being completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Dimitri Gerondidakis

KSC-08pd2374

NASA Image and Video Library

2008-08-12

CAPE CANAVERAL, Fla. – In the Launch Pad 39A flame trench at NASA's Kennedy Space Center, inspectors test the repairs on the wall. Workers sprayed a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the launch of space shuttle Discovery on the STS-124 mission. A 75-foot by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs being completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Dimitri Gerondidakis

KSC-08pd2372

NASA Image and Video Library

2008-08-12

CAPE CANAVERAL, Fla. – This view of the Launch Pad 39A flame trench at NASA's Kennedy Space Center shows the areas on the walls recently repaired. Workers sprayed a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the launch of space shuttle Discovery on the STS-124 mission. A 75-foot by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs being completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Dimitri Gerondidakis

Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.

PubMed

Umemoto, Yuichiroh; Okano, Shinji; Matsumoto, Yoshihiro; Nakagawara, Hidekazu; Matono, Rumi; Yoshiya, Shohei; Yamashita, Yo-Ichi; Yoshizumi, Tomoharu; Ikegami, Toru; Soejima, Yuji; Harada, Mamoru; Aishima, Shinichi; Oda, Yoshinao; Shirabe, Ken; Maehara, Yoshihiko

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined. We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis. High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS. PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson’s disease therapy

PubMed Central

Alcacer, Cristina; Andreoli, Laura; Sebastianutto, Irene; Jakobsson, Johan; Fieblinger, Tim; Cenci, Maria Angela

2017-01-01

Parkinson’s disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways’ contribution to different motor features using SPN type–specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA–induced dyskinesia (LID mice). Using the activatory Gq-coupled human M3 muscarinic receptor (hM3Dq), we found that chemogenetic stimulation of dSPNs mimicked, while stimulation of iSPNs abolished the therapeutic action of L-DOPA in PD mice. In LID mice, hM3Dq stimulation of dSPNs exacerbated dyskinetic responses to L-DOPA, while stimulation of iSPNs inhibited these responses. In the absence of L-DOPA, only chemogenetic stimulation of dSPNs mediated through the Gs-coupled modified rat muscarinic M3 receptor (rM3Ds) induced appreciable dyskinesia in PD mice. Combining D2 receptor agonist treatment with rM3Ds-dSPN stimulation reproduced all symptoms of LID. These results demonstrate that dSPNs and iSPNs oppositely modulate both therapeutic and dyskinetic responses to dopamine replacement therapy in PD. We also show that chemogenetic stimulation of different signaling pathways in dSPNs leads to markedly different motor outcomes. Our findings have important implications for the design of effective antiparkinsonian and antidyskinetic drug therapies. PMID:28112685

iPS models of Parkin and PINK1.

PubMed

Rakovic, Aleksandar; Seibler, Philip; Klein, Christine

2015-04-01

Parkinson disease (PD) is a degenerative disorder of the central nervous system resulting from depletion of dopaminergic neurons and currently remains incurable despite enormous international research efforts. The development of induced pluripotent stem cell (iPSC) technology opened up the unique possibility of studying disease mechanisms in human tissue that was otherwise not accessible, such as the brain. Of particular interest are the monogenetic forms of PD as they closely resemble the more common 'idiopathic' PD and, through the mutated protein, provide a clear research target in iPSC-derived neurons. Recessively inherited Parkin and PTEN-induced putative kinase 1 (PINK1) mutations have been investigated in this context and the present review describes the first insights gained from studies in iPSC-derived dopaminergic neurons, which comprise abnormalities in mitochondrial and dopamine homoeostasis, microtubular stability and axonal outgrowth. These new models of PD have a high translational potential that includes the identification of druggable targets, testing of known and novel therapeutic agents in the disease-relevant tissue using well-defined read-outs and potential regenerative approaches.

Chemiresistive hydrogen gas sensors from gold-palladium nanopeapods

NASA Astrophysics Data System (ADS)

Moon, Chung Hee; Myung, Nosang V.; Haberer, Elaine D.

2014-12-01

Gold-palladium (Au-Pd) nanopeapod-based H2 chemiresistors were fabricated using a gold binding M13 viral template. Peptides displayed along the length of this biological template served as affinity binding sites to direct gold nanoparticle assembly under ambient conditions in an aqueous environment. In addition, the geometry of this filamentous biomolecule readily facilitated the formation of the highly anisotropic nanopeapod structure. Pd electroless deposition controlled peapod diameter, as well as electrical resistance. Sensor performance was determined by overall peapod morphology. Thicker nanopeapods (i.e., ˜15 nm Pd layer) with fully encapsulated Au nanoparticle seeds showed strong evidence of oxygen inclusion during or after Pd deposition, and a modest response (i.e., 0.04%-2.6%) at 2000 ppmv H2 after device conditioning through extended H2 exposure. Thinner nanopeapods (i.e., ˜5 nm Pd layer) with discontinuous Au nanoparticle coverage showed superior performance with a response of 117% at 2000 ppmv H2 in air, a 70% response time (t70%) within 1 min, and a low detection limit of 25 ppmv. The bio-directed formation of these unique thin-shelled, Au-Pd peapod nanostructures and the development of a highly sensitive H2 detector advance both the fields of nanoassembly and gas sensing.

Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing.

PubMed

Hoyte, Ashley C; Jamin, Augusta V; Koneru, Pratibha C; Kobe, Matthew J; Larue, Ross C; Fuchs, James R; Engelman, Alan N; Kvaratskhelia, Mamuka

2017-12-01

The pyridine-based multimerization selective HIV-1 integrase (IN) inhibitors (MINIs) are a distinct subclass of allosteric IN inhibitors. MINIs potently inhibit HIV-1 replication during virion maturation by inducing hyper- or aberrant IN multimerization but are largely ineffective during the early steps of viral replication. Here, we investigated the mechanism for the evolution of a triple IN substitution (T124N/V165I/T174I) that emerges in cell culture with a representative MINI, KF116. We show that HIV-1 NL4-3(IN T124N/V165I/T174I) confers marked (>2000-fold) resistance to KF116. Two IN substitutions (T124N/T174I) directly weaken inhibitor binding at the dimer interface of the catalytic core domain but at the same time markedly impair HIV-1 replication capacity. Unexpectedly, T124N/T174I IN substitutions inhibited proteolytic processing of HIV-1 polyproteins Gag and Gag-Pol, resulting in immature virions. Strikingly, the addition of the third IN substitution (V165I) restored polyprotein processing, virus particle maturation, and significant levels of replication capacity. These results reveal an unanticipated role of IN for polyprotein proteolytic processing during virion morphogenesis. The complex evolutionary pathway for the emergence of resistant viruses, which includes the need for the compensatory V165I IN substitution, highlights a relatively high genetic barrier exerted by MINI KF116. Additionally, we have solved the X-ray structure of the drug-resistant catalytic core domain protein, which provides means for rational development of second-generation MINIs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.

PubMed

Fernández-Santiago, Rubén; Carballo-Carbajal, Iria; Castellano, Giancarlo; Torrent, Roger; Richaud, Yvonne; Sánchez-Danés, Adriana; Vilarrasa-Blasi, Roser; Sánchez-Pla, Alex; Mosquera, José Luis; Soriano, Jordi; López-Barneo, José; Canals, Josep M; Alberch, Jordi; Raya, Ángel; Vila, Miquel; Consiglio, Antonella; Martín-Subero, José I; Ezquerra, Mario; Tolosa, Eduardo

2015-12-01

The epigenomic landscape of Parkinson's disease (PD) remains unknown. We performed a genomewide DNA methylation and a transcriptome studies in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by cell reprogramming of somatic skin cells from patients with monogenic LRRK2-associated PD (L2PD) or sporadic PD (sPD), and healthy subjects. We observed extensive DNA methylation changes in PD DAn, and of RNA expression, which were common in L2PD and sPD. No significant methylation differences were present in parental skin cells, undifferentiated iPSCs nor iPSC-derived neural cultures not-enriched-in-DAn. These findings suggest the presence of molecular defects in PD somatic cells which manifest only upon differentiation into the DAn cells targeted in PD. The methylation profile from PD DAn, but not from controls, resembled that of neural cultures not-enriched-in-DAn indicating a failure to fully acquire the epigenetic identity own to healthy DAn in PD. The PD-associated hypermethylation was prominent in gene regulatory regions such as enhancers and was related to the RNA and/or protein downregulation of a network of transcription factors relevant to PD (FOXA1, NR3C1, HNF4A, and FOSL2). Using a patient-specific iPSC-based DAn model, our study provides the first evidence that epigenetic deregulation is associated with monogenic and sporadic PD. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Kidney stones may increase the risk of coronary heart disease and stroke

PubMed Central

Peng, Jian-Ping; Zheng, Hang

2017-01-01

Abstract Background: We aimed to quantitatively assess the potential relationship between kidney stones and coronary heart disease or stroke. Methods: A meta-analysis was conducted on eligibly studies published before 31 May 2016 in PubMed or Embase. The data were pooled, and the relationship was assessed by the random-effect model with inverse variance-weighted procedure. The results were expressed as relative risk (RR) with 95% confidence intervals (95%CI). Results: Eight studies of 11 cohorts (n = 11) were included in our analysis with 3,658,360 participants and 157,037 cases. We found that a history of kidney stones was associated with increased risk of coronary heart disease (CHD) (RR = 1.24; 95%CI: 1.14–1.36; I2 = 79.0%, n = 11); similar effect on myocardial infarction, a serious condition of CHD, was observed (RR = 1.24; 95%CI: 1.10–1.40; I2 = 80.4%, n = 8). We also found that a history of kidney stones may increase the risk of stroke (RR = 1.21, 95%CI: 1.06–1.38; I2 = 54.7%, n = 4). In subgroup analysis, the risk of coronary heart disease was higher in men (RR = 1.23, 95%CI: 1.02–1.49) while the risk for stroke was higher in women (RR = 1.12; 95%CI: 1.03–1.21). No obvious publications bias was detected (Egger test: P = .47). Conclusion: Kidney stones are associated with increased risk of coronary heart disease and stroke, and the effect may differ by sex. PMID:28834909

Application of a palladium hexacyanoferrate film-modified aluminum electrode to electrocatalytic oxidation of hydrazine.

PubMed

Razmi, Habib; Azadbakht, Azadeh; Sadr, Moayad Hossaini

2005-11-01

A palladium hexacyanoferrate (PdHCF) film as an electrocatalytic material was obtained at an aluminum (Al) electrode by a simple electroless dipping method. The modified Al electrode demonstrated a well-behaved redox couple due to the redox reaction of the PdHCF film. The PdHCF film showed an excellent electrocatalytic activity toward the oxidation of hydrazine. The electrocatalytic oxidation of hydrazine was studied by cyclic voltammetry and rotating disk electrode voltammetry techniques. A calibration graph obtained for the hydrazine consisted of two segments (localized at concentration ranges 0.39-10 and 20-75 mM). The rate constant k and transfer coefficient alpha for the catalytic reaction and the diffusion coefficient of hydrazine in the solution D, were found to be 3.11 x 10(3) M(-1) s(-1), 0.52 and 8.03 x 10(-6) cm2 s(-1) respectively. The modified electrode was used to amperometric determination of hydrazine in photographic developer. The interference of ascorbic acid and thiosulfate were investigated and greatly reduced using a thin film of Nafion on the modified electrode. The modified electrode indicated reproducible behavior and a high level of stability during electrochemical experiments, making it particularly suitable for analytical purposes.

Incidence and mortality trends of aspiration pneumonia in Parkinson's disease in the United States, 1979-2010.

PubMed

Akbar, Umer; Dham, Bhavpreet; He, Ying; Hack, Nawaz; Wu, Samuel; Troche, Michelle; Tighe, Patrick; Nelson, Eugene; Friedman, Joseph H; Okun, Michael S

2015-09-01

Careful examination of long-term analyses and trends is essential in understanding the medico-economic burden of this common complication. We sought to describe the long-term (32-year) trends of incidence and mortality in PD patients hospitalized with aspiration pneumonia (AsPNA). Incidence and mortality of AsPNA in hospitalized PD versus non-PD patients was assessed by logistic regression analysis applied to a national database between the years 1979 and 2010. Covariates such as age-decennium, gender, year AsPNA occurred, and the interactions with PD diagnosis were investigated. Rate of AsPNA and mortality over the 32-years was trended and compared. AsPNA occurred in 3.6% of PD patients and 1.0% of non-PD patients. The average mortality for PD patients was less (17% vs. 22%). Long-term (32-year) trends revealed a nearly 10-fold increase in incidence of AsPNA in PD (0.4% in 1979, 4.9% in 2010), decreasing mortality overtime, higher likelihood in males, and increasing average age of AsPNA patients (steeper increase in PD). All p-values<0.05. In regression analysis, each successive year had a slight increase in odds of AsPNA (OR 1.03 in PD, OR1.06 in non-PD). Trends over 32 years revealed a 10-fold increase in AsPNA among PD and non-PD patients, and an associated decrease in mortality. Our data suggest that PD patients are living longer, have slightly more AsPNA, but a lower mortality than was seen in past decades. Further research should investigate the causes of AsPNA in PD, and also potential interventions to decrease its occurrence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rescue of iCIKs transfer from PD-1/PD-L1 immune inhibition in patients with resectable tongue squamous cell carcinoma (TSCC).

PubMed

Huang, Xiaofeng; Zhang, Jing; Li, Xiaolong; Huang, Hongxing; Liu, Ying; Yu, Mei; Zhang, Yan; Wang, Hua

2018-06-01

The purpose of this study is to evaluate the therapeutic efficacy and the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients treated with radical operation combined with chemotherapy and improving cytokine induced killer cells (iCIKs) transfer. Thirteen patients who received radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1 expression was evaluated in TSCC patients. ICIKs were cultured from patient-derived peripheral blood mononuclear cells (PBMCs) in vitro. The immunological differences underlying iCIKs transfer were investigated through phenotype, cytokine secretion and PD-1/PD-L1 inhibition analysis. The serum PD-L1 levels were elevated in the TSCC patients. PD-L1 was detected on both human TSCC cells and tumour tissue sections. PD-1 expression was much higher on the PBMCs of TSCC patients than on in vitro cultured iCIKs. Interruption of PD-1/PD-L1 interaction enhanced the cytotoxicity of iCIKs in vitro. CD3 + CD8+ T cell proportion and cytokine IL-6 secretion decreased after chemotherapy. The infusion of iCIKs effectively reversed the immunosuppression through the upregulation of the CD3 + CD8+ T cell proportion and Th cell cytokine secretion (IFN-γ, TNF-α, IL-4 and IL-6). Twelve responders are currently alive (95.7+ months), another patient 83 months. Our findings indicated that the PD-1/PD-L1 interaction contributes to the immunosuppression in TSCC patients. ICIKs transfer is an effective therapy to reverse the immunosuppression caused by surgical procedures and chemotherapy and improve immune system function. Copyright © 2018. Published by Elsevier B.V.

In Situ Chemical Modification of Schottky Barrier in Solution-Processed Zinc Tin Oxide Diode.

PubMed

Son, Youngbae; Li, Jiabo; Peterson, Rebecca L

2016-09-14

Here we present a novel in situ chemical modification process to form vertical Schottky diodes using palladium (Pd) rectifying bottom contacts, amorphous zinc tin oxide (Zn-Sn-O) semiconductor made via acetate-based solution process, and molybdenum top ohmic contacts. Using X-ray photoelectron spectroscopy depth profiling, we show that oxygen plasma treatment of Pd creates a PdOx interface layer, which is then reduced back to metallic Pd by in situ reactions during Zn-Sn-O film annealing. The plasma treatment ensures an oxygen-rich environment in the semiconductor near the Schottky barrier, reducing the level of oxygen-deficiency-related defects and improving the rectifying contact. Using this process, we achieve diodes with high forward current density exceeding 10(3)A cm(-2) at 1 V, rectification ratios of >10(2), and ideality factors of around 1.9. The measured diode current-voltage characteristics are compared to numerical simulations of thermionic field emission with sub-bandgap states in the semiconductor, which we attribute to spatial variations in metal stoichiometry of amorphous Zn-Sn-O. To the best of our knowledge, this is the first demonstration of vertical Schottky diodes using solution-processed amorphous metal oxide semiconductor. Furthermore, the in situ chemical modification method developed here can be adapted to tune interface properties in many other oxide devices.

Synthesis, spectral and theoretical studies of Ni(II), Pd(II) and Pt(II) complexes of 5-mercapto-1,2,4-triazole-3-imine-2'-hydroxynaphthaline.

PubMed

Gaber, Mohamed; El-Ghamry, Hoda; Atlam, Faten; Fathalla, Shaimaa

2015-02-25

Ni(II), Pd(II) and Pt(II) complexes of 5-mercapto-1,2,4-triazole-3-imine-2'-hydroxynaphthaline have been isolated and characterized by elemental analysis, IR, (1)H NMR, EI-mass, UV-vis, molar conductance, magnetic moment measurements and thermogravimetric analysis. The molar conductance values indicated that the complexes are non-electrolytes. The magnetic moment values of the complexes displayed diamagnetic behavior for Pd(II) and Pt(II) complexes and tetrahedral geometrical structure for Ni(II) complex. From the bioinorganic applications point of view, the interaction of the ligand and its metal complexes with CT-DNA was investigated using absorption and viscosity titration techniques. The Schiff-base ligand and its metal complexes have also been screened for their antimicrobial and antitumor activities. Also, theoretical investigation of molecular and electronic structures of the studied ligand and its metal complexes has been carried out. Molecular orbital calculations were performed using DFT (density functional theory) at B3LYP level with standard 6-31G(d,p) and LANL2DZ basis sets to access reliable results to the experimental values. The calculations were performed to obtain the optimized molecular geometry, charge density distribution, extent of distortion from regular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), Mulliken atomic charges, reactivity index (ΔE), dipole moment (D), global hardness (η), softness (σ), electrophilicity index (ω), chemical potential and Mulliken electronegativity (χ). Copyright © 2014 Elsevier B.V. All rights reserved.

KSC-08pd2516

NASA Image and Video Library

2008-05-31

CAPE CANAVERAL, Fla. – A new NASA helicopter circles space shuttle Discovery on Launch Pad 39A prior to launch on the STS-124 mission. To the left of the shuttle is the fixed service structure with the 80-foot lightning mast on top. The rotating service structure, normally closed around the shuttle, is open for liftoff. At right of the pad is the 300,000-gallon water tower that provides the water used for sound suppression on the pad during liftoff. In the background is the Atlantic Ocean. Discovery is making its 35th flight. The STS-124 mission is the 26th in the assembly of the space station. It is the second of three flights launching components to complete the Japan Aerospace Exploration Agency's Kibo laboratory.

KSC-08pd1183

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- After completing M113 driving practice, the STS-124 crew stands in front of the armored personnel carrier for a photo. From left are Commander Mark Kelly, Mission Specialists Mike Fossum, Karen Nyberg and Ron Garan, Pilot Ken Ham, and Mission Specialists Akihiko Hoshide and Greg Chamitoff. They are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1168

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- STS-124 crew members get instructions inside an M113 armored personnel carrier about emergency procedures. Clockwise from left are Mission Specialists Greg Chamitoff and Akihiko Hoshide, Commander Mark Kelly, Mission Specialist Ron Garan, instructor Battalion Chief George Hoggard, Pilot Ken Ham and Mission Specialists Karen Nyberg and Mike Fossum. They are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1173

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- Under the supervision of Battalion Chief George Hoggard, STS-124 Mission Specialist Karen Nyberg takes her turn (right) driving the armored personnel carrier, part of emergency training. At left are Mission Specialists Ron Garan and Akihiko Hoshide, who represents the Japan Aerospace Exploration Agency. They and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1177

NASA Image and Video Library

2008-05-07

CAPE CANAVERAL, Fla. -- With Launch Pad 39B in the background, STS-124 Pilot Ken Ham drives the M113 armored personnel carrier as part of emergency training. Behind him at right is Mission Specialist Karen Nyberg. At center is Battalion Chief George Hoggard providing supervision. Ham and other crew members are at NASA's Kennedy Space Center for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

"I Took This Picture Because?…?": Accessing Teachers' Depictions of Change

ERIC Educational Resources Information Center

Parker, Melissa; Patton, Kevin; Sinclair, Christina

2016-01-01

Background: Achieving teacher change and the lofty goals of educational reform initiatives necessitates professional development (PD) designed to help teachers rethink their practice. A key implication for physical education, therefore, is that PD must be organized in ways that utilize teachers' voice, providing opportunities for teachers to build…

PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma.

PubMed

Fontugne, Jacqueline; Augustin, Jérémy; Pujals, Anaïs; Compagnon, Philippe; Rousseau, Benoit; Luciani, Alain; Tournigand, Christophe; Cherqui, Daniel; Azoulay, Daniel; Pawlotsky, Jean-Michel; Calderaro, Julien

2017-04-11

Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression.A series of 58 iCCAs and 41 pCCAs was included in the study. PD-L1, PD-1 and CD3 expression was investigated using immunohistochemistry. Density of TILs was evaluated by immunohistochemistry using a quantitative score of CD3-stained intratumoral lymphocytes.PD-L1 expression by neoplastic cells was observed in 9 cases (9%, 5 iCCAs and 4 pCCAs). PD-L1 positive inflammatory cell aggregates were identified in 46% (n = 46) of the cases (31 iCCAs and 15 pCCAs). PD-L1 expression by either neoplastic or inflammatory cells was associated to high density of CD3-positive TILs (p = 0.01 and p = 0.005, respectively). The number of PD-L1 positive inflammatory cell aggregates was higher in tumors with high PD-1 expression (p < 0.0001).Altogether, PD-L1 in iCCA and pCCA is mainly expressed in tumors with high density of TILs. Our results suggest that CCAs with dense intratumoral lymphocytic infiltration might represent good candidates for PD-L1/PD-1 blocking agents.

Quantitative performance evaluation of 124I PET/MRI lesion dosimetry in differentiated thyroid cancer

NASA Astrophysics Data System (ADS)

Wierts, R.; Jentzen, W.; Quick, H. H.; Wisselink, H. J.; Pooters, I. N. A.; Wildberger, J. E.; Herrmann, K.; Kemerink, G. J.; Backes, W. H.; Mottaghy, F. M.

2018-01-01

The aim was to investigate the quantitative performance of 124I PET/MRI for pre-therapy lesion dosimetry in differentiated thyroid cancer (DTC). Phantom measurements were performed on a PET/MRI system (Biograph mMR, Siemens Healthcare) using 124I and 18F. The PET calibration factor and the influence of radiofrequency coil attenuation were determined using a cylindrical phantom homogeneously filled with radioactivity. The calibration factor was 1.00  ±  0.02 for 18F and 0.88  ±  0.02 for 124I. Near the radiofrequency surface coil an underestimation of less than 5% in radioactivity concentration was observed. Soft-tissue sphere recovery coefficients were determined using the NEMA IEC body phantom. Recovery coefficients were systematically higher for 18F than for 124I. In addition, the six spheres of the phantom were segmented using a PET-based iterative segmentation algorithm. For all 124I measurements, the deviations in segmented lesion volume and mean radioactivity concentration relative to the actual values were smaller than 15% and 25%, respectively. The effect of MR-based attenuation correction (three- and four-segment µ-maps) on bone lesion quantification was assessed using radioactive spheres filled with a K2HPO4 solution mimicking bone lesions. The four-segment µ-map resulted in an underestimation of the imaged radioactivity concentration of up to 15%, whereas the three-segment µ-map resulted in an overestimation of up to 10%. For twenty lesions identified in six patients, a comparison of 124I PET/MRI to PET/CT was performed with respect to segmented lesion volume and radioactivity concentration. The interclass correlation coefficients showed excellent agreement in segmented lesion volume and radioactivity concentration (0.999 and 0.95, respectively). In conclusion, it is feasible that accurate quantitative 124I PET/MRI could be used to perform radioiodine pre-therapy lesion dosimetry in DTC.

The prognostic impact of programmed cell death ligand 1 and human leukocyte antigen class I in pancreatic cancer.

PubMed

Imai, Daisuke; Yoshizumi, Tomoharu; Okano, Shinji; Uchiyama, Hideaki; Ikegami, Toru; Harimoto, Norifumi; Itoh, Shinji; Soejima, Yuji; Aishima, Shinichi; Oda, Yoshinao; Maehara, Yoshihiko

2017-07-01

Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients' prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68 + and FoxP3 + cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8 + T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.

PubMed

Hagag, Adel A; Badraia, Ibrahim M; Elfarargy, Mohamed S; Abd Elmageed, Mohamed M; Abo-Ali, Ehab A

2018-02-13

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide that causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis after exposure to oxidative stress. This five years retrospective study was carried out to study the demographic, clinical and laboratory data of 1000 patients with G6PD deficiency anemia registered in Hematology Unit, Pediatric Department, Tanta University Hospital. Data were collected from patient's files, from November 2011 to November 2016, using the pre-designed questionnaires to obtain the complete history, clinical presentation and laboratory investigations including the complete blood count, red blood cells morphology, liver and renal functions and quantitative assay of G6PD enzyme activity by spectrophotometric method. Males were more commonly affected than females (932 males versus 68 females). The highest prevalence of hemolytic crisis in G6PD deficiency patients was found within the age group of 1-3 years (920 patients; 92%) with mean age of the first presentation of 22.8±15.54 months. Patients presented mainly with pallor (1000 patients; 100%), dark red urine (896 patients; 89.6%) and jaundice (878 patients; 87.8%) after 24-72 hours of exposure to the precipitating factors (mean: 36±17.73 hours). Diets were the most common precipitating factor of hemolysis in patients with G6PD deficiency (834 patients; 83.4% of studied cases) especially fava beans (326 patients; 32.6%) and falafel (194 patients; 19.4%) which were the most common precipitating food products causing hemolysis followed by chick pea (108 patients; 10.8%), broad bean (76 patients; 7.6%), green pea (44 patients; 4.4%), pea nuts (38 patients; 3.8%), lentil (28 patients; 2.8%), and lastly black eyed peas (20 patients; 2 %). Infections were the 2nd most common cause of hemolysis (124 patients; 12.4%) including pneumonia (34 patients; 3.4%), tonsillitis (32 patients; 3.2%), typhoid fever (28 patients; 2.8%), hepatitis A (18 patients; 1.8%) and urinary tract infection (12 patients; 1.2%). Drugs were the least common cause of hemolysis (42 patients; 4.2%) including diclofenac sodium (24 patients; 2.4%), ibuprofen (8 patients; 0.8%), acetylsalicylic acid (4 patients; 0.4%), co-trimoxazole (4 patients; 0.4%) and nitrofurantion (2 patients; 0.2%). There was normocytic normochromic anemia with reticulocytosis and Heinz bodies in pre-transfusion complete blood picture in all studied cases. G6PD assay show marked decrease in enzyme level at time of presentation in all cases with the commonest G6PD enzyme level of 3-4 U/gm Hb (592 patients; 59.2%). G6PD deficiency anemia presented mainly with pallor, dark red urine and jaundice after exposure to certain diets, drugs and diseases and therefore patients with G6PD deficiency should avoid exposure to these precipitating factors of hemolysis. We can also recommend large neonatal screening programs to detect cases of G6PD deficiency before the occurrence of acute hemolysis and molecular studies to detect G6PD enzyme variant in Egypt. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan.

PubMed

Nakao, Masatsugu; Yamamoto, Izumi; Maruyama, Yukio; Nakashima, Akio; Matsuo, Nanae; Tanno, Yudo; Ohkido, Ichiro; Ikeda, Masato; Yamamoto, Hiroyasu; Yokoyama, Keitaro; Yokoo, Takashi

2016-02-01

Peritoneal dialysis-associated peritonitis (PD-associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin-bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection-causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single-bag and conventional PD solutions (S+C group, N = 145), twin-bag and conventional PD solutions (T+C group, N = 171) and twin-bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD-associated peritonitis incidences. Incidences of PD-associated peritonitis (times per patient-months) and peritonitis-free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin-bag system has made a greater contribution to reductions in PD-associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Prognostic Significance of NSCLC and Response to EGFR-TKIs of EGFR-Mutated NSCLC Based on PD-L1 Expression.

PubMed

Kobayashi, Kenichi; Seike, Masahiro; Zou, Fenfei; Noro, Rintaro; Chiba, Mika; Ishikawa, Arimi; Kunugi, Shinobu; Kubota, Kaoru; Gemma, Akihiko

2018-02-01

Recent clinical trials have shown that immune checkpoint blockades that target either PD-1 or PD-L1 yield remarkable responses in a subgroup of patients with non-small cell lung cancer (NSCLC). We retrospectively examined, by immunohistochemical analysis, 211 NSCLC samples. Using 32 independent samples, we also evaluated PD-L1 expression in NSCLC patients with EGFR gene mutations treated by EGFR-TKIs. Overall survival of PD-L1-positive stages I-III NSCLC and stage I NSCLC and stages I-III squamous cell carcinoma (SQ) were significantly shorter than those of PD-L1-negative NSCLC (p<0.01 and p=0.02 and p=0.01, respectively). In stage I NSCLC and stages I-III SQ, PD-L1 expression was found to be independent predictor of death after multivariate analysis. Response to EGFR-TKIs was not significantly different between PD-L1-positive and PD-L1-negative NSCLC patients with EGFR mutations. PD-L1 expression was a significant independent predictor of poor outcome in NSCLC patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A Cost Evaluation of Peritoneal Dialysis and Hemodialysis in the Treatment of End-Stage Renal Disease in São Paulo, Brazil

PubMed Central

de Abreu, Mirhelen Mendes; Walker, David R.; Sesso, Ricardo C.; Ferraz, Marcos B.

2013-01-01

♦ Objective: Conventional hemodialysis (HD) predominates over peritoneal dialysis (PD) around the world. Prospective and comparative studies comparing the costs of these modalities are scarce. In the present prospective assessment, we describe the resources used and total patient costs for both HD and PD. ♦ Methodology: We assessed 249 patients on HD and 228 on PD. All patients were 18 years of age or older and on stable dialysis. The information was collected at three points over 1 year, using standard questionnaires. The sources for costs were the Brazilian public and private health care systems. Societal perspective was considered. ♦ Statistical Analysis: Core trends and dispersions were measured. Regression models assessed the impact of modality on the average total cost per patient per year. ♦ Results: Of the 249 HD patients and 228 PD dialysis patients, 189 (74%) and 160 (70%) respectively completed follow-up. The mean age for women was 55.8 years; for men, it was 59.8 years (p = 0.001). The average total cost per patient-year was US$28 570 for HD and US$27 158 for PD. By category, the costs consisted of direct medical-hospital costs (82.3% for HD, 86.5% for PD), direct nonmedical costs (5.3% for HD, 3.7% for PD), and indirect costs (12.4% for HD, 9.8% for PD). Overall costs were less for PD patients than for their HD counterparts (p = 0.025). ♦ Conclusions: Maintenance dialysis represented the most important source of costs for both modalities; loss of productivity incurred significant costs. Future studies should contemplate the social consequences arising from each modality. PMID:23209041

Automated production of 124I and 64Cu using IBA Terimo and Pinctada metal electroplating and processing modules

NASA Astrophysics Data System (ADS)

Poniger, S. S.; Tochon-Danguy, H. J.; Panopoulos, H. P.; O'Keefe, G. J.; Peake, D.; Rasool, R.; Scott, A. M.

2012-12-01

There is worldwide growing interest for the production of long-lived positron emitters for molecular imaging and the development of novel immuno-PET techniques for drugs discovery. The desire to produce solid target isotopes in Australia has significantly increased over the years and several research projects for labelling of peptides, proteins and biomolecules, including labelling of recombinant antibodies has been limited due to the availability of suitable isotopes. This has led to the recent installation and commissioning of a new lab dedicated to fully automated solid target isotope production, including 124I, 64Cu, 89Zr and 86Y.

Inflatable penile prosthesis implant length with baseline characteristic correlations: preliminary analysis of the PROPPER study

PubMed Central

Henry, Gerard; Karpman, Edward; Brant, William; Jones, LeRoy; Khera, Mohit; Kohler, Tobias; Christine, Brian; Rhee, Eugene; Kansas, Bryan; Bella, Anthony J.

2017-01-01

Background “Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration” (PROPPER) is a large, multi-institutional, prospective clinical study to collect, analyze, and report real-world outcomes for men implanted with penile prosthetic devices. We prospectively correlated co-morbid conditions and demographic data with implanted penile prosthesis size to enable clinicians to better predict implanted penis size following penile implantation. We present many new data points for the first time in the literature and postulate that radical prostatectomy (RP) is negatively correlated with penile corporal length. Methods Patient demographics, medical history, baseline characteristics and surgical details were compiled prospectively. Pearson correlation coefficient was generated for the correlation between demographic, etiology of ED, duration of ED, co-morbid conditions, pre-operative penile length (flaccid and stretched) and length of implanted penile prosthesis. Multivariate analysis was performed to define predictors of implanted prosthesis length. Results From June 2011 to June 2017, 1,135 men underwent primary implantation of penile prosthesis at a total of 11 study sites. Malleable (Spectra), 2-piece Ambicor, and 3-piece AMS 700 CX/LGX were included in the analysis. The most common patient comorbidities were CV disease (26.1%), DM (11.1%), and PD (12.4%). Primary etiology of ED: RP (27.4%), DM (20.3%), CVD (18.0%), PD (10.3%), and Priapism (1.4%), others (22.6%). Mean duration of ED is 6.2¡À4.1 years. Implant length was weakly negatively correlated with White/Caucasian (r=−0.18; P<0.01), history of RP (r=−0.13; P<0.01), PD as comorbidity (r=−0.16; P<0.01), venous leak (r=−0.08; P<0.01), and presence of stress incontinence (r=−0.13; P<0.01). Analyses showed weak positive correlations with Black/AA (r=0.32; P<0.01), CV disease as primary ED etiology (r=0.08; P<0.01) and pre-operative stretched penile length (r=0.18; P<0.01). There is a moderate correlation with pre-operative flaccid penile length (r=0.30; P<0.01). Conclusions Implanted penile prosthesis length is negatively correlated with some ethnic groups, prostatectomy, and incontinence. Positive correlates include CV disease, preoperative stretched penile length, and flaccid penile length. PMID:29354506

The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.

PubMed

Makeyev, Eugene V; Zhang, Jiangwen; Carrasco, Monica A; Maniatis, Tom

2007-08-03

Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in nonneuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2 (nPTB/brPTB/PTBLP), an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay (NMD). During neuronal differentiation, miR-124 reduces PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124 plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing.

Improved synthesis of no-carrier-added p-[124I]iodo-L-phenylalanine and p-[131I]iodo-L-phenylalanine for nuclear medicine applications in malignant gliomas.

PubMed

Israel, Ina; Brandau, Wolfgang; Farmakis, Georgios; Samnick, Samuel

2008-04-01

This work describes the synthesis and the tumor affinity testing of no-carrier-added (n.c.a.) p-[(124)I]iodo-L-phenyalanine ([(124)I]IPA) and n.c.a. p-[(131)I]iodo-l-phenyalanine ([(131)I]IPA) as radiopharmaceuticals for imaging brain tumors with PET and for radionuclid-based therapy, respectively. Parameters for labeling were optimized with regard to the amount of precursor, temperature and time. Thereafter, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were investigated in rat F98 glioma and in primary human A1207 and HOM-T3868 glioblastoma cells in vitro, followed by an in vivo evaluation in CD1 nu/nu mice engrafted with human glioblastoma. No-carrier-added [(124)I]IPA and n.c.a. [(131)I]IPA were obtained in 90+/-6% radiochemical yield and >99% radiochemical purity by iododestannylation of N-Boc-4-(tri-n-butylstannyl)-L-phenylalanine methylester in the presence of chloramine-T, followed by hydrolysis of the protecting groups. The total synthesis time, including the HPLC separation and pharmacological formulation, was less than 60 min and compatible with a clinical routine production. Both amino acid tracers accumulated intensively in rat and in human glioma cells. The radioactivity incorporation in tumor cells following a 15-min incubation at 37 degrees C/pH 7.4 varied from 25% to 42% of the total loaded activity per 10(6) tumor cells (296-540 cpm/1000 cells). Inhibition experiments confirmed that n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were taken up into tumor by the sodium-independent L- and ASC-type transporters. Biodistribution and whole-body imaging by a gamma-camera and a PET scanner demonstrated a high targeting level and a prolonged retention of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA within the xenotransplanted human glioblastoma and a primarily renal excretion. However, an accurate delineation of the tumors in mice was not possible by our imaging systems. Radioactivity accumulation in the thyroid and in the stomach as a secondary indication of deiodination was less than 1% of the injected dose at 24h p.i., confirming the high in vivo stability of the radiopharmaceuticals. In conclusion, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA are new promising radiopharmaceuticals, which can now be prepared in high radiochemical yields and high purity for widespread clinical applications. The specific and high-level targeting of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA to glioma cells in vitro and to glioblastoma engrafts in vivo encourages further in vivo validations to ascertain their clinical potential as agent for imaging and quantitation of gliomas with PET, and for radionuclid-based therapy, respectively.

Athletic Training Student Socialization Part I: Socializing Students in Undergraduate Athletic Training Programs

ERIC Educational Resources Information Center

Mazerolle, Stephanie M.; Bowman, Thomas G.; Dodge, Thomas M.

2014-01-01

Context: Professional socialization is a key process in the professional development of athletic training students. The published athletic training education research has focused on many perspectives regarding socialization; however, it has yet to investigate the program director's (PD's) opinion. Objective: To gain insights from the PD on methods…

Rational design of a low molecular weight, stable, potent, and long-lasting GPR103 aza-β3-pseudopeptide agonist.

PubMed

Neveu, Cindy; Lefranc, Benjamin; Tasseau, Olivier; Do-Rego, Jean-Claude; Bourmaud, Adèle; Chan, Philippe; Bauchat, Patrick; Le Marec, Olivier; Chuquet, Julien; Guilhaudis, Laure; Boutin, Jean A; Ségalas-Milazzo, Isabelle; Costentin, Jean; Vaudry, Hubert; Baudy-Floc'h, Michèle; Vaudry, David; Leprince, Jérôme

2012-09-13

26RFa, a novel RFamide neuropeptide, is the endogenous ligand of the former orphan receptor GPR103. Intracerebroventricular injection of 26RFa and its C-terminal heptapeptide, 26RFa((20-26)), stimulates food intake in rodents. To develop potent, stable ligands of GPR103 with low molecular weight, we have designed a series of aza-β(3)-containing 26RFa((20-26)) analogues for their propensity to establish intramolecular hydrogen bonds, and we have evaluated their ability to increase [Ca(2+)](i) in GPR103-transfected cells. We have identified a compound, [Cmpi(21),aza-β(3)-Hht(23)]26RFa((21-26)), which was 8-fold more potent than 26RFa((20-26)) in mobilizing [Ca(2+)](i). This pseudopeptide was more stable in serum than 26RFa((20-26)) and exerted a longer lasting orexigenic effect in mice. This study constitutes an important step toward the development of 26RFa analogues that could prove useful for the treatment of feeding disorders.

Efficacy of fenbendazole formulated in a commercial primate diet for treating specific pathogen-free baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

PubMed

Reichard, Mason V; Wolf, Roman F; Clingenpeel, Lindsay C; Doan, Sandra K; Jones, Amy N; Gray, Kristene M

2008-11-01

Trichuris trichiura is a common intestinal nematode parasite of captive baboons. We evaluated the efficacy of fenbendazole formulated in a commercial primate diet (FBZ-PD) for treating specific pathogen-free (SPF) baboons (Papio cynocephalus anubis) naturally infected with Trichuris trichiura. Twenty-nine baboons, housed indoors in 3 separate rooms, were fed FBZ-PD for 5 d, whereas 4 baboons housed in another isolated area served as untreated controls. The efficacy of FBZ-PD was measured as reduction in the number of T. trichiura eggs in host feces after treatment as determined by quantitative fecal flotation examination. All baboons that received FBZ-PD stopped shedding T. trichiura eggs by 7 d after initiation of treatment, and remained negative until at least 119 d after treatment. However, eggs of T. trichiura were present in the feces of 3 (10.3%) experimental baboons at 154 d after treatment. Untreated control baboons shed T. trichiura eggs throughout the entire study. Our results indicate that FBZ-PD was efficacious for treating SPF baboons infected with T. trichiura.

Efficacy of Fenbendazole Formulated in a Commercial Primate Diet for Treating Specific Pathogen-free Baboons (Papio cynocephalus anubis) Infected with Trichuris trichiura

PubMed Central

Reichard, Mason V; Wolf, Roman F; Clingenpeel, Lindsay C; Doan, Sandra K; Jones, Amy N; Gray, Kristene M

2008-01-01

Trichuris trichiura is a common intestinal nematode parasite of captive baboons. We evaluated the efficacy of fenbendazole formulated in a commercial primate diet (FBZ-PD) for treating specific pathogen-free (SPF) baboons (Papio cynocephalus anubis) naturally infected with Trichuris trichiura. Twenty-nine baboons, housed indoors in 3 separate rooms, were fed FBZ-PD for 5 d, whereas 4 baboons housed in another isolated area served as untreated controls. The efficacy of FBZ-PD was measured as reduction in the number of T. trichiura eggs in host feces after treatment as determined by quantitative fecal flotation examination. All baboons that received FBZ-PD stopped shedding T. trichiura eggs by 7 d after initiation of treatment, and remained negative until at least 119 d after treatment. However, eggs of T. trichiura were present in the feces of 3 (10.3%) experimental baboons at 154 d after treatment. Untreated control baboons shed T. trichiura eggs throughout the entire study. Our results indicate that FBZ-PD was efficacious for treating SPF baboons infected with T. trichiura. PMID:19049254

In Situ Catalytic Groundwater Treatment Using Pd-Catalysts and Horizontal Flow Treatment Wells

DTIC Science & Technology

2007-02-01

1,2,4-Trichlorobenzene Hexachlorobutadiene Naphthalene 1,2,3-Trichlorobenzene Internal Standards Fluorobenzene 2-Bromo- 1 - chloropropane a Retention...internal standard method using a purge-and-trap. Internal standards were: Fluorobenzene for PID, 2-Bromo- 1 - chloropropane for HECD. b Detector does not...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and

Innovative Procedure for the, in Situ, Measurement of the Resistive Thermal Coefficient of H(D)/Pd during Electrolysis:. Cross-Comparison of New Elements Detected in the Th-Hg-Pd-D(H) Electrolytic Cells

NASA Astrophysics Data System (ADS)

Celani, Francesco; Spallone, A.; Righi, E.; Trenta, G.; Catena, C.; D'Agostaro, G.; Quercia, P.; Andreassi, V.; Marini, P.; di Stefano, V.; Nakamura, M.; Mancini, A.; Sona, P. G.; Fontana, F.; Gamberale, L.; Garbelli, D.; Celia, E.; Falcioni, F.; Marchesini, M.; Novaro, E.; Mastromatteo, U.

2006-02-01

In the framework of cold fusion studies one of the most important parameters is the deuterium (D) to palladium (Pd) ratio, D/Pd. It is well known that the value of this parameter is related to the normalised resistivity (R/R0) of the D-Pd system. When at high D/Pd ratios (i.e. at low R/R0 values) some excess heat occurs, the Pd wire temperature increase and, as a consequence, the apparent R/R0 value also increases. This effect might give raise to ambiguous data interpretation: similar results are in fact expected in case of a Pd wire degassing (i.e. decreasing of D/Pd ratio). To solve this problem, we developed an innovative procedure and a suitable experimental set-up for the in situ measurement of the Resistive Temperature Coefficient (which is affected only by the real D/Pd ratio) during electrolysis. We will report the results on the hydrogen and deuterium loading of thin (50 μm), and long (60cm) Pd wires, immersed in a solution of C2H5OD (or C2H5OH) and D2O (or H2O), with addition of thorium (Th) and mercury (Hg) salts at micromolar concentrations. Evidence of "transmutations" of some elements occasionally present on the Pd surface, and sometimes also in the electrolytic solution, have often been claimed in cold fusion experiments. In the present work, unexpected elements have been detected by high-resolution ICP-MS analysis. Some of these elements have also an isotopic composition different from the natural one.

Prevalence of G6PD deficiency and Plasmodium falciparum parasites in asymptomatic school children living in southern Ghana.

PubMed

Amoah, Linda Eva; Opong, Akua; Ayanful-Torgby, Ruth; Abankwa, Joana; Acquah, Festus K

2016-07-26

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. Although G6PD deficiency is globally distributed it is more prevalent in malaria-endemic countries. Several mutations have been identified in the G6PD gene, which alter enzyme activity. The G6PD genotype predominantly found in sub-Saharan Africa is the G6PDB (G6PD376A) with (G6PD376G) and G6PDA- (G6PD376G/202A, G6PD376G/542T, G6PD376G/680T and G6PD376G/968C) occurring at lower frequencies. The aim of this study was to identify the prevalence of G6PD deficiency and asymptomatic Plasmodium falciparum carriage in children living in southern Ghana and determine whether G6PD deficiency influences asymptomatic carriage of P. falciparum parasites. Blood samples were obtained once a month from 170 healthy Ghanaian school children aged between 5 and 12 years from Basic schools in two communities Obom and Abura with similar rainfall patterns and malaria peak seasons. G6PD enzyme activity was assessed using the qualitative G6PD RDT kit (AccessBIO). G6PD genotyping and asymptomatic parasite carriage was determined by PCR followed by restriction fragment length polymorphism (RFLP) of DNA extracted from dried blood spots. The only sub-Saharan G6PD A- allele detected was the A376G/G202A found in 12.4 % (21/170), of the children and distributed as 4.1 % (7/170) A-, 1.8 % (3/170) A-/A- homozygous deficient males and females and 6.5 % (11/170) A/A- and B/A- heterozygous deficient females. Phenotypically, 10.6 % (15/142) of the children were G6PD deficient. The asymptomatic carriage of P. falciparum by PCR was 50, 29.4, 38.2 and 38.8 % over the months of February through May 2015, respectively, and 28.8, 22.4, 25.9 and 5.9 % by microscopy during the same periods. G6PD deficiency was significantly associated with a lowered risk of PCR-estimated asymptomatic P. falciparum carriage in children during the off peak malaria season in Southern Ghana.

Implications of Parkinson's disease pathophysiology for the development of cell replacement strategies and drug discovery in neurodegenerative diseases.

PubMed

Pan-Montojo, Francisco; Funk, Richard H W

2012-11-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder traditionally characterized by the loss of dopaminergic neurons in the substantia nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells, induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell replacement strategies has lead to numerous studies and clinical trials in this direction. It is now possible to differentiate stem cells into dopaminergic neurons in vitro and clinical trials have shown an improvement in PD-related symptoms after intra-striatal embryonic transplants and acceptable cell survival rates on the mid term. However, clinical improvement is transitory and associated with a strong placebo effect. Interestingly, recent pathological studies in PD patients who received embryonic stem cells show that in PD patients, grafted neurons show PD-related pathology. In this manuscript we review the latest findings regarding PD pathophysiology and give an outlook on the implications of these findings in how cell replacement strategies for PD treatment should be tested. These include changes in the type of animal models used, the preparation/conditioning of the cells before intracerebral injection, specially regarding backbone chronic diseases in iPS cells and determining the optimal proliferation, survival, differentiation and migration capacity of the grafted cells.

Production cross sections of deuteron-induced reactions on natural palladium for Ag isotopes

NASA Astrophysics Data System (ADS)

Ukon, Naoyuki; Aikawa, Masayuki; Komori, Yukiko; Haba, Hiromitsu

2018-07-01

Activation cross sections for deuteron-induced reactions on natural palladium were measured up to 24 MeV using the stacked-foil method and the high resolution gamma-ray spectroscopy. The production cross sections of 103Ag, the parent of a medical radioactive isotope 103Pd, were obtained. We found that our result is in good agreement with the previous data up to 20.3 MeV, and obtained new data at higher energies. In addition, the production cross sections of 104g+mAg, 105Ag, 106mAg, 110mAg and 111Ag were presented.

Glucose-6-phosphate dehydrogenase and NADPH redox regulates cardiac myocyte L-type calcium channel activity and myocardial contractile function.

PubMed

Rawat, Dhwajbahadur K; Hecker, Peter; Watanabe, Makino; Chettimada, Sukrutha; Levy, Richard J; Okada, Takao; Edwards, John G; Gupte, Sachin A

2012-01-01

We recently demonstrated that a 17-ketosteroid, epiandrosterone, attenuates L-type Ca(2+) currents (I(Ca-L)) in cardiac myocytes and inhibits myocardial contractility. Because 17-ketosteroids are known to inhibit glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, and to reduce intracellular NADPH levels, we hypothesized that inhibition of G6PD could be a novel signaling mechanism which inhibit I(Ca-L) and, therefore, cardiac contractile function. We tested this idea by examining myocardial function in isolated hearts and Ca(2+) channel activity in isolated cardiac myocytes. Myocardial function was tested in Langendorff perfused hearts and I(Ca-L) were recorded in the whole-cell patch configuration by applying double pulses from a holding potential of -80 mV and then normalized to the peak amplitudes of control currents. 6-Aminonicotinamide, a competitive inhibitor of G6PD, increased pCO(2) and decreased pH. Additionally, 6-aminonicotinamide inhibited G6PD activity, reduced NADPH levels, attenuated peak I(Ca-L) amplitudes, and decreased left ventricular developed pressure and ±dp/dt. Finally, dialyzing NADPH into cells from the patch pipette solution attenuated the suppression of I(Ca-L) by 6-aminonicotinamide. Likewise, in G6PD-deficient mice, G6PD insufficiency in the heart decreased GSH-to-GSSG ratio, superoxide, cholesterol and acetyl CoA. In these mice, M-mode echocardiographic findings showed increased diastolic volume and end-diastolic diameter without changes in the fraction shortening. Taken together, these findings suggest that inhibiting G6PD activity and reducing NADPH levels alters metabolism and leads to inhibition of L-type Ca(2+) channel activity. Notably, this pathway may be involved in modulating myocardial contractility under physiological and pathophysiological conditions during which the pentose phosphate pathway-derived NADPH redox is modulated (e.g., ischemia-reperfusion and heart failure).

Physics process level discrimination of detections for GATE: assessment of contamination in SPECT and spurious activity in PET.

PubMed

De Beenhouwer, Jan; Staelens, Steven; Vandenberghe, Stefaan; Verhaeghe, Jeroen; Van Holen, Roel; Rault, Erwann; Lemahieu, Ignace

2009-04-01

The GEANT4 application for tomographic emission (GATE) is one of the most detailed Monte Carlo simulation tools for SPECT and PET. It allows for realistic phantoms, complex decay schemes, and a large variety of detector geometries. However, only a fraction of the information in each particle history is available for postprocessing. In order to extend the analysis capabilities of GATE, a flexible framework was developed. This framework allows all detected events to be subdivided according to their type: In PET, true coincidences from others, and in SPECT, geometrically collimated photons from others. The framework of the authors can be applied to any isotope, phantom, and detector geometry available in GATE. It is designed to enhance the usability of GATE for the study of contamination and for the investigation of the properties of current and future prototype detectors. The authors apply the framework to a case study of Bexxar, first assuming labeling with 124I, then with 131I. It is shown that with 124I PET, results with an optimized window improve upon those with the standard window but achieve less than half of the ideal improvement. Nevertheless, 124I PET shows improved resolution compared to 131I SPECT with triple-energy-window scatter correction.

Determinants of pupil diameters and pupil dynamics in an adult Chinese population.

PubMed

Zheng, Ce; de Leon, John Mark S; Cheung, Carol Y; Narayanaswamy, Arun K; Ong, Sim-Heng; Tan, Clement W; Chew, Paul T; Perera, Shamira A; Wong, Tien Y; Aung, Tin

2016-05-01

To investigate the determinants of pupil diameter (PD), amplitude of pupil diameter change (PD-change) and speed of pupil constriction (SPC) using video anterior segment optical coherence tomography (AS-OCT) in a population-based sample of Chinese adults. Chinese adults aged 40 to 80 years who were free from glaucoma were consecutively recruited from the population-based Singapore Chinese Eye Study. The SPC was measured by AS-OCT videography. Univariate and multivariate analyses were performed to examine the effects of demographic and ocular biometric factors (e.g., axial length [AL], anterior chamber depth [ACD], baseline PD, iris thickness at the area of the dilator muscle [ITDMR], iris area [IA], and iris bowing [IB]) on SPC, PD, and PD-change. A total of 266/302 (89.5 %) AS-OCT videos of eligible eyes were available for analysis. Among these subjects, 64.3 % were women, and the mean age (± standard deviation [SD]) was 56 ± 8.3 years. SPC was not associated with sex. In multiple regression analyses, SPC was independently associated with baseline PD (β = 0.116, p = 0.006). Baseline PD was independently associated with ACD (β = 0.341, p < 0.001), TISA 500 (β = -4.513, p < 0.001), IA (β = -2.796, p < 0.001), and ITDMR (β = 6.573, p < 0.001). PD-change was independently associated with ACD (β = 0.256, p < 0.001), IA (β = -1.507, p < 0.001), IB (β = 0.630, p = 0.011), and ITDMR (β = 3.124, p < 0.001). Among normal eyes in an adult Chinese population, SPC was associated with larger baseline PD. Larger baseline PD and greater PD change form dark to light were associated with greater ACD, with smaller IA and thicker ITDMR.

Electrical and NO2 sensing characteristics of Pd/ZnO nanoparticles based Schottky diode at room temperature

NASA Astrophysics Data System (ADS)

Chandra, Lalit; Sahu, Praveen Kumar; Dwivedi, R.; Mishra, V. N.

2017-12-01

The present work deals with Pd/ZnO nanoparticles based Schottky diode for detection of NO2 at room temperature (298 K). To fabricate Pd/ZnO Schottky diode, zinc oxide (ZnO) nanoparticles (NPs) based film was developed on glass substrate using sol-gel spin coating process. Subsequently; Pd was deposited on ZnO using thermal evaporation technique. The structural properties of developed ZnO film were studied using energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). The particles size of the developed film was in range of ~25 to ~110 nm. The response of fabricated Pd/ZnO Schottky diode was studied upon exposure to NO2 in terms of change in I-V characteristics. The magnitude of barrier height and ideality factor has been evaluated with concentration of NO2 ranging from 10 to 50 ppm. The developed sensor has good sensitivity of ~45.2%, with fast response and recovery time; 67 s and 250 s respectively for 50 ppm concentration of NO2 with excellent repeatability. The obtained results have been explained in terms of surface and subsurface adsorption of NO2 on Pd, subsequently dissociation of NO2 and its diffusion, which creates dipole moment at the Pd/ZnO interface.

KSC-08pd1714

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – After their successful STS-124 mission and landing on Runway 15 at NASA's Kennedy Space Center, crew members exit the crew transport vehicle. Leading the way is Commander Mark Kelly, followed by (from left) Mission Specialists Mike Fossum, Karen Nyberg, Akihiko Hoshide and Ron Garan. Behind them is Stephen Lindsay, chief of the Astronaut Corps, and astronaut Janet Kavandi. Space shuttle Discovery's main landing gear touched down at 11:15:19 a.m. EDT on Runway 15. The nose landing gear touched down at 11:15:30 a.m. and wheel stop was at 11:16:19 a.m. The mission completed 5.7 million miles. The STS-124 mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the space station. Photo credit: NASA/Kim Shiflett

KSC-08pd1151

NASA Image and Video Library

2008-05-06

CAPE CANAVERAL, Fla. -- After their arrival at NASA Kennedy Space Center's Shuttle Landing Facility, the crew of space shuttle Discovery's STS-124 mission gather for a group photo. The crew is at Kennedy to take part in the Terminal Countdown Demonstration Test, or TCDT. From left are Mission Specialist Greg Chamitoff, Pilot Ken Ham, Mission Specialist Karen Nyberg, Commander Mark Kelly and Mission Specialists Ron Garan, Mike Fossum and Akihiko Hoshide, who represents the Japan Aerospace Exploration Agency, or JAXA. TCDT is a rehearsal for launch that includes practicing emergency procedures, handling on-orbit equipment, and simulating a launch countdown. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.« less

Atomic Energy Levels. As Derived From the Analyses of Optical Spectra. Volume 3

DTIC Science & Technology

1958-05-01

26756.70 0 1.24 1 27362. 55 1.06 10 1 .98626.50 1.443 S S 0 0 0 0 0 0 0 3® Mt --Coaniued Mo 1-Cmedaned Conf. De @al J Level Intera Oba. C;044 Del6 . J... De , 1 Level Inteval Ob, I Conig. Desig. J Level Interval Ob..g W 2 15. P7 L 146 83° 4 5M. 5 0 1.17 46’ S 51808.89 88 84’ 5 55957.80 1. 14 4w 6 51853...41772 --176.14 1.86 1 85&07 -14&.00 1.4041M4 728 10&3& 32 854 $2408. 07 165 4d0( GD)5 a 4D 31 10516. 34 1.44 4d$(a D)5p s ’ De 34 38560. 87 465. 33 L

KSC-08pd2376

NASA Image and Video Library

2008-08-12

CAPE CANAVERAL, Fla. – A van travels the width of the Launch Pad 39A flame trench at NASA's Kennedy Space Center after tests of the repairs on the wall. Workers sprayed a heat-resistant concrete called Fondue Fyre into steel grid structures, welded to the wall of the flame trench. Fondue Fyre was developed during NASA's Apollo lunar program. Damage to the trench occurred during the launch of space shuttle Discovery on the STS-124 mission. A 75-foot by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs being completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Dimitri Gerondidakis

Factors associated with fear of falling in people with Parkinson’s disease

PubMed Central

2014-01-01

Background This study aimed to comprehensibly investigate potential contributing factors to fear of falling (FOF) among people with idiopathic Parkinson’s disease (PD). Methods The study included 104 people with PD. Mean (SD) age and PD-duration were 68 (9.4) and 5 (4.2) years, respectively, and the participants’ PD-symptoms were relatively mild. FOF (the dependent variable) was investigated with the Swedish version of the Falls Efficacy Scale, i.e. FES(S). The first multiple linear regression model replicated a previous study and independent variables targeted: walking difficulties in daily life; freezing of gait; dyskinesia; fatigue; need of help in daily activities; age; PD-duration; history of falls/near falls and pain. Model II included also the following clinically assessed variables: motor symptoms, cognitive functions, gait speed, dual-task difficulties and functional balance performance as well as reactive postural responses. Results Both regression models showed that the strongest contributing factor to FOF was walking difficulties, i.e. explaining 60% and 64% of the variance in FOF-scores, respectively. Other significant independent variables in both models were needing help from others in daily activities and fatigue. Functional balance was the only clinical variable contributing additional significant information to model I, increasing the explained variance from 66% to 73%. Conclusions The results imply that one should primarily target walking difficulties in daily life in order to reduce FOF in people mildly affected by PD. This finding applies even when considering a broad variety of aspects not previously considered in PD-studies targeting FOF. Functional balance performance, dependence in daily activities, and fatigue were also independently associated with FOF, but to a lesser extent. Longitudinal studies are warranted to gain an increased understanding of predictors of FOF in PD and who is at risk of developing a FOF. PMID:24456482

Enhancement of burning velocity by dissociated oxygen atoms

NASA Astrophysics Data System (ADS)

Akashi, Haruaki; Yoshinaga, Tomokazu; Sasaki, Koichi

2015-09-01

Green technology, such as preventing global warming, has been developed for years. Researches on plasma assisted combustion is one of the technologies and have been done for investigating more efficient combustion, more efficient use of fossil fuel with plasmas or applying electric fields. In the ignition time delay analyses with the dissociated oxygen atoms which is generated by non-equilibrium plasma had significant effect on the ignition time. In this paper, dissociated oxygen could effect on burning velocity or not has been examined using CHEMKIN. As a result, no effect can be seen with dissociation degree of lower than 10-3. But there is an effect on the enhancement of burning velocity with higher degree of 10-3. At the dissociation degree of 5×10-2, the burning velocity is enhanced at a factor of 1.24. And it is found that the distributions of each species in front of preheat zone are completely different. The combustion process is proceeded several steps in advance, and generation of H2O, CO and CO2 can be seen before combustion in higher dissociation case. This work was supported by KAKENHI (22340170).

Exchange coupling interaction in L10-FePd/α-Fe nanocomposite magnets with large maximum energy products.

PubMed

Sakuma, Noritsugu; Ohshima, Tsubasa; Shoji, Tetsuya; Suzuki, Yoshihito; Sato, Ryota; Wachi, Ayako; Kato, Akira; Kawai, Yoichiro; Manabe, Akira; Teranishi, Toshiharu

2011-04-26

Nanocomposite magnets (NCMs) consisting of hard and soft magnetic phases are expected to be instrumental in overcoming the current theoretical limit of magnet performance. In this study, structural analyses were performed on L1(0)-FePd/α-Fe NCMs with various hard/soft volume fractions, which were formed by annealing Pd/γ-Fe(2)O(3) heterostructured nanoparticles and pure Pd nanoparticles. The sample with a hard/soft volume ratio of 82/18 formed by annealing at 773 K had the largest maximum energy product (BH(max) = 10.3 MGOe). In such a sample, the interface between the hard and soft phases was coherent and the phase sizes were optimized, both of which effectively induced exchange coupling. This exchange coupling was directly observed by visualizing the magnetic interaction between the hard and soft phases using a first-order reversal curve diagram, which is a valuable tool to improve the magnetic properties of NCMs.

Performance of a block detector PET scanner in imaging non-pure positron emitters—modelling and experimental validation with 124I

NASA Astrophysics Data System (ADS)

Robinson, S.; Julyan, P. J.; Hastings, D. L.; Zweit, J.

2004-12-01

The key performance measures of resolution, count rate, sensitivity and scatter fraction are predicted for a dedicated BGO block detector patient PET scanner (GE Advance) in 2D mode for imaging with the non-pure positron-emitting radionuclides 124I, 55Co, 61Cu, 62Cu, 64Cu and 76Br. Model calculations including parameters of the scanner, decay characteristics of the radionuclides and measured parameters in imaging the pure positron-emitter 18F are used to predict performance according to the National Electrical Manufacturers Association (NEMA) NU 2-1994 criteria. Predictions are tested with measurements made using 124I and show that, in comparison with 18F, resolution degrades by 1.2 mm radially and tangentially throughout the field-of-view (prediction: 1.2 mm), count-rate performance reduces considerably and in close accordance with calculations, sensitivity decreases to 23.4% of that with 18F (prediction: 22.9%) and measured scatter fraction increases from 10.0% to 14.5% (prediction: 14.7%). Model predictions are expected to be equally accurate for other radionuclides and may be extended to similar scanners. Although performance is worse with 124I than 18F, imaging is not precluded in 2D mode. The viability of 124I imaging and performance in a clinical context compared with 18F is illustrated with images of a patient with recurrent thyroid cancer acquired using both [124I]-sodium iodide and [18F]-2-fluoro-2-deoxyglucose.

Source strength verification and quality assurance of preloaded brachytherapy needles using a CMOS flat panel detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golshan, Maryam, E-mail: maryam.golshan@bccancer.bc.ca; Spadinger, Ingrid; Chng, Nick

2016-06-15

Purpose: Current methods of low dose rate brachytherapy source strength verification for sources preloaded into needles consist of either assaying a small number of seeds from a separate sample belonging to the same lot used to load the needles or performing batch assays of a subset of the preloaded seed trains. Both of these methods are cumbersome and have the limitations inherent to sampling. The purpose of this work was to investigate an alternative approach that uses an image-based, autoradiographic system capable of the rapid and complete assay of all sources without compromising sterility. Methods: The system consists of amore » flat panel image detector, an autoclavable needle holder, and software to analyze the detected signals. The needle holder was designed to maintain a fixed vertical spacing between the needles and the image detector, and to collimate the emissions from each seed. It also provides a sterile barrier between the needles and the imager. The image detector has a sufficiently large image capture area to allow several needles to be analyzed simultaneously.Several tests were performed to assess the accuracy and reproducibility of source strengths obtained using this system. Three different seed models (Oncura 6711 and 9011 {sup 125}I seeds, and IsoAid Advantage {sup 103}Pd seeds) were used in the evaluations. Seeds were loaded into trains with at least 1 cm spacing. Results: Using our system, it was possible to obtain linear calibration curves with coverage factor k = 1 prediction intervals of less than ±2% near the centre of their range for the three source models. The uncertainty budget calculated from a combination of type A and type B estimates of potential sources of error was somewhat larger, yielding (k = 1) combined uncertainties for individual seed readings of 6.2% for {sup 125}I 6711 seeds, 4.7% for {sup 125}I 9011 seeds, and 11.0% for Advantage {sup 103}Pd seeds. Conclusions: This study showed that a flat panel detector dosimetry system is a viable option for source strength verification in preloaded needles, as it is capable of measuring all of the sources intended for implantation. Such a system has the potential to directly and efficiently estimate individual source strengths, the overall mean source strength, and the positions within the seed-spacer train.« less

An experimental palladium-103 seed (OptiSeedexp) in a biocompatible polymer without a gold marker: characterization of dosimetric parameters including the interseed effect.

PubMed

Abboud, F; Scalliet, P; Vynckier, S

2008-12-01

Permanent implantation of 125I (iodine) or 103Pd (palladium) sources is a popular treatment option in the management of early stage prostate cancer. New sources are being developed, some of which are being marketed for different clinical applications. A new technique of adjuvant stereotactic permanent seed breast implant, similar to that used in the treatment of prostate cancer, has been proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058 (2007)] with encouraging results. The presence of artifacts from the metallic seeds, however, can disturb follow-up imaging. The development of plastic seeds has reduced these artifacts. This paper presents a feasibility study of the advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for future clinical applications, and on the effect of the gold marker on the dosimetric characteristics of such seeds. Experimental palladium seeds, OptiSeedexp, were manufactured by International Brachytherapy (IBt), Seneffe, Belgium, from a biocompatible polymer, including the marker. Apart from the absence of a gold marker, the studied seed has an identical design to the OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the quantity of radioactive material needed for a given dose rate and to reduce the anisotropy of the radiation field around the seed. In addition, this design is intended to decrease the interseed effects that can occur as a result of the marker and the encapsulation. Dosimetric measurements were performed using LiF thermoluminescent dosimeters (1 mm3) in solid water phantoms (WT1). Measured data were compared to Monte Carlo simulated data in solid water using the MCNP code, version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As the measured and calculated data were in agreement, Monte Carlo calculations were then performed in liquid water to obtain relevant dosimetric data as required by TG-43U1 recommendations. Comparison of the results with previous studies of OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)], and of InterSource103 [Appl. Radiat. Isot. 57, 805-811 (2002)] showed very good agreement for the dose rate constant and for the radial dose function. With respect to the anisotropy function, the relative dose (anisotropy value relative to 90 degrees) from the polymer seed at a distance of 3 cm was close to unity (105%) at 0 degrees, whereas the relative values for the OptiSeed103 with a gold marker and the titanium-encapsulated InterSource103 seed decreased to 70% and 40%, respectively. The interseed effect from one seed was negligible and in the order of calculation uncertainty, making calculation of the dose rate distribution of the studied seeds, according to TG43U1 recommendations, more accurate and closer to reality. This feasibility study shows that due to the low energy of palladium-103, the negligible interseed effect and the reduced artifacts in postimplant medical imaging, this experimental plastic seed would be a good source for breast brachytherapy. This feasibility study was carried out in collaboration with IBt and will be continued with a study of its visibility in different tissues.

An experimental palladium-103 seed (OptiSeed{sup exp}) in a biocompatible polymer without a gold marker: Characterization of dosimetric parameters including the interseed effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abboud, F.; Scalliet, P.; Vynckier, S.

Permanent implantation of {sup 125}I (iodine) or {sup 103}Pd (palladium) sources is a popular treatment option in the management of early stage prostate cancer. New sources are being developed, some of which are being marketed for different clinical applications. A new technique of adjuvant stereotactic permanent seed breast implant, similar to that used in the treatment of prostate cancer, has been proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058 (2007)] with encouraging results. The presence of artifacts from the metallic seeds, however, can disturb follow-up imaging. The development of plastic seeds has reduced thesemore » artifacts. This paper presents a feasibility study of the advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for future clinical applications, and on the effect of the gold marker on the dosimetric characteristics of such seeds. Experimental palladium seeds, OptiSeed{sup exp}, were manufactured by International Brachytherapy (IBt), Seneffe, Belgium, from a biocompatible polymer, including the marker. Apart from the absence of a gold marker, the studied seed has an identical design to the OptiSeed{sup 103}[Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the quantity of radioactive material needed for a given dose rate and to reduce the anisotropy of the radiation field around the seed. In addition, this design is intended to decrease the interseed effects that can occur as a result of the marker and the encapsulation. Dosimetric measurements were performed using LiF thermoluminescent dosimeters (1 mm{sup 3}) in solid water phantoms (WT1). Measured data were compared to Monte Carlo simulated data in solid water using the MCNP code, version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As the measured and calculated data were in agreement, Monte Carlo calculations were then performed in liquid water to obtain relevant dosimetric data as required by TG-43U1 recommendations. Comparison of the results with previous studies of OptiSeed{sup 103}[Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)], and of InterSource{sup 103}[Appl. Radiat. Isot. 57, 805-811 (2002)] showed very good agreement for the dose rate constant and for the radial dose function. With respect to the anisotropy function, the relative dose (anisotropy value relative to 90 degree sign ) from the polymer seed at a distance of 3 cm was close to unity (105%) at 0 degree sign , whereas the relative values for the OptiSeed{sup 103} with a gold marker and the titanium-encapsulated InterSource{sup 103} seed decreased to 70% and 40%, respectively. The interseed effect from one seed was negligible and in the order of calculation uncertainty, making calculation of the dose rate distribution of the studied seeds, according to TG43U1 recommendations, more accurate and closer to reality. This feasibility study shows that due to the low energy of palladium-103, the negligible interseed effect and the reduced artifacts in postimplant medical imaging, this experimental plastic seed would be a good source for breast brachytherapy. This feasibility study was carried out in collaboration with IBt and will be continued with a study of its visibility in different tissues.« less

Vitamin D and Sunlight Exposure in Newly-Diagnosed Parkinson's Disease.

PubMed

Wang, Juan; Yang, Deyu; Yu, Yu; Shao, Gaohai; Wang, Qunbo

2016-03-04

Circulating vitamin D has previously been found to be lower in patients with Parkinson's disease (PD), while the effects of sunlight exposure have not yet been fully investigated. Therefore, we evaluated the associations between serum vitamin D, vitamin D intake, sunlight exposure, and newly-diagnosed PD patients in a Chinese population. This case-control study measured serum 25-hydroxyvitamin D (25(OH)D) levels and sunlight exposure in 201 patients with newly-diagnosed PD and 199 controls without neurodegenerative diseases. Data on vitamin D intake and sunlight exposure were obtained using a self-report questionnaire. Multivariable logistic regressions were employed to evaluate the associations between serum 25(OH)D levels, sunlight exposure, and PD. Adjustments were made for sex, age, smoking, alcohol use, education, BMI, and vitamin D intake. There were significantly lower levels of serum 25(OH)D (20.6 ± 6.5 ng/mL), daily vitamin D intake (8.3 ± 3.7 g/day), and sunlight exposure (9.7 ± 4.1 h/week) in patients with PD compared to healthy controls (p < 0.05). Crude odds ratios (ORs) for PD in the quartiles of serum 25(OH)D were 1 (reference), 0.710 (0.401, 1.257), 0.631 (0.348, 1.209), and 0.483 (0.267, 0.874), respectively. Crude ORs for PD in quartiles of sunlight exposure were 1 (reference), 0.809 (0.454, 1.443), 0.623 (0.345, 1.124) and 0.533 (0.294, 0.966), respectively. A significant positive correlation between serum 25(OH)D and sunlight exposure was found, but serum 25(OH)D was not correlated with daily vitamin D intake. This study indicates that lower levels of serum 25(OH)D and sunlight exposure are significantly associated with an increased risk for PD.

Panic disorder as a risk factor for post-partum depression: Results from the Perinatal Depression-Research & Screening Unit (PND-ReScU) study.

PubMed

Rambelli, C; Montagnani, M S; Oppo, A; Banti, S; Borri, C; Cortopassi, C; Ramacciotti, D; Camilleri, V; Mula, M; Cassano, G B; Mauri, M

2010-04-01

Although the role of anxiety disorders on the development of Post-partum Depression (PPD) have already been studied in literature, that of individual anxiety disorders has not received specific attention. The aim of this study is to investigate the role of Panic Disorder (PD) and family history for PD as risk factors for PPD. Six hundred women were recruited in a prospective, observational study at the 3rd month of pregnancy and followed up until the 6th month after delivery. At baseline, risk factors for PPD, Axis-I disorders and family history for psychiatric disorders were assessed. We investigated minor and major depression (mMD) occurred at 1st, 3rd and 6th months post-partum. Logistic regression models were used to estimate the association between PD, family history for PD and PPD. Forty women had mMD in the post-partum. PD during pregnancy (RR=4.25; 95%CI:1.48-12.19), a history of PD (RR 2.47; 95%CI:1.11-5.49) and family history for PD (RR=2.1; 95%CI:1.06-4.4) predicted PPD after adjusting for lifetime depression and risk factors for PPD. The response rate is moderately low, but it is similar to other studies. The drop out rate is slightly high, however the 600 women who completed the 6th month follow-up did not differ from the presence of PD at baseline. PD is an independent risk factor for PPD, underscoring need to assess PD symptoms during pregnancy. Furthermore, PD represents an important risk factor for the development of PPD and should be routinely screened in order to develop specific preventive interventions. Copyright 2009 Elsevier B.V. All rights reserved.

5 CFR 894.103 - How do I enroll?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false How do I enroll? 894.103 Section 894.103 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.103 How do I...

5 CFR 894.103 - How do I enroll?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false How do I enroll? 894.103 Section 894.103 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.103 How do I...

5 CFR 894.103 - How do I enroll?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false How do I enroll? 894.103 Section 894.103 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.103 How do I...

Pd nanoparticle-modified electrodes for nonenzymatic hydrogen peroxide detection

NASA Astrophysics Data System (ADS)

Wang, Jue; Chen, Xue-jiao; Liao, Kai-ming; Wang, Guang-hou; Han, Min

2015-08-01

A hydrogen peroxide (H2O2) sensor based on Pd nanoparticles (NPs) and glassy carbon electrodes (GCEs) is fabricated. Pd NPs are deposited on GCEs by using a gas phase cluster beam deposition technique. The NP-deposited electrodes show enhanced electrocatalytic activity in reduction of H2O2. The electrode with an optimized NP coverage of 85 % has a high selective and stable nonenzymatic sensing ability of H2O2 with a low detection limit (3.4 × 10-7 M), high sensitivity (50.9 μA mM-1), and a wide linear range (from 1.0 × 10-6 to 6.0 × 10-3 M). The reduction peak potential of the electrode is close to -0.12 V, which enables high selective amperometric detection of H2O2 at a low applied potential.

Advances in OLED-based oxygen sensors with structurally integrated OLED, sensor film, and thin-film Si photodetector

NASA Astrophysics Data System (ADS)

Ghosh, Debju; Shinar, Ruth; Cai, Yuankun; Zhou, Zhaoqun; Dalal, Vikram L.; Shinar, Joseph

2007-09-01

Steps towards the improvement of a compact photoluminescence (PL)-based sensor array that is fully structurally integrated are described. The approach is demonstrated for oxygen sensing, which can be monitored via its effect on the PL intensity I or decay time τ of oxygen-sensitive dyes such as Pt octaethylporphryn (PtOEP) and its Pd analog (PdOEP). The integrated components include (1) an organic light emitting device (OLED) excitation source, which is an array of coumarin-doped tris(quinolinolate) Al (Alq 3) pixels, (2) the sensor film, i.e., PdOEP embedded in polystyrene, and (3) the photodetector (PD), which is a plasma-enhanced CVD-grown p-i-n or n-i-p structure, based on amorphous or nanocrystalline (Si,Ge):H. These components are fabricated on common or separate substrates that are attached back-to-back, resulting in sensors with a thickness largely determined by that of the substrates. The fully integrated oxygen sensor is demonstrated first by fabricating each of the three components on a separate substrate. The PD was placed in front of a flow cell containing the sensor film, while the OLED array was "behind" the sensor film. This design showed the expected trend in monitoring different concentration of O II via their effect on I, with improved detection sensitivity achieved by shielding the electromagnetic noise synchronous with the pulsed OLED. The detection sensitivity using the I monitoring mode is expected to further increase by reducing the OLED tail emission. The issue of the OLED background can be eliminated by monitoring the oxygen concentration via its effect on τ, where the OLED is pulsed and τ is measured while the OLED is off. Steps therefore focused also on shortening the response time of the PDs, and understanding the factors affecting their speed. Development of a sensor array, where the PD pixels are fabricated between the OLED pixels on the same side of a common substrate, is also discussed.

Towards Solving the Conundrum of Fast-Spread Ocean Crust Formation: Insights from Textural Analysis of Gabbroic Rocks from Pito Deep and Hess Deep, East Pacific Rise

NASA Astrophysics Data System (ADS)

Brown, T. C.; Cheadle, M. J.; John, B. E.; Coogan, L. A.; Gee, J. S.; Karson, J. A.; Meyer, R.; Ceuleneer, G.; Swapp, S.

2014-12-01

Few examples of in situ fast-spread lower ocean crust exist for sampling. Here we present detailed textural analyses of two sample sets that formed at the East Pacific Rise, collected from tectonic windows at Pito (PD) and Hess (HD) deeps. PD samples (collected by ROV) span the upper ~900 m of lower crust. HD samples (collected by seafloor drilling during IODP Exp. 345) come from >1500 m below the sheeted dike gabbro transition (mbsd). PD gabbroic rock textures are consistent with a gabbro glacier flow model generating the uppermost plutonic crust. Shallow samples (41-72 mbsd) likely formed at the distal edge of the magma lens, analogous to similar rocks from Oman. These gabbros are relatively evolved (cpx Mg#75-77, An53-61 and 1-4% Fe-Ti oxides), and have elongate plagioclase grains (aspect ratios up to 1:2:10) exhibiting a strong shape preferred orientation (SPO) with <40% of grains showing dislocation creep textures. Deeper samples (177-876 mbsd) likely began crystallizing in the magma lens then subsided and 'flowed' through the underlying mush zone. These gabbros are more primitive below 386 mbsd (Fo83-88, cpx Mg# 85-89 and An70-82), and plagioclase grains have more equilibrated morphologies (aspect ratios < 1:2:6) that define ~vertical SPOs which increase in strength with depth. Plagioclase exhibits magmatic crystal-lattice preferred orientations (CPOs) which are also vertical. Significantly, the proportion of grains showing dislocation creep textures increases with depth, and plagioclase grain size distributions show a smaller range of sizes at depth; observations that perhaps reflect the effect of increasing strain with depth. IODP Hole U1415I at HD recovered gabbros and troctolitic gabbros from the mid lower crust that show distinctive cm-dm scale modal layering. Strong plagioclase SPOs parallel layering and magmatic CPOs vary dramatically in strength over just 4.5 m of core. Plagioclase grains are relatively equant (aspect ratios < 1:2:4), wrap around large cpx oikocrysts, and exhibit fewer dislocation creep textures than the PD gabbros. These observations perhaps suggest primary crystal accumulation rather than bulk strain/flow. The similar mineralogy and textures of these samples to those from the Rum layered intrusion suggest HD U1415I gabbros may have formed by mid-crust sill injection.

Prevalence of posttraumatic growth hormone deficiency is highly dependent on the diagnostic set-up: results from The Danish National Study on Posttraumatic Hypopituitarism.

PubMed

Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jourgita; Lehman Christensen, Louise; Frystyk, Jan; Andersen, Marianne; Laurberg, Peter; Christiansen, Jens Sandahl; Feldt-Rasmussen, Ulla

2014-01-01

Recent international guidelines suggest pituitary screening in patients with moderate and severe traumatic brain injury (TBI). Predominantly isolated GH deficiency (GHD) was reported in the literature, raising the question of potential methodological bias. Our objective was to assess the prevalence of GHD in patients admitted in 2008 with TBI, with concurrent assessment of methodological bias. We conducted a nationwide population-based cohort study at tertiary referral university hospitals. Participants were Danish patients with a head trauma diagnosis from the Danish Board of Health diagnostic code registry; 439 patients and 124 healthy controls underwent dynamic assessment of GH secretion 2.5 years (median) after TBI. We evaluated the prevalence of GHD given use of 1) local versus guideline cutoffs, 2) insulin tolerance test (ITT), pyridostigmine (PD)-GHRH or GHRH-arginine (arg) test, 3) single versus repeated testing, and 4) GH assessment by assays with different isoform specificities. The prevalence of GHD was lower by local than by guideline cutoffs (12% vs 19% [PD-GHRH/GHRH-arg, P<.001]; 4.5% vs 5% [ITT, P=.9]), and by ITT than by PD-GHRH/GHRH-arg (P=.006 [local cutoffs]; P<.001 [guideline cutoffs]). Only 1% of patients had GHD according to 2 tests. GH assessment by the Immulite or iSYS assay caused no significant diagnostic differences. The study confirmed a high risk of bias in the management of pituitary testing of patients with TBI and stresses the importance of a proper control group and stringent GH testing including confirmatory testing in cohorts with low a priori likelihood of GHD such as in TBI. Our results question the evidence for newly introduced recommendations for routine pituitary assessment in TBI.

Personality disorders in early adolescence and the development of later substance use disorders in the general population

PubMed Central

Cohen, Patricia; Chen, Henian; Crawford, Thomas N.; Brook, Judith S.; Gordon, Kathy

2007-01-01

Assessments of personality disorder (PD) and conduct disorder (CD) in a random community sample at mean age 13 were employed to predict subsequent substance abuse disorder (SUD), trajectories of symptoms of abuse or dependence on alcohol, marijuana, or other illicit substances, and hazard of initiating marijuana use over the subsequent decade. Personality disorders and conduct disorder were associated with diagnoses and symptoms of SUDs in every model and their effects were independent of correlated family risks, participant sex, and other Axis I disorders. Specific elevated PD symptoms in early adolescence were also associated with differential trajectories of already initiated SUD symptoms as well as elevated risk for future onset of SUD symptoms. For several models the greatest of these effects were shown for borderline PD and for conduct disorder, the predecessor of adult antisocial PD. Passive-aggressive PD also showed independent elevation effects on substance use symptoms for alcohol and marijuana. Analyses over 30 years suggest that Cluster B PD (borderline, histrionic, narcissistic) are independent risks for development of SUD and warrant clinical attention. PMID:17227697

Personality disorders in early adolescence and the development of later substance use disorders in the general population.

PubMed

Cohen, Patricia; Chen, Henian; Crawford, Thomas N; Brook, Judith S; Gordon, Kathy

2007-04-01

Assessments of personality disorder (PD) and conduct disorder (CD) in a random community sample at mean age 13 were employed to predict subsequent substance abuse disorder (SUD), trajectories of symptoms of abuse or dependence on alcohol, marijuana, or other illicit substances, and hazard of initiating marijuana use over the subsequent decade. Personality disorders and conduct disorder were associated with diagnoses and symptoms of SUDs in every model and their effects were independent of correlated family risks, participant sex, and other Axis I disorders. Specific elevated PD symptoms in early adolescence were also associated with differential trajectories of already initiated SUD symptoms as well as elevated risk for future onset of SUD symptoms. For several models the greatest of these effects were shown for borderline PD and for conduct disorder, the predecessor of adult antisocial PD. Passive-aggressive PD also showed independent elevation effects on substance use symptoms for alcohol and marijuana. Analyses over 30 years suggest that Cluster B PD (borderline, histrionic, narcissistic) are independent risks for development of SUD and warrant clinical attention.

Development and validation of a yoga module for Parkinson disease.

PubMed

Kakde, Noopur; Metri, Kashinath G; Varambally, Shivarama; Nagaratna, Raghuram; Nagendra, H R

2017-03-25

Background Parkinson's disease (PD), a progressive neurodegenerative disease, affects motor and nonmotor functions, leading to severe debility and poor quality of life. Studies have reported the beneficial role of yoga in alleviating the symptoms of PD; however, a validated yoga module for PD is unavailable. This study developed and validated an integrated yoga module(IYM) for PD. Methods The IYM was prepared after a thorough review of classical yoga texts and previous findings. Twenty experienced yoga experts, who fulfilled the inclusion criteria, were selected validating the content of the IYM. A total of 28 practices were included in the IYM, and each practice was discussed and rated as (i) not essential, (ii) useful but not essential, and (iii) essential; the content validity ratio (CVR) was calculated using Lawshe's formula. Results Data analysis revealed that of the 28 IYM practices, 21 exhibited significant content validity (cut-off value: 0.42, as calculated by applying Lawshe's formula for the CVR). Conclusions The IYM is valid for PD, with good content validity. However, future studies must determine the feasibility and efficacy of the developed module.

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

PubMed

Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

2017-04-06

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59-1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40-0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96-1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57-0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46-1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61-1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

Geochemical behaviour of palladium in soils and Pd/PdO model substances in the presence of the organic complexing agents L-methionine and citric acid.

PubMed

Zereini, Fathi; Wiseman, Clare L S; Vang, My; Albers, Peter; Schneider, Wolfgang; Schindl, Roland; Leopold, Kerstin

2016-01-01

Risk assessments of platinum group metal (PGE) emissions, notably those of platinum (Pt), palladium (Pd) and rhodium (Rh), have been mostly based on data regarding the metallic forms used in vehicular exhaust converters, known to be virtually biologically inert and immobile. To adequately assess the potential impacts of PGE, however, data on the chemical behaviour of these metals under ambient conditions post-emission is needed. Complexing agents with a high affinity for metals in the environment are hypothesized to contribute to an increased bioaccessibility of PGE. The purpose of this study is to examine the modulating effects of the organic complexing agents, L-methionine and citric acid, on the geochemical behavior of Pd in soils and model substances (Pd black and PdO). Batch experimental tests were conducted with soils and model substances to examine the impacts of the concentration of complexing agents, pH and length of extraction period on Pd solubility and its chemical transformation. Particle surface chemistry was examined using X-ray photoelectron spectroscopy (XPS) on samples treated with solutions under various conditions, including low and high O2 levels. Pd was observed to be more soluble in the presence of organic complexing agents, compared to Pt and Rh. Pd in soils was more readily solubilized with organic complexing agents compared to the model substances. After 7 days of extraction, L-methionine (0.1 M) treated soil and Pd black samples, for instance, had mean soluble Pd fractions of 12.4 ± 5.9% and 0.554 ± 0.024%, respectively. Surface chemistry analyses (XPS) confirmed the oxidation of metallic Pd surfaces when treated with organic complexing agents. The type of organic complexing agent used for experimental purposes was observed to be the most important factor influencing solubility, followed by solution pH and time of extraction. The results demonstrate that metallic Pd can be transformed into more bioaccessible species in the presence of organic complexing agents which are ubiquitous in the environment.

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

PubMed Central

Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43–2.17, P<0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25–1.98, P=0.0001) and neural invasion (RR =1.30, 95% CI: 1.03–1.64, P=0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics. PMID:29081663

KSC-08pd1144

NASA Image and Video Library

2008-05-05

CAPE CANAVERAL, Fla. -- Inside space shuttle Discovery's payload bay can be seen the red rain gutters, which prevent leaks into the bay from rain while the shuttle is on the pad. The STS-124 mission payload, the Japanese Experiment Module - Pressurized Module and the Japanese Remote Manipulator System (below the gutters), is being transferred from the Payload Changeout Room into the payload bay. Launch of Discovery is targeted for May 31. Photo credit: NASA/Jim Grossmann

Safinamide (Newron Pharmaceuticals).

PubMed

Chazot, P L

2001-06-01

Safinamide (formerly PNU-151774E), a sodium and calcium channel modulator that also inhibits monoamine oxidase B (MAOB), is under development by Newron Pharmaceuticals for the potential treatment of epilepsy, Parkinson's disease (PD), pain and stroke [345222], [348351]. Phase I trials for epilepsy and PD have been completed, and dose-finding studies for both indications had commenced in March 2001 [401685]. The compound was previously developed by Pharmacia & Upjohn (P&U) for the potential treatment of epilepsy, an indication for which it initially reached phase I trials [294891], [345007]. Newron acquired the rights to safinamide from P&U at the end of 1998. Results from two phase I trials of the compound (single ascending dose and steady state at three doses), completed in March 2000, demonstrated that the drug is well tolerated with good bioavailability and linear pharmacokinetics [359652].

MAO-inhibitors in Parkinson's Disease

PubMed Central

Laux, Gerd

2011-01-01

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD. PMID:22110357

Peripheral dose measurements with diode and thermoluminescence dosimeters for intensity modulated radiotherapy delivered with conventional and un-conventional linear accelerator

PubMed Central

Kinhikar, Rajesh; Gamre, Poonam; Tambe, Chandrashekhar; Kadam, Sudarshan; Biju, George; Suryaprakash; Magai, C. S.; Dhote, Dipak; Shrivastava, Shyam; Deshpande, Deepak

2013-01-01

The objective of this paper was to measure the peripheral dose (PD) with diode and thermoluminescence dosimeter (TLD) for intensity modulated radiotherapy (IMRT) with linear accelerator (conventional LINAC), and tomotherapy (novel LINAC). Ten patients each were selected from Trilogy dual-energy and from Hi-Art II tomotherapy. Two diodes were kept at 20 and 25 cm from treatment field edge. TLDs (LiF:MgTi) were also kept at same distance. TLDs were also kept at 5, 10, and 15 cm from field edge. The TLDs were read with REXON reader. The readings at the respective distance were recorded for both diode and TLD. The PD was estimated by taking the ratio of measured dose at the particular distance to the prescription dose. PD was then compared with diode and TLD for LINAC and tomotherapy. Mean PD for LINAC with TLD and diode was 2.52 cGy (SD 0.69), 2.07 cGy (SD 0.88) at 20 cm, respectively, while at 25 cm, it was 1.94 cGy (SD 0.58) and 1.5 cGy (SD 0.75), respectively. Mean PD for tomotherapy with TLD and diode was 1.681 cGy SD 0.53) and 1.58 (SD 0.44) at 20 cm, respectively. The PD was 1.24 cGy (SD 0.42) and 1.088 cGy (SD 0.35) at 25 cm, respectively, for tomotherapy. Overall, PD from tomotherapy was found lower than LINAC by the factor of 1.2-1.5. PD measurement is essential to find out the potential of secondary cancer. PD for both (conventional LINAC) and novel LINACs (tomotherapy) were measured and compared with each other. The comparison of the values for PD presented in this work and those published in the literature is difficult because of the different experimental conditions. The diode and TLD readings were reproducible and both the detector readings were comparable. PMID:23531765

Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

PubMed

Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

2012-03-31

The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

PubMed

Dewey, D Campbell; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B

2014-10-15

To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. Copyright © 2014 Elsevier B.V. All rights reserved.

Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

PubMed Central

Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

2014-01-01

Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

An Automated Measurement of Ciliary Beating Frequency using a Combined Optical Flow and Peak Detection.

PubMed

Kim, Woojae; Han, Tae Hwa; Kim, Hyun Jun; Park, Man Young; Kim, Ku Sang; Park, Rae Woong

2011-06-01

The mucociliary transport system is a major defense mechanism of the respiratory tract. The performance of mucous transportation in the nasal cavity can be represented by a ciliary beating frequency (CBF). This study proposes a novel method to measure CBF by using optical flow. To obtain objective estimates of CBF from video images, an automated computer-based image processing technique is developed. This study proposes a new method based on optical flow for image processing and peak detection for signal processing. We compare the measuring accuracy of the method in various combinations of image processing (optical flow versus difference image) and signal processing (fast Fourier transform [FFT] vs. peak detection [PD]). The digital high-speed video method with a manual count of CBF in slow motion video play, is the gold-standard in CBF measurement. We obtained a total of fifty recorded ciliated sinonasal epithelium images to measure CBF from the Department of Otolaryngology. The ciliated sinonasal epithelium images were recorded at 50-100 frames per second using a charge coupled device camera with an inverted microscope at a magnification of ×1,000. The mean square errors and variance for each method were 1.24, 0.84 Hz; 11.8, 2.63 Hz; 3.22, 1.46 Hz; and 3.82, 1.53 Hz for optical flow (OF) + PD, OF + FFT, difference image [DI] + PD, and DI + FFT, respectively. Of the four methods, PD using optical flow showed the best performance for measuring the CBF of nasal mucosa. The proposed method was able to measure CBF more objectively and efficiently than what is currently possible.

A novel membrane-less direct alcohol fuel cell

NASA Astrophysics Data System (ADS)

Yi, Qingfeng; Chen, Qinghua; Yang, Zheng

2015-12-01

Membrane-less fuel cell possesses such advantages as simplified design and lower cost. In this paper, a membrane-less direct alcohol fuel cell is constructed by using multi-walled carbon nanotubes (MWCNT) supported Pd and ternary PdSnNi composites as the anode catalysts and Fe/C-PANI composite, produced by direct pyrolysis of Fe-doped polyaniline precursor, as the oxygen reduction reaction (ORR) catalyst. The alcohols investigated in the present study are methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol and sec-butanol. The cathode catalyst Fe/C-PANI is electrochemically inactive to oxidation of the alcohols. The performance of the cell with various alcohols in 1 mol L-1 NaOH solution on either Pd/MWCNT or PdSnNi/MWCNT catalyst has been evaluated. In any case, the performance of the cell using the anode catalyst PdSnNi/MWCNT is considerably better than Pd/MWCNT. For the PdSnNi/MWCNT, the maximum power densities of the cell using methanol (0.5 mol L-1), ethanol (0.5 mol L-1), n-propanol (0.5 mol L-1), iso-propanol (0.5 mol L-1), n-butanol (0.2 mol L-1), iso-butanol (0.2 mol L-1) and sec-butanol (0.2 mol L-1) are 0.34, 1.03, 1.07, 0.44, 0.50, 0.31 and 0.15 mW cm-2, respectively.

The MicroRNA miR-124 Promotes Neuronal Differentiation by Triggering Brain-Specific Alternative Pre-mRNA Splicing

PubMed Central

Makeyev, Eugene V.; Zhang, Jiangwen; Carrasco, Monica A.; Maniatis, Tom

2011-01-01

SUMMARY Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in nonneuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2 (nPTB/brPTB/PTBLP), an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay (NMD). During neuronal differentiation, miR-124 reduces PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124 plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing. PMID:17679093

Palladium-doped-ZrO2-multiwalled carbon nanotubes nanocomposite: an advanced photocatalyst for water treatment

NASA Astrophysics Data System (ADS)

Anku, William Wilson; Oppong, Samuel Osei-Bonsu; Shukla, Sudheesh Kumar; Agorku, Eric Selorm; Govender, Poomani Penny

2016-06-01

The photocatalytic degradation of organic pollutants from water using palladium-doped-zirconium oxide-multiwalled carbon nanotubes (Pd-ZrO2-MWCNTs) nanocomposites is presented. A series of Pd doped-ZrO2-MWCNTs nanocomposites with varying percentage compositions of Pd were prepared by the homogenous co-precipitation method. The photocatalytic applicability of the materials was investigated by the degradation of acid blue 40 dye in water under simulated solar light. The optical, morphological and structural properties of the nanocomposites were evaluated using X-ray powder diffraction, Fourier transformer infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, BET surface area analysis and (UV-Vis) spectroscopy. The Pd-ZrO2-MWCNTs nanocomposites showed enhanced photocatalytic activity toward the degradation of the acid blue 40 dye under visible light compared with bare ZrO2 and ZrO2-MWCNTs alone. The remarkable photocatalytic activity of Pd-ZrO2-MWCNTs nanocomposites in the visible light makes it an ideal photocatalyst for the removal of organic pollutants in water. The 0.5 % Pd-ZrO2-MWCNT was the most efficient photocatalyst with 98 % degradation after 3 h with corresponding K a and band gap values of 16.8 × 10-3 m-1 and 2.79 eV, respectively.

PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis.

PubMed

Hecht, Markus; Büttner-Herold, Maike; Erlenbach-Wünsch, Katharina; Haderlein, Marlen; Croner, Roland; Grützmann, Robert; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold V

2016-09-01

The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value. PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated. RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030). Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extended professional development for systemic curriculum reform

NASA Astrophysics Data System (ADS)

Kubitskey, Mary Elizabeth

Education standards call for adopting inquiry science instruction. Successful adoption requires professional development (PD) to support teachers, increasing the need for research on PD. This dissertation examines the question: What is the influence of high quality, curriculum aligned, long-term group workshops and related practice on teacher learning? I focus on the following subquestions: (1) What is the influence of high quality, curriculum aligned, long-term, group workshops on teacher knowledge and beliefs? (2) What is the impact of the workshops on teacher practice? (3) What is the influence of practice on student response? (4) What is the impact of practice and student response on teacher knowledge and beliefs? I focus on an instance of PD nested within a long-term systemic change initiative, tracing eleven science teachers' learning from workshops and associated enactments. The data included pre and post-unit interviews (n=22), two post-workshop interviews (n=17), workshop observations (n=2), classroom observations (n=24) and student work (n=351). I used mixed-methods analysis. Quantitative analysis measured teacher learning by comparing pre and post-unit interview ratings. Qualitative components included two case study approaches: logic model technique and cross-case synthesis, examining teacher learning within and across teachers. The findings suggested a teacher-learning model incorporating PD, teacher knowledge, beliefs, practice and student response. PD impacts teachers' knowledge by providing teachers with new knowledge, adapting previous knowledge, or convincing them to value existing knowledge they chose not to use. The workshops can influence beliefs, providing teachers with confidence and motivation to adopt the practice. Beliefs can mediate how knowledge manifested itself in practice that, in turn, impacts students' response. Student response influences the teachers' beliefs, either reinforcing or motivating change. This teacher-learning model suggests a PD design model for long-term systemic change, incorporating teacher practice and student response, providing guidance for teachers making adaptations that maintain reform. This dissertation responds to the call for empirical research linking PD to learning outcomes. These models are unique because practice becomes a continuum of PD, rather than outcome and stresses the importance of addressing teachers' beliefs. This PD design provides mechanisms for maintaining equivalence between the written and enacted curriculum, sustaining the integrity of the reform.

To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease.

PubMed

Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2015-04-01

Cognitive decline is a burdensome extra-motor symptom associated with Parkinson's disease (PD). This study aimed at investigating intrinsic functional connectivity (iFC) of the brain in cognitively unimpaired (PD-CU) and impaired PD patients (PD-CI) compared with age-matched healthy controls. "Resting-state" functional magnetic resonance imaging was acquired in 53 subjects, that is, 14 PD-CU patients, 17 PD-CI patients, and 22 control subjects. Cognition and cognitive status for patient classification were assessed using detailed neuropsychological testing. In PD-CU patients versus controls, we demonstrated significantly increased iFC (hyperconnectivity) presenting as network expansions in cortical, limbic, and basal ganglia-thalamic areas. Significantly, decreased iFC in PD-CI patients compared with control subjects was observed, predominantly between major nodes of the default mode network. In conclusion, the increased iFC might be the initial manifestation of altered brain function preceding cognitive deficits. Hyperconnectivity could be an adaptive (compensatory) mechanism by recruiting additional resources to maintain normal cognitive performance. As PD-related pathology progresses, functional disruptions within the default mode networks seem to be considerably associated with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

Sliding and Debonding Inclusions

DTIC Science & Technology

1988-08-15

19 124 List of Publications Published under ARO StonsorshiD during this period 1. R.R. Castles and T. Mura, The analysis of eigenstrains outside of an...slippding interface, J. Aonl. Mech., 53 (1986) 103- 107. 12. N. Kinoshita and T. Mura, An ellipsoidal inclusion with polynomial eigenstrains , Quart...Theory and application of harmonic eigenstrains , O.J.Mech. ADDl Math., 40 (1987) 169-188. 20. T. Mura, The eigenstrains method applied to fracture

President Truman and (the Challenge of) the Potsdam Conference 1945

DTIC Science & Technology

2013-05-23

elsewhere. In Poland a pro -Soviet government was established in which, the exiled Polish government in 6Truman, Memoirs:Year of Decisions, 81-82. 10...import of coal mining equipment and farm machinery.103 Finally, linked with the military sub-line of effort, programs of industrial disarmament and...other satellite states Romania, Bulgaria and Finland . 127 124Joint Chiefs of Staff, “The Berlin conference, comments and recommendations, memorandum

Defense Authorization and Appropriations Bills: FY1970-FY2016

DTIC Science & Technology

2016-04-20

103-335 9/30/94 1996 H.R. 2126 104-208 7/27/95 9/7/95 # 646 (y294-n125) 104-261 9/29/95 # 700 (y151-n267) S. 1087 104-124 7/28/95 Hh...1990, and passed H.R. 5803 in lieu. h. Senate passed S. 1087 , amended by recorded vote # 397 on September 5, 1995, then passed H.R. 2126 in lieu on

Study of activation cross-sections of deuteron induced reactions on rhodium up to 40 MeV

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Takács, S.; Hermanne, A.; Yamazaki, H.; Baba, M.; Mohammadi, A.; Ignatyuk, A. V.

2011-09-01

In the frame of a systematic study of the activation cross-sections of deuteron induced nuclear reactions, excitation functions of the 103Rh(d,x) 100,101,103Pd, 100g,101m,101g,102m,102gRh and 103gRu reactions were determined up to 40 MeV. Cross-sections were measured with the activation method using a stacked foil irradiation technique. Excitation functions of the contributing reactions were calculated using the ALICE-IPPE, EMPIRE-II and TALYS codes. From the measured cross-section data integral production yields were calculated and compared with experimental integral yield data reported in the literature. From the measured cross-sections and previous data, activation curves were deduced to support thin layer activation (TLA) on rhodium and Rh containing alloys.

Large rotating field entropy change in ErFeO3 single crystal with angular distribution contribution

NASA Astrophysics Data System (ADS)

Huang, Ruoxiang; Cao, Shixun; Ren, Wei; Zhan, Sheng; Kang, Baojuan; Zhang, Jincang

2013-10-01

We report the rotating field entropy of ErFeO3 single-crystal in a temperature range of 3-40 K. The giant magnetic entropy change, ΔSM = -20.7 J/(kg K), and the refrigerant capacity, RC = 273.5 J/kg, are observed near T =6 K. The anisotropic constants at 6 K, K1 = 1.24× 103 J/kg, K2 = 0.74 × 103 J/kg, in the bc plane are obtained. By considering the magnetocrystalline anisotropy and Fermi-Dirac angular distribution along the orientation of spontaneous magnetization, the experimental results can be well simulated. Our present work demonstrates that ErFeO3 crystal may find practical use for low temperature anisotropic magnetic refrigeration.

PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma.

PubMed

Melaiu, Ombretta; Mina, Marco; Chierici, Marco; Boldrini, Renata; Jurman, Giuseppe; Romania, Paolo; D'Alicandro, Valerio; Benedetti, Maria C; Castellano, Aurora; Liu, Tao; Furlanello, Cesare; Locatelli, Franco; Fruci, Doriana

2017-08-01

Purpose: This study sought to evaluate the expression of programmed cell death-ligand-1 (PD-L1) and HLA class I on neuroblastoma cells and programmed cell death-1 (PD-1) and lymphocyte activation gene 3 (LAG3) on tumor-infiltrating lymphocytes to better define patient risk stratification and understand whether this tumor may benefit from therapies targeting immune checkpoint molecules. Experimental Design: In situ IHC staining for PD-L1, HLA class I, PD-1, and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T-cell density and correlated with clinical outcome. Surface expression of PD-L1 was evaluated by flow cytometry and IHC in neuroblastoma cell lines and tumors genetically and/or pharmacologically inhibited for MYC and MYCN. A dataset of 477 human primary neuroblastomas from GEO and ArrayExpress databases was explored for PD-L1, MYC, and MYCN correlation. Results: Multivariate Cox regression analysis demonstrated that the combination of PD-L1 and HLA class I tumor cell density is a prognostic biomarker for predicting overall survival in neuroblastoma patients ( P = 0.0448). MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both in vitro and in vivo Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma. Conclusions: The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma. Pharmacologic inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient antitumor immunity in high-risk neuroblastoma. Clin Cancer Res; 23(15); 4462-72. ©2017 AACR . ©2017 American Association for Cancer Research.

Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.

PubMed

Campolo, Jonica; De Maria, Renata; Cozzi, Lorena; Parolini, Marina; Bernardi, Stefano; Proserpio, Paola; Nobili, Lino; Gelosa, Giorgio; Piccolo, Immacolata; Agostoni, Elio C; Trivella, Maria G; Marraccini, Paolo

2016-11-15

We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD. We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin). Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016). Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Dibromochloromethane

Integrated Risk Information System (IRIS)

Dibromochloromethane ; CASRN 124 - 48 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

Impairment of work productivity in panic disorder patients.

PubMed

Lee Park, Yu; Kim, Won; Chae, Jeong-Ho; Seo Oh, Kang; Frick, Kevin D; Woo, Jong-Min

2014-03-01

Panic disorder (PD) has a critical impact on productivity at the workplace. This study aimed to identify the lost productivity time (LPT) for patients with PD. It also assessed change in LPT for patients with PD after 12 weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared with healthy controls. Working patients diagnosed with PD without other major medical or psychiatric illness were enrolled at outpatient psychiatric clinics (N=108). Age and sex-matched healthy controls were recruited through advertisement (N=108). Health and productivity, PD symptoms, and depressive symptoms were assessed using the Korean version of the World Health Organization's Health and Work Performance Questionnaire (HPQ), the Panic Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression (HAM-D), respectively at baseline, week 4, and week 12. At baseline, the PD group showed significantly higher LPT compared to the control group (103.02 vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group displayed significant clinical improvement as well as improved productivity with a marked reduction in LPT. Among the patients who completed the treatment, LPT due to PD was reduced from 104.38 to 55.15h in the past 4 weeks. There may be selection bias due to case-control study design. These data suggest that, after the treatment, there was significant improvement in clinical symptoms, and that productivity loss due to PD was almost entirely recovered to the level of healthy controls after 12 weeks of psychiatric outpatient treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Intranasal gene delivery for treating Parkinson's disease: overcoming the blood-brain barrier.

PubMed

Aly, Amirah E-E; Waszczak, Barbara L

2015-01-01

Developing a disease-modifying gene therapy for Parkinson's disease (PD) has been a high priority for over a decade. However, due to the inability of large biomolecules to cross the blood-brain barrier (BBB), the only means of delivery to the brain has been intracerebral infusion. Intranasal administration offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors, and the genes encoding them, directly to the brain. This review summarizes: i) evidence demonstrating intranasal delivery to the brain of a number of biomolecules having therapeutic potential for various CNS disorders; and ii) evidence demonstrating neuroprotective efficacy of a subset of biomolecules specifically for PD. The intersection of these two spheres represents the area of opportunity for development of new intranasal gene therapies for PD. To that end, our laboratory showed that intranasal administration of glial cell line-derived neurotrophic factor (GDNF), or plasmid DNA nanoparticles encoding GDNF, provides neuroprotection in a rat model of PD, and that the cells transfected by the nanoparticle vector are likely to be pericytes. A number of genes encoding neurotrophic factors have therapeutic potential for PD, but few have been tested by the intranasal route and shown to be neuroprotective in a model of PD. Intranasal delivery provides a largely unexplored, promising approach for development of a non-invasive gene therapy for PD.

13 CFR 124.1013 - How does SBA make disadvantaged status determinations in considering an SDB protest?

Code of Federal Regulations, 2011 CFR

2011-01-01

... status determinations in considering an SDB protest? 124.1013 Section 124.1013 Business Credit and... § 124.1013 How does SBA make disadvantaged status determinations in considering an SDB protest? (a... the contract until: (i) The SBA has made an SDB determination, or (ii) 15 working days have expired...

KSC-08pd1556

NASA Image and Video Library

2008-05-31

CAPE CANAVERAL, Fla. -- Space shuttle Discovery is silhouetted against the clear blue Florida sky as it hurtles toward space on its STS-124 mission to the International Space Station. Beneath the main engine nozzles can be seen the blue cones of light, the shock or mach diamonds that are a formation of shock waves in the exhaust plume of an aerospace propulsion system. Liftoff was on time at 5:02 p.m. EDT. Discovery is making its 35th flight. The STS-124 mission is the 26th in the assembly of the space station. It is the second of three flights launching components to complete the Japan Aerospace Exploration Agency's Kibo laboratory. The shuttle crew will install Kibo's large Japanese Pressurized Module and its remote manipulator system, or RMS. The 14-day flight includes three spacewalks. Photo credit: NASA/Jerry Cannon, George Roberts

KSC-08pd1013

NASA Image and Video Library

2008-04-24

CAPE CANAVERAL, Fla. -- In the Vertical Integration Facility at NASA's Kennedy Space Center, workers on either side monitor the progress of the payload canister as it is raised to a vertical position. The canister contains the Japanese Experiment Module -Pressurized Module, which will be transported to Launch Pad 39A for space shuttle Discovery’s STS-124 mission. At the pad, the payload will be transferred from the canister into the payload changeout room on the rotating service structure. The changeout room is the enclosed, environmentally controlled portion of the service structure that supports cargo delivery to the pad and subsequent vertical installation into an orbiter's payload bay. On the mission, the STS-124 crew will transport the JEM as well as the Japanese Remote Manipulator System to the International Space Station. The launch of Discovery is targeted for May 31. Photo credit: NASA/Jim Grossmann

KSC-08pd1009

NASA Image and Video Library

2008-04-24

CAPE CANAVERAL, Fla. -- In the Vertical Integration Facility at NASA's Kennedy Space Center, technicians monitor the rotation of the payload canister to a vertical position. The canister contains the Japanese Experiment Module -Pressurized Module. The canister will be transported to Launch Pad 39A for space shuttle Discovery’s STS-124 mission. At the pad, the payload will be transferred from the canister into the payload changeout room on the rotating service structure. The changeout room is the enclosed, environmentally controlled portion of the service structure that supports cargo delivery to the pad and subsequent vertical installation into an orbiter's payload bay. On the mission, the STS-124 crew will transport the JEM as well as the Japanese Remote Manipulator System to the International Space Station. The launch of Discovery is targeted for May 31. Photo credit: NASA/Jim Grossmann

KSC-08pd1012

NASA Image and Video Library

2008-04-24

CAPE CANAVERAL, Fla. -- In the Vertical Integration Facility at NASA's Kennedy Space Center, the payload canister containing the Japanese Experiment Module -Pressurized Module is being raised to a vertical position. The canister contains the Japanese Experiment Module -Pressurized Module, which will be transported to Launch Pad 39A for space shuttle Discovery’s STS-124 mission. At the pad, the payload will be transferred from the canister into the payload changeout room on the rotating service structure. The changeout room is the enclosed, environmentally controlled portion of the service structure that supports cargo delivery to the pad and subsequent vertical installation into an orbiter's payload bay. On the mission, the STS-124 crew will transport the JEM as well as the Japanese Remote Manipulator System to the International Space Station. The launch of Discovery is targeted for May 31. Photo credit: NASA/Jim Grossmann

KSC-08pd1014

NASA Image and Video Library

2008-04-24

CAPE CANAVERAL, Fla. -- In the Vertical Integration Facility at NASA's Kennedy Space Center, the payload canister containing the Japanese Experiment Module -Pressurized Module is suspended vertically after rotation from the horizontal. The canister contains the Japanese Experiment Module -Pressurized Module, which will be transported to Launch Pad 39A for space shuttle Discovery’s STS-124 mission. At the pad, the payload will be transferred from the canister into the payload changeout room on the rotating service structure. The changeout room is the enclosed, environmentally controlled portion of the service structure that supports cargo delivery to the pad and subsequent vertical installation into an orbiter's payload bay. On the mission, the STS-124 crew will transport the JEM as well as the Japanese Remote Manipulator System to the International Space Station. The launch of Discovery is targeted for May 31. Photo credit: NASA/Jim Grossmann

KSC-08pd1728

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – The STS-124 mission crew pose for a final group photo before heading to crew quarters after their successful landing aboard space shuttle Discovery on Runway 15 at NASA's Kennedy Space Center. The landing ended a 14-day mission to the International Space Station. From left are Pilot Ken Ham, Mission Specialists Karen Nyberg and Akihiko Hoshide, Commander Mark Kelly, and Mission Specialists Mike Fossum and Ron Garan. Discovery's main landing gear touched down at 11:15:19 a.m. EDT. The nose landing gear touched down at 11:15:30 a.m. and wheel stop was at 11:16:19 a.m. The mission completed 5.7 million miles. The STS-124 mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the space station. Photo credit: NASA/Kim Shiflett

School climate and continuity of adolescent personality disorder symptoms.

PubMed

Kasen, Stephanie; Cohen, Patricia; Chen, Henian; Johnson, Jeffrey G; Crawford, Thomas N

2009-12-01

Schools are key social contexts for shaping development and behavior in youths; yet, little is known of their influence on adolescent personality disturbance. A community-based sample of 592 adolescents was assessed for family and school experiences, Axis I psychiatric disorders, and Axis II personality disorder (PD) symptoms, and followed into young adulthood. Multiple regression analysis was used to estimate associations between adolescent-reported school climate and young adult PD symptoms independent of age, sex, family socioeconomic status; childhood maltreatment; Axis I disorder, PD symptoms, academic grades, and parental punishment in adolescence; and four dimensions of school climate. Schools characterized as high in learning focus were related to cluster B (antisocial, borderline, histrionic, and narcissistic PD) symptom declines, whereas schools characterized as high in opportunities for student autonomy were related to cluster A (paranoid, schizoid, and schizotypal PD) symptom declines. In contrast, schools characterized as conflictual or supporting interpersonal informality/familiarity among students and teachers were related to increases in cluster A symptoms and cluster C (avoidant, dependent, and obsessive-compulsive PD) symptoms. Schools may exert both positive and negative influences on continuity of adolescent personality disturbance. The role of the school in guiding young people toward more favorable developmental pathways and alleviating personality disturbance is discussed.

Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

PubMed Central

Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

2016-01-01

Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo—in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29–38, evident as higher rates of induced action potential firing at low current injections (100–200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26–28) and older animals (PD40–62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits. PMID:27065812

Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion.

PubMed

Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

2016-01-01

Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

What dictates which ion, I- or Br-, mediates the growth of cubic Pd nanocrystals?

PubMed

Wang, Ze-Hong; Wu, Ya-Jiao; Xue, Huan-Huan; Zhou, Lin-Nan; Geng, Wen-Chao; Yi, Hai-Bo; Li, Yong-Jun

2018-04-25

Cubic Pd nanocrystals (CPNCs) as one of typical nanostructures are generally fabricated using I- or Br- as capping ions. However, which ion, I- or Br-, exclusively mediates the growth of CPNCs in a given reaction system is not well understood. Herein, regardless of I- or Br- as the capping ion, we successfully achieved CPNCs in the same reaction system simply by adjusting the pH. Based on the Finke-Watzky kinetic model, an increase in pH accelerates the overall reduction rate of Pd2+, and the formation of CPNCs only occurs over the range of specific solution reduction rate constants (k1). This kinetically illuminates that the reduction rate of Pd2+ is the physicochemical parameter that determines which ion, I- or Br-, dictates the growth of CPNCs. Also, density functional theory (DFT) calculations further elucidate the dependence of the reduction rate of Pd2+ on pH and the configuration of the activated Pd2+ complex.

Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson's Disease Induced by Rotenone.

PubMed

Khadrawy, Yasser A; Salem, Ahmed M; El-Shamy, Karima A; Ahmed, Emad K; Fadl, Nevein N; Hosny, Eman N

2017-09-03

The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinson's disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.p.) for 45 days), protected group injected with caffeine (30 mg/kg, i.p.) and rotenone for 45 days (during the development of PD model), and treated group injected with caffeine (30 mg/kg, i.p.) for 45 days after induction of PD model. The data revealed a state of oxidative and nitrosative stress in the midbrain and the striatum of animal model of PD as indicated from the increased lipid peroxidation and nitric oxide levels and the decreased reduced glutathione level and activities of glutathione-S-transferase and superoxide dismutase. Rotenone induced a decrease in acetylcholinesterase and Na + /K + -ATPase activities and an increase in tumor necrosis factor-α level in the midbrain and the striatum. Protection and treatment with caffeine ameliorated the oxidative stress and the changes in acetylcholinesterase and Na + /K + -ATPase activities induced by rotenone in the midbrain and the striatum. This was associated with improvement in the histopathological changes induced in the two areas of PD model. Caffeine protection and treatment restored the depletion of midbrain and striatal dopamine induced by rotenone and prevented decline in motor activities (assessed by open field test) and muscular strength (assessed by traction and hanging tests) and improved norepinephrine level in the two areas. The present study showed that caffeine offered a significant neuroprotection and treatment against neurochemical, histopathological, and behavioral changes in a rotenone-induced rat model of PD.

Single photon emission computed tomography/positron emission tomography imaging and targeted radionuclide therapy of melanoma: new multimodal fluorinated and iodinated radiotracers.

PubMed

Maisonial, Aurélie; Kuhnast, Bertrand; Papon, Janine; Boisgard, Raphaël; Bayle, Martine; Vidal, Aurélien; Auzeloux, Philippe; Rbah, Latifa; Bonnet-Duquennoy, Mathilde; Miot-Noirault, Elisabeth; Galmier, Marie-Josèphe; Borel, Michèle; Askienazy, Serge; Dollé, Frédéric; Tavitian, Bertrand; Madelmont, Jean-Claude; Moins, Nicole; Chezal, Jean-Michel

2011-04-28

This study reports a series of 14 new iodinated and fluorinated compounds offering both early imaging ((123)I, (124)I, (18)F) and systemic treatment ((131)I) of melanoma potentialities. The biodistribution of each (125)I-labeled tracer was evaluated in a model of melanoma B16F0-bearing mice, using in vivo serial γ scintigraphic imaging. Among this series, [(125)I]56 emerged as the most promising compound in terms of specific tumoral uptake and in vivo kinetic profile. To validate our multimodality concept, the radiosynthesis of [(18)F]56 was then optimized and this radiotracer has been successfully investigated for in vivo PET imaging of melanoma in B16F0- and B16F10-bearing mouse model. The therapeutic efficacy of [(131)I]56 was then evaluated in mice bearing subcutaneous B16F0 melanoma, and a significant slow down in tumoral growth was demonstrated. These data support further development of 56 for PET imaging ((18)F, (124)I) and targeted radionuclide therapy ((131)I) of melanoma using a single chemical structure.

The Gastric/Pancreatic Amylase Ratio Predicts Postoperative Pancreatic Fistula With High Sensitivity and Specificity

PubMed Central

Jin, Shuo; Shi, Xiao-Ju; Sun, Xiao-Dong; Zhang, Ping; Lv, Guo-Yue; Du, Xiao-Hong; Wang, Si-Yuan; Wang, Guang-Yi

2015-01-01

Abstract This article aims to identify risk factors for postoperative pancreatic fistula (POPF) and evaluate the gastric/pancreatic amylase ratio (GPAR) on postoperative day (POD) 3 as a POPF predictor in patients who undergo pancreaticoduodenectomy (PD). POPF significantly contributes to mortality and morbidity in patients who undergo PD. Previously identified predictors for POPF often have low predictive accuracy. Therefore, accurate POPF predictors are needed. In this prospective cohort study, we measured the clinical and biochemical factors of 61 patients who underwent PD and diagnosed POPF according to the definition of the International Study Group of Pancreatic Fistula. We analyzed the association between POPF and various factors, identified POPF risk factors, and evaluated the predictive power of the GPAR on POD3 and the levels of serum and ascites amylase. Of the 61 patients, 21 developed POPF. The color of the pancreatic drain fluid, POD1 serum, POD1 median output of pancreatic drain fluid volume, and GPAR were significantly associated with POPF. The color of the pancreatic drain fluid and high GPAR were independent risk factors. Although serum and ascites amylase did not predict POPF accurately, the cutoff value was 1.24, and GPAR predicted POPF with high sensitivity and specificity. This is the first report demonstrating that high GPAR on POD3 is a risk factor for POPF and showing that GPAR is a more accurate predictor of POPF than the previously reported amylase markers. PMID:25621676

The gastric/pancreatic amylase ratio predicts postoperative pancreatic fistula with high sensitivity and specificity.

PubMed

Jin, Shuo; Shi, Xiao-Ju; Sun, Xiao-Dong; Zhang, Ping; Lv, Guo-Yue; Du, Xiao-Hong; Wang, Si-Yuan; Wang, Guang-Yi

2015-01-01

This article aims to identify risk factors for postoperative pancreatic fistula (POPF) and evaluate the gastric/pancreatic amylase ratio (GPAR) on postoperative day (POD) 3 as a POPF predictor in patients who undergo pancreaticoduodenectomy (PD).POPF significantly contributes to mortality and morbidity in patients who undergo PD. Previously identified predictors for POPF often have low predictive accuracy. Therefore, accurate POPF predictors are needed.In this prospective cohort study, we measured the clinical and biochemical factors of 61 patients who underwent PD and diagnosed POPF according to the definition of the International Study Group of Pancreatic Fistula. We analyzed the association between POPF and various factors, identified POPF risk factors, and evaluated the predictive power of the GPAR on POD3 and the levels of serum and ascites amylase.Of the 61 patients, 21 developed POPF. The color of the pancreatic drain fluid, POD1 serum, POD1 median output of pancreatic drain fluid volume, and GPAR were significantly associated with POPF. The color of the pancreatic drain fluid and high GPAR were independent risk factors. Although serum and ascites amylase did not predict POPF accurately, the cutoff value was 1.24, and GPAR predicted POPF with high sensitivity and specificity.This is the first report demonstrating that high GPAR on POD3 is a risk factor for POPF and showing that GPAR is a more accurate predictor of POPF than the previously reported amylase markers.

Protective effect of tangeritin in transgenic Drosophila model of Parkinson's disease.

PubMed

Fatima, Ambreen; Khanam, Saba; Rahul, Rahul; Jyoti, Smita; Naz, Falaq; Ali, Fahad; Siddique, Yasir Hasan

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder caused due to the loss of dopaminergic neurons in substantia nigra region of midbrain. The disease is characterized by the accumulation of alpha-synuclein into depositions known as lewy bodies. Till date there is no cure for PD but the limited number of medications may provide temporary relief from the PD symptoms. Flavonoids are a group of polyphenols found in plants. The health benefits of flavonoids have been universally accepted. Tangeritin is a pentamethoxy flavone found in the peels of Mandarin oranges ( Citrus reticulata ). The present study was conducted to study the effect of tangeritin on the symptoms of PD exhibited by the PD model transgenic flies ( Drosophila melanogaster) . Tangeritin at a final concentration of 5, 10 and 20 microM was added to the diet and the flies were allowed to feed on it for 24 days. At the same time other set of PD flies were allowed to feed on a diet having 10-3 M of L-Dopa. The effect of tangeritin was studied on the activity pattern, climbing ability, dopamine content, oxidative stress markers (lipid peroxidation, reduced glutathione, glutathione-S-transferase, protein carbonyl content and monoamine oxidase activity) and on the histopathology of the brain of PD model flies. The study showed that the exposure of PD flies to different doses of tangeritin showed a marked delay in the loss of climbing ability and increase in the dopamine content. Tangeritin also showed a reduction in various oxidative stress markers. Hence it is concluded that tangeritin showed a marked reduction in the PD symptoms and thus could be of great importance for further research in treating PD.

The Human Ortholog of Acid-Sensing Ion Channel Gene ASIC1a Is Associated With Panic Disorder And Amygdala Structure And Function

PubMed Central

Smoller, Jordan W.; Gallagher, Patience J.; Duncan, Laramie E.; McGrath, Lauren M.; Haddad, Stephen A.; Holmes, Avram.; Wolf, Aaron B.; Hilker, Sidney; Block, Stefanie R.; Weill, Sydney; Young, Sarah; Choi, Eun Young; Rosenbaum, Jerrold F.; Biederman, Joseph; Faraone, Stephen V.; Roffman, Joshua; Manfro, Gisele G.; Blaya, Carolina; Hirshfeld-Becker, Dina R.; Stein, Murray B.; Van Ameringen, Michael; Tolin, David F.; Otto, Michael W.; Pollack, Mark H.; Simon, Naomi M.; Buckner, Randy L.; Ongur, Dost; Cohen, Bruce M.

2014-01-01

Background Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide (CO2), possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that CO2-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods We conducted a case-control analysis (N=414 PD cases, 846 healthy controls) of ACCN2single nucleotide polymorphisms (SNPs) and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n=1,048) and/or task-evoked reactivity to emotional stimuli (n=103) in healthy individuals. Results Two SNPs at the ACCN2 locus showed evidence of association with PD: rs685012 (OR=1.32, gene-wise corrected p=0.011) and rs10875995 (OR=1.26, gene-wise corrected p=0.046). The association appeared to be stronger when early-onset (age ≤ 20) PD cases and when cases with prominent respiratory symptoms were compared to controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p=0.035), as well as task-evoked amygdala reactivity to fearful and angry faces (p=0.0048). Conclusions Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to anxiety proneness. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD. PMID:24529281

Basic vaginal pH, bacterial vaginosis and aerobic vaginitis: prevalence in early pregnancy and risk of spontaneous preterm delivery, a prospective study in a low socioeconomic and multiethnic South American population.

PubMed

Krauss-Silva, Leticia; Almada-Horta, Antonio; Alves, Mariane B; Camacho, Karla G; Moreira, Maria Elizabeth L; Braga, Alcione

2014-03-19

Bacterial vaginosis (BV) increases the risk of spontaneous preterm deliveries (PD) in developed countries. Its prevalence varies with ethnicity, socioeconomic conditions and gestational age. Aerobic vaginitis (AV) has also been implicated with spontaneous PD. The present study aimed to estimate the prevalence of asymptomatic BV, the accuracy of vaginal pH level to predict BV and to estimate the risk of spontaneous PD <34 and <37 weeks' gestation of BV and AV. Women attending prenatal public services in Rio de Janeiro were screened to select asymptomatic pregnant women, < 20 weeks' gestation, with no indication for elective PD and without risk factors of spontaneous PD. Vaginal smears of women with vaginal pH > = 4.5 were collected to determine the Nugent score; a sample of those smears was also classified according to a modified Donders' score. Primary outcomes were spontaneous PD < 34 and <37 weeks' gestation and abortion. Prevalence of asymptomatic BV was estimated in 28.1% (n = 1699); 42.4% of the smears were collected before 14 weeks' gestation. After an 8-week follow up, nearly 40% of the initially BV positive women became BV negative. The prevalence of BV among white and black women was 28.1% (95% CI: 24.6%-32.0%) and 32.5% (95% CI: 28.2%-37.2%), respectively. The sensitivity of vaginal pH= > 4.5 and = > 5.0 to predict BV status was 100% and 82%, correspondingly; the 5.0 cutoff value doubled the specificity, from 41% to 84%. The incidence of < 37 weeks' spontaneous PDs among BV pregnant women with a pH= > 4.5 was 3.8%. The RR of spontaneous PD < 34 and <37 weeks among BV women with pH > =4.5, as compared with those with intermediate state, were 1.24 and 1.86, respectively (Fisher's exact test, p value = 1; 0.52, respectively, both ns). No spontaneous case of PD or abortion was associated with severe or moderate AV. A high prevalence of asymptomatic BV was observed without statistically significant difference between black and white women. The RRs of spontaneous PD < 34 and <37 weeks among women with BV, as compared with those with intermediate state were not statistically significant but were consistent with those found in the literature.

Matched pairs dosimetry: 124I/131I metaiodobenzylguanidine and 124I/131I and 86Y/90Y antibodies.

PubMed

Lopci, Egesta; Chiti, Arturo; Castellani, Maria Rita; Pepe, Giovanna; Antunovic, Lidija; Fanti, Stefano; Bombardieri, Emilio

2011-05-01

The technological advances in imaging and production of radiopharmaceuticals are driving an innovative way of evaluating the targets for antineoplastic therapies. Besides the use of imaging to better delineate the volume of external beam radiation therapy in oncology, modern imaging techniques are able to identify targets for highly specific medical therapies, using chemotherapeutic drugs and antiangiogenesis molecules. Moreover, radionuclide imaging is able to select targets for radionuclide therapy and to give the way to in vivo dose calculation to target tissues and to critical organs. This contribution reports the main studies published on matched pairs dosimetry with (124)I/(131)I- and (86)Y/(90)Y-labelled radiopharmaceuticals, with an emphasis on metaiodobenzylguanidine (MIBG) and monoclonal antibodies.

Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis

PubMed Central

Wang, Peng-Fei; Chen, Yang; Song, Si-Ying; Wang, Ting-Jian; Ji, Wen-Jun; Li, Shou-Wei; Liu, Ning; Yan, Chang-Xiang

2017-01-01

Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC), colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis), endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency), digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin), respiratory system (pneumonitis, lung infiltration, and interstitial lung disease), and urinary system (increased creatinine, nephritis, and renal failure). In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80) in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00) in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%. Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types. PMID:29093678

KSC-08pd1743

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – Following the successful landing of space shuttle Discovery at NASA's Kennedy Space Center to end the 14-day, STS-124 mission, the crew sits for a press conference. Mission Specialist Ron Garan describes his favorite view from orbit. The mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the International Space Station. The landing was on time at 11:15 a.m. EDT. Photo credit: NASA/Kim Shiflett

Dimethylamine

Integrated Risk Information System (IRIS)

Dimethylamine ; CASRN 124 - 40 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

Serratia marcescens osteomyelitis in an infant.

PubMed

Mayer, Chad W; Bangash, Shahid; Bocchini, Joseph A; Lowery-Nordberg, Mary; Bahna, Sami L

2006-01-01

Neutrophil dysfunction can result from oxidative burst defect or from glucose-6-phosphate dehydrogenase (G6PD) deficiency; we noted both in the same patient. A 4-month-old male infant with G6PD deficiency presented with swelling of the left middle finger, left leg, and right big toe. At 5 weeks of age he was hospitalized for fever for 2 days. A maternal uncle died at 5 years of age and a male maternal cousin died at the age of 21 months, both reportedly diagnosed with chronic granulomatous disease (CGD). On physical examination, he had a swollen erythematous left third finger, left distal leg swelling, and right big toe abscess. None of these areas was significantly tender. WBC was 18.7 x 10(3)/mm(3) with 37% PMN and 5% bands. The x-ray films showed osteomyelitis in the left third proximal phalanx and the distal right first metatarsal. Culture from the toe abscess grew Serratia marcescens. His neutrophil oxidative burst was tested by the dihydrorhodamine-123 assay and was markedly suppressed, typical of CGD. The mother and maternal grandmother were found to be CGD carriers. He was treated with i.v. antibiotics for 4 weeks and was discharged on prophylactic trimethoprim, itraconazole and interferon gamma, with substantial reduction in infections. Infection in this infant was unusual in its nature, in affecting multiple sites, and in its causative organism. Immune deficiency was suspected, particularly of the phagocytic component, but could not be attributed to his moderate degree of primary G6PD deficiency. Additional immunologic evaluation and the family history led to the diagnosis of X-linked CGD.

Crystal structures of five 1-alkyl-4-aryl-1,2,4-triazol-1-ium halide salts.

PubMed

Guino-O, Marites A; Talbot, Meghan O; Slitts, Michael M; Pham, Theresa N; Audi, Maya C; Janzen, Daron E

2015-06-01

The asymmetric units for the salts 4-(4-fluoro-phen-yl)-1-isopropyl-1,2,4-triazol-1-ium iodide, C11H13FN3 (+)·I(-), (1), 1-isopropyl-4-(4-methyl-phen-yl)-1,2,4-triazol-1-ium iodide, C12H16N3 (+)·I(-), (2), 1-isopropyl-4-phenyl-1,2,4-triazol-1-ium iodide, C11H14N3 (+)·I(-), (3), and 1-methyl-4-phenyl-1,2,4-triazol-1-ium iodide, C9H10N3 (+)·I(-), (4), contain one cation and one iodide ion, whereas in 1-benzyl-4-phenyl-1,2,4-triazol-1-ium bromide monohydrate, C15H14N3 (+)·Br(-)·H2O, (5), there is an additional single water mol-ecule. There is a predominant C-H⋯X(halide) inter-action for all salts, resulting in a two-dimensional extended sheet network between the triazolium cation and the halide ions. For salts with para-substitution on the aryl ring, there is an additional π-anion inter-action between a triazolium carbon and iodide displayed by the layers. For salts without the para-substitution on the aryl ring, the π-π inter-actions are between the triazolium and aryl rings. The melting points of these salts agree with the predicted substituent inductive effects.

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial.

PubMed

Pelekanou, Vasiliki; Barlow, William E; Nahleh, Zeina A; Wasserman, Brad; Lo, Ying-Chun; von Wahlde, Marie-Kristin; Hayes, Daniel; Hortobagyi, Gabriel N; Gralow, Julie; Tripathy, Debu; Porter, Peggy; Szekely, Borbala; Hatzis, Christos; Rimm, David L; Pusztai, Lajos

2018-06-01

Our aim was to examine the association of pretreatment tumor-infiltrating lymphocyte (TIL) count and PD-L1 levels with pathologic complete response (pCR) and assess immune marker changes following treatment in tumor specimens from the S0800 clinical trial, which randomized patients to bevacizumab + nab-paclitaxel, followed by doxorubicin/cyclophosphamide (AC) versus two control arms without bevacizumab (varying sequence of AC and nab-paclitaxel). TILs were assessed in 124 pre- and 62 posttreatment tissues (including 59 pairs). PD-L1 was assessed in 120 pre- and 43 posttreatment tissues (including 39 pairs) using the 22C3 antibody. Baseline and treatment-induced immune changes were correlated with pCR and survival using estrogen receptor (ER) and treatment-adjusted logistic and Cox regressions, respectively. At baseline, the mean TIL count was 17.4% (17% had zero TILs, 9% had ≥50% TILs). Posttreatment, mean TIL count decreased to 11% (5% had no TILs, 2% had >50% TILs). In paired samples, the mean TIL change was 15% decrease. Baseline PD-L1 was detected in 43% of cases ( n = 5 in tumor cells, n = 29 stroma, n = 18 tumor + stroma). Posttreatment, PD-L1 expression was not significantly lower (33%). Higher baseline TIL count and PD-L1 positivity rate were associated with higher pCR rate even after adjustment for treatment and ER status ( P = 0.018). There was no association between TIL counts, PD-L1 expression, and survival due to few events. In conclusion, TIL counts, but not PD-L1 expression, decreased significantly after treatment. Continued PD-L1 expression in some residual cancers raises the possibility that adjuvant immune checkpoint inhibitor therapy could improve survival in this patient population. Mol Cancer Ther; 17(6); 1324-31. ©2018 AACR . ©2018 American Association for Cancer Research.

40 CFR 124.214 - What procedures must I follow to make significant changes?

Code of Federal Regulations, 2010 CFR

2010-07-01

... changes to information you provided under 40 CFR 270.275 or to terms and conditions in the supplemental... prepare the draft permit decision. When the use of the 30-day extension is anticipated, you should inform... tentative determination, the procedures in § 124.205 and §§ 124.207 through 124.210 for processing an...

Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinha, Neeharika; Cifter, Gizem; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using themore » Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application with in situ dose painting administered via gold nanoparticle eluters for prostate cancer.« less

HLA class I loss and PD-L1 expression in lung cancer: impact on T-cell infiltration and immune escape

PubMed Central

Perea, Francisco; Sánchez-Palencia, Abel; Gómez-Morales, Mercedes; Bernal, Mónica; Concha, Ángel; García, Míguela Méndez; González-Ramírez, Amanda Rocío; Kerick, Martin; Martin, Javier; Garrido, Federico; Ruiz-Cabello, Francisco; Aptsiauri, Natalia

2018-01-01

Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression. They demonstrated different patterns of tumor infiltration and clinicopathologic characteristics, including the tumor size and lymphatic spread. All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells. It represents a cancer immune escape phenotype that combines two independent mechanisms of immune evasion: loss of HLA-I and upregulation of PD-L1. Using GCH-array analysis of human lung cancer cell lines we found that the loss of heterozygosity (LOH) with complete or partial deletion of HLA-I genes is the principal mechanism of HLA-I alterations. This irreversible defect, which could potentially decrease the clinical efficacy of lung cancer immunotherapy, appears to be underestimated. In conclusion, our results suggest that the analysis of HLA-I is very important for the selection of potential responders to cancer immunotherapy. PMID:29423109

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

PubMed Central

Workel, Hagma H.; Tijans, Aline M.; Terwindt, Anouk L.J.; Brunekreeft, Kim L.; Plat, Annechien; Klip, Harry G.; Eggink, Florine A.; Leffers, Ninke; Helfrich, Wijnand; Samplonius, Douwe F.; Bremer, Edwin; Wisman, G. Bea A.; Daemen, Toos; Duiker, Evelien W.; Hollema, Harry; Nijman, Hans W.; de Bruyn, Marco

2016-01-01

CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis. We further demonstrate that CD103+ TIL were almost exclusively CD3+ TCRαβ+ CD8αβ+ CD4- T cells, but heterogeneously expressed T cell memory and differentiation markers. Activation of peripheral T cells in the presence of HGSC was sufficient to trigger induction of CD103 in over 90% of all CD8+ cells in a T cell receptor (TCR)- and TGFβR1-dependent manner. Finally, CD103+ TIL isolated from primary HGSC showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27. Taken together, our data indicate CD103+ TIL in HGSC are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition. PMID:27650547

High-spin states in 103,105Mo, 103Nb, and the νh11/2 alignment

NASA Astrophysics Data System (ADS)

Hua, H.; Wu, C. Y.; Cline, D.; Hayes, A. B.; Teng, R.; Clark, R. M.; Fallon, P.; Macchiavelli, A. O.; Vetter, K.

2002-06-01

High-spin states in neutron-rich nuclei 103,105Mo,103Nb have been studied using the 238U(α,f) fusion-fission reaction. The deexcitation γ rays were detected by Gammasphere in coincidence with the detection of both fission fragments by the Rochester 4π heavy-ion detector array, CHICO. The measured fission kinematics were used to deduce the masses and velocity vectors for both fission fragments. This allowed Doppler-shift corrections to be applied to the observed γ rays on an event-by-event basis and the origin of γ rays from either fission fragment to be established. With such advantages, the yrast sequences for these nuclei have been extended to the band crossing region. This band crossing is ascribed to the alignment of a pair of h11/2 neutrons, which is supported by the observed blocking effect for the νh11/2 band in 105Mo while there is no evidence for blocking in the alignment measured for either the νd5/2 band in 103Mo or the πg9/2 band in 103Nb. The observed upbend, rather than the sharp backbend seen in the Ru-Pd region, indicates a strong interaction between the ground-state and the aligned h11/2 bands.

Using Smartphones and Machine Learning to Quantify Parkinson Disease Severity: The Mobile Parkinson Disease Score.

PubMed

Zhan, Andong; Mohan, Srihari; Tarolli, Christopher; Schneider, Ruth B; Adams, Jamie L; Sharma, Saloni; Elson, Molly J; Spear, Kelsey L; Glidden, Alistair M; Little, Max A; Terzis, Andreas; Dorsey, E Ray; Saria, Suchi

2018-03-26

Current Parkinson disease (PD) measures are subjective, rater-dependent, and assessed in clinic. Smartphones can measure PD features, yet no smartphone-derived rating score exists to assess motor symptom severity in real-world settings. To develop an objective measure of PD severity and test construct validity by evaluating the ability of the measure to capture intraday symptom fluctuations, correlate with current standard PD outcome measures, and respond to dopaminergic therapy. This observational study assessed individuals with PD who remotely completed 5 tasks (voice, finger tapping, gait, balance, and reaction time) on the smartphone application. We used a novel machine-learning-based approach to generate a mobile Parkinson disease score (mPDS) that objectively weighs features derived from each smartphone activity (eg, stride length from the gait activity) and is scaled from 0 to 100 (where higher scores indicate greater severity). Individuals with and without PD additionally completed standard in-person assessments of PD with smartphone assessments during a period of 6 months. Ability of the mPDS to detect intraday symptom fluctuations, the correlation between the mPDS and standard measures, and the ability of the mPDS to respond to dopaminergic medication. The mPDS was derived from 6148 smartphone activity assessments from 129 individuals (mean [SD] age, 58.7 [8.6] years; 56 [43.4%] women). Gait features contributed most to the total mPDS (33.4%). In addition, 23 individuals with PD (mean [SD] age, 64.6 [11.5] years; 11 [48%] women) and 17 without PD (mean [SD] age 54.2 [16.5] years; 12 [71%] women) completed in-clinic assessments. The mPDS detected symptom fluctuations with a mean (SD) intraday change of 13.9 (10.3) points on a scale of 0 to 100. The measure correlated well with the Movement Disorder Society Unified Parkinson Disease's Rating Scale total (r = 0.81; P < .001) and part III only (r = 0.88; P < .001), the Timed Up and Go assessment (r = 0.72; P = .002), and the Hoehn and Yahr stage (r = 0.91; P < .001). The mPDS improved by a mean (SD) of 16.3 (5.6) points in response to dopaminergic therapy. Using a novel machine-learning approach, we created and demonstrated construct validity of an objective PD severity score derived from smartphone assessments. This score complements standard PD measures by providing frequent, objective, real-world assessments that could enhance clinical care and evaluation of novel therapeutics.

An assessment of Movement Disorder Society Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease.

PubMed

Uysal-Cantürk, P; Hanağası, H A; Bilgiç, B; Gürvit, H; Emre, M

2018-01-01

Cognitive impairment is one of the most disabling non-motor symptoms of Parkinson's disease. Mild cognitive impairment constitutes a major risk for the development of Parkinson's disease dementia in the course of the disease. A Movement Disorder Society Task Force proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI), comprising two operational levels: Level I and Level II. The objective of our study was to test the accuracy of Level I versus Level II diagnostic criteria. Eighty-six consecutive patients with Parkinson's disease were screened and 68 patients without dementia or depression were included in the study. We used the Montreal Cognitive Assessment, Mini-Mental State Examination and Addenbrooke's Cognitive Evaluation-R screening tools for Level I and an extensive neuropsychological battery for Level II assessment. We first diagnosed PD-MCI on the basis of Level II assessment and then calculated sensitivity, specificity and area under the receiver-operator characteristics curve, comparing the performance of the three screening batteries. None of the three screening batteries proposed for Level I assessment provided satisfactory combined sensitivity and specificity for detecting PD-MCI, and their performance was similar. Using the Level II criteria, 29 patients (43%) were diagnosed as having PD-MCI. Lowest cut-off levels that provided at least 80% sensitivity were 24 for the Montreal Cognitive Assessment, 29 for the Mini-Mental State Examination and 87 for the Addenbrooke's Cognitive Evaluation-R. However, specificity levels were below 80% at these cut-off levels. We conclude that Level I assessment alone using screening batteries is not sufficiently sensitive/specific to detect PD-MCI. © 2017 EAN.

Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.

PubMed

Oeda, Tomoko; Umemura, Atsushi; Mori, Yuko; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Inoue, Kimiko; Fujimura, Harutoshi; Hasegawa, Hiroshi; Sugiyama, Hiroshi; Sawada, Hideyuki

2015-12-01

Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction.

PubMed

Messias, Leandro Rocha; Ferreira, Aryanne Guimarães; Miranda, Sandra Marina Ribeiro de; Teixeira, José Antônio Caldas; Azevedo, Jader Cunha de; Messias, Ana Carolina Nader Vasconcelos; Maróstica, Elisabeth; Mesquita, Claudio Tinoco

2016-05-01

More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.

Effects of theta burst stimulation on motor cortex excitability in Parkinson's disease.

PubMed

Zamir, Orit; Gunraj, Carolyn; Ni, Zhen; Mazzella, Filomena; Chen, Robert

2012-04-01

Long-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson's disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD. iTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60 min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS. After iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60 min. Changes in intracortical circuits induced by iTBS were also similar for the different groups. iTBS produced similar effects on cortical excitability for PD patients and controls. Spike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

43 CFR 2806.30 - What are the rents for communication site rights-of-way?

Code of Federal Regulations, 2012 CFR

2012-10-01

... communication use rent schedule on the BLM Home Page on the Internet at http://www.blm.gov. (2) BLM will revise...: Communication Use Rent Schedule Annual Fees [Calendar year 2005] Population Television broadcast Am/FM radio...,000 1,489.63 1,117.22 744.81 124.14 744.81 3,103.39 434.47 1,862.03 93.10 1 Rent for AM Radio is 70...

43 CFR 2806.30 - What are the rents for communication site rights-of-way?

Code of Federal Regulations, 2013 CFR

2013-10-01

... communication use rent schedule on the BLM Home Page on the Internet at http://www.blm.gov. (2) BLM will revise...: Communication Use Rent Schedule Annual Fees [Calendar year 2005] Population Television broadcast Am/FM radio...,000 1,489.63 1,117.22 744.81 124.14 744.81 3,103.39 434.47 1,862.03 93.10 1 Rent for AM Radio is 70...

43 CFR 2806.30 - What are the rents for communication site rights-of-way?

Code of Federal Regulations, 2014 CFR

2014-10-01

... communication use rent schedule on the BLM Home Page on the Internet at http://www.blm.gov. (2) BLM will revise...: Communication Use Rent Schedule Annual Fees [Calendar year 2005] Population Television broadcast Am/FM radio...,000 1,489.63 1,117.22 744.81 124.14 744.81 3,103.39 434.47 1,862.03 93.10 1 Rent for AM Radio is 70...

40 CFR 468.14 - Pretreatment standards for existing sources (PSES).

Code of Federal Regulations, 2011 CFR

2011-07-01

... per 1,000,000 off-pounds of copper or copper alloy hot rolled Chromium 0.045 0.018 Copper 0.195 0.103... rolled English units—pounds per 1,000,000 off-pounds of copper or copper alloy cold rolled Chromium 0.166... drawn Chromium 0.037 0.015 Copper 0.161 0.085 Lead 0.012 0.011 Nickel 0.163 0.107 Zinc 0.124 0.051 TTO 0...

40 CFR 124.211 - What types of changes may I make to my standardized permit?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false What types of changes may I make to my... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Procedures for RCRA Standardized Permit Maintaining A Standardized Permit § 124.211 What types of changes may I make to my standardized permit? You may...

40 CFR 124.211 - What types of changes may I make to my standardized permit?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true What types of changes may I make to my... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Procedures for RCRA Standardized Permit Maintaining A Standardized Permit § 124.211 What types of changes may I make to my standardized permit? You may...

Anionic Palladium(0) and Palladium(II) Ate Complexes.

PubMed

Kolter, Marlene; Böck, Katharina; Karaghiosoff, Konstantin; Koszinowski, Konrad

2017-10-16

Palladium ate complexes are frequently invoked as important intermediates in Heck and cross-coupling reactions, but so far have largely eluded characterization at the molecular level. Here, we use electrospray-ionization mass spectrometry, electrical conductivity measurements, and NMR spectroscopy to show that the electron-poor catalyst [L 3 Pd] (L=tris[3,5-bis(trifluoromethyl)phenyl]phosphine) readily reacts with Br - ions to afford the anionic, zero-valent ate complex [L 3 PdBr] - . In contrast, more-electron-rich Pd catalysts display lower tendencies toward the formation of ate complexes. Combining [L 3 Pd] with LiI and an aryl iodide substrate (ArI) results in the observation of the Pd II ate complex [L 2 Pd(Ar)I 2 ] - . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydrogen bond strengthening induces fluorescence quenching of PRODAN derivative by turning on twisted intramolecular charge transfer

NASA Astrophysics Data System (ADS)

Yang, Yonggang; Li, Donglin; Li, Chaozheng; Liu, YuFang; Jiang, Kai

2017-12-01

Researchers have proposed different effective mechanisms of hydrogen bonding (HB) on the fluorescence of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) and its derivatives. Herein, excited state transition and dynamics analysis confirm that the fluorescence of PD (a derivative of PRODAN with ethyl replaced by 3-hydroxy-2,2-dimethylpropan) emits from the planar intramolecular charge transfer (PICT) state rather than twist ICT (TICT) state, because the fluorescence emission and surface hopping from the TICT state to the twist ground (T-S0) state is energy forbidden. Nevertheless, the strengthening of intramolecular-HB (intra-HB) and intermolecular-HB (inter-HB) of PD-(methanol)2 smooth the pathway of surface hopping from TICT to T-S0 state and the external conversion going to planar ground state by decreasing the energy difference of the two states. This smoothing changes the fluorescence state of PD-(methanol)2 to the TICT state in which fluorescence emission does not occur but surface hopping, leading to the partial fluorescence quenching of PD in methanol solvent. This conclusion is different from previous related reports. Moreover, the inter-HB strengthening of PD-methanol in PICT state induces the cleavage of intra-HB and a fluorescence red-shift of 54 nm compared to PD. This red-shift increases to 66 nm for PD-(methanol)2 for the strengthening of the one intra-HB and two inter-HBs. The dipole moments of PD-methanol and PD-(methanol)2 respectively increase about 10.3D and 8.1D in PICT state compared to PD. The synergistic effect of intra-HB and inter-HB induces partial quenching of PD in methanol solvent by turning on the TICT state and fluorescence red-shift. This work gives a reasonable description on the fluorescence red-shift and partial quenching of PD in methanol solvent, which will bring insight into the study of spectroscopic properties of molecules owning better spectral characteristics.

Hydrogen bond strengthening induces fluorescence quenching of PRODAN derivative by turning on twisted intramolecular charge transfer.

PubMed

Yang, Yonggang; Li, Donglin; Li, Chaozheng; Liu, YuFang; Jiang, Kai

2017-12-05

Researchers have proposed different effective mechanisms of hydrogen bonding (HB) on the fluorescence of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) and its derivatives. Herein, excited state transition and dynamics analysis confirm that the fluorescence of PD (a derivative of PRODAN with ethyl replaced by 3-hydroxy-2,2-dimethylpropan) emits from the planar intramolecular charge transfer (PICT) state rather than twist ICT (TICT) state, because the fluorescence emission and surface hopping from the TICT state to the twist ground (T-S 0 ) state is energy forbidden. Nevertheless, the strengthening of intramolecular-HB (intra-HB) and intermolecular-HB (inter-HB) of PD-(methanol) 2 smooth the pathway of surface hopping from TICT to T-S 0 state and the external conversion going to planar ground state by decreasing the energy difference of the two states. This smoothing changes the fluorescence state of PD-(methanol) 2 to the TICT state in which fluorescence emission does not occur but surface hopping, leading to the partial fluorescence quenching of PD in methanol solvent. This conclusion is different from previous related reports. Moreover, the inter-HB strengthening of PD-methanol in PICT state induces the cleavage of intra-HB and a fluorescence red-shift of 54nm compared to PD. This red-shift increases to 66nm for PD-(methanol) 2 for the strengthening of the one intra-HB and two inter-HBs. The dipole moments of PD-methanol and PD-(methanol) 2 respectively increase about 10.3D and 8.1D in PICT state compared to PD. The synergistic effect of intra-HB and inter-HB induces partial quenching of PD in methanol solvent by turning on the TICT state and fluorescence red-shift. This work gives a reasonable description on the fluorescence red-shift and partial quenching of PD in methanol solvent, which will bring insight into the study of spectroscopic properties of molecules owning better spectral characteristics. Copyright © 2017 Elsevier B.V. All rights reserved.

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941.

PubMed

Raynaud, Florence I; Eccles, Suzanne A; Patel, Sonal; Alix, Sonia; Box, Gary; Chuckowree, Irina; Folkes, Adrian; Gowan, Sharon; De Haven Brandon, Alexis; Di Stefano, Francesca; Hayes, Angela; Henley, Alan T; Lensun, Letitia; Pergl-Wilson, Giles; Robson, Anthony; Saghir, Nahid; Zhyvoloup, Alexander; McDonald, Edward; Sheldrake, Peter; Shuttleworth, Stephen; Valenti, Melanie; Wan, Nan Chi; Clarke, Paul A; Workman, Paul

2009-07-01

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and inhibitors offer considerable therapeutic potential. We previously described the promising tricyclic pyridofuropyrimidine lead and chemical tool compound PI-103. We now report the properties of the pharmaceutically optimized bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting clinical development candidate GDC-0941. All four compounds inhibited phosphatidylinositide 3-kinase p110alpha with IC(50) < or = 10 nmol/L. Despite some differences in isoform selectivity, these agents exhibited similar in vitro antiproliferative properties to PI-103 in a panel of human cancer cell lines, with submicromolar potency in PTEN-negative U87MG human glioblastoma cells and comparable phosphatidylinositide 3-kinase pathway modulation. PI-540 and PI-620 exhibited improvements in solubility and metabolism with high tissue distribution in mice. Both compounds gave improved antitumor efficacy over PI-103, following i.p. dosing in U87MG glioblastoma tumor xenografts in athymic mice, with treated/control values of 34% (66% inhibition) and 27% (73% inhibition) for PI-540 (50 mg/kg b.i.d.) and PI-620 (25 mg/kg b.i.d.), respectively. GDC-0941 showed comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and exhibited 78% oral bioavailability in mice, with tumor exposure above 50% antiproliferative concentrations for >8 hours following 150 mg/kg p.o. and sustained phosphatidylinositide 3-kinase pathway inhibition. These properties led to excellent dose-dependent oral antitumor activity, with daily p.o. dosing at 150 mg/kg achieving 98% and 80% growth inhibition of U87MG glioblastoma and IGROV-1 ovarian cancer xenografts, respectively. Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials.

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941

PubMed Central

Raynaud, Florence I.; Eccles, Suzanne A.; Patel, Sonal; Alix, Sonia; Box, Gary; Chuckowree, Irina; Folkes, Adrian; Gowan, Sharon; De Haven Brandon, Alexis; Di Stefano, Francesca; Hayes, Angela; Henley, Alan T.; Lensun, Letitia; Pergl-Wilson, Giles; Robson, Anthony; Saghir, Nahid; Zhyvoloup, Alexander; McDonald, Edward; Sheldrake, Peter; Shuttleworth, Stephen; Valenti, Melanie; Wan, Nan Chi; Clarke, Paul A.; Workman, Paul

2009-01-01

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and inhibitors offer considerable therapeutic potential. We previously described the promising tricyclic pyridofuropyrimidine lead and chemical tool compound PI-103. We now report the properties of the pharmaceutically optimized bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting clinical development candidate GDC-0941. All four compounds inhibited phosphatidylinositide 3-kinase p110α with IC50 ≤ 10 nmol/L. Despite some differences in isoform selectivity, these agents exhibited similar in vitro antiproliferative properties to PI-103 in a panel of human cancer cell lines, with submicromolar potency in PTEN-negative U87MG human glioblastoma cells and comparable phosphatidylinositide 3-kinase pathway modulation. PI-540 and PI-620 exhibited improvements in solubility and metabolism with high tissue distribution in mice. Both compounds gave improved antitumor efficacy over PI-103, following i.p. dosing in U87MG glioblastoma tumor xenografts in athymic mice, with treated/control values of 34% (66% inhibition) and 27% (73% inhibition) for PI-540 (50 mg/kg b.i.d.) and PI-620 (25 mg/kg b.i.d.), respectively. GDC-0941 showed comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and exhibited 78% oral bioavailability in mice, with tumor exposure above 50% anti-proliferative concentrations for >8 hours following 150 mg/kg p.o. and sustained phosphatidylinositide 3-kinase pathway inhibition. These properties led to excellent dose-dependent oral antitumor activity, with daily p.o. dosing at 150 mg/kg achieving 98% and 80% growth inhibition of U87MG glioblastoma and IGROV-1 ovarian cancer xenografts, respectively. Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials. PMID:19584227

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis

PubMed Central

Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

2017-01-01

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59–1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40–0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96–1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57–0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61–1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender. PMID:28382932

Synthesis and investigation of Pd(I) carbonyl complexes with heteroorganic ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamberov, A.A.; Polovnyak, V.K.; Akhmetov, N.S.

1987-09-10

Pd(I) carbonyl complexes are attracting attention because they have been shown to have catalytic properties in a series of organic syntheses. The stability and catalytic properties of these compounds are determined by the nature of the phosphine ligand and the bridge coordination of the carbonylgroup. Through the partial replacement of carbonyl and acido ligands by heteroorganic ligands in carbonyl halogenide and carbonyl acetate Pd(I) complexes, new stable Pd(I) complexes were obtained: (PdLX)/sub 2/CO, where L = PPh/sub 3/, X = OAc; L = AsPh/sub 3/, X = Cl, Br, OAc; L = SbPh/sub 3/, X = Cl Br, OAc; Lmore » = Ph/sub 2/PCH/sub 2/PPh/sub 2/, Ph/sub 2/AsCH/sub 2/AsPh/sub 2/, X = OAc. Atoms of the heteroorganic and acido ligands are equivalently coordinated to the palladium atoms. The carbonyl group in the complexes has bridge coordination to palladium atoms in the Pd(CO)Pd fragment; in complexes with bidentate heteroorganic ligands the covalent bond between palladium atoms is absent.« less

Optical fiber sensor of partial discharges in High Voltage DC experiments

NASA Astrophysics Data System (ADS)

Búa-Núñez, I.; Azcárraga-Ramos, C. G.; Posada-Román, J. E.; Garcia-Souto, J. A.

2014-05-01

A setup simulating High Voltage DC (HVDC) transformers barriers was developed to demonstrate the effectiveness of an optical fiber (OF) sensor in detecting partial discharges (PD) under these peculiar conditions. Different PD detection techniques were compared: electrical methods, and acoustic methods. Standard piezoelectric sensors (R15i-AST) and the above mentioned OF sensors were used for acoustic detection. The OF sensor was able to detect PD acoustically with a sensitivity better than the other detection methods. The multichannel instrumentation system was tested in real HVDC conditions with the aim of analyzing the behavior of the insulation (mineral oil/pressboard).

CuI/Pd0 cooperative dual catalysis: tunable stereoselective construction of tetra-substituted alkenes.

PubMed

Vercruysse, Sébastien; Cornelissen, Loïc; Nahra, Fady; Collard, Laurent; Riant, Olivier

2014-02-10

This paper describes a tunable and stereoselective dual catalytic system that uses copper and palladium reagents. This cooperative silylcupration and palladium-catalyzed allylation readily affords trisubstituted alkenylsilanes. Fine-tuning the reaction conditions allows selective access to one stereoisomer over the other. This new methodology tolerates different substituents on both coupling partners with high levels of stereoselectivity. The one-pot reaction involving a Cu(I)/Pd(0) cooperative dual catalyst directly addresses the need to develop more time-efficient and less-wasteful synthetic pathways. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson's disease (PD): historical overview and future prospects.

PubMed

Nagatsu, Toshiharu; Nagatsu, Ikuko

2016-11-01

Tyrosine hydroxylase (TH), which was discovered at the National Institutes of Health (NIH) in 1964, is a tetrahydrobiopterin (BH4)-requiring monooxygenase that catalyzes the first and rate-limiting step in the biosynthesis of catecholamines (CAs), such as dopamine, noradrenaline, and adrenaline. Since deficiencies of dopamine and noradrenaline in the brain stem, caused by neurodegeneration of dopamine and noradrenaline neurons, are mainly related to non-motor and motor symptoms of Parkinson's disease (PD), we have studied human CA-synthesizing enzymes [TH; BH4-related enzymes, especially GTP-cyclohydrolase I (GCH1); aromatic L-amino acid decarboxylase (AADC); dopamine β-hydroxylase (DBH); and phenylethanolamine N-methyltransferase (PNMT)] and their genes in relation to PD in postmortem brains from PD patients, patients with CA-related genetic diseases, mice with genetically engineered CA neurons, and animal models of PD. We purified all human CA-synthesizing enzymes, produced their antibodies for immunohistochemistry and immunoassay, and cloned all human genes, especially the human TH gene and the human gene for GCH1, which synthesizes BH4 as a cofactor of TH. This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as L-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.

In vivo characterization of a reporter gene system for imaging hypoxia-induced gene expression.

PubMed

Carlin, Sean; Pugachev, Andrei; Sun, Xiaorong; Burke, Sean; Claus, Filip; O'Donoghue, Joseph; Ling, C Clifton; Humm, John L

2009-10-01

To characterize a tumor model containing a hypoxia-inducible reporter gene and to demonstrate utility by comparison of reporter gene expression to the uptake and distribution of the hypoxia tracer (18)F-fluoromisonidazole ((18)F-FMISO). Three tumors derived from the rat prostate cancer cell line R3327-AT were grown in each of two rats as follows: (1) parental R3327-AT, (2) positive control R3327-AT/PC in which the HSV1-tkeGFP fusion reporter gene was expressed constitutively, (3) R3327-AT/HRE in which the reporter gene was placed under the control of a hypoxia-inducible factor-responsive promoter sequence (HRE). Animals were coadministered a hypoxia-specific marker (pimonidazole) and the reporter gene probe (124)I-2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-iodouracil ((124)I-FIAU) 3 h prior to sacrifice. Statistical analysis of the spatial association between (124)I-FIAU uptake and pimonidazole fluorescent staining intensity was then performed on a pixel-by-pixel basis. Utility of this system was demonstrated by assessment of reporter gene expression versus the exogenous hypoxia probe (18)F-FMISO. Two rats, each bearing a single R3327-AT/HRE tumor, were injected with (124)I-FIAU (3 h before sacrifice) and (18)F-FMISO (2 h before sacrifice). Statistical analysis of the spatial association between (18)F-FMISO and (124)I-FIAU on a pixel-by-pixel basis was performed. Correlation coefficients between (124)I-FIAU uptake and pimonidazole staining intensity were: 0.11 in R3327-AT tumors, -0.66 in R3327-AT/PC and 0.76 in R3327-AT/HRE, confirming that only in the R3327-AT/HRE tumor was HSV1-tkeGFP gene expression associated with hypoxia. Correlation coefficients between (18)F-FMISO and (124)I-FIAU uptakes in R3327-AT/HRE tumors were r=0.56, demonstrating good spatial correspondence between the two tracers. We have confirmed hypoxia-specific expression of the HSV1-tkeGFP fusion gene in the R3327-AT/HRE tumor model and demonstrated the utility of this model for the evaluation of radiolabeled hypoxia tracers.

Studies of an Optical Multi-Processor Interconnect

DTIC Science & Technology

1994-01-01

that the destinations are uniformly distributed, I is given by (E2k-i 2 k(l -(1 -Pd)i)]ýE) N g -1 i+ ( -- Pd)- +2k- 1 2k - 2’-k’ + k(1 -- (1 -- pd)k...15oo 2000- Number of Nodes Figure 5.16: Variation of Maximum User Throughput with Size I I 94I I I I6 Io•MSe P (snowed) g (dsehd) o𔃺.0 OJU/ I£ 0. 00...curves. Table (6.9) shows that the size and topology of the network does not have any significant effect on the number g of threads needed to keep the

2007 Chemical Biological Information Systems

DTIC Science & Technology

2007-01-11

2 ] • P2|1 = P2 and P1|2 = P1 only if sensors are uncorrelated • Define correlation metric ρ – Note: Sensors with different PD & PFA can not have...sensing Sensor 1 AND 2, correlated sensing • Sensor 1: PD = 0.999, PFA = 0.4 • Sensor 2: PD = 0.99, PFA = 0.1 ρ = 0.25 ρ = 1.0 • Sensor 1: PD...0.999, PFA = 0.4 • Sensor 2: PD = 0.99, PFA = 0.1 • Prior Probability of Attack = 10-4 B a y e s i a n C o n f i d e n c e i n a t t a c k 0 0.1

SU-E-J-233: Effect of Brachytherapy Seed Artifacts in T2 and Proton Density Maps in MR Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashouf, S; University of Toronto, Dept of Radiation Oncology, Toronto, Ontario; Fatemi-Ardekani, A

Purpose: This study aims at investigating the influence of brachytherapy seeds on T2 and proton density (PD) maps generated from MR images. Proton density maps can be used to extract water content. Since dose absorbed in tissue surrounding low energy brachytherapy seeds are highly influenced by tissue composition, knowing the water content is a first step towards implementing a heterogeneity correction algorithm using MR images. Methods: An LDR brachytherapy (IsoAid Advantage Pd-103) seed was placed in the middle of an agar-based gel phantom and imaged using a 3T Philips MR scanner with a 168-channel head coil. A multiple echo sequencemore » with TE=20, 40, 60, 80, 100 (ms) with large repetition time (TR=6259ms) was used to extract T2 and PD maps. Results: Seed artifacts were considerably reduced on T2 maps compared to PD maps. The variation of PD around the mean was obtained as −97% to 125% (±1%) while for T2 it was recorded as −71% to 24% (±1%). Conclusion: PD maps which are required for heterogeneity corrections are susceptible to artifacts from seeds. Seed artifacts on T2 maps, however, are significantly reduced due to not being sensitive to B0 field variation.« less

Factors affecting academic leadership in dermatology.

PubMed

Martires, Kathryn J; Aquino, Lisa L; Wu, Jashin J

2015-02-01

Although prior studies have examined methods by which to recruit and retain academic dermatologists, few have examined factors that are important for developing academic leaders in dermatology. This study sought to examine characteristics of dermatology residency programs that affect the odds of producing department or division chairs/chiefs and program directors (PDs). Data regarding program size, faculty, grants, alumni residency program attended, lectures, and publications for all accredited US dermatology residency programs were collected. Of the 103 programs examined, 46% had graduated at least 1 chair/chief, and 53% had graduated at least 1 PD. Results emphasize that faculty guidance and research may represent modifiable factors by which a dermatology residency program can increase its graduation of academic leaders.

31 CFR Appendix B to Subpart I of... - Recertification Regarding Correspodent Accounts for Foreign Banks

Code of Federal Regulations, 2010 CFR

2010-07-01

... TRANSACTIONS Anti-Money Laundering Programs Pt. 103, Subpt. I, App. B Appendix B to Subpart I of Part 103... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recertification Regarding Correspodent Accounts for Foreign Banks B Appendix B to Subpart I of Part 103 Money and Finance: Treasury...

31 CFR Appendix A to Subpart I of... - Certification Regarding Correspondent Accounts for Foreign Banks

Code of Federal Regulations, 2010 CFR

2010-07-01

... Anti-Money Laundering Programs Pt. 103, Subpt. I, App. A Appendix A to Subpart I of Part 103... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Certification Regarding Correspondent Accounts for Foreign Banks A Appendix A to Subpart I of Part 103 Money and Finance: Treasury Regulations...

Electrical behaviour of heterobimetallic [MM'(EtCS2)4] (MM'=NiPd, NiPt, PdPt) and MM'X-chain polymers [PtM(EtCS2)4I] (M=Ni, Pd).

PubMed

Givaja, Gonzalo; Castillo, Oscar; Mateo, Eva; Gallego, Almudena; Gómez-García, Carlos J; Calzolari, Arrigo; di Felice, Rosa; Zamora, Félix

2012-11-26

Herein, we report the isolation of new heterobimetallic complexes [Ni(0.6)Pd(1.4)(EtCS(2))(4)] (1), [NiPt(EtCS(2))(4)] (2) and [Pd(0.4)Pt(1.6)(EtCS(2))(4)] (3), which were constructed by using transmetallation procedures. Subsequent oxidation with iodine furnished the MM'X monodimensional chains [Ni(0.6)Pt(1.4)(EtCS(2))(4)I] (4) and [Ni(0.1)Pd(0.3)Pt(1.6)(EtCS(2))(4)I] (5). The physical properties of these systems were investigated and the chain structures 4 and 5 were found to be reminiscent of the parent [Pt(2)(EtCS(2))(4)I] species. However, they were more sensitively dependent on the localised nature of the charge on the Ni ion, which caused spontaneous breaking of the conduction bands. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of intraoperative dosimetric implant representation with postimplant dosimetry in patients receiving prostate brachytherapy.

PubMed

Stone, Nelson N; Hong, Suzanne; Lo, Yeh-Chi; Howard, Victor; Stock, Richard G

2003-01-01

To compare the results of intraoperative dosimetry with those of CT-based postimplant dosimetry in patients undergoing prostate seed implantation. Seventy-seven patients with T1-T3 prostate cancer received an ultrasound-guided permanent seed implant (36 received (125)I, 7 (103)Pd, and 34 a partial (103)Pd implant plus external beam radiation therapy). The implantation was augmented with an intraoperative dosimetric planning system. After the peripheral needles were placed, 5-mm axial images were acquired into the treatment planning system. Soft tissue structures (prostate, urethra, and rectum) were contoured, and exact needle positions were registered. Seeds were placed with an applicator, and their positions were entered into the planning system. The dose distributions for the implant were calculated after interior needle and seed placement. Postimplant dosimetry was performed 1 month later on the basis of CT imaging. Prostate and urethral doses were compared, by using paired t tests, for the real-time dosimetry in the operating room (OR) and the postimplant dosimetry. The mean preimplant prostate volume was 39.8 cm(3), the postneedle planning volume was 41.5 cm(3) (p<0.001), and the 1-month CT volume was 43.6 cm(3) (p<0.001). The mean difference between the OR dose received by 90% of the prostate (D(90)) and the CT D(90) was 3.4% (95% confidence interval, 2.5-6.6%; p=0.034). The mean dose to 30% of the urethra was 120% of prescription in the OR and 138% on CT. The mean difference was 18% (95% confidence interval, 13-24%; p<0.001). Although small differences exist between the OR and CT dosimetry results, these data suggest that this intraoperative implant dosimetric representation system provides a close match to the actual delivered doses. These data support the use of this system to modify the implant during surgery to achieve more consistent dosimetry results.

Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations.

PubMed

Limousin, Nadège; Konofal, Eric; Karroum, Elias; Lohmann, Ebba; Theodorou, Ioannis; Dürr, Alexandra; Arnulf, Isabelle

2009-10-15

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.

KSC-08pd1888

NASA Image and Video Library

2008-07-08

CAPE CANAVERAL, Fla. – Crews remove bricks from the damaged walls of the flame trench on Launch Pad 39A at NASA's Kennedy Space Center. Damage to the trench occurred during the launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the STS-125 mission. Photo credit: NASA/Jack Pfaller

KSC-08pd1889

NASA Image and Video Library

2008-07-08

CAPE CANAVERAL, Fla. – Crews remove bricks from the damaged walls of the flame trench on Launch Pad 39A at NASA's Kennedy Space Center. Damage to the trench occurred during the launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the STS-125 mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2108

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – Workers weld a steel grid structure to the wall of the flame trench on Launch Pad 39A at NASA's Kennedy Space Center. Damage to the trench occurred during the launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

KSC-08pd2107

NASA Image and Video Library

2008-07-23

CAPE CANAVERAL, Fla. – Workers weld a steel grid structure to the wall of the flame trench on Launch Pad 39A at NASA's Kennedy Space Center. Damage to the trench occurred during the launch of Discovery on the STS-124 mission. A 75- by 20-foot section of the east wall was destroyed and debris scattered as far as the pad perimeter fence. Repairs are expected to be completed before the targeted Oct. 8 launch of Atlantis on the NASA Hubble Space Telescope servicing mission. Photo credit: NASA/Jack Pfaller

Improved Catalytic Activity and Stability of a Palladium Pincer Complex by Incorporation into a Metal-Organic Framework.

PubMed

Burgess, Samantha A; Kassie, Abebu; Baranowski, Sarah A; Fritzsching, Keith J; Schmidt-Rohr, Klaus; Brown, Craig M; Wade, Casey R

2016-02-17

A porous metal-organic framework Zr6O4(OH)4(L-PdX)3 (1-X) has been constructed from Pd diphosphinite pincer complexes ([L-PdX](4-) = [(2,6-(OPAr2)2C6H3)PdX](4-), Ar = p-C6H4CO2(-), X = Cl, I). Reaction of 1-X with PhI(O2CCF3)2 facilitates I(-)/CF3CO2(-) ligand exchange to generate 1-TFA and I2 as a soluble byproduct. 1-TFA is an active and recyclable catalyst for transfer hydrogenation of benzaldehydes using formic acid as a hydrogen source. In contrast, the homogeneous analogue (t)Bu(L-PdTFA) is an ineffective catalyst owing to decomposition under the catalytic conditions, highlighting the beneficial effects of immobilization.

KSC-08pd1719

NASA Image and Video Library

2008-06-14

CAPE CANAVERAL, Fla. – After their successful STS-124 mission and landing on Runway 15 at NASA's Kennedy Space Center, Mission Specialists Karen Nyberg and Akihiko Hoshide, Pilot Ken Ham and Mission Specialist Ron Garan are greeted by the Japan Aerospace Exploration Agency's Director of Program Management and Integration Yuichi Yamaura and Vice President Kaoru Mamiya, Center Director Bill Parsons and Associate Administrator for Space Operations Bill Gerstenmaier. Following Garan is Chief of the Astronaut Corps Stephen Lindsay and astronaut Janet Kavandi. Space shuttle Discovery's main landing gear touched down at 11:15:19 a.m. EDT on Runway 15. The nose landing gear touched down at 11:15:30 a.m. and wheel stop was at 11:16:19 a.m. The mission completed 5.7 million miles. The STS-124 mission delivered the Japan Aerospace Exploration Agency's large Japanese Pressurized Module and its remote manipulator system to the space station. Photo credit: NASA/Kim Shiflett

KSC-08pd1205

NASA Image and Video Library

2008-05-08

CAPE CANAVERAL, Fla. -- At the slidewire landing area of Launch Pad 39A at NASA's Kennedy Space Center, the STS-124 crew poses for a final group photo following the media question-and-answer event. From left are Commander Mark Kelly, Pilot Ken Ham, and Mission Specialists Karen Nyberg, Ron Garan, Mike Fossum, Akihiko Hoshide and Greg Chamitoff. Hoshide represents the Japan Aerospace Exploration Agency. In the background is the fixed service structure (center) and the 300-gallon water tower (left). The crew is at Kennedy for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

KSC-08pd1206

NASA Image and Video Library

2008-05-08

CAPE CANAVERAL, Fla. -- The STS-124 crew holds a good-luck banner presented to Mission Specialist Karen Nyberg that was created and signed by students at Henning Public School in the town of Henning, Minn. Holding the banner are (from left) Mission Specialist Mike Fossum, Pilot Ken Ham, Commander Mark Kelly, Nyberg, Mission Specialists Ron Garan, Akihiko Hoshide and Greg Chamitoff. Hoshide represents the Japan Aerospace Exploration Agency. In the background is the 300-gallon water tower (left) and the fixed service structure. The crew is at Kennedy for a dress launch rehearsal called the terminal countdown demonstration test. TCDT provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. On the STS-124 mission, the crew will deliver and install the Japanese Experiment Module – Pressurized Module and Japanese Remote Manipulator System. Discovery's launch is targeted for May 31. Photo credit: NASA/Kim Shiflett

Growth of 2 Inch Eu-doped SrI2 single crystals for scintillator applications

NASA Astrophysics Data System (ADS)

Yoshikawa, Akira; Shoji, Yasuhiro; Yokota, Yuui; Kurosawa, Shunsuke; Hayasaka, Shoki; Chani, Valery I.; Ito, Tomoki; Kamada, Kei; Ohashi, Yuji; Kochurikhin, Vladimir

2016-10-01

A vertical Bridgman (VB) crystal growth process was established using modified micro-pulling-down (μ-PD) crystal growth system with a removable chamber that was developed for the growth of deliquescent halide single crystals because conventional μ-PD method does not allow growth of large bulk single crystals. Eu:SrI2 crystals were grown from the melt of (Sr0.98Eu0.02)I2 composition using carbon crucibles. Undoped μ-PD SrI2 crystals were used as seeds that were affixed to the bottom of the crucible. All the preparations preceding the growths and the hot zone assembling were performed in a glove box with Ar gas. Then the removable chamber was taken out of the glove box, attached to the μ-PD system, connected with a Turbo Molecular pump, and evacuated down to 10-4 Pa at 300 °C. After the baking procedure, high purity Ar gas (6N) was injected into the chamber. The crucible was heated by a high frequency induction coil up to the melting point of Eu:SrI2. After melting the starting materials, the crucible was displaced in downward direction for the crystal growth and then cooled down to room temperature. Thus, 2 in. and crack-free Eu:SrI2 bulk crystals were produced. The crystals had high transparency and did not contain any visible inclusions. The crystals were cut and polished in the glove box and then sealed in an aluminum container with an optical window for characterization. The details of the crystal growth are discussed.

[Immune checkpoint inhibitors (antibodies to PD1 and PD-L1), a new therapeutic weapon against non-small cell bronchial carcinoma].

PubMed

Berghmans, T; Grigoriu, B; Sculier, J P; Meert, A P

2018-02-01

Classical therapeutic strategy for advanced and metastatic non-small cell lung cancer, without activable oncogenic driver mutation, has been based mainly on cytotoxic chemotherapy with modest benefits in terms of increased survival. A better understanding of the mechanisms involved in the regulation of the immune system led to the development of antibodies directed against immune checkpoints such as PD-L1. The first encouraging clinical data from phase I studies assessing anti-PD1 and anti-PD-L1 antibodies have been confirmed in randomised phase III trials. These new drugs now constitute a standard second-line treatment for metastatic tumours and in the future, at least for pembrolizumab, in the first line. Their adjuvant role after locoregional treatment with curative intent is currently under investigation. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The role of social support in anxiety and depression among Parkinson's disease patients.

PubMed

Ghorbani Saeedian, Radka; Nagyova, Iveta; Krokavcova, Martina; Skorvanek, Matej; Rosenberger, Jaroslav; Gdovinova, Zuzana; Groothoff, Johan W; van Dijk, Jitse P

2014-01-01

To explore how social support is associated with anxiety and depression in Parkinson's disease (PD) patients controlling for gender, disease duration and disease severity. The sample consisted of 124 patients (52.4% male; mean age 68.1 ± 8.4 years; mean disease duration 6.3 ± 5.5 years). Anxiety and depression were measured with the Hospital Anxiety and Depression Scale, social support with the Multidimensional Scale of Perceived Social Support and disease severity with the Unified Parkinson Disease Rating Scale. Data were analyzed using linear regression. Gender, disease duration, disease severity and social support explained 31% of the total variance in anxiety in younger PD patients but did not significantly contribute to the explanation of depression. In the older group, this model explained 41% of the variance in depression but did not significantly contribute to the explanation of anxiety. PD patients experience the positive influence of social support differently according to age. In the younger group, disease duration plays the primary role regarding anxiety. In the older group, poor social support especially from friends is associated with more depression after controlling for the relevant variables. Implications of Rehabilitation PD is a disease of older age with a neurodegenerative character and treatment should focus on increasing quality of life. Anxiety and depression are common co-morbidities in PD patients. The support network should also be screened regularly and involved in enhancing the quality of life.

DNA as a Target for Anticancer Phen-Imidazole Pd(II) Complexes.

PubMed

Heydari, Maryam; Moghadam, Mahboube Eslami; Tarlani, AliAkbar; Farhangian, Hossein

2017-05-01

Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of [Pd(phen)(FIP)](NO 3 ) 2 and [Pd(FIP) 2 ]Cl 2 , that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and [Pd(phen)(FIP)](NO 3 ) 2 (K f  = 127 M -1 G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP) 2 ]Cl 2 (K f  = 13 M -1 G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for [Pd(phen)(FIP)](NO 3 ) 2 (K SV  = 58 mM -1 ) was higher than [Pd(FIP) 2 ]Cl 2 (K SV  = 12 mM -1 ). Also, [Pd(FIP) 2 ]Cl 2 interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and [Pd(phen)(FIP)](NO 3 ) 2 can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP) 2 ]Cl 2 can bind to DNA via groove binding while intercalation mode of binding is observed for [Pd(phen)(FIP)](NO 3 ) 2 .

NXL-103, a combination of flopristin and linopristin, for the potential treatment of bacterial infections including community-acquired pneumonia and MRSA

PubMed Central

Politano, Amani D; Sawyer, Robert G

2011-01-01

Novexel is developing a new, orally active, semisynthetic streptogramin, NXL103, with potential therapeutic application in the treatment of community-acquired pneumonia, community-acquired or nosocomial MRSA and VRE, and complicated skin and soft tissue infections. NXL103 is a 70/30 mixture of streptogramin A/streptogramin B components [1]. The spectrum of activity for NXL103 includes GPCs, fastidious GNRs, and anaerobes, and it has been shown to have bactericidal activity against S. aureus in a biofilm model [2–4]. In multiple in vitro experiments, NXL103 showed potent activity against many bacteria, such as S. aureus, including CA- and HA-MRSA, S. pneumoniae, S. pyogenes, E. faecium, E. faecalis, H. influenzae, and H. parainfluenzae [1–3, 5–10]. NXL103 was not affected by the resistance profiles of bacteria against other commonly used antibiotics [1, 3, 5–9, 11, 12]. In phase I trials, NXL103 achieved bactericidal levels in plasma and was generally well-tolerated, with primary side effects on the gastrointestinal system [13–19]. The first phase II trial performed for the evaluation of community-acquired pneumonia showed non-inferiority of NXL103 to amoxicillin [20]. NXL103 shows promise to become an important agent in the treatment of community-acquired pneumonia and complex skin and soft tissue infections, pending further development. PMID:20112172

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

Synthesis of disaccharides using β-glucosidases from Aspergillus niger, A. awamori and Prunus dulcis.

PubMed

da Silva, Ayla Sant'Ana; Molina, Javier Freddy; Teixeira, Ricardo Sposina Sobral; Valdivieso Gelves, Luis G; Bon, Elba P S; Ferreira-Leitão, Viridiana S

2017-11-01

Glucose conversion into disaccharides was performed with β-glucosidases from Prunus dulcis (β-Pd), Aspergillus niger (β-An) and A. awamori (β-Aa), in reactions containing initial glucose of 700 and 900 g l -1 . The reactions' time courses were followed regarding glucose and product concentrations. In all cases, there was a predominant formation of gentiobiose over cellobiose and also of oligosaccharides with a higher molecular mass. For reactions containing 700 g glucose l -1 , the final substrate conversions were 33, 38, and 23.5% for β-An, β-Aa, and β-Pd, respectively. The use of β-An yielded 103 g gentiobiose l -1 (15.5% yield), which is the highest reported for a fungal β-glucosidase. The increase in glucose concentration to 900 g l -1 resulted in a significant increase in disaccharide synthesis by β-Pd, reaching 128 g gentiobiose l -1 (15% yield), while for β-An and β-Aa, there was a shift toward the synthesis of higher oligosaccharides. β-Pd and the fungal β-An and β-Aa β-glucosidases present quite dissimilar kinetics and selective properties regarding the synthesis of disaccharides; while β-Pd showed the highest productivity for gentiobiose synthesis, β-An presented the highest specificity.

Three-dimensional modeling of glucose-6-phosphate dehydrogenase-deficient variants from German ancestry.

PubMed

Kiani, Farooq; Schwarzl, Sonja; Fischer, Stefan; Efferth, Thomas

2007-07-18

Loss of function of dimeric glucose-6-phosphate dehydrogenase (G6PD) represents the most common inborn error of metabolism throughout the world affecting an estimated 400 million people. In Germany, this enzymopathy is very rare. On the basis of G6PD crystal structures, we have analyzed six G6PD variants of German ancestry by three-dimensional modeling. All mutations present in the German population are either close to one of the three G6P or NADP(+) units or to the interface of the two monomers. Two of the three mutated amino acids of G6PD Vancouver are closer to the binding site of NADP(+). The G6PD Aachen mutation is also closer to the second NADP(+) unit. The G6PD Wayne mutation is closer to the G6P binding region. These mutations may affect the binding of G6P and NADP(+) units. Three mutations, i.e. G6PD Munich, G6PD Riverside and G6PD Gastonia, lie closer to the interface of the two monomers. These may also affect the interface of two monomers. None of these G6PD variants share mutations with the common G6PD variants known from the Mediterranean, Near East, or Africa indicating that they have developed independently. The G6PD variants have been compared with mutants from other populations and the implications for survival of G6PD variants from natural selection have been discussed.

Serum Ionized Calcium Quantification for Staging Canine Periodontal Disease: A Preliminary Study.

PubMed

Miguel Carreira, L; Daniela, Dias; Pedro, Azevedo

2015-06-01

Periodontal diseases (PD) are infectious, inflammatory, progressive diseases of the oral cavity affecting people and dogs. PD takes 2 forms: gingivitis and periodontitis. Diagnosing or staging PD can be achieved only with dental x-rays and periodontal probing, both of which require the use of general anesthesia in dogs. This study aimed to determine whether serum ionized calcium ([iCa(2+)]) levels can be useful in preliminary PD staging in dogs. A sample of 40 dogs (n = 40) was divided into 4 groups (n = 10 each) based on the following PD stages: G1 (gingivitis), G2 (initial periodontitis), G3 (moderate periodontitis), and G4 (severe periodontitis). The groups were then subjected to [iCa(2+)] quantification. Statistically significant differences were observed between PD stages and [iCa(2+)] for all stages except G3 and G4. Therefore, this parameter can be used as an additional tool to establish and monitor preliminary PD status. Copyright © 2015 Elsevier Inc. All rights reserved.

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to...) C3 to C1 200 (124) 133 (83) 70 (43) C3to C0 215 (134) 152 (94) 81 (50) C3 to C 226 (140) 165 (103) 90...

47 CFR 73.215 - Contour protection for short-spaced assignments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... station pursuant to 47 CFR 73.211(b)(3): 6 kW ERP/240 meters HAAT—Class A 25 kW ERP/150 meters HAAT—Class B1 50 kW ERP/472 meters HAAT—Class B (b) Applicants requesting short-spaced assignments pursuant to...) C3 to C1 200 (124) 133 (83) 70 (43) C3to C0 215 (134) 152 (94) 81 (50) C3 to C 226 (140) 165 (103) 90...

Delayed and lasting effects of deep brain stimulation on locomotion in Parkinson's disease

NASA Astrophysics Data System (ADS)

Beuter, Anne; Modolo, Julien

2009-06-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a variety of motor signs affecting gait, postural stability, and tremor. These symptoms can be improved when electrodes are implanted in deep brain structures and electrical stimulation is delivered chronically at high frequency (>100 Hz). Deep brain stimulation (DBS) onset or cessation affects PD signs with different latencies, and the long-term improvements of symptoms affecting the body axis and those affecting the limbs vary in duration. Interestingly, these effects have not been systematically analyzed and modeled. We compare these timing phenomena in relation to one axial (i.e., locomotion) and one distal (i.e., tremor) signs. We suggest that during DBS, these symptoms are improved by different network mechanisms operating at multiple time scales. Locomotion improvement may involve a delayed plastic reorganization, which takes hours to develop, whereas rest tremor is probably alleviated by an almost instantaneous desynchronization of neural activity in subcortical structures. Even if all PD patients develop both distal and axial symptoms sooner or later, current computational models of locomotion and rest tremor are separate. Furthermore, a few computational models of locomotion focus on PD and none exploring the effect of DBS was found in the literature. We, therefore, discuss a model of a neuronal network during DBS, general enough to explore the subcircuits controlling locomotion and rest tremor simultaneously. This model accounts for synchronization and plasticity, two mechanisms that are believed to underlie the two types of symptoms analyzed. We suggest that a hysteretic effect caused by DBS-induced plasticity and synchronization modulation contributes to the different therapeutic latencies observed. Such a comprehensive, generic computational model of DBS effects, incorporating these timing phenomena, should assist in developing a more efficient, faster, durable treatment of distal and axial signs in PD.

Retrospective assessment of movement disorder society criteria for mild cognitive impairment in Parkinson's disease.

PubMed

Loftus, Andrea M; Bucks, Romola S; Thomas, Meghan; Kane, Robert; Timms, Caitlin; Barker, Roger A; Gasson, Natalie

2015-02-01

A Movement Disorder Society (MDS) taskforce recently proposed diagnostic criteria for Parkinson's disease with features of mild cognitive impairment (PD-MCI). This study first examined the prevalence and nature of PD-MCI in a non-demented cohort using the MDS criteria. Using the generic Monte Carlo simulation method developed by Crawford and colleagues (2007), this study then estimated the base rate of the representative population who would demonstrate PD-MCI due to chance alone. A total of 104 participants with idiopathic PD underwent extensive motor and neuropsychological testing at baseline and 2 years later. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess motor symptoms of PD and a range of established neuropsychological tests was used to assess PD-MCI in accord with MDS criteria. In accord with MDS criteria, 38% of this cohort demonstrated PD-MCI at baseline and 48% at follow-up. Of the 36 participants in the multiple-domain PD-MCI subtype at time-1, 9 (25%) demonstrated no PD-MCI at follow up. Analysis revealed that approximately 13% of the representative population would demonstrate abnormally low scores for 2 of the 9 tests used, thereby meeting MDS criteria for PD-MCI. Clinicians and researchers need to approach a single diagnosis (i.e., based on one assessment) of PD-MCI with considerable caution.

Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

PubMed Central

Huang, Hongbin; Peng, Cong; Liu, Yong; Liu, Xu; Chen, Qicong; Huang, Zunnan

2016-01-01

Abstract Background: Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results. Methods: Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association. Results: The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09–1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32–2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26–2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02–1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66–0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03–1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility. Conclusion: The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility. PMID:27749554

Prevalence and risk factors for low back pain among professional cooks working in school lunch services

PubMed Central

Nagasu, Miwako; Sakai, Kazuhiro; Ito, Akiyoshi; Tomita, Shigeru; Temmyo, Yoshiomi; Ueno, Mitsuo; Miyagi, Shigeji

2007-01-01

Background The prevalence of self-reported low back pain among professional cooks was estimated to examine the effects of daily life conditions, job-related factors, and psychological factors on this disorder. Methods Data was collected using a mailed self-administered questionnaire. Results Of 7100 cooks, 5835 (82%) replied to the questionnaire, including 1010 men and 4825 women. The mean age was 41.4 for men and 47.5 for women. The prevalence of low back pain during a 1-month period was 72.2% among men and 74.7% among women, with no significant differences between groups. By logistic regression analyses, factors significantly associated with the prevalence of low back pain in 1 month were female gender (prevalence ratio [PR] 1.32; 95% CI, 1.03–1.68), current smoking (PR 1.57; 95% CI, 1.24–1.98), and past smoking (PR 1.35; 95% CI, 1.01–1.79). As for job-related factors, the number of cooked lunches per person (PR 1.28; 95% CI, 1.05–1.56), breaks in the morning session (PR 1.33; 95% CI, 1.13–1.56), kitchen environment (PR 1.09; 95%, CI, 1.03–1.15), and height of cooking equipment (PR 1.13; 95% CI, 1.08–1.19) were associated with the prevalence of low back pain. As for psychological factors, job satisfaction (PR 1.22; 95% CI, 1.03–1.45), stress at work (PR 1.68; 95% CI, 1.42–1.99), financial constraints (PR 1.23; 95% CI, 1.03–1.47), health-related stress (PR 1.31; 95% CI, 1.08–1.59) and worries about the future (PR 1.24; 95% CI, 1.01–1.52) were similarly associated. Conclusion Daily life conditions, job-related factors, and psychological factors are associated with the occurrence of low back pain. It is important to take comprehensive preventive measures to address a range of work and life conditions that can be improved to decrease the incidence of low back pain for professional cooks. PMID:17650300

Bicycle-vehicle interactions at mid-sections of mixed traffic streets: Examining passing distance and bicycle comfort perception.

PubMed

Apasnore, Peter; Ismail, Karim; Kassim, Ali

2017-09-01

This paper studies the relevant factors in mixed urban traffic that may impact the lateral spacing between bicycles and vehicles (passing distance, PD), and their resulting effect on a bicyclists' comfort based on a study of six sites in Ottawa, Canada. The observations are: [i] the average position of bicycles from the curb is 0.57m, and lesser (i.e. 0.35m) in the presence of parking; [ii] 90% of passes exceed 1.23m; [iii] PD is positively correlated with motor vehicle speed, lane width, and bicycle position from adjacent curb edge line, whiles inversely correlated to ambient traffic density and bicycle speed; [iv] motor vehicle speed has the highest prediction of PD variability; [v] PD and ambient traffic density (ATD) are found to be the most important factors to a bicyclists' comfort perception (BCP). Two linear regression models for PD and BCP were developed and significant variables are identified as: motor vehicle speed, bicycle speed, ATD, number of lanes, and lane width. The presence or absence of a grade slope is found to be significant to the PD model and not to BCP. The models both exhibit limited predictive ability, however residual plots and significance of included variables are indicative of correct assumptions for the models. It is recommended that speed calming, sharrows, road signs instructing road sharing, and educating road users against "dooring" crashes be considered in improving road sharing, especially for narrow lanes (i.e. less than 3.6m) and lanes wider than 4.5m. It is also prudent for designers to avoid installing parking zones on narrow shared roads. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers.

PubMed

Krishnamurthy, A; Jimeno, A

2017-04-01

In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell-mediated immune response against cancer cells. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby enhancing T-cell activity against tumor cells. Atezolizumab has been shown to be well tolerated with no dose-limiting toxicities in phase I trials. Atezolizumab was approved by the U.S. Food and Drug Administration in 2016 for the treatment of platinum-resistant metastatic non-small cell lung cancer (NSCLC) and urothelial cancer based on phase II and preliminary phase III studies that have shown significant improvement in objective response rate and median overall survival. There are 117 ongoing clinical trials of atezolizumab currently. Given its efficacy in NSCLC and urothelial carcinoma, atezolizumab holds much potential in the future of cancer therapeutics. Copyright 2017 Clarivate Analytics.

A three-electrode column for Pd-catalytic oxidation of TCE in groundwater with automatic pH-regulation and resistance to reduced sulfur compound foiling.

PubMed

Yuan, Songhu; Chen, Mingjie; Mao, Xuhui; Alshawabkeh, Akram N

2013-01-01

A hybrid electrolysis and Pd-catalytic oxidation process is evaluated for degradation of trichloroethylene (TCE) in groundwater. A three-electrode, one anode and two cathodes, column is employed to automatically develop a low pH condition in the Pd vicinity and a neutral effluent. Simulated groundwater containing up to 5 mM bicarbonate can be acidified to below pH 4 in the Pd vicinity using a total of 60 mA with 20 mA passing through the third electrode. By packing 2 g of Pd/Al(2)O(3) pellets in the developed acidic region, the column efficiency for TCE oxidation in simulated groundwater (5.3 mg/L TCE) increases from 44 to 59 and 68% with increasing Fe(II) concentration from 0 to 5 and 10 mg/L, respectively. Different from Pd-catalytic hydrodechlorination under reducing conditions, this hybrid electrolysis and Pd-catalytic oxidation process is advantageous in controlling the fouling caused by reduced sulfur compounds (RSCs) because the in situ generated reactive oxidizing species, i.e., O(2), H(2)O(2) and OH, can oxidize RSCs to some extent. In particular, sulfite at concentrations less than 1 mM even greatly increases TCE oxidation by the production of SO(4)(•-), a strong oxidizing radical, and more OH. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ancestral effect on HOMA-IR levels quantitated in an American population of Mexican origin.

PubMed

Qu, Hui-Qi; Li, Quan; Lu, Yang; Hanis, Craig L; Fisher-Hoch, Susan P; McCormick, Joseph B

2012-12-01

An elevated insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) is more commonly seen in the Mexican American population than in European populations. We report quantitative ancestral effects within a Mexican American population, and we correlate ancestral components with HOMA-IR. We performed ancestral analysis in 1,551 participants of the Cameron County Hispanic Cohort by genotyping 103 ancestry-informative markers (AIMs). These AIMs allow determination of the percentage (0-100%) ancestry from three major continental populations, i.e., European, African, and Amerindian. We observed that predominantly Amerindian ancestral components were associated with increased HOMA-IR (β = 0.124, P = 1.64 × 10(-7)). The correlation was more significant in males (Amerindian β = 0.165, P = 5.08 × 10(-7)) than in females (Amerindian β = 0.079, P = 0.019). This unique study design demonstrates how genomic markers for quantitative ancestral information can be used in admixed populations to predict phenotypic traits such as insulin resistance.

Cerebellum cholinergic muscarinic receptor (subtype-2 and -3) and cytoarchitecture after developmental exposure to methylmercury: an immunohistochemical study in rat.

PubMed

Roda, Elisa; Coccini, Teresa; Acerbi, Davide; Castoldi, Anna; Bernocchi, Graziella; Manzo, Luigi

2008-05-01

The developing central nervous system (CNS) is a target of the environmental toxicant methylmercury (MeHg), and the cerebellum seems the most susceptible tissue in response to this neurotoxicant. The cholinergic system is essential for brain development, acting as a modulator of neuronal proliferation, migration and differentiation processes; its muscarinic receptors (MRs) play pivotal roles in regulating important basic physiologic functions. By immunohistochemistry, we investigated the effects of perinatal (GD7-PD21) MeHg (0.5 mg/kg bw/day in drinking water) administration on cerebellum of mature (PD36) and immature (PD21) rats, evaluating the: (i) M2- and M3-MR expression; (ii) presence of gliosis; (iii) cytoarchitecture alterations. Regarding to M2-MRs, we showed that: at PD21, MeHg-treated animals did not display any differences compared to controls, while, at PD36 there was a significant increase of M2-immunopositive Bergmann cells in the molecular layer (ML), suggesting a MeHg-related cytotoxic effect. Similarly to M2-MRs, at PD21 the M3-MRs were not affected by MeHg, while, at PD36 a lacking immunoreactivity of the granular layer (IGL) was observed after MeHg treatment. In MeHg-treated rats, at both developmental points, we showed reactive gliosis, e.g. a significant increase in Bergmann glia of the ML and astrocytes of the IGL, identified by their expression of glial fibrillar acidic protein. No MeHg-related effects on Purkinje cells were detected neither at weaning nor at puberty. These findings suggest: (i) a delayed MeHg exposure-related effect on M2- and M3-MRs, (ii) an overt MeHg-related cytotoxic effect on cerebellar oligodendroglia, e.g. reactive gliosis, (iii) a selective vulnerability of granule cells and Purkinje neurons to MeHg, with the latter that remain unharmed.

Carbon nanotube intramolecular p-i-n junction diodes with symmetric and asymmetric contacts

PubMed Central

Chen, Changxin; Liao, Chenghao; Wei, Liangming; Zhong, Hanqing; He, Rong; Liu, Qinran; Liu, Xiaodong; Lai, Yunfeng; Song, Chuanjuan; Jin, Tiening; Zhang, Yafei

2016-01-01

A p-i-n junction diode based on the selectively doped single-walled carbon nanotube (SWCNT) had been investigated, in which two opposite ends of individual SWCNT channel were doped into the p- and n-type SWCNT respectively while the middle segment of SWCNT was kept as the intrinsic. The symmetric and asymmetric contacts were used to fabricate the p-i-n junction diodes respectively and studied the effect of the contact on the device characteristics. It was shown that a low reverse saturation current of ~20 pA could be achieved by these both diodes. We found that the use of the asymmetric contact can effectively improve the performance of the p-i-n diode, with the rectification ratio enhanced from ~102 for the device with the Au/Au symmetric contact to >103 for the one with the Pd/Al asymmetric contact. The improvement of the device performance by the asymmetric-contact structure was attributed to the decrease of the effective Schottky-barrier height at the contacts under forward bias, increasing the forward current of the diode. The p-i-n diode with asymmetric contact also had a higher rectification ratio than its counterpart before doping the SWCNT channel, which is because that the p-i-n junction in the device decreased the reverse saturated current. PMID:26915400

Peyronie's disease intervention trials: methodological challenges and issues.

PubMed

Müller, Alexander; Mulhall, John P

2009-03-01

Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.

Glucose-6-phosphate dehydrogenase is a regulator of vascular smooth muscle contraction.

PubMed

Gupte, Rakhee S; Ata, Hirotaka; Rawat, Dhawjbahadur; Abe, Madoka; Taylor, Mark S; Ochi, Rikuo; Gupte, Sachin A

2011-02-15

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway and a major source of nicotinamide adenine dinucleotide phosphate reduced (NADPH), which regulates numerous enzymatic (including glutathione reductase and NADPH oxidase that, respectively, generates reduced glutathione and reactive oxygen species) reactions involved in various cellular actions, yet its physiological function is seldom investigated. We, however, recently showed that inhibiting G6PD causes precontracted coronary artery (CA) to relax in an endothelium-derived relaxing factor- and second messenger-independent manner. Here we assessed the role of G6PD in regulating CA contractility. Treating bovine CAs for 20 min with potassium chloride (KCl; 30 mM), amphotericin B (50 μM), or U46619 (100 nM) significantly (p < 0.05) increased both G6PD activity and glucose flux through the pentose phosphate pathway. The effect was Ca(2+) independent, and there was a corresponding increase in protein kinase C (PKC) activity. Activation of G6PD by KCl was blocked by the PKCδ inhibitor rottlerin (10 μM) or by knocking down PKCδ expression using siRNA. Phorbol 12, 13-dibutyrate (10 μM), a PKC activator, significantly increased G6PD phosphorylation and activity, whereas single (S210A, T266A) and double (S210A/T266A) mutations at sites flanking the G6PD active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity. Knocking down G6PD decreased NADPH and reactive oxygen species generation, and reduced KCl-evoked increases in [Ca(2+)](i) and myosin light chain phosphorylation, thereby reducing CA contractility. Similarly, aortas from G6PD-deficient mice developed less KCl/phorbol 12, 13-dibutyrate-evoked force than those from their wild-type littermates. Conversely, overexpression of G6PD augmented KCl-evoked increases in [Ca(2+)](i), thereby augmenting CA contraction. Our findings demonstrate that G6PD activity and NADPH is increased in activated CA in a PKCδ-dependent manner and that G6PD modulates Ca(2+) entry and CA contractions evoked by membrane depolarization.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach.

PubMed

Wang, Liu; Tian, Ye; Chen, Wenmin; Liu, Hong; Zhan, Peng; Li, Dongyue; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

2014-10-06

Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives were rationally designed via structure-based core refining approach, synthesized through the readily accessible synthetic methods and evaluated for their anti-HIV activities in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against the wild-type HIV-1 IIIB. Particularly, compound 7n was the most potent inhibitor against wild-type and K103N/Y181C double resistant mutant strain of HIV-1, possessing EC50 values of 0.02 μM and 7.6 μM, respectively, which were much better than or similar to nevirapine (NVP, EC50 = 0.15 μM, 2.9 μM) and delavirdine (DLV, EC50 = 0.07 μM, >36 μM). Besides, some other compounds, 5b, 7c, 7e, 7f, and 7m, were also endowed with favorable anti-HIV-1 potency (EC50 = 0.07, 0.05, 0.05, 0.07, and 0.05 μM, respectively), which were better than or similar to those of NVP and DLV, suggesting a high potential to further develop this type of bridgehead nitrogen heterocycle as a novel class of NNRTIs with improved antiviral efficacy and resistance profile. The selected compound, 7i, was found moderately inhibitory towards RT (IC50 = 0.39 μM), which was higher than for ETV (IC50 = 0.56 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogues were detailed in this manuscript. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Differential effects of severe vs mild GBA mutations on Parkinson disease.

PubMed

Gan-Or, Ziv; Amshalom, Idan; Kilarski, Laura L; Bar-Shira, Anat; Gana-Weisz, Mali; Mirelman, Anat; Marder, Karen; Bressman, Susan; Giladi, Nir; Orr-Urtreger, Avi

2015-03-03

To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10(-6) for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10(-5)). These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up. © 2015 American Academy of Neurology.

Comparison of response to 2-years' growth hormone treatment in children with isolated growth hormone deficiency, born small for gestational age, idiopathic short stature, or multiple pituitary hormone deficiency: combined results from two large observational studies.

PubMed

Lee, Peter A; Sävendahl, Lars; Oliver, Isabelle; Tauber, Maithé; Blankenstein, Oliver; Ross, Judith; Snajderova, Marta; Rakov, Viatcheslav; Pedersen, Birgitte Tønnes; Christesen, Henrik Thybo

2012-07-12

Few studies have compared the response to growth hormone (GH) treatment between indications such as isolated growth hormone deficiency (IGHD), born small for gestational age (SGA), idiopathic short stature (ISS), and multiple pituitary hormone deficiency (MPHD). The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I) response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark). Analysis of auxologic data from two ongoing prospective observational studies, NordiNet® International Outcomes Study (NordiNet® IOS) and NovoNet®/American Norditropin® Web-enabled Research (ANSWER) Program®. 4,582 children aged <18 years were included: IGHD, n = 3,298; SGA, n = 678; ISS, n = 334; and MPHD, n = 272. After two years' GH treatment, change in height standard deviation score (SDS) was +1.03 in SGA and +0.84 in ISS vs. +0.97 in IGHD (p = 0.047; p < 0.001 vs. IGHD, respectively). Height gain was comparable between IGHD and MPHD. In pre-pubertal children vs. total population, height SDS change after two years was: IGHD, +1.24 vs. +0.97; SGA, +1.17 vs. +1.03; ISS, +1.04 vs. +0.84; and MPHD, +1.16 vs. +0.99 (all p < 0.001). After two years' GH treatment, change in height SDS was greater in SGA and less in ISS, compared with IGHD; the discrepancy in responses may be due to the disease nature or confounders (i.e. age). Height SDS increase was greatest in pre-pubertal children, supporting early treatment initiation to optimize growth outcomes.

Short-term and practice effects of metronome pacing in Parkinson's disease patients with gait freezing while in the 'on' state: randomized single blind evaluation.

PubMed

Cubo, Esther; Leurgans, Sue; Goetz, Christopher G

2004-12-01

In a randomized single blind parallel study, we tested the efficacy of an auditory metronome on walking speed and freezing in Parkinson's disease (PD) patients with freezing gait impairment during their 'on' function. No pharmacological treatment is effective in managing 'on' freezing in PD. Like visual cues that can help overcome freezing, rhythmic auditory pacing may provide cues that help normalize walking pace and overcome freezing. Non-demented PD patients with freezing during their 'on' state walked under two conditions, in randomized order: unassisted walking and walking with the use of an audiocassette with a metronome recording. The walking trials were randomized and gait variables were rated from videotapes by a blinded evaluator. Outcome measures were total walking time (total trial time-total freezing time), which was considered the time over a course of specified length, freezing time, average freeze duration and number of freezes. All outcomes were averaged across trials for each person and then compared across conditions using Signed Rank tests. Twelve non-demented PD patients with a mean age of 65.8 +/- 11.2 years, and mean PD duration of 12.4 +/- 7.3 years were included. The use of the metronome slowed ambulation and increased the total walking time (P < 0.0005) only during the first visit, without affecting any freezing variable. In the nine patients who took the metronome recording home and used it daily for 1 week while walking, freezing remained unimproved. Though advocated in prior publications as a walking aid for PD patients, auditory metronome pacing slows walking and is not a beneficial intervention for freezing during their 'on' periods.

Improvements in Critical Dosimetric Endpoints Using the Contura Multilumen Balloon Breast Brachytherapy Catheter to Deliver Accelerated Partial Breast Irradiation: Preliminary Dosimetric Findings of a Phase IV Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.ed; Vicini, Frank A.; Todor, Dorin A.

2011-01-01

Purpose: Dosimetric findings in patients treated with the Contura multilumen balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional Phase IV registry trial are presented. Methods and Materials: Computed tomography-based three-dimensional planning with dose optimization was performed. For the trial, new ideal dosimetric goals included (1) {>=}95% of the prescribed dose (PD) covering {>=}90% of the target volume, (2) a maximum skin dose {<=}125% of the PD, (3) maximum rib dose {<=}145% of the PD, and (4) the V150 {<=}50 cc and V200 {<=}10 cc. The ability to concurrently achieve these dosimetric goals usingmore » the Contura MLB was analyzed. Results: 144 cases were available for review. Using the MLB, all dosimetric criteria were met in 76% of cases. Evaluating dosimetric criteria individually, 92% and 89% of cases met skin and rib dose criteria, respectively. In 93% of cases, ideal target volume coverage goals were met, and in 99%, dose homogeneity criteria (V150 and V200) were satisfied. When skin thickness was {>=}5 mm to <7 mm, the median skin dose was limited to 120.1% of the PD, and when skin thickness was <5 mm, the median skin dose was 124.2%. When rib distance was <5 mm, median rib dose was reduced to 136.5% of the PD. When skin thickness was <7 mm and distance to rib was <5 mm, median skin and rib doses were jointly limited to 120.6% and 142.1% of the PD, respectively. Conclusion: The Contura MLB catheter provided the means of achieving the imposed higher standard of dosimetric goals in the majority of clinical scenarios encountered.« less

Motor and non-motor symptoms of Parkinson's disease and their impact on quality of life and on different clinical subgroups.

PubMed

Berganzo, K; Tijero, B; González-Eizaguirre, A; Somme, J; Lezcano, E; Gabilondo, I; Fernandez, M; Zarranz, J J; Gómez-Esteban, J C

The aim of the present study is to analyse the influence that motor and non-motor symptoms have on the quality of life (QoL) of patients with Parkinson's disease (PD), and to study the relationship between the two types of symptoms. This cross-sectional study included 103 patients with PD (55 men and 48 women). Quality of life was measured on the PDQ-39 scale. The UPDRS scale (I-IV) was also used, and different items were grouped to analyse the presence of tremor, rigidity, bradykinesia, and axial symptoms. The non-motor symptoms scale (NMSS) was administered to assess non-motor symptoms. We performed correlation analyses between different scales to analyse the influence of motor and non-motor symptoms on QoL. Correlations were observed between the PDQ-39 summary index (PDQ39_SI) and the NMSS (correlation coefficient [cc], 0.56; p<.001), UPDRS III (cc, 0.44; p< .001) and UPDRS IV (cc, 0.37; p<.001) scores. The strongest correlation was between cognitive symptoms and mood. The analysis pointed to a direct relationship between the NMSS score and axial symptoms (cc, 0.384; p<.01), bradykinesia (cc, 0.299; p<.01), and to a lesser extent, rigidity (cc, 0.194; p<.05). No relationship was observed between presence of tremor and the NMSS score. Cognitive symptoms and mood exert the most influence on QoL of patients with PD. We found at least two phenotypes; one with predominantly axial symptoms, with significant involvement of non-motor symptoms, and a tremor-associated phenotype in which these symptoms are less prevalent. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

PubMed

Barker, Mikaela K; Henderson, Amanda M; Naguib, Karimah; Vercauteren, Suzanne M; Devlin, Angela M; Albert, Arianne Y; Bahizire, Esto; Tugirimana, Pierrot L; Akilimali, Pierre Z; Boy, Erick; Green, Tim J; Karakochuk, Crystal D

2017-09-01

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and α-thalassemia deletions. Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population. © 2017 American Society for Nutrition.

DJ-1 deficiency in astrocytes selectively enhances mitochondrial Complex I inhibitor-induced neurotoxicity

PubMed Central

Mullett, Steven J.; Hinkle, David A.

2011-01-01

Parkinson’s disease (PD) brains show evidence of mitochondrial respiratory Complex I deficiency, oxidative stress, and neuronal death. Complex I-inhibiting neurotoxins, such as the pesticide rotenone, cause neuronal death and parkinsonism in animal models. We have previously shown that DJ-1 over-expression in astrocytes augments their capacity to protect neurons against rotenone, that DJ-1 knock-down impairs astrocyte-mediated neuroprotection against rotenone, and that each process involves astrocyte-released factors. To further investigate the mechanism behind these findings, we developed a high-throughput, plate-based bioassay that can be used to assess how genetic manipulations in astrocytes affect their ability to protect co-cultured neurons. We used this bioassay to show that DJ-1 deficiency-induced impairments in astrocyte-mediated neuroprotection occur solely in the presence of pesticides that inhibit Complex I (rotenone, pyridaben, fenazaquin, and fenpyroximate); not with agents that inhibit Complexes II-V, that primarily induce oxidative stress, or that inhibit the proteasome. This is a potentially PD-relevant finding because pesticide exposure is epidemiologically-linked with an increased risk for PD. Further investigations into our model suggested that astrocytic glutathione and heme oxygenase-1 anti-oxidant systems are not central to the neuroprotective mechanism. PMID:21219333

Computation and Experiment: A Powerful Combination to Understand and Predict Reactivities.

PubMed

Sperger, Theresa; Sanhueza, Italo A; Schoenebeck, Franziska

2016-06-21

Computational chemistry has become an established tool for the study of the origins of chemical phenomena and examination of molecular properties. Because of major advances in theory, hardware and software, calculations of molecular processes can nowadays be done with reasonable accuracy on a time-scale that is competitive or even faster than experiments. This overview will highlight broad applications of computational chemistry in the study of organic and organometallic reactivities, including catalytic (NHC-, Cu-, Pd-, Ni-catalyzed) and noncatalytic examples of relevance to organic synthesis. The selected examples showcase the ability of computational chemistry to rationalize and also predict reactivities of broad significance. A particular emphasis is placed on the synergistic interplay of computations and experiments. It is discussed how this approach allows one to (i) gain greater insight than the isolated techniques, (ii) inspire novel chemistry avenues, and (iii) assist in reaction development. Examples of successful rationalizations of reactivities are discussed, including the elucidation of mechanistic features (radical versus polar) and origins of stereoselectivity in NHC-catalyzed reactions as well as the rationalization of ligand effects on ligation states and selectivity in Pd- and Ni-catalyzed transformations. Beyond explaining, the synergistic interplay of computation and experiments is then discussed, showcasing the identification of the likely catalytically active species as a function of ligand, additive, and solvent in Pd-catalyzed cross-coupling reactions. These may vary between mono- or bisphosphine-bound or even anionic Pd complexes in polar media in the presence of coordinating additives. These fundamental studies also inspired avenues in catalysis via dinuclear Pd(I) cycles. Detailed mechanistic studies supporting the direct reactivity of Pd(I)-Pd(I) with aryl halides as well as applications of air-stable dinuclear Pd(I) catalysts are discussed. Additional combined experimental and computational studies are described for alternative metals, these include the discussion of the factors that control C-H versus C-C activation in the aerobic Cu-catalyzed oxidation of ketones, and ligand and additive effects on the nature and favored oxidation state of the active catalyst in Ni-catalyzed trifluoromethylthiolations of aryl chlorides. Examples of successful computational reactivity predictions along with experimental verifications are then presented. This includes the design of a fluorinated ligand [(CF3)2P(CH2)2P(CF3)2] for the challenging reductive elimination of ArCF3 from Pd(II) as well as the guidance of substrate scope (functional group tolerance and suitable leaving group) in the Ni-catalyzed trifluoromethylthiolation of C(sp(2))-O bonds. In summary, this account aims to convey the benefits of integrating computational studies in experimental research to increase understanding of observed phenomena and guide future experiments.

dAcquisition setting optimization and quantitative imaging for 124I studies with the Inveon microPET-CT system.

PubMed

Anizan, Nadège; Carlier, Thomas; Hindorf, Cecilia; Barbet, Jacques; Bardiès, Manuel

2012-02-13

Noninvasive multimodality imaging is essential for preclinical evaluation of the biodistribution and pharmacokinetics of radionuclide therapy and for monitoring tumor response. Imaging with nonstandard positron-emission tomography [PET] isotopes such as 124I is promising in that context but requires accurate activity quantification. The decay scheme of 124I implies an optimization of both acquisition settings and correction processing. The PET scanner investigated in this study was the Inveon PET/CT system dedicated to small animal imaging. The noise equivalent count rate [NECR], the scatter fraction [SF], and the gamma-prompt fraction [GF] were used to determine the best acquisition parameters for mouse- and rat-sized phantoms filled with 124I. An image-quality phantom as specified by the National Electrical Manufacturers Association NU 4-2008 protocol was acquired and reconstructed with two-dimensional filtered back projection, 2D ordered-subset expectation maximization [2DOSEM], and 3DOSEM with maximum a posteriori [3DOSEM/MAP] algorithms, with and without attenuation correction, scatter correction, and gamma-prompt correction (weighted uniform distribution subtraction). Optimal energy windows were established for the rat phantom (390 to 550 keV) and the mouse phantom (400 to 590 keV) by combining the NECR, SF, and GF results. The coincidence time window had no significant impact regarding the NECR curve variation. Activity concentration of 124I measured in the uniform region of an image-quality phantom was underestimated by 9.9% for the 3DOSEM/MAP algorithm with attenuation and scatter corrections, and by 23% with the gamma-prompt correction. Attenuation, scatter, and gamma-prompt corrections decreased the residual signal in the cold insert. The optimal energy windows were chosen with the NECR, SF, and GF evaluation. Nevertheless, an image quality and an activity quantification assessment were required to establish the most suitable reconstruction algorithm and corrections for 124I small animal imaging.

Crytosporidiosis, Isosporiasis, Cyclosporiasis & Sarcocystosis

DTIC Science & Technology

2011-06-01

States and in 30%-50% of patients with AIDS in the developing world .12 The serological prevalence of Cryptosporidium Report Documentation Page Form...species.47 Virchow observed I. belli, the species that infects humans, in 1860. During World War I Isospora belli was detected in the stools of ...3. Xiao L. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol. 2010;124:80-89. 4. Abrahamsen MS, Templeton TJ, Enomoto S

30 CFR 1206.103 - How do I value oil that is not sold under an arm's-length contract?

Code of Federal Regulations, 2011 CFR

2011-07-01

... arm's-length contract? 1206.103 Section 1206.103 Mineral Resources OFFICE OF SURFACE MINING... Oil § 1206.103 How do I value oil that is not sold under an arm's-length contract? This section... affiliates' arm's-length contracts for the purchase or sale of production from the field or area during the...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2012 CFR

2012-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2011 CFR

2011-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2010 CFR

2010-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2013 CFR

2013-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2014 CFR

2014-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non-Small Cell Lung Cancer.

PubMed

Sepesi, Boris; Cuentas, Edwin Parra; Canales, Jaime Rodriguez; Behrens, Carmen; Correa, Arlene M; Vaporciyan, Ara; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar; Swisher, Stephen; Wistuba, Ignacio

2017-01-01

Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis. Statistics included recursive partitioning, univariable, multivariable, and Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87) experienced significantly better overall survival (OS) (P = 0.001) than patients with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N = 24) also experienced significantly better (P = 0.005) OS than patients with >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1 expression in both tumor and macrophages with 5-year OS of 94% (N = 17). Contrarily, patients with high PD-L1 expression in both tumor and macrophages experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in the TIMs was independently associated with survival in multivariable analysis (P = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and in the TIMs seems to be associated with significantly better OS in surgically resected stage I lung cancer. Additional studies are needed to validate PD-L1 as a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2017-05-01

REPORT DATE : May 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May 2017 2. REPORT TYPE Annual 3. DATES ... methods developed for stannylation of the molecule such that it can be effectively radioiodinated with either 131I or 124I. Two paths of synthesis