Background
We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with
99m
Tc-methylene ...diphosphonate (MDP) or
99m
Tc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis.
Methods
Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a “surrogate truth” reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake.
Results
On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUV
c
) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUV
c
> 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUV
c
> 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUV
c
> 8.61 (xQ) or > 13.4 (xB).
Conclusion
The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.
Bone cells' early responses to estrogen and mechanical strain were investigated in the ROS 17/2.8 cell line. Immunoblotting with antiphosphorylated estrogen receptor α (ER‐α) antibody showed that ...when these cells were exposed for 10 minutes to estrogen (10−8 M) or a single period of cyclic dynamic strain (peak 3400 μϵ, 1Hz, 600 cycles), there was an increase in the intensity of a 66‐kDa band, indicating phosphorylation of ser122 in the amino terminus of ER‐α. Increased phosphorylation was detected within 5 minutes of exposure to estrogen and 5 minutes after the end of the period of strain. Estrogen and strain also activated the mitogen‐activated protein kinase (MAPK) family member extracellular regulated kinase‐1 (ERK‐1). Increases in ERK activation coincided with increased ER‐α phosphorylation. Activation of ERK‐1 and the phosphorylation of ER‐α, by both estrogen and strain, were prevented by the MAP kinase kinase (MEK) inhibitor U0126 and the protein kinase A (PKA) inhibitor (PKI). These data support previous suggestions that resident bone cells' early responses to strain and estrogen share a common pathway, which involves ER‐α. This pathway also appears to involve PKA and ERK‐mediated phosphorylation of ser122 within the amino terminus of ER‐α. Reduced availability of this pathway when estrogen levels are reduced could explain diminished effectiveness of mechanically related control of bone architecture after the menopause.
Background: Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. ...Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulosecontaining materials, is an attractive candidate as a biomarker of wood smoke exposure. Objectives: In the present study, Balb/c mice and children were assessed for LG in urine to determine its feasibility as a biomarker. Methods: We performed urinary detection of LG by gas chromatography/mass spectrometry after intranasal instillations of LG or concentrated PM (mice) or biomass exposure (mice or humans). Results: After instillation, we recovered most of the LG within the first 4 hr. Experiments using glucose instillation proved the specificity of our system, and instillation of concentrated PM from wood smoke, ambient air, and diesel exhaust supported a connection between wood smoke and LG. In addition, LG was detected in the urine of mice exposed to wood smoke. Finally, a pilot human study proved our ability to detect LG in urine of children. Conclusions: These results demonstrate that LG in the lungs is detectable in the urine of both mice and humans and that it is a good candidate as a biomarker of exposure to biomass smoke.
A search is presented for the four-body decay B0→ppp¯p¯ in a sample of 471 million BB¯ pairs collected with the BABAR detector, operated at the SLAC PEP-II asymmetric-energy e+e− collider. The ...center-of-mass energy is 10.58 GeV. From a fit to the distribution of the energy-substituted mass mES, the branching fraction B(B0→ppp¯p¯)=(1.1±0.5±0.2)×10−7 is extracted, where the first uncertainty is statistical and the second is systematic. The significance of the signal, including the systematic uncertainty, is 2.9 standard deviations. The upper limit on the branching fraction is determined to be 2.0×10−7 at 90% confidence level.
Controlling phase separation in polymer systems has shown significant promise in combining properties of different components into an integrated polymer system. In this work, we investigate the ...effect of photoinduced phase separation on polymer morphology and properties in hybrid radical/cationic systems composed of butyl acrylate (BA) and difunctional oxetane (DOX). We show that the irradiation intensity has a significant effect on the formation of phase-separated domains. By increasing the irradiation intensity at fixed co-monomer composition, the morphology changes from one with a continuous soft BA domain to one with co-continuous BA (soft) and DOX (hard) domains. At higher irradiation intensity, the domain size of each phase is decreased because of fast photopolymerization, which significantly limits monomer/polymer diffusion. The smaller domain size enhances the flexibility and strength of the phase-separated polymers. On the other hand, the irradiation intensity has little to no effect on the polymer structure or properties for systems that do not phase-separate. Dynamic mechanical analysis demonstrates that phase separation associated with higher irradiation intensity during cure contributes to a 40-fold increase in toughness and up to fivefold higher elongation at break. This behavior is attributed to the formation of polymers with co-continuous hard/soft domains and decreased domain size. This study demonstrates that the morphology and properties of photoinduced phase-separated materials can be controlled by altering the initiation irradiation intensity for hybrid radical/cationic materials.
A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at ...10.58 GeV, using data collected in the BABAR experiment. Data corresponding to an integrated luminosity of 398 fb^{-1} are analyzed. No evidence for a signal is observed. Branching fraction upper limits in the range from 10^{-7}-10^{-5} are obtained at 90% confidence level for masses of 1.0<m_{ψ_{D}}<4.3 GeV/c^{2}. The result is also reinterpreted to provide the first limits on a supersymmetric model with R-parity violation and a light neutralino.
A virtual or in silicoscreening approach makes it much easier to identify the molecular structure that best combines efficacy for a specific task with safety and minimum environmental or health ...impacts. In this approach, software is used to generate a larger number of possible molecular structures and then to use QSARs (quantitative structure-activity relationships) to predict properties related to performance, safety, health and environmental impact. The structures are then given scores on criteria (such as flash point or toxicity) and an overall score. The method identifies compounds that have high scores for the 3 performance criteria and 7 health, safety, and environmental criteria. This method allows for larger-scale and faster screening than can be performed using human intellect and a benchtop approach. The success of this approach is demonstrated by its application to the identification of new and possibly greener switchable-hydrophilicity solvents (SHS). Three SHS were identified using this method. This approach to molecular design is entirely modular and can be applied to the design of almost any type of chemical. However, limitations of the method include the fact that it does not take into consideration the health and environmental costs of manufacturing the chemical.
A mechanistic hypothesis is presented for how water-soluble guanidinium-rich transporters attached to small cargoes (MW ca. <3000) can migrate across the non-polar lipid membrane of a cell and enter ...the cytosol. Positively charged and water-soluble, arginine oligomers can associate with negatively charged, bidentate hydrogen bond acceptor groups of endogenous membrane constituents, leading to the formation of membrane-soluble ion pair complexes. The resultant less polar, ion pair complexes partition into the lipid bilayer and migrate in a direction, and with a rate, influenced by the membrane potential. The complex dissociates on the inner leaf of the membrane and the transporter conjugate enters the cytosol. This mechanism could also be involved in the translocation of guanidinium-rich molecules that are endocytosed due to their size or the conditions of the assay, across the endosomal membrane.
Migratory animals are threatened by human-induced global change. However, little is known about how stopover habitat, essential for refuelling during migration, affects the population dynamics of ...migratory species. Using 20 years of continent-wide citizen science data, we assess population trends of ten shorebird taxa that refuel on Yellow Sea tidal mudflats, a threatened ecosystem that has shrunk by >65% in recent decades. Seven of the taxa declined at rates of up to 8% per year. Taxa with the greatest reliance on the Yellow Sea as a stopover site showed the greatest declines, whereas those that stop primarily in other regions had slowly declining or stable populations. Decline rate was unaffected by shared evolutionary history among taxa and was not predicted by migration distance, breeding range size, non-breeding location, generation time or body size. These results suggest that changes in stopover habitat can severely limit migratory populations.
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