OBJECTIVES: There is a significant unmet need for a blood test with adequate sensitivity to detect colorectal cancer (CRC) and adenomas. We describe a novel circulating tumor cell (CTC) platform to capture colorectal epithelial cells associated with CRC and adenomas. METHODS: Blood was collected from 667 Taiwanese adults from 2012 to 2018 before a colonoscopy. The study population included healthy control subjects, patients with adenomas, and those with stage I–IV CRC. CTCs were isolated from the blood using the CellMax platform. The isolated cells were enumerated, and an algorithm was used to determine the likelihood of detecting adenoma or CRC. Nominal and ordinal logistic regression demonstrated that CTC counts could identify adenomas and CRC, including CRC stage. RESULTS: The CellMax test demonstrated a significant association between CTC counts and worsening disease status (Cuzick's P value < 0.0001) with respect to the adenoma-carcinoma sequence. The test showed high specificity (86%) and sensitivity across all CRC stages (95%) and adenomatous lesions (79%). The area under the curve was 0.940 and 0.868 for the detection of CRC and adenomas, respectively. DISCUSSION: The blood-based CTC platform demonstrated high sensitivity in detecting adenomas and CRC, as well as reasonable specificity in an enriched symptomatic patient population. TRANSLATIONAL IMPACT: If these results are reproduced in an average risk population, this test has the potential to prevent CRC by improving patient compliance and detecting precancerous adenomas, eventually reducing CRC mortality.
Using x-ray and ultraviolet photoelectron spectroscopy (XPS and UPS), we have studied the formation of metal/organic interfaces in organic electroluminescent devices. Oligo(p-phenylenevinylenes) (OPV) and tris-(8-hydroxyquinoline)aluminum (Alq3) were used as the organic materials and Ca was used as the metallic layer. Interfaces are formed differently by depositing organic layer on Ca and Ca on organic substrate. For Ca/OPV, UPS revealed a clear evidence for interface state formation upon Ca deposition. The evolution of XPS core level peak as a function of Ca layer thickness was consistent with the energy level bending picture. The XPS and UPS spectra for OPV/Ca as a function of organic layer thickness also confirmed the energy level bending. The data obtained allowed us to deduce the energy level diagram near the interface. Similar data for Alq3/Ca indicated that no electron injection barrier exists at this interface if the Alq3 optical band gap in the literature was used for estimating the energy position of the lowest unoccupied state.
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Photoconductive and photovoltaic properties of Al/PPV/ITO sandwich devices were investigated by measuring steady-state photocurrents resulting from illumination through the Al electrode. A built-in potential (Vbi) was detected at the Al/PPV interface. The voltage dependence of the photocurrent in the vicinity of Vbi was measured at 1 mW/cm2 of incident illumination to give an open-circuit voltage and a short-circuit current of 1.2 V and 6 × 10−7 A/cm2, respectively. The dependences of the short-circuit current on excitation wavelength and illumination intensity are presented and the C-V characteristics of the Al/PPV interface are analyzed. The quantum collection efficiency decreased from 5% to 1% as the intensity of illumination increased from 10−5 to 1 mW/cm2. The photovoltaic conversion power efficiency was about 0.07% for intensities approaching 1 mW/cm2. The Vbi value was accounted for by surface band-bending at the Al/PPV interface.
Abstract We report on our recent x‐ray photoemission spectroscopy investigations of the interface formation of metals with poly( p ‐phenylene vinylene) (PPV) prepared under various conditions. We have found that during deposition the metal reacts with residual hydroxyl groups in the polymer. In addition, we have found that Schottky barrier formation and the associated band bending depend strongly on surface preparation. In the case of Al deposition, samples converted in situ , containing 5% surface oxygen, show band bending that depends on the thickness of the metal overlayer, with effects arising after as little as 1 Å of metal. On the other hand, a sample converted ex situ , with 10% surface oxygen, is insensitive to aluminium deposition. We feel that surface impurities and adsorbed species may delay Schottky barrier formation by acting as a buffer layer that prevents the PPV substrate from interacting with the growing layer of Al. By contrast, the Ca/PPV surface exhibits delayed band bending, with strong interactions between surface oxygen and Ca. Our results indicate that band bending at the metal/PPV interface is governed by the metallicity of the metal overlayer, which itself is influenced by the interface reaction of the deposited metal with the PPV substrate or the surface residual impurities. Finally, the degree of band bending observed did not correlate directly with the differences in work functions between the metals and PPV.
We demonstrate that the gap states at the interface of Ca and a phenylene vinylene oligomer thin film are responsible for the dramatic quenching of its photoluminescence (PL). Upon oxidation of the Ca layer, the midgap states are removed, and the PL intensity recovers. From the cumulative Ca deposition and oxidation study, a 30 \AA{} Ca oxide layer between the oligomer and the Ca metal prevents PL quenching due to metal induced midgap states. The implications of these results in the design and operation of organic light-emitting devices are discussed.
1555 Background: Colonoscopic polypectomy is the primary reason for declining colorectal cancer incidence and mortality. Epidemiological evidence has ordered the timing and risk of pre-cancerous adenomas, localized and invasive cancer along a 7-10 year continuum. The increased size and number of index polyps are correlated with an increased probability of progression to cancer and informs surveillance colonoscopies. Methods: A single-center, IRB-approved, prospective, blinded study was conducted at the VA Palo Alto Health Care System. Results for 354 patients with no prior diagnosis of CRC who were scheduled for colonoscopy are presented. Indications for colonoscopy were 86% asymptomatic and 14% with symptoms or positive-FIT. Patients had blood drawn immediately prior to colonoscopy. The test analyzes three biomarkers: circulating gastrointestinal epithelial cells (CEC), validated somatic mutations, and methylation (SEPTIN9) of cell-free DNA and uses incident risk to calculate a CMx Score, scaled from 0 to 100. Multivariate regression methods were used to assess the degree of association between the pre-defined CMx Scores and polyp sizes and number, adjusting for both DNA mutation and DNA methylation status. Results: There is a significant association between CMx Scores and polyp size (F value = 5.80, p-value = 0.017). DNA mutation (F value = 1.29, p-value = 0.263) and methylation status (F value = 0.34, p-value = 0.560) were non-significant. Similarly, there is a significant association between CMx Scores and number of polyps (F value = 23.71, p-value < 0.0001). Again, DNA mutation (F value = 1.57, p-value = 0.210) and methylation status (F value = 1.34, p-value = 0.248) were non-significant. These results suggest that CMx Scores, which incorporate CEC, are providing predictive information of polyp sizes and number above and beyond DNA mutation and methylation status alone. Conclusions: A novel noninvasive multimodal blood-based assay that analyzes cell-free DNA for somatic mutations and methylation, CEC and integrates SEER incidence risk is significantly associated with polyp size and number. The opportunity to track progression and potentially inform colonoscopy interval is notable. [Table: see text]
50 Background: Many of the 50,000 annual colorectal cancer (CRC) deaths can be attributed to 1/3 eligible Americans not following screening guidelines or approximately 1/2 of the population not adherent to the follow-up post-polypectomy guidelines. The new understanding of the natural history and shared etiology of adenomas and CRC inform integration of clinically relevant biomarkers. The two objectives of CRC screening and surveillance are early detection to improve survival and prevention of CRC through removal of adenomas using colonoscopy. Adenomas account for 98% of actionable colonoscopies. Stool tests have low sensitivity for advanced adenomas (AA, 24-42%). Methods: A prospective, blinded study was conducted at the VA Palo Alto Health Care System. Patients had blood drawn prior to colonoscopy. The test analyzes two biomarkers: circulating gastrointestinal epithelial cells and somatic mutations of cell-free DNA. The probability of advanced neoplasia was obtained by ordinal/nominal logistic regression methods together with SEER-incidence rate and prior history of AA on a training set of 346 subjects. The cutpoint for the quantitative score was fixed and the remaining 112 subjects were tested. Results: Interim results for 458 patients with no prior diagnosis of colorectal cancer (CRC) are presented. The cohort included both screening (239) and surveillance (219) subjects. Indications for colonoscopy were 86% asymptomatic and 14% with symptoms or positive-FIT. Balanced distribution of roughly 3/4 th subjects in each disease category were randomly selected for training and algorithm development and the remaining 1/4 th subjects were used for validation. A cutpoint was selected to obtain a test specificity (non-neoplastic finding or negative colonoscopy) of 90% resulting in a sensitivity of 100% and 80.0% for detection of CRC and advanced neoplasia (AN = CRC+AA), respectively, on the training subjects. The area under the ROC curve is 0.91. Validation using the fixed cutpoint and 112 test subjects achieved 91.4% specificity and 100% and 75.0% sensitivity for CRC and AN. Conclusions: This blood test has high sensitivity for colorectal advanced neoplasia while retaining high specificity. The quantitative nature of the score has the potential to enable stratification of patients for screening or post-polypectomy surveillance colonoscopy. [Table: see text]
Abstract Reservoir simulation for a full field heterogeneous model with millions of grid blocks demands significant computational time so improving the computational efficiency becomes crucial in designing a reservoir simulator. Graphics Processing Unit (GPU), a new high-profile parallel processor with hundreds of microprocessors, stands out in parallel simulation because of its efficient power utilization and high computational efficiency. Also, its cost is relatively low, making large-scale parallel reservoir simulation possible for most of desktop users. In this paper several GPU-based parallel preconditoners, in conjunction with a new GPU-based GMRES algorithm, are proposed and coupled with an in-house black-oil simulator to speedup reservoir simulation. In particular, massively parallel ILU preconditioners (ILU(0), ILUT, block ILU(0), block ILUT), which are usually regarded as data dependence and highly sequential preconditioners, are developed on GPUs. In the numerical experiments performed, the SPE 10 problem, a 3D heterogeneous benchmark model with over one million grid blocks, is selected to test the speedup of our GPU solver and preconditioners. On the state-of-the-art CPU and GPU platform, the new GPU implementation can achieve a speedup of over eight times in solving linear systems arising from this SPE 10 problem compared with the CPU based serial solver. Moreover, our GPU solver is successfully coupled with the in-house black-oil simulator to test the performance of the whole parallel simulation process, with a speedup of about six times. The excellent speedup and accurate results demonstrate that the GPU-based parallel linear solver and preconditioners have the great potential in parallel reservoir simulation.
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