Portable acetylene frequency references inside sealed hollow-core kagome photonic crystal fiber

A continuous-wave diode laser is stabilized to a near-infrared acetylene transition inside a sealed kagome photonic crystal fiber. Stability and absolute frequency are measured with a frequency comb, and polarization sensitivity is observed

An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy

A plethora of individual candidate biomarkers for predicting PSA relapse in localized prostate cancer (PCa) have been proposed. Combined biomarkers may improve prognostication, and ensuring validation against more clinically relevant endpoints are required. The Australian PCa Research Centre NSW has contributed to numerous studies of molecular biomarkers associated with PSA relapse. In the current study, these biomarkers were re-analysed for PSA relapse, metastatic relapse and PCa death with extended follow-up. Biomarkers of significance were then used to develop a combined prognostic model for clinical outcomes and validated in a large independent cohort. The discovery cohort (n=324) was based on 12 biomarkers with a median follow-up of 16 years. Seven biomarkers were significantly associated with PSA relapse. Three biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was associated with PCa death. In their individual and combinational forms, AZGP1 and Ki67 as a dual BM signature was the most robust predictor of metastatic relapse (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis in the univariable (HR 7.2, 95% CI, 1.6-32; P=0.01) and multivariable analysis (HR 5.4, 95% CI, 1.2-25; P=0.03). The dual biomarker signature marginally improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, P<0.001). Our findings indicate that PSA relapse is not an adequate surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.Alison Y. Zhang, Karen Chiam ... Tina Bianco‐Miotto, Carmela Ricciardelli … Wayne Tilley, Lisa M. Butler ... et al

An analysis of multiple biomarkers to better predict prostate cancer metastasis and death after radical prostatectomy

Abstract 54 Background: Identification of potentially lethal disease at the time of diagnosis with localized prostate cancer (PCa) remains a significant clinical issue despite a plethora of candidate biomarkers. This study evaluates a range of biomarkers previously associated with biochemical relapse (BR) in localized PCa to determine whether a combined expression model can improve detection of clinically significant cases. Methods: The Australian PCa Research Centre NSW has completed 23 studies of molecular biomarkers associated with BR in a well-described localized PCa cohort (n=324, median followup 16 years). 12 studies were excluded due to missing data. Each biomarker was analyzed as a marker for metastatic-free survival (MFS) and prostate cancer specific survival (PCSS) and then used to develop a prognostic model for clinical outcomes incorporating clinico-pathological factors. This model is currently being validated in an independent cohort. Results: The PCa cohort experienced 39 metastatic relapses (12%) and 23 PCa deaths (7%). Of 12 biomarkers (AR, AZPG1, C0S, Cyclin D1a, Cyclin D1b, E6AP, H3K18Ac, H3K4me2, Ki67, p53, PML, SGTA) assessed, only AZGP1 and Ki67 were associated with MFS (HR 2.9, 95% CI, 1.4-5.6; P=0.002, and HR 1.2, 95% CI, 1.0-1.4; P=0.03, respectively) and PCSS (HR 4.2, 95% CI, 1.7-10.5; P=0.002; and HR 1.2, 95% CI, 1.0-1.5; P=0.04, respectively). The combined panel of AZGP1 and Ki67 was an independent predictor of MFS (HR 1.9, 95% CI, 1.1-3.2; P=0.01), and PCSS (HR 3.3, 95% CI, 1.5-7.3; P=0.002) when modeled with known clinicopathological variables. The panel was more robust in predicting MFS and PCSS compared to the individual biomarkers alone and superior to other prognostic models (See table). Data from the validation cohort will be available for the meeting. Conclusions: Our novel signature of AZPG1 and Ki67 improves existing prognostication tools in predicting PCa metastasis and death. [Table: see text] Alison Yan Zhang, Karen Chiam, Ygal Haupt, Stephen B. Fox, Simone Birch, Wayne Tilley, Lisa Butler, Karen E. Knudsen, Christopher Cornstock, Krishan Rasiah, Judith Grogan, Kate Lynette Mahon, Tina Bianco-Miotto, Maret Bohm, Susan M. Henshall, Warick Delprado, Phillip Stricker, Lisa Horvath, James Kenc

Modification of Hematopoietic Stem/Progenitor Cells with CD19-Specific Chimeric Antigen Receptors as a Novel Approach for Cancer Immunotherapy

Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells to specifically target B-lineage malignant cells in animal models and clinical trials, with efficient tumor cell lysis. However, in some cases, there has been insufficient persistence of effector cells, limiting clinical efficacy. We propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel approach to deliver the CD19-specific CAR, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells. Assessments were performed using in vitro myeloid or natural killer (NK) cell differentiation of human HSPCs transduced with lentiviral vectors carrying first and second generations of CD19-specific CAR. Gene transfer did not impair hematopoietic differentiation and cell proliferation when transduced at 1–2 copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive cells, with second-generation CAR including CD28 domains being more efficient in NK cells. Our results provide evidence for the feasibility and efficacy of the modification of HSPC with CAR as a strategy for generating multiple lineages of effector cells for immunotherapy against B-lineage malignancies to augment graft-versus-leukemia activity

Dolerites of Svalbard, north-west Barents Sea Shelf: age, tectonic setting and significance for geotectonic interpretation of the High-Arctic Large Igneous Province

The dolerites of Svalbard are mineralogically and geochemically homogeneous with geochemical features typical of continental within-plate tholeiites. Their geochemistry is similar to tholeiites belonging to a bimodal suite defined as the High-Arctic Large Igneous Province (HALIP). K–Ar dating of numerous dolerites sampled from many locations across Svalbard define a narrow time span of this magmatism from 125.5±3.6 to 78.3±2.6 Mya. Discrete peaks of intensive activity occurred at 115.3, 100.8, 91.3 and 78.5 Mya corresponding to (1) breakup of the continental crust and formation of an initial rift as a result of mantle plume activity, located in the southern part of the Alpha Ridge; (2) magmatic activity related to spreading along the Alpha Ridge that led to the development of the initial oceanic crust and (3) continuation of spreading along the Alpha Ridge and termination of magmatic activity related to HALIP (last two peaks at 91.3 and 78.5 Mya)