Advances in the Assessment of Habitat Fragmentation and Protection in the NAFO Regulatory Area

NAFO has used kernel density analyses to identify VMEs dominated by large-sized sponges, sea pens, small and large gorgonian corals, erect bryozoans, sea squirts (Boltenia ovifera), and black corals. That analysis generates polygons of significant concentrations of biomass for each VME indicator which are spread across the spatial domain of the NAFO fishing footprint. There is potential for bottom contact fishing to induce changes in both the amount and configuration of habitat (e.g., decreased polygon size, increased polygon isolation, and increased edge area) through direct and indirect impacts, and it is unknown to what degree such changes may already have taken place given the long fishing history of the area. In the Report of the 13th Meeting of the NAFO Scientific Council Working Group on Ecosystem Science and Assessment (WGE-ESA), preliminary work on assessing and monitoring habitat fragmentation was presented. Here we continue that work by recalculating the indices after removing connections that are not identified through particle tracking models. We have reanalyzed the nearest neighbour distances and PX, a proximity index, for the VME polygons noted above, and for the new closed areas that will come into effect 1 January 2022. We show that PX when applied to the new closures appears sensitive to their spatial configuration which bodes will for the ability of this index to identify habitat fragmentation in the future, brought about through fishing activities and/or natural disturbances.Versión del edito

Expression of poly-ADP-ribose polymerase (PARP) in endometrial adenocarcinoma: Prognostic potential

© 2020 Background: In the United States endometrial carcinoma is the most common female gynecologic malignancy. An average of more than 60,000 new cases of endometrial carcinomas have been diagnosed yearly over the past 5 years, with a higher incidence occurring in the central Appalachian states of Ohio and West Virginia. In the U.S., the national average of newly diagnosed endometrial carcinomas is 26.8 in every 100,000 women, while in the states of Ohio and West Virginia the average is 30.5 and 31.1 in every 100,000 women, respectively. This notable increase in the incidence of endometrial carcinomas may be due a variety of elevated risk factors including but not limited to: tobacco use, obesity, and genetic predisposition of the predominant demographic. The American Cancer Society estimates that approximately 55,000 new cases of endometrial carcinoma will be diagnosed in 2020 yet, this disease is widely considered understudied and under-represented in mainstream cancer research circles. Methods: The aim of this study was to quantitate the co-expression of two DNA repair proteins poly-ADP-ribose polymerase 1 and 2 (Parp-1 and Parp-2) by enzyme- linked immuno-sorbent assay (ELISA) in 60 endometrioid endometrial tumor samples and compare their expression to matched non-malignant endometrial tissue from the same corresponding donors from central Appalachia. Results: We found that Parp-1 was significantly overexpressed in endometrial carcinoma relative to corresponding normal tissue. This overexpression implicates Parp inhibition therapy as a possible treatment for the disease. Our results also found a protective effect of native Parp-2 expression in non-malignant endometrial tissue with each 1 ng/mL increase in PARP-2 concentration in normal tissue was associated with a 10 % reduction in the hazard of tumor progression (HR = 0.90; p = 0.039) and a 21 % reduction in the hazard of death (HR = 0.79; p = 0.044). Conclusions: This study demonstrated the over-expression of the druggable target Parp-1 in endometrial adenocarcinoma and observed a strong negative correlation of native Parp-2 expression and disease progression via the quantification of the Parp proteins using enzyme- linked immuno-sorbent assay (ELISA) assays

Clinical relevance of cancer stem cell chemotherapeutic assay for recurrent ovarian cancer

© 2020 Introduction: Disease recurrence and progression of ovarian cancer is common with the development of platinum-resistant or refractory disease. This is due in large part to the presence of chemo-resistant cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. We developed a CSCs drug cytotoxicity assay (ChemoID) to identify the most effective chemotherapy treatment from a panel of FDA approved chemotherapies. Methods: Ascites and pleural fluid samples were collected under physician order from 45 consecutive patients affected by 3rd-5th relapsed ovarian cancer. Test results from the assay were used to treat patients with the highest cell kill drugs, taking into consideration their health status and using dose reductions, as needed. A retrospective chart review of CT and PET scans was used to determine patients\u27 outcomes for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Results: We observed that recurrent ovarian cancer patients treated with high-cell kill chemotherapy agents guided by the CSCs drug response assay had an improvement in the median PFS corresponding to 5.4 months (3rd relapse), 3.6 months (4th relapse), and 3.9 months (5th relapse) when compared to historical data. Additionally, we observed that ovarian cancer patients identified as non-responders by the CSC drug response assay had 30 times the hazard of death compared to those women that were identified as responders with respective median survivals of 6 months vs. 13 months. We also found that ChemoID treated patients on average had an incremental cost-effectiveness ratio (ICER) between -$18,421 and$7,241 per life-year saved (LYS). Conclusions: This study demonstrated improved PFS and OS for recurrent ovarian cancer patients treated with assay-guided chemotherapies while decreasing the cost of treatment

Kernel Density Surface Modelling as a Means to Identify Significant Concentrations of Vulnerable Marine Ecosystem Indicators

The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME) from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO) produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE) to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO) Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify ‘‘significant concentrations’’ of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores), and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here and elsewhere.Versión del editor4,411

Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series

© 2020 BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21–63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0–10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. Importance of the Study: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp\u27s protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient\u27s derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1–10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies

Comparative Effectiveness of Tumor Response Assessment Methods: Standard of Care Versus Computer-Assisted Response Evaluation

Purpose To compare the effectiveness of metastatic tumor response evaluation with computed tomography using computer-assisted versus manual methods. Materials and Methods In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study, 11 readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria by using paired baseline and initial post-therapy computed tomography studies from 20 randomly selected patients with metastatic renal cell carcinoma who were treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard of care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data and image archiving. A crossover design, patient randomization, and 2-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. Results The standard-of-care method, on average, was associated with one or more errors in 30.5% (6.1 of 20) of patients, whereas CARE had a 0.0% (0.0 of 20) error rate (P < .001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range, 1 to 3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 minutes v 13.1 minutes; P < .001). Conclusion CARE reduced errors and time of evaluation, which indicated better overall effectiveness than manual tumor response evaluation methods that are the current standard of care

Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival of Patients With Recurrent Glioblastoma in a Randomized Trial

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world

Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms

[EN] We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.This work was supported by the Spanish Ministry of Economy and Innovation (MINECO) through Project TEC2016-80976-R. NJ and SJ acknowledge financial support from Generalitat Valenciana through grants APOSTD/2017/042, ACIF/2017/045 and GV/2018/11. FC acknowledges financial support from Agencia Valenciana de la Innovacio through grant INNCON00/18/9 and European Regional Development Fund (IDIFEDER/2018/022).Jiménez-Gambín, S.; Jimenez, N.; Benlloch Baviera, JM.; Camarena Femenia, F. (2019). 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