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Detection of geophysical signatures associated with a geologic event, such as a volcanic eruption, is key to understanding the underlying physical processes and making an accurate hazard assessment. Magma reservoirs are the main repositories for eruptible magma, and understanding them requires the ability to detect and interpret changes in the magmatic system from surface measurements. Traditionally, monitoring for these changes has been done with seismic and geodetic approaches, both of which require dynamic ‘active’ changes within the magmatic system. Seismic monitoring relies on the number and location of earthquakes, to indicate magma migrating within the magmatic system. In contrast, geodetic efforts rely on identifying ground inflation events which have traditionally been interpreted to represent recharge of magma from a deep parental source into shallower crustal reservoirs. Neither of these techniques is sensitive to the petrology or temperature of the magma though. Thus, additional monitoring techniques able to detect ‘static’ phase changes in the evolving magma and the thermal structure of the magma reservoir are needed. The magnetotelluric method, measures subsurface electrical properties and is sensitive to both ‘magma on the move’ and these petrological changes that occur within the magma reservoir itself. Using Mount St Helens where a detailed magnetotelluric survey was completed during the most recent dome building eruptive phase 2005-06, and is now in a period of quiescence, we compare the original measurements from 2005-06 to repeated measurements in the same locations in 2022 to develop the temporal analysis approaches required for monitoring application. In addition to the repeat campaign we have deployed 4 long-term monitoring stations with continuous data observation and telemetry to local servers. First, qualitative, comparisons of the data from different time periods indicate some significant changes in subsurface conductivity. We will present an overview of the newly acquired data and the monitoring setup and discuss where the most significant changes occur.

The initiation of androgen-deprivation therapy (ADT) induces susceptibilities in prostate cancer cells that make them vulnerable to synergistic treatment and enhanced cell death. Senescence results in cell-cycle arrest, but cells remain viable. In this study, we investigated the mechanisms by which prostate cancer cells undergo senescence in response to ADT, and determined whether an FDA-approved antidiabetic drug metformin has a synergistic effect with ADT in prostate cancer both in vitro and in vivo. Our results show that longer term exposure to ADT induced senescence associated with p16INK4a and/or p27kip2 induction. The activation of PI3K/AKT and inactivation of AMPK in senescent cells resulted in mTORC1 activation. In addition, the antiapoptotic protein XIAP expression was increased in response to ADT. The addition of metformin following ADT induced apoptosis, attenuated mTOR activation, reduced senescent cell number in vitro, and inhibited tumor growth in prostate cancer patient-derived xenograft models. This study suggests that combining ADT and metformin may be a feasible therapeutic approach to remove persistent prostate cancer cells after ADT.

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The initiation of androgen-deprivation therapy (ADT) induces susceptibilities in prostate cancer cells that make them vulnerable to synergistic treatment and enhanced cell death. Senescence results in cell-cycle arrest, but cells remain viable. In this study, we investigated the mechanisms by which prostate cancer cells undergo senescence in response to ADT, and determined whether an FDA-approved antidiabetic drug metformin has a synergistic effect with ADT in prostate cancer both in vitro and in vivo. Our results show that longer term exposure to ADT induced senescence associated with p16INK4a and/or p27kip2 induction. The activation of PI3K/AKT and inactivation of AMPK in senescent cells resulted in mTORC1 activation. In addition, the antiapoptotic protein XIAP expression was increased in response to ADT. The addition of metformin following ADT induced apoptosis, attenuated mTOR activation, reduced senescent cell number in vitro, and inhibited tumor growth in prostate cancer patient-derived xenograft models. This study suggests that combining ADT and metformin may be a feasible therapeutic approach to remove persistent prostate cancer cells after ADT.

While much of the workflow for geophysical data processing and analysis is automated, final quality assurance typically requires the decisions of skilled human analysts and interpreters. The quality and reliability of geophysical inverse models depends directly on the effectiveness of input data. The influence of spurious data on derived data products used in the inversion has been reduced by this effectiveness. Failure to identify and mitigate bias in data products can lead to costly errors. By applying supervised machine learning (ML), a neural network can be trained to recognize features in data that a human domain expert would identify as characteristic of poor data quality. In this study, we use magnetotelluric (MT) data as an example of a geophysical data set appropriate for such a training exercise. While MT data are used to estimate the resistivity structure of the subsurface, the concepts we discuss are universal to seismic, potential fields, and other geophysical data sets. We train a neural network, pyMAGIQ (Python-based magnetotelluric impedance qualifier), with multiple hidden layers and demonstrate that it successfully generates the nonlinear mapping function required to assess the quality of MT data. The training set is a large database of frequency-domain MT impedance tensors from the National Science Foundation-funded EarthScope MT project. A human-assigned quality index is associated with each impedance. We apply pyMAGIQ to unrated MT data from the United States and Canada and confirm that the ML-assigned quality factors are consistent with those assigned by trained human operators. We also apply sensitivity analysis to the trained neural network. This reveals that the human- and ML-assigned data quality index depends on the magnitude of the confidence limits on (1) the phases and (2) the continuity of the apparent resistivities and phases with respect to frequency.

BACKGROUND Exocrine Pancreatic Insufficiency (EPI) is a disorder caused by multiple etiologies leading to decreased pancreatic function. EPI presents with nonspecific symptoms and is largely unknown by the public, making EPI a difficult diagnosis. Awareness campaigns for EPI have been supported by AbbVie, a pharmaceutical company that manufactures the only available treatment for EPI (Creon), but it is unknown whether the campaigns have led to increased EPI awareness. OBJECTIVE We sought to assess changes in EPI awareness over time evidenced by internet searches in the United States. Findings from this study may reveal how awareness campaigns, such as radio ads, have influenced the public awareness of EPI. METHODS Google Trends is a popular and validated infodemiology tool.1 Using Google Trends allows for real-time data analysis that reflects public awareness over time, which is reported as relative search volume (RSV). RSV represents a relative percent change in Google searches for selected terms over a given time period. We observed trends for the term “Exocrine Pancreatic Insufficiency” over the date range January 1, 2011 to October 1, 2021 to capture search trends before and after AbbVie’s advertisement campaigns. We used an ARIMA model to forecast expected search volumes based on search data before Abbvie’s campaign for Creon. RESULTS We found many statistically significant increases in RSV since the launch of AbbVie’s campaign, with peak RSV occurring in August and September of 2021, together representing a 122.5% increase compared to expected values (P CONCLUSIONS Results from our study suggest that the US public interest in EPI has increased steadily over the last 5 years compared to the 5 years prior, possibly reflecting the success of Abbvie advertisement campaigns. AbbVie has steadily increased advertisement spending since 2016, with reported net revenue for Creon following a similar trend. The success of AbbVie’s radio, TV, and internet advertisements may have served to educate patients on EPI, prompting them to search Google for more information or to find a physician who could evaluate them for EPI. Increasing awareness may support quicker and more accurate diagnosis of EPI.

Persistent pulmonary hypertension of the newborn (PPHN) is a failure of pulmonary vascular resistance to decline at birth rapidly. One principal mechanism implicated in PPHN development is mitochondrial oxidative stress. Expression and activity of mitochondrial SOD2 (superoxide dismutase) are decreased in PPHN; however, the mechanism remains unknown. Recently, OLA1 (Obg-like ATPase-1) was shown to act as a critical regulator of proteins controlling cell response to stress including Hsp70, an obligate chaperone for SOD2. Here, we investigated whether OLA1 is causally linked to PPHN. Compared with controls, SOD2 expression is reduced in distal-pulmonary arteries (PAs) from patients with PPHN and fetal-lamb models. Disruptions of the SOD2 gene reproduced PPHN phenotypes, manifested by elevated right ventricular systolic pressure, PA-endothelial cells apoptosis, and PA-smooth muscle cells proliferation. Analyses of SOD2 protein dynamics revealed higher ubiquitinated-SOD2 protein levels in PPHN-lambs, suggesting dysregulated protein ubiquitination. OLA1 controls multiple proteostatic mechanisms and is overexpressed in response to stress. We demonstrated that OLA1 acts as a molecular chaperone, and its activity is induced by stress. Strikingly, OLA1 expression is decreased in distal-PAs from PPHN-patients and fetal-lambs. OLA1 deficiency enhanced CHIP affinity for Hsp70-SOD2 complexes, facilitating SOD2 degradation. Consequently, mitochondrial H 2 O 2 formation is impaired, leading to XIAP (X-linked inhibitor of apoptosis) overexpression that suppresses caspase activity in PA-smooth muscle cells, allowing them to survive and proliferate, contributing to PA remodeling. In-vivo, o la1 −/− downregulated SOD2 expression, induced distal-PA remodeling, and right ventricular hypertrophy. We conclude that decreased OLA1 expression accounts for SOD2 downregulation and, therefore, a therapeutic target in PPHN treatments.

Subduction of hydrated oceanic lithosphere can carry water deep into the Earth, with important consequences for a range of tectonic and magmatic processes. Most fluid is released at relatively shallow depths in the forearc where it is thought to play a critical role in controlling mechanical properties and seismic behavior of the subduction megathrust. Here we present results from three-dimensional inversion of nearly 400 long-period magnetotelluric sites, including 64 offshore, to provide new insights into the distribution of fluids in the forearc of the Cascadia subduction zone. Our amphibious dataset provides new constraints on the geometry of the electrically resistive Siletzia terrane, a thickened section of oceanic crust accreted to North America in the Eocene, and the conductive accretionary complex, which is being underthrust all along the margin. Fluids accumulate, over time-scales likely exceeding 1 My, above the plate interface in metasedimentary units, while the mafic rocks of Siletzia remain dry. Fluids in metasediments tend to peak at fixed slab-depths of 17.5 and 30 km, suggesting control by metamorphic processes, but also concentrate around the edges of Siletzia, suggesting that this mafic block is impermeable, with dehydration fluids escaping up-dip along the megathrust. Our results demonstrate that lithology of the overriding crust can play a critical role in controlling fluid transport and sequestration in a subduction zone, with potentially important implications for mechanical properties.

A novel low loss E-plane Substrate Integrated Waveguide narrow wall slot antenna is proposed in this paper. The antenna operating frequency is centered at 18GHz and is built by soldering four printed circuit boards together as well as two copper sheets, one on the bottom that is solid and one on the top with slots cut in it. A waveguide has both vertical and horizontal current, copper strips are used for the horizontal current and plated vias are used for the vertical current. A short is placed at the end using the same method to create a standing wave.

We present the discovery and optical follow-up of the faintest supernova-like transient known. The event (SN 2019gsc) was discovered in a star-forming host at 53\,Mpc by ATLAS. A detailed multi-colour light curve was gathered with Pan-STARRS1 and follow-up spectroscopy was obtained with the NOT and Gemini-North. The spectra near maximum light show narrow features at low velocities of 3000 to 4000 km s$^{-1}$, similar to the extremely low luminosity SNe 2010ae and 2008ha, and the light curve displays a similar fast decline (\dmr $0.91 \pm 0.10$ mag). SNe 2010ae and 2008ha have been classified as type Iax supernovae, and together the three either make up a distinct physical class of their own or are at the extreme low luminosity end of this diverse supernova population. The bolometric light curve is consistent with a low kinetic energy of explosion ($E_{\rm k} \sim 10^{49}$ erg s$^{-1}$), a modest ejected mass ($M_{\rm ej} \sim 0.2$ \msol) and radioactive powering by $^{56}$Ni ($M_{\rm Ni} \sim 2 \times 10^{-3}$ \msol). The spectra are quite well reproduced with radiative transfer models (TARDIS) and a composition dominated by carbon, oxygen, magnesium, silicon and sulphur. Remarkably, all three of these extreme Iax events are in similar low-metallicity star-forming environments. The combination of the observational constraints for all three may be best explained by deflagrations of near $M_{\rm Ch}$ hybrid carbon-oxygen-neon white dwarfs which have short evolutionary pathways to formation., Comment: 12 pages, 5 figures, accepted to ApJL, minor changes to submitted version

The important scientific questions that will form the basis of a full proposal to drill a deep well to the ductile–brittle transition zone (T>400 ∘C) at Newberry Volcano, central Oregon state, USA, were discussed during an International Continental Drilling Program (ICDP) sponsored workshop held at the Oregon State University-Cascades campus in Bend, Oregon, from 10 to 13 September 2017. Newberry Volcano is one of the largest geothermal heat reservoirs in the USA and has been extensively studied for the last 40 years. The Newberry Deep Drilling Project (NDDP) will be located at an idle geothermal exploration well, NWG 46-16, drilled in 2008, 3500 m deep and 340–374 ∘C at bottom, which will be deepened another 1000 to 1300 m to reach 500 ∘C. The workshop concluded by setting ambitious goals for the NDDP: (1) test the enhanced geothermal system (EGS) above the critical point of water, (2) collect samples of rocks within the brittle–ductile transition, (3) investigate volcanic hazards, (4) study magmatic geomechanics, (5) calibrate geophysical imaging techniques, and (6) test technology for drilling, well completion, and geophysical monitoring in a very high-temperature environment. Based on these recommendations, a full drilling proposal was submitted in January 2018 to the ICDP for deepening an existing well. The next steps will be to continue building a team with project, technology, and investment partners to make the NDDP a reality.

In a subduction zone, the volcanic arc marks the location where magma, generated via flux melting in the mantle wedge, migrates through the crust and erupts. While the location of deep magma broadly defines the arc position, here we argue that crustal structures, identified in geophysical data from the Washington Cascades magmatic arc, are equally important in controlling magma ascent and defining the spatial distribution and compositional variability of erupted material. As imaged by a three-dimensional resistivity model, a broad lower-crustal mush zone containing 3–10% interconnected melt underlies this segment of the arc, interpreted to episodically feed upper-crustal magmatic systems and drive eruptions. Mount St Helens is fed by melt channelled around a mid-Tertiary batholith also imaged in the resistivity model and supported by potential–field data. Regionally, volcanism and seismicity are almost exclusive of the batholith, while at Mount St Helens, along its margin, the ascent of viscous felsic melt is enabled by deep-seated metasedimentary rocks. Both the anomalous forearc location and composition of St Helens magmas are products of this zone of localized extension along the batholith margin. This work is a compelling example of inherited structural control on local stress state and magmatism. Crustal structures are as important as deep mantle melting in controlling magma ascent and the composition and distribution of erupted material, according to 3D resistivity modelling, geophysical data and the distribution of Quaternary volcanism.

This paper is the primary deliverable of the very first NASA Living With a Star Institute Working Group, Geomagnetically Induced Currents (GIC) Working Group. The paper provides a broad overview of the current status and future challenges pertaining to the science, engineering, and applications of the GIC problem. Science is understood here as the basic space and Earth sciences research that allows improved understanding and physics-based modeling of the physical processes behind GIC. Engineering, in turn, is understood here as the “impact” aspect of GIC. Applications are understood as the models, tools, and activities that can provide actionable information to entities such as power systems operators for mitigating the effects of GIC and government agencies for managing any potential consequences from GIC impact to critical infrastructure. Applications can be considered the ultimate goal of our GIC work. In assessing the status of the field, we quantify the readiness of various applications in the mitigation context. We use the Applications Readiness Level (ARL) concept to carry out the quantification.

In reaching across traditional disciplinary boundaries, solid-Earth geophysicists and space physicists are forging new collaborations to map magnetic-storm hazards for electric-power grids. Future progress in evaluation storm time geoelectric hazards will come primarily through monitoring, surveys, and modeling of related data.

Background An epigenetic field of cancer susceptibility exists for prostate cancer (PC) that gives rise to multifocal disease in the peripheral prostate. In previous work, genome-wide DNA methylation profiling identified altered regions in the normal prostate tissue of men with PC. In the current multicenter study, we examined the predictive strength of a panel of loci to detect cancer presence and grade in patients with negative biopsy tissue. Results Four centers contributed benign prostate biopsy tissues blocks from 129 subjects that were either tumor associated (TA, Grade Group [GG] ≥ 2, n = 77) or non-tumor associated (NTA, n = 52). Biopsies were analyzed using pyrosequencing for DNA methylation encompassing CpG loci near CAV1, EVX1, FGF1, NCR2, PLA2G16, and SPAG4 and methylation differences were detected within all gene regions (p < 0.05). A multiplex regression model for biomarker performance incorporating a gene combination discriminated TA from NTA tissues (area under the curve [AUC] 0.747, p = 0.004). A multiplex model incorporating all the above genes and clinical information (PSA, age) identified patients with GG ≥ 2 PC (AUC 0.815, p < 0.0001). In patients with cancer, increased variation in gene methylation levels occurs between biopsies across the prostate. Conclusions A widespread epigenetic field defect is utilized to detect GG ≥ 2 PC in patients with histologically negative biopsies. These alterations in non-tumor cells display increased heterogeneity of methylation extent and are spatially distant from tumor foci. These findings have the potential to decrease the need for repeated prostate biopsy.

INTRODUCTION AND OBJECTIVES:Prostate cancer (PC) is typically found in multifocal locations within the prostate raising the possibility of molecular field defect in histologically normal prostate t...

Ground level electric fields arising from geomagnetic disturbances (GMDs) are used by the electric power industry to calculate geomagnetically induced currents (GICs) in the power grid. Current industry practice is limited to electric fields associated with 1-D ground electrical conductivity structure, yet at any given depth in the crust and mantle lateral (3-D) variations in conductivity can span at least three orders of magnitude, resulting in large deviations in electric fields relative to 1-D models. Solving Maxwell's equations for electric fields associated with GMDs above a 3-D Earth is computationally burdensome and currently impractical for industrial applications. A computationally light algorithm is proposed as an alternative. Real-time data from magnetic observatories are projected through multivariate transfer functions to locations of previously occupied magnetotelluric (MT) stations. MT time series and impedance tensors, such as those publically available from the NSF EarthScope Program, are used to scale the projected magnetic observatory data into local electric field predictions that can then be interpolated onto points along power grid transmission lines to actively improve resilience through GIC modeling. Preliminary electric field predictions are tested against previously recorded time series, idealized transfer function cases, and existing industry methods to assess the validity of the algorithm for potential adoption by the power industry. Some limitations such as long period diurnal drift are addressed, and solutions are suggested to further improve the method before direct comparisons with actual GIC measurements are made.

BackgroundProstate cancer (PC) is a multifocal disease. DNA methylation alterations are not restricted to the immediate peritumor environment, but spatially widespread in the adjacent and distant histologically normal prostate tissues. In the current study, we utilized high-throughput methylation arrays to identify epigenetic changes in the urine from men with and without cancer.Design, setting, and participantsDNA urine samples were enriched for methylated fragments using MBD methyl-binding antibodies and applied to high density CytoScanHD arrays. Significant loci were validated using quantitative pyrosequencing and binary logistic regression modeling applied to urine sample analyses in a training (n = 83) and validation approach (n = 84). Methylation alterations in prostate tissues using pyrosequencing at the PLA2G16 locus were examined in 38 histologically normal specimens from men with (TA, n = 26) and without (NTA, n = 12) cancer and correlated to gene expression.ResultsMethylation microarrays identified 3,986 loci showing significantly altered methylation in the urine samples from patients with PC compared to those without (TA vs NTA; pConclusionPLA2G16 methylation defines an extensive field defect in histologically normal prostate tissue associated with PC. PLA2G16 methylation in urine and prostate tissues can detect the presence of PC.

The spread betting market is a prevalent form of prediction market. In the spread betting market, participants bet on the outcome of a certain future event. The market maker quotes cutoff lines as "prices," and bettors take sides on whether the event outcome exceeds the quoted spread lines. We study how the market maker should move the spread lines to maximize profit. In our model, anonymous bettors with heterogeneous strategic behavior and information levels participate in the market. The market maker has limited information on the event outcome distribution. She aims to extract information from the market's responses to her spread lines (i.e., "learning") while guarding against an informed bettor's strategic manipulation (i.e., "bluff-proofing"). In terms of effective policies to adjust the market maker's spread lines, we show that Bayesian policies (BPs) that ignore bluffing are typically vulnerable to the informed bettor's strategic manipulation. To be more precise, the regret for the market maker is linear in the number of bets, and we identify certain strategies of the informed bettor that are profitable. We also show that the poor performance of BPs in our setting is not due to incomplete learning: when the informed bettor is absent in our setting, many simple policies eventually learn the event outcome distribution and achieve a bounded regret. Full Paper: https://ssrn.com/abstract=3283392

Small Unmanned Aerial Systems (sUAS) operations are increasing in demand and complexity. Using multiple cooperative sUAS (i.e., a swarm) can be beneficial and is sometimes necessary to perform certain tasks (e.g. precision agriculture, mapping, surveillance) either independent or collaboratively. However, controlling the flight of multiple sUAS autonomously and in real-time in a challenging environment in terms of obstacles and navigation requires highly accurate absolute and relative position and velocity information for all platforms in the swarm. This information is also necessary to effectively and efficiently resolve possible collision encounters between the sUAS. In our swarm, each platform is equipped with a Global Navigation Satellite System (GNSS) sensor, an inertial measurement unit (IMU), a baro-altimeter and a relative range sensor (range radio). When GNSS is available, its measurements are tightly integrated with IMU and baro-altimeter measurements to obtain the platform's absolute position. At the same time, the raw measurements are exchanged with the other platforms to obtain a highly accurate relative position and velocity solution with integrity. In the presence of GNSS, this relative position and velocity is used to calibrate the range radios. When GNSS is not available due to external factors (e.g., obstructions, interference), the position and velocity estimators switch to an integrated solution based on IMU, baro and relative range measurements, to maintain an accurate relative position estimate, and reduce the drift in the swarm's absolute position estimate as is typical of an IMU-based system. Multiple multi-copter data collection platforms have been developed and equipped with GNSS, inertial sensors and range radios, which were developed at Ohio University. This paper outlines the underlying methodology, the platform hardware components and analyzes and discusses sUAS flight data results.

This paper discusses the preliminary design and implementation of a simultaneous navigation, and mapping method for operation of multi-copter unmanned aircraft systems (UAS) in forest environments under the canopy. A data collection platform has been developed using a 3DR hexacopter platform equipped with laser scanners, cameras, GNSS and inertial sensors to observe the environment and used as an input to the SNAM methods. Details on this flight prototype are addressed. Furthermore, the paper will include preliminary flight test results of our hexacopter UAS operating in a forest environment. In addition to these discussions, the paper will address some application-specific issues, specifically with respect to biological, civil engineering and archeological applications.

This paper discusses a positioning and navigation algorithm to support autonomous flight of a small-size unmanned aircraft system in a structured GNSS-denied environment during a maintenance mission. The proposed method is based on the integration of depth imagery and outputs from an inertial measurement unit (IMU). In addition, 2D images of a low resolution long-wave IR (LWIR) sensor are used to aid the navigation process and support the maintenance mission by creating a thermal map of the indoor environment. A platform has been built with the appropriate sensors and data has been collected. The paper describes the methodology, the test platform and some preliminary results from mostly the preprocessing steps.

SUMMARY We develop a non-linear conjugate gradient inversion for global long period electromagnetic induction studies. The scheme requires computation of derivatives of the regularized penalty functional. We derive analytical and numerical expressions for these derivatives, and the associated Jacobian, and show how these can be efficiently implemented by generalizing and extending an existing finite difference forward solver. Using layered spherical harmonics to parametrize the model space, we invert a range of synthetic data sets to test the inversion, and to study vertical and horizontal resolution of currently available data sets. We conclude that the currently available long-period global geomagnetic observatory data in the period range 5–107 d can resolve large scale (300–500 km vertically, thousands of km horizontally) heterogeneities in mantle electrical conductivity reliably at depths ∼ 670–1600 km. By extending induction response to 0.2–5 d (including daily variation periods), upper-mantle structure could also be resolved.

SUMMARY We report on a new compilation of functions representing the geoelectromagnetic response of the Earth’s mantle. The c response functions and newly defined d response functions, the latter of which constitutes a sensitive indicator of lateral heterogeneities in conductivity, were estimated for periods from 5 to 106.7 days. The spatial coverage and statistical quality of these response-function estimates were improved over previous compilations, in part by making use of a newly assembled global catalogue of magnetic observatory hourly mean values, and by applying a statistically robust form of empirical orthogonal function (EOF) analysis. The EOF results suggest that for periods longer than 5 days, the geomagnetic field variation can be represented predominantly by a single eigenmode. We have identified that the primarysource fields of the dominant mode consist of two current systems in the same direction: an equatorial ring current in the magnetosphere, and two conjugate auroral oval ring currents in the ionosphere. The influence of the auroral current system is seen at surprisingly low latitudes, 40 ◦ and 50 ◦ for the vertical and northern components, respectively, which results in non-negligible bias on the conventional c response at high latitudes. A preliminary correction of the auroral current effect has been made on the c and d responses obtained for data from 55 and 52 observatories, respectively, at latitudes from −60 ◦ to 60 ◦ . We also present a set of approximate equivalent internal (mantle) electrical current distributions that prove a useful indicator of the presence of deep Earth heterogeneities. These new sets of electromagnetic information will increase the resolving power of 3D distribution of electrical conductivity in the Earth’s mantle.

Background: An epigenetic field of cancer susceptibility exists for prostate cancer that gives rise to multifocal disease in the peripheral zone. In a previous studies (Neoplasia 2013, J Urol 2014) we identified using methylation arrays over 50 altered regions in normal prostate tissue of men with prostate cancer. In the current multicenter study, a validation was performed to determine the predictive strength of this approach. Methods: We evaluated 2 archived, cancer negative prostate biopsy core tissue from 129 subjects from 4 urological centers. All negative cases (controls) underwent 2 or more repeat negative biopsies within 24 mo with a central review of all histopathology. Cancer cases were negative biopsies selected from patients who ultimately went prostate removal to confirm a final grade >Gleason Score 7. Biopsies were analyzed using pyrosequencing for DNA methylation changes at multiple CpGs surrounding the genes EVX1, CAV1, PLA2G16, FGF1, SPAG4 and NCR2. Analyses used multiplex logistic regression modeling with backward elimination. Results: Patients diagnosed with GS>7 cancer (77) and the control group (52) were similarly matched except for PSA (7 vs 5.8; p7 prostate cancers (AUC 0.808, p=0.001). Conclusions: A widespread epigenetic field defect can be used to detect GS>7 prostate cancers in patients with histologically negative biopsies. This assay is sensitive in requiring only 2 biopsies and detects alterations in nontumor cells at distance from the cancer. This has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications. Support: UW Ignitor; Gen X foundation Citation Format: Bing Yang, Johnathon McCormick, Adam Schultz, Glen Leverson, Geoffrey Sonn, Cristina Magi-Galluzi, Eric A. Klein, Michael Fumo, David F. Jarrard. Clinical validation of an epigenetic field of susceptibility to detect significant prostate cancer from 2 non-tumor biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2390. doi:10.1158/1538-7445.AM2017-2390

Homotopy is a powerful tool for solving nonlinear equations. It is used here to solve small‐dimensional geophysical inverse problems by locating the solutions of the governing normal equations. An Euler‐Newton numerical continuation scheme is used to map trajectories in model space that start from a prescribed solution to a trivial set of equations and terminate at a solution to the inverse problem. The trajectories often map out a continuum of equivalent solutions that are caused by model equivalences or overparameterization. This allows exploration of the solution space topology. The homotopy method, in this application, is relatively insensitive to the choice of starting model. Several examples based on synthetic controlled‐source electromagnetic (CSEM) responses are shown to illustrate the method. An inversion of actual CSEM data from the Canadian Shield is also provided.