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Fracture injection/shut-in tests are commonly used to measure the state of stress in the subsurface. Injection creates a hydraulic fracture (or in some cases, opens a preexisting fracture), and then the pressure after shut-in is monitored to identify fracture closure. Different interpretation procedures have been proposed for estimating closure, and the procedures sometimes yield significantly different results. In this study, direct, in-situ strain measurements are used to observe fracture reopening and closure. The tests were performed as part of the EGS Collab project, a mesoscale project performed at 1.25 and 1.5 km depth at the Sanford Underground Research Facility. The tests were instrumented with the SIMFIP tool, a double-packer probe with a high-resolution three-dimensional borehole displacement sensor. The measurements provide a direct observation of the fracture closure signature, enabling a high-fidelity estimate of the fracture closure stress (ie, the normal stress on the fracture). In two of the four tests, injection created an opening mode fracture, and so the closure stress can be interpreted as the minimum principal stress. In the other two tests, injection probably opened preexisting natural fractures, and so the closure stress can be interpreted as the normal stress on the fractures. The strain measurements are compared against different proposed methods for estimating closure stress from pressure transients. The shut-in transients are analyzed with two techniques that are widely used in the field of petroleum engineering – the ‘tangent’ method and the ‘compliance’ method. In three of the four tests, the tangent method significantly underestimates the closure stress. The compliance method is reasonably accurate in all four tests. Closure stress is also interpreted using two other commonly-used methods – ‘first deviation from linearity’ and the method of (Hayashi and Haimson, 1991). In comparison with the SIMFIP data, these methods tend to overestimate the closure stress, evidently because they identify closure from early-time transient effects, such as near-wellbore tortuosity. In two of the tests, microseismic imaging provides an independent estimate of the size of the fracture created by injection. When combined with a simple mass balance calculation, the SIMFIP stress measurements yield predictions of fracture size that are reasonably consistent with the estimates from microseismic. The calculations imply an apparent fracture toughness 2-3x higher than typical laboratory-derived values.

The EGS Collab project, supported by the US Department of Energy, is performing intensively monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory to address challenges in implementing enhanced geothermal systems (EGS). Data and observations from the field tests are compared to simulations to understand processes and build confidence in numerical modeling of the processes. We have completed Experiment 1 (of 3), which examined hydraulic fracturing in a well-characterized underground fractured phyllite test bed at a depth of approximately 1.5 km at the Sanford Underground Research Facility (SURF) in Lead, South Dakota. Testbed characterization included fracture mapping, borehole acoustic and optical televiewers, full waveform sonic, conductivity, resistivity, temperature, campaign p- and s-wave investigations and electrical resistance tomography. Borehole geophysical techniques including passive seismic, continuous active source seismic monitoring, electrical resistance tomography, fiber-based distributed strain, distributed temperature, and distributed acoustic monitoring, were used to carefully monitor stimulation events and flow tests. More than a dozen stimulations and nearly one year of flow tests were performed. Quality data and detailed observations were collected and analyzed during stimulation and water flow tests using ambient temperature and chilled water. We achieved adaptive control of the tests using real-time monitoring and rapid dissemination of data and near-real-time simulation. More detailed numerical simulation was performed to answer key experimental design questions, forecast fracture propagation trajectories and extents, and analyze and evaluate results. Data are freely available from the Geothermal Data Repository. Experiment 2 examines the potential for hydraulic shearing in amphibolite at a depth of about 1.25 km at SURF. This site has a different set of stress and fracture conditions than Experiment 1. The Experiment 2 testbed consists of nine subhorizontal boreholes configured in two fans of two boreholes which surround the testbed and contain grouted-in electrical resistance tomography, seismic sensors, active seismic sources and distributed fiber sensors. A “five-spot” set of test wells that extends from a custom mined alcove includes an injection well and four production/monitoring wells. The testbed was characterized geophysically and hydrologically, and three stimulations have been performed using the Step-Rate Injection Method for Fracture In-Situ Properties (SIMFIP) tool to measure strains, and a new strain quantifying tool (downhole robotic strain analysis tool -DORSA) was deployed in a monitoring hole during stimulation. Real-time data were broadcast during stimulations to allow real-time response to arising issues.

The EGS Collab project is performing well-monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory to inform challenges in implementing enhanced geothermal systems (EGS). This project, supported by the US Department of Energy, is gathering data and observations from the field tests and comparing these to simulation results to understand processes and to build confidence in numerical modeling of the processes. Experiment 1 (now complete) examined hydraulic fracturing in an underground test bed at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, at a depth of approximately 1.5 km in a well-characterized phyllite. Geophysical monitoring instrumentation in six of eight sub-horizontal boreholes monitored stimulation events and flow tests. The other two boreholes were used to perform and carefully measure water injection and production. More than a dozen stimulations and nearly one year of flow tests in the testbed were performed. Detailed observations of processes occurring during stimulation and dynamic flow tests were collected and analyzed. Flow tests using ambient-temperature and chilled water were performed with intermittent tracer tests to examine system behavior. We achieved adaptive control of the tests using close monitoring of rapidly disseminated data and near-real-time simulation. Numerical simulation was critical in answering key experimental design questions, forecasting fracture behavior, and analyzing results. We were successful in performing many simulations in near-real-time in conjunction with the field experiments, with more detailed simulations performed later. The primary objective of Experiment 2 is to examine hydraulic shearing of natural fractures at a depth of 1.25 km in amphibolite at SURF. The stresses, rock type, and fracture conditions are different than in Experiment 1. The testbed consists of 9 boreholes, in addition to two earlier-drilled characterization boreholes. One borehole is used for injection, two fans of 2 monitoring wells have several geophysical measurement tools grouted in, and four open boreholes surrounding the injection hole are adaptively used for production and monitoring. We have encountered approximately five fracture set orientations in the testbed, and designed our testbed accordingly to maximize the potential for shear stimulation. Three stimulations have been performed to date from the injection borehole, each intersecting at least one production borehole. Different methods have been used for each stimulation, including a ramped flow, a high flow rate, and oscillating pressure.

The EGS Collab project, supported by the US Department of Energy, is addressing challenges in implementing enhanced geothermal systems (EGS). This includes improving understanding of the stimulation of crystalline rock to create appropriate flow pathways, and the ability to effectively simulate both the stimulation and the flow and transport processes in the resulting fracture network. The project is performing intensively monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory. Data and observations from the field test are compared to simulations to understand processes and to build confidence in numerical modeling of the processes. In Experiment 1, we examined hydraulic fracturing an underground test bed at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, at a depth of approximately 1.5 km. We drilled eight sub-horizontal boreholes in a well-characterized phyllite. Six of the boreholes were instrumented with many sensor types to allow careful monitoring of stimulation events and flow tests, and the other two boreholes were used for water injection and production. We performed a number of stimulations and flow tests in the testbed. Our monitoring systems allowed detailed observations and collection of numerous data sets of processes occurring during stimulation and during dynamic flow tests. Long-term ambient temperature and chilled water flow tests were performed in addition to many tracer tests to examine system behavior. Data were rapidly analyzed, allowing adaptive control of the tests. Numerical simulation was used to answer key experimental design questions, to forecast fracture propagation trajectories and extents, and to analyze and evaluate results. Many simulations were performed in near-real-time in conjunction with the field experiments, with more detailed process study simulations performed on a longer timeframe. Experiment 2 will examine hydraulic shearing in a test bed being built at the SURF at a depth of about 1.25 km in amphibolite under a different set of stress and fracture conditions than Experiment 1. Five sets of fracture orientations were considered in design, and three orientations seem to be consistently observed.

Enhanced Geothermal Systems could provide a substantial contribution to the global energy demand if their implementation could overcome inherent challenges. Examples are insufficient created permeability, early thermal breakthrough, and unacceptable induced seismicity. Here we report on the seismic response of a mesoscale hydraulic fracturing experiment performed at 1.5-km depth at the Sanford Underground Research Facility. We have measured the seismic activity by utilizing a 100-kHz, continuous seismic monitoring system deployed in six 60-m length monitoring boreholes surrounding the experimental domain in 3-D. The achieved location uncertainty was on the order of 1 m and limited by the signal-to-noise ratio of detected events. These uncertainties were corroborated by detections of fracture intersections at the monitoring boreholes. Three intervals of the dedicated injection borehole were hydraulically stimulated by water injection at pressures up to 33 MPa and flow rates up to 5 L/min. We located 1,933 seismic events during several injection periods. The recorded seismicity delineates a complex fracture network comprised of multistrand hydraulic fractures and shear-reactivated, preexisting planes of weakness that grew unilaterally from the point of initiation. We find that heterogeneity of stress dictates the seismic outcome of hydraulic stimulations, even when relying on theoretically well-behaved hydraulic fractures. Once hydraulic fractures intersected boreholes, the boreholes acted as a pressure relief and fracture propagation ceased. In order to create an efficient subsurface heat exchanger, production boreholes should not be drilled before the end of hydraulic stimulations.

We investigate the influence of foliation orientation and fine-scale folding on the static and dynamic elastic properties and unconfined strength of the Poorman schist. Measurements from triaxial and uniaxial laboratory experiments reveal a significant amount of variability in the static and dynamic Young’s modulus depending on the sample orientation relative to the foliation plane. Dynamic P-wave modulus and S-wave modulus are stiffer in the direction parallel to the foliation plane as expected for transversely isotropic mediums with average Thomsen parameters values 0.133 and 0.119 for epsilon and gamma, respectively. Static Young’s modulus varies significantly between 21 and 117 GPa, and a peculiar trend is observed where some foliated sample groups show an anomalous decrease in the static Young’s modulus when the symmetry axis (x3-axis) is oriented obliquely to the direction of loading. Utilizing stress and strain relationships for transversely isotropic medium, we derive the analytical expression for Young’s modulus as a function of the elastic moduli E1, E3, ν31, and G13 and sample orientation to fit the static Young’s modulus measurements. Regression of the equation to the Young’s modulus data reveals that the decrease in static Young’s modulus at oblique symmetry axis orientations is directly influenced by a low shear modulus, G13, which we attribute to shear sliding along foliation planes during static deformation that occurs as soon as the foliation is subject to shear stress. We argue that such difference between dynamic and static anisotropy is a characteristic of near-zero porosity anisotropic rocks. The uniaxial compressive strength also shows significant variability ranging from 21.9 to 194.6 MPa across the five sample locations and is the lowest when the symmetry axis is oriented 45° or 60° from the direction of loading, also a result of shear sliding along foliation planes during static deformation.

Copyright 2019 ARMA, American Rock Mechanics Association. The EGS (Enhanced Geothermal Systems) Collab project is performing stimulation and flow experiments in highly-monitored and well-characterized intermediate-scale (approximately10 to 20 meter) field test beds at a depth of approximately 1,500 meters in the Sanford Underground Research Facility (SURF) in the Black Hills of South Dakota. Our fracture stimulation and interwell flow tests are performed to better understand processes that control formation of effective subsurface heat exchangers that are critical to the development and success of EGS. Different EGS Collab stimulations will be performed under dissimilar stress conditions to produce data for model comparisons that better differentiate stimulation mechanisms and the evolution of permeability enhancement in crystalline rock. EGS Collab experiments provide a means of testing tools, concepts, and strategies that could later be employed under geothermal reservoir conditions at DOE’s Frontier Observatory for Research in Geothermal Energy (FORGE) and other enhanced geothermal systems. Key to the project is using numerical simulations in the experiment design and interpretation of

Resource-intensive interventions and education are susceptible to a lack of long-term sustainability and regression to the mean. The respiratory culture nudge changed reporting to "Commensal Respiratory Flora only: No S. aureus /MRSA or P. aeruginosa. " This study demonstrated sustained reduction in broad-spectrum antibiotic duration and long-term sustainability 3 years after implementation., (© The Author(s) 2022.)

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1 to 3 previous therapies received Bendamustine (90 mg/m 2 , day 1 + 2) and Rituximab (375 mg/m 2 , day 1) with Temsirolimus in doses from 25 to 75 mg in phase I and 50 mg Temsirolimus in phase II, added on day 1, 8, 15 of a 28 days cycle. The primary endpoint of the phase II was ORR at the end of treatment. Overall, 39 (29 MCL, 10 FL) patients were included. Median age was 71 years and median pretreatment number was 2. Grade 3/4 non-hematologic adverse events were rare and included hyperglycemia in 3 patients (7%) and angioedema in 2 patients (5%). Infectious complications grade 3/4 were observed in 9 patients (23%). Hematologic grade 3/4 events included leukopenia in 22 (56%), neutropenia in 18 (46%), lymphopenia in 16 (41%) and thrombocytopenia in 14 patients (36%). An objective response (best response) was observed in 33/39 patients (89%; 24 MCL (89%) and 9 FL (90%)), including 14 CR (38%; 12 MCL (36%) and 2 FL (20%)). Median PFS is 1.5y for MCL and 1.82 years for FL, and median OS has not been reached for either entity. This data demonstrates promising efficacy of Temsirolimus in r/r MCL and FL with acceptable toxicity. The BeRT regimen may be used as a treatment option for both entities., Competing Interests: Conflicts of interest: JA: Pfizer, Roche: Honoraria., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Pentaerythritol tetranitrate (PETN) differs from other organic nitrates by the lack of tolerance induction and by antioxidative properties. The purpose of this study was to determine the effect of PETN on endothelial function in patients with coronary artery disease (CAD). We hypothesized that the treatment with PETN improves endothelial function in patients with CAD., Methods: In a prospective, double-blind study, we randomly assigned 80 patients to treatment for 8 weeks with oral PETN 80 mg t.i.d. (PETN) or placebo (C). The primary endpoint was the absolute change in brachial artery flow-mediated dilation (FMD) from baseline to follow-up. Furthermore, changes in nitroglycerin-mediated dilation (NMD), digital peripheral arterial tonometry (PAT) index, vascular shear stress, mean flow velocity, plasma bilirubin, C-reactive protein (CRP) and thiobarbituric acid reactive substances (TBARS), serum ferritin, and the activity of the PETN bioactivating enzyme aldehyde dehydrogenase-2 (ALDH-2) in peripheral blood mononuclear cells were analyzed. Raw data entry, data monitoring and statistical analysis were performed independently., Results: The treatment groups were comparable regarding demographics, cardiovascular risk and concomitant medication. There was no difference in the change in FMD between the two treatment groups (mean +/- SD: PETN: +1.6 +/- 3.3% vs. C: +1.4 +/- 4.1%; P = 0.7). NMD increased after treatment with PETN and was higher compared with C (PETN: +3.8 +/- 5.5% vs. C: +0.6 +/- 4.2%; P = 0.004). Mean PAT index and ALDH-2 activity remained unchanged. Relative changes in mean flow volume (P = 0.04) and mean flow velocity (P = 0.01) upon ischemia increased in the PETN group versus C. Changes in bilirubin, ferritin, TBARS and CRP did not differ between the groups., Conclusions: We conclude that chronic PETN therapy in patients with CAD may be established for symptomatic treatment without adverse effects on endothelial function and with beneficial effects on the microcirculation.