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With the goal of better understanding stimulation in crystalline rock for improving enhanced geothermal systems (EGS), the EGS Collab Project performed a series of stimulations and flow tests at 1.25 and 1.5 km depths. The tests were performed in two well-instrumented testbeds in the Sanford Underground Research Facility in Lead, South Dakota, United States. The testbed for Experiment 1 at 1.5 km depth contained two open wells for injection and production and six instrumented monitoring wells surrounding the targeted stimulation zone. Four multi-step stimulation tests targeting hydraulic fracturing and nearly year-long ambient temperature and chilled water flow tests were performed in Experiment 1. The testbed for Experiments 2 and 3 was at 1.25 km depth and contained five open wells in an outwardly fanning five-spot pattern and two fans of well-instrumented monitoring wells surrounding the targeted stimulation zone. Experiment 2 targeted shear stimulation, and Experiment 3 targeted low-flow, high-flow, and oscillating pressure stimulation strategies. Hydraulic fracturing was successful in Experiments 1 and 3 in generating a connected system wherein injected water could be collected. However, the resulting flow was distributed dynamically, and not entirely collected at the anticipated production well. Thermal breakthrough was not observed in the production well, but that could have been masked by the Joule-Thomson effect. Shear stimulation in Experiment 2 did not occur – despite attempting to pressurize the fractures most likely to shear – because of the inability to inject water into a mostly-healed fracture, and the low shear-to-normal stress ratio. The EGS Collab experiments are described to provide a background for lessons learned on topics including induced seismicity, the correlation between seismicity and permeability, distributed and dynamic flow systems, thermoelastic and pressure effects, shear stimulation, local geology, thermal breakthrough, monitoring stimulation, grouting boreholes, modeling, and system management.

Genetic testing has the potential to revolutionize primary care, but few health systems have developed the infrastructure to support precision population medicine applications or attempted to evaluate its impact on patient and provider outcomes. In 2018, Sanford Health, the nation’s largest rural nonprofit health care system, began offering genetic testing to its primary care patients. To date, more than 11,000 patients have participated in the Sanford Chip Program, over 90% of whom have been identified with at least one informative pharmacogenomic variant, and about 1.5% of whom have been identified with a medically actionable predisposition for disease. This manuscript describes the rationale for offering the Sanford Chip, the programs and infrastructure implemented to support it, and evolving plans for research to evaluate its real-world impact.

Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques.

Enhanced geothermal systems (EGS) require cost-effective monitoring of fracture networks. We validate the capability of using borehole distributed acoustic sensing (DAS) ambient noise for fracture monitoring using core photos and core logs. The EGS Collab project has conducted 10 m scale field experiments of hydraulic fracture stimulation using 50-60 m deep experimental wells at the Sanford Underground Research Facility (SURF) in Lead, South Dakota. The first EGS Collab testbed is located at 1616.67 m (4850 ft) depth at SURF and consists of one injection well, one production well, and six monitoring wells. All wells are drilled subhorizontally from an access tunnel called a drift. The project uses a single continuous fiber-optic cable installed sequentially in the six monitoring wells to record DAS data for monitoring hydraulic fracturing during stimulation. We analyze 60 s time records of the borehole DAS ambient noise data and compute the noise root-mean-square (rms) amplitude on each channel (points along the fiber cable) to obtain DAS ambient noise rms amplitude depth profiles along the monitoring wellbore. Our noise rms amplitude profiles indicate amplitude peaks at distinct depths. We compare the DAS noise rms amplitude profiles with borehole core photos and core logs and find that the DAS noise rms amplitude peaks correspond to the locations of fractures or lithologic changes indicated in the core photos or core logs. We then compute the hourly DAS noise rms amplitude profiles in two monitoring wells during three stimulation cycles in 72 h and find that the DAS noise rms amplitude profiles vary with time, indicating the fracture opening/growth or closing during the hydraulic stimulation. Our results demonstrate that borehole DAS passive ambient noise can be used to detect fractures and monitor fracturing processes in EGS reservoirs.

In early 2022, the Human Anatomy & Physiology Society (HAPS) Curriculum & Instruction Lab Survey subcommittee launched the third survey of instructors for introductory undergraduate-level courses in human anatomy and physiology. This manuscript presents analyses of questions regarding the laboratory activities and learning outcomes (LOs) section of the survey and compares results to the first (2014) and second (2017) offerings of the lab survey. Laboratory instruction continues to be a valued component of anatomy and physiology instruction, although a greater variety of resources are now being used. New questions on curriculum development revealed that respondents utilize many techniques and resources to develop their curricula, though respondents at 2-year institutions report significantly lower levels of influence on their A&P curricula compared to respondents at 4-year institutions. Identification of anatomical structure LOs appeared to be prioritized over LOs for each structure's physiological role. Dissections, plastic model manipulations, use of human subjects for physiological experiments, and use of computer simulations have remained stable across all three surveys, although use of anatomical donors and computer simulations have increased over time. Collectively, we observed respondents developing intentional, outcome-directed changes to laboratory instruction while also being limited by historical practices at their institutions. Results also indicated that the COVID-19 pandemic has increased the speed at which instructors are making long-term curricular changes.

In 2022, a subset of the Human Anatomy and Physiology Society (HAPS) Curriculum & Instruction Committee administered the third offering of the HAPS lab survey. This survey included a three-part framework of (1) demographics, (2) lab activities and learning outcomes, and, (3) the impact of a global pandemic on instruction. Here we report on demographics of respondents, their institutions, and students. Survey results related to lab activities and outcomes, and COVID-19 impacts, will be addressed in subsequent manuscripts. The duration of teaching service has been stable with 54.3% to 58.3% of respondents serving at least ten years in their current position, and 88% of respondents working at a single institution. Job responsibilities focused on teaching (98.9%) as well as multiple other commitments including service and lab and/or course coordination. The number of respondents with a terminal degree increased and there has been a decrease in the percentage of respondents working at 2-year institutions, with 50% of respondents working at 4-year institutions, of which a slight majority had graduate programs. Career goals of enrolled students remained focused on allied-health and instructors indicated nursing as the most common student career goal, with a range of other careers also mentioned. Overall, the results affirmed the importance of anatomy and physiology (A&P) instruction and the multiple roles that A&P instructors serve at their institutions.

The EGS Collab project performed well-monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory to inform challenges in implementing enhanced geothermal system (EGS) technology. This project, supported by the US Department of Energy, gathered data and observations from the field tests and compared these to simulation results to understand processes and to build confidence in numerical modeling of the processes. The project consisted of 3 Experiments, each comprising test and testbed design, many individual tests, numerical simulation, and analysis. The Experiments were performed in two deep underground testbeds at the Sanford Underground Research Facility (SURF) in Lead, South Dakota. Field experiments are now complete, significant data sets have been collected and analyzed, and some analysis continues. Experiments using underground test facilities have many advantages in that they allow:•Three-dimensional characterization of the stimulated volume by complementary geophysical methods surrounding the experiment•Using techniques that are currently not applicable under geothermal condition to provide processes insight •Comprehensive tracer testing and detailed characterization of complex fluid movements•Understanding the geometry of the stimulated network at the meso-scale and its implications for effective fracture surface area, rock block size, and heat exchange.Underground testing has its own set of complications, however, which affect the ability to perform tests as desired and affect the experiment results. Included here are the inability to flow at desired injection rates due to stress gradients caused by drift cooling, and the need to strongly limit induced seismicity because the distance to people and equipment.Experiment 1 examined hydraulic fracturing at a depth of 1.5 km in a well-characterized phyllite. Eight subhorizontal boreholes were used in this Experiment. Geophysical monitoring instrumentation was deployed in six boreholes to monitor 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. Experiment 2 was intended to examine hydraulic shearing of natural fractures at a depth of 1.25 km in amphibolite. The stresses, rock type, and fracture conditions are different than in Experiment 1. The testbed consists of 9 boreholes, in addition to 2 exploratory characterization boreholes. Four boreholes drilled as two fans of 2 monitoring holes contained grouted-in monitoring sensors. The remaining five open boreholes drilled in a five-spot pattern were adaptively used for injection, production, and monitoring. Approximately five fracture set orientations were encountered in the testbed along with a low-stress rhyolite sill at 35 m below the access drift in exploratory well TV4100. The testbed was designed to optimize the potential for shear stimulation while also avoiding the low-stress rhyolite. Experiment 2 focused on stimulating a fracture in the most likely orientation to shear, however shear stimulation did not occur probably due to cementation from natural secondary mineralization. Other fracture sets encountered were also cemented and had orientations less likely to shear.Experiment 3 consisted of several stimulations in the same testbed as Experiment 2 allowing different stimulation approaches including ramped-rate injection, rapid injection, and oscillating-pressure injection. Ultimately these methods created hydraulic fractures, one of which was used for a medium-duration cold water injection test. The major findings of the EGS Collab Project include: 1.Significant shear stimulation did not occur during our stimulation attempts. Shear stimulation may occur but under a limited set of conditions not encountered.2.Our stimulations resulted in hydraulic fractures that required hydraulic propping. Pumping at pressures exceeding the minimum principal stress may not be feasible in an enhanced geothermal system.3.The systems we generated were complex hydraulic fracture/natural fracture systems, and these systems changed over time in response to applied pressures and flowrates and to unknown stimuli.4.The project attempted alternative stimulation methods, which did not provide significant flow improvement. 5.Thermal breakthrough was not achieved as designed, most likely because flow to production boreholes was not adequate. 6.The combination of geophysical tools used provided excellent understanding of many important processes. 7.Microearthquakes (MEQs) didn’t necessarily identify flow paths.8.Engineering tools bounding expected seismicity are needed.This report provides a summary of tests and analyses performed for EGS Collab Experiment 2 (Shear Stimulation in Testbed 2) and Experiment 3 (Alternative Stimulation methods). Much of the EGS Collab work has been published in journals and conference papers, presented in conferences, included in written reports, and submitted in data sets to the Geothermal Data Repository (GDR). The entirety of these written works is included as an appendix to this report, and this report serves as a summary and framework pointing to these published papers, presentations, and reports.

We conducted a time-lapse seismic experiment utilizing automated active seismic source and sensor arrays to monitor a reactivated fault within the Opalinus clay formation at the Mont Terri Rock Laboratory (Switzerland), an analog caprock for geologic carbon storage. A series of six brine injections were conducted into the so-called Main Fault to reactivate it. Seismic instrumentation in five monitoring boreholes on either side of the fault was used to continuously probe changes in P-wave travel-times associated with fault displacement and leakage. We performed time-lapse travel-time tomography on five hundred sequential data sets; this revealed a zone of decreased P-wave velocity, up to 16 m/s, during each injection cycle, followed by a velocity increase during shut-in. These results demonstrate varying elastic property perturbations, both spatially and temporally, along the fault plane during reactivation. We then interpreted these velocity changes in terms of fault dilation induced by pressurized fluids along the fault.

Although the small airway component of chronic asthma is becoming a more important topic, its impact in the daily assessment of pediatric asthma is limited. The intrinsic airway autonomic control in asthma suggests some potential mechanisms by which more distal obstruction may dominate in some situations. We suggest theoretical possibilities for small airway dominance and present clinical data supporting this possibility.

In a mixed-methods approach, this paper explores student views of plurilingual foreign-language (FL) teaching of English among primary-school students in grade 4. We investigate whether students who were raised in the majority language only and those who grew up speaking an additional minority language differ in their appreciation of plurilingual FL teaching and whether plurilingual FL teaching appeals to students with different profiles in linguistic, cognitive, attitudinal, or individual background factors. One-hundred and thirty-two students took part in a six-month teaching intervention, in which 20% of FL lesson time was devoted to plurilingual teaching. A qualitative analysis of student interviews shows mixed views of plurilingual FL teaching, with students speaking additional minority languages evaluating plurilingual teaching more favourably than majority-language-only students. In a quantitative analysis, we compare the groups of students who appreciated and those who did not appreciate plurilingual FL teaching in terms of their linguistic, cognitive or individual background factors. Students who appreciate plurilingual FL teaching display significantly more positive attitudes to the FL and a greater sense of academic achievement. Moreover, students appreciative of plurilingual FL teaching demonstrate significantly higher learning gains in productive vocabulary than non-appreciative students. In all, these findings indicate that attitudinal factors modulate the appreciation and the learning outcomes in plurilingual FL teaching.

This study investigates whether cross-linguistic differences affect how adult second language (L2) learners use different types of verb subcategorization information for prediction in real-time sentence comprehension. Using visual world eye-tracking, we tested if first language (L1) German and L1 Turkish intermediate-to-advanced learners of L2 English make use of categorical and gradient probabilistic selectional information of ditransitive verbs to predict whether the verbs would be followed by prepositional-object or double-object dative constructions. L1 German learners used both categorical ("pay/*donate the woman the money") and gradient ("pay/#send the woman the money") constraints for prediction in a target-like manner. In contrast, L1 Turkish learners were delayed in recruiting categorical verb information and were only selectively sensitive to gradient verb information. We argue that target-like predictive processing across categorical and gradient verb information is attainable for L2 learners, but differences in L1-L2 word order may curtail the utility of prediction by verb subcategorization information in L2 processing.

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.

ImportanceEvidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).ObjectiveTo evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA.Design, setting, and participantsThis randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023.InterventionImplant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively.Main outcomes and measuresPrimary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale).ResultsAmong 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol.Conclusions and relevanceThis randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI.Trial registrationClinicalTrials.gov Identifier: NCT02263859.