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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.

Combined radial and ulnar artery injuries are associated with a >35% amputation rate when not revascularized promptly. We describe a patient who suffered a penetrating injury to both the radial and ulnar arteries. Despite the ulnar artery being ligated and the radial artery primary repair becoming occluded after the index operation, his hand remained salvageable, likely because of collateral arterial pathways. The patient obtained a delayed radial-radial artery bypass and afterward achieved meaningful neuromotor function. This case emphasizes the importance of forearm vascular anatomy variability and the need for prompt management of arterial injuries to reduce limb loss and disability.

The options for Artificial intelligence (AI) tools used in teacher education are increasing daily, but more is only sometimes better for teachers working in already complex classroom settings. This team discusses the increase of AI in schools and provides an example from administrators, teacher educators, and computer scientists of an AI virtual agent and the research to support student learning and teachers in classroom settings. The authors discuss the creation and potential of virtual characters in elementary classrooms, combined with biometrics and facial emotional recognition, which in this study has impacted student learning and offered support to the teacher. The researchers share the development of the AI agent, the lessons learned, the integration of biometrics and facial tracking, and how teachers use this emerging form of AI both in classroom-based center activities and to support students' emotional regulation. The authors conclude by describing the application of this type of support in teacher preparation programs and a vision of the future of using AI agents in instruction.

In lactating mothers, the high calcium (Ca2+) demand for milk production triggers significant bone loss1. Although oestrogen normally counteracts excessive bone resorption by promoting bone formation, this sex steroid drops precipitously during this postpartum period. Here we report that brain-derived cellular communication network factor 3 (CCN3) secreted from KISS1 neurons of the arcuate nucleus (ARCKISS1) fills this void and functions as a potent osteoanabolic factor to build bone in lactating females. We began by showing that our previously reported female-specific, dense bone phenotype2 originates from a humoral factor that promotes bone mass and acts on skeletal stem cells to increase their frequency and osteochondrogenic potential. This circulatory factor was then identified as CCN3, a brain-derived hormone from ARCKISS1 neurons that is able to stimulate mouse and human skeletal stem cell activity, increase bone remodelling and accelerate fracture repair in young and old mice of both sexes. The role of CCN3 in normal female physiology was revealed after detecting a burst of CCN3 expression in ARCKISS1 neurons coincident with lactation. After reducing CCN3 in ARCKISS1 neurons, lactating mothers lost bone and failed to sustain their progeny when challenged with a low-calcium diet. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone for both sexes and define a new maternal brain hormone for ensuring species survival in mammals.

Powered mobility technology can be a powerful tool to facilitate self-initiated exploration and play for toddlers with motor disabilities. The joystick-controlled Permobil Explorer Mini is currently the only commercially available powered mobility device for children ages 1-3 years in the United States. However, many open questions persist regarding how joystick-based mobility technologies should be designed to optimally suit the developmental needs of toddlers. The purpose of this study was to quantify how toddlers with motor disabilities use the Explorer Mini during free exploration and play. For this work, we developed a custom-instrumented Explorer Mini with embedded sensors to measure joystick interactions and wheel rotations. Nine children with motor disabilities (ages 12-36 months) participated in 12 in-lab visits, and during each visit they engaged in two 15-20 minute play sessions. For each session, we calculated several quantitative outcome metrics, including the time spent using the joystick, distance traveled, and the number, duration, and complexity of joystick interactions. Every participant independently interacted with the joystick and moved the Explorer Mini during every session. Over 12 visits, participants significantly increased their distance traveled and the time spent with the joystick active. Surprisingly, we found that only 48% of joystick interactions resulted in device movement, which has important implications for learning. These results can serve as a benchmark for caregivers and clinicians to understand early device use patterns. Furthermore, this knowledge can be used to inform the design of new powered mobility technologies for toddlers with disabilities or support the refinement of existing devices.

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.

OBJECTIVES:. Providers vary in their impact on clinical outcomes, but this is rarely accounted for in healthcare research. By failing to identify the provider responsible for a patient’s care, investigators miss an opportunity to account for nonrandom variation in outcomes. Prior methods of identifying responsible providers have relied on manual chart review, which is time-consuming and expensive, or analysis of claims data, which has been demonstrated to be inaccurate. To address these gaps, we sought to develop an algorithm using electronic health record (EHR) data to identify the responsible provider for each day of a patient’s hospitalization. DESIGN:. A multicenter retrospective cohort study. SETTING:. Midwest healthcare system. PATIENTS:. Hospitalized patients and their providers. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We first confirmed high inter-rater reliability of manual chart review to identify the responsible provider. Using manual chart review as the gold standard, we then assessed the accuracy of an automated algorithm in a set of randomly selected patients. The agreement between two independent physicians in their determination of the responsible provider by chart review was 100%. Among 200 randomly selected patients, the algorithm identified the same responsible provider as the physician chart reviewer on 93% (3372/3626; 95% CI, 92–94%) of patient-days. CONCLUSIONS:. Readily available EHR data can be used to assign patients to providers daily with a high degree of accuracy. This methodology could be applied in healthcare research to identify sources of variation other than the intervention being studied.

Summary: White-rot fungi (WRF) are the most efficient lignin-degrading organisms in nature. However, their capacity to use lignin-related aromatic compounds, such as 4-hydroxybenzoate, as carbon sources has only been described recently. Previously, the hydroxyquinol pathway was proposed for the bioconversion of these compounds in fungi, but gene- and structure-function relationships of the full enzymatic pathway remain uncharacterized in any single fungal species. Here, we characterize seven enzymes from two WRF, Trametes versicolor and Gelatoporia subvermispora, which constitute a four-enzyme cascade from 4-hydroxybenzoate to β-ketoadipate via the hydroxyquinol pathway. Furthermore, we solve the crystal structure of four of these enzymes and identify mechanistic differences with the closest bacterial and fungal structural homologs. Overall, this research expands our understanding of aromatic catabolism by WRF and establishes an alternative strategy for the conversion of lignin-related compounds to the valuable molecule β-ketoadipate, contributing to the development of biological processes for lignin valorization.

Combined radial and ulnar artery injuries are associated with a >35% amputation rate when not revascularized promptly. We describe a patient who suffered a penetrating injury to both the radial and ulnar arteries. Despite the ulnar artery being ligated and the radial artery primary repair becoming occluded after the index operation, his hand remained salvageable, likely because of collateral arterial pathways. The patient obtained a delayed radial-radial artery bypass and afterward achieved meaningful neuromotor function. This case emphasizes the importance of forearm vascular anatomy variability and the need for prompt management of arterial injuries to reduce limb loss and disability.

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3-5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.

Abstract Feedstock variability represents a challenge in lignocellulosic biorefineries, as it can influence both lignocellulose deconstruction and microbial conversion processes for biofuels and biochemicals production. The impact of feedstock variability on microbial performance remains underexplored, and predictive tools for microbial behaviour are needed to mitigate risks in biorefinery scale‐up. Here, twelve batches of corn stover were deconstructed via deacetylation, mechanical refining, and enzymatic hydrolysis to generate lignin‐rich and sugar streams. These batches and their derived streams were characterised to identify their chemical components, and the streams were used as substrates for producing muconate and butyrate by engineered Pseudomonas putida and wildtype Clostridium tyrobutyricum, respectively. Bacterial performance (growth, product titers, yields, and productivities) differed among the batches, but no strong correlations were identified between feedstock composition and performance. To provide metabolic insights into the origin of these differences, we evaluated the effect of twenty‐three isolated chemical components on these microbes, including three components in relevant bioprocess settings in bioreactors, and we found that growth‐inhibitory concentrations were outside the ranges observed in the streams. Overall, this study generates a foundational dataset on P. putida and C. tyrobutyricum performance to enable future predictive models and underscores their resilience in effectively converting fluctuating lignocellulose‐derived streams into bioproducts.

Adaptations to infectious and dietary pressures shape mammalian physiology and disease risk. How such adaptations affect sex-biased diseases remains insufficiently studied. In this study, we show that sex-dependent hepatic gene programs confer a robust (~300%) survival advantage for male mice during lethal bacterial infection. The transcription factor B cell lymphoma 6 (BCL6), which masculinizes hepatic gene expression at puberty, is essential for this advantage. However, protection by BCL6 protein comes at a cost during conditions of dietary excess, which result in overt fatty liver and glucose intolerance in males. Deleting hepatic BCL6 reverses these phenotypes but markedly lowers male survival during infection, thus establishing a sex-dependent trade-off between host defense and metabolic systems. Our findings offer strong evidence that some current sex-biased diseases are rooted in ancient evolutionary trade-offs between immunity and metabolism.

Abstract Background Learning health systems (LHSs) iteratively generate evidence that can be implemented into practice to improve care and produce generalizable knowledge. Pragmatic clinical trials fit well within LHSs as they combine real‐world data and experiences with a degree of methodological rigor which supports generalizability. Objectives We established a pragmatic clinical trial unit (“RapidEval”) to support the development of an LHS. To further advance the field of LHS, we sought to further characterize the role of health information technology (HIT), including innovative solutions and challenges that occur, to improve LHS project delivery. Methods During the period from December 2021 to February 2023, eight projects were selected out of 51 applications to the RapidEval program, of which five were implemented, one is currently in pilot testing, and two are in planning. We evaluated pre‐study planning, implementation, analysis, and study closure approaches across all RapidEval initiatives to summarize approaches across studies and identify key innovations and learnings by gathering data from study investigators, quality staff, and IT staff, as well as RapidEval staff and leadership. Implementation (Results) Implementation approaches spanned a range of HIT capabilities including interruptive alerts, clinical decision support integrated into order systems, patient navigators, embedded micro‐education, targeted outpatient hand‐off documentation, and patient communication. Study approaches include pre‐post with time‐concordant controls (1), randomized stepped‐wedge (1), cluster randomized across providers (1) and location (3), and simple patient level randomization (2). Conclusions Study selection, design, deployment, data collection, and analysis required close collaboration between data analysts, informaticists, and the RapidEval team.

This article explores the cultural, economic, and ecological challenges of the Die Bevryde Grond Trust and communities of the larger Valley of Grace in the Breede River Basin of South Africa. It examines how ‘Deep Forgiveness’ inspires acts of practical love through reconciliation, restoration, and regeneration. This is the story of Aletta Venter, a South African farmer and descendent of European colonials, who created the Die Bevryde Grond Trust, or Freed Land Trust, to prioritize land stewardship over land ownership. It chronicles Venter’s pursuit of emerging technologies (Decentralized Autonomous Organizations, blockchain, tokenization, and community currencies) as the new plows and seeders to actualize her bold dream to free the land. Venter’s story touches on all four cornerstones of Riane Eisler’s Partnership Framework: Gender, Family/Childhood, Economics, and Language/Narrative. Eisler urges that clarity of vision is required for new ideas to be translated into new realities. Venter embodies this vision by partnering with Indigenous farmers, technologists, and social scientists, to forge a new narrative of our enduring relationship with The Land.

Helping Our Women (HOW), a small 501(c)3 nonprofit organization serving women living with chronic or serious health conditions in the rural coastal region of Cape Cod, Massachusetts, US, has been operating as a partnership model for thirty years. This article reveals how Riane Eisler’s “right mindset” was present in the community culture that fostered HOW’s formation and is still present in its organizational DNA and explores how economically challenged rural communities value caring as essential work through their generosity and altruism. Rick Mauer’s Levels of Resistance model is used as a tool to explain some of the challenges of actualizing Eisler’s partnership ideal. Eisler’s foundational emphasis on mutual respect, accountability, spiritual courage, and equity is recognized as the through-line of continuous evolution and community resilience.

The role of central estrogen in cognitive, metabolic, and reproductive health has long fascinated the lay public and scientists alike. In the last two decades, insight into estrogen signaling in the brain and its impact on female physiology is beginning to catch up with the vast information already established for its actions on peripheral tissues. Using newer methods to manipulate estrogen signaling in hormone-sensitive brain regions, neuroscientists are now identifying the molecular pathways and neuronal subtypes required for controlling sex-dependent energy allocation. However, the immense cellular complexity of these hormone-sensitive brain regions makes it clear that more research is needed to fully appreciate how estrogen modulates neural circuits to regulate physiological and behavioral end points. Such insight is essential for understanding how natural or drug-induced hormone fluctuations across lifespan affect women's health.

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.

BackgroundThe current national burden of emergency general surgery (EGS) illnesses and the extent of surgeon involvement in the care of these patients remain largely unknown. To inform needs assessments, research, and education, we sought to: (1) translate previously developed International Classification of Diseases (ICD), 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes representing EGS conditions to ICD 10th Revision, CM (ICD-10-CM) codes and (2) determine the national burden of and assess surgeon involvement across EGS conditions.MethodsWe converted ICD-9-CM codes to candidate ICD-10-CM codes using General Equivalence Mappings then iteratively refined the code list. We used National Inpatient Sample 2016 to 2017 data to develop a national estimate of the burden of EGS disease. To evaluate surgeon involvement, using Wisconsin Hospital Association discharge data (January 1, 2016 to June 30, 2018), we selected adult urgent/emergent encounters with an EGS condition as the principal diagnosis. Surgeon involvement was defined as a surgeon being either the attending provider or procedural physician.ResultsFour hundred and eighty-five ICD-9-CM codes mapped to 1,696 ICD-10-CM codes. The final list contained 985 ICD-10-CM codes. Nationally, there were 2,977,843 adult patient encounters with an ICD-10-CM EGS diagnosis. Of 94,903 EGS patients in the Wisconsin Hospital Association data set, most encounters were inpatient as compared with observation (75,878 [80.0%] vs. 19,025 [20.0%]). There were 57,780 patients (60.9%) that underwent any procedure. Among all Wisconsin EGS patients, most had no surgeon involvement (64.9% [n = 61,616]). Of the seven most common EGS diagnoses, surgeon involvement was highest for appendicitis (96.0%) and biliary tract disease (77.1%). For the other five most common conditions (skin/soft tissue infections, gastrointestinal hemorrhage, intestinal obstruction/ileus, pancreatitis, diverticular disease), surgeons were involved in roughly 20% of patient care episodes.ConclusionSurgeon involvement for EGS conditions ranges from highly likely (appendicitis) to relatively unlikely (skin/soft tissue infections). The wide range in surgeon involvement underscores the importance of multidisciplinary collaboration in the care of EGS patients.Level of evidencePrognostic/epidemiological, Level III.