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Predicting the evolution of fractured media is challenging due to coupled thermal, hydrological, chemical and mechanical processes that occur over a broad range of spatial scales, from the microscopic pore scale to field scale. We present a software framework and scientific workflow that couples the pore scale flow and reactive transport simulator Chombo-Crunch with the field scale geomechanics solver in GEOS to simulate fracture evolution in subsurface fluid-rock systems. This new multiphysics coupling capability comprises several novel features. An HDF5 data schema for coupling fracture positions between the two codes is employed and leverages the coarse resolution of the GEOS mechanics solver which limits the size of data coupled, and is, thus, not taxed by data resulting from the high resolution pore scale Chombo-Crunch solver. The coupling framework requires tracking of both before and after coarse nodal positions in GEOS as well as the resolved embedded boundary in Chombo-Crunch. We accomplished this by developing an approach to geometry generation that tracks the fracture interface between the two different methodologies. The GEOS quadrilateral mesh is converted to triangles which are organized into bins and an accessible tree structure; the nodes are then mapped to the Chombo representation using a continuous signed distance function that determines locations inside, on and outside of the fracture boundary. The GEOS positions are retained in memory on the Chombo-Crunch side of the coupling. The time stepping cadence for coupled multiphysics processes of flow, transport, reactions and mechanics is stable and demonstrates temporal reach to experimental time scales. The approach is validated by demonstration of 9 days of simulated time of a core flood experiment with fracture aperture evolution due to invasion of carbonated brine in wellbore-cement and sandstone. We also demonstrate usage of exascale computing resources by simulating a high resolution version of the validation problem on OLCF Frontier.

Deaths related to opioid overdoses continue to climb, and there remains a need for innovative strategies to address this ongoing crisis. Harm reduction (HR), a nonjudgmental philosophy aimed at reducing consequences associated with drug use and other potentially unsafe behavior, has emerged as a compassionate and effective approach. Harm reduction further emphasizes overdose prevention and fosters a shift in perspective that recognizes substance use disorder as a disease and not a moral failing. The tenets of HR collectively advocate for the well-being of individuals who use substances and support any positive change as defined by the individual. Given the high rate of morbidity and mortality associated with substance misuse and barriers or ambivalence to receiving treatment, awareness of and advocacy for HR practice is essential. This manuscript aims to describe evidence-based HR interventions, provide a foundation for the implementation of services, and further promote the importance of providing humanistic care without judgment. As valued members of the multidisciplinary treatment team, Board-Certified Psychiatric Pharmacists should implement and engage in HR services in the settings where people with substance use disorders receive care.

Reporting interventions thoroughly and consistently in the literature allows for study reproducibility or implementation of the intervention into practice. Although there is currently no standard for describing Board-Certified Psychiatric Pharmacist (BCPP) interventions in the published literature, there are multiple checklists or guides that have been developed for reporting clinical interventions, including the template for intervention description and replication and the pharmacist patient care intervention reporting (PaCIR) checklist, that seek to improve the quality of reporting interventions in the literature. The purpose of this paper is to describe a proposed guide for reporting BCPP interventions in the literature by expanding the PaCIR checklist. Authors use a logic model developed by the American Association of Psychiatric Pharmacists to ensure all elements of the process are addressed in the expanded guide.

Axonal regeneration following surgical nerve repair is slow and often incomplete, resulting in poor functional recovery which sometimes contributes to lifelong disability. Currently, there are no FDA-approved therapies available to promote nerve regeneration. Tacrolimus accelerates axonal regeneration, but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery. The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site, with suitable properties for scalable production and clinical application, aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure. Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days. Size and drug loading are adjustable for applications in small and large caliber nerves, and the wrap degrades within 120 days into biocompatible byproducts. Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80% compared with systemic delivery. Given its surgical suitability and preclinical efficacy and safety, this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Abstract Background Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse transcriptase inhibitor-based regimens. Resolution of symptoms have occurred with switches to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; however, little is known regarding the development of angiolipomas when switching from NNRTI- to modern, integrase strand transfer inhibitor-based regimens. We describe a patient who underwent switch therapy from tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) to tenofovir alafenamide/FTC/bictegravir (TAF/FTC/BIC) who later developed angiolipomas. Case Presentation A 55-year-old male had been on TDF/FTC/EFV for 8 years before switching to TAF/FTC/BIC. Nineteen months after antiretroviral switch, the patient presented with multiple lesions in the upper extremities and abdomen. Diagnostic biopsies revealed non-encapsulated angiolipomas and HHV-8 and non-alcoholic fatty liver disease was ruled out. New lesions continued to appear 29 months after ART switch, after which now lesions appeared and prior lesions remained stable with no increase in size noted. No surgical intervention or change in antiretroviral therapy was needed. Conclusions Angiogenesis may have been suppressed with TDF/FTC/EFV treatment, however when switched to TAF/FTC/BIC, promoted the growth of angiolipomas. Clinicians should be aware of the impact of switching to modern ART therapies resulting in possible adipogenesis.

Introduction Despite the prevalence of corticosteroid injections in athletes, little is known about their efficacy in triathletes. We aim to assess attitudes, use, subjective effectiveness, and time to return to sport with corticosteroid injections compared to alternative methods in triathletes with knee pain. Methods This is an observational study during the COVID-19 pandemic. Triathletes answered a 13-question survey posted to three triathlon-specific websites. Results Sixty-one triathletes responded, 97% of whom experienced knee pain at some point in their triathlete career; 63% with knee pain received a corticosteroid injection as treatment (average age 51 years old). The most popular attitude (44.3%) regarding corticosteroid injections was "tried them, with good improvement". Most found the cortisone injection helpful for two to three months (28.6%), or more than one year (28.6%); of individuals who found the injections useful for more than one year, four-eight (50%) had received multiple injections during that same period. After injection, 80.6% returned to sport within one month. The average age of people using alternative treatment methods was 39 years old; most returned to sport within one month (73.7%). Compared to alternative methods, there was an ~80% higher odds of returning to sport within one month using corticosteroid injections; however, this relationship was not significant (OR=1.786, p=0.480, 95% CI:0.448-7.09). Conclusion This is the first study to examine corticosteroid use in triathletes. Corticosteroid use is more common in older triathletes and results in subjective pain improvement. A strong association does not exist for a quicker return to sport using corticosteroid injections compared to alternative methods. Triathletes should be counseled on the timing of injections, duration of side effects, and be aware of potential risks.

Terrestrial open water evaporation is difficult to measure both in situ and remotely yet is critical for understanding changes in reservoirs, lakes, and inland seas from human management and climatically altered hydrological cycling. Multiple satellite missions and data systems (e.g., ECOSTRESS, OpenET) now operationally produce evapotranspiration (ET), but the open water evaporation data produced over millions of water bodies are algorithmically produced differently than the main ET data and are often overlooked in evaluation. Here, we evaluated the open water evaporation algorithm, AquaSEBS, used by ECOSTRESS and OpenET against 19 in situ open water evaporation sites from around the world using MODIS and Landsat data, making this one of the largest open water evaporation validations to date. Overall, our remotely sensed open water evaporation retrieval captured some variability and magnitude in the in situ data when controlling for high wind events (instantaneous: r2 = 0.71; bias = 13% of mean; RMSE = 38% of mean). Much of the instantaneous uncertainty was due to high wind events (u > mean daily 7.5 m·s-1) when the open water evaporation process shifts from radiatively-controlled to atmospherically-controlled; not accounting for high wind events decreases instantaneous accuracy significantly (r2 = 0.47; bias = 36% of mean; RMSE = 62% of mean). However, this sensitivity minimizes with temporal integration (e.g., daily RMSE = 1.2-1.5 mm·day-1). To benchmark AquaSEBS, we ran a suite of 11 machine learning models, but found that they did not significantly improve on the process-based formulation of AquaSEBS suggesting that the remaining error is from a combination of the in situ evaporation measurements, forcing data, and/or scaling mismatch; the machine learning models were able to predict error well in and of itself (r2 = 0.74). Our results provide confidence in the remotely sensed open water evaporation data, though not without uncertainty, and a foundation by which current and future missions may build such operational data.

Upper extremity amputations represent a prime opportunity to restore function through replantation. There are a variety of options that treating surgeons use to protect neurovascular repairs and restore function including Kirschner wire fixation, external fixation, wrist arthrodesis, and proximal row carpectomy. Additionally, the dorsal spanning plate may be a valuable tool for protecting neurovascular repairs. Compared to temporary immobilization with Kirschner wire fixation, which has previously been described in conjunction with upper extremity replantation, dorsal spanning plates can be left in place for longer durations with a lower risk of loosening and loss of fixation and for preventing postoperative sabotage or repeat amputation of the replant by the patient. In this article, we describe a unique case of a patient with acute psychiatric illness that presented with a self-inflicted amputation through the radiocarpal joint and was initially treated with emergent replantation and application of a dorsal spanning plate to protect the neurovascular repair from patient sabotage and allow for early rehabilitation. We found the dorsal spanning plate to be an effective option in this complex clinical scenario. This case illustrates the utility of the dorsal spanning plate in protecting complex neurovascular repairs in the setting of severe skeletal and psychiatric instability.

Abstract Substantial literature documents the impact of mass traumatic events on post-traumatic stress disorder (PTSD) in populations. However, the trajectory of PTSD in the US population during the pandemic and the association between assets, Covid-19 related stressors, and PTSD over time remains unclear. The Covid-19 and Life Stressors Impact on Mental Health and Well-Being (CLIMB) is a nationally representative, longitudinal panel of US adults in Spring 2020 (N = 1270), 2021 (N = 1182), and 2022 (N = 1091). Using the four-item PC-PTSD-4, we assessed the prevalence of probable PTSD in the US population over three years. Using generalized estimating equations (GEE) and logistic regression at each wave, we estimated associations of demographics, assets, and stressors with probable PTSD. Here we report that the overall prevalence of PTSD decreases from 22.2% in 2020 to 16.8% in 2022 (p = 0.02). Persons with household incomes below $20,000 report higher prevalence of probable PTSD compared to other income groups. The GEE model shows higher odds of probable PTSD among persons with household incomes below $20,000 (OR = 2.17 (95%CI: 1.35,3.50)) relative to $75,000 or more; and high stressor scores (OR = 2.33 (95%CI: 1.72,3.15)) compared to low stressor scores. High stressor scores are associated with higher odds of probable PTSD in 2020 (OR = 2.69 (95%CI: 1.56,4.66)), 2021 (OR = 4.58 (95%CI: 2.52,8.30)), and 2022 (OR = 3.89 (95%CI: 2.05,7.38)) compared to low stressor scores. This analysis highlights the pandemic’s prolonged influence on population mental health, particularly among persons with fewer economic assets and those experiencing more pandemic-related stressors. Reducing mental health disparities requires interventions to address inequities.

Introduction Pharmacists focusing on psychotropic medication management and practicing across a wide variety of healthcare settings have significantly improved patient-level outcomes. The Systematic Literature Review Committee of the American Association of Psychiatric Pharmacists was tasked with compiling a comprehensive database of primary literature highlighting the impact of psychiatric pharmacists on patient-level outcomes. Methods A systematic search of literature published from January 1, 1961, to December 31, 2022, was conducted using PubMed and search terms based on a prior American Association of Psychiatric Pharmacists literature review. Publications describing patient-level outcome results associated with pharmacist provision of care in psychiatric/neurologic settings and/or in relation to psychotropic medications were included. The search excluded articles for which there was no pharmacist intervention, no psychiatric disorder treatment, no clinical outcomes, no original research, no access to full text, and/or no English-language version. Results A total of 4270 articles were reviewed via PubMed, with 4072 articles excluded based on title, abstract, and/or full text in the initial pass and 208 articles selected for inclusion. A secondary full-text review excluded 11 additional articles, and 5 excluded articles were ultimately included based on a secondary review, for a final total of 202 articles meeting the inclusion criteria. A comprehensive database of these articles was compiled, including details on their study designs and outcomes. Discussion The articles included in the final database had a wide range of heterogeneity. While the overall impact of psychiatric pharmacists was positive, the study variability highlights the need for future publications to have more consistent, standardized outcomes with stronger study designs.

Conserving bird populations is a key goal for management of the Sacramento–San Joaquin Delta ecosystem and is likely to have effects well beyond its boundaries. To inform bird- conservation strategies, we identified Priority Bird Conservation Areas for riparian landbirds and waterbirds in the Delta, defined as the most valuable 5% of the landscape for each group. We synthesized data from 2,547 surveys for riparian landbirds and 7,820 surveys for waterbirds to develop predictive distribution models, which then informed spatial prioritization analyses. We identified a total of 26,019 ha that are a high priority for conserving riparian landbirds, waterbirds, or both, representing the most important places in the Delta to protect and manage, as well as strategic areas where adjacent restoration could expand valuable habitat. These Priority Bird Conservation Areas include the Yolo Bypass Wildlife Area, Cosumnes River Preserve, Stone Lakes National Wildlife Refuge, and bufferlands that surround the Sacramento County Regional Sanitation District. However, we also found that over 60% of the Priority Bird Conservation Areas are not currently protected, indicating a vulnerability to changes in land cover or land use. We recommend advancing strategies for bird conservation in the Delta by developing more specific objectives and priorities, extending these analyses to include other bird species, and planning to mitigate the loss of Priority Bird Conservation Areas where they are most vulnerable to land cover change. The predictive models and analysis framework we developed represent the current state of the science on areas important to bird conservation, while also providing a foundation for an evolving bird-conservation strategy that reflects the Delta’s continuously evolving knowledge base and landscape.

Abstract Cellular phenotypes and functional responses are modulated by the signals present in their microenvironment, including extracellular matrix (ECM) proteins, tissue mechanical properties, soluble signals and nutrients, and cell–cell interactions. To better recapitulate and analyze these complex signals within the framework of more physiologically relevant culture models, high throughput culture platforms can be transformative. High throughput methodologies enable scientists to extract increasingly robust and broad datasets from individual experiments, screen large numbers of conditions for potential hits, better qualify and predict responses for preclinical applications, and reduce reliance on animal studies. High throughput cell culture systems require uniformity, assay miniaturization, specific target identification, and process simplification. In this review, we detail the various techniques that researchers have used to face these challenges and explore cellular responses in a high throughput manner. We highlight several common approaches including two‐dimensional multiwell microplates, microarrays, and microfluidic cell culture systems as well as unencapsulated and encapsulated three‐dimensional high throughput cell culture systems, featuring multiwell microplates, micromolds, microwells, microarrays, granular hydrogels, and cell‐encapsulated microgels. We also discuss current applications of these high throughput technologies, namely stem cell sourcing, drug discovery and predictive toxicology, and personalized medicine, along with emerging opportunities and future impact areas.

Abstract The continued emergence of highly pathogenic viruses, which either thwart immune- and small molecule-based therapies or lack interventions entirely, mandates alternative approaches, particularly for prompt and facile pre- and post-exposure prophylaxis. Many highly pathogenic viruses, including coronaviruses, employ the six-helix bundle heptad repeat membrane fusion mechanism to achieve infection. Although heptad-repeat-2 decoys can inhibit viral entry by blocking six-helix bundle assembly, the biophysical and pharmacologic liabilities of peptides have hindered their clinical development. Here, we develop a chemically stapled lipopeptide inhibitor of SARS-CoV-2 as proof-of-concept for the platform. We show that our lead compound blocks infection by a spectrum of SARS-CoV-2 variants, exhibits mucosal persistence upon nasal administration, demonstrates enhanced stability compared to prior analogs, and mitigates infection in hamsters. We further demonstrate that our stapled lipopeptide platform yields nanomolar inhibitors of respiratory syncytial, Ebola, and Nipah viruses by targeting heptad-repeat-1 domains, which exhibit strikingly low mutation rates, enabling on-demand therapeutic intervention to combat viral outbreaks.

AbstractFrom the first cases in 2019, COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have resulted in over 6 million human deaths in a worldwide pandemic. SARS-CoV-2 is commonly spread from human to human through close contact and is capable of infecting both humans and animals. Worldwide, there have been over 675 animal outbreaks reported that resulted in over 2000 animal infections including domestic and wild animals. As the role of animal infections in the transmission, pathogenesis, and evolution of SARS-CoV-2 is still unfolding, accurate and reliable animal diagnostic tests are critical to aid in managing both human and animal health. This review highlights key animal samples and the three main diagnostic approaches used for animal testing: PCR, serology, and Next Generation Sequencing. Diagnostic results help inform (often difficult) clinical decision-making, but also possible ways to mitigate spread among pets, food supplies, or wildlife. A One Health approach has been key to monitoring the SARS-CoV-2 pandemic, as consistent human-animal interactions can lead to novel variants. Having multiple animal diagnostic tests for SARS-CoV-2 available is critical to ensure human, animal, and environmental health.