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Background—Autologous stem cell transplant (ASCT) is integral to the treatment of multiple myeloma (MM), although its absolute necessity in first remission has been recently questioned. We report real-world factors that influence clinical decision-making and outcomes from ASCT in 733 patients with MM. Results—Similar to recent prospective data, we found a significant progression-free survival (PFS) benefit with early versus deferred ASCT (median PFS of 5.1 years versus 2.6 years, p < 0.001); however, there was no significant difference in overall survival (median OS of 8.3 years and 8.6 years, p = 0.21). Patient preference, age, marital status, body mass index, and comorbidities influence ASCT timing. Conclusion—These findings highlight the emerging role of an individualized, shared decision-making model regarding the timing of ASCT between patients and physicians with the myriad of treatment options available in the contemporary era.

Summary: We assess the role of multi-day to seasonal long-duration energy storage (LDES) in a transmission-constrained system that lacks clean firm generation buildout. In this system, unless LDES is extremely inexpensive, short-duration energy storage (SDES) delivers 6–10× more electricity and has a consistently lower levelized cost. LDES substitutes for the role of a dispatchable firm resource. Next, we introduce the concept of a substitution ratio, which quantifies the interchangeability of different generation and storage resources. We show that in this system, 1 MW of LDES has the same system value as 14–19 MW of solar or wind with SDES, emphasizing that LDES is difficult to replace as a dispatchable baseload resource. Unlike other valuation metrics such as levelized cost, substitution ratios can quantify the system-level value of many different resources. Science for society: If emissions-free power from controllable sources such as nuclear energy or fossil fuels with carbon capture and storage is not accessible, long-duration energy storage (LDES) is essential for decarbonizing the electricity grid, as it helps balance supply and demand of electricity over extended periods when solar and wind power are unavailable. Our modeling shows that when LDES is affordable, it can reliably provide steady power, filling a role that is difficult for solar, wind, and other storage technologies to replace. Importantly, our study shows that short-duration energy storage (SDES) from batteries is also very valuable for the grid and that decarbonization is most cost effective when a portfolio of multiple generation and storage options is available. This research offers guidance for policy-makers and industry leaders to accelerate and lower the costs of grid decarbonization.

Knowledge of the reproductive biology of fishes is essential for effective fisheries management. Information derived from an understanding of fish reproduction, such as size and age at maturity, is used in models to assess fish stocks and can affect estimates of important ecological processes such as recruitment, abundance, and trophic interactions. Common practices for determining the reproductive status of teleost fishes include macroscopic evaluation of gonads as well as histological analysis. However, macroscopic evaluation can be biased and histological analysis is time-consuming, resulting in limitations to spatial and temporal data availability. Here, we explore Raman spectroscopy of ovaries as a novel approach to rapidly determine the reproductive status of walleye pollock (Gadus chalcogrammus), a commercially and ecologically important species in the North Pacific. We used a two-stage partial least-squares (PLS) regression analysis followed by a linear discriminant analysis (LDA) to classify walleye pollock ovary samples as physiologically mature or immature and to subsequently predict their histologically-determined reproductive stage based on the Raman spectra. Biologically mature samples with visible yolk differentiated from mature and immature samples (non-yolked; 99% accuracy). Non-yolked ovaries that were physiologically mature (either mature non-developing or previously spawned) were further differentiated from physiologically immature ovaries (93% accuracy). In addition, detailed, histologically-determined reproductive stages of yolked samples also differentiated via Raman spectroscopy, but with reduced accuracy (79% - 86% accuracy). Our results indicate that accurate identification of maturity status and the reproductive staging of oocytes of walleye pollock based on spectral data from ovaries is possible. This can provide a fast and efficient way to increase the availability of a key component of reproductive data to inform fisheries research and management.

Commonly used adenine-induced chronic kidney disease (CKD) murine models often employ C57BL/6 mice; however, this strain has inherent limitations due to its natural resistance to developing key pathological features of CKD, such as tubulointerstitial fibrosis and inflammation. There have been attempts to overcome these barriers by using multiple concentrations of adenine-supplemented diets or by performing prolonged experiments up to 20 weeks. Here, we demonstrate that SKH1 Elite mice develop clinically relevant CKD phenotypes (e.g., polyuria, proteinuria, inflammation, and renal fibrosis) over the course of only 6 weeks of low-dose (0.15%) adenine supplementation. As a docile, immunocompetent, and hairless strain, SKH1 Elite mice offer several logistical advantages over C57BL/6 mice, including ease of handling and the ability to study dermal conditions, which are often secondary to CKD.

We have conducted 0D, 1D, 2D, and 3D simulations of an idealized coaxial impedance-matched Marx generator (IMG) [Phys. Rev. Accel. Beams 20, 040402 (2017)PRABCJ2469-988810.1103/PhysRevAccelBeams.20.040402]. The 0D calculations were conducted with a four-element circuit model; the 1D, 2D, and 3D calculations were conducted with highly resolved, fully electromagnetic representations. The IMG consists of 30 stages distributed axially and connected electrically in series. Each stage is powered by two bricks separated by 180° and connected electrically in parallel. Each brick comprises two opposite-polarity capacitors in series with a single switch. The bricks drive an internal impedance-matched coaxial transmission line terminated by a resistive load. The simulations neglect effects due to the switch-triggering circuit, the capacitor-charging circuit, external conducting boundaries, and reactive components of the load. We find dimensionality does not significantly affect the electrical power delivered by the IMG to its load: peak load powers estimated by the 0D, 1D, 2D, and 3D simulations agree to within 1%. The 3D calculations demonstrate that electromagnetic power radiated by the bricks, and axial gaps between stages, reduces the peak load power by less than ∼1%. Each simulation assumes the load impedance is 34% above that at which the load power is maximized. Operating an IMG with such an overmatched load offers several advantages while decreasing the peak load power by only 2%. The 0D, 1D, 2D, and 3D models outlined herein could be adapted to assess computationally competing IMG designs, and conduct a variety of numerical IMG experiments, before an IMG is constructed.

Summary: The increasing cooling needs in commercial buildings, exacerbated by climate change, warrant immediate attention. These buildings, characterized by their long lifespans and slow stock turnover, change consumption over time. This study develops simple, interpretable data-driven models using weather- and occupancy-related features to analyze the cooling in different types of co-located buildings. Over five years, our models effectively predict the cooling load across buildings with R-squared values of 81%–87%. Factoring out geography-driven differences, we identify strong heterogeneity within and across different buildings. The average estimated base load cooling varies between 0.50 and 4.4 MJ/m2/day across buildings, with healthcare facilities exhibiting the highest loads and residences the lowest. Consumption increases by 7.6%–9.8% for every 1°C increase in mean daily outside temperature, with up to 27% reductions in offices on weekends. These insights enable diagnoses of inefficiencies, post-retrofitting performance tracking, and proactive planning for climate-related impacts.

Background: Accidents and injuries constitute a sizable share of mortality and morbidity in low- and middle-income countries. This affects the most productive age group and increases disability-adjusted life years (DALYs). It results in a substantial financial burden on the households. To explore the economic burden of accidents and Injuries on Indian households and to find how the catastrophic health expenditure (CHE) from accidents and injuries affects the population. Another objective is to explore Catastrophic out-of-pocket expenditures (OOPE) patterns and distressed financing of households in India. Materials and Methods: The study used data from the 75th round of nationally representative surveys, that is, the National Sample Survey (NSS). Authors have analyzed the data using descriptive binary logistic regression analysis to estimate the rate and average days of hospitalization, average OOPE, and share of the population experiencing the catastrophic impact from the health expenditure separately from the public and private healthcare institutions. Results: The study observed that hospitalization in the private sector imposes 72% of households incur CHE at more than 10% cut-off and 41% at more than 25% cut-off. In comparison, it is less in the public sector, with 22% of households incurring CHE at more than 10% of annual per capita household income and 9% at more than 25%. Conclusion: The increasing incidence of road traffic accidents (RTA) is a concern for the overstretched health system. The government should provide better healthcare facilities and universal health insurance coverage to ensure patients' speedy recovery and financial security.

The study discussed the telemedicine trends in the Philippines during the COVID-19 pandemic from 2019 to 2023. Determining the frequency of use of telemedicine, the factors that influenced its use before and during the COVID-19 pandemic, and the effects of telemedicine in improving the healthcare system in the Philippines. A systematic review was conducted using thematic analysis and the PRISMA checklist. The results presented a pattern indicating that teleconsultation usage corresponded to increased COVID-19 cases. Furthermore, telemedicine utilization surged from March 2020 to March 2022, with video consultations increasing from 5 to 495 monthly visits between 2019 and 2022. The study concluded that it was driven by increased mobile phone usage, improved patient satisfaction, government support, and increased video consultations, offering alternative healthcare delivery. Future studies should include more regions and timeframes to comprehensively present telemedicine trends in the Philippines.

Abstract As amniote vertebrates, lizards are the most closely related organisms to humans capable of appendage regeneration. Lizards can autotomize, or release their tails as a means of predator evasion, and subsequently regenerate a functional replacement. Green anoles (Anolis carolinensis) can regenerate their tails through a process that involves differential expression of hundreds of genes, which has previously been analyzed by transcriptomic and microRNA analysis. To investigate protein expression in regenerating tissue, we performed a whole proteomic analysis of regenerating tail tip and base. This is the first proteomic data set available for any anole lizard. We identified a total of 2646 proteins—976 proteins only in the regenerating tail base, 796 only in the tail tip, and 874 in both tip and base. For over 90% of these proteins in these tissues, we were able to assign a clear orthology to gene models in either the Ensembl or NCBI databases. For 13 proteins in the tail base, 9 proteins in the tail tip, and 10 proteins in both regions, the gene model in Ensembl and NCBI matched an uncharacterized protein, confirming that these predictions are present in the proteome. Ontology and pathways analysis of proteins expressed in the regenerating tail base identified categories, including actin filament‐based process, ncRNA metabolism, regulation of phosphatase activity, small GTPase‐mediated signal transduction, and cellular component organization or biogenesis. Analysis of proteins expressed in the tail tip identified categories, including regulation of organelle organization, regulation of protein localization, ubiquitin‐dependent protein catabolism, small GTPase‐mediated signal transduction, morphogenesis of epithelium, and regulation of biological quality. These proteomic findings confirm pathways and gene families activated in tail regeneration in the green anole as well as identify uncharacterized proteins whose role in regrowth remains to be revealed. This study demonstrates the insights that are possible from the integration of proteomic and transcriptomic data in tail regrowth in the green anole, with potentially broader application to studies in other regenerative models. KEY POINTS This research is highly interdisciplinary, combining our previous analyses with these most recent findings: Appendage regeneration is a conserved trait among vertebrates and has been characterized in animals ranging from teleost fish (zebrafish), urodele amphibians (axolotl), anuran amphibians (Xenopus frog), squamate reptiles (various species of lizards), and even crocodilians (American alligator). Comparative genomic and proteomic analysis of this process allows us to identify the genetic pathways and cellular processes under evolutionary selection for this regrowth capacity. Activating these conserved genetic pathways and cellular processes will be critical to developing regenerative medical therapies in humans. The identification of proteins expressed in regeneration extends analyses based only on predicted proteins from transcriptomic analysis, and permits integration with protein‐expression studies of regrowing nervous and musculoskeletal structures.

BackgroundAllogeneic stem cell transplant (allo-SCT) plays a key role in the treatment of patients with both acute myeloid leukemia (AML) and myelodysplastic (MDS). Outcomes of allo-SCT have improved with optimization of transplant practices. We sought to evaluate trends in survival in AML and MDS patients undergoing allo-SCT at our institution from 1984 to 2018.MethodsA retrospective analysis of 900 consecutive AML and MDS patients undergoing allo-SCT was performed. Patients were divided by year of transplant for analysis. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints included non-relapse mortality (NRM), graft-versus-host disease (GVHD), GVHD-free relapse free survival (GRFS), and transplant complications.ResultsWe found a significant improvement in survival from 1984 to 2018 with 5-year PFS and OS improving from 17% to 49% and 17% to 53%, respectively (statistically significant difference since 2004; p

Despite substantial recent advances in treatment, multiple myeloma (MM) remains an incurable disease, with a shortage of treatment options for patients with high-risk disease, warranting the need for novel therapeutic targets and treatment approaches. Threonine and tyrosine kinase (TTK), also known as monopolar spindle 1 (MPS1), is a kinase essential for the mitotic spindle checkpoint whose expression correlates to unfavorable prognosis in several cancers. Here, we report the importance of TTK in MM, and the effects of the TTK inhibitor OSU-13. Elevated TTK expression correlated with amplification/ gain of 1q21 and decreased overall and event-free survival in MM. Treatment with OSU-13 inhibited TTK activity efficiently and selectively at a similar concentration range to other TTK inhibitor clinical candidates. OSU-13 reduced proliferation and viability of primary human MM cells and cell lines, especially those with high 1q21 copy numbers, and triggered apoptosis through caspase 3 and 7 activation. In addition, OSU-13 induced DNA damage and severe defects in chromosome alignment and segregation, generating aneuploidy. In vivo, OSU-13 decreased tumor growth in mice with NCI-H929 xenografts. Collectively, our findings reveal that inhibiting TTK with OSU-13 is a potential therapeutic strategy for MM, particularly for a subset of high-risk patients with poor outcome.

Pumping energy is a key component of the groundwater governance challenge, yet it is largely missing in the discourse on agricultural use of groundwater. A sub-category of the literature studying groundwater-energy nexus tends to focus on groundwater depletion hotspots where entrenched interests and long-standing histories restrict the range of feasible energy pricing options. Using an agent-based model, we estimate the expected impact of expanding groundwater irrigation under five different energy provision models in Odisha, an Indian state with among the lowest irrigation coverage, and, therefore, is free of path-dependent policies. We find that aquifer properties play a crucial role in mediating the groundwater-energy nexus. In this study region, on average, the maximum volume of water that can be pumped from a well of a specific depth in an alluvial aquifer is approximately 150 times the volume that can be pumped from a well in a hard-rock aquifer. Therefore, the risk of over-consumption and aquifer depletion is a far greater challenge in alluvial than hard-rock aquifers. Risks of groundwater consumption and depletion can be limited in hard-rock aquifers provided the number and depths of wells can be controlled. Capital subsidies for well construction could be an effective policy to increase irrigated areas as long as economic incentives for digging deeper are not distorted. Our results imply that solar pumps are a relatively safe option for hard-rock regions where deep drawdowns naturally limit the extent of over-extraction. Solar pumps are also estimated to be among the most economical for expanding irrigation. Using a novel data set comprising biophysical and socioeconomic data, we find hard-rock regions to have limited irrigation coverage, high availability of annually replenishable groundwater, and high concentrations of marginalized farmers. Therefore, groundwater irrigation expansion in hard-rock areas could have dual benefits of ensuring future food security and targeting poverty reduction.

Objective To measure univariate and covariate‐adjusted trends in children's mental health‐related emergency department (MH‐ED) use across geographically diverse areas of the U.S. during the first wave of the Coronavirus‐2019 (COVID‐19) pandemic. Method This is a retrospective, cross‐sectional cohort study using electronic health records from four academic health systems, comparing percent volume change and adjusted risk of child MH‐ED visits among children aged 3–17 years, matched on 36‐week (3/18/19–11/25/19 vs. 3/16/20–11/22/20) and 12‐week seasonal time intervals. Adjusted incidence rate ratios (IRR) were calculated using multivariate Poisson regression. Results Visits declined during spring‐fall 2020 (n = 3892 vs. n = 5228, −25.5%) and during spring (n = 1051 vs. n = 1839, −42.8%), summer (n = 1430 vs. n = 1469, −2.6%), and fall (n = 1411 vs. n = 1920, −26.5%), compared with 2019. There were greater declines among males (28.2% vs. females −22.9%), children 6–12‐year (−28.6% vs. −25.9% for 3–5 years and −22.9% for 13–17 years), and Black children (−34.8% vs. −17.7% to −24.9%). Visits also declined for developmental disorders (−17.0%) and childhood‐onset disorders (e.g., attention deficit and hyperactivity disorders; −18.0%). During summer‐fall 2020, suicide‐related visits rose (summer +29.8%, fall +20.4%), but were not significantly elevated from 2019 when controlling for demographic shifts. In contrast, MH‐ED use during spring‐fall 2020 was significantly reduced for intellectual disabilities (IRR 0.62 [95% CI 0.47–0.86]), developmental disorders (IRR 0.71 [0.54–0.92]), and childhood‐onset disorders (IRR 0.74 [0.56–0.97]). Conclusions The early pandemic brought overall declines in child MH‐ED use alongside co‐occurring demographic and diagnostic shifts. Children vulnerable to missed detection during instructional disruptions experienced disproportionate declines, suggesting need for future longitudinal research in this population.

Digital mental health solutions are now well recognized as critical to solving the global mental health crisis. As research accelerates, it is now clear that solutions ranging from computer-based therapy programs to virtual reality headsets and smartphone apps to large language model chatbots are of interest, feasible, and hold exciting potential to improve mental health. This research should now consider the next generation of scientific and clinical questions regarding if these new approaches are equitable, valid, effective, implementable, efficacious, and even cost-effective. This paper outlines several of the new frontiers for the next generation of research and introduces JMIR Publications’ partnership with the Society of Digital Psychiatry to further advance these aims.

Background: Each year, nearly 300,000 women and 5 million fetuses or neonates die during childbirth or shortly thereafter, a burden concentrated disproportionately in low- and middle-income countries. Identifying women and their fetuses at risk for intrapartum-related morbidity and death could facilitate early intervention. Methods: The Limiting Adverse Birth Outcomes in Resource-Limited Settings (LABOR) Study is a multi-country, prospective, observational cohort designed to exhaustively document the course and outcomes of labor, delivery, and the immediate postpartum period in settings where adverse outcomes are frequent. The study is conducted at four hospitals across three countries in Ghana, India, and Zambia. We will enroll approximately 12,000 women at presentation to the hospital for delivery and follow them and their fetuses/newborns throughout their labor and delivery course, postpartum hospitalization, and up to 42 days thereafter. The co-primary outcomes are composites of maternal (death, hemorrhage, hypertensive disorders, infection) and fetal/neonatal adverse events (death, encephalopathy, sepsis) that may be attributed to the intrapartum period. The study collects extensive physiologic data through the use of physiologic sensors and employs medical scribes to document examination findings, diagnoses, medications, and other interventions in real time. Discussion: The goal of this research is to produce a large, sharable dataset that can be used to build statistical algorithms to prospectively stratify parturients according to their risk of adverse outcomes. We anticipate this research will inform the development of new tools to reduce peripartum morbidity and mortality in low-resource settings.

Abstract Background There is growing recognition that wellness interventions should occur in context and acknowledge complex contributors to wellbeing, including individual needs, institutional and cultural barriers to wellbeing, as well as systems issues which propagate distress. The authors conducted a multiple-methods study exploring contributors to wellbeing for junior residents in diverse medical environments who participated in a brief resilience and stress-reduction curriculum, the Stress Management and Resiliency Training Program for Residents (SMART-R). Methods Using a waitlist-controlled design, the curriculum was implemented for post-graduate year (PGY)-1 or PGY-2 residents in seven residency programs across three sites. Every three months, residents completed surveys, including the Perceived Stress Scale-10, General Self-Efficacy Questionnaire, a mindfulness scale (CAMSR), and a depression screen (PHQ-2). Residents also answered free-text reflection questions about psychological wellbeing and health behaviors. Results The SMART-R intervention was not significantly associated with decreased perceived stress. Linear regression modeling showed that depression was positively correlated with reported stress levels, while male sex and self-efficacy were negatively correlated with stress. Qualitative analysis elucidated differences in these groups: Residents with lower self-efficacy, those with a positive depression screen, and/or female residents were more likely to describe experiencing lack of control over work. Residents with higher self-efficacy described more positive health behaviors. Residents with a positive depression screen were more self-critical, and more likely to describe negative personal life events. Conclusions This curriculum did not significantly modify junior residents’ stress. Certain subpopulations experienced greater stress than others (female residents, those with lower self-efficacy, and those with a positive depression screen). Qualitative findings from this study highlight universal stressful experiences early in residency, as well as important differences in experience of the learning environment among subgroups. Tailored wellness interventions that aim to support diverse resident sub-groups may be higher yield than a “one size fits all” approach. Trial registration NCT02621801 , Registration date: December 4, 2015 – Retrospectively registered.

Abstract Background Metastasis is most often the root cause of cancer-related death. Human short stature homeobox 2 (SHOX2), a homeodomain transcription factor, is a novel inducer of epithelial-to-mesenchymal transition in breast cancer cells, though its exact role and underlying mechanisms in metastasis are not well understood. Methods TCGA analysis was performed to identify the clinical relevance of SHOX2 in breast cancer. Gene depletion was achieved by short hairpin RNA and small interfering RNA. Molecular regulations and alterations were assessed by Western blotting, immunoprecipitation, immunohistochemistry, qRT-PCR, chromatin immunoprecipitation coupled with qPCR (ChIP-qPCR), and ChIP/re-ChIP. The impact of SHOX2 signaling on tumor growth and metastasis was evaluated in orthotopic breast tumor mice. Results The expression level of SHOX2 is strongly associated with poor distant metastasis-free survival in breast cancer patients and inactivation of SHOX2 suppresses breast tumor growth and metastasis in mice. In breast cancer cells, SHOX2 directly activates Wiskott-Aldridge syndrome protein family member 3 (WASF3), a metastasis-promoting gene, at the transcriptional level, leading to a significant increase in metastatic potential. Mechanistically, SHOX2 activates signal transducer and activator of transcription 3 (STAT3) and recruits it to the WASF3 promoter, where STAT3 cooperates with SHOX2 to form a functional immunocomplex to promote WASF3 transcriptional activity in breast cancer cells. WASF3 knockdown abrogates SHOX2-induced metastasis, but not SHOX2-dependent tumorigenesis. Conclusions These findings provide a critical link between the SHOX2-STAT3-WASF3 signaling axis and metastasis and suggest that the targeting of this signaling node may represent a valuable alternative strategy for combating breast cancer metastasis.

Objectives: The prevalence and burden of neurological diseases are high among the older age group. Stroke and other neurological diseases significantly impair functional capacity and lead to poor quality of life. This study aims to provide a national-level estimate for palliative and supportive care needs among older Indian adults with stroke and other neurological diseases. Materials and Methods: The Longitudinal Ageing Study in India (LASI), a national-level survey of older adults, was used as a representative sample to estimate palliative and supportive care needs. The supportive and palliative care indicator tool income setting (SPICT-LIS) was used to identify palliative care needs in older adults with stroke and other neurological diseases. A total of 31,902 older adults aged 60 years and above were identified from the LASI data, and among them, 1458 older adults with stroke and other neurological diseases were selected for the analysis. The SPICT-LIS indicators were compared with the selected LASI data. Both univariate analysis and multivariate logistic regression were performed to determine the association between supportive and palliative care needs and background characteristics of older adults. Results: The analysis showed that 63.6% of older adults with stroke and other neurological diseases in India have supportive and palliative care needs. In regression analysis, the burden of supportive and palliative care needs was observed to be high among older adults who were in the underweight, overweight/obese category, who experienced ill-treatment, and who had diabetes and hypertension. In contrast, the burden of supportive and palliative care needs was observed to be low among older adults with stroke and neurological diseases who belonged to richer and richest economic quintiles, those receiving at least one social support scheme, those engaged in social activity and those performing physical activity. Conclusion: The palliative care needs among the older adult population with stroke and other neurological diseases in India are high. The findings of this study underscore the importance of screening for supportive and palliative care needs among patients with stroke and other neurological diseases to identify these unmet needs. The workforce trained in the provision of generalist and specialist palliative care will be required to meet this need, and the population of older adults is estimated to double in the next three decades. [ABSTRACT FROM AUTHOR]

BackgroundElectronic health records (EHRs) with large sample sizes and rich information offer great potential for dementia research, but current methods of phenotyping cognitive status are not scalable. ObjectiveThe aim of this study was to evaluate whether natural language processing (NLP)–powered semiautomated annotation can improve the speed and interrater reliability of chart reviews for phenotyping cognitive status. MethodsIn this diagnostic study, we developed and evaluated a semiautomated NLP-powered annotation tool (NAT) to facilitate phenotyping of cognitive status. Clinical experts adjudicated the cognitive status of 627 patients at Mass General Brigham (MGB) health care, using NAT or traditional chart reviews. Patient charts contained EHR data from two data sets: (1) records from January 1, 2017, to December 31, 2018, for 100 Medicare beneficiaries from the MGB Accountable Care Organization and (2) records from 2 years prior to COVID-19 diagnosis to the date of COVID-19 diagnosis for 527 MGB patients. All EHR data from the relevant period were extracted; diagnosis codes, medications, and laboratory test values were processed and summarized; clinical notes were processed through an NLP pipeline; and a web tool was developed to present an integrated view of all data. Cognitive status was rated as cognitively normal, cognitively impaired, or undetermined. Assessment time and interrater agreement of NAT compared to manual chart reviews for cognitive status phenotyping was evaluated. ResultsNAT adjudication provided higher interrater agreement (Cohen κ=0.89 vs κ=0.80) and significant speed up (time difference mean 1.4, SD 1.3 minutes; P

For over a century the nervous system of decapod crustaceans has been a workhorse for the neurobiology community. Many fundamental discoveries including the identification of electrical and inhibitory synapses, lateral and pre-synaptic inhibition, and the Na+/K+-pump were made using lobsters, crabs, or crayfish. Key among many advantages of crustaceans for neurobiological research is the unique access to large, accessible, and identifiable neurons, and the many distinct and complex behaviors that can be observed in lab settings. Despite these advantages, recent decades have seen work on crustaceans hindered by the lack of molecular and genetic tools required for unveiling the cellular processes contributing to neurophysiology and behavior. In this perspective paper, we argue that the recently sequenced marbled crayfish, Procambarus virginalis, is suited to become a genetic model system for crustacean neuroscience. P. virginalis are parthenogenetic and produce genetically identical offspring, suggesting that germline transformation creates transgenic animal strains that are easy to maintain across generations. Like other decapod crustaceans, marbled crayfish possess large neurons in well-studied circuits such as the giant tail flip neurons and central pattern generating neurons in the stomatogastric ganglion. We provide initial data demonstrating that marbled crayfish neurons are accessible through standard physiological and molecular techniques, including single-cell electrophysiology, gene expression measurements, and RNA-interference. We discuss progress in CRISPR-mediated manipulations of the germline to knock-out target genes using the ‘Receptor-mediated ovary transduction of cargo’ (ReMOT) method. Finally, we consider the impact these approaches will have for neurophysiology research in decapod crustaceans and more broadly across invertebrates.

Summary: Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.

BackgroundAllogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT.MethodsWe performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS).ResultsOf the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence.ConclusionOur study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers.

Although representations of female scientists in the media have increased over time, stereotypical portrayals of science persist. In-depth, contemporary profiles of scientists’ roles have an opportunity to reflect or to challenge stereotypes of science and of gender. We employed content and linguistic analyses to examine whether publicly available profiles of scientists from New York Times and The Scientist Magazine support or challenge pervasive beliefs about science. Consistent with broader stereotypes of STEM fields, these portrayals focused more on agency than communality. However, profiles also challenged stereotypes through integrating communality, purpose, and growth. This analysis also found similar presence of communal and agentic constructs for both female and male scientists. The current findings highlight the importance of considering counterstereotypic representations of science in the media: Communicating messages to the public that challenge existing beliefs about the culture of science may be one path toward disrupting stereotypes that dissuade talented individuals from choosing science pathways.

Carbon capture and storage (CCS) is an essential technology for achieving carbon neutrality. Depositional environments with sandstone and interbedded shale layers are promising for CO2 storage because they can retain CO2 beneath continuous and discontinuous shale layers. However, conventional numerical simulation of shale–sandstone systems is computationally challenging due to the large contrast in properties between the shale and sandstone layers and significant impact of thin shale layers on CO2 migration. Extending recent advancements in Fourier neural operators (FNOs), we propose a new deep learning architecture, the RU-FNO, to predict CO2 migration in complex shale–sandstone reservoirs under various reservoir conditions, injection designs, and rock properties. The gas saturation plume and pressure buildup predictions of the RU-FNO model are 8000-times faster than traditional numerical models and exhibit remarkable accuracy. We utilize the model’s fast prediction to investigate the impact of shale layer characteristics on plume migration and pressure buildup. These case studies show that shale–sandstone reservoirs with moderate heterogeneity and spatial continuity can minimize the plume footprint and maximize storage efficiency.

Telehealth services have expanded dramatically during the coronavirus disease-2019 pandemic; we provide estimates of telehealth use and satisfaction based on a nationally representative, random survey of 3454 U.S. households. Fifty percent of households reported using telehealth because they could not receive medical care in person. Satisfaction was high among telehealth users (86%). However, satisfaction with telehealth was lower (65%) among households who reported experiences of delayed medical care for serious problems. Telehealth use was lower among rural households than urban households (46% vs. 53%) and among

Background: Temperature elevation, a classic marker of infection and local temperature elevation, might be a useful predictor of early infection. However temperature measurement around the spine is not readily accessible. The purpose of this study was to explore whether a temperature sensing implant might reproducibly detect local temperature change associated with peri-implant wound infection, in a rabbit model. Methods: Twelve adult rabbits were implanted with a spinal screw-rod construct. Temperature probes were placed at the implantation site as well as at a separate scapular site away from the surgical site to serve as control. Animals were inoculated with S. aureus: group 1 (saline control), group 2 (low dose 1 × 102 CFU/site), group 3 (medium dose 1 × 104 CFU/site), and group 4 (high dose 1 × 106 CFU/site) and monitored for 7 days prior to euthanasia. Results: The scapular control temperature and implant site temperature in the non-infected animals remained similar throughout the study period. Both the scapular control and implant site temperatures were elevated in the infected animals compared to the non-infected animals. There was a statistically significant difference in the scapular control temperature and implant site temperature in all infected animals but not in the non-infected animals. Difference in temperature elevation between implant site and control scapular site were greatest for the animals with worst clinical appearance during the post-mortem evaluation. Conclusions: This rabbit model demonstrates that local temperature measured in proximity to a spinal implant is elevated in the presence of infection with greater elevations associated with worse infections. Availability of an implantable temperature sensor may yield valuable information for the assessment and treatment of suspected spinal wound infection in the clinical setting.

An improved implementation of the perfectly matched layer (PML) is developed for the Transmission Line Modelling (TLM) method based on a mapping of the symmetrical condensed node (SCN) to an analytically extended geometric space. By mapping the TLM node, a medium - circuit equivalence is developed which maps transmission line parameters from real to complex domain. This consequently modifies the TLM scatter-connect process. The PML implementation is demonstrated for canonical cases where it is shown to have a comparable absorption performance and a significantly improved temporal stability relative to previously published TLM-PML formulations.

LEED v4 for Neighborhood Development (LEED-ND) is a neighborhood sustainability assessment tool developed through a collaborative effort between the United States Green Building Council, the Congress for the New Urbanism, and the Natural Resources Defense Council. LEED-ND utilizes a credit-based ratings system that serves as a template for the development of green, sustainable neighborhoods. This research study analyzes the locational and demographic attributes of 246 proposed, completed, and/or in progress LEED-ND sites to better understand whether LEED-ND and its ratings system are achieving its goal of promoting greater social equity. This study analyzes the temporal changes of eight demographic variables that are indicative of neighborhood gentrification. These variables include educational attainment, median income, median rent, median land values, household size, median age, percent non-white, and racial diversity. Statistically significant changes to educational attainment, median rent, and diversity were observed at various geographic levels. It was also determined that the effects of LEED-ND developments are likely felt beyond the physical boundaries of the sites. The findings suggest that LEED-ND developments may function as catalysts of neighborhood gentrification rather than promoting greater social equity.