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PURPOSE: Systemic therapy with atezolizumab and bevacizumab can extend life for patients with advanced hepatocellular carcinoma (HCC). However, there is substantial variability in response to therapy and overall survival. Although current prognostic models have been validated in HCC, they primarily consider covariates that may be reflective of the severity of the underlying liver disease of patients with HCC. We developed and internally validated a classification and regression tree (CART) to identify patient characteristics associated with risks of early mortality, at or before 6 months from treatment initiation. METHODS: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived deidentified database and included patients with a diagnosis of HCC after January 1, 2020, who received initial systemic therapy with atezolizumab and bevacizumab. CART was developed from available baseline clinical and demographic information to predict mortality within 6 months from treatment initiation. Model characteristics were compared to the albumin-bilirubin (ALBI) model and was further validated against a contemporary validation cohort of patients after a data update. RESULTS: A total of 293 patients were analyzed. The CART identified seven cohorts of patients from baseline demographic and laboratory characteristics. The model had an area under the receiver operating curve (AUROC) of 0.739 (95% CI, 0.683 to 0.794) for predicting 6-month mortality. This model was internally valid and performed more favorably than the ALBI model, which had an AUROC of 0.608 (95% CI, 0.557 to 0.660). The model applied to the contemporary validation cohort (n = 111) had an AUROC of 0.666 (95% CI, 0.506 to 0.826). CONCLUSION: Using CART, we identified unique cohorts of patients with HCC treated with atezolizumab and bevacizumab with distinct risks of early mortality. This approach outperformed the ALBI model and used clinical and laboratory characteristics that are readily available to oncologists caring for these patients.
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Anticuerpos Monoclonales Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Masculino , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
There is growing interest in material candidates with properties that can be engineered beyond traditional design limits. Compositionally complex oxides (CCO), often called high entropy oxides, are excellent candidates, wherein a lattice site shares more than four cations, forming single-phase solid solutions with unique properties. However, the nature of compositional complexity in dictating properties remains unclear, with characteristics that are difficult to calculate from first principles. Here, compositional complexity is demonstrated as a tunable parameter in a spin-transition oxide semiconductor La1- x(Nd, Sm, Gd, Y)x/4CoO3, by varying the population x of rare earth cations over 0.00≤ x≤ 0.80. Across the series, increasing complexity is revealed to systematically improve crystallinity, increase the amount of electron versus hole carriers, and tune the spin transition temperature and on-off ratio. At high a population (x = 0.8), Seebeck measurements indicate a crossover from hole-majority to electron-majority conduction without the introduction of conventional electron donors, and tunable complexity is proposed as new method to dope semiconductors. First principles calculations combined with angle resolved photoemission reveal an unconventional doping mechanism of lattice distortions leading to asymmetric hole localization over electrons. Thus, tunable complexity is demonstrated as a facile knob to improve crystallinity, tune electronic transitions, and to dope semiconductors beyond traditional means.
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This national US study determined the causal impact of shared decision making (SDM) on pain outcomes, including any overall pain and the subcategories of any acute pain and any chronic pain. We additionally examined whether the causal impact of SDM on overall pain is moderated by gender, race-ethnicity, clinician-patient racial-ethnic concordance, and clinician-patient gender concordance. We used national US data from the 2003-2017 Medical Expenditure Panel Survey, which were externally valid to the US national non-institutionalized population, employed a standard measure of shared decision making, and applied an internally-valid two-stage least squares approach that used the peer SDM behavior of similar clinicians as an instrument. The instrument was sufficiently strong and statistically uncorrelated with patient characteristics. We found a large impact of SDM on both female and male chronic pain outcomes, where the effect for females was approximately 50% larger than for males, with a 10 percentage point increase in SDM quality resulted fewer females experiencing chronic pain that interfered with everyday activities (-24.8 percentage points; 95% confidence interval [CI]: 43.3, -6.4) than males (-16.5 percentage points; 95% CI: 32.9, -1.0). We estimated that a 10 percentage point national increase in the SDM index would thus result in 10.1 million fewer females and 5.7 million fewer males in the US experiencing chronic pain that interfered with their daily activities. Policy implications include both increasing the quality of SDM for all patients and educating male patients on the value of SDM.
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Toma de Decisiones Conjunta , Humanos , Masculino , Femenino , Factores Sexuales , Persona de Mediana Edad , Adulto , Estados Unidos , Dolor Crónico/psicología , Anciano , Encuestas y Cuestionarios , Relaciones Médico-PacienteRESUMEN
INTRODUCTION: Despite several therapeutic advancements, the proportion of patients with advanced biliary tract cancers (BTC) surviving 5 years from diagnosis remains dismal. The increasing recognition of targetable genetic alterations in BTCs has ushered in a new era in the treatment of these patients. Newer therapeutic agents targeting mutations such as isocitrate dehydrogenase (IDH), fibroblastic growth factor receptor (FGFR), human epidermal growth factor receptor (HER), and so on have established a new standard of care for treatment upon progression on frontline therapy in patients with disease harboring these mutations. AREAS COVERED: The current review aims to concisely summarize progress with various targeted therapy options for BTC. We also briefly discuss future directions in clinical and translational research for the adoption of a personalized approach for the treatment of unresectable or advanced BTC. EXPERT OPINION: Several new agents continue to emerge as feasible treatment options for patients with advanced BTC harboring targetable mutations. There is a growing need to identify mechanisms to conquer primary and acquired resistance to these agents. The identification of potential biomarkers that predict response to targeted therapy may be helpful in adopting a more tailored approach. All patients receiving treatment for advanced BTC should undergo tissue genomic profiling at diagnosis.
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Antineoplásicos , Neoplasias del Sistema Biliar , Terapia Molecular Dirigida , Mutación , Medicina de Precisión , Humanos , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/genética , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Resistencia a Antineoplásicos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Tasa de Supervivencia , Progresión de la Enfermedad , AnimalesRESUMEN
Neuroimaging is a popular method to map brain structural and functional patterns to complex human traits. Recently published observations cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional magnetic resonance imaging (MRI). We leverage baseline data from thousands of children in the Adolescent Brain Cognitive DevelopmentSM Study to inform the replication sample size required with univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 41 individuals in the replication sample for working memory-related functional MRI, and ~ 100 subjects for structural and resting state MRI. Even with 100 random re-samplings of 100 subjects in discovery, prediction can be adequately powered with 66 subjects in replication for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many research programs and grants.
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Encéfalo , Cognición , Imagen por Resonancia Magnética , Neuroimagen , Humanos , Adolescente , Imagen por Resonancia Magnética/métodos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Masculino , Femenino , Cognición/fisiología , Neuroimagen/métodos , Memoria a Corto Plazo/fisiología , Niño , Desarrollo del Adolescente/fisiología , Mapeo Encefálico/métodosRESUMEN
Heat dissipation is a natural consequence of operating any electronic system. In nearly all computing systems, such heat is usually minimized by design and cooling. Here, we show that the temporal dynamics of internally produced heat in electronic devices can be engineered to both encode information within a single device and process information across multiple devices. In our demonstration, electronic NbOx Mott neurons, integrated on a flexible organic substrate, exhibit 18 biomimetic neuronal behaviours and frequency-based nociception within a single component by exploiting both the thermal dynamics of the Mott transition and the dynamical thermal interactions with the organic substrate. Further, multiple interconnected Mott neurons spatiotemporally communicate purely via heat, which we use for graph optimization by consuming over 106 times less energy when compared with the best digital processors. Thus, exploiting natural thermal processes in computing can lead to functionally dense, energy-efficient and radically novel mixed-physics computing primitives.
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Light exposure is a vital regulator of physiology and behavior in humans. However, monitoring of light exposure is not included in current wearable Internet of Things (IoT) devices, and only recently have international standards defined [Formula: see text] -optic equivalent daylight illuminance (EDI) measures for how the eye responds to light. This article reports a wearable light sensor node that can be incorporated into the IoT to provide monitoring of EDI exposure in real-world settings. We present the system design, electronic performance testing, and accuracy of EDI measurements when compared to a calibrated spectral source. This includes consideration of the directional response of the sensor, and a comparison of performance when placed on different parts of the body, and a demonstration of practical use over 7 days. Our device operates for 3.5 days between charges, with a sampling period of 30 s. It has 10 channels of measurement, over the range 415-910 nm, balancing accuracy and cost considerations. Measured [Formula: see text]-opic EDI results for 13 devices show a mean absolute error of less than 0.07 log lx, and a minimum between device correlation of 0.99. These findings demonstrate that accurate light sensing is feasible, including at wrist worn locations. We provide an experimental platform for use in future investigations in real-world light exposure monitoring and IoT-based lighting control.
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We developed a significantly improved genetically encoded quantitative adenosine triphosphate (ATP) sensor to provide real-time dynamics of ATP levels in subcellular compartments. iATPSnFR2 is a variant of iATPSnFR1, a previously developed sensor that has circularly permuted superfolder green fluorescent protein (GFP) inserted between the ATP-binding helices of the ε-subunit of a bacterial F0-F1 ATPase. Optimizing the linkers joining the two domains resulted in a ~fivefold to sixfold improvement in the dynamic range compared to the previous-generation sensor, with excellent discrimination against other analytes, and affinity variants varying from 4 µM to 500 µM. A chimeric version of this sensor fused to either the HaloTag protein or a suitable spectrally separated fluorescent protein provides an optional ratiometric readout allowing comparisons of ATP across cellular regions. Subcellular targeting the sensor to nerve terminals reveals previously uncharacterized single-synapse metabolic signatures, while targeting to the mitochondrial matrix allowed direct quantitative probing of oxidative phosphorylation dynamics.
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Adenosina Trifosfato , Proteínas Fluorescentes Verdes , Animales , Humanos , Adenosina Trifosfato/análisis , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Técnicas Biosensibles/métodos , Proteínas Fluorescentes Verdes/metabolismo , Proteínas Fluorescentes Verdes/genética , Fosforilación Oxidativa , ATPasas de Translocación de Protón/metabolismo , ATPasas de Translocación de Protón/genéticaRESUMEN
Single-molecule localization microscopy (SMLM) uses activatable or switchable fluorophores to create non-diffraction limited maps of molecular location in biological samples. Despite the utility of this imaging technique, the portfolio of appropriate labels for SMLM remains limited. Here, we describe a general strategy for the construction of "glitter bomb" labels by simply combining rhodamine and coumarin dyes though an amide bond. Condensation of the ortho-carboxyl group on the pendant phenyl ring of rhodamine dyes with a 7-aminocoumarin yields photochromic or spontaneously blinking fluorophores depending on the parent rhodamine structure. We apply this strategy to prepare labels useful super-resolution experiments in fixed cells using different attachment techniques. This general glitter bomb strategy should lead to improved labels for SMLM, ultimately enabling the creation of detailed molecular maps in biological samples.
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While digital computers rely on software-generated pseudo-random number generators, hardware-based true random number generators (TRNGs), which employ the natural physics of the underlying hardware, provide true stochasticity, and power and area efficiency. Research into TRNGs has extensively relied on the unpredictability in phase transitions, but such phase transitions are difficult to control given their often abrupt and narrow parameter ranges (e.g., occurring in a small temperature window). Here we demonstrate a TRNG based on self-oscillations in LaCoO3 that is electrically biased within its spin crossover regime. The LaCoO3 TRNG passes all standard tests of true stochasticity and uses only half the number of components compared to prior TRNGs. Assisted by phase field modeling, we show how spin crossovers are fundamentally better in producing true stochasticity compared to traditional phase transitions. As a validation, by probabilistically solving the NP-hard max-cut problem in a memristor crossbar array using our TRNG as a source of the required stochasticity, we demonstrate solution quality exceeding that using software-generated randomness.
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Spontaneously blinking fluorophores permit the detection and localization of individual molecules without reducing buffers or caging groups, thus simplifying single-molecule localization microscopy (SMLM). The intrinsic blinking properties of such dyes are dictated by molecular structure and modulated by environment, which can limit utility. We report a series of tuned spontaneously blinking dyes with duty cycles that span two orders of magnitude, allowing facile SMLM in cells and dense biomolecular structures.
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Introduction Research is an important aspect of residency and fellowship programs across the country. Developing strategies to foster research productivity is worthwhile. An annual research project is one strategy that some programs implement. Methods All resident and fellow (Sports Medicine, Adult Reconstruction, Spine) presentations at an orthopedic surgery department's annual research symposium from June 2016 through June 2021 were identified. Abstract titles, title keywords, and author names were searched in PubMed and Google Scholar to identify the presence of a peer-reviewed publication. Using the total number of research symposium presentations given, the publication rate was calculated for each year, as well as collectively for 2016 to 2021. In addition to publication rate, first author percent, number of citations, Altmetric score, and journal impact factor were recorded. Current PGY-2 through PGY-5 residents completed a survey to assess the perceived value of the annual research symposium. Results Ninety-eight research symposium presentations were reviewed (69 residents, 29 fellows). Forty (58%) resident studies were published and 28 were first-author publications (70%). Thirteen (45%) fellow studies were published and seven were first-author publications (54%). Combining residents and fellows, the overall publication rate was 54% (53/98), and 66% of these (35/53) were first-author publications. There was a wide range of published manuscript journal impact factors, Altmetric scores, and number of citations. All residents surveyed reported finding value in the research symposium. Conclusion The overall publication rate of presentations at an annual orthopedic surgery department research symposium between 2016 and 2021 was 54%, consistent with publication rates reported at National Orthopedic Surgery Society meetings. All residents reported finding value in the annual research symposium. The results of this study support the academic value of implementing a required annual research project and may provide a useful gauge to inform residency and fellowship curricula at other institutions.
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BACKGROUND: Intraosseous (IO) administration of vancomycin at the time of total knee arthroplasty (TKA) has been shown to be safer and more effective than intravenous (IV) administration at preventing early periprosthetic joint infection. Previous studies have relied on tourniquet inflation to enhance local tissue concentrations and mitigate systemic release. METHODS: A single-blinded, randomized clinical trial was performed on 20 patients (10 IV, 10 IO) undergoing primary TKA. The control (IV) group received weight-dosed vancomycin approximately 1 hour prior to the incision and weight-dosed cefazolin immediately prior to the incision. The interventional (IO) group received weight-dosed cefazolin immediately prior to the incision and 500 mg of vancomycin delivered via the IO technique at the time of the incision. Systemic samples for vancomycin levels were taken prior to the incision and at closure. During the procedure, tissue samples were taken from the distal femur, proximal tibia, and suprapatellar synovium. There were no differences in patient demographics or changes in serum creatinine from preoperative to postoperatively between groups. RESULTS: Significant differences in systemic vancomycin levels (ug/mL) were found at the start of the case (IV = 27.9 ± 4.9 versus IO = 0 ± 0, P = .0004) and at the end of the case (IV = 19.6 ± 2.6 versus IO = 7.8 ± 1.0, P = .001). No significant differences were seen in the average vancomycin concentration in the distal femur (IV = 61.0 ± 16.0 versus IO = 66.2 ± 12.3, P = .80), proximal tibia (IV = 52.8 ± 13.5 versus IO = 57.1 ± 17.0, P = .84), or suprapatellar synovial tissue (IV = 10.7 ± 5.3 versus IO = 9.0 ± 3.3, P = .80). There were no complications associated with vancomycin administration in either group. CONCLUSIONS: This study demonstrates the utility of IO vancomycin in tourniquetless TKA with similar local tissue and significantly lower systemic concentrations than IV administration. LEVEL OF EVIDENCE: Level 1 therapeutic randomized trial.
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Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use.
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Experimentación Animal , Animales de Laboratorio , Animales , Reproducibilidad de los Resultados , Ritmo Circadiano/fisiología , MamíferosRESUMEN
Importance: Suicide rates in the US increased by 35.6% from 2001 to 2021. Given that most individuals die on their first attempt, earlier detection and intervention are crucial. Understanding modifiable risk factors is key to effective prevention strategies. Objective: To identify distinct suicide profiles or classes, associated signs of suicidal intent, and patterns of modifiable risks for targeted prevention efforts. Design, Setting, and Participants: This cross-sectional study used data from the 2003-2020 National Violent Death Reporting System Restricted Access Database for 306â¯800 suicide decedents. Statistical analysis was performed from July 2022 to June 2023. Exposures: Suicide decedent profiles were determined using latent class analyses of available data on suicide circumstances, toxicology, and methods. Main Outcomes and Measures: Disclosure of recent intent, suicide note presence, and known psychotropic usage. Results: Among 306â¯800 suicide decedents (mean [SD] age, 46.3 [18.4] years; 239â¯627 males [78.1%] and 67â¯108 females [21.9%]), 5 profiles or classes were identified. The largest class, class 4 (97â¯175 [31.7%]), predominantly faced physical health challenges, followed by polysubstance problems in class 5 (58â¯803 [19.2%]), and crisis, alcohol-related, and intimate partner problems in class 3 (55â¯367 [18.0%]), mental health problems (class 2, 53â¯928 [17.6%]), and comorbid mental health and substance use disorders (class 1, 41â¯527 [13.5%]). Class 4 had the lowest rates of disclosing suicidal intent (13â¯952 [14.4%]) and leaving a suicide note (24â¯351 [25.1%]). Adjusting for covariates, compared with class 1, class 4 had the highest odds of not disclosing suicide intent (odds ratio [OR], 2.58; 95% CI, 2.51-2.66) and not leaving a suicide note (OR, 1.45; 95% CI, 1.41-1.49). Class 4 also had the lowest rates of all known psychiatric illnesses and psychotropic medications among all suicide profiles. Class 4 had more older adults (23â¯794 were aged 55-70 years [24.5%]; 20â¯100 aged ≥71 years [20.7%]), veterans (22â¯220 [22.9%]), widows (8633 [8.9%]), individuals with less than high school education (15â¯690 [16.1%]), and rural residents (23â¯966 [24.7%]). Conclusions and Relevance: This study identified 5 distinct suicide profiles, highlighting a need for tailored prevention strategies. Improving the detection and treatment of coexisting mental health conditions, substance and alcohol use disorders, and physical illnesses is paramount. The implementation of means restriction strategies plays a vital role in reducing suicide risks across most of the profiles, reinforcing the need for a multifaceted approach to suicide prevention.
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Análisis de Clases Latentes , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Estados Unidos/epidemiología , Ideación Suicida , Anciano , Intento de Suicidio/estadística & datos numéricos , Intento de Suicidio/psicología , Adulto Joven , Suicidio Completo/estadística & datos numéricos , Suicidio Completo/psicología , Factores de Riesgo , Suicidio/estadística & datos numéricos , Suicidio/psicología , Adolescente , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
BACKGROUND: Disparities in diabetes care quality may have increased for patients with limited English language proficiency (LEP) compared to non-LEP patients during the COVID-19 pandemic. Changes in diabetes care quality for adult LEP and non-LEP patients of community health centers (CHCs) were examined from 2019 to 2020. METHODS: Adults with Type 2 diabetes (n = 15 965) of 88 CHC sites in California and with 1+ visit/year in 2019 and 2020 from OCHIN electronic health record data were included. Multivariable regression models estimated the association of LEP status and changes in diabetes care quality from 2019 to 2020, controlling for patient sociodemographic and clinical characteristics. Interaction terms (LEP × 2020) were used to estimate differential over time changes in (1) blood pressure screening, (2) blood pressure control (<140/90 mm Hg), and (3) hemoglobin A1c control (HbA1c <8%) for LEP versus non-LEP patients. RESULTS: LEP and non-LEP patients with diabetes had comparable blood pressure screening and control in 2019 and in 2020. LEP patients were less likely than non-LEP patients to have their HbA1c under control in 2019 (OR = 0.85, 95% CI = 0.77, 0.96, P = .006) and 2020 (OR = 0.83, 95% CI = 0.75, 0.92, P = .001). There were no differential changes in HbA1c control over time for LEP and non-LEP patients. DISCUSSION: Although LEP patients were less likely than non-LEP patients to have their HbA1c under control, CHCs maintained quality of care equally for LEP and non-LEP patients with diabetes during the early pandemic period.
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COVID-19 , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Pandemias , Hemoglobina Glucada , Barreras de Comunicación , Calidad de la Atención de Salud , Lingüística , California , Centros Comunitarios de SaludRESUMEN
Background: In the COVID-19 era, there has been increasing interest in same-day discharge (SDD) after total joint arthroplasty (TJA). However, patient perception of SDD is not well reported. Purpose: We sought to understand patients' perceptions and preferences of postoperative care by surveying patients who have completed both an overnight stay (ONS) and an SDD after TJA. Methods: We emailed survey links to 67 patients who previously underwent either 2 total hip arthroplasties (THAs) or 2 total knee arthroplasties (TKAs). Results: Fifty-two patients (78%) responded to the survey. Thirty-four (65%) patients underwent staged, bilateral TKAs, and 18 (35%) patients underwent staged, bilateral THAs. Overall, 63% of patients preferred their SDD, 12% had no preference, and 25% preferred their ONS, with no difference in preference between TKA and THA groups. Those who preferred their SDD reported being more comfortable at home. Those who preferred their ONS felt their pain and concerns were better addressed. No differences were found in comfort, sleep quality, appetite, burden on family, return to function, feelings of being discharged too soon, overall experience, 30-day emergency department (ED) visits, or readmissions within 30 days between patients' SDD and ONS. There was a small statistically significant difference between patients' perception of safety between SDD and ONS. Conclusion: Our survey found that most patients reported a preference for SDD after TJA over ONS. Although there was a small difference in patient perception of safety, there were no differences in return to the ED or readmissions after SDD and ONS.
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The endoplasmic reticulum (ER) is an important regulator of Ca2+ in cells and dysregulation of ER calcium homeostasis can lead to numerous pathologies. Understanding how various pharmacological and genetic perturbations of ER Ca2+ homeostasis impacts cellular physiology would likely be facilitated by more quantitative measurements of ER Ca2+ levels that allow easier comparisons across conditions. Here, we developed a ratiometric version of our original ER-GCaMP probe that allows for more quantitative comparisons of the concentration of Ca2+ in the ER across cell types and sub-cellular compartments. Using this approach we show that the resting concentration of ER Ca2+ in primary dissociated neurons is substantially lower than that in measured in embryonic fibroblasts.