N-Containing Na2VTi(PO4)3/C for Aqueous Sodium-Ion Batteries.

Phosphates featuring a 3D framework offer a promising alternative to aqueous sodium-ion batteries, known for their safety, cost-effectiveness, scalability, high power density, and tolerance to mishandling. Nevertheless, they often suffer from poor reversible capacity stemming from limited redox couples. Herein, N-containing Na2VTi(PO4)3 is synthesized for aqueous sodium-ion storage through multi-electron redox reactions. It demonstrates a capacity of 155.2 mAh g-1 at 1 A g-1 (≈ 5.3 C) and delivers an ultrahigh specific energy of 55.9 Wh kg-1 in a symmetric aqueous sodium-ion battery. The results from in situ X-ray diffraction analysis, ex situ X-ray photoelectron spectroscopy analysis, and first-principle calculations provide insights into the local chemical environment of sodium ions, the mechanisms underlying capacity decay during cycling, and the dynamics of ion and electron transfer at various states of charge. This understanding will contribute to the advancement of electrode materials for aqueous sodium-ion batteries.

Cost-effectiveness of goal-directed and outcome-based financial incentives for weight loss in low-income populations: the FIReWoRk randomized clinical trial.

BACKGROUND: The Financial Incentives for Weight Reduction (FIReWoRk) clinical trial showed that financial incentive weight-loss strategies designed using behavioral economics were more effective than provision of weight-management resources only. We now evaluate cost-effectiveness. METHODS: Cost-effectiveness analysis of a multisite randomized trial enrolling 668 participants with obesity living in low-income neighborhoods. Participants were randomized to (1) goal-directed incentives (targeting behavioral goals), (2) outcome-based incentives (targeting weight-loss), and (3) resources only, which were provided to all participants and included a 1-year commercial weight-loss program membership, wearable activity monitor, food journal, and digital scale. We assessed program costs, time costs, quality of life, weight, and incremental cost-effectiveness in dollars-per-kilogram lost. RESULTS: Mean program costs at 12 months, based on weight loss program attendance, physical activity participation, food diary use, self-monitoring of weight, and incentive payments was $1271 in the goal-directed group, $1194 in the outcome-based group, and $834 in the resources-only group (difference, $437 [95% CI, 398 to 462] and $360 [95% CI, 341-363] for goal-directed or outcome-based vs resources-only, respectively; difference, $77 [95% CI, 58-130] for goal-directed vs outcome-based group). Quality of life did not differ significantly between the groups, but weight loss was substantially greater in the incentive groups (difference, 2.34 kg [95% CI, 0.53-4.14] and 1.79 kg [95% CI, -0.14 to 3.72] for goal-directed or outcome-based vs resources only, respectively; difference, 0.54 kg [95% CI, -1.29 to 2.38] for goal-directed vs outcome-based). Cost-effectiveness of incentive strategies based on program costs was $189/kg lost in the goal-directed group (95% CI, $124/kg to $383/kg) and $186/kg lost in the outcome-based group (95% CI, $113/kg to $530/kg). CONCLUSIONS: Goal-directed and outcome-based financial incentives were cost-effective strategies for helping low-income individuals with obesity lose weight. Their incremental cost per kilogram lost were comparable to other weight loss interventions.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Preferences for Hypertension Care in Malawi: A Discrete Choice Experiment Among People Living with Hypertension, With and Without HIV.

Hypertension is the most common non-communicable disease diagnosed among people in sub-Saharan Africa. However, little is known about client preferences for hypertension care. We performed a discrete choice experiment in Malawi among people with hypertension, with and without HIV. Participants were asked to select between two care scenarios, each with six attributes: distance, waiting time, provider friendliness, individual or group care, antihypertensive medication supply, and antihypertensive medication dispensing frequency (three versus one month). Eight choice sets (each with two scenarios) were presented to each individual. Mixed effects logit models quantified preferences for each attribute. Estimated model coefficients were used to predict uptake of hypothetical models of care. Between July 2021 and April 2022 we enrolled 1003 adults from 14 facilities in Malawi; half were living with HIV and on ART for a median of 11 years. Median age of respondents was 57 years (IQR 49-63), 58.2% were female, and median duration on antihypertensive medications was 4 years (IQR 2-7). Participants strongly preferred seeing a provider alone versus in a group (OR 11.3, 95% CI 10.4-12.3), with stronger preference for individual care among those with HIV (OR 15.4 versus 8.6, p < 0.001). Three-month versus monthly dispensing was also strongly preferred (OR 4.2; 95% CI 3.9-4.5). 72% of respondents would choose group care if all other facility attributes were favorable, although PLHIV were less likely to make this trade-off (66% versus 77%). These findings have implications for the scale-up of hypertension care in Malawi and similar settings.

Evolution of Oxygen Content of Graphene Oxide for Humidity Sensing.

Graphene oxide (GO) has shown significant potential in humidity sensing. It is well accepted that the oxygen-containing functional groups in GO significantly influence its humidity sensing performance. However, the relationship between the content of these groups and the humidity sensing capability of GO-based sensors remains unclear. In the present work, we investigate the role of oxygen-containing functional groups in the humidity sensing performance by oxidizing graphite with mesh numbers 80-120, 325, and 8000 using the Hummers method, resulting in GO-80, GO-325, and GO-8000. Infrared spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) were used to identify the types and quantification of oxygen-containing functional groups. Molecular dynamics simulation is used to simulate the adsorption energy, intercalation dynamics, and hydrogen bonding of water molecules. Electrochemical tests were used to compare the adsorption/desorption time and response sensitivity of graphene oxide to humidity. It is proposed that hydroxyl and carboxyl groups are the main contributing groups to humidity sensing. GO-8000 shows a relatively fast response time, but the large number of carboxyl groups will hinder intercalation of water molecules, thus exhibiting lower sensitivity. This research provides a reference for the future development of graphene-based sensors, catalysts, and environmental materials.

The 3 Wishes Program Improves Families' Experience of Emotional and Spiritual Support at the End of Life.

BACKGROUND: The end-of-life (EOL) experience in the intensive care unit (ICU) is emotionally challenging, and there are opportunities for improvement. The 3 Wishes Program (3WP) promotes the dignity of dying patients and their families by eliciting and implementing wishes at the EOL. AIM: To assess whether the 3WP is associated with improved ratings of EOL care. PROGRAM DESCRIPTION: In the 3WP, clinicians elicit and fulfill simple wishes for dying patients and their families. SETTING: 2-hospital academic healthcare system. PARTICIPANTS: Dying patients in the ICU and their families. PROGRAM EVALUATION: A modified Bereaved Family Survey (BFS), a validated tool for measuring EOL care quality, was completed by families of ICU decedents approximately 3 months after death. We compared patients whose care involved the 3WP to those who did not using three BFS-derived measures: Respectful Care and Communication (5 questions), Emotional and Spiritual Support (3 questions), and the BFS-Performance Measure (BFS-PM, a single-item global measure of care). RESULTS: Of 314 completed surveys, 117 were for patients whose care included the 3WP. Bereaved families of 3WP patients rated the Emotional and Spiritual Support factor significantly higher (7.5 vs. 6.0, p = 0.003, adjusted p = 0.001) than those who did not receive the 3WP. The Respectful Care and Communication factor and BFS-PM were no different between groups. DISCUSSION: The 3WP is a low-cost intervention that may be a feasible strategy for improving the EOL experience.

Telephone Outreach Enhances Recruitment of Underrepresented Seriously Ill Patients for an Advance Care Planning Pragmatic Trial.

BACKGROUND: Patients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals. OBJECTIVE: To assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California. DESIGN: Retrospective cohort study PATIENTS: Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone. MAIN MEASURES: Effect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)). RESULTS: Across the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively). CONCLUSIONS: Phone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.

Single mRNA detection of Wnt signaling pathway in the human limbus.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their close microenvironment. It has been shown that Wnt signaling pathway is crucial for LSCs regulation. Previous differential gene profiling studies confirmed the preferential expression of specific Wnt ligands (WNT2, WNT6, WNT11, WNT16) and Wnt inhibitors (DKK1, SFRP5, WIF1, FRZB) in the limbal region compared to the cornea. Among all frizzled receptors, frizzled7 (Fzd7) was found to be preferentially expressed in the basal limbal epithelium. However, the exact localization of Wnt signaling molecules-producing cells in the limbus remains unknown. The current study aims to evaluate the in situ spatial expression of these 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7. Wnt ligands, DKK1, and Fzd7 expression were scattered within the limbal epithelium, at a higher abundance in the basal layer than the superficial layer. SFRP5 expression was diffuse among the limbal epithelium, whereas WIF1 and FRZB expression was clustered at the basal limbal epithelial layer corresponding to the areas of high levels of Fzd7 expression. Quantitation of the fluorescence intensity showed that all 4 Wnt ligands, 3 Wnt inhibitors (WIF1, DKK1, FRZB), and Fzd7 were highly expressed at the basal layer of the limbus, then in a decreasing gradient toward the superficial layer (P < 0.05). The expression levels of all 4 Wnt ligands, FRZB, and Fzd7 in the basal epithelial layer were higher in the limbus than the central cornea (P < 0.05). All 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7 were also highly expressed in the limbal stroma immediately below the epithelium but not in the corneal stroma (P < 0.05). In addition, Fzd7 had a preferential expression in the superior limbus compared to other limbal quadrants (P < 0.05). Taken together, the unique expression patterns of the Wnt molecules in the limbus suggests the involvement of both paracrine and autocrine effects in LSCs regulation, and a fine balance between Wnt activators and inhibitors to govern LSC fate.

The Utility of Ultrasound Guidance to Improve the Safety of Closure of Antegrade Common Femoral Artery Access after Lower Limb Revascularization.

This study aimed to investigate the feasibility of ultrasound (US)-guidance in reducing adverse event (AE) rates when using Angioseal device during antegrade lower limb angioplasty via common femoral artery access. From December 2016 to November 2022, 1,322 patients were identified, including 1,131 (85.6%) patients who underwent US-guided closure and 191 (14.4%) who underwent non-US-guided closure. Moderate AEs were encountered in 10 (5.2%) patients in the non-US-guided closure group compared to 38 (3.4%) patients in the US-guided closure group (P = .208). Severe AEs were encountered in 4 (2.1%) patients in the non-US-guided closure group compared to 3 (0.3%) patients in the US-guided closure group (P = .010). Overall AEs occurred in 14 (7.3%) patients in the non-US-guided closure group compared to 41 (3.6%) patients in the US-guided closure group (P = .029). Binary logistic regression showed that only non-US guidance was an independent risk factor for the occurrence of severe AEs (P = .008).

Evaluation of behavioral economic strategies to raise influenza vaccination rates across a health system: Results from a randomized clinical trial.

Influenza vaccination rates are low. Working with a large US health system, we evaluated three health system-wide interventions using the electronic health record's patient portal to improve influenza vaccination rates. We performed a two-arm RCT with a nested factorial design within the treatment arm, randomizing patients to usual-care control (no portal interventions) or to one or more portal interventions. We included all patients within this health system during the 2020-2021 influenza vaccination season, which overlapped with the COVID-19 pandemic. Through the patient portal, we simultaneously tested: pre-commitment messages (sent September 2020, asking patients to commit to a vaccination); monthly portal reminders (October - December 2020), direct appointment scheduling (patients could self-schedule influenza vaccination at multiple sites); and pre-appointment reminder messages (sent before scheduled primary care appointments, reminding patients about influenza vaccination). The main outcome measure was receipt of influenza vaccine (10/01/2020-03/31/2021). We randomized 213,773 patients (196,070 adults ≥18 years, 17,703 children). Influenza vaccination rates overall were low (39.0%). Vaccination rates for study arms did not differ: Control (38.9%), pre-commitment vs no pre-commitment (39.2%/38.9%), direct appointment scheduling yes/no (39.1%/39.1%), pre-appointment reminders yes/no (39.1%/39.1%); p > 0.017 for all comparisons (p value cut-off adjusted for multiple comparisons). After adjusting for age, gender, insurance, race, ethnicity, and prior influenza vaccination, none of the interventions increased vaccination rates. We conclude that patient portal interventions to remind patients to receive influenza vaccine during the COVID-19 pandemic did not raise influenza immunization rates. More intensive or tailored interventions are needed beyond portal innovations to increase influenza vaccination.

Evaluating the accessibility and value of U.S. ambulatory care among Medicaid expansion states and non-expansion states, 2012-2015.

BACKGROUND: While the Affordable Care Act's Medicaid expansion improved healthcare coverage and access for millions of uninsured Americans, less is known about its effects on the overall accessibility and quality of care across all payers. Rapid volume increases of newly enrolled Medicaid patients might have unintentionally strained accessibility or quality of care. We assessed changes in physician office visits and high- and low-value care associated with Medicaid expansion across all payers. METHODS: Prespecified, quasi-experimental, difference-in-differences analysis pre and post Medicaid expansion (2012-2015) in 8 states that did and 5 that did not choose to expand Medicaid. Physician office visits sampled from the National Ambulatory Medical Care Survey, standardized with U.S. Census population estimates. Outcomes included visit rates per state population and rates of high or low-value service composites of 10 high-value measures and 7 low-value care measures respectively, stratified by year and insurance. RESULTS: We identified approximately 143 million adults utilizing 1.9 billion visits (mean age 56; 60% female) during 2012-2015. Medicaid visits increased in expansion states post-expansion compared to non-expansion states by 16.2 per 100 adults (p = 0.031 95% CI 1.5-31.0). New Medicaid visits increased by 3.1 per 100 adults (95% CI 0.9-5.3, p = 0.007). No changes were observed in Medicare or commercially-insured visit rates. High or low-value care did not change for any insurance type, except high-value care during new Medicaid visits, which increased by 4.3 services per 100 adults (95% CI 1.1-7.5, p = 0.009). CONCLUSIONS: Following Medicaid expansion, the U.S. healthcare system increased access to care and use of high-value services for millions of Medicaid enrollees, without observable reductions in access or quality for those enrolled in other insurance types. Provision of low-value care continued at similar rates post-expansion, informing future federal policies designed to improve the value of care.

Effects of Fecal Occult Blood Immunoassay Screening for Colorectal Cancer-Experience from a Hospital in Central Taiwan.

Background and Objectives: In 2004, the Health Administration of Taiwan began to promote a hospital-based cancer screening quality improvement program, under the principle that "prevention is better than therapy". The aim of this study was to evaluate the effectiveness of colorectal cancer (CRC) screening in patients who received a fecal immunochemical test (FIT) at a hospital in central Taiwan. Materials and Methods: This was a retrospective study. Results: Fecal occult blood immunoassays for CRC screening were conducted in 58,891 participants, of whom 6533 were positive (positive detection rate 11.10%). The positive patients then underwent colonoscopy, and the detection rates of polyps and CRC accounted for 53.6% and 2.4% of all colonoscopy-confirmed diagnoses (3607), respectively. We further enrolled data from patients diagnosed with CRC at our hospital from 2010 to 2018. The patients with CRC were divided into two groups according to whether or not they had received fecal occult blood screening. Among the 88 patients with CRC by screening, 54 had detailed medical records including cancer stage. Of these 54 patients, 1 (1.8%) had pre-stage, 11 (20.4%) had stage I, 24 (44.4%) had stage II, 10 (18.5%) had stage III, and 8 (14.8%) had stage IV CRC. The early cancer detection rates of the screening and non-screening groups were 66.7% and 52.7%, respectively, and the difference was significant (p = 0.00130). Conclusions: In this study, screening with FIT significantly increased the early detection of CRC. The main advantage of FIT is the non-invasiveness and low cost. It is hoped that the further adoption of early screening can increase the detection rates of colorectal polyps or early cancer to improve survival, reduce the high cost of subsequent cancer treatment, and reduce the burden on the patient and healthcare system.

Effect of Personalized Messages Sent by a Health System's Patient Portal on Influenza Vaccination Rates: a Randomized Clinical Trial.

BACKGROUND: Adult influenza vaccination rates are low. Tailored patient reminders might raise rates. OBJECTIVE: Evaluate impact of a health system's patient portal reminders: (1) tailored to patient characteristics and (2) incorporating behavioral science strategies, on influenza vaccination rates among adults. DESIGN: Pragmatic 6-arm randomized trial across a health system during the 2019-2020 influenza vaccination season. The setting was one large health system-53 adult primary care practices. PARTICIPANTS: All adult patients who used the patient portal within 12 months, stratified by the following: young adults (18-64 years, without diabetes), older adults (≥65 years, without diabetes), and those with diabetes (≥18 years). INTERVENTIONS: Patients were randomized within strata to either (1) pre-commitment reminder alone (1 message, mid-October), (2) pre-commitment + loss frame messages, (3) pre-commitment + gain frame messages, (4) loss frame messages alone, (5) gain frame messages alone, or (6) standard of care control. Patients in the pre-commitment group were sent a message in mid-October, asking if they planned on getting an influenza vaccination. Patients in loss or gain frame groups were sent up to 3 portal reminders (late October, November, and December, if no documented influenza vaccination in the EHR) about importance and safety of influenza vaccine. MAIN MEASURES: Receipt of 1 influenza vaccine from 10/01/2019 to 03/31/2020. KEY RESULTS: 196,486 patients (145,166 young adults, 29,795 older adults, 21,525 adults with diabetes) were randomized. Influenza vaccination rates were as follows: for young adults 36.8%, for older adults 55.6%, and for diabetics 60.6%. On unadjusted and adjusted (for age, gender, insurance, race, ethnicity, and prior influenza vaccine history) analyses, influenza vaccination rates were not statistically different for any study group versus control. CONCLUSIONS: Patient reminders sent by a health system's patient portal that were tailored to patient demographics (young adults, older adults, diabetes) and that incorporated two behavioral economic messaging strategies (pre-commitment and loss/gain framing) were not effective in raising influenza vaccination rates. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT04110314).

Perception of risk and treatment decisions in the management of differentiated thyroid cancer.

BACKGROUND AND OBJECTIVES: The recent de-escalation of care for differentiated thyroid cancer (DTC) has broadened the range of initial treatment options. We examined the association between physicians' perception of risk and their management of DTC. METHODS: Thyroid specialists were surveyed with four clinical vignettes: (1) indeterminate nodule (2) tall cell variant papillary thyroid cancer (PTC), (3) papillary thyroid microcarcinoma (mPTC), and (4) classic PTC. Participants judged the operative risks and likelihood of structural cancer recurrence associated with more versus less aggressive treatments. A logistic mixed effect model was used to predict treatment choice. RESULTS: Among 183 respondents (13.4% response rate), 44% were surgical and 56% medical thyroid specialists. Risk estimates and treatment recommendation varied markedly in each case. Respondents' estimated risk of 10-year cancer recurrence after lobectomy for a 2.0-cm PTC ranged from 1% to 53% (interquartile range [IQR]: 3%-12%), with 66% recommending lobectomy and 34% total thyroidectomy. Respondents' estimated 5-year risk of metastastic disease during active surveillance of an 0.8-cm mPTC ranged from 0% to 95% (IQR: 4%-15%), with 36% choosing active surveillance. Overall, differences in perceived risk reduction explained 10.3% of the observed variance in decision-making. CONCLUSIONS: Most of the variation in thyroid cancer treatment aggressiveness is unrelated to perceived risk of cancer recurrence.

Survival After Severe COVID-19: Long-Term Outcomes of Patients Admitted to an Intensive Care Unit.

BACKGROUND: Understanding the long-term sequelae of severe COVID-19 remains limited, particularly in the United States. OBJECTIVE: To examine long-term outcomes of patients who required intensive care unit (ICU) admission for severe COVID-19. DESIGN, PATIENTS, AND MAIN MEASURES: This is a prospective cohort study of patients who had severe COVID-19 requiring an ICU admission in a two-hospital academic health system in Southern California. Patients discharged alive between 3/21/2020 and 12/31/2020 were surveyed approximately 6 months after discharge to assess health-related quality of life using Patient-Reported Outcomes Measurement Information System (PROMIS®)-29 v2.1, post-traumatic stress disorder (PTSD) and loneliness scales. A preference-based health utility score (PROPr) was estimated using 7 PROMIS domain scores. Patients were also asked their attitude about receiving aggressive ICU care. KEY RESULTS: Of 275 patients admitted to the ICU for severe COVID-19, 205 (74.5%) were discharged alive and 132 (64%, median age 59, 46% female) completed surveys a median of 182 days post-discharge. Anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, pain interference, and cognitive function were not significantly different from the U.S. general population, but physical function (44.2, SD 11.0) was worse. PROPr mean score of 0.46 (SD 0.30, range -0.02 to 0.96 [<0 is worse than dead and 1 represents perfect health]) was slightly lower than the U.S. general population, with an even distribution across the continuum. Poor PROPr was associated with chronic medical conditions and receipt of life-sustaining treatments, but not demographics or social vulnerability. PTSD was suspected in 20% and loneliness in 29% of patients. Ninety-eight percent of patients were glad they received life-saving treatment. CONCLUSION: Most patients who survive severe COVID-19 achieve positive outcomes, with health scores similar to the general population at 6 months post-discharge. However, there is marked heterogeneity in outcomes with a substantial minority reporting severely compromised health.

Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with systemic inflammation, yet what mechanisms regulate PAHs' inflammatory effects are less understood. This study evaluated the change of arachidonic acid (ARA) metabolites and inflammatory biomarkers in response to increased exposure to PAHs among 26 non-smoking healthy travelers from Los Angeles to Beijing. Traveling from Los Angeles to Beijing significantly increased urinary metabolites of dibenzofuran (800%), fluorene (568%), phenanthrene (277%), and pyrene (176%), accompanied with increased C-reactive protein, fibrinogen, IL-8, and IL-10, and decreased MCP-1, sCD40L, and sCD62P levels in the blood. Meanwhile, the travel increased the levels of ARA lipoxygenase metabolites that were positively associated with a panel of pro-inflammatory biomarkers. Concentrations of cytochrome P450 metabolite were also increased in Beijing and were negatively associated with sCD62P levels. In contrast, concentrations of ARA cyclooxygenase metabolites were decreased in Beijing and were negatively associated with anti-inflammatory IL-10 levels. Changes in both inflammatory biomarkers and ARA metabolites were reversed 4-7 weeks after participants returned to Los Angeles and were associated with urinary PAH metabolites, but not with other exposures such as secondhand smoke, stress, or diet. These results suggested possible roles of ARA metabolic alteration in PAHs-associated inflammatory effects.

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

OBJECTIVE: Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. METHODS: We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. RESULTS: Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. CONCLUSION: Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

Trends in Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer in California, 2003-2017.

BACKGROUND: External beam radiation therapy (EBRT) is rarely used to treat patients with differentiated or medullary thyroid cancer. Although EBRT is generally administered to patients with high-risk or unresectable diseases, neither its indications for the use nor the associated outcomes are well-defined. We used a statewide cohort to assess the trends in EBRT use and postradiation outcomes in California. METHODS: A population-based study of patients within the California Cancer Registry who underwent EBRT after surgery for nonanaplastic thyroid cancer (2003-2017) was conducted. The primary outcome was the annual utilization rate of EBRT. The secondary outcomes included Kaplan-Meier analysis for cause-specific survival and identifying factors associated with improved survival after EBRT. RESULTS: Among the 57 607 patients with nonanaplastic thyroid cancer from 2003 to 2017, 344 (0.6%) patients received EBRT. EBRT was utilized in 0.4% of papillary, 1.1% of follicular, and 7.7% of medullary thyroid cancers in California. Overall, 99 (28.8%) patients treated with EBRT died of thyroid cancer. The 10-year cause-specific survival of all patients with thyroid cancer after EBRT was 61.5% (95% CI: 54.8%-69.1%) and that of patients without distant disease was 80.3% (95% CI: 73.5%-87.8%). The survival outcomes varied by tumor size, histology, disease stage, patient age at diagnosis, and the presence of extrathyroidal extension (P < .05). CONCLUSIONS: The use of adjuvant EBRT for nonanaplastic thyroid cancer remained stable and low in California from 2003 to 2017. The comparative efficacy of EBRT was not discernible in this study, but disease control appeared durable in select patients. Well-controlled observational studies and/or prospective studies are needed to better define which patients benefit from EBRT.

Activated macrophages of CD 163 gene edited pigs generated by direct cytoplasmic microinjection with CRISPR gRNA/Cas9 mRNA are resistant to PRRS virus assault.

Porcine reproductive and respiratory syndrome virus (PRRSV) infects placental and lung macrophages, causing a global epidemic with economic loss. Attempts to develop an effective vaccine to control the disease have not been effective. Currently, developing PRRSV disease-resistant pigs via a gene editing (GE) strategy to mutate the PRRSV receptor or to delete the binding domain on the macrophage appears promising. In this study, we used the strategy of Edinburg University to construct two guide RNAs (gRNAs) located on the proximal front and post sites of exon 7. Directive microinjection of two gRNAs and Cas9 mRNA into the cytoplasm of pronuclear zygotes efficiently generated four piglets confirmed as CD163 knockout (KO) and/or CD163 exon 7 deleted (CD163ΔE7). In four GE piglets, three pigs carried two chromosome CD163 KO or ΔE7. Peripheral blood mononuclear cells (PBMCs) from three GE and wild-type (WT) pigs were activated into macrophages for in vitro transfection. The results showed that the activated macrophages from all GE pigs were significantly more viable than those from WT pig. Current results suggest that we have successfully generated PRRSV-resistant pigs, although in vivo challenge is needed to validate that the pigs are PRRSV resistant.

Monitoring and Analysis of Ground Surface Settlement in Mining Clusters by SBAS-InSAR Technology.

In this paper, we use the small baseline set technology and the early geological hazard identification method based on the selection of Permanent Scatter (PS) and Distributed Scatter (DS) points to carry out the research on surface deformation monitoring caused by underground activities in mining cluster areas. We adopted the Small Baseline Subset InSAR (SBAS-InSAR) technique to process Sentinel-1A SAR images over the research area from March 2017 to May 2021. The deformation estimation technology based on the robustness of PS points and DS points can be used for early identification of high-density surface subsidence in a large area of mines. The surface subsidence information can be obtained quickly and accurately, and the advantages of using InSAR technology to monitor long-time surface subsidence in complex mining cluster areas was explored in this study. By comparing the monitoring data of the Global Navigation Satellite System (GNSS) ground monitoring equipment, the accuracy error of large-scale surface settlement information is controlled within 8 mm, which has high accuracy. Meanwhile, according to the spatial characteristics of cluster mining areas, it is analyzed that the relationship between adjacent mining areas through groundwater easily leads to regional associated large-area settlement changes. Compared with the D-InSAR (Differential InSAR) technology applied in mine monitoring at the early stage, this proposed method can monitor a large range of long time series and optimize the problem of decoherence to some extent in mining cluster areas. It has important reference significance for early monitoring and early warning of subsidence disaster evolution in mining intensive areas.