Rural-urban stroke mortality gaps in the United States.

INTRODUCTION: Disparities in stroke outcomes, influenced by the use of systemic thrombolysis, endovascular therapies, and rehabilitation services, have been identified. Our study assesses these disparities in mortality after stroke between rural and urban areas across the United States (US). METHODS: We analyzed the CDC data on deaths attributed to cerebrovascular disease from 1999 to 2020. Data was categorized into rural and urban regions for comparative purposes. Age-adjusted mortality rates (AAMR) were computed using the direct method, allowing us to examine the ratios of rural to urban deaths for the cumulative population and among demographic subpopulations. Linear regression models were used to assess temporal changes in mortality ratios over the study period, yielding beta-coefficients (ß). RESULTS: There was a total of 628,309 stroke deaths in rural regions and 2,556,293 stroke deaths within urban regions. There were 1.13 rural deaths for each one urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.41). The rural-urban mortality ratio in Hispanic populations decreased from 1.32 rural deaths for each urban death per 100,000 population in 1999 to 0.85 in 2020 (ß = -0.011, ptrend < 0.001). For non-Hispanic populations, mortality remained stagnant with 1.12 rural deaths for each urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.543). Regionally, the Southern US exhibited the highest disparity with a urban-rural mortality ratio of 1.19, followed by the Northeast (1.13), Midwest (1.04), and West (1.01). CONCLUSIONS: Our findings depict marked disparities in stroke mortality between rural and urban regions, emphasizing the importance of targeted interventions to mitigate stroke-related disparities.

Pulsed Field Ablation and Neurocardiology: Inert to Efferents or Delayed Destruction?

Background: The therapeutic use of irreversible electroporation in clinical cardiac laboratories, termed pulsed field ablation (PFA), is gaining pre-regulatory approval momentum among rhythm specialists for the mitigation of arrhythmogenic substrate without increased procedural risk. Though electroporation has been utilized in other branches of science and medicine for decades, apprehension regarding all the possible off-target complications of PFA have yet to be thoroughly identified and investigated. Methods: This brief review will summarize the preclinical and adult clinical data published to date on PFA's effects on the autonomic system that interplays closely with the cardiovascular system, termed the neurocardiovascular system. These data are contrasted with the findings of efferent destruction secondary to thermal cardiac ablation modalities, namely radiofrequency energy and liquid nitrogen-based cryoablation. Results: In vitro neurocardiology findings, in vivo neurocardiology findings, and clinical neurocardiology findings to date nearly unanimously support the preservation of a critical mass of perineural structures and extracellular matrices to allow for long-term nervous regeneration in both cardiac and non-cardiac settings. Conclusions: Limited histopathologic data exist for neurocardiovascular outcomes post-PFA. Neuron damage is not only theoretically possible, but has been observed with irreversible electroporation, however regeneration is almost always concomitantly described.

Running in the wild: Energetics explain ecological running speeds.

Human runners have long been thought to have the ability to consume a near-constant amount of energy per distance traveled, regardless of speed, allowing speed to be adapted to particular task demands with minimal energetic consequence.1-3 However, recent and more precise laboratory measures indicate that humans may in fact have an energy-optimal running speed.4-6 Here, we characterize runners' speeds in a free-living environment and determine if preferred speed is consistent with task- or energy-dependent objectives. We analyzed a large-scale dataset of free-living runners, which was collected via a commercial fitness tracking device, and found that individual runners preferred a particular speed that did not change across commonly run distances. We compared the data from lab experiments that measured participants' energy-optimal running speeds with the free-living preferred speeds of age- and gender-matched runners in our dataset and found the speeds to be indistinguishable. Human runners prefer a particular running speed that is independent of task distance and is consistent with the objective of minimizing energy expenditure. Our findings offer an insight into the biological objectives that shape human running preferences in the real world-an important consideration when examining human ecology or creating training strategies to improve performance and prevent injury.

Assessment of the COVID-19 infection risk at a workplace through stochastic microexposure modeling.

BACKGROUND: The COVID-19 pandemic has a significant impact on economy. Decisions regarding the reopening of businesses should account for infection risks. OBJECTIVE: This paper describes a novel model for COVID-19 infection risks and policy evaluations. METHODS: The model combines the best principles of the agent-based, microexposure, and probabilistic modeling approaches. It takes into account specifics of a workplace, mask efficiency, and daily routines of employees, but does not require specific inter-agent rules for simulations. Likewise, it does not require knowledge of microscopic disease related parameters. Instead, the risk of infection is aggregated into the probability of infection, which depends on the duration and distance of every contact. The probability of infection at the end of a workday is found using rigorous probabilistic rules. Unlike previous models, this approach requires only a few reference data points for calibration, which are more easily collected via empirical studies. RESULTS: The application of the model is demonstrated for a typical office environment and for a real-world case. CONCLUSION: The proposed model allows for effective risk assessment and policy evaluation when there are large uncertainties about the disease, making it particularly suitable for COVID-19 risk assessments.

Infective Endocarditis-Like Presentation of Felty Syndrome: A Case Report.

Felty syndrome (FS) and infective endocarditis (IE) can present with similar signs and symptoms. FS is a diagnosis of exclusion, which poses a challenge for the clinician since accurate diagnosis is required to treat this condition effectively. A 52-year-old woman with a 15-year history of rheumatoid arthritis (RA) was admitted due to dyspnea and pain in the right ankle and left arm for two weeks. She was hemodynamically stable and afebrile. Physical examination revealed right ankle swelling and tenderness, left forearm tenderness, abdominal distension, and swan-neck finger deformities. Laboratory tests were notable for pancytopenia with a white blood cell (WBC) count of 2900 × 103/µL (absolute neutrophil count (ANC) of 1800/µL). Rheumatoid factor and anti-cyclic citrullinated peptide tests were positive. Synovial fluid analysis of the right ankle showed no crystals or bacteria, and a WBC count of 192 × 103/µL. Left upper extremity computed tomography (CT) revealed two abscesses, in the forearm and elbow, respectively. CT chest and abdomen revealed a wedge-shaped consolidation in the left upper lobe, multiple bilateral pulmonary nodules, and splenomegaly. Abdominal ultrasonography showed portal hypertension with no clear findings of cirrhosis. Blood cultures were negative. Transthoracic echocardiography (TTE) and transesophageal echocardiography showed no vegetation. Incision and drainage were performed for the right ankle swelling, and left forearm and elbow abscesses. Left forearm abscess culture revealed Staphylococcus hemolyticus. Transbronchial needle aspiration and culture of the left upper lobe lesion showed acute and chronic inflammation with no signs of malignancy or microbial growth. Repeat TTE and blood cultures were negative. Bone marrow biopsy and flow cytometry showed no evidence of large granular lymphocytic (LGL) leukemia. The patient was diagnosed with FS complicated by disseminated infections and pulmonary necrobiotic nodules. Empiric ceftriaxone and vancomycin were initiated. The patient was discharged after the resolution of her symptoms. FS is a rare extra-articular presentation of RA with a triad of a > 10-year history of RA, neutropenia (ANC < 2000/µL), and splenomegaly. IE can also present with disseminated infections and splenomegaly. Repeat TTE and blood cultures were performed due to concerns regarding the high mortality rate of IE and the possibility of false-negative echocardiography results. LGL leukemia also presents with RA and neutropenia, which was deemed less likely in our patient based on unremarkable bone marrow biopsy and flow cytometry results. FS is a rare condition. Therefore, it is important to keep its possibility in mind in the setting of RA while performing workup for the most likely conditions.

Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells.

The corneal epithelium is consistently regenerated by limbal stem/progenitor cells (LSCs), a very small population of adult stem cells residing in the limbus. Several Wnt ligands, including Wnt6, are preferentially expressed in the limbus. To investigate the role of Wnt6 in regulating proliferation and maintenance of human LSCs in an in vitro LSC expansion setting, we generated NIH-3T3 feeder cells to overexpress different levels of Wnt6. Characterization of LSCs cultured on Wnt6 expressing 3T3 cells showed that high level of Wnt6 increased proliferation of LSCs. Medium and high levels of Wnt6 also increased the percentage of small cells (diameter ≤ 12 µm), a feature of the stem cell population. Additionally, the percentage of cells expressing the differentiation marker K12 was significantly reduced in the presence of medium and high Wnt6 levels. Although Wnt6 is mostly known as a canonical Wnt ligand, our data showed that canonical and non-canonical Wnt signaling pathways were activated in the Wnt6-supplemented LSC cultures, a finding suggesting that interrelationships between both pathways are required for LSC regulation.

Hospitalization among street-involved youth who use illicit drugs in Vancouver, Canada: a longitudinal analysis.

BACKGROUND: Street-involved youth who use illicit drugs are at high risk for health-related harms; however, the profile of youth at greatest risk of hospitalization has not been well described. We sought to characterize hospitalization among street-involved youth who use illicit drugs and identify the most frequent medical reasons for hospitalization among this population. METHODS: From January 2005 to May 2016, data were collected from the At-Risk Youth Study (ARYS), a prospective cohort study of street-involved youth in Vancouver, Canada. Multivariable generalized estimating equation (GEE) was used to identify factors associated with hospitalization. RESULTS: Among 1216 participants, 373 (30.7%) individuals reported hospitalization in the previous 6 months at some point during the study period. The top three reported medical reasons for hospital admission were the following: mental illness (37.77%), physical trauma (12.77%), and drug-related issues (12.59%). Factors significantly associated with hospitalization were the following: past diagnosis of a mental illness (adjusted odds ratio [AOR] = 1.85; 95% confidence interval [95% CI] 1.47-2.33), frequent cocaine use (AOR = 2.15; 95% CI 1.37-3.37), non-fatal overdose (AOR = 1.76; 95% CI 1.37-2.25), and homelessness (AOR = 1.40; 95% CI 1.16-1.68) (all p < 0.05). CONCLUSIONS: Findings suggest that mental illness is a key driver of hospitalization among our sample. Comprehensive approaches to mental health and substance use in addition to stable housing offer promising opportunities to decrease hospitalization among this vulnerable population.

Medication-assisted treatment for youth with opioid use disorder: Current dilemmas and remaining questions.

The prevalence of risky opioid use, opioid use disorder, and related harms continue to rise among youth (adolescents and young adults age 15-25) in North America. With an increasing number of opioid overdoses, there remain significant barriers to care for youth with opioid use disorder, and there is an urgent need to expand evidence-based care for treatment of opioid use disorder among this population. Based on the extensive literature on treatment of opioid use disorder among adults, medicated-assisted treatment is likely to be an important or even essential component of treatment of opioid use disorder for most youth. In this article, we outline the current dilemmas and questions regarding the use of medication-assisted treatment among youth with opioid use disorder and propose some potential solutions based on the current evidence.

A Case of Opioid Overdose and Subsequent Death After Medically Supervised Withdrawal: The Problematic Role of Rapid Tapers for Opioid Use Disorder.

BACKGROUND: Relapse to opioid use is common after rapid opioid withdrawal. As a result, short-term tapers of opioid agonist/partial agonist medications, such as methadone and buprenorphine/naloxone, are no longer recommended by recent clinical care guidelines for the management of opioid use disorder. Nonetheless, rapid tapers are still commonplace in medically supervised withdrawal settings. CASE SUMMARY: We report a case of an individual with opioid use disorder who was prescribed a rapid buprenorphine/naloxone taper in a medically supervised withdrawal facility and who had a subsequent opioid overdose and death after discharge. DISCUSSION: The fatal outcome in this case study underscores the potential severe harms associated with use of rapid tapers. Given the increased overdose risk, tapers should be avoided and continuing care strategies, such as maintenance pharmacotherapy, should be initiated in medically supervised withdrawal settings.

Socioeconomic factors associated with cessation of injection drug use among street-involved youth.

BACKGROUND: Although the initiation of injection drug use has been well characterized among at-risk youth, factors that support or impede cessation of injection drug use have received less attention. We sought to identify socioeconomic factors associated with cessation of injection drug use among street-involved youth. METHODS: From September 2005 to May 2015, data were collected from the At-Risk Youth Study (ARYS), a prospective cohort study of street-involved youth in Vancouver, Canada. Multivariate extended Cox regression was utilized to identify socioeconomic factors associated with cessation of injection drug use for six months or longer among youth who were actively injecting. RESULTS: Among 383 participants, 171 (44.6%) youth reported having ceased injection (crude incidence density 22 per 100 person-years; 95% confidence interval [CI], 19-26) at some point during study follow-up. Youth who had recently dealt drugs (adjusted hazard ration [AHR], 0.50; 95% CI, 0.29-0.87), engaged in prohibited street-based income generation (AHR, 0.41; 95% CI, 0.24-0.69), and engaged in illegal income generating activities (AHR, 0.19; 95% CI, 0.06-0.61) were significantly less likely to report cessation of injection drug use. CONCLUSIONS: Our findings suggest that socioeconomic factors, in particular engagement in prohibited street-based and illegal income generating activities, may pose barriers to ceasing injection drug use among this population. Effort to improve access to stable and secure income, as well as employment opportunities may assist youth in transitioning away from injection drug use. TRIAL REGISTRATION: Our study is not a randomized controlled trial; thus the trial registration is not applicable.

Phase-mismatched localized fields in A-PPLN waveguide devices.

Highly phase-mismatched nonlinear interactions can generate spatially localized optical fields that can affect the performance of nonlinear optical devices. We present a theoretical description of the generation of such spatially localized optical fields by ultrafast pulses. The effects of temporal walk-off and pump depletion are discussed, along with methods for suppression of the localized field while maintaining the performance of the nonlinear device. The model is validated by the measurement of the spatial profile of the localized field in a quasi-phase-matched (QPM) aperiodically poled lithium niobate (A-PPLN) waveguide. Finally, we fabricate and characterize A-PPLN devices with a 33% duty cycle to reduce the locally generated field by 90%.

Complex-transfer-function analysis of optical-frequency converters.

The measurement of the magnitude and phase of the complex transfer function (CTF) of aperiodically poled lithium niobate waveguide devices using frequency resolved optical gating (FROG) is demonstrated. We investigate the sources of CTF distortions which are related to variations in the spatial distribution of the nonlinear coefficient and phase-mismatch profile and present a method to infer fabrication errors from the CTF discussed.

Characteristics and instabilities of mode-locked quantum-dot diode lasers.

Current pulse measurement methods have proven inadequate to fully understand the characteristics of passively mode-locked quantum-dot diode lasers. These devices are very difficult to characterize because of their low peak powers, high bandwidth, large time-bandwidth product, and large timing jitter. In this paper, we discuss the origin for the inadequacies of current pulse measurement techniques while presenting new ways of examining frequency-resolved optical gating (FROG) data to provide insight into the operation of these devices. Under the assumptions of a partial coherence model for the pulsed laser, it is shown that simultaneous time-frequency characterization is a necessary and sufficient condition for characterization of mode-locking. Full pulse characterization of quantum dot passively mode-locked lasers (QD MLLs) was done using FROG in a collinear configuration using an aperiodically poled lithium niobate waveguide-based FROG pulse measurement system.

104 MHz rate single-shot recording with subpicosecond resolution using temporal imaging.

We demonstrate temporal imaging for the measurement and characterization of optical arbitrary waveforms and events. The system measures single-shot 200 ps frames at a rate of 104 MHz, where each frame is time magnified by a factor of -42.4x. Impulse response tests show that the system enables 783 fs resolution when placed at the front end of a 20 GHz oscilloscope. Modulated pulse trains characterize the system's impulse response, jitter, and frame-to-frame variation.

Optimization of circular photonic crystal cavities - beyond coupled mode theory.

We study comprehensively using numerical simulations a new class of resonators, based on a circular photonic crystal reflector. The dependence of the resonator characteristics on the reflector design and parameters is studied in detail. The numerical results are compared to analytic results based on coupled mode theory. High quality factors and small modal volumes are found for a wide variety of design parameters.