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The mixed finite element (MFE) method is well adapted for the simulation of fluid flow in heterogeneous porous media. However, when employed for the transport equation, it can generate solutions with strong unphysical oscillations because of the hyperbolic nature of advection. In this work, a robust upwind MFE scheme is proposed to avoid such unphysical oscillations. The new scheme is a combination of the upwind edge/face centered finite volume method with the hybrid formulation of the MFE method. The scheme ensures continuity of both advective and dispersive fluxes between adjacent elements and allows to maintain the time derivative continuous, which permits employment of high-order time integration methods via the method of lines (MOL). Numerical simulations are performed in both saturated and unsaturated porous media to investigate the robustness of the new upwind MFE scheme. Results show that, contrarily to the standard scheme, the upwind MFE method generates stable solutions without under and overshoots. The simulation of contaminant transport into a variably saturated porous medium highlights the robustness of the proposed upwind scheme when combined with the MOL for solving nonlinear problems.

Flocculation between inorganic sediment, salt ions and microscopic organic matter present in the marine environment might play an important role in the dynamics of turbidity currents. The ability to predict, understand, and potentially leverage the effect of flocculation on turbidity currents will help to minimize the impact of human interventions such as dredging, trenching, and deep-sea mining. To better characterize the effect of flocculation on the benthic turbidity currents generated by these activities, a series of laboratory experiments were performed. Turbidity currents were created by means of lock exchange experiments. The present work focuses on the flocculation of clays that are representative for abyssal regions where deep-sea mining is performed, but most of the conclusions of this work are generic and can be applied to other types of benthic flows, occuring in harbours and channels. The effect of salt and organic material as flocculant agent was investigated. Various concentrations of clay and organic flocculant were tested. Video analysis was used to determine the head velocity of the plume. Samples at different run-out lengths were collected at the end of the lock exchange experiments for particle size and settling velocity measurements. The velocities of the turbidity currents in fresh and saline water (when no organic matter was present) were found to be similar, which was expected considering the timescales of salt-induced flocculation (about 30 min or more compared to the duration of lock exchange experiment

Background: The insertion of a PIVC is the most commonly performed invasive procedure in healthcare. Despite its frequency in placement in hospitalized patients, PIVCs are generally perceived as being safe; however, the prevalence of failure ranges from 35%-50%. Additionally, complications are common and often deemed 'acceptable' by clinicians. Healthcare provider and clinician foundational knowledge and competency is lacking nationally. Considering the mere volume of PIVCs placed, the failure and complication rates, the human impact is significant., Methods: The Association for Vascular Access (AVA) has led a collaborative effort with representatives from the Infusion Nurses Society (INS), the American Association of Critical Care Nurses (AACN), ECRI, and content experts representing nursing vascular access, infusion therapy, infection prevention, critical care, pediatrics, healthcare leadership, a physician, and a patient representative. Our aim is to provide concise guidance that will enhance and standardize practices related to PIVC. By consolidating current standards of practice into a comprehensive document, our framework seeks to advance the quality of care and improve patient safety., Results: This document has undergone meticulous scrutiny to ensure its quality, including incorporation of current standards, methodology for consensus from the expert panel, and input received from public comments., Conclusions: We anticipate that this work will have a significant impact on healthcare professionals, policymakers, and, most importantly, patients' experiences by the promotion of consistent, high-quality treatment, safety, and comfort for patients receiving a PIVC.

This manuscript describes the development and characterization of electrospun nanofibers incorporating bioactive hydrolysates obtained from the microbial bioconversion of feathers, a highly available agro-industrial byproduct. The electrospun nanofibers were characterized using different instrumental methods, and their antioxidant properties and toxicological potential were evaluated. Keratin hydrolysates (KHs) produced by Bacillus velezensis P45 were incorporated at 1, 2.5, and 5% ( w / w ) into poly-ε-caprolactone (PCL; 10 and 15%, w / v solutions) before electrospinning. The obtained nanofibers were between 296 and 363 nm in diameter, showing a string-like morphology and adequate structural continuity. Thermogravimetric analysis showed three weight loss events, with 5% of the mass lost up to 330 °C and 90% from 350 to 450 °C. Infrared spectroscopy showed typical peaks of PCL and amide bands corresponding to keratin peptides. The biological activity was preserved after electrospinning and the hemolytic activity was below 1% as expected for biocompatible materials. In addition, the antioxidant capacity released from the nanofibers was confirmed by DPPH and ABTS radical scavenging activities. The DPPH scavenging activity observed for the nanofibers was greater than 30% after 24 h of incubation, ranging from 845 to 1080 µM TEAC (Trolox equivalent antioxidant capacity). The antioxidant activity for the ABTS radical assay was 44.19, 49.61, and 56.21% (corresponding to 972.0, 1153.3, and 1228.7 µM TEAC) for nanofibers made using 15% PCL with 1, 2.5, and 5% KH, respectively. These nanostructures may represent interesting antioxidant biocompatible materials for various pharmaceutical applications, including wound dressings, topical drug delivery, cosmetics, and packaging.

Purpose: Few studies have examined the relationship between poor atrial fibrillation-related quality of life (AFQoL) and a battery of geriatric factors. The objective of this study is to describe factors associated with poor AFQoL in older adults with atrial fibrillation (AF) with a focus on sociodemographic and clinical factors and a battery of geriatric factors., Methods: Cross-sectional analysis of a prospective cohort study of participants aged 65+ with high stroke risk and AF. AFQoL was measured using the validated Atrial Fibrillation Effect on Quality of Life (score 0-100) and categorized as poor (<80) or good (80-100). Chi-square and t -tests evaluated differences in factors across poor AFQoL and significant characteristics ( P  < 0.05) were entered into a logistic regression model to identify variables related to poor AFQoL., Results: Of 1244 participants (mean age 75.5), 42% reported poor AFQoL. Falls in the past 6 months, pre/frail and frailty, depression, anxiety, social isolation, vision impairment, oral anticoagulant therapy, rhythm control, chronic obstructive pulmonary disease and polypharmacy were associated with higher odds of poor AFQoL. Marriage and college education were associated with a lower odds of poor AFQoL., Conclusions: More than 4 out of 10 older adults with AF reported poor AFQoL. Geriatric factors associated with higher odds of reporting poor AFQoL include recent falls, frailty, depression, anxiety, social isolation and vision impairment. Findings from this study may help clinicians screen for patients with poor AFQoL who could benefit from tailored management to ensure the delivery of patient-centered care and improved well being among older adults with AF., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Introduction: The Apple watch (AW) irregular rhythm notification (IRN) feature uses photoplethysmography to identify prolonged episodes of irregular rhythm suggestive of atrial fibrillation (AF). IRN is FDA cleared for those with no previous history of AF, however, these devices are increasingly being used for AF management.  The objective of the present study was to determine the accuracy of the IRN in subjects with a previous diagnosis of nonpermanent AF., Methods: Subjects with a history of nonpermanent AF and either an insertable cardiac monitor (ICM) or cardiac implanted electronic device (CIED) with <5% ventricular pacing were fitted with an AW Series 5 for 6 months. AF episodes were compared between the ICM/CIED and IRN. The primary endpoints were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IRN by subject for AF ≥1 h. Secondary endpoints were sensitivity and PPV by AF episode ≥1 h. Analysis was limited to a maximum of 10 ICM/CIED episodes per subject and included only those AF episodes occurring during active AW use confirmed by activity data., Results: Thirty participants were enrolled. Mean age was 65.4 ± 12.2 years and 40% were female. There were 10 ICMs and 20 CIEDs. Eleven subjects had AF on ICM/CIED while the AW was worn, of whom 8 were detected by IRN. There were no false positive IRN detections by subject ("by subject" 72% sensitivity, 100% specificity, 100% PPV, and 90% NPV). Five subjects had AF only when the AW was not worn. There were a total of 70 AF episodes on ICM/CIED, 35 of which occurred while the AW was being worn. Of these, 21 were detected by IRN with 1 false positive ("by episode" sensitivity = 60.0%, PPV = 95.5%)., Conclusion: In a population with known AF, the AW IRN had a low rate of false positive detections and high specificity. Sensitivity for detection by subject and by AF episode was lower. The current IRN algorithm appears accurate for AF screening as currently cleared, but increased sensitivity and wear times would be necessary for disease management., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

The open ocean beyond national jurisdiction covers nearly half of Earth's surface and is largely unexplored. It is also an emerging frontier for new types of human activity. Understanding how new activities interact with high seas ecosystems is critical for our management of this other half of Earth. Using The Ocean Cleanup (TOC) as a model, we demonstrate why it is important to account for uncertainty when assessing and evaluating impacts of novel high seas activities on marine ecosystems. TOC's aim is to remove plastic from the ocean surface by collecting it with large nets. However, this approach also results in the collection of surface marine life (neuston) as by-catch. Using an interdisciplinary approach, we explore the social-ecological implications of this activity. We use population models to quantify potential impacts on the surface ecosystem; we determine the links between these ecosystems and society through an ecosystem services approach; and we review the governance setting relevant to the management of activities on the high seas. We show that the impact of ocean surface plastic removal largely depends on neuston life histories, and ranges from potentially mild to severe. We identify broader social-ecological implications that could be felt by stakeholders both beyond and within national jurisdiction. The legal framework applicable to TOC's activities is insufficiently specific to address both the ecological and social uncertainty we describe, demonstrating the urgent need for detailed rules and procedures on environmental impact assessment and strategic environmental assessment to be adopted under the new International Agreement on the conservation and sustainable use of marine biological diversity of areas beyond national jurisdiction which is currently being negotiated., Competing Interests: The authors declare there are no competing interests., (©2023 Spencer et al.)

Aims: Limited data exist to describe the prognostic impact of atrial fibrillation (AF) and oral anticoagulation on patients with alcoholic cardiomyopathy (ACM) compared with dilated cardiomyopathy (DCM) and were investigated in this study., Methods: Using Danish nationwide registries, a cohort analysis was conducted to assess the prognostic differences for patients with a first diagnosis of ACM versus DCM with and without AF 1994-2018 (followed until end 2019). Our study also assessed differences in mortality following initiation of anticoagulation in both populations., Results: Totally, 1237 patients with ACM (33% with AF) and 17,211 individuals with DCM (33% with AF) were included. Those with ACM were more often men (89 versus 71%) and younger than patients with DCM (mean age 56 versus 64 years). Cumulative 5-year mortality was greater among patients with ACM, compared with DCM, regardless of AF (ACM with AF 49% [95% CI: 44-54%], ACM without AF 48% [45-53%], DCM with AF 41% [39-42%], DCM without AF 30% [29-31%], P < 0.0001). The prognosis associated with AF was statistically significantly different in people with ACM and DCM (adjusted hazards ratio 0.85 [95% CI: 0.74-0.98] versus 1.04 [1.00-1.09] in ACM and DCM, P < 0.0001). The mortality associated with oral anticoagulation was similar in ACM and DCM (hazards ratio 0.81 [0.61-1.07] versus 0.87 [0.80-0.94], P = 0.49)., Conclusions: Patients with ACM had a worse prognosis when compared with patients with DCM, but this did not appear to be driven by AF. Patients with ACM were observed to have similar associated risk benefits of oral anticoagulation as DCM., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: In older patients with atrial fibrillation (AF), cognitive impairment and frailty are prevalent. It is unknown whether the risk and benefit of anticoagulation differ by cognitive function and frailty., Methods: A total of 1244 individuals with AF with age ≥65 years and a CHADSVASC score ≥2 were recruited from clinics in Massachusetts and Georgia between 2016 and 18 and followed until 2020. At baseline, frailty status and cognitive function were assessed. Hazard ratios of anticoagulation on physician adjudicated outcomes were adjusted by the propensity for receiving anticoagulation and stratified by cognitive function and frailty status., Results: The average age was 75.5 (± 7.1) years, 49% were women, and 86% were prescribed oral anticoagulants. At baseline, 528 (42.4%) participants were cognitively impaired and 172 (13.8%) were frail. The adjusted hazard ratios of anticoagulation for the composite of major bleeding or death were 2.23 (95% confidence interval: 1.08-4.61) among cognitively impaired individuals and 0.94 (95% confidence interval: 0.49-1.79) among cognitively intact individuals (P for interaction = 0.08). Adjusted hazard ratios for anticoagulation were 1.84 (95% confidence interval: 0.66-5.13) among frail individuals and 1.39 (95% confidence interval: 0.84-2.40) among not frail individuals (P for interaction = 0.67)., Conclusion: Compared with no anticoagulation, anticoagulation is associated with more major bleeding episodes and death in older patients with AF who are cognitively impaired., (© 2022 The American Geriatrics Society.)

Background: As patient prices for many medications have risen steeply in the United States, patients may engage in cost-reducing behaviors (CRBs) such as asking for generic medications or purchasing medication from the Internet., Objective: The objective of this study is to describe patterns of CRB, cost-related medication nonadherence, and spending less on basic needs to afford medications among older adults with atrial fibrillation (AF) and examine participant characteristics associated with CRB., Methods: Data were from a prospective cohort study of older adults at least 65 years with AF and a high stroke risk (CHA 2 DS 2 VASc ≥ 2). CRB, cost-related medication nonadherence, and spending less on basic needs to afford medications were evaluated using validated measures. Chi-square and t tests were used to evaluate differences in characteristics across CRB, and statistically significant characteristics (P < 0.05) were entered into a multivariable logistic regression to examine factors associated with CRB., Results: Among participants (N = 1224; mean age 76 years; 49% female), 69% reported engaging in CRB, 4% reported cost-related medication nonadherence, and 6% reported spending less on basic needs. Participants who were cognitively impaired (adjusted odds ratio 0.69 [95% CI 0.52-0.91]) and those who did not identify as non-Hispanic white (0.66 [0.46-0.95]) were less likely to engage in CRB. Participants who were married (1.88 [1.30-2.72]), had a household income of $20,000-$49,999 (1.52 [1.02-2.27]), had Medicare insurance (1.38 [1.04-1.83]), and had 4-6 comorbidities (1.43 [1.01-2.01]) had significantly higher odds of engaging in CRB., Conclusion: Although CRBs were common among older adults with AF, few reported cost-related medication nonadherence and spending less on basic needs. Patients with cognitive impairment may benefit from pharmacist intervention to provide support in CRB and patient assistance programs., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Penile abscess with involvement of the corpus cavernosum is a relatively rare condition and is typically associated with cavernosography, intracavernosal injections, penile prosthesis, open trauma, priapism, and seeding from a distant infection. Less commonly, it can be seen following penile fracture, particularly in patients with identified risk factors of uncontrolled diabetes mellitus or other immunosuppression. We report a case of a healthy 24-year-old man with a penile abscess discovered during repair of a one-month-old, imaging confirmed, neglected penile fracture., (© 2022 The Authors. Published by Elsevier Inc.)

Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent. we show that EA dose-dependently stimulates GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts. In addition, EA induces L-cells to secrete peptide YY (PYY). EA induces a rapid increase in intracellular [Ca 2+ ] i and the production of inositol trisphosphate in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling. Consistently, inhibition of (PLC) or Gα q ablates EA-stimulated increase of [Ca 2+ ] i and GLP-1 secretion. In vivo , a single dose of EA acutely stimulates GLP-1 and PYY secretion in mice, accompanied with an improved glucose tolerance and insulin levels. Oral administration of EA at a dose of 50 mg/kg/day for 2 weeks normalized the fasting blood glucose and restored glucose tolerance in high-fat diet-induced obese (DIO) mice to levels that were comparable to chow-fed mice. In addition, EA suppresses appetite, reduces food intake, promotes weight loss, and reverses perturbated metabolic variables in obese mice. These results suggest that EA could be a dual-action agent as an alternative or adjuvant treatment for both T2D and obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wu, Wang, Wang, Alkhalidy, Helm, Zhang, Ma, Zhang, Gilbert, Xu and Liu.)

Background: In older patients with atrial fibrillation (AF), physical, cognitive, and psychosocial limitations are prevalent. The prognostic value of these conditions for major bleeding is unclear., Objective: To determine whether geriatric conditions are prospectively associated with major bleeding in older patients with AF on anticoagulation., Design: Multicenter cohort study with 2-year follow-up from 2016 to 2020 in Massachusetts and Georgia from cardiology, electrophysiology, and primary care clinics., Participants: Diagnosed with AF, age 65 years or older, CHA 2 DS 2 -VASc score of 2 or higher, and taking oral anticoagulant (n=1,064). A total of 6507 individuals were screened., Main Measures: A six-component geriatric assessment of frailty, cognitive function, social support, depressive symptoms, vision, and hearing. Main outcome was major bleeding adjudicated by a physician panel., Key Results: At baseline, participants were, on average, 75.5 years old and 49% were women. Mean CHA 2 DS 2 -VASc score was 4.5 and the mean HAS-BLED score was 3.3. During 2.0 (± 0.4) years of follow-up, 95 (8.9%) participants developed an episode of major bleeding. After adjusting for key covariates and accounting for competing risk from death, cognitive impairment (hazard ratio [HR] 1.62, 95% confidence interval [CI]: 1.02-2.56) and frailty (HR 2.77, 95% CI 1.38-5.58) were significantly associated with the development of major bleeding., Conclusions: In older patients with AF taking anticoagulants, cognitive impairment and frailty were independently associated with major bleeding., (© 2022. The Author(s) under exclusive licence to Society of General Internal Medicine.)

The distribution of the black rat (Rattus rattus) has been heavily influenced by its association with humans. The dispersal history of this non-native commensal rodent across Europe, however, remains poorly understood, and different introductions may have occurred during the Roman and medieval periods. Here, in order to reconstruct the population history of European black rats, we first generate a de novo genome assembly of the black rat. We then sequence 67 ancient and three modern black rat mitogenomes, and 36 ancient and three modern nuclear genomes from archaeological sites spanning the 1st-17th centuries CE in Europe and North Africa. Analyses of our newly reported sequences, together with published mitochondrial DNA sequences, confirm that black rats were introduced into the Mediterranean and Europe from Southwest Asia. Genomic analyses of the ancient rats reveal a population turnover in temperate Europe between the 6th and 10th centuries CE, coincident with an archaeologically attested decline in the black rat population. The near disappearance and re-emergence of black rats in Europe may have been the result of the breakdown of the Roman Empire, the First Plague Pandemic, and/or post-Roman climatic cooling., (© 2022. The Author(s).)