Search

Background: The combination of active compression-decompression cardiopulmonary resuscitation (ACD-CPR) with an impedance threshold device (ITD) and controlled head-up positioning (AHUP-CPR) is associated with improved outcomes compared with conventional CPR (C-CPR). This study focused on the role of active decompression (AD) during AHUP-CPR., Methods: Farm pigs (n = 10, ∼40 kg) were anesthetized, intubated and ventilated. Physiological parameters and right ventricular pressure-volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins, followed by automated C-CPR (2 min), ACD + ITD CPR in the flat position (2 min), and then AHUP-CPR with 3 cm of lift above the neutral chest position. After 15 min of CPR, AD was discontinued and then restarted incrementally to 4 cm. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs., Results: Upon cessation of AD during AHUP-CPR, decompression right atrial pressure (+59%) increased (p < 0.01), whereas multiple hemodynamic parameters positively associated with perfusion, including coronary (-25%) and cerebral perfusion pressures (-11%), end-tidal CO2 (-13%), stroke volume and cardiac output (-26%), decreased immediately and significantly with p < 0.05. Restoration of AD reduced right atrial pressure and increased positive perfusion parameters in an incremental manner. Only with ≥ 3 cm of AD were all hemodynamic parameters restored to ≥ 90% of pre-AD discontinuation levels., Conclusion: Full chest wall lift, achieved with ≥ 3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. These findings should be considered when optimizing care with this new approach., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We confirm that this work is original and has not been submitted, nor is it under consideration for publication elsewhere. Lastly, the source of funding and conflicts of interest have been declared, and all authors have read and agreed to the final version of the manuscript. Two co-authors, Drs. Keith Lurie and Anja Metzger work, in part, for AdvancedCPR Solutions, the company that makes a human patient positioning system for Head Up CPR. While the device used for this porcine research is not one that can be used in humans, the relationship with AdvancedCPR Solutions is a potential conflict of interest. No other co-authors have any financial conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Several symptomatic cases of HEV infections were reported to the New Caledonia Island Public Health Service between August and December 2023. This prompted epidemiological and virological investigations to identify the source of infection., Approach and Results: HEV RNA was assessed in symptomatic patients, various food items, and pig farms on the Island. HEV strains were characterized by sequencing. A seroprevalence study was also conducted on asymptomatic blood donors before and after the outbreak. One hundred twenty-seven symptomatic cases were reported. Hospitalization was required for 29/127 patients (22.8%). Hospitalized patients presented more frequently with comorbidities, including liver and cardiovascular diseases (80.7% vs. 27%, p < 0.01), and 3 persons died (2.3%). Among the 100 HEV RNA-positive samples received at the French National Reference Centre for HEV, viral sequencing was possible for 76 samples. All strains were identified as HEV genotype 3, and 74/76 strains were grouped together (nucleotide identity: 98%-100%). Full-length sequencing indicated a new HEV-3 subtype within HEV-3 subclade abk. Only genotype 3f strains were detected on the Island's pig farms. No food items tested positive for HEV RNA. The seroprevalence of HEV IgG and IgM in blood donors was 9.2% (9/98) and 0%, respectively, in 2020, rising to 17.3% (17/98) and 2% (2/98) in 2024., Conclusions: Although all previous large-scale epidemics in Asia and Africa were associated with HEV-1 or 2, the New Caledonia outbreak was linked to HEV-3. A high number of symptomatic cases were admitted to the hospital, with a case-fatality rate of 2.3%., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Humanity's strive to understand why and how life appeared on planet Earth dates back to prehistoric times. At the beginning of the 19th century, empirical biology started to tackle this question yielding both Charles Darwin's Theory of Evolution and the paradigm that the crucial trigger putting life on its tracks was the appearance of organic molecules. In parallel to these developments in the biological sciences, physics and physical chemistry saw the fundamental laws of thermodynamics being unraveled. Towards the end of the 19th century and during the first half of the 20th century, the tensions between thermodynamics and the "organic-molecules-paradigm" became increasingly difficult to ignore, culminating in Erwin Schrödinger's 1944 formulation of a thermodynamics-compliant vision of life and, consequently, the prerequisites for its appearance. We will first review the major milestones over the last 200 years in the biological and the physical sciences, relevant to making sense of life and its origins and then discuss the more recent reappraisal of the relative importance of metal ions vs. organic molecules in performing the essential processes of a living cell. Based on this reassessment and the modern understanding of biological free energy conversion (aka bioenergetics), we consider that scenarios wherein life emerges from an abiotic chemiosmotic process are both thermodynamics-compliant and the most parsimonious proposed so far.

Radioactive particles often contain very high radioactivity concentrations and are widespread. They pose a potential risk to human health and the environment. Their detection, quantification, and characterization are crucial if we are to understand their impact. Here, we present the use of a real-time autoradiography gaseous detector (using parallel ionization multiplier) to expedite and improve the accuracy of radioactive particle screening in complex environmental samples. First, standard particles were used to assess the detector capabilities (spatial resolution, spectrometry, and artefact contributions), then, we applied the technique to more complex and environmentally relevant samples. The real-time autoradiography technique provides data with a spatial resolution (≲100 µm) suitable for particle analysis in complex samples. Further, it can differentiate between particles predominantly emitting alpha and beta radiation. Here, the technique is applied to radioactive cesium-rich microparticles collected from the Fukushima Daiichi nuclear exclusion zone, showing their accurate detection, and demonstrating the viability of real-time autoradiography in environmental scenarios. Indeed, for more complex samples (radioactive particles in a less radioactive heterogeneous background mix of minerals), the technique permits relatively high selectivity for radioactive particle screening (up to 61.2% success rate) with low false positive percentages (~ 1%)., (© 2024. The Author(s).)

The measurement of 226 Ra and the identification of 226 Ra-bearing minerals are important for studying the behavior of radium in the environment. Various instruments for measuring 226 Ra are currently used: among the radiometric techniques that measure in bulk (no spatialization), there are gamma spectrometers and alpha spectrometers. Other instruments such as SEM-EDS can map the chemical elements thus providing information on the distribution of 226 Ra, but are limited for ultra-trace analyses on natural geomaterials. Finally, autoradiography techniques can locate radioactivity, but are limited to the identification of the contribution of 226 Ra when the 238 U series is complete. This study focuses on spectroscopic autoradiography, a method for measuring both the energy of the alpha particle emissions and their positions on the autoradiograph. A gas detector based on a parallel ionization multiplier technology was used for this purpose. Alpha particle energy is dependent on the emitting radionuclides. In order to track the 226 Ra, the energy spectrum of the 238 U series was studied with modeling software. It appears possible to apply a thresholding on the energy spectrum to discriminate the 226 Ra from the first alpha emitters of the 238 U decay chain (i.e. 238 U, 234 U and 230 Th, all below 5 MeV). The developed method was applied to a U-mill tailing sample prepared as a thin section. The sample was heterogeneous in terms of radioactivity and was not at secular equilibrium with 238 U, as expected. The 226 Ra was identified and localized, and different regions of interest were also analyzed with SEM-EDS elements cartography. This revealed 226 Ra-rich barite (BaSO₄) phases measured at 3 ppm Ra on average and containing no uranium; and uranium in siderite (FeCO 3 ), showing a strong 226 Ra deficit compared with secular equilibrium. Spectroscopic autoradiography opens up possibilities for the analysis of heterogeneous geological samples containing natural alpha emitters such as 238 U and 226 Ra: the 226 Ra can be localized and quantified at ultra-trace content, and the method developed can also identify newly (young) uranium phases by measuring 238 U/ 226 Ra activity disequilibrium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Significant race and sex disparities exist in the prevalence, diagnosis, and outcomes of peripheral artery disease (PAD). However, clinical trials evaluating treatments for PAD often lack representative patient populations. This systematic review aims to summarize the demographic representation and enrollment strategies in clinical trials of lower-extremity endovascular interventions for PAD., Methods: Following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched multiple sources (Medline, EMBASE, Cochrane, Clinicaltrials.gov, WHO clinical trial registry) for randomized controlled trials (RCTs), RCT protocols, and peer-reviewed journal publications of RCTs conducted between January 2012 and December 2022. Descriptive analysis was used to summarize trial characteristics, publication or study protocol characteristics, and the reporting of demographic characteristics. Meta-regression was used to explore associations between demographic characteristics and certain trial characteristics., Results: A total of 2,374 records were identified. Of these, 59 met the inclusion criteria, consisting of 35 trials, 14 publications, and 10 protocols. Information regarding demographic representation was frequently missing. While all 14 trial publications reported age and sex, only 4 reported race/ethnicity, and none reported socioeconomic or marital status. Additionally, only 4 publications reported clinical outcomes by demographic characteristics. Meta-regression analysis revealed that 6% more women were enrolled in non-European trials (36%) than in European trials (30%)., Conclusions: The findings of this review highlight potential issues that may compromise the reliability and external validity of study findings in lower-extremity PAD RCTs when applied to the real-world population. Addressing these issues is crucial to enhance the generalizability and impact of clinical trial results in the field of PAD, ultimately leading to improved clinical outcomes for patients in underrepresented populations., Registration: The systematic review methodology was published in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022378304)., (© 2024. The Author(s).)

Objective: Audits are essential for reviewing and improving the medication-use process. Identifying areas for improvement can limit the risk of errors when preparing and administering drugs. Pediatric centers face specific challenges in ensuring the safety of the medication-use process. The objective of this study was to observe and compare compliance with criteria for the preparation and administration of medications by nurses in a mother-and-child university hospital center over two consecutive years., Methods: This observational cross-sectional study was conducted in a Canadian mother-and-child university hospital center. Audits were conducted over a 1-month period in 16 and 18 nursing care sectors in 2021 and 2022, respectively. The standardized audit evaluated compliance with prespecified criteria related to the preparation and administration of medication by nursing staff (77 criteria for 2021 and 82 criteria for 2022). The auditors comprised nurses and a pharmacist trained by the research team. Compliance was compared between years and assessed through a chi-square test., Results: The audit consisted of 522 observations in 2021 and 448 observations in 2022. Overall compliance was 76% in 2021 and 66% in 2022. The compliance rate by criterion ranged from 16% to 100%. In 2021 and 2022, 51 (84%) and 52 (87%) of the criteria, respectively, had compliance rates of more than 75%, and 12 (20%) and eight (13%), respectively, had 100% compliance. There were statistically significant decreases in compliance for nine of the 39 criteria for preparation of medications, notably prior hand hygiene (91%% vs. 84%, p = 0.002), and for six of the 17 criteria for administration of medications, including mentioning possible adverse effects to the patient (41% vs- 30%, p = 0.008)., Conclusion: In this study, compliance was over 75% for most of the criteria. However, for a few criteria, we observed a decrease in compliance from 2021 to 2022. Various hypotheses are proposed to explain these decreases, such as the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Epidemiological evidence links the proprotein convertase subtilisin/kexin 7 (PCSK7) to triglyceride (TG) metabolism. We associated the known PCSK7 gain-of-function non-coding SNP rs236918 with higher levels of plasma apolipoprotein B (apoB) and the loss-of-function coding variant p.Pro777Leu (SNP rs201598301) with lower apoB and TG. Herein, we aimed to unravel the in vivo role of liver PCSK7., Methods: We biochemically defined the functional role of PCSK7 in lipid metabolism using hepatic cell lines and Pcsk7 -/- mice. Our findings were validated following subcutaneous administration of hepatocyte-targeted N-acetylgalactosamine (GalNAc)-antisense oligonucleotides (ASOs) against Pcsk7., Results: Independent of its proteolytic activity, membrane-bound PCSK7 binds apoB100 in the endoplasmic reticulum and enhances its secretion. Mechanistically, the loss of PCSK7/Pcsk7 leads to apoB100 degradation, triggering an unfolded protein response, autophagy, and β-oxidation, eventually reducing lipid accumulation in hepatocytes. Non-alcoholic fatty liver disease (NAFLD) was induced by a 12-week high fat/fructose/cholesterol diet in wild type (WT) and Pcsk7 -/- mice that were then allowed to recover on a 4-week control diet. Pcsk7 -/- mice recovered more effectively than WT mice from all NAFLD-related liver phenotypes. Finally, subcutaneous administration of GalNAc-ASOs targeting hepatic Pcsk7 to WT mice validated the above results., Conclusions: Our data reveal hepatic PCSK7 as one of the major regulators of apoB, and its absence reduces apoB secretion from hepatocytes favoring its ubiquitination and degradation by the proteasome. This results in a cascade of events, eventually reducing hepatic lipid accumulation, thus supporting the notion of silencing PCSK7 mRNA in hepatocytes for targeting NAFLD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nabil G Seidah has patent METHOD FOR REDUCING HEPATIC TRIGLYCERIDES pending to Nabil G Seidah., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To determine if controlled head and thorax elevation, active compression-decompression cardiopulmonary resuscitation (CPR), and an impedance threshold device combined, termed automated head-up positioning CPR (AHUP-CPR), should be initiated early, as a basic (BLS) intervention, or later, as an advanced (ALS) intervention, in a severe porcine model of cardiac arrest., Methods: Yorkshire pigs (n = 22) weighing ∼40 kg were anesthetized and ventilated. After 15 minutes of untreated ventricular fibrillation, pigs were randomized to AHUP-CPR for 25 minutes (BLS group) or conventional CPR for 10 minutes, followed by 15 minutes of AHUP-CPR (ALS group). Thereafter, epinephrine, amiodarone, and defibrillation were administered. Neurologic function, the primary endpoint, was assessed 24-hours later with a Neurological Deficit Score (NDS, 0 = normal and 260 = worst deficit score or death). Secondary outcomes included return of spontaneous circulation (ROSC), cumulative survival, hemodynamics and epinephrine responsivity. Data, expressed as mean ± standard deviation, were compared using Fisher's Exact, log-rank, Mann-Whitney U and unpaired t-tests., Results: ROSC was achieved in 10/11 pigs with early AHUP-CPR versus 6/11 with delayed AHUP-CPR (p = 0.14), and cumulative 24-hour survival was 45.5% versus 9.1%, respectively (p < 0.02). The NDS was 203 ± 80 with early AHUP-CPR versus 259 ± 3 with delayed AHUP-CPR (p = 0.035). ETCO2, rSO2, and responsiveness to epinephrine were significantly higher in the early versus delayed AHUP-CPR., Conclusion: When delivered early rather than late, AHUP-CPR resulted in significantly increased hemodynamics, 24-hour survival, and improved neurological function in pigs after prolonged cardiac arrest. Based on these findings, AHUP-CPR should be considered a BLS intervention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Keith Lurie is a co-inventor of devices that can be used to perform AHUP-CPR. He is a co-founder of AdvancedCPR Solutions LLC, which manufactures a patient positioning system for AHUP-CPR. Anja Metzger also works for AdvancedCPR Solution LLC. None of the other co-authors have any financial conflicts of interest with this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Botulinum toxin injections are commonly used for the treatment of spasticity. However, injection procedures are associated with pain and procedural anxiety. While pharmacological approaches are commonly used to reduce these, innovative technology might be considered as a potential non-pharmacological alternative. Given this context, immersive virtual reality (VR) has shown effectiveness in the management of procedural pain. Our retrospective pilot study aimed to assess the potential added value of virtual reality in the management of pain and anxiety during intramuscular injections of botulinum toxin., Materials and Methods: Seventeen adult patients receiving botulinum toxin injections were included. A numerical rating scale was used to assess pain and anxiety during the injection procedure. The patients reported the pain experienced during previous injections without VR before injection and the pain experienced in the current procedure with VR after the end of the procedure. The level of satisfaction of VR experience, whether or not they agreed to reuse VR for the subsequent toxin botulinum injection, and whether or not they would recommend VR to other patients were assessed., Results: The use of virtual reality led to a decrease of 1.8 pain-related points compared to the procedure without technology. No significant improvement in the level of anxiety was reported. Patients were very satisfied with their VR experiences (7.9 out of 10), and many would agree to reuse VR in their next injection procedure (88%) and to recommend the use of VR in other patients (100%)., Conclusion: VR was useful for managing procedural pain related to botulinum toxin injection in adults, with a high level of satisfaction reported by the patients. VR should be considered as a valuable alternative to pharmacological approaches to manage procedural pain during botulinum toxin injection in adults.

Despite high prevalence of cardiovascular disease (CVD) and CVD risk factors among American Indian or Alaska Native adults (AI/AN), there is little information on aspirin use in this population. This survey-based study seeks to understand prevalence of aspirin use in a sample of AI/AN adults in the Upper Midwestern United States. In-person and telephone based surveys were conducted querying self-reported CVD and CVD risk factors, aspirin use, and aspirin related discussion with clinicians. A total of 237 AI/AN participants were included: mean age (SD) was 60.8 (8.4) years; 143 (60 %) were women; 59 (25 %) reported CVD history. CVD risk factors were common particularly smoking (37 %) and diabetes (37 %). Aspirin use was much higher among those with CVD (secondary prevention, 76 %) than those without (primary prevention, 33 %). Primary prevention aspirin use was significantly associated with age and all CVD risk factors in unadjusted analyses. After adjustment for demographics and CVD risk factors, only age (aRR 1.13 per 5 years, 95 % CI 1.02, 1.25) and diabetes (aRR 2.44, 95 % CI 1.52, 3.92) remained significantly associated with aspirin. Regardless of CVD status, a higher proportion of those taking aspirin reported a conversation about aspirin with their doctor compared to those not taking aspirin. Among participants with no CVD, those who had such a conversation were 2.6 times more likely to use aspirin than those who did not have a conversation (aRR 2.64, 95 % CI 1.58, 4.44). The findings of this study emphasize the importance of the patient-provider relationship for preventive therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Liposomes are versatile lipid-based vesicles with interesting physicochemical properties, making them excellent candidates for interdisciplinary applications in the medicinal, biological, and environmental sciences. The synthesis of mineral-liposome hybrid systems lends normally inert vesicles with the catalytic, magnetic, electrical, and optical properties of the integrated mineral species. Such applications require an understanding of the physicochemical interactions between organic molecules and inorganic crystal structures. This review provides an overview on these interactions and details on synthesis and characterization methods for these systems., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Aim: This review provides a study protocol for a systematic review of peripheral artery disease (PAD) clinical trials to examine the eligibility criteria, demographic representation, and enrollment strategies among PAD patients undergoing lower extremity (LE) endovascular interventions. Methods: This systematic review will be conducted according to the Cochrane Collaboration methodology for systematic reviews and following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Eligible studies will include randomized controlled trials (RCTs) between January 2012 and December 2022. The primary outcome will be a description and summary of the frequency of the reporting of demographic characteristics. The feasibility of a meta-analysis or meta-regression will be explored, but if determined to be infeasible, the Synthesis Without Meta-analysis (SWiM) reporting guideline will be followed for the reporting of findings. Discussion: The findings may help to quantify existing inequities in clinical trial participation that may be addressed through optimizing enrollment strategies for future PAD trials. Systematic review registration: PROSPERO (CRD42022378304).

Background: Patients taking beta-blockers (BBs) commonly experience weight gain. There is limited research exploring how BBs impact weight loss after bariatric surgery., Objectives: We examined how BBs impact 12-month weight loss in patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)., Setting: Large midwest health system., Methods: We reviewed health records of SG and RYGB patients (2011-2022) and categorized them by BB usage (none, pre-, post-, or pre- and postoperative). Multivariable linear regression models examined the relation between BB use, percent total body weight loss (%TBWL), and percent excess body mass index lost (%EBMIL)., Results: A total of 889 individuals (SG, n = 485; RYGB, n = 404) had complete data. RYGB led to greater %TBWL compared to SG (31% versus 26%, P < .01) and greater %EBMIL (79% versus 64%, P < .01). BB status did not significantly affect 12-month %TBWL or %EBMIL., Conclusions: BB use may not significantly affect weight loss 12 months after bariatric surgery. This finding could enable physicians to prescribe BBs for improved blood pressure control in bariatric surgery patients with less concern of blunting weight loss. Longer term follow-up with a larger sample size would be an important next step to better characterize the relationship between BB usage and bariatric surgery., (Copyright © 2023. Published by Elsevier Inc.)

Background: Nursing home admission remains a central outcome in many healthcare systems and community-based programs. The objective of this meta-analysis was to determine the efficacy of pharmacological and nonpharmacological interventions in preventing nursing home admission for adults aged 65 years or older., Methods: MEDLINE, EMBASE, PsycInfo, CINAHL, and the Cochrane Library were all last searched in March 2022 to identify up-to-date eligible studies for the meta-analysis. Two reviewers screened each abstract independently. In instances where reviewers disagreed as to inclusion, all reviewers convened to review the Abstract to come to a consensus decision regarding inclusion. Two reviewers independently collected data from each report. Disagreements were resolved using group consensus. The first author reviewed the narrative descriptions of intervention components to create a categorization scheme for the various interventions evaluated in selected studies. These categorizations were reviewed with the co-authors (second-fifth) and collapsed to create the final classification of intervention type. Study risk of bias was assessed using an instrument developed based on Agency for Healthcare Research & Quality (AHRQ) guidance. Differences between the percentages of participants in treatment versus control arms was the outcome of interest., Results: Two-hundred and eighty-three studies with a total of 203,735 older persons were included in the meta-analysis. Specialty geriatrics care (OR = 0.77, 95% CI, 0.60-0.99), multicomponent interventions (OR = 0.82, 95% CI, 0.67-0.99), and cognitive stimulation (OR = 0.60, 95% CI, 0.38-0.96) were associated with less frequent nursing home admission. Home-based and inpatient/discharge management interventions approached statistical significance but were not associated with reduced institutionalization., Conclusions: Even in the face of complex care needs, older adults wish to live at home. Effectively disseminating and implementing geriatric care principles across healthcare encounters could achieve a highly valued and preferred outcome in older adulthood: aging in place., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Fluorinated polyimides incorporated with triptycene units have gained growing attention over the last decade since they present potentially interesting selectivities and a higher free volume with respect to their triptycene-free counterparts. This work examines the transport of single-gas and mixed-gas N 2 and CH 4 in the triptycene-based 6FDA-BAPT homopolyimide and in a block 15,000 g mol -1 /15,000 g mol -1 6FDA-mPDA/BAPT copolyimide by using molecular dynamics (MD) simulations. The void-space analyses reveal that, while the free volume consists of small-to-medium holes in the 6FDA-BAPT homopolyimide, there are more medium-to-large holes in the 6FDA-mPDA/BAPT copolyimide. The single-gas sorption isotherms for N 2 and CH 4 over the 0-70 bar range at 338.5 K show that both gases are more soluble in the block copolyimide, with a higher affinity for methane. CH 4 favours sites with the most favourable energetic interactions, while N 2 probes more sites in the matrices. The volume swellings remain limited since neither N 2 nor CH 4 plasticise penetrants. The transport of a binary-gas 2:1 CH 4 /N 2 mixture is also examined in both polyimides under operating conditions similar to those used in current natural gas processing, i.e., at 65.5 bar and 338.5 K. In the mixed-gas simulations, the solubility selectivities in favour of CH 4 are enhanced similarly in both matrices. Although diffusion is higher in 6FDA-BAPT/6FDA-mPDA, the diffusion selectivities are also close. Both triptycene-based polyimides under study favour, to a similar extent, the transport of methane over that of nitrogen under the conditions studied.

Background Recent guidelines have emphasized the use of medical management, early diagnosis, and a multidisciplinary team to effectively treat patients with critical limb ischemia (CLI). Previous literature briefly highlighted the current racial disparities in its intervention. Herein, we analyze the trend over a 14-year time period to investigate whether the disparities gap in CLI management is closing. Methods and Results The National Inpatient Sample was queried between 2005 and 2018 for hospitalizations involving CLI. Nontraumatic amputations and revascularization were identified. Utilization trends of these procedures were compared between races (White, Black, Hispanic, Asian and Pacific Islander, Native American, and Other). Multivariable regression assessed differences in race regarding procedure usage. There were 6 904 562 admissions involving CLI in the 14-year study period. The rate of admissions in White patients who received any revascularization decreased by 0.23% ( P <0.001) and decreased by 0.25% ( P =0.025) for Asian and Pacific Islander patients. Among all patients, the annual rate of admission in White patients who received any amputation increased by 0.21% ( P <0.001), increased by 0.19% ( P =0.001) for Hispanic patients, and increased by 0.19% ( P =0.012) for the Other race patients. Admissions involving Black, Hispanic, Asian and Pacific Islander, or Other race patients had higher odds of receiving any revascularization compared with White patients. All races had higher odds of receiving major amputation compared with White patients. Conclusions Our analysis highlights disparities in CLI treatment in our nationally representative sample. Non-White patients are more likely to receive invasive treatments, including major amputations and revascularization for CLI, compared with White patients.

Shared coordination geometries between metal ions within reactive minerals and enzymatic metal cofactors hints at mechanistic and possibly evolutionary homology between particular abiotic chemical mineralogies and biological metabolism. The octahedral coordination of reactive Fe 2+/3+ minerals such as green rusts, endemic to anoxic sediments and the early Earth's oceans, mirrors the di-iron reaction centre of soluble methane monooxygenase (sMMO), responsible for methane oxidation in methanotrophy. We show that methane oxidation occurs in tandem with the oxidation of green rust to lepidocrocite and magnetite, mimicking radical-mediated methane oxidation found in sMMO to yield not only methanol but also halogenated hydrocarbons in the presence of seawater. This naturally occurring geochemical pathway for CH 4 oxidation elucidates a previously unidentified carbon cycling mechanism in modern and ancient environments and reveals clues into mineral-mediated reactions in the synthesis of organic compounds necessary for the emergence of life.

Background A total of 40% of patients with severe aortic stenosis (AS) have low-gradient AS, raising uncertainty about AS severity. Aortic valve calcification, measured by computed tomography (CT), is guideline-endorsed to aid in such cases. The performance of different CT-derived aortic valve areas (AVAs) is less well studied. Methods and Results Consecutive adult patients with presumed moderate and severe AS based on echocardiography (AVA measured by continuity equation on echocardiography <1.5 cm 2 ) who underwent cardiac CT were identified retrospectively. AVAs, measured by direct planimetry on CT (AVA CT ) and by a hybrid approach (AVA measured in a hybrid manner with echocardiography and CT [AVA Hybrid ]), were measured. Sex-specific aortic valve calcification thresholds (≥1200 Agatston units in women and ≥2000 Agatston units in men) were applied to adjudicate severe or nonsevere AS. A total of 215 patients (38.0% women; mean±SD age, 78±8 years) were included: normal flow, 59.5%; and low flow, 40.5%. Among the different thresholds for AVA CT and AVA Hybrid , diagnostic performance was the best for AVA CT <1.2 cm 2 (sensitivity, 85%; specificity, 26%; and accuracy, 72%), with no significant difference by flow status. The percentage of patients with correctly classified AS severity (correctly classified severe AS+correctly classified moderate AS) was as follows; AVA measured by continuity equation on echocardiography <1.0 cm 2 , 77%; AVA CT <1.2 cm 2 , 73%; AVA CT <1.0 cm 2 , 58%; AVA Hybrid <1.2 cm 2 , 59%; and AVA Hybrid <1.0 cm 2 , 45%. AVA CT cut points of 1.52 cm 2 for normal flow and 1.56 cm 2 for low flow, provided 95% specificity for excluding severe AS. Conclusions CT-derived AVAs have poor discrimination for AS severity. Using an AVA CT <1.2-cm 2 threshold to define severe AS can produce significant error. Larger AVA CT thresholds improve specificity.

Cesium-134 and -137 are prevalent, long-lived, radio-toxic contaminants released into the environment during nuclear accidents. Large quantities of insoluble, respirable Cs-bearing microparticles (CsMPs) were released into the environment during the Fukushima Daiichi nuclear accident. Monitoring for CsMPs in environmental samples is essential to understand the impact of nuclear accidents. The current detection method used to screen for CsMPs (phosphor screen autoradiography) is slow and inefficient. We propose an improved method: real-time autoradiography that uses parallel ionization multiplier gaseous detectors. This technique permits spatially resolved measurement of radioactivity while providing spectrometric data from spatially heterogeneous samples-a potential step-change technique for use after nuclear accidents for forensic analysis. With our detector configuration, the minimum detectable activities are sufficiently low for detecting CsMPs. Further, for environmental samples, sample thickness does not detrimentally affect detector signal quality. The detector can measure and resolve individual radioactive particles ≥465 μm apart. Real-time autoradiography is a promising tool for radioactive particle detection., Competing Interests: The authors declare the following competing financial interest(s): The authors declare the following personal relationship which may be considered as a potential competing interest: This research was performed in collaboration with a private company, S.A.S. ai4r, and several of the authors work for the company., (© 2023 The Authors. Published by American Chemical Society.)

There is currently a lack of uniformity in methods of aortic diameter measurements across different imaging modalities. In this study, we sought to evaluate the accuracy of transthoracic echocardiography (TTE) in comparison with magnetic resonance angiography (MRA) for the measurement of proximal thoracic aorta diameters. This is a retrospective analysis of 121 adult patients at our institution who had TTE and electrocardiogram  (ECG)-gated MRA performed within 90 days of each other between 2013 and 2020. Measurements were made at the level of sinuses of Valsalva (SoV), sinotubular junction (STJ), and ascending aorta (AA) using leading edge-to-leading edge (LE) convention for TTE and inner-edge-to-inner-edge (IE) convention for MRA. Agreement was assessed using Bland-Altman methods. Intra- and interobserver variability were assessed by intraclass correlation. The average age of patients in the cohort was 62 years, and 69% of patients were male. The prevalence of hypertension, obstructive coronary artery disease, and diabetes was 66%, 20%, and 11%, respectively. The mean aortic diameter by TTE was SoV 3.8 ± 0.5 cm, STJ 3.5 ± 0.4 cm, and AA 4.1 ± 0.6 cm. The TTE-derived measurements were larger than the MRA ones by 0.2 ± 2 mm, 0.8 ± 2 mm, and 0.4 ± 3 mm at the level of SoV, STJ, and AA, respectively, but the differences were not statistically significant. There were no significant differences in the aorta measurements by TTE compared with MRA, when stratified by gender. In conclusion, transthoracic echocardiogram-derived proximal aorta measurements are comparable to MRA measurements. Our study validates current recommendations that TTE is an acceptable modality for screening and serial imaging of the proximal aorta., Competing Interests: Disclosures The authors have no conflicts of interest to declare. The data that support the findings of this study are available from the corresponding author, (S.K.), upon reasonable request., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The reactivity of aryl monocarboxylic acids (benzoic, 1- or 2-naphtoic, 4'-methylbiphenyl-4-carboxylic, and anthracene-9-carboxylic acids) as complexing agents for the ethoxide niobium(V) (Nb(OEt) 5 precursor has been investigated. A total of eight coordination complexes were isolated with distinct niobium(V) nuclearities as well as carboxylate complexation states. The use of benzoic acid gives a tetranuclear core Nb 4 (μ 2 -O) 4 (L) 4 (OEt) 8 ] (L=benzoate (1)) with four Nb-(μ 2 -O)-Nb linkages in a square plane configuration. A similar tetramer, 7, was obtained with 2-naphtoic acid by using a 55 % humid atmosphere synthetic route. Two types of dinuclear brick were identified with one central Nb-(μ 2 -O)-Nb linkage; they differ in their complexation state, with one bridging carboxylate ([Nb 2 (μ 2 -O)(μ 2 -OEt)(L)(OEt) 6 ], with L=1-naphtoate (3) or anthracene-9-carboxylate (5)) or two bridging carboxylate groups ([Nb 2 (μ 2 -O)(L) 2 (OEt) 6 ], with L=4'-methylbiphenyl-4-carboxylic (4) or anthracene-9-carboxylate (6)). An octanuclear moiety [Nb 8 (μ 2 -O) 12 (L) 8 (η 1 -L) 4-x (OEt) 4+x ] (with L=2-naphtoate, x=0 or 2; 8) was obtained by using a solvothermal route in acetonitrile; it has a cubic configuration with niobium centers at each node, linked by 12 μ 2 -O groups. The formation of the niobium oxo clusters was characterized by infrared and liquid 1 H NMR spectroscopy in order to analyze the esterification reaction, which induces the release of water molecules that further react through oxolation with niobium atoms, in different {Nb 2 O}, {Nb 4 O 4 } and {Nb 8 O 12 } nuclearities., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Aims: Inappropriate sinus tachycardia (IST) is a syndrome characterized by an elevated sinus rate unassociated with known physiological, pathological, or pharmacological causes. Despite published consensus documents, IST definitions appear to vary in the literature. In this study, we reviewed IST publications to evaluate IST definition variability and ascertain the degree to which consensus definitions are being adopted., Methods and Results: English-language articles in PubMed, Ovid MEDLINE, Ovid Embase, and Google Scholar published from 1 January 1970 to 1 June 2021 with the title terms 'inappropriate sinus tachycardia,' 'non-paroxysmal sinus tachycardia,' or 'permanent sinus tachycardia' were searched. In each, the IST definition used, qualifying characteristics, and publications cited to support each definition were recorded. We identified 138 publications meeting the search criteria. Inappropriate sinus tachycardia definitions were provided in 114 of 138 articles (83%). A majority of definitions (92/114, 81%) used distinct heart rate (HR) thresholds. Among these, the most common threshold was ≥100 beats per minute (BPM) (75/92, 82%), mainly measured at rest (54/92, 59%). Most definitions (47/92, 51%) included a second criterion to qualify for IST; these were most often an HR threshold of 90 BPM measured over 24 h by ambulatory electrocardiogram (37/47, 79%). Diagnosis of exclusion was a common criterion (75/92, 82%) but symptom status was not (41/92, 45%). The 2015 Heart Rhythm Society IST consensus was commonly cited but adopted in only 37% of definitions published after 2015., Conclusions: Inappropriate sinus tachycardia definitions in current literature are inconsistent, and professional society consensus IST definitions have, to date, had limited impact., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The reactivity of 2,3-pyridine-dicarboxylic (known as quinolinic or H 2 qui) acid and 2,5-pyridine-dicarboxylic (known as isocinchomeronic or H 2 icc) acid has been investigated as a complexing agent toward the niobium(IV) tetrachloride precursor (NbCl 4 ·2THF) in different organic solvent mixtures. It resulted in the isolation of four crystalline assemblies of mononuclear coordination complexes 1-4 [Nb( H L) 4 ·solvent], where H L is the monoprotonated quinolinate (Hqui) ligand (complexes 1 - 3 ) or the monoprotonated isocinchomeronate ligand (complex 4 ). For each complex, the discrete niobium(IV) center is eightfold coordinated to four oxygen atoms from the deprotonated carboxylate arm and four nitrogen atoms from the pyridine part of the dicarboxyl ligand with a dodecahedral environment [NbO 4 N 4 ]. The remaining carboxyl arm (either in 3 or in 5 position) remained under its protonated form, leading to neutral [Nb( H L) 4 ] moieties for compounds 1 , 2 , and 4 , or the anionic [Nb(qui)( H qui) 3 ] - moiety for compound 3 . The complexes are observed in various molecular arrangements, involving intercalated solvent molecules such as acetonitrile in compound 1 ([Nb( H qui) 4 ·0.8(CH 3 CN)], obtained at room temperature), a mixture of acetonitrile and pyridine in compound 2 ([Nb( H qui) 4 ·0.7CH 3 CN·2PYR], obtained via the solvothermal reaction at 80 °C), a mixture of pyridine and triethylamine, in addition with water and chloride species, in compound 3 ( [Nb(qui)( H qui) 3 ·Cl· H PYR· H TEA·1.5H 2 O], obtained via solvothermal reaction at 80 °C), and N , N -dimethylformamide in compound 4 ([Nb( H icc) 4 ·6DMF], obtained at room temperature). The d 1 configuration expected for the niobium(IV) centers has been analyzed by magnetic measurements, as well as by EPR and XPS. An anti-ferromagnetism transition has been observed at very low temperatures for complexes 1 (3.6 K) and 4 (3.3 K), for which the shortest Nb···Nb interatomic lengths occur.

Background: Survival after out-of-hospital cardiac arrest (OHCA) remains poor. A physiologically distinct cardiopulmonary resuscitation (CPR) strategy consisting of (1) active compression-decompression CPR and/or automated CPR, (2) an impedance threshold device, and (3) automated controlled elevation of the head and thorax (ACE) has been shown to improve neurological survival significantly versus conventional (C) CPR in animal models. This resuscitation device combination, termed ACE-CPR, is now used clinically., Objectives: To assess the probability of OHCA survival to hospital discharge after ACE-CPR versus C-CPR., Methods: As part of a prospective registry study, 227 ACE-CPR OHCA patients were enrolled 04/2019-07/2020 from 6 pre-hospital systems in the United States. Individual C-CPR patient data (n = 5196) were obtained from three large published OHCA randomized controlled trials from high-performing pre-hospital systems. The primary study outcome was survival to hospital discharge. Secondary endpoints included return of spontaneous circulation (ROSC) and favorable neurological survival. Propensity-score matching with a 1:4 ratio was performed to account for imbalances in baseline characteristics., Results: Irrespective of initial rhythm, ACE-CPR (n = 222) was associated with higher adjusted odds ratios (OR) of survival to hospital discharge relative to C-CPR (n = 860), when initiated in <11 min (3.28, 95 % confidence interval [CI], 1.55-6.92) and < 18 min (1.88, 95 % CI, 1.03-3.44) after the emergency call, respectively. Rapid use of ACE-CPR was also associated with higher probabilities of ROSC and favorable neurological survival., Conclusions: Compared with C-CPR controls, rapid initiation of ACE-CPR was associated with a higher likelihood of survival to hospital discharge after OHCA., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Cardiopulmonary stress test (CPX) is routinely performed when evaluating patient candidacy for left ventricular assist device (LVAD) implantation. The predictive value of hypotensive systolic blood pressure (SBP) response during CPX on clinical outcomes is unknown. This study aims to determine the effect of hypotensive SBP response during to clinical outcomes among patients who underwent LVAD implantation., Methods and Results: This was a retrospective single center study enrolling consecutive patients implanted with a continuous flow LVAD between 2011 and 2022. Hypotensive SBP response was defined as peak exercise SBP below the resting value. Multivariable Cox-regression analysis was performed to evaluate the relationship between hypotensive SBP response and all-cause mortality within 30 and 90 days of LVAD implantation. A subgroup analysis was performed for patients implanted with a HeartMate III (HM III) device. Four hundred thirty-two patients underwent LVAD implantation during the pre-defined period and 156 with INTERMACS profiles 3-6 met our inclusion criteria. The median age was 63 years (IQR 54-69), and 52% had ischaemic cardiomyopathy. Hypotensive SBP response was present in 35% of patients and was associated with increased 90 day all-cause mortality (unadjusted HR 9.16, 95% CI 1.98-42; P = 0.0046). Hazard ratio remained significant after adjusting for age, INTERMACS profile, serum creatinine, and total bilirubin. Findings were similar in the HM III subgroup., Conclusions: Hypotensive SBP response on pre-LVAD CPX is associated with increased perioperative and 90 day mortality after LVAD implantation. Additional studies are needed to determine the mechanism of increased mortality observed., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Enteric methane emissions from dairy cows are an environmental problem as well as a gross feed energy loss to the animal. Methane is generated in the rumen by methanogenic archaea from hydrogen (H 2 ) + carbon dioxide and from H 2 + methanol or methylamines. The methanogenic substrates are provided by non-methanogens during feed fermentation. Methane mitigation approaches have yielded variable results, partially due to an incomplete understanding of the contribution of hydrogenotrophic and methylotrophic archaea to methanogenesis. Research indicates that 3-nitrooxypropanol (3-NOP) reduces enteric methane formation in dairy cows by inhibiting methyl-coenzyme M reductase (MCR), the enzyme responsible for methane formation. The purpose of this study was to utilize metagenomic and metatranscriptomic approaches to investigate the effect of 3-NOP on the rumen microbiome and to determine the fate of H 2 that accumulates less than expected under inhibited methanogenesis., Results: The inhibitor 3-NOP was more inhibitory on Methanobrevibacter species than methanol-utilizing Methanosphaera and tended to reduce the gene expression of MCR. Under inhibited methanogenesis by 3-NOP, fluctuations in H 2 concentrations were accompanied by changes in the expression of [FeFe] hydrogenases in H 2 -producing bacteria to regulate the amount of H 2 production. No previously reported alternative H 2 sinks increased under inhibited methanogenesis except for a significant increase in gene expression of enzymes involved in the butyrate pathway., Conclusion: By taking a metatranscriptomic approach, this study provides novel insights on the contribution of methylotrophic methanogens to total methanogenesis and regulation of H 2 metabolism under normal and inhibited methanogenesis by 3-NOP in the rumen. Video Abstract., (© 2022. The Author(s).)

Aims: Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho-vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline-recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFrEF., Methods and Results: An individual patient data (IPD) meta-analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline-directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6-month changes in 6-min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT-proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of -13 points (95% CI -17, -10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT-proBNP &lt;1600 pg/ml, regardless of the cardiac resynchronization therapy indication status., Conclusion: An IPD meta-analysis suggests that BAT improves exercise capacity, NYHA class, and QoL in HFrEF patients receiving GDMT. These clinically meaningful improvements were consistent across the range of patients studies. BAT was also associated with an improvement in NT-proBNP in subjects with a lower baseline NT-proBNP., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

High-performance polymers with polybenzoxazole (PBO) structures, formed via thermal rearrangement (TR) of aromatic polyimide precursors, have been developed for gas separation applications. The present work compares the transport of N 2 and CH 4 in a 6FDA-bisAPAF polyimide precursor and in its TR-PBO derivative using molecular dynamics (MD) simulations. The modelling closely mimicked the experimental approach by transforming a 6FDA-bisAPAF atomistic model into its corresponding TR-PBO structure via a specific algorithm. The densities and void spaces of both precursor and TR polymers were found to compare well to experimental data. An iterative technique was used to obtain the single-gas sorption isotherms of N 2 and CH 4 at 338.5 K in both polymers over a range of feed pressures up to and exceeding 65 bar. CH 4 was systematically found to be more soluble than N 2 . Solubilities in both matrices were quite similar with those in TR-PBO being slightly higher due to its larger fraction of significant volume. Volume dilation analyses confirmed a higher resistance to plasticization for TR-PBO. Extended single-gas N 2 and CH 4 simulations and 2 : 1 binary CH 4 /N 2 mixed-gas simulations were then conducted in both matrices at 338.5 K and at a pressure of ∼65 bar corresponding to natural gas processing conditions. Mixed-gas sorption was modelled using a modification of the aforementioned iterative method, which fixed the pressure and iterated to convergence the number of molecules of each type of penetrant. The gas diffusion coefficients were estimated using the Trajectory-Extending Kinetic Monte Carlo (TEKMC) procedure. As found experimentally, significantly higher diffusivities and permeabilities were observed in the TR polymer, which led to a slightly lower ideal N 2 /CH 4 permselectivity for TR-PBO (∼2.6) when compared to its 6FDA-bisAPAF precursor (∼3.8). However, both models showed a reduced N 2 /CH 4 separation efficiency under 2 : 1 binary CH 4 /N 2 mixed-gas conditions bordering on the loss of selectivity. For 6FDA-bisAPAF, both permeabilities decreased in the mixed-gas case, but more for N 2 than for CH 4 . For TR-PBO, the permeability of the faster N 2 decreased while the permeability of the slower CH 4 increased under mixed-gas conditions. This confirms that single-gas simulations are not sufficient for the prediction of the actual mixed-gas permselectivity behaviour in such polymers.

Since the emergence of chemical, biological, radiological, and nuclear risks, significant efforts have been made to create efficient personal protection equipment. Recently, metal-organic framework (MOF) materials have emerged as new promising candidates for the capture and degradation of various threats, like chemical warfare agents (CWAs) or radioactive species. Herein, we report a new synthesis method of MOF-textile composites by microwave irradiation, with direct anchoring of MOFs on textiles. The resistance of the composite has been tested using normed abrasion measurements, and non-stable samples were optimized. The protection capacity of the MOF-textile composite has been tested against dimethyl 4-nitrophenyl phosphate, a common CWA simulant, showing short degradation half-life (30 min). Radiological/nuclear protection has also been tested through uranium uptake (up to 15 mg g -1 adsorbent) and the capture of Kr or Xe gas at 0.9 and 2.9 cm 3 /g, respectively.

Background Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan-Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment-naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44-68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow-up time of 489 days (281-812 days). The 1-, 2-, and 3-year mortality was 8% (95% CI, 6%-10%), 16% (95% CI, 13%-19%), and 21% (95% CI, 17%-25%), respectively. When stratified into low-, intermediate-, and high-risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment-naïve patients, initial combination therapy was associated with better 1-year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19-0.95]; P =0.037). Conclusions Mortality in the intermediate- and high-risk patients with PAH remains unacceptably high in the PHAR, suggesting the importance for early diagnosis, aggressive use of available therapies, and the need for better therapeutics.

Importance: Low-dose aspirin is used for primary prevention of cardiovascular disease in approximately one-third of the US adult population. Overuse and underuse are common and not concordant with guidelines., Objective: To test a community and clinic education intervention to improve guideline-based aspirin use for the primary prevention of cardiovascular disease., Design, Setting, and Participants: The Ask About Aspirin project was a nonrandomized controlled trial conducted from, July 1, 2015, to March 31, 2020, using professional education, traditional media, and digital media to improve guideline-based aspirin use. The adult population (aged 45-79 years for men and 55-79 years for women) and primary care clinics in Minnesota were the education targets. The 4 adjacent states were controls., Interventions: The statewide campaign distributed billboards, newspaper articles and other print material, and radio announcements. An Ask About Aspirin website was heavily promoted. Primary care clinics identified appropriate aspirin candidates, and clinicians received continuing education about aspirin., Main Outcomes and Measures: Guideline-based aspirin use by the target population., Results: Cross-sectional random telephone surveys of 8342 men aged 45 to 79 years and women aged 55 to 79 years were conducted at baseline, 2 years, and 4 years after the intervention. Participation was similar between men and women (baseline: 973 [49%] vs 1001 [51%]; year 4: 912 [50%] vs 930 [50%]). Age during the study also was similar (baseline: 64.7 [IQR, 64.4-65.1] years; year 4: 66.2 [IQR, 65.8-66.5] years). A validated questionnaire evaluated aspirin use. The Ask About Aspirin website had more than 1 million visits; 124 primary care clinics with more than 1000 participating clinicians were part of the education program. Small, nonsignificant increases in discussions with clinicians regarding aspirin resulted (baseline: 341 of 1001 [34%]; year 4: 339 of 930 [36%]; P = .27). Overall aspirin use decreased after the release of new US Preventive Services Task Force guidelines in 2016 and 3 aspirin randomized clinical trials in 2018 suggested reduced aspirin use (baseline: 816 of 1974 [41%]; year 4: 629 of 1842 [34%]; P < .001). Decreases were also noted from year 2 to year 4 in appropriate use (year 2: 597 of 1208 [49%]; year 4: 478 of 1191 [40%]; P < .001) and overuse (year 2: 170 of 602 [28%]; year 4: 151 of 651 [23%]; P = .04). There were no significant differences between Minnesota and the control states., Conclusions and Relevance: In this nonrandomized controlled trial, a multiyear statewide campaign was not associated with increased appropriate aspirin use for cardiovascular disease prevention. Contextual factors during the project, including guideline changes and media controversy following the new trials, undermined study goals. These findings suggest that although education programs using social media for cardiovascular disease prevention can result in millions of hits, the use of this strategy to encourage behavior change is problematic, even with supportive clinical sites., Trial Registration: ClinicalTrials.gov Identifier: NCT02607917.

A series of Zr-based UiO-n MOF materials (n=66, 67, 68) have been studied for iodine capture. Gaseous iodine adsorption was collected kinetically from a home-made set-up allowing the continuous measurement of iodine content trapped within UiO-n compounds, with organic functionalities (-H, -CH 3 , -Cl, -Br, -(OH) 2 , -NO 2 , -NH 2 , (-NH 2 ) 2 , -CH 2 NH 2 ) by in-situ UV-Vis spectroscopy. This study emphasizes the role of the amino groups attached to the aromatic rings of the ligands connecting the {Zr 6 O 4 (OH) 4 } brick. In particular, the preferential interaction of iodine with lone-pair groups, such as amino functions, has been experimentally observed and is also based on DFT calculations. Indeed, higher iodine contents were systematically measured for amino-functionalized UiO-66 or UiO-67, compared to the pristine material (up to 1211 mg/g for UiO-67-(NH 2 ) 2 ). However, DFT calculations revealed the highest computed interaction energies for alkylamine groups (-CH 2 NH 2 ) in UiO-67 (-128.5 kJ/mol for the octahedral cavity), and pointed out the influence of this specific functionality compared with that of an aromatic amine. The encapsulation of iodine within the pore system of UiO-n materials and their amino-derivatives has been analyzed by UV-Vis and Raman spectroscopy. We showed that a systematic conversion of molecular iodine (I 2 ) species into anionic I - ones, stabilized as I - ⋅⋅⋅I 2 or I 3 - complexes within the MOF cavities, occurs when I 2 @UiO-n samples are left in ambient light., (© 2022 Wiley-VCH GmbH.)

data around survival and adverse events of cardiogenic shock (CS) patients supported with axillary or subclavian artery 5.0 Impella are presently unavailable. We performed a systematic search of studies reporting the outcomes of axillary or subclavian access 5.0 Impella for refractory CS in PubMed, EMBASE, and the Cochrane Library. The primary outcome was 30-day survival. Secondary outcomes included survival to next therapy and adverse events on support. Proportional meta-analysis was used to pool across studies. Of the 795 potential studies identified, 13 studies were included in the meta-analysis (n = 256 patients). The average age of patients across studies was 56 ± 5 years. Thirty-day survival for the overall cohort was 66% (95% CI: 59-73). Survival to the next therapy was 68% (95% CI: 60-76). The occurrence of adverse events over an average of 13 (95% CI: 12-14) days of support was the following: stroke 5.9%, hemolysis 27%, pump thrombosis 4.4%, limb ischemia 0.1%, major bleeding 5.4%, device malfunction 10.6%, exchange 6.6%, and infection 14%. In this systematic review and meta-analysis, we report survival and adverse event rates of axillary or subclavian access 5.0 Impella for CS. Such summary data can inform clinician decision-making., Competing Interests: Disclosure: Dr. John has received research grants from Abbott Lab and serves as a speakers bureau. Dr. Cogswell has received employment from Medtronic—husband’s employment and Heart Failure Advisory Board—and is speakers bureau of Abbott Lab. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Background: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). We hypothesized that there would be differences in myocardial mechanics, measured by global longitudinal strain (GLS) recovery in patients with four subtypes of severe AS after transcatheter aortic valve replacement (TAVR), stratified based upon flow and gradient., Methods: We retrospectively evaluated 204 patients with severe AS who underwent TAVR and were followed post-TAVR at our institution for clinical outcomes. Speckle-tracking transthoracic echocardiography was performed pre- and post-TAVR. Patients were classified as: (1) normal-flow and high-gradient, (2) normal-flow and high-gradient with reduced LV ejection fraction (LVEF), (3) classical low-flow and low-gradient, or (4) paradoxical low-flow and low-gradient., Results: Both GLS (-13.9 ± 4.3 to -14.8 ± 4.3, P < 0.0001) and LVEF (55 ± 15 to 57 ± 14%, P = 0.0001) improved immediately post-TAVR. Patients with low-flow AS had similar improvements in LVEF (+2.6 ± 9%) and aortic valve mean gradient (-23.95 ± 8.34 mmHg) as patients with normal-flow AS. GLS was significantly improved in patients with normal-flow (-0.93 ± 3.10, P = 0.0004) compared to low-flow AS. Across all types of AS, improvement in GLS was associated with a survival benefit, with GLS recovery in alive patients (mean GLS improvement of -1.07 ± 3.10, P < 0.0001)., Conclusions: LV mechanics are abnormal in all patients with subtypes of severe AS and improve immediately post-TAVR. Recovery of GLS was associated with a survival benefit. Patients with both types of low-flow AS showed significantly improved, but still impaired, GLS post-TAVR, suggesting underlying myopathy that does not correct post-TAVR., 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 Wani, Harland, Bajwa, Kroboth, Ammar, Allaqaband, Duval, Khandheria, Tajik and Jain.)

Objective: To assess cardiovascular disease (CVD) and CVD risk factors and their association with sociodemographic characteristics and health beliefs among African American (AA) adults in Minnesota., Methods: A cross-sectional analysis was conducted of a community-based sample of AA adults enrolled in the Minnesota Heart Health Program Ask About Aspirin study from May 2019 to September 2019. Sociodemographic characteristics, health beliefs, and self-reported CVD and CVD risk factors were collected. Prevalence ratio (PR) estimates were calculated using Poisson regression modeling to assess the association between participants' characteristics and age- and sex-adjusted CVD risk factors., Results: The sample included 644 individuals (64% [412] women) with a mean age of 61 years. Risk factors for CVD were common: hypertension (67% [434]), hyperlipidemia (47% [301]), diabetes (34% [219]), and current cigarette smoking (25% [163]); 19% (119) had CVD. Those with greater perceived CVD risk had a higher likelihood of prevalent hyperlipidemia (PR, 1.34; 95% CI, 1.14 to 1.57), diabetes (PR, 1.61; 95% CI, 1.30 to 1.98), and CVD (PR 1.61; 95% CI, 1.16 to 2.23) compared with those with lower perceived risk. Trust in health care provider was high (83% [535]) but was not associated with CVD or CVD risk factors., Conclusion: In this community sample of AAs in Minnesota, CVD risk factors were high, as was trust in health care providers. Those with greater CVD risk perceptions had higher CVD prevalence. Consideration of sociodemographic and psychosocial influences on CVD and CVD risk factors could inform development of effective cardiovascular health promotion interventions in the AA Minnesota community., (Published by Elsevier Inc.)

Objectives: Resuscitation in the Head Up position improves outcomes in animals treated with active compression decompression cardiopulmonary resuscitation and an impedance threshold device (ACD + ITD CPR).We assessed impact of time to deployment of an automated Head Up position (AHUP) based bundle of care after out-of-hospital cardiac arrest on return of spontaneous circulation (ROSC)., Methods: Observational data were analyzed from a patient registry. Patients received treatment with 1) ACD + and/or automated CPR 2) an ITD and 3) an AHUP device. Probability of ROSC (ROSCprob) from the 9-1-1 call to AHUP device placement was assessed with a restricted cubic spline model and linear regression., Results: Of 11 sites, 6 recorded the interval from 9-1-1 to AHUP device (n = 227). ROSCprobfor all rhythms was 34%(77/227). Median age (range) was 66 years (19-101) and 68% men. TheROSCprobfor shockable rhythms was 47%(18/38). Minutes from 9-1-1 to AHUP device (median, range) varied between sites: 1) 6.4(4,15), 2) 8.0(5,19), 3) 9.9(4, 12), 4) 14.1(6, 36), 5) 15.9(6, 34), 6) 19.0(8, 38),(p = 0.0001).ROSCprobalso varied; 1) 55.1%(16/29), 2) 60%(3/5), 3) 50%(3/6), 4) 22.7%(17/75), 5) 26.4%(9/34), and 6) 37.1%(29/78), (p = 0.019). For all rhythms between 4 and 12 min (n = 85),ROSCprobdeclined 5.6% for every minute elapsed (p = 0.024). For shockable rhythms, between 6 and 15 min (n = 23),ROSCprobdeclined 9.0% for every minute elapsed (p = 0.006)., Conclusions: Faster time to deployment of an AHUP based bundle of care is associated with higher incidence of ROSC. This must be considered when evaluating and implementing this bundle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In 134 patients with stable coronary artery disease, high-risk plaque features at CT and physiologic stenosis were found to act in a synergistic fashion to predict adverse outcomes., Competing Interests: Disclosures of Conflicts of Interest: A.K. No relevant relationships. P.S.V. No relevant relationships. B.K. No relevant relationships. S.D. No relevant relationships. P.S.N. No relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Substituted polyhydroquinolines are ubiquitous skeletal cores found in drugs and bioactive natural products. As a new route to access this motif, we successfully developed a one-pot cyclization cascade with high chemocontrol and diastereoselectivity. The sequence generates two cycles, three carbon-carbon bonds, and an all-carbon quaternary center in a highly convergent process. Functionalized polyhydroquinolines and congeners can be accessed from commercially available amino acids. This versatile and robust strategy was applied to the synthesis of (±)-Δ 7 -mesembrenone.

Purpose: Coronary computed tomography angiography (CCTA) plaque quantification has been proposed to be of incremental value in the prediction of ischemia, although prior studies have shown conflicting results. We aimed to determine whether CCTA plaque features assessed on a commercial vendor platform predict invasive fractional flow reserve (FFR)/instantaneous wave-free ratio (IFR)., Methods: Consecutive patients who underwent CCTA for evaluation of suspected stable coronary artery disease followed by invasive coronary physiology testing within 60 days at a single academic center were identified retrospectively. Semiautomated plaque quantification of the vessel proximal to the location of FFR/IFR measurement was carried out in TeraRecon, along with simple visual assessment for high-risk plaque features of positive remodeling, spotty calcification, low-attenuation plaque (LAP), and lesion length. Ischemia was defined by FFR ≤0.80 or IFR ≤0.89., Results: A total of 134 patients (62% male, mean age 62±10 y) were included in this study. On univariate logistic regression, the following visual plaque analysis parameters were predictive of ischemia: positive remodeling (odds ratio [OR] with 95% confidence interval [CI]: 4.96; 2.25-10.95; P<0.001), lesion length (OR for every 1 mm with 95% CI: 1.24; 1.14-1.34; P<0.001), spotty calcification (OR with 95% CI: 6.67; 1.67-26.64; P=0.007), and LAP (OR with 95% CI: 30; 3.78-246; P=0.001). None of the semiautomated plaque quantification parameters, such as noncalcified plaque volume or LAP volume, were predictive of ischemia. On stepwise multivariable logistic regression, lesion length (OR with 95% CI: 1.25; 1.14-1.37; P<0.0001) and LAP (OR with 95% CI: 43; 4.4-438; P=0.001) were significant predictors of ischemia, improving the area under the curve of CCTA from 0.53 to 0.87., Conclusions: Simple visual plaque assessment for high-risk plaque features improved the performance of CCTA to predict ischemia. Semiautomated plaque quantification performed on a commercial vendor platform was not predictive of ischemia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Organized health promotion efforts sometimes compete with news media, social media, and other sources when providing recommendations for healthy behavior. In recent years, patients have faced a complicated information environment regarding aspirin use as a prevention tool for heart health. We explored the possibility that campaign promotion of low-dose aspirin use might have been undermined by news coverage in the USA detailing controversies regarding aspirin use. Using time series data on low-dose aspirin sales in Minnesota, USA, we assessed whether news coverage of aspirin or audience engagement with the Ask About Aspirin campaign website predicted subsequent changes in low-dose aspirin sales, over and above any secular trend. News coverage predicted actual low-dose aspirin purchases whereas exposure to a state-level campaign did not. While a campaign effort to encourage people at risk to discuss low-dose aspirin use with their health care providers did not generate substantive changes in low-dose aspirin tablet sales in the areas of Minnesota monitored for this study, past news coverage about aspirin use, including news about negative side effects, may have suppressed low-dose aspirin sales during this same period. The extent of news coverage about aspirin and heart health had a negative effect on tablet sales recorded in greater Minnesota approximately a month later in an ARIMA time series model, coefficient = -.014, t = -2.33, p = .02. Presented evidence of news coverage effect suggests health campaign assessment should consider trends in the public information environment as potential countervailing forces., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Our aim was to evaluate the predictive value of a battery of 10 non-invasive tests of cardiovascular structural and functional health on the future risk of cardiovascular morbid events., Methods and Results: A total of 1900 asymptomatic adults concerned about their risk for cardiovascular disease underwent non-invasive assessment with 10 tests of vascular and cardiac structure and function. A disease score (DS) was calculated for each individual based on these 10 tests. Follow-up (mean 9.2 years) for cardiovascular morbidity and mortality was available for 1442 individuals (mean age 53.2 years, 48.2% women). Those in the lowest DS tertile (0-2) experienced 0.16 cardiovascular events per 100 patient-years (PY), those in the middle tertile (3-5) experienced 0.86 events per 100 PY, and those in the highest tertile (6+) experienced 1.3 events per 100 PY (p < .001). Sensitivity analysis, assuming a neutral effect of DS on projected events in subjects not followed, did not alter statistical significance. Risk assessment using the Framingham risk score (FRS) also predicted morbid events but the two methods differed in identifying individuals at high risk. The net reclassification index was improved by 0.11 (p = 0.01) when DS was added to FRS., Conclusions: Assessing the biological disease process in the arteries and heart of asymptomatic adults provides a guide to the risk of a future cardiovascular morbid event. Larger and longer studies are needed to determine whether risk factor algorithms, the severity of the biological process or some combination is the optimal method for identifying individuals in need of intervention to delay morbid events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.

Cardiovascular disease (CVD) disproportionately affects African Americans. Aspirin has long been recommended to reduce cardiovascular events. However, national guideline changes in 2016 limited the aspirin recommended population and several clinical trials questioning the utility of primary prevention aspirin were published in 2018. In light of the recent guidelines and study findings, we investigated primary prevention aspirin use among urban African American adults. Using three cross-sectional surveys, we collected data from self-identified African Americans with no CVD in 2015, 2017 and 2019, querying information on CVD risk factors, health behaviors and beliefs, and aspirin use. Poisson regression modeling was used to estimate age- and risk-factor adjusted aspirin prevalence, trends and associations. A total of 1491 African Americans adults, ages 45-79, were included in this analysis; 61% were women. There was no change in age- and risk factor-adjusted aspirin use over the 3 surveys for women (37%, 34% and 35% respectively) or men (27%, 25%, 30% respectively). However, fewer participants believed aspirin was helpful in 2019 compared to 2015-75% versus 84% (p < 0.001). Aspirin discussions with a health care practitioner were highly associated with aspirin use (adjusted RR 2.97, 95% CI 2.49-3.54) and aspirin use was 2.56 times higher (adjusted RR 95% CI 2.17-3.03) in respondents who agreed that people close to them thought they should take aspirin compared with those who disagreed or did not know. Despite major changes in national guidelines, overall primary prevention aspirin use did not significantly change in these African American samples from 2015 to 2019., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: Randomized trials have shown that biennial fecal occult blood test (FOBT) screening reduces mortality from colorectal cancer (CRC), but not overall mortality. Differences in benefit for men vs women, and by age, are unknown. We sought to evaluate long-term reduction in all-cause and CRC-specific mortality in men and women who comply with offered screening, and in different age groups, using individual participant data from 2 large randomized trials of biennial FOBT screening, compared with an intention to treat analysis., Methods: We updated the CRC and all-cause mortality from the Danish CRC screening trial (n = 61,933) through 30 years of follow up and pooled individual participant data with individual 30-year follow-up data from the Minnesota Colon Cancer Control trial (n = 46,551). We compared the biennial screening groups to usual care (controls) in individuals 50-80 years old using Kaplan Meier estimates of relative risks and risk differences, adjusted for study differences in age, sex, and compliance., Results: Through 30 years of follow up, there were 33,478 (71.9%) and 33,479 (72.2%) total deaths and 1023 (2.2%) and 1146 (2.5%) CRC deaths in the biennial screening (n = 46,553) and control groups (n = 46,358), respectively. Among compliers, biennial FOBT screening significantly reduced CRC mortality by 16% (relative risk [RR], 0.84; 95% CI, 0.74-0.96) and all-cause mortality by 2% (RR, 0.98; 95% CI, 0.97-0.99). Among compliers, the reduction in CRC mortality was larger for men (RR, 0.75; 95% CI, 0.62-0.90) than women (RR, 0.91; 95% CI, 0.75-1.09). The largest reduction in CRC mortality was in compliant men 60-69 years old (RR, 0.59; 95% CI, 0.42-0.81) and women 70 years and older (RR, 0.53; 95% CI, 0.30-0.94)., Conclusions: Long-term CRC mortality outcomes of screening among compliers using biennial FOBT are sustained, with a statistically significant reduction in all-cause mortality. The reduction in CRC mortality is greater in men than women-the benefit in women lags that of men by about 10 years., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nontraumatic lower-extremity amputation is a devastating complication of peripheral artery disease (PAD) with a high mortality and medical expenditure. There are ≈150 000 nontraumatic leg amputations every year in the United States, and most cases occur in patients with diabetes. Among patients with diabetes, after an ≈40% decline between 2000 and 2009, the amputation rate increased by 50% from 2009 to 2015. A number of evidence-based diagnostic and therapeutic approaches for PAD can reduce amputation risk. However, their implementation and adherence are suboptimal. Some racial/ethnic groups have an elevated risk of PAD but less access to high-quality vascular care, leading to increased rates of amputation. To stop, and indeed reverse, the increasing trends of amputation, actionable policies that will reduce the incidence of critical limb ischemia and enhance delivery of optimal care are needed. This statement describes the impact of amputation on patients and society, summarizes medical approaches to identify PAD and prevent its progression, and proposes policy solutions to prevent limb amputation. Among the actions recommended are improving public awareness of PAD and greater use of effective PAD management strategies (eg, smoking cessation, use of statins, and foot monitoring/care in patients with diabetes). To facilitate the implementation of these recommendations, we propose several regulatory/legislative and organizational/institutional policies such as adoption of quality measures for PAD care; affordable prevention, diagnosis, and management; regulation of tobacco products; clinical decision support for PAD care; professional education; and dedicated funding opportunities to support PAD research. If these recommendations and proposed policies are implemented, we should be able to achieve the goal of reducing the rate of nontraumatic lower-extremity amputations by 20% by 2030.

Background: USPSTF evidence-based recommendations for the use of low-dose aspirin for primary prevention of cardiovascular disease were published in 2009. We describe a statewide campaign using innovative methods to educate the public and health communities about appropriate aspirin use., Methods/design: The "Ask About Aspirin" initiative is designed to lower the number of first heart attacks and strokes in the State of Minnesota by promoting the appropriate use of low dose aspirin. A health system intervention combined with an aspirin awareness media campaign will be evaluated in a pragmatic group randomized controlled trial including 267 primary care clinics within 84 health systems over a four year period. Matched pairs of geographic territories will be randomized to intervention (12 territories) or control (12 territories). The primary outcome of appropriate aspirin use will be measured at the individual level, by community-based telephone surveys of 100 participants in each of the 24 geographically determined clusters., Discussion: We briefly describe the rationale for the interventions being studied, as well as the major design choices. Rigorous research designs such as the one described here are necessary to determine whether evidence-based recommendations can be effectively disseminated in multiple health systems., Trial Registration: ClinicalTrials.gov: NCT02607917., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)