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Research in Southern Belize has produced a 1000-year record of coupled human and environmental relationships at the ancient Maya city Uxbenká. Located at the southeastern margin of the Maya Lowlands, this region has excellent agricultural land and some of the highest rainfall in the Maya region. Uxbenká was the founding political center in southern Belize after 100 BCE. After 850 years, Uxbenká experienced a long geopolitical disintegration ending in depopulation as part of broad regional collapse. We use kernel density and summed probability distributions of 167 high-precision AMS 14C dates to reconstruct relative changes in population and investments in the built environment throughout the growth and decline of the polity. Those data are compared to an annually resolved speleothem paleoclimate record from Yok Balum cave, located less than 3 km from Uxbenká's civic ceremonial core. With no Classic Period wetland fields or evidence for large-scale landscape investments in agricultural intensification, food production would have been rainfall dependent as was water availability for household use. Using a 30 m SRTM DEM, we compute flow accumulation and the upvalley extents of river networks while varying the input precipitation to reflect hypothesized changes in paleorainfall over time. Our data suggest that Uxbenká experienced rapid growth following a severe drought at 200 CE, as well as cycles of growth and contraction until just after 750 CE. We find that geopolitical disintegration in southern Belize was already underway when a severe drought began at 830 CE. That six-decade drought likely contributed to the abandonment of Uxbenká and limited geopolitical reorganization. [ABSTRACT FROM AUTHOR]

Background: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment.Objective: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce.Methods: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature.Results: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems.Conclusions: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goal of this study was to compare prose and pictorial-based information pamphlets about the medication methotrexate in the domains of free recall, cued recall, comprehension and utility. METHODS: A single blind, randomized trial of picture versus prose-based information pamphlets including 100 participants aged 18-65 years of age, who had not completed high school, could read English, and had no prior knowledge about methotrexate. Superiority of pamphlet type was assessed using immediate free recall, cued recall and comprehension. RESULTS: There were no differences between picture and prose pamphlets in free recall, cued recall, and comprehension either immediately or after a 1-week interval. Immediate free recall of important information was 17-26%; free recall fell even lower to 7-16% after 1 week. The pictorial pamphlet was preferred over the prose-based pamphlet. CONCLUSION: This study found no benefit in free recall, cued recall, or comprehension through the addition of pictograms to a simple prose-based medication pamphlet. PRACTICE IMPLICATIONS: In order for them to be effective in clinical practice, even simple medication information pamphlets that have been assessed for patients' ability to comprehend them cannot be used as the sole means for conveying important medication-related information to patients. [ABSTRACT FROM AUTHOR]

Objective.To determine the frequency of pericardial and pleural effusions in scleroderma. [ABSTRACT FROM PUBLISHER]

Purpose of Review: The present review will discuss the evolution of diagnostic criteria for amyotrophic lateral sclerosis (ALS) and biomarker considerations., Recent Findings: To address the limitations of existing ALS diagnostic criteria, a consortium of key stakeholders developed the Gold Coast consensus criteria (GCC). The GCC has similar or greater sensitivity compared with the revised El Escorial (rEEC) and Awaji criteria (AC), particularly for atypical phenotypes, maintained across disease duration, severity, and site of onset. In addition to improving diagnostic sensitivity, using the GCC in clinical trials may promote an increased enrolment of up to 50% of ALS patients who do not currently meet the full diagnostic eligibility requirements of the rEEC. Future inclusion of genetic biomarkers may mitigate some limitations of the GCC, to further improve diagnostic utility. In advance of such a process, validation of these biomarkers will be required before inclusion as additional criteria., Summary: The GCC are simpler to use than previous consensus criteria, with demonstrated greater sensitivity and, enabling an earlier and more definitive ALS diagnosis, thereby facilitating wider enrolment into clinical trials. Broader implementation of the GCC in clinical trial settings is currently underway, globally., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure defibrillation lead is a novel, small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform., Objective: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead., Methods: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively., Results: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD)., Conclusion: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures., Competing Interests: Disclosures G.H.C.: speaker at Medtronic and Philips; consultant for Medtronic and Boston Scientific. P.S.: reports having served on the advisory boards of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, and Boston Scientific; and the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Becton-Dickson. B.H.: reports funding from Medtronic and CVRx. P.D.F.: consultant fees and travel support from Medtronic, Boston Scientific, Abbott, and Biotronik as well as honoraria and advisory board participation for Medtronic, Abbott, and Biotronik. M.J.S.: consultant for Medtronic and Tenaya Therapeutics. M.S.: speaker honorarium from Medtronic Japan and financial endowments to our clinical research division from Biotronik Japan, Medtronic Japan, Boston Scientific Japan, and Abbott Japan. S.K.K.: member of the speakers bureau for Bayer/Schering Pharma, Boston Scientific, Medtronic, and Pfizer; speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member for Novartis, Medtronic, Boehringer-Ingelheim, Boston Scientific, and Bayer. T.D.R.: consultant for Medtronic, Johnson and Johnson, and Philips; research funding from Medtronic and Abbott. F.P.: speaker at Medtronic and Boston Scientific; consultant for Medtronic and Boston Scientific; research funding from Medtronic and Boston Scientific. J.S.Z.: consultant for Medtronic. H.F.T.: consultant and speaker fee and research grant from Abbott, BMS/Pfizer, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi-Sankyo, Medtronic, and Sanofi. D.P.S.: institutional funding from Medtronic. C.S.: received scientific grants from Medtronic. R.K.P.: reports that Canberra Heart Rhythm Foundation has received on his behalf lecture and/or consulting fees from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. G.M.: received honoraria from Medtronic. J.S.C.: consultant for Medronic, Biosense Webster, and Boston Scientific. B.T.: honorarium from Boston scientific. M.B.W.: consultant for Medtronic. B.M.R.: consultant for Medtronic. X.H.: consultant for Medtronic. B.B.: consultant for Medtronic. R.C., M.L.P., A.K.H., T.G, and A.E.T.: employees of Medtronic, Inc. P.K.M.: consultant for Medtronic, Boston Scientific, and Cook as well as honoraria from Medtronic and Cook., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Defibrillation leads remain the Achilles heel of implantable cardioverter-defibrillators. As patients with implantable cardioverter-defibrillators are living longer and battery longevity increases, more durable leads are needed. The LEADR trial evaluated the novel, lumenless, small-diameter, OmniaSecure defibrillation lead and demonstrated favorable safety and efficacy profile as well as zero fractures through 12.7 ± 4.8 months and remains in clinical follow-up. To augment the clinical trial, advanced cardiac lead reliability modeling was used to project long-term lead durability., Objective: We aimed to project the 10-year fracture-free survival of the OmniaSecure defibrillation lead using reliability modeling., Methods: The validated reliability model, which incorporates patient and bench test data, was used to project the 10-year fracture-free survival of the OmniaSecure lead. A subset of LEADR trial patients underwent biplane fluoroscopy imaging during cardiac and patient motion to evaluate the lead's bending curvature in vivo. Bench tests then reproduced these use conditions with greater bending curvatures than observed in patients to exaggerate stress on the lead and to evaluate the lead fatigue strength., Results: The reliability modeling projects a 98.2% fracture-free survival rate of the OmniaSecure lead at 10 years, including a 10-year fracture-free survival rate of 97.9% in adolescents, exceeding both the modeled and clinical 10-year performance of the highly reliable, larger diameter Sprint Quattro lead., Conclusion: Consistent with early clinical trial experience, modeling projects highly durable 10-year performance of the OmniaSecure lead, including within the active adolescent pediatric population, which may uniquely benefit from a novel 4.7F defibrillation lead designed for reliability., Gov Identifier: NCT04863664., Competing Interests: Disclosures G.H.C.: speaker at Medtronic and Philips; consultant for Medtronic and Boston Scientific. P.K.M.: consultant for Medtronic, Boston Scientific, and Cook as well as honoraria from Medtronic and Cook. B.H.: reports funding from Medtronic and CVRx. P.D.F.: consultant fees and travel support from Medtronic, Boston Scientific, Abbott, and Biotronik; honoraria and advisory board participation for Medtronic, Abbott, and Biotronik. M.J.S.: consultant for Medtronic and Tenaya Therapeutics. F.P.: speaker at Medtronic and Boston Scientific; consultant for Medtronic and Boston Scientific; research funding from Medtronic and Boston Scientific. D.S.: institutional funding from Medtronic. T.D.R.: consultant for Medtronic, Johnson and Johnson, and Philips; research funding from Medtronic and Abbott. M.B.W.: consultant for Medtronic. JayD.: consultant for Boston Scientific, Abbott, and Medtronic. J.D., A.H., L.S., and A.E.T: employees of Medtronic, Inc. P.S.: reports having served on the advisory boards of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, and Boston Scientific; and the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Becton-Dickson., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Substernal lead placement of the extravascular implantable cardioverter-defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous ICDs and effective antitachycardia pacing (ATP), while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. We aim to report the performance and safety of the EV ICD system throughout the study., Methods: The EV ICD Pivotal study was a prospective, global, single-arm, pre-market clinical study. Individuals with a class I or IIa indication for a single-chamber ICD per guidelines were enrolled. Freedom from major system- or procedure-related complications, as well as appropriate and inappropriate therapy rates, were assessed through 3 years using the Kaplan-Meier method. Anti-tachycardia pacing success was calculated using simple proportions., Results: An implant was attempted in 316 patients [25.3% female, 53.8±13.1 years old, 81.6% primary prevention, LVEF 38.9%±15.4%]. Of 299 patients with a successful implant, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with either ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier-estimated rate of first any appropriate therapy of 9.2% at 3 years. Antitachycardia pacing was successful in 77.1% (37/48) of episodes, and ATP usage significantly increased from discharge to last follow-up visit (P<0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure., Conclusions: From implant to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile.

Despite the existing literature assessing various aspects of marriage, there is a lack of understanding of adults' motives for pursuing marriage. Thus, this research advanced the literature by assessing adults' motives for marriage via four novel studies in which the Motives for Marriage Scale (MMS) was developed, refined, and validated. In study one, semi-structured focus groups were conducted to capture the range of motives for marriage. In study two, the factor structure of the MMS was assessed. The factor structure was then validated and the psychometric properties were established in study three. Finally, the temporal consistency of the scale was established in study four. The results confirmed that adults' marital motives are complex and that they are best conceptualized using Social Determination Theory (i.e., intrinsic, extrinsic, and instrumental motives). Investigation of the psychometric properties demonstrated the MMS to be reliable and valid. Implications for investigators and practitioners are discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sexual satisfaction contributes significantly to one's quality of life and offers a variety of mental and physical health benefits. Consequently, numerous studies have examined ways to improve sexual satisfaction. However, no research has investigated how sexual nostalgia (i.e., "the sentimental longing for or wistful reflection on past sexual memories," p. 1539) with one's current partner impacts sexual satisfaction. Thus, this program of research was designed to develop the Sexual Nostalgia Inventory, assess the relationship between sexual nostalgia and sexual satisfaction, and to examine the moderating role of romantic attachment. The results of Study One ( N = 227) indicated that the content of sexual memories can be conceptualized into one factor. The results from Study Two ( N = 619) revealed that sexual nostalgia was positively related to sexual satisfaction and that romantic attachment moderated these relationships. In particular, the positive association between sexual nostalgia and satisfaction was greatest for those insecurely attached (i.e., those high in anxious and avoidant attachment). These findings have important implications for researchers looking to establish the causal link between nostalgia and satisfaction and clinicians working with couples experiencing low sexual desire and/or unmet sexual needs.

Research indicates that idealized romantic expectations and the extent to which they are met, are important predictors of relationship outcomes (e.g., love). However, no studies have investigated the impact of idealized beliefs associated with specific behaviors (e.g., kissing) on reports of romantic love. Thus, the two studies comprising this research assessed the association between idealized beliefs related to one's first romantic kiss with their current partner, unmet first kiss expectations, and reports of romantic love. Romantic attachment was also examined as a moderator. In Study One, the First Kiss Beliefs Scale was created and the results from 208 adults revealed that increased endorsement of idealized first kiss beliefs was associated with greater romantic love ( r = 0.25). Romantic attachment also moderated this relationship, such that idealized first kiss beliefs significantly predicted love for those high in attachment anxiety and low in avoidance ( β = 0.68 and β = 0.18, respectively). In Study Two, the First Kiss Beliefs Scale was modified to assess outcomes and expectations to capture unmet expectations. The results from 234 adults indicated that idealized first kiss beliefs predicted a greater proportion of the variance in romantic love ( sr 2 = 0.10) than did unmet expectations ( sr 2 = 0.07). A three-way interaction was also detected such that, among those low in attachment anxiety, the relationship between kissing beliefs and love was positive for those high in attachment avoidance and negative for those low. These results indicate that idealized first kiss expectations with one's current romantic partner are important predictors of love (beyond whether these expectations were met), particularly for those high in attachment insecurity. Implications are discussed for practitioners and those in the primary stages of romantic relationships., 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 © 2023 Thompson, Hill and Record.)

The extravascular implantable cardioverter-defibrillator (EV ICD) with lead implantation in the substernal space may provide clinical advantages over transvenous and subcutaneous systems. This is the first reported examination of substernal infection in large animals implanted with the EV ICD system.The system was implanted in 13 large animals (canine, porcine, and ovine). The porcine were co-implanted with a transvenous cardiac resynchronization therapy with defibrillator (CRT-D) system. Infection was promoted through a cadence of immunosuppressive monitors and study interventions. The animals were monitored for clinical presentation of infection over 12-18 weeks, and cultures were collected to confirm infection. Treatment was bifurcated: 1) some infections were treated only with antibiotics ( "antibiotics only" ), whereas 2) some infections were treated with system removal and antibiotics ( "antibiotics + explant" ). Histopathology was conducted at the study closure.Five infections were confirmed over the course of the study, four of which involved infection of the EV ICD system and one infection of only the concomitantly implanted transvenous CRT-D system without EV ICD-related infection. Among the four EV ICD infections, two of two infections treated with antibiotics only did not resolve whereas two of two infections treated with antibiotics + explant resolved, as shown by histology. The transvenous CRT-D system infection progressed to septicemia and endocarditis, requiring early study discontinuation. No EV ICD-related infection progressed to blood stream infection, and the sternal bone did not become infected when infection was present in the substernal tissues.The study findings suggest that EV ICD-related infections are treatable with system removal and antibiotic therapy.

Research on interpersonal interaction dynamics in relationships between persons with dementia and their family caregivers has been limited. We examine the role of these dynamics in decisions to transition a family member from home care to congregate care, with a particular focus on the role of fear of incompetence. Fear of incompetence is the fear of being unable to interact, communicate in a meaningful way, or take care of a close family member with dementia. In this study ( N   =  350 family caregivers), perceived negative changes in the family member with dementia predicted increased perceived dependency, which predicted both increased caregiver burden and greater fear of incompetence in caregivers, which, in turn, predicted stronger care transition desire. Strategies should be aimed not only at reducing dependency of the care recipient but also teaching family caregivers interaction skills that decrease their fear of interactional incompetence and thus promote home care continuation.

The motor phenomena accompanying frontal lobe disease are diverse, reflecting the various roles the frontal lobes play in the organization of motor control. The principal frontal motor areas, the primary motor cortex, the premotor cortex, and the supplementary motor area, have different but interrelated functions in motor control. The principal efferent pathway of the primary motor cortex is the corticospinal tract which conducts fine motor control. Damage to the primary motor cortex and the corticospinal tract results in paralysis and loss of skilled, particularly distal, motor function. Lesions of the premotor cortex interfere with the preparation for the execution of movements and coordinating sequences of limb movement. Mediated through cortico-reticulospinal pathways, the premotor cortex adjusts axial and limb muscle activities. The fine motor skills of the corticospinal tract are superimposed upon these stabilizing movements. Supplementary motor area lesions interrupt self-initiated movements, release alien limb behaviors, and result in grasping. Paralysis, primitive reflexes, and frontal gait disorders are readily observed on examination, but difficulties initiating and sequencing movements are more subtle signs of perturbed higher motor control and require special examination procedures. Prefrontal motor syndromes include motor behaviors that only become apparent when the subject performs spontaneous or self-directed activities, unconstrained by instructions from the examiner. Clinical observation also reveals a slowness to respond to instruction with long delays before initiating action (inertia), but once underway they may be unable to stop (perseveration). Patients sit motionless without spontaneous movement or interest in their surrounds (apathy), yet exhibit distractibility, diverting attention to an incidental peripheral stimulus or an object with which they may then fiddle (environmental dependency and utilization behavior). Little spontaneous speech is initiated (abulia) but echolalia may be stimulated by the examiner's conversation. Restlessness, distractibility, perseveration, and environmentally dependent utilization behaviors coexist with apathy, inertia, and abulia. Mutism and akinesia may alternate with stereotypies and agitation in catatonia. These paradoxical combinations are of considerable diagnostic significance in recognizing frontal lobe motor syndromes., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glyceraldehyde phosphate dehydrogenase (GAPDH) is a highly conserved, essential, and abundant enzyme that catalyzes a rate-determining step of glycolysis. GAPDH catalyzes the nicotinamide adenine dinucleotide (NAD + )- and inorganic phosphate-dependent oxidation and phosphorylation of glyceraldehyde phosphate (GAP) to form 1,3-bisphosphoglycerate (BPG). As part of its mechanism of action, GAPDH employs a redox-sensitive cysteine that serves as a nucleophile to form a covalent adduct with GAP in order to set-up subsequent oxidation and phosphorylation steps. As a result of the redox sensitivity of the active site cysteine residue, GAPDH is susceptible to oxidative inactivation by oxidants such as hydrogen peroxide (H 2 O 2 ). Indeed, numerous studies have demonstrated that oxidative inactivation of GAPDH has important metabolic consequences for adaptation to life in air and oxidative stress since decreased GAPDH activity results in the rerouting of carbon flux away from glycolysis and toward the pentose phosphate pathway to produce the key cellular reductant and antioxidant, NADPH. Thus, the ability to probe GAPDH oxidation and activity provides an important snapshot of the intracellular redox environment and glycolytic flux. Herein, we describe methods to measure reduced and oxidized GAPDH using thiol alkylation assays as well as GAPDH enzymatic activity., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network originated over 20 years ago to foster research to optimize the care of critically ill infants and children. Over this period, PALISI has seen two major evolutions: formalization of our network infrastructure and a broadening of our clinical research focus. First, the network is unique in that its activities and meetings are funded by subscriptions from members who now comprise a multidisciplinary group of investigators from over 90 PICUs all over the United States (US) and Canada, with collaborations across the globe. In 2020, the network converted into a standalone, nonprofit organizational structure (501c3), making the PALISI Network formally independent of academic and clinical institutions or professional societies. Such an approach allows us to invest in infrastructure and future initiatives with broader opportunities for fund raising. Second, our research investigations have expanded beyond the original focus on sepsis and acute lung injury, to incorporate the whole field of pediatric critical care, for example, efficient liberation from mechanical ventilator support, prudent use of blood products, improved safety of intubation practices, optimal sedation practices and glucose control, and pandemic research on influenza and COVID-19. Our network approach in each field follows, where necessary, the full spectrum of clinical and translational research, including: immunobiology studies for understanding basic pathologic mechanisms; surveys to explore contemporary clinical practice; consensus conferences to establish agreement about literature evidence; observational prevalence and incidence studies to measure scale of a clinical issue or question; case control studies as preliminary best evidence for design of definitive prospective studies; and, randomized controlled trials for informing clinical care. As a research network, PALISI and its related subgroups have published over 350 peer-reviewed publications from 2002 through September 2022., Competing Interests: Dr. Randolph’s institution received funding from Centers for Disease Control and Prevention (CDC) and National Institute of Allergy and Infectious Diseases, and she received funding from UptoDate. Drs. Randolph and Flori received support for article research from National Institutes of Health (NIH). Dr. Bembea’s institution received funding from the NIH/National Institute of Neurological Disorders and Stroke and Grifols Investigator Sponsored Research Grant. Dr. Cheifetz received funding from Philips, Medtronic, UptoDate, and Tim Peters and Co. Dr. Curley’s institution received funding from National Institute of Child Health and Human Development and National Heart, Lung, and Blood Institute. Dr. Flori’s institution received funding from CDC, Society of Critical Care Medicine, and NIH; she received funding from Aerogen Pharma and Lucira Health; and she disclosed she is an Executive Committee Member for Pediatric Acute Lung Injury and Sepsis Investigators Network. Dr. Khemani received funding from Orange Med and Nihon Kohden. Dr. Nishisaki’s institution received funding from Agency for Healthcare Research and Quality (AHRQ) R03HS026939, AHRQ R18HS024511, and AHRQ R18HS022464, and he received unrestricted grant support by Chiesi, Inc to describe neonatal surfactant administration. Dr. Lacroix’s institution received funding from Canadian Institutes of Health Research. Dr. Thomas received funding from Bayer AG. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method-combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups-to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization., Competing Interests: The authors have declared that no competing interests exist.

Background: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known., Methods: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%., Results: A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period., Conclusions: In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Epigenetics refers to inheritable phenotypic changes that occur in the absence of genetic alteration. Such adaptations can provide phenotypic plasticity in reaction to environmental cues. While prior studies suggest that epigenetics plays a role in the response to DNA damage, no direct demonstration of epigenetically inheritable processes have been described in this context., Results: Here we report the identification of an epigenetic response to ultraviolet (UV) radiation in the baker's yeast Saccharomyces cerevisiae. Cells that have been previously exposed to a low dosage of UV exhibit dramatically increased survival following subsequent UV exposure, which we refer to as UV hyper-resistance (UVHR). This phenotypic change persists for multiple mitotic generations, without any indication of an underlying genetic basis. Pre-exposed cells experience a notable reduction in the amount of DNA damage caused by the secondary UV exposure. While the mechanism for the protection is not fully characterized, our results suggest that UV-induced cell size increases and/or cell wall changes are contributing factors. In addition, we have identified two histone modifications, H3K56 acetylation and H3K4 methylation, that are important for UVHR, potentially serving as mediators of UV protective gene expression patterns, as well as epigenetic marks to propagate the phenotype across cell generations., Conclusions: Exposure to UV radiation triggers an epigenetically inheritable protective response in baker's yeast that increases the likelihood of survival in response to subsequent UV exposures. These studies provide the first demonstration of an epigenetically inheritable dimension of the cellular response to DNA damage., (© 2022. The Author(s).)

Research reveals that a substantial proportion of North American adults report interest in and experience with mixed-sex threesomes (MSTs; sexual activity involving three people at the same time in which persons of more than one sex are present). Despite the prevalence of MST participation, little is known about the outcomes of MST experiences. Thus, the current study assessed MST outcomes using various metrics including the extent to which one's most recent MST met expectations, the likelihood of participating in the MST again, and whether an orgasm was experienced. In addition, the extent to which one's sex, the sex of those involved, and the inclusion of one's romantic partner impacted outcomes was examined. Data from 276 heterosexual adults (217 men, 59 women) revealed that, overall, adults report fairly positive outcomes from their most recent MST and that males reported more positive outcomes than did females (particularly when engaging in a MST with two members of the other sex). In addition, MSTs involving one's romantic partner resulted in more positive outcomes than did those with casual partners. These results confirm that MSTs can be a satisfying experience particularly for heterosexual males and those participating with a romantic partner. Implications for educators looking to destigmatize various forms of nonmonogamies and for practitioners who intend to assist adults interested in safely exploring multi-person sexual behavior are discussed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: There is a relationship between both the magnitude and variability of C-reactive protein (CRP) levels and disease activity level in rheumatoid arthritis (RA). It seems that CRP levels remain low and stable in clinical remission then increase and become erratic in active disease. The purpose of this research was to determine if there is a difference in the variability of CRP levels over time in patients in clinical remission versus those with active disease., Methods: Patients with a diagnosis of RA with a minimum of 3 CRP readings in the previous 12-month period were included at a single site. At each visit the patient was evaluated by an experienced rheumatologist to determine current disease activity - remission versus active disease. The primary outcome measure was the difference between the coefficient of variation of the CRP (CRP-COV) in patients in remission versus those with active disease., Results: 272 patients were enrolled into the study. The mean CRP and CRP-COV was significantly smaller for patients in clinical remission versus active disease, for patients in CDAI remission (<2.6), and for those who did not require a change in treatment. Smokers, on average, had higher mean CRP readings regardless of clinical status., Conclusions: We have identified a new clinical outcome measure of disease activity in RA that captures longitudinal variability in disease activity and identifies those patients with clinically active disease despite a "normal" CRP level due to the higher variability of CRP if not in remission.

Introduction: The extravascular implantable cardioverter-defibrillato (EV ICD) system with substernal lead placement is a novel nontransvenous alternative to current commercially available ICD systems. The EV ICD provides defibrillation and pacing therapies without the potential long-term complications of endovascular lead placement but requires a new procedure for implantation with a safety profile under evaluation., Methods: This paper summarizes the development of the EV ICD, including the preclinical and clinical evaluations that have contributed to the system and procedural refinements to date., Results: Extensive preclinical research evaluations and four human clinical studies with >140 combined acute and chronic implants have enabled the development and refinement of the EV ICD system, currently in worldwide pivotal study., Conclusion: The EV ICD may represent a clinically valuable solution in protecting patients from sudden cardiac death while avoiding the long-term consequences of transvenous hardware. The EV ICD offers advantages over transvenous and subcutaneous systems by avoiding placement in the heart and vasculature; relative to subcutaneous systems, EV ICD requires less energy for defibrillation, enabling a smaller device, and provides pacing features such as antitachycardia and asystole pacing in a single system., (© 2022 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Aims: The aim of this study is to provide a thorough, quantified assessment of the substernal space as the site of extravascular implantable cardioverter-defibrillator (ICD) lead placement using computed tomography (CT) scans and summarizing adverse events and defibrillation efficacy across anatomical findings. Subcutaneous ICDs are an alternative to transvenous defibrillators but have limitations related to ICD lead distance from the heart. An alternative extravascular system with substernal lead placement has the potential to provide defibrillation at lower energy and pacing therapies from a single device., Methods and Results: A multi-centre, non-randomized, retrospective analysis of 45 patient CT scans quantitatively and qualitatively assessing bony, cardiac, vascular, and other organ structures from two human clinical studies with substernal lead placement. Univariate logistic regression was used to evaluate 15 anatomical parameters for impact on defibrillation outcome and adjusted for multiple comparisons. Adverse events were summarized. Substernal implantation was attempted or completed in 45 patients. Defibrillation testing was successful in 37 of 41 subjects (90%) using ≥10 J safety margin. There were two intra-procedural adverse events in one patient, including reaction to anaesthesia and an episode of transient atrial fibrillation during ventricular fibrillation induction. Anatomical factors associated with defibrillation failure included large rib cage width, myocardium extending very posteriorly, and a low heart position in the chest (P-values <0.05), though not significant adjusting for multiple comparisons., Conclusion: Retrospective analysis demonstrates the ability to implant within the substernal space with low intra-procedural adverse events and high defibrillation efficacy despite a wide range of anatomical variability., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The extravascular implantable cardioverter-defibrillator (EV ICD) with lead implantation in the substernal space may provide an alternative to transvenous and subcutaneous systems. This is the first-reported chronic extraction experience for EV ICD leads. The aim of the study is to evaluate the chronic encapsulation and extractability of EV ICD leads., Methods: Two EV ICD leads and one transvenous lead were implanted in each of 24 mature sheep. A subset of animals was evaluated yearly for histology and lead extractability. Extractions were performed using simple traction or extraction tools. Histology evaluated the encapsulating tissue., Results: At 1 year, extraction was performed successfully for two of five EV ICD leads with traction alone using ≤3.1 kg-force (kgf) and the remainder extracted successfully with extraction tools; no transvenous leads were removed with traction alone. At 2 years, no EV ICD or transvenous leads were extracted with traction alone, while at 3 years, one of eight EV ICD leads and two of four transvenous leads were extracted with traction (0.8 and ≤2.3 kgf, respectively). There was one observation of hemopericardium resulting in tamponade with EV ICD extraction but without injury to cardiovascular structures and related to the unique implant tract. Among transvenous leads, inversion of the ventricle with loss of cardiac output resulted in abandonment of traction for two animals., Conclusions: Chronic extraction of EV ICD leads from the substernal space was successfully performed using traction and simple tools through 3 years in sheep with one observation of hemopericardium that did not originate from cardiovascular injury., (© 2022 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O 2 •- ) by catalyzing its conversion to dioxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O 2 availability to promote NADPH production. The mechanism involves Sod1-derived H 2 O 2 oxidatively inactivating the glycolytic enzyme, GAPDH, which in turn reroutes carbohydrate flux to the oxidative phase of the pentose phosphate pathway (oxPPP) to generate NADPH. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1. Thus, Sod1 senses O 2 via O 2 •- to balance glycolytic and oxPPP flux, through control of GAPDH activity, for adaptation to life in air. Importantly, this mechanism for Sod1 antioxidant activity requires the bulk of cellular Sod1, unlike for its role in protection against O 2 •- toxicity, which only requires <1% of total Sod1. Using mass spectrometry, we identified proteome-wide targets of Sod1-dependent redox signaling, including numerous metabolic enzymes. Altogether, Sod1-derived H 2 O 2 is important for antioxidant defense and a master regulator of metabolism and the thiol redoxome., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

The Centers for Disease Control and Prevention recommends tracking risk-adjusted antimicrobial prescribing. Prior studies have used prescribing variation to drive quality improvement initiatives without adjusting for severity of illness. The present study aimed to determine the relationship between antimicrobial prescribing and risk-adjusted ICU mortality in the Pediatric Health Information Systems (PHIS) database, assessed by IBM-Watson risk of mortality. A nested analysis sought to assess an alternative risk model incorporating laboratory data from federated electronic health records., Methods: Retrospective cohort study of pediatric ICU patients in PHIS between 1/1/2010 and 12/31/2019, excluding patients admitted to a neonatal ICU, and a nested study of PHIS+ from 1/1/2010 to 12/31/2012. Hospital antimicrobial prescription volumes were assessed for association with risk-adjusted mortality., Results: The cohort included 953,821 ICU encounters (23,851 [2.7%] nonsurvivors). There was 4-fold center-level variability in antimicrobial use. ICU antimicrobial use was not correlated with risk-adjusted mortality assessed using IBM-Watson. A risk model incorporating laboratory data available in PHIS+ significantly outperformed IBM-Watson (c-statistic 0.940 [95% confidence interval 0.933-0.947] versus 0.891 [0.881-0.901]; P < 0.001, area under the precision recall curve 0.561 versus 0.297). Risk-adjusted mortality was inversely associated with antimicrobial prescribing in this smaller cohort using both the PHIS+ and Watson models ( P = 0.05 and P < 0.01, respectively)., Conclusions: Antimicrobial prescribing among pediatric ICUs in the PHIS database is variable and not associated with risk-adjusted mortality as assessed by IBM-Watson. Expanding existing administrative databases to include laboratory data can achieve more meaningful insights when assessing multicenter antibiotic prescribing practices., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Viewing online pornography is common among US adults, with mixed-sex threesome (MST) videos being one of the top 10 most popular categories of pornography for both men and women. The current content analysis applied sexual script theory to understand the themes present in these mixed-sex threesome videos. Independent coders viewed a total of 50 videos (25 MMF and 25 FFM) at each timepoint (2012, 2015, 2020) and coded for different sexual behaviors and themes in each video. By examining both same-sex (female-female, male-male) and other-sex (female-male) behaviors, as well as themes of aggression and sexual initiation in different videos and across three timepoints, it was determined that other-sex behaviors are more common in MST videos than same-sex behaviors. Same-sex behaviors between two female actors were more common than same-sex behaviors between two male actors. Aggression was a common theme in videos, with male actors being more aggressive on average than female actors. Most of these trends did not change across 8 years, suggesting that the impacts of traditional sexual scripts are pervasive in pornography, even in current online content. Important implications for both researchers and clinical professionals are discussed.

Despite the abundance of studies investigating individual differences associated with extradyadic behavior (EB), nearly all have adopted retrospective measures in which the data is likely plagued by recall biases. In addition, few studies have explored individual differences or outcomes associated with EB between those with consenting and nonconsenting primary partners. Thus, the current study investigated the extent to which Ashley Madison users participated in a wide range of EBs, whether age, gender, and sexual identity predicted participation, and the extent to which outcomes were impacted by partner consent. The results from 1460 adults (962 men, 498 women) revealed that users reported engaging in three categories of behaviors: sexual/explicit, technology/online, and emotional/affectionate behaviors and that women and those older in age reported participating in EBs more frequently than men and those younger in age. Finally, 16.9% of the sample had a primary partner that consented to their Ashley Madison use and those with consenting partners reported greater perceived improvement in their primary relationship than did those with nonconsenting partners. Our findings highlight the importance of assessing the multitude of behaviors that Ashley Madison users participate in and whether consent was obtained. Implications for educators and practitioners are discussed.

Mixed-gender threesomes (MGTs) are a type of consensually nonmonogamous sexual encounter involving three people of more than one gender. Little research has been conducted on MGTs, and what little work does exist is limited to college students, who may actually be less experienced with MGTs than older adults. The present study investigated attitudes toward, interest in, experiences with, and outcomes of MGTs in two samples (college N = 231; online N = 1342), comprised of 907 heterosexual and 666 sexual minority participants in total. Results indicated that participants reported neutral-to-positive attitudes toward and moderate-to-high levels of interest in MGTs (81% indicated some degree of interest). MGTs involving familiar others were preferred to those involving strangers. Men, sexual minority individuals, and participants from the online sample reported more favorable attitudes toward and greater interest in MGTs as compared to women, heterosexual individuals, and participants from the student sample. In addition, 30% of participants indicated having experience with a MGT. Sexual minority individuals reported more experience with MGTs and more positive outcomes than did heterosexual individuals. In addition, on average, participants reported that their MGT experiences "met expectations." Overall, these results indicate that MGTs are a common sexual behavior that often results in positive outcomes, especially among sexual minority individuals. Additional research on this understudied topic is needed, particularly as it relates to outcomes and the role of MGTs in consensually nonmonogamous relationships.

Although many young adults are interested in mixed-gender threesomes (MGTs), little research has assessed attitudes toward them. Yet, MGTs offer a rare context to investigate how consensually nonmonogamous sexual encounters and involvement with same-sex others influence attitudes. Thus, by adopting sexual script theory as a framework, the current study compared three dimensions of character judgments (cognitive abilities, morality, partner quality) and assumptions about the sexual history of hypothetical males and females who initiated a MGT (two females and one male; two males and one female) or mixed-sex dyadic sexual activity with a casual or committed partner. To do so, a between-subject design was adopted in which 690 U.S. adults (405 women, 285 men) evaluated a hypothetical initiator described in one of 12 vignettes. On average, participants made neutral judgments about the initiator, yet those initiating dyadic sexual behavior were judged more favorably and as having a less extensive sexual history than MGT initiators. Male initiators were judged more favorably than female initiators, particularly by men. Those initiating in the context of a committed relationship were judged as more moral and as higher-quality partners than those initiating within a casual relationship; female (but not male) initiators in the committed context were judged as having a less extensive sexual history than female initiators in the casual context. These results confirm the presence of mononormativity biases and the sexual double standard and have implications for educators and practitioners related to stigma reduction and the promotion of inclusive sexual education.

Inequality is present to varying degrees in all human societies, pre-modern and contemporary. For archaeological contexts, variation in house size reflects differences in labor investments and serves as a robust means to assess wealth across populations small and large. The Gini coefficient, which measures the degree of concentration in the distribution of units within a population, has been employed as a standardized metric to evaluate the extent of inequality. Here, we employ Gini coefficients to assess wealth inequality at four nested socio-spatial scales-the micro-region, the polity, the district, and the neighborhood-at two medium size, peripheral Classic Maya polities located in southern Belize. We then compare our findings to Gini coefficients for other Classic Maya polities in the Maya heartland and to contemporaneous polities across Mesoamerica. We see the patterning of wealth inequality across the polities as a consequence of variable access to networks of exchange. Different forms of governance played a role in the degree of wealth inequality in Mesoamerica. More autocratic Classic Maya polities, where principals exercised degrees of control over exclusionary exchange networks, maintained high degrees of wealth inequality compared to most other Mesoamerican states, which generally are characterized by more collective forms of governance. We examine how household wealth inequality was reproduced at peripheral Classic Maya polities, and illustrate that economic inequity trickled down to local socio-spatial units in this prehispanic context., Competing Interests: The authors have declared that no competing interests exist.