Religions are reemerging in the social, political, and economic spheres previously occupied and dominated by secular institutions and ideologies. In the wake of crises exposing the limits of secular ...modernity, religions have again become significant players in domestic and international politics. At the same time, the Catholic Church has sought a "holy alliance" among the world's faiths to recentralize devout influence, an important, albeit little-noticed, evolution in international relations.Holy Wars and Holy Allianceexplores the nation-state's current crisis in order to better understand the religious resurgence's implications for geopolitics. Manlio Graziano looks at how the Catholic Church promotes dialogue and action linking world religions, and examines how it has used its material, financial, and institutional strength to gain power and increase its profile in present-day international politics. Challenging the idea that modernity is tied to progress and secularization, Graziano documents the "return" or the "revenge" of God in all facets of life. He shows that tolerance, pluralism, democracy, and science have not triumphed as once predicted. To fully grasp the destabilizing dynamics at work today, he argues, we must appreciate the nature of religious struggles and political holy wars now unfolding across the international stage.
In this work, Direct Numerical Simulation (DNS) is used to qualitatively and quantitatively investigate the structure of turbulence near an interface, and how these structures promote mass transfer. ...The canonical flow used in this work is that of open channel flow, that is, gravity-driven flow over a slightly inclined flat plate, bounded above by a free surface (e.g. a gas phase). To clarify the affect of these assumptions on channel flow, three different DNS were performed, each differing only by the boundary conditions employed at the free surface. In the first, or base, case, the clean, rigid slip-surface was imposed. In the second simulation, insoluble surfactants were introduced to the rigid slip-surface. In the last simulation, the rigid surface was replaced with a linearized version of the actual continuity of stress conditions. Surfactants were not present in the ‘linearized’ free surface. In order to assess the affect of these boundary conditions on the liquid-side mass transfer coefficient, a passive scalar concentration field was coupled to these three simulations. The average diffusional flux at the surface was used to compute the mass transfer coefficients. The passive concentration field was also simulated using experimental velocity data, measured by Kumar et. a1.22. The experimental velocity data consisted of a time series of velocities measured from an experiment, and was used to drive the passive scalar equation. This numerical experiment spans the gap between the ‘fully’ simulated case (i.e. both velocity and passive scalar concentration) and the experimental results found in the literature. The main result of this thesis is that the rigid slip-surface does not significantly change the characteristics of turbulence near the interface, especially at length scales important for mass transfer. This result is limited to flows without wind shear and with waves of low steepness. The effect of surfactant concentration on the near interface turbulence is much more dramatic. The turbulent intensities at the interface are damped, and there is a modification of the turbulent energy transfer at the interface. For a clean surface, normal motions (i.e. upwellings), are redistributed into surface-parallel motions near the interface. For a contaminated surface, this energy transfer process is shifted further below the interface, resulting in less surface renewal. (Abstract shortened by UMI.)
Whether protein translation occurs in the nucleus is contentious. To address this question, we developed the ribopuromycylation method (RPM), which visualizes translation in cells via standard ...immunofluorescence microscopy. The RPM is based on ribosome-catalyzed puromycylation of nascent chains immobilized on ribosomes by antibiotic chain elongation inhibitors followed by detection of puromycylated ribosome-bound nascent chains with a puromycin (PMY)-specific monoclonal antibody in fixed and permeabilized cells. The RPM correlates localized translation with myriad processes in cells and can be applied to any cell whose translation is sensitive to PMY. In this paper, we use the RPM to provide evidence for translation in the nucleoplasm and nucleolus, which is regulated by infectious and chemical stress.
An estimated 100,306 people died from an overdose from May 2020 to April 2021. Emergency Medical Services (EMS) are often the first responder to opioid overdose, and EMS encounter records can provide ...granular epidemiologic data on opioid overdose. This study describes the demographic, temporal, and geographic epidemiology of suspected opioid overdose in Baltimore City using data from Baltimore City Fire Department EMS encounters with the administration of the opioid antagonist naloxone.
The present analyses used patient encounter data from 2012 to 2017 from the Baltimore City Fire Department, the city's primary provider of EMS services. The analytic sample included patient encounters within the city that involved naloxone administration to patients 15 years of age or older (n = 20,592). Negative binomial regression was used to calculate the incidence rates based on demographic characteristics, year, and census tract. Choropleth maps were used to show the geographic distribution of overdose incidence across census tracts in 2013, 2015, and 2017.
From 2012 to 2017, the annual number of EMS encounters with naloxone administrations approximately doubled every 2 years, and the temporal pattern of naloxone administration was similar to the pattern of fatal opioid-related overdoses. For most census tracts, incidence rates significantly increased over time. Population-based incidence of naloxone administration varied significantly by socio-demographic characteristics. Males, non-whites, and those 25-69 years of age had the highest incidence rates.
The incidence of naloxone administration increased dramatically over the study period. Despite significant cross-sectional variation in incidence across demographically and geographically defined groups, there were significant proportional increases in incidence rates, consistent with fatal overdose rates over the period. This study demonstrated the value of EMS data for understanding the local epidemiology of opioid-related overdose.
Key Messages
Patterns of EMS encounters with naloxone administration appear to be an excellent proxy for patterns of opioid-related overdoses based on the consistency of fatal overdose rates over time.
EMS plays a central role in preventing fatal opioid-related overdoses through the administration of naloxone, provision of other emergency services, and transportation to medical facilities.
EMS encounters with naloxone administration could also be used to evaluate the impact of overdose prevention interventions and public health services.
Summary Background Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess ...the contribution of ultra-rare genetic variation to common epilepsies. Methods We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. Findings We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio OR 2·3, 95% CI 1·7–3·2, p=9·1 × 10−8 ; familial non-acquired focal epilepsy 3·6, 2·7–4·9, p=1·1 × 10−17 ). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10−8 ) that were lower than expected from a random sampling of genes. Interpretation We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. Funding National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK.
Intensifying livestock production to meet the demands of a growing global population coincides with increases in both the administration of veterinary antibiotics and manure inputs to soils. These ...trends have the potential to increase antibiotic resistance in soil microbial communities. The effect of maintaining increased antibiotic resistance on soil microbial communities and the ecosystem processes they regulate is unknown. We compare soil microbial communities from paired reference and dairy manure-exposed sites across the USA. Given that manure exposure has been shown to elicit increased antibiotic resistance in soil microbial communities, we expect that manure-exposed sites will exhibit (i) compositionally different soil microbial communities, with shifts toward taxa known to exhibit resistance; (ii) greater abundance of antibiotic resistance genes; and (iii) corresponding maintenance of antibiotic resistance would lead to decreased microbial efficiency. We found that bacterial and fungal communities differed between reference and manure-exposed sites. Additionally, the β-lactam resistance gene ampC was 5.2-fold greater under manure exposure, potentially due to the use of cephalosporin antibiotics in dairy herds. Finally, ampC abundance was positively correlated with indicators of microbial stress, and microbial mass-specific respiration, which increased 2.1-fold under manure exposure. These findings demonstrate that the maintenance of antibiotic resistance associated with manure inputs alters soil microbial communities and ecosystem function.
Microbial communities drive soil ecosystem function but are also susceptible to environmental disturbances. We investigated whether exposure to manure sourced from cattle either administered or not ...administered antibiotics affected microbially mediated terrestrial ecosystem function. We quantified changes in microbial community composition via amplicon sequencing, and terrestrial elemental cycling via a stable isotope pulse‐chase. Exposure to manure from antibiotic‐treated cattle caused: (i) changes in microbial community structure; and (ii) alterations in elemental cycling throughout the terrestrial system. This exposure caused changes in fungal : bacterial ratios, as well as changes in bacterial community structure. Additionally, exposure to manure from cattle treated with pirlimycin resulted in an approximate two‐fold increase in ecosystem respiration of recently fixed‐carbon, and a greater proportion of recently added nitrogen in plant and soil pools compared to the control manure. Manure from antibiotic‐treated cattle therefore affects terrestrial ecosystem function via the soil microbiome, causing decreased ecosystem carbon use efficiency, and altered nitrogen cycling.
Molecular excitons are useful for applications in light harvesting, organic optoelectronics, and nanoscale computing. Electronic energy transfer (EET) is a process central to the function of devices ...based on molecular excitons. Achieving EET with a high quantum efficiency is a common obstacle to excitonic devices, often owing to the lack of donor and acceptor molecules that exhibit favorable spectral overlap. EET quantum efficiencies may be substantially improved through the use of heteroaggregatesaggregates of chemically distinct dyesrather than individual dyes as energy relay units. However, controlling the assembly of heteroaggregates remains a significant challenge. Here, we use DNA Holliday junctions to assemble homo- and heterotetramer aggregates of the prototypical cyanine dyes Cy5 and Cy5.5. In addition to permitting control over the number of dyes within an aggregate, DNA-templated assembly confers control over aggregate composition, i.e., the ratio of constituent Cy5 and Cy5.5 dyes. By varying the ratio of Cy5 and Cy5.5, we show that the most intense absorption feature of the resulting tetramer can be shifted in energy over a range of almost 200 meV (1600 cm–1). All tetramers pack in the form of H-aggregates and exhibit quenched emission and drastically reduced excited-state lifetimes compared to the monomeric dyes. We apply a purely electronic exciton theory model to describe the observed progression of the absorption spectra. This model agrees with both the measured data and a more sophisticated vibronic model of the absorption and circular dichroism spectra, indicating that Cy5 and Cy5.5 heteroaggregates are largely described by molecular exciton theory. Finally, we extend the purely electronic exciton model to describe an idealized J-aggregate based on Förster resonance energy transfer (FRET) and discuss the potential advantages of such a device over traditional FRET relays.
Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with ...suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts.
The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the
test, χ
statistics, and logistic regression analyses.
A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts.
In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.
Class 1C antiarrhythmic drugs (AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction. Consensus guidelines have advocated that these ...drugs not be used in patients with stable coronary artery disease (CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation (AF) in patients with CAD without a prior myocardial infarction.
In 24,315 patients treated with the initiation of AADs, two populations were evaluated: (1) propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n = 1,114, vs class-3 AAD, n = 1,114) and (2) AF patients who had undergone a percutaneous coronary intervention or coronary artery bypass graft (flecainide, n = 150, and class-3 AAD, n = 1,453). Outcomes at 3 years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups.
At 3 years, mortality (9.1% vs 19.3%, P < .0001), HF hospitalization (12.5% vs 18.3%, P < .0001), MACE (22.9% vs 36.6%, P < .0001), and VT (5.8% vs 8.5%, P = .02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs 25.8%, P = .26), HF hospitalization (24.5% vs 26.1%, P = .73), VT (10.9% vs 14.7%, P = .28) and MACE (44.5% vs 49.5%, P = .32).
Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.
Display omitted .
PDF
