bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes of the pentaspline pulsed-field ablation catheter for the treatment of paroxysmal atrial fibrillation: results of the prospective, multicentre FARA-Freedom Study
Authors: Metzner Andreas , Fiala Martin , Vijgen Johan , Ouss Alexandre , Gunawardene Melanie , Hansen Jim , Kautzner Josef , Schmidt Boris , Duytschaever Mattias , Reichlin Tobias , Blaauw Yuri , Sommer Philipp , Vanderper Annelies , Achyutha Anitha B , Johnson Madeline , Raybuck Jonathan D , Neuzil Petr
Published: February 2024

Aims

Pulmonary vein isolation (PVI) is a well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long-term efficacy and safety data demonstrating single-procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate the long-term efficacy and safety of PFA using the pentaspline catheter for PAF.

Methods and results

FARA-Freedom, a prospective, non-randomized, multicentre study, enrolled patients with PAF undergoing de novo PVI with PFA, who were followed for 12 months with weekly transtelephonic monitoring and a 72-h Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success, which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. The study enrolled 179 PAF patients (62 ± 10 years, 39% female) at 13 centres. At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high, with 88.4 and 90.3% with weekly events and 72-h Holter monitors, respectively. Freedom from the composite primary effectiveness endpoint was 66.6%, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in two patients (1.1%), one tamponade and one transient ischaemic attack. There was no coronary spasm, PV stenosis, or AE fistula. There were four cases of transient phrenic nerve palsy, but all resolved during the index procedure.

Conclusion

In this prospective, non-randomized, multicentre study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigourous endpoint definitions and high monitoring compliance and demonstrated favourable safety.

Registration

Clinical Trials.gov Identifier: NCT05072964 (sponsor: Boston Scientific Corporation).
The Warburg Effect Reinterpreted 100 yr on: A First-Principles Stoichiometric Analysis and Interpretation from the Perspective of ATP Metabolism in Cancer Cells
Authors: Nath Sunil , Balling Rudi
Published: February 2024

The Warburg Effect is a longstanding enigma in cancer biology. Despite the passage of 100 yr since its discovery, and the accumulation of a vast body of research on the subject, no convincing biochemical explanation has been given for the original observations of aerobic glycolysis in cancer cell metabolism. Here, we have worked out a first-principles quantitative analysis of the problem from the principles of stoichiometry and available electron balance. The results have been interpreted using Nath’s unified theory of energy coupling and adenosine triphosphate (ATP) synthesis, and the original data of Warburg and colleagues have been analyzed from this new perspective. Use of the biomass yield based on ATP per unit substrate consumed, ${{Y}_{X/S}}\ ATP$, or the Nath-Warburg number, NaWa has been shown to excellently model the original data on the Warburg Effect with very small standard deviation values, and without employing additional fitted or adjustable parameters. Based on the results of the quantitative analysis, a novel conservative mechanism of synthesis, utilization, and recycling of ATP and other key metabolites (eg, lactate) is proposed. The mechanism offers fresh insights into metabolic symbiosis and coupling within and/or among proliferating cells. The fundamental understanding gained using our approach should help in catalyzing the development of more efficient metabolism-targeting anticancer drugs.
Bursts of coalescence within population pedigrees whenever big families occur
Authors: Diamantidis Dimitrios , Fan Wai-Tong (Louis) , Birkner Matthias , Wakeley John
Published: February 2024

We consider a simple diploid population-genetic model with potentially high variability of offspring numbers among individuals. Specifically, against a backdrop of Wright–Fisher reproduction and no selection, there is an additional probability that a big family occurs, meaning that a pair of individuals has a number of offspring on the order of the population size. We study how the pedigree of the population generated under this model affects the ancestral genetic process of a sample of size two at a single autosomal locus without recombination. Our population model is of the type for which multiple-merger coalescent processes have been described. We prove that the conditional distribution of the pairwise coalescence time given the random pedigree converges to a limit law as the population size tends to infinity. This limit law may or may not be the usual exponential distribution of the Kingman coalescent, depending on the frequency of big families. But because it includes the number and times of big families, it differs from the usual multiple-merger coalescent models. The usual multiple-merger coalescent models are seen as describing the ancestral process marginal to, or averaging over, the pedigree. In the limiting ancestral process conditional on the pedigree, the intervals between big families can be modeled using the Kingman coalescent but each big family causes a discrete jump in the probability of coalescence. Analogous results should hold for larger samples and other population models. We illustrate these results with simulations and additional analysis, highlighting their implications for inference and understanding of multilocus data.
First referral hospitals in low- and middle-income countries: the need for a renewed focus
Authors: Jeffries Mazhar Rosanna , Willows Tamara Mulenga , Bhattarai Suraj , Tinn Chit-Su , Misago Nadine , English Mike
Published: February 2024

First referral hospitals (FRHs) are the hospitals closest to the community, which offer expertise or technologies to complement more widely available ‘basic’ ambulatory care or inpatient care. Despite having been a subject of interest in global health policy in the latter half of the 20th century, in more recent decades, they appear to have been overshadowed. This paper reviews what is understood by FRH, drawing on both academic and policy literature, complemented by specific country case studies. We undertook three reviews: a grey literature review of global and regional policy reports and documents, a structured review of the academic literature on FRH and a review of FRH-related policies in eight countries. Our findings indicate that there is confusion regarding the definitions and roles of FRH; they have fallen off the policy agenda globally and they suffer from lack of advocates in part related to the absence of cohesive definition. Meanwhile, these facilities continue to fulfil important functions in health systems in low- and middle-income countries, and expectations for service delivery remain high. In light of these findings, this paper calls for renewed interest and investment in FRH from the global health academic and policy-making community.
A guide for a student-led doctoral-level qualitative methods short course in epidemiology: faculty and student perspectives
Authors: Gille Felix , Frei Anja , Kaufmann Marco , Lehmann Anja , Muñoz Laguna Javier , Papadopoulos Kimon , Spörri Angela , Stanikić Mina , Tušl Martin , Zavattaro Federica , Puhan Milo Alan
Published: February 2024

Qualitative research and mixed methods are core competencies for epidemiologists. In response to the shortage of guidance on graduate course development, we wrote a course development guide aimed at faculty and students designing similar courses in epidemiology curricula. The guide combines established educational theory with faculty and student experiences from a recent introductory course for epidemiology and biostatistics doctoral students at the University of Zurich and Swiss Federal Institute of Technology, Zurich. We propose a student-centred course with inverse classroom teaching and practice exercises with faculty input. Integration of student input during the course development process helps align the course syllabus with student needs. The proposed course comprises six sessions that cover learning outcomes in comprehension, knowledge, application, analysis, synthesis and evaluation. Following an introductory session, the students engage in face-to-face interviews, focus group interviews, observational methods, analysis and how qualitative and quantitative methods are integrated in mixed methods. Furthermore, the course covers interviewer safety, research ethics, quality in qualitative research and a practice session focused on the use of interview hardware, including video and audio recorders. The student-led teaching characteristic of the course allows for an immersive and reflective teaching-learning environment. After implementation of the course and learning from faculty and student perspectives, we propose these additional foci: a student project to apply learned knowledge to a case study; integration in mixed-methods; and providing faculty a larger space to cover theory and field anecdotes.
Prevention of experimental autoimmune encephalomyelitis by targeting 6-sulfo sialyl Lewis X glycans involved in lymphocyte homing
Authors: Liu Qianqian , Xiong Wei , Obara Sachiyo , Abo Hirohito , Nakatsukasa Hiroko , Kawashima Hiroto
Published: February 2024

Lymphocyte homing to peripheral lymph nodes (PLN) is critical for immune surveillance. However, autoimmune diseases such as multiple sclerosis (MS) can occur due to excessive immune responses in the PLN. Here we show that 6-sulfo sialyl Lewis X (6-sulfo sLex) glycans on high endothelial venules that function as ligands for l-selectin on lymphocytes play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2 double-knockout mice lacking the expression of 6-sulfo sLeX glycans, the EAE symptoms and the numbers of effector Th1 and Th17 cells in the draining lymph nodes (dLN) and spinal cords (SC) were significantly reduced. To determine whether 6-sulfo sLeX could serve as a target for MS, we also examined the effects of anti-glycan monoclonal antibody (mAb) SF1 against 6-sulfo sLeX in EAE. Administration of mAb SF1 significantly reduced EAE symptoms and the numbers of antigen-specific effector T cells in the dLN and SC in association with suppression of critical genes including Il17a and Il17f that are involved in the pathogenesis of EAE. Taken together, these results suggest that 6-sulfo sLeX glycan would serve as a novel target for MS.
Isolation of a widespread giant virus implicated in cryptophyte bloom collapse
Authors: Vieira Helena H , Bulzu Paul-Adrian , Kasalický Vojtěch , Haber Markus , Znachor Petr , Piwosz Kasia , Ghai Rohit
Published: February 2024

Photosynthetic cryptophytes are ubiquitous protists that are major participants in the freshwater phytoplankton bloom at the onset of spring. Mortality due to change in environmental conditions and grazing have been recognized as key factors contributing to bloom collapse. In contrast, the role of viral outbreaks as factors terminating phytoplankton blooms remains unknown from freshwaters. Here, we isolated and characterized a cryptophyte virus contributing to the annual collapse of a natural cryptophyte spring bloom population. This viral isolate is also representative for a clade of abundant giant viruses (phylum Nucleocytoviricota) found in freshwaters all over the world.
The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis
Authors: Singh Shivani , Boyd Simon , Schilling William H K , Watson James A , Mukaka Mavuto , White Nicholas J
Published: February 2024

Background

Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear.

Methods

A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14 days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR). The VCRR is the ratio of viral clearance rates between the intervention and control arms. The relationship between the clinical and virological treatment effects was assessed by mixed-effects meta-regression.

Results

From 57 potentially eligible RCTs, VCRRs were derived for 44 (52 384 participants); 32 had ≥1 clinical endpoint in each arm. Overall, 9.7% (R2) of the variation in clinical benefit was explained by variation in VCRRs with an estimated linear coefficient of −0.92 (95% CI: −1.99 to 0.13; P = 0.08). However, this estimate was highly sensitive to the inclusion of the recent very large PANORAMIC trial. Omitting this outlier, half the variation in clinical benefit (R2 = 50.4%) was explained by variation in VCRRs [slope −1.47 (95% CI −2.43 to −0.51); P = 0.003], i.e. higher VCRRs were associated with an increased clinical benefit.

Conclusion

Methods of determining viral clearance in COVID-19 studies and the relationship to clinical outcomes vary greatly. As prohibitively large sample sizes are now required to show clinical treatment benefit in antiviral therapeutic assessments, viral clearance is a reasonable surrogate endpoint.
The synergic and addictive activity of biogenic silver nanoparticle associated with meropenem against carbapenem-resistant Acinetobacter baumannii
Authors: Allend Suzane Olachea , Oliveira Garcia Marcelle , da Cunha Kamila Furtado , de Albernaz Déborah Trota Farias , Panagio Luciano Aparecido , Nakazaro Gerson , Reis Guilherme Fonseca , Oliveira Thaís Larré , Neto Amilton Clair Pinto Seixas , Hartwig Daiane Drawanz
Published: February 2024

Aims

Antibiotic management of infections caused by Acinetobacter baumannii often fails due to antibiotic resistance (especially to carbapenems) and biofilm-forming strains. Thus, the objective here was to evaluate in vitro the antibacterial and antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) combined with meropenem, against multidrug-resistant isolates of A. baumannii.

Methods and results

In this study, A. baumannii ATCC® 19606™ and four carbapenem-resistant A. baumannii (Ab) strains were used. The antibacterial activity of Bio-AgNP and meropenem was evaluated through broth microdilution. The effect of the Bio-AgNP association with meropenem was determined by the checkboard method. Also, the time-kill assay and the integrity of the bacterial cell membrane were evaluated. Furthermore, the antibiofilm activity of Bio-AgNP and meropenem alone and in combination was determined. Bio-AgNP has antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 0.46 to 1.87 μg ml−1. The combination of Bio-AgNP and meropenem showed a synergistic and additive effect against Ab strains, and Bio-AgNP was able to reduce the MIC of meropenem from 4- to 8-fold. Considering the time-kill of the cell, meropenem and Bio-AgNP when used in combination reduced bacterial load to undetectable levels within 10 min to 24 h after treatment. Protein leakage was observed in all treatments evaluated. When combined, meropenem/Bio-AgNP presents biofilm inhibition for Ab2 isolate and ATCC® 19606™, with 21% and 19%, and disrupts the biofilm from 22% to 50%, respectively. The increase in nonviable cells in the biofilm can be observed after treatment with Bio-AgNP and meropenem in carbapenem-resistant A. baumannii strains.

Conclusions

The combination of Bio-AgNP with meropenem can be a therapeutic option in the treatment of infections caused by carbapenem-resistant A. baumannii.
Production of CA125 with Tn antigens using a glycosylphosphatidylinositol anchoring system
Authors: Tang Yu-He , Leng Ji-Xiong , Yang Ganglong , Gao Xiao-Dong , Liu Yi-Shi , Fujita Morihisa
Published: February 2024

Cancer antigen 125 (CA125) is a serum marker associated with ovarian cancer. Despite its widespread use, CA125 levels can also be elevated in benign conditions. Recent reports suggest that detecting serum CA125 that carries the Tn antigen, a truncated O-glycan containing only N-acetylgalactosamine on serine or threonine residues, can improve the specificity of ovarian cancer diagnosis. In this study, we engineered cells to express CA125 with a Tn antigen. To achieve this, we knocked out C1GALT1 and SLC35A1, genes encoding Core1 synthase and a transporter for cytidine-5′-monophospho-sialic acid respectively, in human embryonic kidney 293 (HEK293) cells. In ClGALT1-SLC35A1-knockout (KO) cells, the expression of the Tn antigen showed a significant increase, whereas the expression of the T antigen (galactose-β1,3-N-acetylgalactosamine on serine or threonine residues) was decreased. Due to the inefficient secretion of soluble CA125, we employed a glycosylphosphatidylinositol (GPI) anchoring system. This allowed for the expression of GPI-anchored CA125 on the cell surface of ClGALT1-SLC35A1-KO cells. Cells expressing high levels of GPI-anchored CA125 were then enriched through cell sorting. By knocking out the PGAP2 gene, the GPI-anchored form of CA125 was converted to a secretory form. Through the engineering of O-glycans and the use of a GPI-anchoring system, we successfully produced CA125 with Tn antigen modification.
Morphinan Evolution: The Impact of Advances in Biochemistry and Molecular Biology
Authors: Kajino Keita , Tokuda Akihisa , Saitoh Tsuyoshi
Published: February 2024

Morphinan-based opioids, derived from natural alkaloids like morphine, codeine and thebaine, have long been pivotal in managing severe pain. However, their clinical utility is marred by significant side effects and high addiction potential. This review traces the evolution of the morphinan scaffold in light of advancements in biochemistry and molecular biology, which have expanded our understanding of opioid receptor pharmacology. We explore the development of semi-synthetic and synthetic morphinans, their receptor selectivity and the emergence of biased agonism as a strategy to dissociate analgesic properties from undesirable effects. By examining the molecular intricacies of opioid receptors and their signaling pathways, we highlight how receptor-type selectivity and signaling bias have informed the design of novel analgesics. This synthesis of historical and contemporary perspectives provides an overview of the morphinan landscape, underscoring the ongoing efforts to mitigate the problems facing opioids through smarter drug design. We also highlight that most morphinan derivatives show a preference for the G protein pathway, although detailed experimental comparisons are still necessary. This fact underscores the utility of the morphinan skeleton in future opioid drug discovery.
Social media mindsets: a new approach to understanding social media use and psychological well-being
Authors: Lee Angela Y , Hancock Jeffrey T
Published: February 2024

Social media mindsets are the core beliefs that orient individuals’ expectations, behaviors, attributions, and goals about social media’s role in their lives. In four survey studies (N = 2,179), we show people hold distinct mindsets about the amount of agency they have over their social media use (“in control” vs. “out of control”) and the valence of its effects (“enhancing” vs. “harmful”) that are meaningfully related to psychological well-being. We develop and apply the Social Media Mindsets scale, revealing that agentic, positive mindsets are associated with better well-being and low-agency, and negative mindsets are associated with worse well-being (Studies 1, 2a, and 2b). Notably, these mindsets explained more variance in relational well-being and psychological distress than other measures (Study 3) and were related to differences in how people used social media and interpreted the time they spent on it (Studies 3 and 4). Our findings introduce a novel potential explanation for heterogeneous social media effects on well-being.
Religion, Pluralism, and the Australian State after Same-Sex Marriage
Authors: Tregenza Ian
Published: February 2024

Since the passing of same-sex marriage legislation in 2017, religious freedom has become a prominent feature of Australian public debate. Overwhelmingly, such debates are conducted within a human rights framework where principles such as individual autonomy and protection from discrimination are prioritized over the communal and associational elements of religious life. This in turn tends to augment the power of the state vis-à-vis religious communities and institutions. In important respects, the dominance of human rights represents a new manifestation of the kind of “liberal-statism”—a public philosophy of liberal individualism that accepts the primacy of the state in the management of cultural and religious diversity—that has been a central feature of Australian religion–state relations over time. After some historical discussion of Australian church–state practice, this article argues for a reconsideration of a largely overlooked approach deriving from the English pluralists of the early twentieth century, which promoted greater degrees of group autonomy in relation to a rapidly growing state. It is argued that this tradition has greater potential in responding to the religious diversity of our time than does the current human rights approach with its tendency to reinforce an individualistic or privatized conception of religion, diminish associational life, and thereby reinforce state power.
Bacterial resistance response and resource availability mediate viral coexistence
Authors: Butt Lisa , Meyer Justin R , Lindsay Richard J , Beardmore Robert E , Gudelj Ivana
Published: February 2024

Viruses that infect bacteria, known as bacteriophages or phages, are the most prevalent entities on Earth. Their genetic diversity in nature is well documented, and members of divergent lineages can be found sharing the same ecological niche. This viral diversity can be influenced by a number of factors, including productivity, spatial structuring of the environment, and host-range trade-offs. Rapid evolution is also known to promote diversity by buffering ecological systems from extinction. There is, however, little known about the impact of coevolution on the maintenance of viral diversity within a microbial community. To address this, we developed a 4 species experimental system where two bacterial hosts, a generalist and a specialist phage, coevolved in a spatially homogenous environment over time. We observed the persistence of both viruses if the resource availability was sufficiently high. This coexistence occurred in the absence of any detectable host-range trade-offs that are costly for generalists and thus known to promote viral diversity. However, the coexistence was lost if two bacteria were not permitted to evolve alongside the phages or if two phages coevolved with a single bacterial host. Our findings indicate that a host’s resistance response in mixed-species communities plays a significant role in maintaining viral diversity in the environment.
Making international trade work for sustainable development: toward a new WTO framework for subsidies
Authors: Cima Elena , Esty Daniel C
Published: February 2024

Government subsidies for fossil fuels, agricultural production, and fisheries amount to trillions of dollars per year. This funding harms economic efficiency, disrupts trade, and actively exacerbates the global environmental and climate crises. Moreover, the scale of these subsidies far exceeds the support provided to industries and activities that contribute to the transition towards a low-carbon and sustainable future economy. In seeking to discipline such subsidies, trade law has traditionally focused on whether the funding distorts trade without regard to the rationale or purpose of the subsidies. In this article, we argue that this approach to subsidies is at once incompatible with (i) the original vision of multilateral trade law, (ii) what is needed to manage international economic interdependence in today’s world, and (iii) the present moment’s urgent need to take seriously sustainable development as the ultimate objective of the trading system. The reform package we present in this article calls for a reframing of WTO subsidies rules on a foundation that gauges alignment with sustainable development alongside trade distortions, with sustainability becoming the first and foremost test of whether subsidies should be permitted—consistent with the sustainable development mandate in the Marrakesh Agreement that established the WTO.
A rare case of small cell carcinoma of the ovary, hypercalcemic type
Authors: Boujida Ismail , Mahdi Y , Khmou M , Ech-charif S , Horache K , El-Aoufir O , Gamra L , El-Khannoussi B
Published: February 2024

Small cell carcinoma of ovary, hypercalcemic type (SCCOHT) is an unusual malignant tumor that most commonly affects young women. Unfortunately, it has a very poor prognosis. We describe here an unusual case of a Moroccan young woman with a left ovarian mass and a symptomatic hypercalcemia. Morphologically, there are some malignant tumors that resemble SCCOHT; thus, it is very challenging to diagnose, and immunohistochemistry has a great contribution in it. Hopefully, molecular tools and new therapies will improve the management of these cases in the near future.
Untranslated yet indispensable—UTRs act as key regulators in the environmental control of gene expression
Authors: Hardy Emma C , Balcerowicz Martin
Published: February 2024

To survive and thrive in a dynamic environment, plants must continuously monitor their surroundings and adjust their development and physiology accordingly. Changes in gene expression underlie these developmental and physiological adjustments, and are traditionally attributed to widespread transcriptional reprogramming. Growing evidence, however, suggests that post-transcriptional mechanisms also play a vital role in tailoring gene expression to a plant’s environment. Untranslated regions (UTRs) act as regulatory hubs for post-transcriptional control, harbouring cis-elements that affect an mRNA’s processing, localization, translation, and stability, and thereby tune the abundance of the encoded protein. Here, we review recent advances made in understanding the critical function UTRs exert in the post-transcriptional control of gene expression in the context of a plant’s abiotic environment. We summarize the molecular mechanisms at play, present examples of UTR-controlled signalling cascades, and discuss the potential that resides within UTRs to render plants more resilient to a changing climate.
Chloroplast thiol redox dynamics through the lens of genetically encoded biosensors
Authors: Müller-Schüssele Stefanie J
Published: February 2024

Chloroplasts fix carbon by using light energy and have evolved a complex redox network that supports plastid functions by (i) protecting against reactive oxygen species and (ii) metabolic regulation in response to environmental conditions. In thioredoxin- and glutathione/glutaredoxin-dependent redox cascades, protein cysteinyl redox steady states are set by varying oxidation and reduction rates. The specificity and interplay of these different redox-active proteins are still under investigation, for example to understand how plants cope with adverse environmental conditions by acclimation. Genetically encoded biosensors with distinct specificity can be targeted to subcellular compartments such as the chloroplast stroma, enabling in vivo real-time measurements of physiological parameters at different scales. These data have provided unique insights into dynamic behaviours of physiological parameters and redox-responsive proteins at several levels of the known redox cascades. This review summarizes current applications of different biosensor types as well as the dynamics of distinct protein cysteinyl redox steady states, with an emphasis on light responses.
A post-merger enhancement only in star-forming Type 2 Seyfert galaxies: the deep learning view
Authors: Avirett-Mackenzie M S , Villforth C , Huertas-Company M , Wuyts S , Alexander D M , Bonoli S , Lapi A , Lopez I E , Ramos Almeida C , Shankar F
Published: February 2024

Supermassive black holes require a reservoir of cold gas at the centre of their host galaxy in order to accrete and shine as active galactic nuclei (AGN). Major mergers have the ability to drive gas rapidly inwards, but observations trying to link mergers with AGN have found mixed results due to the difficulty of consistently identifying galaxy mergers in surveys. This study applies deep learning to this problem, using convolutional neural networks trained to identify simulated post-merger galaxies from survey-realistic imaging. This provides a fast and repeatable alternative to human visual inspection. Using this tool, we examine a sample of ∼8500 Seyfert 2 galaxies ($L[\mathrm{O\, {\small III}}] \sim 10^{38.5 - 42}$ erg s−1) at z < 0.3 in the Sloan Digital Sky Survey and find a merger fraction of $2.19_{-0.17}^{+0.21}$ per cent compared with inactive control galaxies, in which we find a merger fraction of $2.96_{-0.20}^{+0.26}$ per cent, indicating an overall lack of mergers among AGN hosts compared with controls. However, matching the controls to the AGN hosts in stellar mass and star formation rate reveals that AGN hosts in the star-forming blue cloud exhibit a ∼2 × merger enhancement over controls, while those in the quiescent red sequence have significantly lower relative merger fractions, leading to the observed overall deficit due to the differing M*–SFR distributions. We conclude that while mergers are not the dominant trigger of all low-luminosity, obscured AGN activity in the nearby Universe, they are more important to AGN fuelling in galaxies with higher cold gas mass fractions as traced through star formation.
The Atacama cosmology telescope: flux upper limits from a targeted search for extragalactic transients
Authors: Hervías-Caimapo Carlos , Naess Sigurd , Hincks Adam D , Calabrese Erminia , Devlin Mark J , Dunkley Jo , Dünner Rolando , Gallardo Patricio A , Hilton Matt , Ho Anna Y Q , Huffenberger Kevin M , Ma Xiaoyi , Madhavacheril Mathew S , Niemack Michael D , Orlowski-Scherer John , Page Lyman A , Partridge Bruce , Puddu Roberto , Salatino Maria , Sifón Cristóbal , Staggs Suzanne T , Vargas Cristian , Vavagiakis Eve M , Wollack Edward J
Published: February 2024

We have performed targeted searches of known extragalactic transient events at millimetre wavelengths using nine seasons (2013–2021) of 98, 150, and 229 GHz Atacama Cosmology Telescope (ACT) observations that mapped ∼40 per cent of the sky for most of the data volume. Our data cover 88 gamma-ray bursts (GRBs), 12 tidal disruption events (TDEs), and 203 other transients, including supernovae (SNe). We stack our ACT observations to increase the signal-to-noise ratio of the maps. In all cases but one, we do not detect these transients in the ACT data. The single candidate detection (event AT2019ppm), seen at ∼5σ significance in our data, appears to be due to active galactic nuclei activity in the host galaxy coincident with a transient alert. For each source in our search we provide flux upper limits. For example, the medians for the 95 per cent confidence upper limits at 98 GHz are 15, 18, and 16 mJy for GRBs, SNe, and TDEs, respectively, in the first month after discovery. The projected sensitivity of future wide-area cosmic microwave background surveys should be sufficient to detect many of these events using the methods described in this paper.
Clinical Presentation, Risk Factors, and Comparison of Laboratory Diagnostics for Seasonal Influenza Virus Among Cambodians From 2007 to 2020
Authors: Rachmat Agus , Kelly Gerard C , Tran Long Khanh , Christy Nathaniel , Supaprom Chonthida , Heang Vireak , Dul Sokha , Garcia-Rivera Jose A , Prom Satharath , Sopheab Heng , Brooks John S , Sutherland Ian J , Corson Karen S , Letizia Andrew G
Published: February 2024

Background

Despite its global significance, challenges associated with understanding the epidemiology and accurately detecting, measuring, and characterizing the true burden of seasonal influenza remain in many resource-poor settings.

Methods

A prospective observational study was conducted in Cambodia at 28 health facilities between 2007 and 2020 utilizing passive surveillance data of patients presenting with acute undifferentiated febrile illness (AUFI) to describe the prevalence of influenza A and B and characterize associated risk factors and symptoms using a questionnaire. A comparison of rapid influenza diagnostic tests (RIDTs) and real-time reverse transcription polymerase chain reaction (rRT-PCR) results was also conducted.

Results

Of 30 586 total participants, 5634 (18.4%) tested positive for either influenza A or B, with 3557 (11.6%) positive for influenza A and 2288 (7.5%) positive for influenza B during the study. Influenza A and B were strongly associated with the rainy season (odds ratio [OR], 2.30; P < .001) and being from an urban area (OR, 1.45; P < .001). Analysis of individual symptoms identified cough (OR, 2.8; P < .001), chills (OR, 1.4; P < .001), and sore throat (OR, 1.4; P < .001) as having the strongest positive associations with influenza among patients with AUFI. Analysis comparing RIDTs and rRT-PCR calculated the overall sensitivity of rapid tests to be 0.492 (95% CI, 0.479–0.505) and specificity to be 0.993 (95% CI, 0.992–0.994) for both influenza type A and B.

Conclusions

Findings from this 14-year study include describing the epidemiology of seasonal influenza over a prolonged time period and identifying key risk factors and clinical symptoms associated with infection; we also demonstrate the poor sensitivity of RIDTs in Cambodia.
Combination Antifungal Therapy for Invasive Mucormycosis in Immunocompromised Hosts: A Single-Center Experience
Authors: Lu Brian , Ha David , Shen Sa , Ferguson Toll Jessica , Kim Ailin , Kim Sarah , Mui Emily , Deresinski Stan , Holubar Marisa , Alegria William
Published: February 2024

Combination antifungal therapy for invasive mucormycosis remains controversial and is inconsistently defined in prior studies. In a cohort of patients with immunocompromised status and invasive mucormycosis, we found no difference in 6-week mortality with up-front or salvage combination therapy as compared with monotherapy.
Venice
Authors: Romano Dennis
Published: February 2024

No city stirs the imagination more than Venice. From the richly ornamented palaces emerging from the waters of the Grand Canal to the dazzling sites of Piazza San Marco, visitors and residents alike sense they are entering, as fourteenth-century poet Petrarch remarked, “another world.” During the Middle Ages and Renaissance, Venice was celebrated as a model republic in an age of monarchs. In the seventeenth and eighteenth centuries, it became famous for its freewheeling lifestyle characterized by courtesans, casinos, and Carnival. When the city fell on hard times following the collapse of the Republic in 1797, a darker vision of Venice as a place of decay, disease, and death took hold. Today tourists from around the globe flock to the world heritage site as rising sea level threatens its very foundations. This comprehensive account reveals the adaptations to its geographic setting that have been a constant feature of living on water from Venice’s origins to the present. It examines the lives of the women and men, noble and common, rich and poor, Christian and Jew, who built the city and its vast empire that stretched from Northern Italy to the eastern Mediterranean. It details Venice’s urban transformations in response to environmental vulnerability, industrialization, and mass tourism. It also considers the city’s dramatically changing political role—its power as a city-state, regional-state, and overseas empire, and its impact on the development of fascism. Throughout, the city’s cultural achievements in architecture, painting, and music are highlighted.
From Ducal to Communal Venice
Authors: Romano Dennis
Published: February 2024

This chapter charts the evolution of Venice from a monarchical (ducal or dogal) form of government into a communal one, an early form of republican government. This was a twofold process: the reining in of the doge through the requirement that he swear an oath of office known as the promissione, and the development of new, more representative bodies (the Greater and Lesser councils) that restricted his power to act independently. Other changes accompanied this evolution: the bureaucracy grew and the city took on a new form. The church of San Marco was rebuilt for a third and final time, Piazza San Marco was expanded, and Rialto emerged as the city’s wholesale market. The city became more compact and other lagoon settlements declined as Rialto/Venice rose.
The Fourth Crusade and the Creation of a Mediterranean Empire
Authors: Romano Dennis
Published: February 2024

This chapter charts the course of the Fourth Crusade which resulted in the overthrow of the Byzantine Empire and the creation of Venice’s overseas domain, known as the stato da mar. It examines the ways by which Venice acquired empire: conquest, purchase, settlement. Not interested in territory per se, Venice wanted trading posts and water refueling stations for its ships. It explores the huge expansion of Venetian trade and trade routes, including into the Black Sea, and the trade routes to India and China, the latter pioneered by Marco Polo. It also shows how urban infrastructure projects, especially the creation of fondachi (hospice/warehouses) for foreign merchants, the Arsenal, and the Mint, supported Venetian trade. The chapter considers how Venice used both hard and soft power to assert its trade monopoly over the Adriatic and its growing trade and military rivalry with Genoa.
Society and Politics in the Thirteenth Century
Authors: Romano Dennis
Published: February 2024

This chapter explores the evolution of Venetian society and politics over the course of the thirteenth century. At the beginning of the century, the nobility remained ill-defined; and for the first time, the popolo and their organization into guilds and confraternities comes into focus. But many remained outside these structures. As the city continued to grow, the communal government and bureaucracy expanded. The increasing density of the urban environment fostered greater surveillance and police powers as the commune asserted its control over streets and canals. A particular type of domestic architecture developed that was adapted to the city’s amphibious environment. The mendicant orders also played a major role in urban expansion. By the end of the century, the popolo had been excluded from power, and the nobility (defined by the event known as the Serrata) had emerged as a hereditary caste. The Venetian Republic was born.
EU Law and Sports: A Match Made in Hell or in Heaven?
Authors: Maduro Miguel Poiares
Published: February 2024

This chapter challenges the current model of sports governance autonomy and argues that only the EU is in a position to bring democratic accountability and rule of law principles into sports governance and ought to do so. The chapter starts by reviewing the extent to which sports private governance bodies are failing in delivering on the public good entrusted to them from sports integrity to the openness and competitive balance of sports competitions. It then proceeds to link those failures to systemic governance failures in those bodies. It identifies and challenges the traditional justifications put forward to justify the almost absolute form of regulatory autonomy and private governance granted to sports governance bodies. It goes on to argue not only that autonomy ought to be limited but that, even when and where it does make sense to recognize such autonomy, it needs to be conditional on subjecting their structures of governance to principles of democracy, rule of law, fundamental rights, accountability, and transparency. The final section argues that only the EU is in a position to do this and puts forward different alternatives on how it can be achieved. It also argues that, in doing so, the EU presents to its citizens an important democratic added value.
The Crusade for the Holy Grail of Competitive Balance
Authors: Mataija Mislav , Mavroidis Petros C
Published: February 2024

The specificity of sport is a concept acknowledged on both sides of the Atlantic. In the US it is linked to a (limited) exception from antitrust laws. In Europe, the application of the rules on free movement of persons, services, and workers, as well as antitrust, has left some room for it. But whereas the US has gone full steam ahead to regulate competitive balance, Europe has not. In this contribution, inspired by the work of Steve Weatherill and others, we ask the question whether the observed differentiated approach is justified because of the nature of competition on the two sides of the Atlantic, ie closed leagues in the US, and promotion/relegation in Europe.
(Teaching) The Integrity of the EU’s Internal Market
Authors: Shuibhne Niamh Nic , Baleva Dayana , Dimitrijewitsch Jovan , Jukes Rhian , Kotrba Antonín , Schaupp Lukas
Published: February 2024

This co-produced chapter traces the teaching and learning of the ‘Integrity of the EU’s Internal Market’ LLM course at Edinburgh Law School during the spring semester of the 2020–21 academic year. It shows how Steve Weatherill’s research—especially his Yearbook of European Law article on ‘The Several Internal Markets’ (2017) and his subsequent work on Brexit—underpinned the foundations of the course and provoked both teacher and students to interrogate and reflect more deeply on the nature, coherence, and fragility of the internal market. It considers questions of integrity from a conceptual perspective and then tests and evolves them in the context of complexities within and across the internal market’s four freedoms; with respect to how market and non-market objectives intersect; and in terms of how the EU’s internal market relates to the markets beyond its borders. It concludes by offering post-course thoughts from the students on what it was like to learn through this thematic approach and from the teacher on the future of education on EU internal market law.
Animist Time and the White Anthropocene
Authors: Allen-Paisant Jason
Published: February 2024

This chapter examines Aimé Césaire’s commitment to more-than-human existence alongside that of a number of other African/diasporic thinkers, setting his work in relation to a rigorously accounted for set of predecessors—life philosophy, anthropology, poetics of Africa and its diasporas—and establishing a continuity of diasporic thought around the body and around interspecies collaboration and co-existence. While the age of climate disaster has begun to turn the Western civilizational ethos of the human person into an object for thought in many quarters, the author’s entry point into the conversation is through Afro-diasporic knowledge systems that evidence construals of the human being not rooted in the Western paradigm of the individual. The chapter emphasizes the fact that animist thinking systems have for centuries, due to the violences of modernity, existed in a parallel space and time to what the author calls ‘capitalist time’ and proposes that the failures and crises of Western industrial/technological civilization warrant renewed examinations of their benefits in human living practices. This comes full circle on the opening discussion (in Chapter 1) of the fate of a certain view of ‘poetry’ (as incantation, participation, cultivation) in modernity.
Introduction
Authors: Davenport Caillan , Malik Shushma
Published: February 2024

This book consists of a series of case studies examining the representation of Roman emperors across more than two thousand years of history from antiquity to the present. The case studies cover a range of different texts, media, and contexts, ranging from histories, coins, and statues of the Roman imperial period to twentieth-century novels and museum exhibitions. This introductory chapter sets out the methodological and theoretical frameworks for the case studies and the volume as a whole. It first examines the mechanics of representation and theories of classical reception before exploring several key themes: the relationship between history and fiction; the rhetoric and creativity of images; the transmission of the Roman past; and the representation of Rome in imperialistic contexts.
Epilogue
Authors: Davenport Caillan , Malik Shushma
Published: February 2024

This chapter draws together the main themes of the volume. It argues that Roman emperors have functioned (and continue to function) not only as models of kingship, but as a way of structuring the past, present, and future of states and individuals and of expressing the relationships between them. The ideas of contingency, collection, and curation that lie behind these phenomena are summed up by the concept of representation. We argue that representation is a process which arises from the interaction of human imagination with specific media, genres, and discourses.
An Introduction to Courts’ and Principles-Based Interpretivism
Authors: Lamandini Marco , Muñoz David Ramos
Published: February 2024

This book focuses on courts and financial disputes. We speak of ‘constitutional law’, ‘civil law’, or ‘administrative law’, but of ‘financial regulation’ as if finance’s rules and norms were something alien to, or distinct from, ‘law’. This emphasizes finance’s peculiarities, including the presence of regulatory norms, the use of soft law, the norm-producing status of administrative authorities, and the relevance of global standard-setting bodies i. In turn, finance presents unique problems for the law. Yet, this chapter shows that only law and courts can answer those problems by providing finance with the certainty it needs to operate, and the elasticity it needs to evolve. It offers many examples where, using principles-based interpretivism, courts reconcile finance’s technical complexity with a respect for the rule of law, especially when different pieces of legislation are inspired by different, sometimes competing goals or ‘narratives’. The chapter also argues that courts’ principles-based interpretivism can correct certain biases, and bolster the legitimacy of financial law. Alternative views, such as rules-based positivism or pragmatism do not fully capture the role of courts in financial law.