bluuebunny/crossref_metadata_2025 huggingface dataset:
Recoverability of causal effects under presence of missing data: a longitudinal case study
Authors: Holovchak Anastasiia , McIlleron Helen , Denti Paolo , Schomaker Michael
Published: November 2024

Missing data in multiple variables is a common issue. We investigate the applicability of the framework of graphical models for handling missing data to a complex longitudinal pharmacological study of children with HIV treated with an efavirenz-based regimen as part of the CHAPAS-3 trial. Specifically, we examine whether the causal effects of interest, defined through static interventions on multiple continuous variables, can be recovered (estimated consistently) from the available data only. So far, no general algorithms are available to decide on recoverability, and decisions have to be made on a case-by-case basis. We emphasize the sensitivity of recoverability to even the smallest changes in the graph structure, and present recoverability results for three plausible missingness-directed acyclic graphs (m-DAGs) in the CHAPAS-3 study, informed by clinical knowledge. Furthermore, we propose the concept of a “closed missingness mechanism”: if missing data are generated based on this mechanism, an available case analysis is admissible for consistent estimation of any statistical or causal estimand, even if data are missing not at random. Both simulations and theoretical considerations demonstrate how, in the assumed MNAR setting of our study, a complete or available case analysis can be superior to multiple imputation, and estimation results vary depending on the assumed missingness DAG. Our analyses demonstrate an innovative application of missingness DAGs to complex longitudinal real-world data, while highlighting the sensitivity of the results with respect to the assumed causal model.
Risk factors and protective measures for desmoid tumours in familial adenomatous polyposis: retrospective cohort study
Authors: Rausa Emanuele , Duroni Valeria , Ferrari Davide , Signoroni Stefano , Ciniselli Chiara M , Lauricella Sara , Brignola Clorinda , Ricci Maria T , Gronchi Alessandro , Verderio Paolo , Vitellaro Marco
Published: November 2024

Background

Familial adenomatous polyposis is a cancer-predisposing syndrome caused by germline pathogenic variants of the adenomatous polyposis coli gene, leading to numerous colorectal polyps and a high risk of colorectal cancer. Desmoid tumours have become significant in the management of familial adenomatous polyposis after a colectomy, yet the exact incidence remains undetermined due to a lack of dedicated surveillance.

Methods

This retrospective study accessed data from the prospectively maintained Hereditary Digestive Tumours Registry from 2000 to 2023. Desmoid-free survival was analysed using Cox regression and Kaplan–Meier curves.

Results

A total of 202 patients with familial adenomatous polyposis who underwent colorectal surgery were enrolled. Of the patients, 21 (10.4%) developed intra-abdominal desmoid tumours after surgery. Desmoid tumours were associated with surgical procedure, histology of cancer at the time of surgery, and family history of intra-abdominal desmoid tumours. The overall desmoid-free survival probability at a median follow-up of 84 months was 90%. Histology of cancer at the time of surgery (HR 0.25 (95% c.i. 0.10 to 0.59)), family history of intra-abdominal desmoid tumours (HR 2.92 (95% c.i. 1.22 to 6.97)), an open approach compared with a laparoscopic approach (HR 2.43 (95% c.i. 1.03 to 5.73)), and a proctocolectomy compared with a rectal-sparing total colectomy (HR 3.01 (95% c.i. 1.28 to 7.10)) emerged as significant prognostic factors affecting desmoid-free survival.

Conclusion

A minimally invasive rectal-sparing total colectomy appears protective against the development of desmoid tumours. Early surgery does not seem to increase desmoid tumour risk. A dedicated surveillance regimen for desmoid tumours in patients with familial adenomatous polyposis is needed to improve outcomes and quality of life.
Strengths-Based Screeners for K–8 Students: A Scoping Review
Authors: Nelson Tiffany , Raines James C
Published: November 2024

Students are increasingly experiencing social–emotional, behavioral, and mental health challenges. Although it is necessary to pinpoint students’ academic, social–emotional, and behavioral deficits, it is essential to focus on assessing the student’s strengths as a central component in intervention planning to improve student outcomes. A scoping review was conducted to identify rating scales recognized as strengths-based screeners in the literature for K–8 students and examine those scales based on 12 rating scale criteria. Four online databases and standard reference books were used to identify screeners in the literature from 1997 to 2024 that met the eligibility criteria. The RAND Education Assessment Finder was used to identify gray literature. The screeners found in the literature were examined using the 12 rating scale criteria. Research of the literature resulted in 110 sources reviewed. Twenty screeners were identified from the 46 sources screened for evidence, resulting in three scales that best met the criteria for a strengths-based screener: Social–Emotional Assets and Resilience Scales, Devereux Student Strengths Assessment-Mini, and Social Skills Improvement System Social and Emotional Learning Brief Scales. Many screeners are referred to as strengths-based but focus on student deficits. This scoping review synthesizes the literature, discusses gaps in knowledge, and highlights 12 rating scale criteria as one approach to identifying strengths-based brief screening tools. As a vital member of the school-based team, school social workers can assist in selecting strength-based screeners to enhance Tier 2 interventions and student outcomes.
C–C Motif chemokine receptor-2 blockade ameliorates pulmonary hypertension in rats and synergizes with a pulmonary vasodilator
Authors: Tsuboya Naoki , Sawada Hirofumi , Mitani Yoshihide , Oshita Hironori , Ohya Kazunobu , Takeoka Mami , Kabwe Jane Chanda , Miyasaka Yoshiki , Ito Hiromasa , Yodoya Noriko , Ohashi Hiroyuki , Maruyama Junko , Okamoto Ryuji , Mashimo Tomoji , Dohi Kaoru , Nishimura Yuhei , Maruyama Kazuo , Hirayama Masahiro
Published: November 2024

Aims

We investigated whether the disruption of C–C motif chemokine receptor (CCR) 2 may attenuate the development of pulmonary arterial hypertension (PAH) in any rat models with the reversal of the associated pro-inflammatory state and vascular dysfunction, and synergize with a conventional pulmonary vasodilator.

Methods and results

Using Ccr2(−/−) rats generated by CRISPR/Cas9, we investigated pulmonary hypertension (PH) in Ccr2(+/+) or Ccr2(−/−) rats treated with monocrotaline (MCT), SU5416/hypoxia (SuHx) and chronic hypoxia (CH). Ccr2(−/−) decreased the right ventricular systolic pressure, an index of right ventricular hypertrophy and mortality rate, and reversed increased expression of inflammatory cytokines/chemokines [interleukin-6, tumour necrosis factor-α, C–C motif chemokine receptor (CCL)-2, interleukin-1β, transforming growth factor-β] in rats 3weeks after MCT injection, but not in SuHx or CH models. Consistently, Ccr2(−/−) decreased indices of pulmonary vascular diseases (PVDs) and perivascular macrophage infiltration, as well as reversed impaired bone morphogenetic protein receptor type 2 signalling, increased endothelial apoptosis and impaired nitric oxide signalling and decreased phosphodiesterase-5 (PDE5) expression in lungs in MCT-treated rats. Gene expression of receptors for prostaglandin I2 and endothelin was not changed by Ccr2(−/−) in MCT-treated rats. In cultured pulmonary arterial smooth muscle cells (PASMCs), Ccr2(−/−) suppressed CCL2-induced hyperproliferation and dedifferentiation as well as reversed CCL2-induced decrease in PDE5 expression. The whole-genome RNA sequencing analysis identified differentially expressed genes in CCL2-stimulated Ccr2(−/−) PASMCs, which are related to the regulation of cellular differentiation and contraction. Based on studies in rats and cultured PASMCs, we investigated whether a PDE5 inhibitor, tadalafil, synergizes with Ccr2(−/−). Tadalafil administration ameliorated PH and PVDs in MCT-treated Ccr2(−/−) rats but not in Ccr2(+/+) rats. Tadalafil further improved survival in MCT-treated Ccr2(−/−) rats.

Conclusion

The present findings demonstrated that CCR2 disruption ameliorated PAH in MCT-treated rats, which was associated with the reversal of dysregulated inflammatory pathways and vascular dysfunction and synergized with tadalafil. These findings suggest that CCR2 may be a therapeutic target in intractable PAH patients with a certain CCR2-related inflammatory phenotype and refractory to conventional pulmonary vasodilators.
An infusion port for recurrent massive pericardial effusion: a case report
Authors: Zhao Yuechen , He Ying , Zou Fengwei , Hou Xiaofeng
Published: November 2024

Background

Patients with recurrent massive pericardial effusion are at risk of recurrent cardiac tamponade. The current standard of care includes repeat pericardiocentesis or pericardial window when recurrent effusions cause haemodynamic compromise. Here, we report a case of a patient in whom an infusion port was used for drainage of recurrent pericardial effusion. Patient was followed up for 10 months demonstrating convenience and safety of use without evidence of cardiac tamponade.

Case summary

We present a patient with recurrent massive pericardial effusion after previously undergoing two difficult pericardiocenteses of posteriorly located pericardial effusion causing tamponade. An infusion port was implanted and periodical follow-up and drainage through the port were performed. During follow-up, there was no evidence of tamponade caused by recurrence of pericardial effusion and no complications from the port.

Discussion

Pericardiocentesis can be challenging in certain circumstances such as loculated or posteriorly located pericardial effusion. For patients with recurrent effusion, there is an incremental risk of serious complications with every pericardiocentesis. This case illustrates the feasibility of using an infusion port in recurrent pericardial effusion. After subcutaneous implantation of the infusion port, repeat pericardiocentesis and its related complications were avoided. Later pericardial decompression and intrapericardial administration of medications were simple and safe by accessing the port top.
Influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism: a cohort study
Authors: Araujo-Castro Marta , Paja Fano Miguel , González-Boillos Marga , Pascual-Corrales Eider , Parra Ramírez Paola , Martín Rojas-Marcos Patricia , García-Cano Ana , Ruiz-Sanchez Jorge Gabriel , Vicente Almudena , Gómez-Hoyos Emilia , Casterás Ana , Puig-Perez Albert , García Sanz Iñigo , Recasens Mònica , Barahona San Millan Rebeca , Picón César María José , Díaz Guardiola Patricia , Perdomo Carolina , Manjón-Miguélez Laura , Rebollo Román Ángel , Robles Lázaro Cristina , María Recio José , Morales-Ruiz Manuel , Calatayud María , Jiménez López Noemi , Meneses Diego , Sampedro Nuñez Miguel , Ribas Elena Mena , Sanmartín Sánchez Alicia , Gonzalvo Diaz Cesar , Lamas Cristina , del Castillo Tous María , Serrano Joaquín , Michalopoulou Theodora , Tenes Rodrigo Susana , Roa Chamorro Ricardo , Jaén Aguila Fernando , Moya Mateo Eva María , Gutiérrez-Medina Sonsoles , Hanzu Felicia Alexandra
Published: November 2024

Aim

To evaluate the influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism (PA).

Methods

Multicentre retrospective study of patients with PA evaluated in 36 Spanish tertiary hospitals with available information on smoking habits [smokers and non-smokers (never smokers and ex-smokers)].

Results

A total of 881 patients were included, of whom 180 (20.4%) were classified as smokers and 701 as non-smokers. At diagnosis, smokers and non-smokers did not differ in blood pressure or serum potassium levels between. However, smokers had a higher prevalence of left ventricular hypertrophy (LVH) than non-smokers [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.23-3.25], and smokers were more likely to have severe LVH than non-smokers (12.5% vs 6.6%, P = .164). A larger mean tumour size of the adrenal nodule/s was observed in the smoking group (18.6 ± 9.66 vs 15.8 ± 8.66 mm, P = .002). In addition, the odds of mild autonomous cortisol secretion (MACS) was greater in smokers than in non-smokers (OR 2.1, 95% CI 1.14-4.06), but these differences disappeared when adjusted for the size of the adrenal nodule/s (adjusted OR 1.6, 95% CI 0.76-3.37). The rate of biochemical and hypertension cure was similar in both groups; however, hypertension cure tended to be more frequent in the non-smoker group (41.2% vs 29.9%, P = .076).

Conclusions

Patients with PA who smoke have a higher prevalence of LVH and MACS and larger adrenal nodule/s than non-smokers. Smoking has no significant effect on the probability of hypertension response after adrenalectomy in patients with PA; however, a tendency to a lower probability of hypertension cure is observed in smokers compared to non-smokers.
Secretin infusion decreases food intake in healthy men—a randomized, placebo-controlled, double-blind, crossover study
Authors: Heimbürger Sebastian M N , Bentzen Maria J , Kizilkaya Hüsün S , Hartmann Bolette , Holst Jens J , Rosenkilde Mette M , Dela Flemming , Hansen Svend H , Rehfeld Jens F , Christensen Mikkel B , Knop Filip K
Published: November 2024

Design

The hormone secretin, best known for regulating pH in the duodenum, has anorectic properties in mice proposedly mediated via secretin-induced brown adipose tissue (BAT) activation. We investigated the effects of exogenous secretin on ad libitum food intake, BAT activity, and postprandial physiology in healthy male volunteers.

Methods

In a randomized, placebo-controlled, double-blind, crossover study, 25 healthy men underwent two 5-h i.v. infusions of secretin (1 pmol/kg/min) and placebo (saline), respectively, with an interposed 2-month wash-out period. After 30 min of infusion, a standardized liquid-mixed meal was ingested, and after 5 h, food intake and meal duration were assessed during an ad libitum meal test. Brown adipose tissue activity was assessed regularly by thermal imaging-measured supraclavicular skin temperature.

Results

Compared with placebo, secretin significantly decreased ad libitum food intake by 173 ± 88 kcal (95% CI, 0.76-0.99, P = .039) but did not alter ad libitum meal duration. Secretin acutely decreased BAT activity but increased it postprandially compared with placebo. Acetaminophen-assessed gastric emptying was not affected by exogenous secretin, but secretin increased gallbladder volume, bile acid synthesis, and circulating levels of lipase, amylase, and triglycerides, while decreasing plasma Na+. Compared with placebo, secretin infusion was associated with 24.0 ± 10.8% (95% CI, 0.3-1, P = .025) more adverse events (headache, nausea, diarrhea, and vomiting).

Conclusions

In healthy men, secretin infusion decreased ad libitum food intake concomitantly with a postprandial increase in BAT activity as assessed by thermal imaging-measured supraclavicular skin temperature.

Clinical trial registration number

Clinicaltrials.gov, NCT04613700
Productivity and growth decomposition: a novel single-index smooth-coefficient stochastic frontier approach
Authors: Sun Kai , Kumbhakar Subal C , Lien Gudbrand
Published: November 2024

Our paper investigates productivity, output growth and total factor productivity (TFP) growth using a novel single-index smooth-coefficient stochastic frontier approach and two firm-level datasets respectively from the high technology (high-tech) manufacturing and Knowledge Intensive Business Services (KIBS) sectors in Norway. The approach considers input productivity and technical inefficiency to be flexible functions of production environmental variables indexed with unknown parameters for more precise estimation of marginal effects of these variables on the frontier and inefficiency. Output growth is decomposed into technical change (TC), input-driven component (IDC) and efficiency change (EC), while TFP growth is decomposed into TC, scale component and EC. The primary objective is to (i) maximise output through the frontier and efficiency channels and (ii) enhance productivity growth through such channels as technical progress and efficiency improvement, specifically tailored for the manufacturing and services industries. The empirical results reveal substantial heterogeneity in technology across firms. Overall speaking, geographical industrial concentration, export intensity and urbanisation positively influence output in both sectors. Technical progress contributes to TFP growth in both sectors; however, TC is biased towards capital in the high-tech sector and driven by labour in the KIBS sector. In addition to TC, TFP growth in the high-tech and KIBS sectors also benefits from EC and IDC, respectively.
Hiring intentions at the intersection of gender, parenthood, and social status. A factorial survey experiment in the UK labour market
Authors: Zamberlan Anna , Gioachin Filippo , Barbieri Paolo
Published: November 2024

Extant literature points to the gender, parenthood, and social status of job applicants as crucial factors influencing employers’ hiring preferences and behaviours. However, little is known about whether and to what extent the intersection of these attributes leads to specific forms of hiring discrimination. This study aims to fill this research gap by examining whether labour market (dis)advantages related to gender, parenthood, and social status occur in an additive or interactive relationship. We conducted a factorial survey experiment in which more than 2,500 UK-based individuals with recruiting experience rated the profiles of fictitious candidates for various job vacancies. We found significant and substantial discrimination against mothers, indicating the existence of a cumulative disadvantage between being a woman and having children, while high-status candidates were more favourably positioned, albeit with noteworthy differences depending on how social status was signalled. Most interestingly, the motherhood penalty was significantly reduced (up to almost half) for high-status candidates, suggesting a compensatory effect of signalling a high status. This novel evidence in the British context highlights the importance of examining the intersection of different dimensions of discrimination and inequality.
Genetic architecture underlying the parallel evolution of leaf ecomorphs in Viburnum
Authors: Moeglein Morgan K , Eaton Deren A R , Maya-Lastra Carlos A , Sweeney Patrick W , Dion Kirstin , Olson Mark E , Cacho N Ivalu , Donoghue Michael J , Edwards Erika J
Published: November 2024

In a neotropical lineage of the plant clade Viburnum (Adoxaceae) several leaf ecomorphs evolved independently and repeatedly as the group radiated through cloud forests of North and South America. Here, we focus on one pair of co-occurring sister species within this radiation with strongly contrasting leaf morphotypes and document the presence of phenotypically diverse and genetically admixed hybrid individuals in multiple hybrid swarms. Hybrid phenotypes are generally intermediate in form, but sometimes show parental or entirely novel and transgressive combinations of leaf traits, suggesting that parental leaf ecomorphs can be functionally and genetically dissociated. We used admixture mapping within hybrid swarms to investigate the genetic architecture of key traits comprising these leaf ecomorphs and uncovered loci proximal to known genes implicated in leaf development, including some that may alter multiple leaf traits simultaneously, potentially facilitating the emergence of leaf syndromes. We conclude that the shared genetic architecture underlying some traits, such as leaf size and marginal teeth, could promote the repeated evolution of these traits in concert, while low levels of genetic linkage between other leaf traits supports the hypothesis that selection promoted the repeated assembly of particular combinations of leaf traits as Viburnum radiated throughout the neotropics.
Juvenile and total reproductive values for sexual reproduction under any genetic system
Authors: Rautiala Petri , Lehtonen Jussi
Published: November 2024

Reproductive value (RV) is the expected contribution of genes by an individual or class of individuals to the gene pool in the distant future, and it plays a crucial role in understanding adaptation in long-term evolution. Class RVs are linked to the genetic system and to life history: for diploid genetics, Grafen derived expressions for relative RVs of female and male juveniles, and for the absolute RVs of all females and of all males. Subsequently, Gardner presented a derivation for relative RVs of juvenile females and males under haplodiploidy. Here we generalise these results to any genetic system for biparental sexual reproduction, such that RV is explicitly linked to parameters of the genetic system and life history. The earlier results by Grafen and Gardner arise as special cases. Finally, we derive expressions for absolute juvenile and total reproductive values of both sexes under any genetic system.
Bellymount-pulsed tracking: a novel approach for real-time in vivo imaging of Drosophila abdominal tissues
Authors: Balachandra Shruthi , Amodeo Amanda A
Published: November 2024

Quantitative live imaging is a valuable tool that offers insights into cellular dynamics. However, many fundamental biological processes are incompatible with current live-imaging modalities. Drosophila oogenesis is a well-studied system that has provided molecular insights into a range of cellular and developmental processes. The length of the oogenesis, coupled with the requirement for inputs from multiple tissues, has made long-term culture challenging. Here, we have developed Bellymount-pulsed tracking (Bellymount-PT), which allows continuous, noninvasive live imaging of Drosophila oogenesis inside the female abdomen for up to 16 h. Bellymount-PT improves upon the existing Bellymount technique by adding pulsed anesthesia with periods of feeding that support the long-term survival of flies during imaging. Using Bellymount-PT, we measure key events of oogenesis, including egg chamber growth, yolk uptake, and transfer of specific proteins to the oocyte during nurse cell dumping with high spatiotemporal precision within the abdomen of a live female.
Climate and health: a path to strategic co-financing?
Authors: Borghi Josephine , Cuevas Soledad , Anton Blanca , Iaia Domenico , Gasparri Giulia , Hanson Mark A , Soucat Agnès , Bustreo Flavia , Langlois Etienne V
Published: November 2024

Leveraging the co-benefits of investments in health and climate can be best achieved by moving away from isolated financing approaches and adopting co-financing strategies, which aim to improve the outcomes of both sectors. We propose a framework for studying co-financing for health and climate that considers the degree of integration between sector funding, and whether arrangements are ‘passive’, when cross-sectoral goals are indirectly affected, or ‘strategic’, when they are pre-emptively supported to build resilience and sustainability. We conducted a rigorous, evidence-focused review to describe co-financing mechanisms according to a framework, including the context in which they have been employed, and to identify enablers and barriers to implementation. We searched the international literature using Pubmed and Web of Science from 2013 to 2023, the websites of key health and climate agencies for grey literature and consulted with stakeholders. Our review underscores the significant impact of climate change and related hazards on government, health insurance and household health-related costs. Current evidence primarily addresses passive co-financing, reflecting the financial consequences of inaction. Strategic co-financing is under explored, as are integrative co-financing models demanding cross-sectoral coordination. Current instances of strategic co-financing lack sufficient funding to demonstrate their effectiveness. Climate finance, an under used resource for health, holds potential to generate additional revenue for health. Realizing these advantages necessitates co-benefit monitoring to align health, climate mitigation and adaptation goals, alongside stronger advocacy for the economic and environmental benefits of health investments. Strategic co-financing arrangements are vital at all system levels, demanding increased cross-sectoral collaboration, additional funding and skills for climate integration within health sector plans and budgets, and mainstreaming health into climate adaptation and mitigation plans. Supporting persistent health needs post-disasters, promoting adaptive social protection for health and climate risks, and disseminating best practices within and among countries are crucial, supported by robust evaluations to enhance progress.
Thinking politically about intersectoral action: Ideas, Interests and Institutions shaping political dimensions of governing during COVID-19
Authors: Baum Fran , Musolino Connie , Freeman Toby , Flavel Joanne , Ceukelaire Wim De , Chi Chunhuei , Dardet Carlos Alvarez , Falcão Matheus Zuliane , Friel Sharon , Gesesew Hailay Abrha , Giugliani Camila , Howden-Chapman Philippa , Huong Nguyen Thanh , Kim Sun , London Leslie , McKee Martin , Nandi Sulakshana , Paremoer Lauren , Popay Jennie , Serag Hani , Thiagarajan Sundararaman , Tangcharoensathien Viroj , Villar Eugenio
Published: November 2024

Our paper examines the political considerations in the intersectoral action that was evident during the SAR-COV-2 virus (COVID-19) pandemic through case studies of political and institutional responses in 16 nations (Australia, Belgium, Brazil, Ethiopia, India, New Zealand, Nigeria, Peru, South Africa, South Korea, Spain, Taiwan, Thailand, Vietnam, UK, and USA). Our qualitative case study approach involved an iterative process of data gathering and interpretation through the three Is (institutions, ideas and interests) lens, which we used to shape our understanding of political and intersectoral factors affecting pandemic responses. The institutional factors examined were: national economic and political context; influence of the global economic order; structural inequities; and public health structures and legislation, including intersectoral action. The ideas explored were: orientation of governments; political actors’ views on science; willingness to challenge neoliberal policies; previous pandemic experiences. We examined the interests of political leaders and civil society and the extent of public trust. We derived five elements that predict effective and equity-sensitive political responses to a pandemic. Firstly, effective responses have to be intersectoral and led from the head of government with technical support from health agencies. Secondly, we found that political leaders’ willingness to accept science, communicate empathetically and avoid ‘othering’ population groups was vital. The lack of political will was found in those countries stressing individualistic values. Thirdly, a supportive civil society which questions governments about excessive infringement of human rights without adopting populist anti-science views, and is free to express opposition to the government encourages effective political action in the interests of the population. Fourthly, citizen trust is vital in times of uncertainty and fear. Fifthly, evidence of consideration is needed regarding when people’s health must be prioritized over the needs of the economy. All these factors are unlikely to be present in any one country. Recognizing the political aspects of pandemic preparedness is vital for effective responses to future pandemics and while intersectoral action is vital, it is not enough in isolation to improve pandemic outcomes.
Equivariant Elliptic Cohomology, Toric Varieties, and Derived Equivalences
Authors: Scherotzke Sarah , Sibilla Nicolò
Published: November 2024

In this article we study the equivariant elliptic cohomology of complex toric varieties. We prove a reconstruction theorem showing that equivariant elliptic cohomology encodes considerable non-trivial information on the equivariant 1-skeleton of a toric variety $X$ (although it is not a complete invariant of its GKM graphs). We obtain a complete characterization of smooth and proper toric surfaces with isomorphic equivariant elliptic cohomology. Contrary to ordinary cohomology and K-theory, elliptic cohomology is expected not to be a derived invariant of algebraic varieties. We verify this prediction by showing that elliptic cohomology distinguishes derived equivalent varieties. More precisely, we show that there exist pairs of equivariantly derived equivalent toric varieties with non-isomorphic equivariant elliptic cohomology.
Treatment-related characteristics of communities in districts characterized by persistent trachoma: an exploratory descriptive study
Authors: Buda Dawit Seyum , Nkoane Naomi Lorrain , Netangaheni Thinavhuyo Robert
Published: November 2024

Background

Despite the implementation of surgery, antibiotics mass administration, facial cleanliness and environmental improvement, commonly known as the SAFE strategy for several years, the persistence and recrudescence of trachoma is a prevailing challenge in Ethiopia. This study explores the treatment-related characteristics of communities within districts characterized by persistent trachoma in southern Ethiopia.

Methods

Nyangatom and Uba Debretsehay districts are predominantly inhabited by pastoralist and farming communities, respectively. A community-based, exploratory descriptive qualitative study was conducted from June to October 2023. A total of 11 key informant interviews and six focus group discussions were conducted. The interviews and discussions were digitally recorded, transcribed and thematically analysed using Atlas ti. 23.

Results

Districts characterized by persistent trachoma are characterized by segments of populations that have never been treated or suboptimally treated. This is due to the competing priorities faced by providers, the nature of campaigns and the limited ability of logistics to reach the ‘must reach’ population. Other barriers include limited social support and terrain hindering full geographical and population coverage. Treatment slippage is of particular concern because of treatment fatigue, misinformation and the unavailability of treatments for routine care.

Conclusions

Communities in districts characterized by persistent and recrudescent trachoma face various socioecological barriers that impact the outcome of SAFE strategy implementation. A mix of both random and systematic omissions of people who need treatment most, such as children and women, was evident.
Cyber Diplomacy through Official Public Attribution: Paving the Way for Global Norms
Authors: Baram Gil
Published: November 2024

International discussions on establishing and implementing norms for behavior in cyberspace have spanned over two decades. However, differences in what constitutes ‘acceptable conduct’ have hindered progress in forming these norms. In recent years, Western countries have adopted a strategy to signal what is considered unacceptable behavior by publicly attributing cyberattacks and intrusions. I argue that this act of official public attribution serves as a practice for countries to express their disapproval of inappropriate cyberspace behavior and condemnation and can cumulatively shape international practices, holding the attacking state accountable. I explore this by (1) analyzing new data from the European Repository of Cyber Incidents, which shows patterns of official public attributions for the years 2000–2023, providing exploratory directions and trends, and (2) examining the Iranian cyberattack against Albania in 2022 and its subsequent official public attributions as an illustrative case study. I demonstrate how repeated instances of official public attribution can contribute to the development of a common practice that signals dissatisfaction of a specific behavior. As state-sponsored cyberattacks and intrusions are on the rise, this practice could have an accumulative effect.
Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy
Authors: Andreatta Kristen , Sax Paul E , Wohl David , D’Antoni Michelle L , Liu Hui , Hindman Jason T , Callebaut Christian
Published: November 2024

Objective

Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes.

Methods

Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA.

Results

Altogether, 2622 participants (B/F/TAF: n = 1306; DTG + 2 NRTIs: n = 1316) were categorized as having high (≥95%), intermediate (≥85% to <95%) or low (<85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA < 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (<95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF.

Conclusions

Participants with suboptimal (<85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS.
Parenteral aciclovir for suspected herpes simplex virus infection in children: 0–18 years
Authors: Berkhout Angela , Clark Julia E , Jones Cheryl A , Grimwood Keith , McMullan Brendan , Britton Philip N , Palasanthiran Pamela , Lim Selina , Yeoh Daniel K , Wong Shirley , Cheng Daryl R , Gwee Amanda , Cross Jack , Nguyen Tran , Jeffs Emma , Walls Tony , Mahony Michelle , Yan Jennifer , Nourse Clare
Published: November 2024

Background

Variations in neonatal aciclovir prescribing for suspected herpes simplex virus (HSV) disease are well-known, but there are limited data describing aciclovir prescribing in older children.

Methods

Medical records of neonates (≤28 days) and children (29 days to 18 years) prescribed intravenous aciclovir for suspected HSV disease (1 January 2019–12 December 2019) in eight Australian and New Zealand hospitals were reviewed. Prescribing indication, HSV testing, aciclovir prescription details, adverse events and discharge diagnosis were recorded.

Results

1426 received empirical aciclovir. For neonates (n = 425), the median duration was 1 day (IQR 1–3), 411/425 underwent HSV investigations and 13/425 had HSV disease (two with disseminated encephalitis, four with encephalitis and seven with skin, eye, mouth disease). Of the 1001 children, 906 were immunocompetent. 136/906 suspected of mucocutaneous disease received aciclovir for a median of 2 days (1–2), 121/136 underwent HSV testing, and 69/136 had proven disease. 770/906 received aciclovir for suspected disseminated disease or encephalitis for a median of 1 day (1–2), 556/770 underwent HSV testing, and 5/770 had disseminated disease or encephalitis. Among 95 immunocompromised children, 53/58 with suspected mucocutaneous disease had HSV testing and this was confirmed in 22. Disseminated disease or encephalitis was suspected in 37/95, HSV testing conducted in 23/37 and detected in one. The median aciclovir duration was 3 (2–7) days for immunocompromised children. Nephrotoxicity occurred in 7/1426 and 24/1426 had an extravasation injury.

Conclusion

Frequent and often unnecessary intravenous aciclovir prescribing for suspected HSV encephalitis or disseminated disease occurred in children, as evidenced by incomplete HSV investigations and only 5/770 older children having the diagnosis confirmed.
Spatio-temporal quasi-experimental methods for rare disease outcomes: the impact of reformulated gasoline on childhood haematologic cancer
Authors: Vega Sofia L , Nethery Rachel C
Published: November 2024

Although some pollutants emitted in vehicle exhaust, such as benzene, are known to cause leukaemia in adults with high exposure levels, less is known about the relationship between traffic-related air pollution (TRAP) and childhood haematologic cancer. In the 1990s, the US EPA enacted the reformulated gasoline program in select areas of the U.S., which drastically reduced ambient TRAP in affected areas. This created an ideal quasi-experiment to study the effects of TRAP on childhood haematologic cancers. However, existing methods for quasi-experimental analyses can perform poorly when outcomes are rare and unstable, as with childhood cancer incidence. We develop Bayesian spatio-temporal matrix completion methods to conduct causal inference in quasi-experimental settings with rare outcomes. Selective information sharing across space and time enables stable estimation, and the Bayesian approach facilitates uncertainty quantification. We evaluate the methods through simulations and apply them to estimate the causal effects of TRAP on childhood leukaemia and lymphoma.
EU Banking Law and Regulation
Authors: Lo Schiavo Gianni
Published: November 2024

The COVID-19 pandemic, Brexit, and the rise of Fintech are just a few factors driving the expansion in scope, tasks, and requirements European banking law has experienced over the last two decades. As such, European banks are now being regulated differently, and a new institutional and substantive supranational framework in EU law and policy has been established. Against this backdrop, this book provides a comprehensive, critical, and contextual account of a new supranational framework. The book reveals this burgeoning field by addressing it through various lenses: (i) institutionally, through the development such as the set-up of European frameworks for regulation, supervision, and restructuring of credit institutions, such as the SSM and SRM; (ii) substantially, with the creation of the Single Rulebook for banks, and (iii) theoretically, as this framework situates European banking policy as a substantive EU policy within European integration and harmonisation. Drawing on hard and soft law at EU banking regulation level, judgments of the European Court of Justice, and guidelines from the Basel Committee on Banking Supervision, the book covers supranational banking regulations, and the resulting financial and economic impact. The book provides tools for the interpretation on norms, procedures, and measures adopted by EU regulators and supervisory authorities.
Introduction
Authors: Lo Schiavo Gianni
Published: November 2024

This introductory chapter provides an overview of EU banking law and regulation. The development of EU banking regulation has been affected by three key factors. These include the regional implementation of the Basel Committee’s standards, setting the prudential framework for banks worldwide; the progressive harmonisation of financial services in Europe as part of the European agenda to integrate (financial) markets; and the supranational regulatory response posed to challenges arising from financial crises affecting Europe. This book argues that since the financial and euro crisis of 2008, banking regulation has developed as a substantially autonomous field of law and regulation in EU law. It analyses the level of European integration achieved by the European Banking Union and the Single Rulebook in banking. Ultimately, the book takes into account the intricacies of banking regulation as a technically complex area of the law and intends to structure the framework adopting a primarily supranational approach on rules applicable to banks.
The Definition and Role of Banks in EU Law and Policy
Authors: Lo Schiavo Gianni
Published: November 2024

This chapter outlines the overall framework of banks in the European Union (EU) and as regulated entities in EU law and policy. As financial service providers, banks are among the most important regulated entities and constitute an essential component of the European economy. The role of banks and the services they provide to markets are predominant when compared to other financial services providers in Europe. The chapter begins by looking at banks from a more general perspective and assessing their impact from different angles, namely the definition of banks in EU law and policy, the scope of activities, the role of banks, the strengths and challenges of banking in Europe, and the business models of banking. It then briefly examines the most important events in European regulation affecting banks, such as the regulatory efforts to address the pitfalls of the 2008 financial crisis and the creation of the European Banking Union.
EU Prudential Banking Regulation
Authors: Lo Schiavo Gianni
Published: November 2024

This chapter examines EU prudential banking law regulation and how it affects the existence and operations of banks in Europe. It focuses on the Capital Requirements Regulation (CRR) and the Capital Requirements Directive (CRD), which impose substantive rules for banks. These rules, together with other EU secondary law and hard and soft law rules existing in EU law, constitute the Single Rulebook for prudential rules of banks. These binding rules affect the internal structures of credit institutions and provide the basic requirements on capital, credit, market, and operational risks. These rules have been substantially changed mainly because of the regulatory response to the financial crisis and the standard-setting body activities undertaken in the last decade. The chapter then looks at the recent review to the CRR/CRD framework, which has recently been adopted in 2024.
EU Supervision of Banks
Authors: Lo Schiavo Gianni
Published: November 2024

This chapter assesses the rules of banking supervision for credit institutions in EU banking law and policy. It starts with a brief overview of the theories of supervision, distinguishing between the micro- and macro-levels. Micro-supervision refers to the surveillance of the profile and activities of individual market operators, particularly institutions with systemic relevance in the markets. Meanwhile, the level of macro-supervision refers to the analysis of trends and imbalances in the financial system as a whole and supervisory tools for that effect, with specific attention to systemic risk. The chapter then examines the institutional framework for banking supervision and looks at the rules and functioning of the different levels of supervision: prudential, anti-money laundering, market conduct, and deposit insurance. It focuses, in particular, on the rules on supervision provided in the Capital Requirements Directive and the Single Supervisory Mechanism as the supranational framework for prudential supervision where the European Central Bank directly supervises credit institutions.
A General Practice: Whose Practice? What Practice?
Authors: Wood Michael , Sender Omri
Published: November 2024

This chapter considers whose practice and what kinds of practice may be creative, or expressive, of customary international law. In so doing it considers the primary role of State practice and the possible contribution, in certain cases, of the practice of international organizations; it moreover explains that the conduct of other actors does not directly contribute to a general practice as a constituent element of customary international law (but may have an important indirect role by stimulating or recording the practice of States and international organizations). The chapter then provides an overview of the main forms of practice, including inaction, and discusses the question of confidential conduct. It also explains the importance of taking account of, and appreciating as a whole, all the available practice of the State (or organization) concerned. customary international law
Judicial Decisions and Teachings as Subsidiary Means for the Determination of Rules of Customary International Law
Authors: Wood Michael , Sender Omri
Published: November 2024

This chapter discusses the significance of judicial decisions and the teachings of publicists as subsidiary means for the determination of rules of customary international law. It explains that both judicial decisions and teachings have a special place among the materials to which recourse may be had in identifying customary international law, as is clear from Article 38.1(d) of the Statute of the International Court of Justice (ICJ). The chapter cautions that the value of judicial decisions and teachings as evidence of customary international law may vary greatly and provides guidance as to how their weight may be assessed. The place and role of the output of the International Law Commission (ILC) is considered in this regard as well. customary international law
Uniform lyndon interpolation for basic non-normal modal and conditional logics
Authors: Akbar Tabatabai Amirhossein , Iemhoff Rosalie , Jalali Raheleh
Published: November 2024

In this paper, a proof-theoretic method to prove uniform Lyndon interpolation (ULIP) for non-normal modal and conditional logics is introduced and applied to show that the logics, $\textsf{E}$, $\textsf{M}$, $\textsf{EN}$, $\textsf{MN}$, $\textsf{MC}$, $\textsf{K}$, and their conditional versions, $\textsf{CE}$, $\textsf{CM}$, $\textsf{CEN}$, $\textsf{CMN}$, $\textsf{CMC}$, $\textsf{CK}$, in addition to $\textsf{CKID}$ have that property. In particular, it implies that these logics have uniform interpolation (UIP). Although for some of them the latter is known, the fact that they have uniform LIP is new. Also, the proof-theoretic proofs of these facts are new, as well as the constructive way to explicitly compute the interpolants that they provide. On the negative side, it is shown that the logics $\textsf{CKCEM}$ and $\textsf{CKCEMID}$ enjoy UIP but not uniform LIP. Moreover, it is proved that the non-normal modal logics, $\textsf{EC}$ and $\textsf{ECN}$, and their conditional versions, $\textsf{CEC}$ and $\textsf{CECN}$, do not have Craig interpolation, and whence no uniform (Lyndon) interpolation.
AcrIIIA1 is a protein–RNA anti-CRISPR complex that targets core Cas and accessory nucleases
Authors: Chou-Zheng Lucy , Howell Olivia , Boyle Tori A , Hossain Motaher , Walker Forrest C , Sheriff Emma K , Aslan Barbaros , Hatoum-Aslan Asma
Published: November 2024

Clustered regularly-interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins protect bacteria and archaea from their viruses, and anti-CRISPRs (Acrs) are small virus-encoded proteins that inhibit CRISPR-Cas immunity. Over 80 families of Acrs have been described to date; however, only three of these subvert Type III CRISPR-Cas immunity. Type III systems employ a complex network of Cas and accessory nucleases to degrade viral nucleic acids. Here, we discover and characterize AcrIIIA1, the first Type III-A specific anti-CRISPR protein. We demonstrate that AcrIIIA1 binds to Csm2 within the Cas10-Csm effector complex and attenuates Cas10’s DNase activity and second messenger production. Additionally, AcrIIIA1 associates with fragmented t(m)RNAs (acrIIIA1-RNAs), and we show that they co-purify with the Cas10-Csm complex during phage infection. Although the precise role(s) of acrIIIA1-RNAs remain unclear, we found that they bind stably to RNase R, a host-encoded nuclease known to bolster immunity, and RNase R has the capacity to degrade them. Altogether, our results support a model in which AcrIIIA1 and its associated RNAs target both core Cas and accessory nucleases to provide robust protection against Type III CRISPR-Cas immunity.