bluuebunny/crossref_metadata_2025 huggingface dataset:
CArdiac MagnEtic resonance assessment of bi-Atrial fibrosis in secundum atrial septal defects patients: CAMERA-ASD study
Authors: O’Neill Louisa , Sim Iain , O’Hare Daniel , Whitaker John , Mukherjee Rahul K , Razeghi Orod , Niederer Steven , Wright Matthew , Chiribiri Amedeo , Frigiola Alessandra , O’Neill Mark D , Williams Steven E
Published: September 2021

Aims

Atrial septal defects (ASD) are associated with atrial arrhythmias, but the arrhythmia substrate in these patients is poorly defined. We hypothesized that bi-atrial fibrosis is present and that right atrial fibrosis is associated with atrial arrhythmias in ASD patients. We aimed to evaluate the extent of bi-atrial fibrosis in ASD patients and to investigate the relationships between bi-atrial fibrosis, atrial arrhythmias, shunt fraction, and age.

Methods and results

Patients with uncorrected secundum ASDs (n = 36; 50.4 ± 13.6 years) underwent cardiac magnetic resonance imaging with atrial late gadolinium enhancement. Comparison was made to non-congenital heart disease patients (n = 36; 60.3 ± 10.5 years) with paroxysmal atrial fibrillation (AF). Cardiac magnetic resonance parameters associated with atrial arrhythmias were identified and the relationship between bi-atrial structure, age, and shunt fraction studied. Bi-atrial fibrosis burden was greater in ASD patients than paroxysmal AF patients (20.7 ± 14% vs. 10.1 ± 8.6% and 14.8 ± 8.5% vs. 8.6 ± 6.1% for right and left atria respectively, P = 0.001 for both). In ASD patients, right atrial fibrosis burden was greater in those with than without atrial arrhythmias (33.4 ± 18.7% vs. 16.8 ± 10.3%, P = 0.034). On receiver operating characteristic analysis, a right atrial fibrosis burden of 32% had a 92% specificity and 71% sensitivity for predicting the presence of atrial arrhythmias. Neither age nor shunt fraction was associated with bi-atrial fibrosis burden.

Conclusion

Bi-atrial fibrosis burden is greater in ASD patients than non-congenital heart disease patients with paroxysmal AF. Right atrial fibrosis is associated with the presence of atrial arrhythmias in ASD patients. These findings highlight the importance of right atrial fibrosis to atrial arrhythmogenesis in ASD patients.
Primary care consultations for respiratory tract symptoms during the COVID-19 pandemic: a cohort study including 70,000 people in South West England
Authors: Dambha-Miller Hajira , Hounkpatin Hilda O , Morgan-Harrisskitt Jeffrey , Stuart Beth , Fraser Simon D S , Roderick Paul
Published: September 2021

Background

Primary care consultations for respiratory tract symptoms including identifying and managing COVID-19 during the pandemic have not been characterized.

Methods

A retrospective cohort analysis using routinely collected records from 70,431 adults aged 18+ in South England within the Electronic Care and Health Information Analytics (CHIA) database. Total volume and type of consultations (face-to-face, home visits, telephone, email/video, or out of hours) for respiratory tract symptoms between 1 January and 31 July 2020 (during the first wave of the pandemic) were compared with the equivalent period in 2019 for the same cohort. Descriptive statistics were used to summarize consultations by sociodemographic and clinical characteristics, and by COVID-19 diagnosis and outcomes (death, hospitalization, and pneumonia).

Results

Overall consultations for respiratory tract symptoms increased by 229% during the pandemic compared with the preceding year. This included significant increases in telephone consultations by 250%, a 1,574% increase in video/email consultations, 105% increase in home visits, and 92% increase in face-to-face consultations. Nearly 60% of people who presented with respiratory symptoms were tested for COVID-19 and 16% confirmed or clinically suspected to have the virus. Those with complications including pneumonia, requiring hospitalization, and who died were more likely to be seen in-person.

Conclusion

During the pandemic, primary care substantially increased consultations for respiratory tract symptoms to identify and manage people with COVID-19. These findings should be balanced against national reports of reduced GP workload for non-COVID care.
Frequent lineage-specific substitution rate changes support an episodic model for protein evolution
Authors: Prabh Neel , Tautz Diethard
Published: September 2021

Since the inception of the molecular clock model for sequence evolution, the investigation of protein divergence has revolved around the question of a more or less constant change of amino acid sequences, with specific overall rates for each family. Although anomalies in clock-like divergence are well known, the assumption of a constant decay rate for a given protein family is usually taken as the null model for protein evolution. However, systematic tests of this null model at a genome-wide scale have lagged behind, despite the databases’ enormous growth. We focus here on divergence rate comparisons between very closely related lineages since this allows clear orthology assignments by synteny and reliable alignments, which are crucial for determining substitution rate changes. We generated a high-confidence dataset of syntenic orthologs from four ape species, including humans. We find that despite the appearance of an overall clock-like substitution pattern, several hundred protein families show lineage-specific acceleration and deceleration in divergence rates, or combinations of both in different lineages. Hence, our analysis uncovers a rather dynamic history of substitution rate changes, even between these closely related lineages, implying that one should expect that a large fraction of proteins will have had a history of episodic rate changes in deeper phylogenies. Furthermore, each of the lineages has a separate set of particularly fast diverging proteins. The genes with the highest percentage of branch-specific substitutions are ADCYAP1 in the human lineage (9.7%), CALU in chimpanzees (7.1%), SLC39A14 in the internal branch leading to humans and chimpanzees (4.1%), RNF128 in gorillas (9%), and S100Z in gibbons (15.2%). The mutational pattern in ADCYAP1 suggests a biased mutation process, possibly through asymmetric gene conversion effects. We conclude that a null model of constant change can be problematic for predicting the evolutionary trajectories of individual proteins.
Deep learning for velocity model building with common-image gather volumes
Authors: Geng Zhicheng , Zhao Zeyu , Shi Yunzhi , Wu Xinming , Fomel Sergey , Sen Mrinal
Published: September 2021

Subsurface velocity model building is a crucial step for seismic imaging. It is a challenging problem for conventional methods such as full-waveform inversion (FWI) and wave equation migration velocity analysis (WEMVA), due to the highly nonlinear relationship between subsurface velocity values and seismic responses. In addition, traditional FWI and WEMVA methods are often computationally expensive. In this paper, we propose to apply a deep learning technique to construct subsurface velocity models automatically from common-image gather (CIG) volumes. In our method, pairs of synthetic velocity models and CIG volumes are generated to train a convolutional neural network. Our proposed network achieves promising results on different synthetic data sets. The training performance of several commonly used loss functions is also studied.
Priority setting and equity in COVID-19 pandemic plans: a comparative analysis of 18 African countries
Authors: Kapiriri Lydia , Kiwanuka Suzanne , Biemba Godfrey , Velez Claudia , Razavi S Donya , Abelson Julia , Essue Beverley M , Danis Marion , Goold Susan , Noorulhuda Mariam , Nouvet Elysee , Sandman Lars , Williams Iestyn
Published: September 2021

Priority setting represents an even bigger challenge during public health emergencies than routine times. This is because such emergencies compete with routine programmes for the available health resources, strain health systems and shift health-care attention and resources towards containing the spread of the epidemic and treating those that fall seriously ill. This paper is part of a larger global study, the aim of which is to evaluate the degree to which national COVID-19 preparedness and response plans incorporated priority setting concepts. It provides important insights into what and how priority decisions were made in the context of a pandemic. Specifically, with a focus on a sample of 18 African countries’ pandemic plans, the paper aims to: (1) explore the degree to which the documented priority setting processes adhere to established quality indicators of effective priority setting and (2) examine if there is a relationship between the number of quality indicators present in the pandemic plans and the country’s economic context, health system and prior experiences with disease outbreaks. All the reviewed plans contained some aspects of expected priority setting processes but none of the national plans addressed all quality parameters. Most of the parameters were mentioned by less than 10 of the 18 country plans reviewed, and several plans identified one or two aspects of fair priority setting processes. Very few plans identified equity as a criterion for priority setting. Since the parameters are relevant to the quality of priority setting that is implemented during public health emergencies and most of the countries have pre-existing pandemic plans; it would be advisable that, for the future (if not already happening), countries consider priority setting as a critical part of their routine health emergency and disease outbreak plans. Such an approach would ensure that priority setting is integral to pandemic planning, response and recovery.
Adaptation of the heart to frataxin depletion: evidence that integrated stress response can predominate over mTORC1 activation
Authors: Vásquez-Trincado César , Patel Monika , Sivaramakrishnan Aishwarya , Bekeová Carmen , Anderson-Pullinger Lauren , Wang Nadan , Tang Hsin-Yao , Seifert Erin L
Published: September 2021

Friedreich’s ataxia is an inherited disorder caused by depletion of frataxin (FXN), a mitochondrial protein required for iron–sulfur cluster (ISC) biogenesis. Cardiac dysfunction is the main cause of death. Yet pathogenesis, and, more generally, how the heart adapts to FXN loss, remains poorly understood, though it is expected to be linked to an energy deficit. We modified a transgenic (TG) mouse model of inducible FXN depletion that permits phenotypic evaluation of the heart at different FXN levels and focused on substrate-specific bioenergetics and stress signaling. When FXN protein in the TG heart was 17% of normal, bioenergetics and signaling were not different from control. When, 8 weeks later, FXN was ~ 97% depleted in the heart, TG heart mass and cardiomyocyte cross-sectional area were less, without evidence of fibrosis or apoptosis. mTORC1 signaling was activated, as was the integrated stress response, evidenced by greater phosphorylation of eIF2α relative to total eIF2α, and decreased protein translation. We interpret these results to suggest that, in TG hearts, an anabolic stimulus was constrained by eIF2α phosphorylation. Cardiac contractility was maintained in the 97% FXN-depleted hearts, possibly contributed by an unexpected preservation of β-oxidation, though pyruvate oxidation was lower. Bioenergetics alterations were matched by changes in the mitochondrial proteome, including a non-uniform decrease in abundance of ISC-containing proteins. Altogether, these findings suggest that the FXN-depleted heart can suppress a major ATP-demanding process such as protein translation, which, together with some preservation of β-oxidation, could be adaptive, at least in the short term.
Sarcospan increases laminin-binding capacity of α-dystroglycan to ameliorate DMD independent of Galgt2
Authors: Mamsa Hafsa , Stark Rachelle L , Shin Kara M , Beedle Aaron M , Crosbie Rachelle H
Published: September 2021

In Duchenne muscular dystrophy (DMD), mutations in dystrophin result in a loss of the dystrophin-glycoprotein complex (DGC) at the myofiber membrane, which functions to connect the extracellular matrix with the intracellular actin cytoskeleton. The dystroglycan subcomplex interacts with dystrophin and spans the sarcolemma where its extensive carbohydrates (matriglycan and CT2 glycan) directly interact with the extracellular matrix. In the current manuscript, we show that sarcospan overexpression enhances the laminin-binding capacity of dystroglycan in DMD muscle by increasing matriglycan glycosylation of α-dystroglycan. Furthermore, we find that this modification is not affected by loss of Galgt2, a glycotransferase, which catalyzes the CT2 glycan. Our findings reveal that the matriglycan carbohydrates, and not the CT2 glycan, are necessary for sarcospan-mediated amelioration of DMD. Overexpression of Galgt2 in the DMD mdx murine model prevents muscle pathology by increasing CT2 modified α-dystroglycan. Galgt2 also increases expression of utrophin, which compensates for the loss of dystrophin in DMD muscle. We found that combined loss of Galgt2 and dystrophin reduced utrophin expression; however, it did not interfere with sarcospan rescue of disease. These data reveal a partial dependence of sarcospan on Galgt2 for utrophin upregulation. In addition, sarcospan alters the cross-talk between the adhesion complexes by decreasing the association of integrin β1D with dystroglycan complexes. In conclusion, sarcospan functions to re-wire the cell to matrix connections by strengthening the cellular adhesion and signaling, which, in turn, increases the resilience of the myofiber membrane.
Combined effects of chronic PM2.5 exposure and habitual exercise on cancer mortality: a longitudinal cohort study
Authors: Bo Yacong , Yu Tsung , Chang Ly-Yun , Guo Cui , Lin Changqing , Zeng Yiqian , Huang Bo , Tam Tony , Lau Alexis K H , Wong Samuel Y S , Lao Xiang Qian
Published: September 2021

Background

Exercise may increase the inhalation and deposition of air pollutants, which may counteract its beneficial effects. We thus examined the combined effects of chronic exposure to fine particulate matter (PM2.5) and habitual exercise on the risk of death from cancer in Taiwan.

Patients and methods

A total of 384 128 adults (≥18 years of age) were recruited for a medical screening programme between 2001 and 2016, yielding 842 384 medical-examination records. All participants were followed up until 31 May 2019. Vital data were obtained from the National Death Registry of Taiwan and the ambient PM2.5 exposure was estimated using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. The time-dependent Cox-regression model was used to evaluate the combined effects.

Results

A greater amount of habitual exercise was associated with lower risk of death from cancer, whilst a higher level of PM2.5 exposure was associated with a higher risk of death from cancer. The inverse associations of habitual exercise with death from cancer were not modified by chronic exposure to PM2.5. The participants in the group with a high level of exercise and a low level of PM2.5 exposure exhibited a 35% lower risk of death from cancer than those in the group with a low level of exercise and a high level of PM2.5 exposure (95% confidence interval: 28%, 42%).

Conclusions

Increased levels of exercise and reduced exposure levels of PM2.5 are associated with a lower risk of death from cancer. Habitual exercise reduces the risk of death from cancer regardless of the levels of chronic PM2.5 exposure. Our results indicate that habitual exercise is a suitable health-promotion strategy even for people who reside in moderately polluted regions.
The Impact of Real-Time Whole-Genome Sequencing in Controlling Healthcare-Associated SARS-CoV-2 Outbreaks
Authors: Francis Rodric V , Billam Harriet , Clarke Mitch , Yates Carl , Tsoleridis Theocharis , Berry Louise , Mahida Nikunj , Irving William L , Moore Christopher , Holmes Nadine , Ball Jonathan K , Loose Matthew , McClure C Patrick ,   COVID-19 Genomics UK (COG-UK) consortium
Published: September 2021

Nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have severely affected bed capacity and patient flow. We utilized whole-genome sequencing (WGS) to identify outbreaks and focus infection control resources and intervention during the United Kingdom’s second pandemic wave in late 2020. Phylogenetic analysis of WGS and epidemiological data pinpointed an initial transmission event to an admission ward, with immediate prior community infection linkage documented. High incidence of asymptomatic staff infection with genetically identical viral sequences was also observed, which may have contributed to the propagation of the outbreak. WGS allowed timely nosocomial transmission intervention measures, including admissions ward point-of-care testing and introduction of portable HEPA14 filters. Conversely, WGS excluded nosocomial transmission in 2 instances with temporospatial linkage, conserving time and resources. In summary, WGS significantly enhanced understanding of SARS-CoV-2 clusters in a hospital setting, both identifying high-risk areas and conversely validating existing control measures in other units, maintaining clinical service overall.
Quantifying the Impact of COVID-19 Nonpharmaceutical Interventions on Influenza Transmission in the United States
Authors: Qi Yuchen , Shaman Jeffrey , Pei Sen
Published: September 2021

Background

Nonpharmaceutical interventions (NPIs) have been implemented to suppress transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence indicates that NPIs against coronavirus disease 2019 (COVID-19) may also have effects on transmission of seasonal influenza.

Methods

In this study, we use an absolute humidity-driven susceptible-infectious-recovered-susceptible (SIRS) model to quantify the reduction of influenza incidence and transmission in the United States and US Department of Health and Human Services regions after implementation of NPIs in 2020. We investigate long-term effect of NPIs on influenza incidence by projecting influenza transmission at the national scale over the next 5 years, using the SIRS model.

Results

We estimate that incidence of influenza A/H1 and B, which circulated in early 2020, was reduced by more than 60% in the United States during the first 10 weeks following implementation of NPIs. The reduction of influenza transmission exhibits clear geographical variation. After the control measures are relaxed, potential accumulation of susceptibility to influenza infection may lead to a large outbreak, the scale of which may be affected by length of the intervention period and duration of immunity to influenza.

Conclusions

Healthcare systems need to prepare for potential influenza patient surges and advocate vaccination and continued precautions.
From kolkHoz to pulpit: Rashida abïstay and female religious authority in Soviet and post-Soviet Russia
Authors: Garipova Rozaliya
Published: September 2021

This article focuses on the life and activities of Rashida Iskhaki, an ordinary Soviet woman from a kolkhoz near Kazan who became one of the most authoritative religious figures in Soviet and post-Soviet Tatarstan. Her path-breaking career demonstrates the development of the institution of female religious authority, abïstay, in post-WWII Russia and under the anti-religious Soviet regime. While the male religious elite was decimated before the war and remained under strict state control in the post-war period, women played a crucial role in the transmission of Islamic knowledge. Making use of public and private spaces Rashida Iskhaki developed into a full-fledged religious authority among the Muslims of Kazan. She contributed immensely to the formation of the female and male religious elite of early post-Soviet Russia. She and other women actively connected Muslims in and around the city of Kazan through home classes and majlises. The article suggests rethinking the dichotomies between ‘male’ and ‘female’ spheres, between ‘official’ and ‘unofficial’ Islam and argues that contemporary abïstays are very much a ‘Soviet phenomenon’, whose authority developed in the conditions of the Soviet regime and its collapse.
The chromatin remodelling ATPase BRAHMA interacts with GATA-family transcription factor GNC to regulate flowering time in Arabidopsis
Authors: Yang Jie , Xu Yingchao , Wang Jianhao , Gao Sujuan , Huang Yisui , Hung Fu-Yu , Li Tao , Li Qing , Yue Lin , Wu Keqiang , Yang Songguang
Published: September 2021

BRAHMA (BRM) is the ATPase of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodelling complex, which is indispensable for transcriptional inhibition and activation, associated with vegetative and reproductive development in Arabidopsis thaliana. Here, we show that BRM directly binds to the chromatin of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), which integrates multiple flowering signals to regulate floral transition, leading to flowering. In addition, genetic and molecular analysis showed that BRM interacts with GNC (GATA, NITRATE-INDUCIBLE, CARBON METABOLISM INVOLVED), a GATA transcription factor that represses flowering by directly repressing SOC1 expression. Furthermore, BRM is recruited by GNC to directly bind to the chromatin of SOC1. The transcript level of SOC1 is elevated in brm-3, gnc, and brm-3/gnc mutants, which is associated with increased histone H3 lysine 4 tri-methylation (H3K4Me3) but decreased DNA methylation. Taken together, our results indicate that BRM associates with GNC to regulate SOC1 expression and flowering time.
International Environmental Law
Authors: Rajamani Lavanya , Peel Jacqueline
Published: September 2021

This chapter provides an overview of international environmental law, which is the legal and regulatory framework devised by the community of sovereign states to address global environmental problems. These problems include the potential for runaway climate change, vanishing biodiversity, increasing freshwater scarcity, and severe degradation of marine resources and ocean ecosystems. In the last decade, international environmental law has acquired further breadth, depth, nuance, complexity, and reach. In particular, it is more deeply interconnected with policy and legal efforts in many other fields, including international trade and investment, human rights and migration, energy, disaster response, armed conflict, technology innovation and intellectual property protection. The chapter then explores and illustrates the ways in which international environmental law has evolved over the last decade. It highlights how the field has adapted to a changing geo-political context, as well as to the possibilities and limits of global regulation in addressing the complex, polycentric, and intractable nature of environmental harms.
Instrument Choice
Authors: Driesen David
Published: September 2021

This chapter addresses the problem of choosing environmental law instruments in international environmental law. It begins with a discussion of the various environmental protection instruments, such as environmental benefit trading, pollution taxes, subsidies, and traditional regulation. The chapter suggests that, for the most part, international environmental law has left the choice between traditional regulation and market-based instruments to nation-states. Efforts to create new international environmental law focus more upon forging agreement about goals than on how to achieve goals, since states play such a huge role in implementation and countries can achieve any given goal in a variety of ways. But some devices, which some experts treat as environmental instruments—such as subsidies, liability, and trade sanctions—more often become part of international environmental law. The chapter then discusses the extent to which the desire for international environmental benefit trading has driven a departure from the norm of leaving the choice between market mechanisms and traditional standards to implementing polities.
Economics
Authors: Faure Michael
Published: September 2021

This chapter explains that the starting point for the economic approach to both domestic as well as international environmental law is that environmental problems (including but not limited to environmental pollution) constitute a market failure. From this economic perspective transboundary environmental pollution emerges. Moreover, global environmental quality is, from an economic perspective, a so-called public good of which all states will benefit. But since no state can exclude others from benefitting from this global environmental good, there is a danger of ‘free-riding’ as a result of which this global public good (environmental quality) may be insufficiently produced. These starting points provide a basis for the emergence of international environmental law, more particularly treaty law. However, a classic paradigm in what has become known as the law and economics literature is the Coase Theorem. The chapter then addresses the likelihood of Coasean solutions to emerge as a remedy to transboundary environmental pollution. It also looks at reasons for states to conclude treaties.
The Role of Science
Authors: Johnston Sam
Published: September 2021

This chapter reflects on the crucial and multifaceted role of science in international environmental law, identifying and framing its challenges, threats, and problems. The role of science in international environmental law has been the subject of vigorous debate, focusing around competing claims concerning the need for action in almost every area of environmental regulation, such as climate change, restrictions on use of areas or resources such as fisheries, and restrictions on ‘dangerous’ substances such as genetically modified organisms (GMOs). The developing jurisprudence on the role of science in international environmental law articulated by various international tribunals such as the International Court of Justice (ICJ) highlights the important role that science plays in this field. The chapter then considers how science has influenced international environmental law and in turn, how international environmental law has contributed to the promotion of science. An emerging issue highlighted in the chapter is the increasing politicization of science and the need to understand the limitations of science.
Differentiation
Authors: Cullet Philippe
Published: September 2021

This chapter explores differential treatment, which is one of the main instruments that exist in international environmental law to foster equity. It builds on ideas of global distributive justice and helps to rebalance some of the most visible inequalities arising between formally equal states of very different size, power, and natural resource endowments. The principle that reflects differential treatment in international environmental law is that of common but differentiated responsibilities (CBDR). The chapter discusses the conceptual bases for and development of differential treatment. This confirms the significance of the break proposed to the traditional international legal framework and explains the continuing opposition to differential treatment by some countries. The chapter then highlights the different manifestations of differential treatment in international environmental law and shows that differential treatment pervades the whole field. It also looks at some of the critiques of differentiation and the forms of differential treatment that have evolved over the past couple of decades.
Good Faith
Authors: Shibata Akiho
Published: September 2021

This chapter studies the principle of good faith, which has been declared by the International Court of Justice (ICJ) as ‘a well-established principle of international law’. Through judicial pronouncements and state practice, it has come to acquire concrete legal content. The principle of good faith is closely linked to the concept of legal security; it provides certainty and foreseeability in society, and as such is fundamental and necessary to any legal system. The chapter examines the role that the principle of good faith could play, first, in general international law relating to the environment, focusing on three broad areas of environmental treaty performance, environmental cooperation, and due diligence. It then considers the more concrete role that the principle of good faith could play within multilateral environmental agreements (MEAs) as special legal regimes. Finally, the chapter analyses two concrete contexts within which the principle of good faith could be engaged to perform specific normative functions in the operation of MEAs, namely in non-compliance and ‘pledge and review’ mechanisms.
Business and Industry
Authors: Richardson Benjamin J. , Sjåfjell Beate
Published: September 2021

This chapter studies how, in the study of international environmental law, business corporations are typically viewed as actors under the auspices of various regulatory regimes developed by nation-states, or recognized as having some tacit influence over the agenda setting and implementation of such regimes. This perspective might also acknowledge the limited accountability of corporations under international law. Another perspective is the business sector's initiative in shaping its own environmental agenda, often in the name of ‘corporate social responsibility’ (CSR). The chapter then surveys the role of corporate law and corporate governance in shaping environmental performance, and introduces the goals, mechanisms, and actors of the global CSR movement. It examines the governance of business in international environmental law, including corporate liability for wrongdoing. The chapter also looks at examples of new forms of multi-stakeholder environmental collaboration involving the business sector.
India, Bangladesh, and Pakistan
Authors: Ghosh Shibani
Published: September 2021

This chapter focuses on international environmental law (IEL) in the courts of India, Bangladesh, and Pakistan. Review of the case law reveals that Indian courts have led the adoption of the IEL principles in this region, with occasional references to IEL by Bangladeshi and Pakistani courts. This appears to follow the trend of non-environmental cases, where also the Bangladeshi and Pakistani judiciary is more reluctant than the Indian courts to turn to international law. Although courts in the three countries have engaged with IEL, it has mostly been at a superficial level. Their reliance on IEL is not always accompanied by strong judicial reasoning, making it difficult to determine their content and scope, and even their relevance in particular scenarios. Given development imperatives in these countries, courts are often faced with the ‘economy/development versus environment’ question. In such situations, the courts rely on IEL in an instrumental fashion in support of the final outcome of the case, rather than engaging with the substantive content of the IEL principle.
The natural occurring Y129F polymorphism in Rhizopus oryzae (R. arrhizus) Cyp51Ap accounts for its intrinsic voriconazole resistance
Authors: Macedo Daiana , Leonardelli Florencia , Cabeza Matias S , Gamarra Soledad , Garcia-Effron Guillermo
Published: September 2021

Rhizopus oryzae (heterotypic synonym: R. arrhizus) intrinsic voriconazole and fluconazole resistance has been linked to its CYP51A gene. However, the amino acid residues involved in this phenotype have not yet been established. A comparison between R. oryzae and Aspergillus fumigatus Cyp51Ap sequences showed differences in several amino acid residues. Some of them were already linked with voriconazole resistance in A. fumigatus. The objective of this work was to analyze the role of two natural polymorphisms in the intrinsic voriconazole resistance phenotype of R. oryzae (Y129F and T290A, equivalent to Y121F and T289A seen in triazole-resistant A. fumigatus). We have generated A. fumigatus chimeric strains harboring different R. oryzae CYP51A genes (wild-type and mutants). These mutant R. oryzae CYP51A genes were designed to carry nucleotide changes that produce mutations at Cyp51Ap residues 129 and 290 (emulating the Cyp51Ap protein of azole susceptible A. fumigatus). Antifungal susceptibilities were evaluated for all the obtained mutants. The polymorphism T290A (alone or in combination with Y129F) had no impact on triazole MIC. On the other hand, a > 8-fold decrease in voriconazole MICs was observed in A. fumigatus chimeric strains harboring the RoCYP51Ap-F129Y. This phenotype supports the assumption that the naturally occurring polymorphism Y129F at R. oryzae Cyp51Ap is responsible for its voriconazole resistance phenotype. In addition, these chimeric mutants were posaconazole hypersusceptible. Thus, our experimental data demonstrate that the RoCYP51Ap-F129 residue strongly impacts VRC susceptibility and that it would be related with posaconazole-RoCYP51Ap interaction.

Lay summary

Rhizopus oryzae is intrinsically resistant to voriconazole, a commonly used antifungal agent. In this work, we analyze the role of two natural polymorphisms present in the target of azole drugs. We established that F129 residue is responsible of the intrinsic voriconazole resistance in this species.
A 15.5 GHz detection of the galaxy cluster minihalo in RXJ1720.1+2638
Authors: Perrott Yvette C , Carvalho Pedro , Elwood Patrick J , Grainge Keith J B , Green David A , Javid Kamran , Jin Terry Z , Rumsey Clare , Saunders Richard D E
Published: September 2021

RXJ1720.1+2638 is a cool-core, ‘relaxed-appearing’ cluster with a minihalo previously detected up to 8.4 GHz, confined by X-ray-detected cold fronts. We present observations of the minihalo at 13–18 GHz with the Arcminute Microkelvin Imager telescope, simultaneously modelling the Sunyaev–Zel’dovich signal of the cluster in conjunction with Planck and Chandra data in order to disentangle the non-thermal emission of the minihalo. We show that the previously reported steepening of the minihalo emission at 8.4 GHz is not supported by the AMI data and that the spectrum is consistent with a single power law up to 18 GHz. We also show the presence of a larger scale component of the minihalo extending beyond the cold fronts. Both of these observations could be explained by the ‘hadronic’ or ‘secondary’ mechanism for the production of relativistic electrons, rather than the currently favoured ‘re-acceleration’ mechanism and/or multiple episodes of jet activity from the active galactic nucleus in the brightest cluster galaxy.
Streamlined CRISPR genome engineering in wild-type bacteria using SIBR-Cas
Authors: Patinios Constantinos , Creutzburg Sjoerd C A , Arifah Adini Q , Adiego-Pérez Belén , Gyimah Evans A , Ingham Colin J , Kengen Servé W M , van der Oost John , Staals Raymond H J
Published: September 2021

CRISPR-Cas is a powerful tool for genome editing in bacteria. However, its efficacy is dependent on host factors (such as DNA repair pathways) and/or exogenous expression of recombinases. In this study, we mitigated these constraints by developing a simple and widely applicable genome engineering tool for bacteria which we termed SIBR-Cas (Self-splicing Intron-Based Riboswitch-Cas). SIBR-Cas was generated from a mutant library of the theophylline-dependent self-splicing T4 td intron that allows for tight and inducible control over CRISPR-Cas counter-selection. This control delays CRISPR-Cas counter-selection, granting more time for the editing event (e.g. by homologous recombination) to occur. Without the use of exogenous recombinases, SIBR-Cas was successfully applied to knock-out several genes in three wild-type bacteria species (Escherichia coli MG1655, Pseudomonas putida KT2440 and Flavobacterium IR1) with poor homologous recombination systems. Compared to other genome engineering tools, SIBR-Cas is simple, tightly regulated and widely applicable for most (non-model) bacteria. Furthermore, we propose that SIBR can have a wider application as a simple gene expression and gene regulation control mechanism for any gene or RNA of interest in bacteria.
Impact of social contacts on SARS-CoV-2 exposure among healthcare workers
Authors: Emecen A N , Keskin S , Boncukcu Eren E , Yildirim Ustuner B , Celik S G , Suner A F , Sezgin E , Siyve N , Basoglu Sensoy E , Tutal Altas E , Demiral Y
Published: September 2021

Background

Healthcare workers (HCWs) have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. Strict measures generally focus on the patient-to-HCW contacts. However, interactions between the HCWs also pose a high risk for SARS-CoV-2 exposure.

Aims

This study was aimed to investigate the effect of social contacts on the level of SARS-CoV-2 exposure risk among workers by broadening the current risk assessment algorithm.

Methods

Contact tracing records of the workers in a large university hospital between 19th March and 31st December 2020 were analysed. Multivariate conditional logistic regression models were estimated to evaluate factors associated with high-risk exposure for contacts among workers.

Results

Of the 329 exposed clusters, 260 (79%) were HCW-to-HCW contacted clusters. High-risk exposure was higher in the HCW-to-HCW contacts (44%), when compared to the patient-to-HCW contacts (5%) (P < 0.001). A total of 1827 HCWs contacted a laboratory-confirmed COVID-19-positive co-worker. Among the HCW-to-HCW contacts, high-risk exposure was higher in the support staff (49%, P < 0.001), in non-patient care settings (47%, P < 0.001) and in the social contacts (57%, P < 0.001). Social contacts between workers increased the high-risk exposure (adjusted odds ratio: 3.50, 95% confidence interval 2.62–4.69) in multivariate analysis.

Conclusions

A significant association between social contacts among workers and high-risk exposure of SARS-CoV-2 was observed. The results of the study emphasize the need for policies regarding the improved protection of HCWs in social settings in addition to patient care services.
Uniform Mortgage Regulation and Distortion in Capital Allocation
Authors: Zhang Tim
Published: September 2021

The federal mortgage policy, the conforming loan limit (CLL), was spatially uniform before the 2008 crisis, despite remarkable heterogeneity across geography. I show that in areas that experienced a larger decline in the jumbo loan share following an increase in the CLL, lenders raised jumbo loan approval rates, lowered mortgage rates to defend short-term market share, extended credit to riskier borrowers, and incurred deteriorated asset quality in the long run. This result is not explained away by credit supply or demand changes, the bunching effect, or reverse causality. Instead, my evidence is consistent with a competition channel: the effect of CLL increases on jumbo loan credit expansion is significantly exaggerated in a more competitive jumbo-lending market. Overall, my findings suggest that the securitization policies of the government-sponsored enterprises can induce spillovers on the jumbo market segment and influence credit allocation.
Forward Guidance and Corporate Lending
Authors: Delis Manthos D , Hong Sizhe , Paltalidis Nikos , Philip Dennis
Published: September 2021

We suggest that forward guidance, via publicly committing the central bank to future actions and creating associated expectations, fundamentally affects bank lending decisions independently of other forms of monetary policy. To test this hypothesis, we build a forward guidance measure based on the language used in the Federal Open Market Committee meetings and match this measure with syndicated loans. Our results show that expansionary forward guidance decreases corporate loan spreads and that this effect is stronger for well-capitalized banks lending to riskier firms. Forward guidance also affects nonprice lending terms, such as covenants, performance pricing provisions, and the loan syndicate structure. Additionally, banks tend to initiate new lending relationships with lower spreads after forward guidance issuance.
Varieties of Sugar Dating in Sweden: Content, Compensation, Motivations
Authors: Gunnarsson Lena , Strid Sofia
Published: September 2021

With the emergence and global proliferation of “sugar dating” websites, the phenomenon of sugar dating is increasingly on the public agenda. Sugar dating is described by these sites as dating arrangements based on an exchange of intimacy and companionship for financial or other forms of support. Given that sex is often part of the arrangements, claims are widespread, yet disputed, that sugar dating is a form of prostitution. Based on interviews and a survey questionnaire, this article maps the practice of heterosexual sugar dating in Sweden as described by “sugar babies” and “sugar daddies” themselves. It shows a striking diversity in regard to what sugar dating means for participants, both in terms of what they do when sugar dating and in terms of how money and/or other material goods are involved in arrangements. A further key difference between sugar dating arrangements is whether “sugar babies” enter them for purely instrumental reasons or enjoy them in and of themselves. Although not all kinds of sugar dating include sex, we argue that sugar dating sites should be seen as key actors in the expansion of the sex (and intimacy) industry, drawing on and articulating pre-existing tendencies within it.
Moving Toward a Functional Cure for HIV-1
Authors: Kang Wen , Sun Yongtao
Published: September 2021

Despite the recent success of suppressing human immunodeficiency virus 1 (HIV-1) replication in the peripheral blood with antiretroviral therapy, elimination of the provirus from infected cells remains challenging because the virus can integrate into the host genome and become a latent proviral reservoir. The removal of these latent viral reservoirs from tissue containing infected resting memory CD4+ T cells remains a major barrier to developing a cure for HIV-1. Several novel strategies have recently been developed for curing HIV infection. These include stem cell transplantation with CCR5-Δ32 mutated cells, initial antiretroviral treatment in the very early stage of HIV infection, gene editing to excise the HIV genome or generate CCR5-mutated HIV-1-resistant cells, “shock-and-kill” to reactivate latent HIV using latency reversal agents combined with enhanced immune clearance methods, and an emerging “block-and-lock” strategy to reactivate latent HIV using latency reversal agents combined with enhanced immune clearance methods. However, the high risks and limitations to scale-up in clinics, as well as poor performance in clinical trials, have hampered these efforts. This review aims to describe the present efforts that are being made to combat HIV latency, and critically discuss the limitations and future of the cure for HIV-1.
Chlorhexidine and other alternatives for povidone–iodine in ophthalmic surgery: review of comparative studies
Authors: Kanclerz Piotr , Myers William G.
Published: September 2021

Povidone–iodine (PVI) is a universally accepted antiseptic agent used in ophthalmic surgery. Insufficient antisepsis in patients with self-reported allergies to iodine has led to devastating complications. The aim of this study was to review the current evidence for alternatives to PVI in ocular surgery. Aqueous chlorhexidine has been used as a primary antiseptic agent in Sweden for several years and has proven efficiency and safety; in a study of a large series of intravitreal injections in Australia, the endophthalmitis rates were similar to those after the use of PVI. The evidence related to using other disinfectants such as picloxydine, hypochlorous acid solution, and polyhexanide is scarce. Single studies have shown lower patient discomfort after conjunctival lavage with chlorhexidine or hypochlorous acid than with PVI. No evidence was found to suggest changing from PVI to other antiseptic agents. Disinfectant solutions other than PVI or chlorhexidine will require further investigations to show their utility in ocular surgery.
Clinical features of endophthalmitis clusters after cataract surgery and practical recommendations to mitigate risk: systematic review
Authors: Park Jeff , Popovic Marko M. , Balas Michael , El-Defrawy Sherif R. , Alaei Ravin , Kertes Peter J.
Published: September 2021

Intraocular transmission of exogenous pathogens in cataract surgery can lead to endophthalmitis. This review evaluates the features of endophthalmitis clusters secondary to pathogen transmission in cataract surgery. Articles reporting on pathogen transmission in cataract surgery were identified via searches of Ovid MEDLINE, EMBASE, and Cochrane CENTRAL, and a total of 268 eyes from 24 studies were included. The most common source of infectious transmission was attributed to a contaminated intraocular solution (ie, irrigation solution, viscoelastic, or diluted antibiotic; n = 10). Visual acuity at presentation with infectious features was 1.89 logMAR (range: 1.35 to 2.58; ∼counting fingers) and 1.33 logMAR (range: 0.04 to 3.00; Snellen: ∼20/430) at last follow-up. Patients with diabetes had worse outcomes compared with patients without diabetes. The most frequently isolated pathogen from the infectious sources was Pseudomonas sp. (50.0%). This review highlights the various routes of pathogen transmission during cataract surgery and summarizes recommendations for the detection, prevention, and management of endophthalmitis clusters.
Measuring pain care quality in the Veterans Health Administration primary care setting
Authors: Luther Stephen L. , Finch Dezon K. , Bouayad Lina , McCart James , Han Ling , Dobscha Steven K. , Skanderson Melissa , Fodeh Samah J. , Hahm Bridget , Lee Allison , Goulet Joseph L. , Brandt Cynthia A. , Kerns Robert D.
Published: September 2021

The lack of a reliable approach to assess quality of pain care hinders quality improvement initiatives. Rule-based natural language processing algorithms were used to extract pain care quality (PCQ) indicators from documents of Veterans Health Administration primary care providers for veterans diagnosed within the past year with musculoskeletal disorders with moderate-to-severe pain intensity across 2 time periods 2013 to 2014 (fiscal year [FY] 2013) and 2017 to 2018 (FY 2017). Patterns of documentation of PCQ indicators for 64,444 veterans and 124,408 unique visits (FY 2013) and 63,427 veterans and 146,507 visits (FY 2017) are described. The most commonly documented PCQ indicators in each cohort were presence of pain, etiology or source, and site of pain (greater than 90% of progress notes), while least commonly documented were sensation, what makes pain better or worse, and pain's impact on function (documented in fewer than 50%). A PCQ indicator score (maximum = 12) was calculated for each visit in FY 2013 (mean = 7.8, SD = 1.9) and FY 2017 (mean = 8.3, SD = 2.3) by adding one point for every indicator documented. Standardized Cronbach alpha for total PCQ scores was 0.74 in the most recent data (FY 2017). The mean PCQ indicator scores across patient characteristics and types of healthcare facilities were highly stable. Estimates of the frequency of documentation of PCQ indicators have face validity and encourage further evaluation of the reliability, validity, and utility of the measure. A reliable measure of PCQ fills an important scientific knowledge and practice gap.