bluuebunny/crossref_metadata_2025 huggingface dataset:
CLoNe: automated clustering based on local density neighborhoods for application to biomolecular structural ensembles
Authors: Träger Sylvain , Tamò Giorgio , Aydin Deniz , Fonti Giulia , Audagnotto Martina , Dal Peraro Matteo
Published: August 2020

Motivation

Proteins are intrinsically dynamic entities. Flexibility sampling methods, such as molecular dynamics or those arising from integrative modeling strategies, are now commonplace and enable the study of molecular conformational landscapes in many contexts. Resulting structural ensembles increase in size as technological and algorithmic advancements take place, making their analysis increasingly demanding. In this regard, cluster analysis remains a go-to approach for their classification. However, many state-of-the-art algorithms are restricted to specific cluster properties. Combined with tedious parameter fine-tuning, cluster analysis of protein structural ensembles suffers from the lack of a generally applicable and easy to use clustering scheme.

Results

We present CLoNe, an original Python-based clustering scheme that builds on the Density Peaks algorithm of Rodriguez and Laio. CLoNe relies on a probabilistic analysis of local density distributions derived from nearest neighbors to find relevant clusters regardless of cluster shape, size, distribution and amount. We show its capabilities on many toy datasets with properties otherwise dividing state-of-the-art approaches and improves on the original algorithm in key aspects. Applied to structural ensembles, CLoNe was able to extract meaningful conformations from membrane binding events and ligand-binding pocket opening as well as identify dominant dimerization motifs or inter-domain organization. CLoNe additionally saves clusters as individual trajectories for further analysis and provides scripts for automated use with molecular visualization software.

Availability and implementation

www.epfl.ch/labs/lbm/resources, github.com/LBM-EPFL/CLoNe.

Supplementary information

Supplementary data are available at Bioinformatics online.
Immune correlates analysis using vaccinees from test negative designs
Authors: Follmann Dean A , Dodd Lori
Published: August 2020

Determining the effect of vaccine-induced immune response on disease risk is an important goal of vaccinology. Typically, immune correlates analyses are conducted prospectively with immune response measured shortly after vaccination and subsequent disease status regressed on immune response. In outbreaks and rare disease settings, collecting samples from all vaccinees is not feasible. The test negative design is a retrospective design used to measure vaccine efficacy where symptomatic individuals who present at a clinic are assessed for relevant disease (cases) or some other disease (controls) and vaccination status ascertained. This article proposes that test negative vaccinees have immune response to vaccine assessed both for relevant (e.g., Ebola) and irrelevant (e.g., vector) proteins. If the latter immune response is unaffected by active (Ebola) infection, and is correlated with the relevant immune response, it can serve as a proxy for the immune response of interest proximal to infection. We show that logistic regression using imputed immune response as the covariate and case disease as outcome can estimate the prospective immune response slope and detail the assumptions needed for unbiased inference. The method is evaluated by simulation under various scenarios including constant and decaying immune response. A simulated dataset motivated by ring vaccination for an ongoing Ebola outbreak is analyzed.
Individual Differences in Intrinsic Brain Networks Predict Symptom Severity in Autism Spectrum Disorders
Authors: Pua Emmanuel Peng Kiat , Thomson Phoebe , Yang Joseph Yuan-Mou , Craig Jeffrey M , Ball Gareth , Seal Marc
Published: August 2020

The neurobiology of heterogeneous neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) is still unknown. We hypothesized that differences in subject-level properties of intrinsic brain networks were important features that could predict individual variation in ASD symptom severity. We matched cases and controls from a large multicohort ASD dataset (ABIDE-II) on age, sex, IQ, and image acquisition site. Subjects were matched at the individual level (rather than at group level) to improve homogeneity within matched case–control pairs (ASD: n = 100, mean age = 11.43 years, IQ = 110.58; controls: n = 100, mean age = 11.43 years, IQ = 110.70). Using task-free functional magnetic resonance imaging, we extracted intrinsic functional brain networks using projective non-negative matrix factorization. Intrapair differences in strength in subnetworks related to the salience network (SN) and the occipital-temporal face perception network were robustly associated with individual differences in social impairment severity (T = 2.206, P = 0.0301). Findings were further replicated and validated in an independent validation cohort of monozygotic twins (n = 12; 3 pairs concordant and 3 pairs discordant for ASD). Individual differences in the SN and face-perception network are centrally implicated in the neural mechanisms of social deficits related to ASD.
Aging Modulates Prefrontal Plasticity Induced by Executive Control Training
Authors: Najberg Hugo , Wachtl Laura , Anziano Marco , Mouthon Michael , Spierer Lucas
Published: August 2020

While declines in inhibitory control, the capacity to suppress unwanted neurocognitive processes, represent a hallmark of healthy aging, whether this function is susceptible to training-induced plasticity in older populations remains largely unresolved. We addressed this question with a randomized controlled trial investigating the changes in behavior and electrical neuroimaging activity induced by a 3-week adaptive gamified Go/NoGo inhibitory control training (ICT). Performance improvements were accompanied by the development of more impulsive response strategies, but did not generalize to impulsivity traits nor quality of life. As compared with a 2-back working-memory training, the ICT in the older adults resulted in a purely quantitative reduction in the strength of the activity in a medial and ventrolateral prefrontal network over the 400 ms P3 inhibition-related event-related potentials component. However, as compared with young adults, the ICT induced distinct configurational modifications in older adults’ 200 ms N2 conflict monitoring medial–frontal functional network. Hence, while older populations show preserved capacities for training-induced plasticity in executive control, aging interacts with the underlying plastic brain mechanisms. Training improves the efficiency of the inhibition process in older adults, but its effects differ from those in young adults at the level of the coping with inhibition demands.
Predicting the fMRI Signal Fluctuation with Recurrent Neural Networks Trained on Vascular Network Dynamics
Authors: Sobczak Filip , He Yi , Sejnowski Terrence J , Yu Xin
Published: August 2020

Resting-state functional MRI (rs-fMRI) studies have revealed specific low-frequency hemodynamic signal fluctuations (<0.1 Hz) in the brain, which could be related to neuronal oscillations through the neurovascular coupling mechanism. Given the vascular origin of the fMRI signal, it remains challenging to separate the neural correlates of global rs-fMRI signal fluctuations from other confounding sources. However, the slow-oscillation detected from individual vessels by single-vessel fMRI presents strong correlation to neural oscillations. Here, we use recurrent neural networks (RNNs) to predict the future temporal evolution of the rs-fMRI slow oscillation from both rodent and human brains. The RNNs trained with vessel-specific rs-fMRI signals encode the unique brain oscillatory dynamic feature, presenting more effective prediction than the conventional autoregressive model. This RNN-based predictive modeling of rs-fMRI datasets from the Human Connectome Project (HCP) reveals brain state-specific characteristics, demonstrating an inverse relationship between the global rs-fMRI signal fluctuation with the internal default-mode network (DMN) correlation. The RNN prediction method presents a unique data-driven encoding scheme to specify potential brain state differences based on the global fMRI signal fluctuation, but not solely dependent on the global variance.
Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Asymptomatic Infections in 2 Large Academic Health Systems in Wisconsin
Authors: Rivera Frida , Safdar Nasia , Ledeboer Nathan , Schaack Grace , Chen Derrick J , Munoz-Price L Silvia
Published: August 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic infections may play a critical role in disease transmission. We aim to determine the prevalence of asymptomatic SARS-CoV-2 infection at 2 hospital systems in 2 counties in Wisconsin. The SARS-CoV-2 prevalence was 1% or lower at both systems despite the higher incidence of coronavirus disease 2019 (COVID-19) in Milwaukee County.
Labour market polarisation as a localised process: evidence from Sweden
Authors: Henning Martin , Eriksson Rikard H
Published: August 2020

The present article creates a link between contemporary labour market polarisation and regional divergence and analyses the spatial patterns of labour market polarisation in Swedish municipalities during the period 2002–2012. The results show that the national pattern of labour market polarisation is driven by polarisation in clusters of previously manufacturing-dominated municipalities with low- and medium-skill production, as well as increasing labour market polarisation and spatial selection within the fast-growing top-tier metropolitan regions. Outside these polarising spaces, most municipalities still experience job upgrading. The much-discussed abandonment of the traditional Western European job-upgrading model towards a polarising trajectory is thus not unequivocal. Regional labour market change and metropolitan selection cause great variation in labour market trajectories across space.
Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations
Authors: Lenaerts Liesbeth , Che Huiwen , Brison Nathalie , Neofytou Maria , Jatsenko Tatjana , Lefrère Hanne , Maggen Charlotte , Villela Darine , Verheecke Magali , Dehaspe Luc , Croitor Anca , Hatse Sigrid , Wildiers Hans , Neven Patrick , Vandecaveye Vincent , Floris Giuseppe , Vermeesch Joris Robert , Amant Frédéric
Published: August 2020

Background

Numerous publications have reported the incidental detection of occult malignancies upon routine noninvasive prenatal testing (NIPT). However, these studies were not designed to evaluate the NIPT performance for cancer detection.

Methods

We investigated the sensitivity of a genome-wide NIPT pipeline, called GIPSeq, for detecting cancer-specific copy number alterations (CNAs) in plasma tumor DNA (ctDNA) of patients with breast cancer. To assess whether a pregnancy itself, with fetal cell-free DNA (cfDNA) in the maternal circulation, might influence the detection of ctDNA, results were compared in pregnant (n = 25) and nonpregnant (n = 25) cancer patients. Furthermore, the ability of GIPSeq to monitor treatment response was assessed.

Results

Overall GIPSeq sensitivity for detecting cancer-specific CNAs in plasma cfDNA was 26%. Fifteen percent of detected cases were asymptomatic at the time of blood sampling. GIPSeq sensitivity mainly depended on the tumor stage. Also, triple negative breast cancers (TNBC) were more frequently identified compared to hormone-positive or HER2-enriched tumors. This might be due to the presence of high-level gains and losses of cfDNA or high ctDNA loads in plasma of TNBC. Although higher GIPSeq sensitivity was noted in pregnant (36%) than in nonpregnant women (16%), the limited sample size prohibits a definite conclusion. Finally, GIPSeq profiling of cfDNA during therapy allowed monitoring of early treatment response.

Conclusions

The results underscore the potential of NIPT-based tests, analyzing CNAs in plasma cfDNA in a genome-wide and unbiased fashion for breast cancer detection, cancer subtyping and treatment monitoring in a pregnant and nonpregnant target population.
Three-step preoperative sequential planning for pulmonary valve replacement in repaired tetralogy of Fallot using computed tomography
Authors: Ferraz Cavalcanti Paulo Ernando , Sá Michel Pompeu Barros Oliveira , Lins Ricardo Felipe de Albuquerque , Cavalcanti Catarina Vasconcelos , Lima Ricardo de Carvalho , Cvitkovic Tomislav , Bobylev Dmitry , Boethig Dietmar , Beerbaum Philipp , Sarikouch Samir , Haverich Axel , Horke Alexander
Published: August 2020

OBJECTIVES

Our goal was to compare results between a standard computed tomography (CT)-based strategy, the ‘three-step preoperative sequential planning’ (3-step PSP), for pulmonary valve replacement in repaired tetralogy of Fallot versus a conventional planning approach.

METHODS

We carried out a retrospective study with unmatched and matched groups. The 3-step PSP comprised the planning of mediastinal re-entry, cannulation for cardiopulmonary bypass (CPB) and the main procedure, using standard 3-dimensional videos. Operative times (skin incision to CPB, CPB time, end of CPB to skin closure and cross-clamp time) as well as postoperative length of stay and in-hospital mortality were compared.

RESULTS

Eighty-two patients (49% classical tetralogy of Fallot) underwent an operation (85% with pulmonary homograft) with 1.22% in-hospital mortality. The 3-step PSP (n = 14) and the conventional planning (n = 68) groups were compared. There were no statistically significant differences in the preoperative characteristics. Differences were observed in the total operative time (P = 0.009), skin incision to CPB (P = 0.034) and cross-clamp times (74 ± 33 vs 108 ± 47 min; P = 0.006), favouring the 3-step PSP group. Eight matched pairs were compared showing differences in the total operative time (263 ± 44 vs 360 ± 66 min; P = 0.008), CPB time (123 ± 34 vs 190 ± 43 min; P = 0.008) and postoperative length of stay (P = 0.031), favouring the 3-step PSP group.

CONCLUSIONS

In patients with repaired tetralogy of Fallot undergoing pulmonary valve replacement, preoperative planning using a standard CT-based strategy, the 3-step PSP, is associated with shorter operative times and shorter postoperative length of stay.
Edward Thomas and Hedges: England’s going out of Stile
Authors: Brooks Martin
Published: August 2020

Edward Thomas’s life and writing are marked by his attentiveness to rural England. With an overview of Thomas’ prose writings and then a set of close readings of his poetry, this essay describes how he presented hedges as an especially important part of the English countryside. Examining Thomas’s prose, the essay sets out how he saw hedges bringing natural life together into concentrated versions of landscapes, and how he argued that these concentrations could represent the English national identity. As the essay demonstrates, these ideas came into his poetry. His speakers see English field life as intricately interwoven. Some respond to the ongoing First World War by building on this intricacy. Their sense of being at home in England and belonging there is fuelled by treating hedges as portals to an eternal and a pre-industrial England. By considering the roles that hedges have in his poems, this essay shows how Thomas shaped them into a focal point for portraying speakers who have a connection to the national identity.
Primary care and all-cause mortality in urban China: a mixed-level analysis
Authors: Zhang Quan
Published: August 2020

Background

There is still a lack of evidence focusing on primary care supply in developing countries where the educational achievement of primary care practitioners is relatively low.

Objectives

By using a nationally representative longitudinal and prospective cohort study, this study examined whether primary care supply, measured by the availability and the number of community health centres (CHCs), was associated with 4-year mortality risk among community-dwelling participants aged 45 and above in urban China.

Methods

Using the 2011 and 2015 waves of the China Health and Retirement Longitudinal Survey (CHARLS), we conducted a longitudinal mixed-level logistic analysis to study the impact of the availability and the number of CHC on 4-year follow-up mortality risk, after adjusting community- and individual-level covariates.

Results

Individuals living in communities with CHC were 31% less likely to die during the 4-year follow-up (P < 0.05) conditional on community-level characteristics, including the basic facilities availability, population size and physical area, and individuals’ socio-demographic and health characteristics and health behaviours. Also, an increased number of community-level CHC was shown to decrease residents’ 4-year mortality risk significantly (odds ratio = 0.82, P < 0.05). Furthermore, the association was more pronounced among adults aged 65 and above.

Conclusion

This study provides additional evidence of the health-promoting effect of primary care supply among urban residents in China. Improving primary care coverage in China should be necessary to improve health care access, thus promoting population health.
Abundance, diversity and mobility potential of antibiotic resistance genes in pristine Tibetan Plateau soil as revealed by soil metagenomics
Authors: Li Bo , Chen Zeng , Zhang Fan , Liu Yongqin , Yan Tao
Published: August 2020

Widespread occurrence of antibiotic resistance genes (ARGs) has become an important clinical issue. Studying ARGs in pristine soil environments can help to better understand the intrinsic soil resistome. In this study, 10 soil samples were collected from a high elevation and relatively pristine Tibetan area, and metagenomic sequencing and bioinformatic analyses were conducted to investigate the microbial diversity, the abundance and diversity of ARGs and the mobility potential of ARGs as indicated by different mobile genetic elements (MGEs). A total of 48 ARG types with a relative abundance of 0.05–0.28 copies of ARG/copy of 16S rRNA genes were detected in Tibetan soil samples. The observed ARGs were mainly associated with antibiotics that included glycopeptide and rifamycin; the most abundant ARGs were vanRO and vanSO. Low abundance of MGEs and potentially plasmid-related ARGs indicated a low horizontal gene transfer risk of ARGs in the pristine soil. Pearson correlation and redundancy analyses showed that temperature and total organic carbon were the major environmental factors controlling both microbial diversity and ARG abundance and diversity.
Shotgun metagenomics reveals a heterogeneous prokaryotic community and a wide array of antibiotic resistance genes in mangrove sediment
Authors: Imchen Madangchanok , Kumavath Ranjith
Published: August 2020

Saline tolerant mangrove forests partake in vital biogeochemical cycles. However, they are endangered due to deforestation as a result of urbanization. In this study, we have carried out a metagenomic snapshot of the mangrove ecosystem from five countries to assess its taxonomic, functional and antibiotic resistome structure. Chao1 alpha diversity varied significantly (P < 0.001) between the countries (Brazil, Saudi Arabia, China, India and Malaysia). All datasets were composed of 33 phyla dominated by eight major phyla covering >90% relative abundance. Comparative analysis of mangrove with terrestrial and marine ecosystems revealed the strongest heterogeneity in the mangrove microbial community. We also observed that the mangrove community shared similarities to both the terrestrial and marine microbiome, forming a link between the two contrasting ecosystems. The antibiotic resistant genes (ARG) resistome was comprised of nineteen level 3 classifications dominated by multidrug resistance efflux pumps (46.7 ± 4.3%) and BlaR1 family regulatory sensor-transducer disambiguation (25.2 ± 4.8%). ARG relative abundance was significantly higher in Asian countries and in human intervention datasets at a global scale. Our study shows that the mangrove microbial community and its antibiotic resistance are affected by geography as well as human intervention and are unique to the mangrove ecosystem. Understanding changes in the mangrove microbiome and its ARG is significant for sustainable development and public health.
The type of microorganism and substrate determines the odor fingerprint of dried bacteria targeting microbial protein production
Authors: Sakarika Myrsini , Tzompa-Sosa Daylan A , Depoortere Mathilde , Rottiers Hayley , Ganigué Ramon , Dewettinck Koen , Rabaey Korneel
Published: August 2020

The rapidly increasing demand for protein has led to the pursuit of new protein sources, among which microbial protein (MP) is one of the most promising. Although the nutritional properties of MP are important and often well-studied, the sensory properties of the microbial cells will in part determine the commercial success of the product and are much less investigated. Here we assessed the odor fingerprint of dried bacteria originating from pure cultures and enriched mixed microbial communities using an electronic nose (e-nose). The e-nose discriminated between the different MP sources, while the choice of culture and substrate substantially affected their volatile organic compound (VOC) profile. The most dominant odor descriptors (>20% of VOC peak area) were sweet, fruity and fishy, while the mixed cultures presented higher peak areas indicating potentially more intense aromas than the pure cultures. The e-nose can detect the suitability of new MP sources and determine their best end-use.
Analysis of 5′-NAD capping of mRNAs in dormant spores of Bacillus subtilis
Authors: Craft D Levi , Korza George , Zhang Yaqing , Frindert Jens , Jäschke Andres , Caimano Melissa J , Setlow Peter
Published: August 2020

Spores of Gram-positive bacteria contain 10s–1000s of different mRNAs. However, Bacillus subtilis spores contain only ∼ 50 mRNAs at > 1 molecule/spore, almost all transcribed only in the developing spore and encoding spore proteins. However, some spore mRNAs could be stabilized to ensure they are intact in dormant spores, perhaps to direct synthesis of proteins essential for spores’ conversion to a growing cell in germinated spore outgrowth. Recent work shows that some growing B. subtilis cell mRNAs contain a 5′-NAD cap. Since this cap may stabilize mRNA in vivo, its presence on spore mRNAs would suggest that maintaining some intact spore mRNAs is important, perhaps because they have a translational role in outgrowth. However, significant levels of only a few abundant spore mRNAs had a 5′-NAD cap, and these were not the most stable spore mRNAs and had likely been fragmented. Even higher levels of 5′-NAD-capping were found on a few low abundance spore mRNAs, but these mRNAs were present in only small percentages of spores, and had again been fragmented. The new data are thus consistent with spore mRNAs serving only as a reservoir of ribonucleotides in outgrowth.
Function-Focused Person–Environment Fit for Long-Term Care Residents With Dementia: Impact on Apathy
Authors: Jao Ying-Ling , Liu Wen , Chaudhury Habib , Parajuli Jyotsana , Holmes Sarah , Galik Elizabeth
Published: August 2020

Background and Objectives

Apathy is a common symptom in dementia and is associated with rapid cognitive decline, poor quality of life, and higher mortality. Lawton’s Competence and Environmental Press model suggests that an individual’s behavior and affect are influenced by the fit of their functional abilities with the environmental demands. Yet, empirical evidence on the association between person–environment (P–E) fit and apathy is lacking. Thus, this study examined the relationship between P–E fit and apathy in dementia. Specifically, this study focused on the extent the physical environment fits individual functional limitations.

Research Design and Methods

This is a cross-sectional study using the baseline data from long-term care residents with dementia. The sample included 199 residents with moderate-to-severe cognitive impairment from 4 assisted living and 4 nursing homes. Function-focused P–E fit was measured using the Housing Enabler scale. Apathy was measured using the Apathy Evaluation Scale. Multilevel linear models were used to analyze the relationship between P–E fit and apathy.

Results

Findings revealed that greater P–E fit, specifically indoor environment, was significantly associated with lower apathy after controlling for age, gender, and years living in the facility. Yet, the association became not significant after controlling for individual physical function.

Discussion and Implications

Findings support the association between function-focused P–E fit and apathy, but the association is no longer significant after physical function is adjusted. Future research may explore other aspects of P–E fit and the impact of social and organizational environment on apathy in dementia.
The chromosome-level draft genome of Dalbergia odorifera
Authors: Hong Zhou , Li Jiang , Liu Xiaojin , Lian Jinmin , Zhang Ningnan , Yang Zengjiang , Niu Yongchao , Cui Zhiyi , Xu Daping
Published: August 2020

Background

Dalbergia odorifera T. Chen (Fabaceae) is an International Union for Conservation of Nature red-listed tree. This tree is of high medicinal and commercial value owing to its officinal, insect-proof, durable heartwood. However, there is a lack of genome reference, which has hindered development of studies on the heartwood formation.

Findings

We presented the first chromosome-scale genome assembly of D. odorifera obtained on the basis of Illumina paired-end sequencing, Pacific Biosciences single-molecule real-time sequencing, 10x Genomics linked reads, and Hi-C technology. We assembled 97.68% of the 653.45 Mb D. odorifera genome with scaffold N50 and contig sizes of 56.16 and 5.92 Mb, respectively. Ten super-scaffolds corresponding to the 10 chromosomes were assembled, with the longest scaffold reaching 79.61 Mb. Repetitive elements account for 54.17% of the genome, and 30,310 protein-coding genes were predicted from the genome, of which ~92.6% were functionally annotated. The phylogenetic tree showed that D. odorifera diverged from the ancestor of Arabidopsis thaliana and Populus trichocarpa and then separated from Glycine max and Cajanus cajan.

Conclusions

We sequence and reveal the first chromosome-level de novo genome of D. odorifera. These studies provide valuable genomic resources for the research of heartwood formation in D. odorifera and other timber trees. The high-quality assembled genome can also be used as reference for comparative genomics analysis and future population genetic studies of D. odorifera.
Lava dome morphology inferred from numerical modelling
Authors: Tsepelev Igor , Ismail-Zadeh Alik , Melnik Oleg
Published: August 2020

Lava domes form when highly viscous magmas erupt on the surface. Several types of lava dome morphology can be distinguished depending on the flow rate and the rheology of magma. Here, we develop a 2-D axisymmetric model of magma extrusion on the surface and lava dome evolution and analyse the dome morphology using a finite-volume method implemented in Ansys Fluent software. The magma/lava viscosity depends on the volume fraction of crystals and temperature. We show that the morphology of domes is influenced by two parameters: the characteristic time of crystal content growth (CCGT) and the discharge rate (DR). At smaller values of the CCGTs, that is, at rapid lava crystallization, obelisk-shaped structures develop at low DRs and pancake-shaped structures at high DRs; at longer CCGTs, lava domes feature lobe- to pancake-shaped structures. A thick carapace of about 70 per cent crystal content evolves at smaller CCGTs. We demonstrate that cooling does not play the essential role during a lava dome emplacement, because the thermal thickness of the evolving carapace remains small in comparison with the dome's height. A transition from the endogenic to exogenic regime of the lava dome growth occurs after a rapid increase in the DR. A strain-rate-dependent lava viscosity leads to a more confined dome, but the influence of this viscosity on the dome morphology is not well pronounced. The model results can be used in assessments of the rates of magma extrusion, the lava viscosity and the morphology of active lava domes..
2. Liberty
Authors: Carter Ian
Published: August 2020

This chapter examines the concept of liberty. There are different rival interpretations of liberty. These interpretations can be discussed in terms of a well-known distinction: that between negative and positive liberty. Negative liberty is the absence of something: normally, the absence of external obstacles imposed by other human agents. Positive liberty is the presence of something: the exercise of our choice-making capacities in ways that put us in control of our own lives. Much of the recent literature on liberty has focused on a new challenge to these conceptions of liberty. The challenge comes from thinkers inspired by the neo-roman or republican idea of liberty as the antithesis of slavery. Republicans define liberty as the absence of domination. Meanwhile, some libertarians, who hold that liberty is best realized through the protection of private property and contract, have argued that liberty is always limited by the pursuit of economic equality.
5. Power
Authors: Owen David
Published: August 2020

This chapter assesses power, a basic concept of political theory. In its most fundamental sense, power is a dispositional concept that refers to the capacity to affect some feature of the world and the capacity to produce effects with respect to those feature of the world. The concept of power is closely bound in social and political contexts to the concepts of freedom and responsibility. There are different modes of power: power to, power with, power over, and power of. The power of an agent typically depends on the context of power in which they are situated and on the relations in which they stand to other agents within broader social structures. Moreover, exercises of power are always mediated — and, indeed, we often distinguishes forms of social and political power in terms of prominent general media through which they are exercised. The chapter then considers the three-dimensional view of power.
6. Equality and social justice
Authors: Wolff Jonathan
Published: August 2020

This chapter addresses equality and social justice. In the 1980s and 1990s, the goal of social justice was challenged both on political and philosophical grounds and was largely supplanted by an emphasis on economic growth and individual responsibility. Although still given little emphasis in the United States, considerations of social justice came back onto the political agenda in the United Kingdom following the election of the new Labour government in 1997. To rehabilitate social justice, it was necessary to decouple it from traditional socialist ideas of common ownership of the means of production. Key debates on social justice concern theories of equality, priority, and sufficiency, and how inequality should be defined and measured. Of particular concern has been the place of personal responsibility for disadvantages causing inequalities. The chapter then considers equality of opportunity and social relations.
11. Human Rights
Authors: Campbell Tom
Published: August 2020

This chapter focuses on human rights. Human rights are derived historically from the idea of natural law as it developed on a strong religious basis in late medieval Europe and, later, in a more secularized form during the more rationalist period of the Enlightenment. Meanwhile, the contemporary human rights movement stems from the aftermath of World War II. It is associated, domestically, with constitutional bills of rights and, internationally, with the work of the United Nations. Human rights may be defined as universal rights of great moral and political significance that belong to all human beings by virtue of their humanity. They are said to be overriding and absolute. Human rights may be divided into three overlapping groups: civil and political rights; economic, social, and cultural rights; and group or collective rights for development and self-determination.
9. Post-positivism in IR
Authors: Jackson Robert , Sørensen Georg , Møller Jørgen
Published: August 2020

This chapter examines post-positivist approaches in international relations (IR). Post-positivism rejects any claim of an established truth valid for all. Instead, its focus is on analysing the world from a large variety of political, social, cultural, economic, ethnic, and gendered perspectives. The chapter considers three of the most important issues taken up by post-positivist approaches: post-structuralism, which is concerned with language and discourse; post-colonialism, which adopts a post-structural attitude in order to understand the situation in areas that were conquered by Europe, particularly Africa, Asia, and Latin America; and feminism, which argues that women are a disadvantaged group in the world, in both material terms and in terms of a value system which favours men over women. The chapter concludes with an overview of criticisms against post-positivist approaches and the post-positivist research programme.
15. Societal Security
Authors: Roe Paul
Published: August 2020

This chapter focuses on the concept of societal security. It first considers how society came to be conceived as a referent object of security in its own right before discussing the Copenhagen School’s understanding of both society and societal identity. It then examines threats to societal security, which can be categorised into migration, horizontal competition, and vertical competition, by giving examples relating to immigration and the rise of the political right, genocide, ‘culturecide’, and the Yugoslav wars. The chapter also describes a number of those means that can prevent or hinder the reproduction of collective identity, and how societies may react to such perceived threats. Finally, it evaluates some of the main critiques of the concept of societal security as an analytical tool.
11. Irregular Warfare: Terrorism and Insurgency
Authors: Kiras James D.
Published: August 2020

This chapter examines two types of irregular warfare: terrorism and insurgency. It first considers the problematic definitions given to irregular warfare, terrorism and insurgency before discussing the theory and practice of irregular warfare. In particular, it highlights the role of time, space, legitimacy, and/or support in insurgent and terrorist campaigns. It then analyses counterinsurgency and counterterrorism in theory and practice, focusing on three important elements of successful campaigns against insurgents and terrorists, namely, location, isolation, and eradication. It also explores contemporary and future irregular threats and how they are driven by a combination of culture, religious fanaticism, and technology. Finally, it comments on the role to be played by information technology in irregular wars of the future, which some observers expect to be fought in cyberspace.
14. Conventional Power and Contemporary Warfare
Authors: Ferris John
Published: August 2020

This chapter examines how conventional power shapes warfare in the contemporary world. It considers the present and emerging state of conventional military power, how conventional forces function in areas such as distant strike and urban warfare, and how their role differs from that of other forms of force, including terrorism and weapons of mass destruction (WMDs). The chapter first provides a historical background to demonstrate the important role played by conventional power in war before discussing the rise of new world orders in 1945, 1989 and 2001. It then describes states possessing power and hyperpower, along with the revolution in military affairs and how developing countries may trump it through various strategies. It also shows how the distribution of conventional power is changing, noting that Western countries are in decline and new world powers are emerging, especially China and India.
22. The Practice of Strategy
Authors: Gray Colin S. , Johnson Jeannie L.
Published: August 2020

This chapter focuses on the requirements of what a good practice of strategy should be. It first provides an overview of the importance of strategic expertise and the reasons why good strategists are hard to find. It then highlights the qualities a good strategist needs to be effective, along with the obstacles to competent strategic performance and the flaws of contemporary strategic education, including insufficient attention to strategic classics and strategic history. It also offers a remedy called The General Theory of Strategy, the core components of which are: understanding the nature and character of strategy, making strategies based on seven contexts (political, sociocultural, economic, technological, military, geographical, historical), and executing strategies. The chapter concludes by calling for a regular reassessment of strategic plans and engagements, driven by questions that examine the extent to which strategy has enabled, and will continue to enable, achievement of political objectives.
23. Does Strategic Studies Have a Future?
Authors: Freedman Lawrence
Published: August 2020

This chapter considers whether the field of strategic studies has a future, first by tracing its development in universities and think tanks as traditional military patterns of thought and how it has evolved into a broad field of enquiry by the end of the cold war. It then describes the ‘golden age’ of strategic studies that created a market for professionally trained civilian strategists and examines how strategic studies had become more diffuse as the political context of international relations changed. It also explains how the study of strategy posed a particular challenge to the social sciences, and how ethical and practical difficulties created tensions between academics and policymakers. The chapter goes on to discuss elements of realism that are useful in the study of strategy, strategic studies' focus on the role of armed force both in peacetime and in war, and future prospects for strategic studies.
6. The Puzzle of Political Reform in the Middle East
Authors: Norton Augustus Richard
Published: August 2020

This chapter assesses the critical issue of political reform in the Middle East. The Arab world has been slow to respond to the global processes of democratization. The chapter then highlights the political economy of states, the persistence of conflict, regime type, and the ambiguity over the relationship between democracy and Islam. This relationship is not necessarily a contradictory one. Islamic discourse is marked by participation and diversity rather than by rigidity and intolerance. Further, as the Arab Spring has illustrated, civil society is vibrant and growing in many states across the region. Meanwhile, responses from the West to political reform have been lukewarm, with stability and regional alliances privileged over democracy. The evidence from the region, even before the Arab uprisings, is that peoples want better and more representative government, even if they remain unclear as to what type of government that should be.
7. The Politics of Identity in Middle East International Relations
Authors: Hinnebusch Raymond
Published: August 2020

This chapter offers critical reviews of the explanatory power of identity and culture in understanding international relations in the Middle East. It focuses on Arabism and other regional ethnicities as sources of political identity. The importance of these identities within the region has been accentuated because of the poor fit between identity and states and regimes — a colonial legacy, but one that remains pertinent today, as revealed in the Arab uprisings. Indeed, the persistence of conflict in the Middle East must be understood through this ‘incongruence of identity and material structures’. Focusing on pan-Arabism, as well as the irredentist and separatist movements that have characterized the history and political development of the region, the chapter shows how the interaction of identity with state formation and development has contributed to numerous wars, and most recently to the evolution of regional developments following the Arab Spring.
8. Islam and International Relations in the Middle East: From Umma to Nation State
Authors: Mandaville Peter
Published: August 2020

This chapter addresses the role of Islam in the international relations in the Middle East. In a historically informed account, it shows how Islam has interacted with the domestic, regional, and international politics of the region in a variety of forms. Its influence, however, has ebbed and flowed alongside different currents in regional and international relations. In this regard, globalization has been a facilitator of transnational Islam, but by no means a force for union. Notwithstanding its evident importance, there has been little substantive presence of religion in the foreign policies of Middle Eastern states, even in those more overtly Islamic ones such as Saudi Arabia and Iran. However, the popular uprisings in the Arab world created new opportunities and challenges for the Islamic movement, which continue to affect states' foreign policies notably through the phenomenon of ‘sectarianization’.
Introduction: The Middle East and International Relations
Authors: Fawcett Louise
Published: August 2020

This introductory chapter provides an overview of the study of international relations in the Middle East. The two disciplines of international relations and Middle East studies are highly interdependent. No book on the contemporary politics of the Middle East can possibly ignore the way in which external forces have shaped the development of the region's politics, economics, and societies. Similarly, no international relations text can ignore the rich cases that the Middle East has supplied, and how they illuminate different theories and concepts of the discipline, whether in respect of patterns of war and peace, identity politics, or international political economy. The chapter then looks at some of the particular problems that arise in studying the international relations of the Middle East.
Epidemiological characteristics of patients with severe COVID-19 infection in Wuhan, China: evidence from a retrospective observational study
Authors: Wang Fang , Cao Jinhong , Yu Yong , Ding Jianbo , Eshak Ehab S , Liu Keyang , Mubarik Sumaira , Shi Fang , Wen Haoyu , Zeng Zixin , Bai Jianjun , Yu Chuanhua
Published: August 2020

Background

The new coronavirus (COVID-19) rapidly resulted in a pandemic. We report the characteristics of patients with severe or critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan city, China, and the risk factors related to infection severity and death.

Methods

We extracted the demographic and clinical data of 7283 patients with severe COVID-19 infection from designated Wuhan hospitals as of 25 February 2020. Factors associated with COVID-19 critical illness and mortality were analysed using logistic- and Cox-regression analyses.

Results

We studied 6269 patients with severe COVID-19 illness and 1014 critically ill patients. The median (IQR) age was 64 (53–71) years; 51.2% were male, 38.9% were retirees and 7.4% had self-reported histories of chronic disease. Up to the end of the study, 1180 patients (16.2%) recovered and were discharged, 649 (8.9%) died and the remainder were still receiving treatment. The number of daily confirmed critical cases peaked between 23 January and 1 February 2020. Patients with advanced age [odds ratio (OR), 1.03; 95% confidence intervals (CIs), 1.03–1.04], male sex (OR, 1.57; 95% CI, 1.33–1.86) and pre-existing diabetes (OR, 2.11), hypertension (OR, 2.72), cardiovascular disease (OR, 2.15) or respiratory disease (OR, 3.50) were more likely to be critically ill. Compared with those who recovered and were discharged, patients who died were older [hazard ratio (HR), 1.04; 95% CI, 1.03–1.05], more likely to be male (HR, 1.74; 95% CI, 1.44–2.11) and more likely to have hypertension (HR, 5.58), cardiovascular disease (HR, 1.83) or diabetes (HR, 1.67).

Conclusion

Advanced age, male sex and a history of chronic disease were associated with COVID-19 critical illness and death. Identifying these risk factors could help in the clinical monitoring of susceptible populations.
Vaginal and Penile Microbiome Associations With Herpes Simplex Virus Type 2 in Women and Their Male Sex Partners
Authors: Mehta Supriya D , Nandi Debarghya , Agingu Walter , Green Stefan J , Bhaumik Dulal K , Bailey Robert C , Otieno Fredrick
Published: August 2020

Background

We determined how the vaginal and penile microbiomes contribute to herpes simplex virus type 2 (HSV-2) serostatus within sexual partnerships.

Methods

Microbiomes were characterized in cervicovaginal lavage and penile meatal swab specimens through high-throughput 16s ribosomal RNA gene amplicon sequencing. HSV-2 antibody was detected in serum specimens. We modeled vaginal and penile taxa and covariates contributing to HSV-2 status in women and men using bivariate probit analysis.

Results

Among 231 couples, HSV-2 was detected in both partners in 78 couples (33.8%), in the woman only in 52 (22.5%),in the man only in 27 (11.7%), and in neither in 74 (32.0%). Among the women (median age, 22 years) 10.9% had human immunodeficiency virus (HIV), and 21.4% had Bacterial vaginosis. Among men (median age, 26 years), 11.8% had HIV, and 55.0% circumcised. In an analysis with adjustment for sociodemographics and Bacterial vaginosis, enrichment of vaginal Gardnerella vaginalis and Lactobacillus iners was associated with increased likelihood of HSV-2 in both partners. Penile taxa (including Ureaplasma and Aerococcus) were associated with HSV-2 in women.

Conclusions

We demonstrate that penile taxa are associated with HSV-2 in female partners, and vaginal taxa are associated with HSV-2 in male partners. Our findings suggest that couples-level joint consideration of genital microbiome and sexually transmitted infection or related outcomes could lead to new avenues for prevention.
Organized immune cell interactions within tumors sustain a productive T-cell response
Authors: Cardenas Maria A , Prokhnevska Nataliya , Kissick Haydn T
Published: August 2020

Tumor-infiltrating CD8 T cells are associated with improved patient survival and response to immunotherapy in various cancers. Persistent antigen leads to CD8 T-cell exhaustion, where proliferation/self-renewal and killing are divided within distinct subsets of CD8 T cells in the tumor. CD8 T-cell responses in chronic antigen settings must be maintained for long periods of time, suggesting that mechanisms that regulate chronic CD8 T-cell responses may differ from those in acute settings. Currently, factors that regulate the maintenance of stem-like CD8 T cells in the tumor or their differentiation into terminally differentiated cells are unknown. In this review, we discuss the role of dendritic cells in the activation and differentiation of CD8 T-cell subsets within secondary lymphoid tissue and tumors. In addition, we examine changes in CD4 T-cell differentiation in response to chronic antigens and consider how subset-specific mechanisms could assist the stem-like and terminally differentiated CD8 T-cell subsets. Finally, we highlight how tumor-infiltrating CD4 T cells and dendritic cells interact with CD8 T cells within organized lymphoid-like areas in the tumor and propose a CD8 T-cell differentiation model that requires the collaboration of CD4 T cells and dendritic cells. These organized interactions coordinate the anti-tumor response and control disease progression by mechanisms that regulate CD8 T-cell differentiation, which permit the maintenance of an effective balance of stem-like and terminally differentiated CD8 T cells.