bluuebunny/crossref_metadata_2025 huggingface dataset:
The Archive
Authors: Earlie Paul
Published: February 2021

This chapter examines Derrida’s writings on the archive and, more particularly, his reflections on the archive of psychoanalysis. Although texts such as Mal d’archive (Archive Fever) have often been held as heralding a ‘theoretical’ turn in archival studies, Derrida’s writings on the archive continually question the limitations of any theory, concept, or science of the archive. Part of the archive’s resistance to conceptualization lies in its relationship to what calls Derrida ‘originary technicity’, a structure which concerns not only the material space of paper but also the psyche as a mnemic archive and the virtual or digital archive. If a firm distinction between these three types of archive can never be guaranteed, this indistinction has important consequences for psychoanalytic therapy and for the ‘positive’ science of history. The latter is explored here through Derrida’s reading of Yosef Hayim Yerushalmi’s Freud’s Moses: Judaism Terminable and Interminable. For Derrida, the archive’s structural resistance to interpretation—what he elsewhere calls its ‘absolute secrecy’—means that it is always the site of passionate investments. Freud’s account of the psyche as a space of archival preservation already suggests this imbrication of affect and technicity, as Derrida shows in his reading of Freud’s Delusion and Dream in Jensen’s Gradiva.
Due Diligence in International Anti-terrorism Law
Authors: Österdahl Inger
Published: February 2021

This chapter investigates the content of the due diligence principle in the area of anti-terrorism law. It emphasises that the substance of potential due diligence obligations in the area of anti-terrorism law is largely unexplored and they are not mapped. With a particular focus on UN Security Council Resolution 2396 of 2017, the chapter analyses whether a minimum consensus on required state measures against terrorism, such as criminalisation, international cooperation, or information sharing, can be detected. To that end, the chapter examines the language of the Security Council Resolution as an indicator of varying degrees of obligation of due diligence requirements in this field.
Due Diligence in World Bank Project Financing
Authors: Desierto Diane A.
Published: February 2021

This chapter analyses due diligence practices of institutional lenders, such as the World Bank and other multilateral development banks, in the course of international project financing. Such due diligence practices include taking into account country risks, political risks, environmental risks, and social risks. The chapter lays particular focus on the Sustainability Framework of the International Finance Corporation of the World Bank Group which provides the international benchmark practices for the assessment of environmental and social risks. The chapter traces the Framework’s influence on the Equator Principles on Environmental and Social Risk Management adopted by other international private and public financial institutions for international project financing. It argues that due diligence in the area of international project finance may be headed towards possible convergence with international human rights obligations, particularly with environmental and social treaty commitments of States.
Reading Śrīkaṇṭha’s Commentary
Authors: Duquette Jonathan
Published: February 2021

This chapter introduces Appaya’s Śivādvaita Vedānta works, paying special attention to its most important piece, the Śivārkamaṇidīpikā. The chapter first discusses Appaya’s doxography of Vedānta schools, the Caturmatasārasaṃgraha, and highlights how it might have been used to introduce Śrīkaṇṭha’s teachings to a wider scholarly audience and lend them authority in the process. It then discusses how Appaya creatively reads Śrīkaṇṭha’s commentary, with special reference to Śrīkaṇṭha’s theory of transformation (pariṇāmavāda), with a view to aligning its teachings with the doctrine of apparent transformation (vivartavāda) held by tenants of pure non-dualism (Advaita Vedānta). Finally, it investigates Appaya’s interpretation of the pāśupatādhikaraṇa (BS 2.2.35–38) in his Śivārkamaṇidīpikā, and shows how his commitment to Advaita Vedānta impacts his broad understanding of Śaiva scriptures and makes him read passages from those scriptures rather differently than his Śaiva co-religionists.
Enabling Change
Authors: Rouse William B.
Published: February 2021

This chapter provides a pragmatic perspective on enabling the changes needed to substantially enhance failure management practices. The behavioral and social nature of human decision making is reviewed. Decision-making vignettes are provided to illustrate the general human phenomena of interest. Societal views and practices of system maintenance are considered. Broader perspectives on economic, legal, political, and social aspects of change are reviewed. Numerous examples of computational approaches to change are summarized.
The dorsal visual system
Authors: Rolls Edmund T.
Published: February 2021

The dorsal visual system computes information about where objects are in space, and their motion, and this is used for actions performed in space. This requires coordinate transforms from retinal coordinates to head based coordinates, and then in parietal cortex areas to coordinates for reaching into space, and for allocentric, world-based, spatial coordinates. Recent approaches to how these transforms are performed, with analogies to transform invariance learning in the ventral visual system, are described.
The motor cortical areas
Authors: Rolls Edmund T.
Published: February 2021

Premotor cortical areas have outputs to the motor cortex, and receive inputs from the parietal cortex to implement actions such as reaching into space and grasping objects. Neurons in some premotor areas respond not only to movements being performed, but also to the sight of movements being performed, and are termed ‘mirror neurons’.
Cerebellar cortex
Authors: Rolls Edmund T.
Published: February 2021

The cerebellar cortex appears to be involved in predictive feedforward control to generate smooth movements. There is a beautiful network architecture which suggests that the granule cells perform expansion recoding of the inputs; that these connect to the Purkinje cells via an architecture that ensures regular sampling; and that each Purkinje cell has a single teacher, the climbing fibre, which produces associative long-term synaptic depression as part of perceptron-like learning.
The prefrontal cortex
Authors: Rolls Edmund T.
Published: February 2021

The prefrontal cortex receives perceptual information from the temporal and parietal cortices, and is in a position to perform ‘off-line’ processing, including holding items in a short-term memory when the items are no longer present in the input processing streams. This off-line capacity develops into a capability of manipulating and rearranging items in short-term memory, and this is called working memory, which is also implemented in the prefrontal cortex. This ability in humans develops into systems that can plan ahead, and then can control behaviour according to such plans, which is referred to as ‘executive function’. Attractor networks are fundamental to understanding the functions of the prefrontal cortex in short-term and working memory; and in providing the source of the top-down bias in top-down models of attention
Grothendieck Fibrations
Authors: Johnson Niles , Yau Donald
Published: February 2021

In this chapter, Grothendieck fibrations are defined, and the Grothendieck Fibration Theorem is proved. After discussing some basic definitions, properties, and examples of fibrations, this chapter constructs a 2-monad and proves in detail that its pseudo algebras are precisely cloven fibrations. Moreover, the strict algebras of this 2-monad are shown to be precisely split fibrations.
PHILIP CASHIAN (b. 1963)The Sun’s Great Eye (2008)
Authors: Manning Jane
Published: February 2021

This chapter highlights British composer Philip Cashian’s The Sun’s Great Eye (2008). In this short but arresting work, Cashian manages, with an impressive display of sleight-of-hand craftsmanship, to assimilate some of the more obvious characteristics of fashionable minimalism within a scheme that combines repeated patterns with asymmetrical rhythmic contours. The result, ingenious and highly concentrated, is not in the least mechanical, but has charm and a natural musicality. The fascinating piano part is written on just one stave, to be shared by both hands. This emphasizes the close interweaving of both protagonists as equal partners, and adds subtly to the feeling of intimacy and unforced expression. Through elliptical rhythmic hurdles and differing alignments, the voice glides in and out, in supple, lilting fragments which must seem effortless, bearing no hint of the hard work needed to acquire perfect coordination and accurate pitching, or the necessity of counting beats in groups of two and three.
CHERYL FRANCES-HOAD (b. 1980)One Life Stand (2011)
Authors: Manning Jane
Published: February 2021

This chapter addresses Cheryl Frances-Hoad’s One Life Stand (2011). This major work was conceived as a companion piece to Schumann’s loved cycle Frauenliebe und Leben, Op. 42 (1830). It sets eight vivid contemporary poems by Sophie Hannah—charting the often turbulent emotional journey experienced by the present-day woman in love—in starkest contrast to the more conventional, submissive attitudes portrayed in the Schumann. Each song subtly, even obliquely, evokes a movement of the Schumann, ingeniously mirroring aspects of its musical setting, particularly in the relationships between voice and piano. It constitutes a compelling narrative of contemporary feminine experience, and a rewarding tour de force for a mezzo and pianist of interpretative and technical accomplishment. The work is written in standard notation and the voice part, set straightforwardly with a few curving melismas at key points, eschews extremes of range and ‘extended vocal techniques’. The singer will, however, need to call on reserves of stamina for some lengthy high-lying passages, although there is plenty of light relief in the fast movements with their quicksilver parlando delivery.
EMILY HOWARD (b. 1979)Wild Clematis in Winter (2008)
Authors: Manning Jane
Published: February 2021

This chapter focuses on Emily Howard’s Wild Clematis in Winter (2008). In this piece, perfect control and precision of intonation are required of the singer. Even from the start, the mezzo is left exposed on long-held pitches, often in the potentially vulnerable register-break area. The piano sets the atmosphere with delicate, oscillating semitones, merged by the pedal, grounded by a constantly repeating G natural in the bass. This pattern is to continue through much of the song. Meanwhile, the singer’s exquisitely poised, hypnotic lines gradually gather intensity over a wide spectrum of dynamics. Phrases become more passionate, with single repeated notes conveying a wealth of meaning in their carefully graded dynamics. Throughout, the accompaniment stays within a restricted pitch area, and there are plenty of cues to keep the singer anchored.
BETSY JOLAS (b. 1926)L’Oeil égaré (1961–2002)
Authors: Manning Jane
Published: February 2021

This chapter addresses French-American composer Betsy Jolas’s L’Œil égaré (1961–2002), a powerful cycle written over a wide span of years. In this piece, the composer’s bold, innovative spirit bursts from every page. A welter of technical, musical, and interpretative challenges are offered, but these should not daunt advanced singers with a high standard of musicianship. The six short settings are full of contrasts within a richly diverse stylistic palette. There is, however, a keen awareness of practicality regarding the baritone range—the few instances of upper and lower extremes are approached either via portamentos or loud climaxes when energy level is high. Each movement is vivid enough to be performed individually. The texts resonate with colourful imagery. To sing in the original language is, of course, ideal, but the composer’s translations are impressive in managing to preserve their heightened lyricism and searching insights, as well as matching small subtleties of syllabic emphasis.
DON KAY (b. 1934)Four Bird Songs from Shaw Neilson (2005)
Authors: Manning Jane
Published: February 2021

This chapter describes Tasmanian composer Dan Kay’s Four Bird Songs from Shaw Neilson (2005). The texts for this pleasing, fluent cycle are by the farmworker-poet Shaw Neilson, and reflect his close affinity with the natural world, especially the life of waterbirds. Kay’s palpable empathy with these unsophisticated but burningly sincere poems draws music of clarity and refinement. The frequent modal melodies and minor harmonies cannot help but call to mind Vaughan Williams and the English folk-song tradition, but Kay manages to inject an individual flavour by means of chromatic shifts and varied rhythms, especially in the last two, slightly longer, songs. A light young baritone with a safe high register would be ideal here. The piano writing is clear and uncluttered, with simple, repeated figurations, and there is no need to force the voice. Standard notation is used throughout.
JOCELYN MORLOCK (b. 1969)Involuntary Love Songs (2008)
Authors: Manning Jane
Published: February 2021

This chapter explores Canadian composer Jocelyn Morlock’s Involuntary Love Songs (2008). Morlock’s lively, distinctive voice and clear vision are immediately evident in this trio of satisfying, ear-catching songs, written in an accessible style that recalls elements of an earlier North American ‘art-song’ tradition. The cycle will be an asset to any recital programme. The vibrantly evocative poems by Alan Ashton are ideal musical vehicles, and Morlock responds to them with spontaneity and empathy, mirroring their emotional surges and bracing contrasts. An enviably uncluttered musical language often has modal overtones, and she favours spare, lean textures, with frequent open fifths and fourths anchored to a stable, tonic base. Words are set so as to ring out clearly and vocal lines stay within a practical range, following the contours of natural speech. The piece was originally written for soprano, but, in keeping with a current trend, exists in different transposed versions, each also open to adaptation for individual performers.
“Psychoanalysis and Laxatives,” or Democracy in America
Authors: Nadel Ira
Published: February 2021

Roth and misogyny, highlighted by attacks by Vivian Gornick, Claire Bloom, and Carmen Callil initiate this chapter and its persistent question: did Roth treat women only as one-dimensional sex objects or as fully rounded personalities with agency and power? Roth’s response, in a series of private documents, argues that women, at least in his life, were always respected and treated equally. He itemizes the key women in his professional career, from his early agent Candida Donadio through such late friendships such as Janet Malcolm, Judith Thurman, Zadie Smith, and Nicole Krauss. The issue of Roth and his father and the writing of Patrimony and the function of writing in the midst of trauma expand the chapter, plus his unparalleled productivity in the 1990s. The focus is on Operation Shylock, Sabbath’s Theater, and the American Trilogy—all this against the background of untangling himself from Claire Bloom, complicated by illness and depression. The impact and misrepresentations in Bloom’s Leaving a Doll’s House, however, complicated by Roth’s contradictory behavior with Bloom, created difficulties, personally and professionally. The increasing presence of death in his writing noted in Sabbath’s Theater and I Married a Communist shape the final pages as Roth’s evolving American identity comes into focus.
Quintet, or The Jersey Style
Authors: Nadel Ira
Published: February 2021

Roth’s late re-creation of the past, from Everyman to Nemesis is the focus of the chapter which begins with the causes for his look back and the emergence of a sustained melancholic tone to his writing presented in shorter fictions. The development of a “Jersey style” soon appears in his late works, preferring transparency and direct language instead of the embellished, piled-on prose of syntactic complexity seen earlier. An important discussion of The Plot Against America and its meaning for Roth and his readers shapes the center of the chapter, with a focus on children in the novel, equal in importance to its politics. His relationship with a new companion assisted in completing the novel, although he was constantly challenged by severe back pain which led to a back operation on 2002; heart problems requiring a series of stents also arose. And friends were dying: Bellow in 2005, Styron in 2006, Kitaj in 2007, and his brother in 2009. A consideration of the last three novels—Indignation, The Humbling, and Nemesis—precedes commentary on Roth’s final preparation of materials for his official biographer.
Coda: “It’s a Miserable Life”
Authors: Nadel Ira
Published: February 2021

This chapter begins with Roth’s comic assessment of his own career as an author shared with a young writer and then analyzes his final volume, the essay collection Why Write? It then examines how he spent his time after he gave up writing fiction, while noting his final public reading on 8 May 2014 in New York. His death in New York on 22 May 2018 and the international reaction to the news follows. His funeral at Bard College in May 2018 and his memorial service held at the New York Public Library on 25 September 2018 were occasions to honor and remember the writer. His efforts to complete his personal story, even from the grave, via instructions to his biographer and others. He always meant to be in control.
In situ automated imaging, using the Plankton Imager, captures temporal variations in mesozooplankton using the Celtic Sea as a case study
Authors: Scott James , Pitois Sophie , Close Hayden , Almeida Nevena , Culverhouse Phil , Tilbury Julian , Malin Gill
Published: February 2021

The Plankton Imager (PI) is an underway semi-automated, high-speed imaging instrument, which takes images of all passing particles and classifies the mesozooplankton present. We used data (temperature, salinity and mesozooplankton abundance) collected in the Celtic Sea in spring and autumn from 2016 to 2019 to assess the ability of the PI to describe temporal changes in the mesozooplankton community and to capture the seasonality of individual taxa. The description obtained using the PI identified both seasonal and interannual changes in the mesozooplankton community. Variation was higher between years than seasons due to the large variation in the community between years in autumn, attributed to the breaking down of summer stratification. The spring community was consistent between years. The seasonality of taxa broadly adhered to those presented in the literature. This demonstrates the PI as a robust method to describe the mesozooplankton community. Finally, the potential future applications and how to make best use of the PI are discussed.
Motif-based endomembrane trafficking
Authors: Arora Deepanksha , Damme Daniёl Van
Published: February 2021

Endomembrane trafficking, which allows proteins and lipids to flow between the different endomembrane compartments, largely occurs by vesicle-mediated transport. Transmembrane proteins intended for transport are concentrated into a vesicle or carrier by undulation of a donor membrane. This is followed by vesicle scission, uncoating, and finally, fusion at the target membrane. Three major trafficking pathways operate inside eukaryotic cells: anterograde, retrograde, and endocytic. Each pathway involves a unique set of machinery and coat proteins that pack the transmembrane proteins, along with their associated lipids, into specific carriers. Adaptor and coatomer complexes are major facilitators that function in anterograde transport and in endocytosis. These complexes recognize the transmembrane cargoes destined for transport and recruit the coat proteins that help form the carriers. These complexes use either linear motifs or posttranslational modifications to recognize the cargoes, which are then packaged and delivered along the trafficking pathways. In this review, we focus on the different trafficking complexes that share a common evolutionary branch in Arabidopsis (Arabidopsis thaliana), and we discuss up-to-date knowledge about the cargo recognition motifs they use.
COVID-19 and the rise of social activism in Southeast Asia: a public health concern
Authors: Corpuz Jeff Clyde G
Published: February 2021

The current public health crisis has radically altered the social and civic involvement in Southeast Asia. Although the virus has shifted the landscape of engagement, it has not dampened the enthusiasm of the public. In 2020–2021, more people than ever seem to be paying attention and even getting involved in activism. Many dramatic events happened during the coronavirus crisis such as from protests in support of the Black Lives Matter movement, public activism around the environment, economic inequality, authoritarianism and human rights violations. In Indonesia, the Philippines, Malaysia, Thailand and just recently Myanmar. The journal has lately published about the ‘Relationship of George Floyd protests to increases in COVID-19 cases using event study methodology’ and it has rightly expressed that the Centers for Disease Control and Prevention (CDC)-recommended social distancing guidelines must be followed in a protest situation. In response to the situation of social activism in Southeast Asia, one must follow the CDC-recommended and World Health Organization (WHO) guidelines in the Region. Although protesting is an individual human right, one must also be cautious and be aware of the deadly virus since we are still in a pandemic and the COVID-19 virus continues to mutate.
Psychospiritual care for parents during the COVID-19 pandemic
Authors: Quendan Randy G , Lingad Reiner B , Gozum Ivan Efreaim A
Published: February 2021

In a recent article, energy poverty increases the likelihood of depression in parents. The authors responded that this situation must be given attention because parental well-being can influence child development and outcomes. With this, we propose, in this paper, that an avenue that can be done is by providing a psychospiritual care for parents especially during the COVID-19 pandemic in which anxieties among family members arise.
Impact of psoriasis disease activity and other risk factors on serum urate levels in patients with psoriasis and psoriatic arthritis—a post-hoc analysis of pooled data from three phase 3 trials with secukinumab
Authors: Dehlin Mats , Fasth Andreas E R , Reinhardt Maximilian , Jacobsson Lennart T H
Published: February 2021

Objectives

Our aims were to determine if the Psoriasis Area Severity Index (PASI) score and serum urate (SU) levels were associated at baseline and whether the change in PASI score during 12 weeks of treatment resulted in a significant change in SU, adjusted for relevant confounders.

Methods

Data from patients with psoriasis/PsA (n = 1042/204) in three phase 3 randomized control trials treated with secukinumab (dose 300 mg, n = 628) or placebo (n = 414) were pooled. At baseline, values for SU, PASI and the following covariates were assessed: age, sex, BMI, estimated glomerular filtration rate, and medication with diuretics. To assess the changes in PASI (ΔPASI) and SU (Δurate), the differences (week 12 minus baseline) in patients receiving the active drug were used. Multivariable linear regression, adjusting for covariates, was used to assess the association between PASI and SU at baseline with all patients pooled and to assess the association between Δurate and ΔPASI over 12 weeks of treatment with secukinumab.

Results

The degree of skin involvement of psoriasis showed a statistically significant, albeit modest, association with SU (R2 = 0.014, P < 0.0001 univariately), whereas known risk factors for hyperuricaemia had a much larger impact cross-sectionally at baseline (R2 = 0.33, P < 0.0001). Furthermore, a substantial improvement in PASI score resulted in only a modest decrease of SU over 12 weeks of treatment with secukinumab (R2 = 0.014, P < 0.0001 univariately).

Conclusions

There is a statistically significant, albeit modest, association with both extent and change in PASI score and SU in patients with psoriasis, compatible with a potential pathophysiological relationship between urate and psoriasis.

Trial Registration

ERASURE: clinicaltrials.gov, https://clinicaltrials.gov, NCT01365455; FIXTURE: clinicaltrials.gov, https://clinicaltrials.gov, NCT01358578; SCULPTURE: clinicaltrials.gov, https://clinicaltrials.gov, NCT01406938
Competing for Talent: Firms, Managers, and Social Networks
Authors: Hacamo Isaac , Kleiner Kristoph
Published: February 2021

Do social networks help firms recruit talented managers? In our setting, firms are randomly connected to prospective young managers through former employees. Under a discrete choice model, we find networks increase the likelihood firms hire high-ability managers, while having no effect on the hiring rate of low-ability managers. Effects are greatest for nonlocal firms, strong ties, and peers living in the same neighborhood. Survey evidence suggests social networks promote recruitment by providing information about firm fundamentals to potential applicants. Our results help rationalize why the majority of managers hold prior connections to the firm.
PRACTICAL GUIDANCE ON THE REGULATORY MANAGEMENT OF RADIOACTIVE LIQUID DISCHARGES FROM MEDICAL, EDUCATIONAL AND RESEARCH LABORATORIES
Authors: Carinou E , Housiadas C
Published: February 2021

License applicants are often faced with the need to perform a radiological impact assessment study for the liquid discharges in public sewers, even for practices with short-lived isotopes used in medical, educational or research laboratories. The present paper addresses the regulatory management challenges in performing such assessments and provides a practical calculation toolbox that enables more realistic derivation of doses to critical members, based on a simple calculation means. The proposed methodology is validated through comparisons with results from other models. The effectiveness of the method is illustrated by considering relevant examples of hospitals and education and research establishments in Greece. The results show that the proposed method is a sound tool that achieves a more realistic estimation of the induced doses. In most cases a reduction in the initial screening dose estimates by several orders of magnitude is attained, thus greatly facilitating the effort needed to ascertain regulatory compliance.
Legislative Regulation of Criminal Liability for Environmental Crimes in the BRICS Countries
Authors: Ivanova Liliya V , Minin Roman V , Perezhogina Galina V
Published: February 2021

One of the areas of cooperation between the BRICS countries is the joint solution of environmental problems, in particular, air and water pollution by harmful emissions, waste management, climate change, biodiversity conservation, as well as the implementation of joint ‘green’ environmental projects. The aim of the study is to identify the features of criminal environmental protection in the BRICS countries. The leading method for studying this problem is the method of analysis of legal acts of the Russian Federation, the Federative Republic of Brazil, the Republic of India, the People’s Republic of China, and the Republic of South Africa, which establish criminal liability for infringements in the field of environmental protection. As a result of the study, the norms contained in the Brazilian Law on Environmental Crimes, in the Criminal Code of Russia, China, as well as in the laws of India and South Africa, which protect the air, land, water, animal, and plant life, were studied. The practical significance of the study is determined by the necessity to introduce liability for environmental crimes in individual countries that are members of the BRICS. It was concluded that it is necessary to develop supranational provisions to ensure environmental protection by legal means.
Antibiotic Response to Pediatric Scrub Typhus in South India: Is Clinical Failure to Azithromycin to be Worried?
Authors: Veerappan Ilamaran , Ramar Rathisharmila , Palanisamy Soundararajan
Published: February 2021

Background

Scrub typhus is typically associated with a rapid defervescence and clinical improvement within 48 h of initiation of appropriate antibiotics. But increasing reports of resistance to anti-rickettsial medications in scrub typhus are being reported in the literature.

Methods

This is a retrospective observational study of children up to the age of 14 years admitted between July 2017 and March 2020, to a private medical college hospital in southern part of India. The aim of this study was to compare the clinical response to antibiotic therapy with doxycycline and azithromycin in pediatric scrub typhus infection.

Results

One hundred thirty-eight children with scrub typhus infection were included for analysis. The median fever control time (h) was 12 (IQR = 6–29) and 24 (IQR = 10–52) with doxycycline and azithromycin respectively (p < 0.001*). Rapid fever control within 48 h was observed in 92% with doxycycline and in 74% with azithromycin (p < 0.001*). The clinical failure rate (defined by the necessity to change the antibiotics due to: (i) worsening of symptoms and signs of scrub typhus despite 48 h of antibiotics or (ii) persistence of fever and other symptoms of scrub typhus beyond 72 h), was significantly less with doxycycline (1%) compared with azithromycin (9.6%).

Conclusion

There has been a significant delayed clinical response to azithromycin in the treatment of scrub typhus in India, when compared to doxycycline. Hence it is preferable to use doxycycline as the first line of antibiotic for undifferentiated fever in scrub typhus endemic areas.

Lay summary

This retrospective study aims to compare the clinical response to doxycycline or azithromycin in the treatment of scrub typhus infection in children. The median fever control time, clinical failure rate and the proportion of children with rapid defervescence of fever within 48 h were significantly superior with doxycycline as compared to azithromycin. The findings of this study and those of similar studies in India represent a spectrum of delayed clinical response of Orientia tsutsugamushi to azithromycin as compared to doxycycline in this region.
Basal Rachis Internode Injection: A Novel Inoculation Method to Evaluate Wheat Resistance to Fusarium Head Blight
Authors: Zhang Yuhui , Li Aiai , Zhu Suqin , Li Lei , He Xinyao , Sun Zhengxi , Li Tao
Published: February 2021

Fusarium head blight (FHB) is one of the most destructive fungal diseases of wheat. However, difficulties in reliably phenotyping of this disease have greatly hindered the understanding of the mechanism of wheat–pathogen interaction and genetic improvement of FHB resistance. Here we report a novel inoculation method called basal rachis internode injection (BRII), in which inoculum is injected into the basal internode of a rachis instead of a floret, as is done in single floret inoculation (SFI). One of the prominent advantages of BRII over SFI and other traditional methods lies in its independence from the moisture-maintaining system that is necessary for all existing methods, making it insensitive to environmental humidity and hence cost-effective. Another unique feature of BRII is that this method produces nearly clear-cut reaction types, by which FHB resistance can be treated as a qualitative trait because generally no FHB symptoms appear on the spikelets of resistant genotypes. In addition, BRII outperformed SFI with a higher infection rate and better goodness of fit with known FHB resistance and quantitative trait locus components in a panel of 15 genotypes, as well as two populations of recombinant inbred lines segregating in Fhb1. Note that BRII and SFI methods are not mutually exclusive but rather complementary because each method has its own advantages in differentiating FHB resistance between genotypes. Combining these two methods would significantly improve the reliability and consistency of FHB phenotyping in wheat.
On the emergence, spread and resistance of Candida auris: host, pathogen and environmental tipping points
Authors: Chakrabarti Arunaloke , Sood Prashant
Published: February 2021

Over a decade ago, a multidrug-resistant nosocomial fungus Candida auris emerged worldwide and has since become a significant challenge for clinicians and microbiologists across the globe. A resilient pathogen, C. auris survives harsh disinfectants, desiccation and high-saline environments. It readily colonizes the inanimate environment, susceptible patients and causes invasive infections that exact a high toll. Prone to misidentification by conventional microbiology techniques, C. auris rapidly acquires multiple genetic determinants that confer multidrug resistance. Whole-genome sequencing has identified four distinct clades of C. auris, and possibly a fifth one, in circulation. Even as our understanding of this formidable pathogen grows, the nearly simultaneous emergence of its distinct clades in different parts of the world, followed by their rapid global spread, remains largely unexplained. We contend that certain host–pathogen–environmental factors have been evolving along adverse trajectories for the last few decades, especially in regions where C. auris originally appeared, until these factors possibly reached a tipping point to compel the evolution, emergence and spread of C. auris. Comparative genomics has helped identify several resistance mechanisms in C. auris that are analogous to those seen in other Candida species, but they fail to fully explain how high-level resistance rapidly develops in this yeast. A better understanding of these unresolved aspects is essential not only for the effective management of C. auris patients, hospital outbreaks and its global spread but also for forecasting and tackling novel resistant pathogens that might emerge in the future. In this review, we discuss the emergence, spread and resistance of C. auris, and propose future investigations to tackle this resilient pathogen.
Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care
Authors: Roberts Leah W. , Forde Brian M. , Hurst Trish , Ling Weiping , Nimmo Graeme R. , Bergh Haakon , George Narelle , Hajkowicz Krispin , McNamara John F. , Lipman Jeffrey , Permana Budi , Schembri Mark A. , Paterson David , Beatson Scott A. , Harris Patrick N. A.
Published: February 2021

Background. Infections caused by carbapenem-resistant

Acinetobacter baumannii

(CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016–2018.

Methods. A. baumannii, Klebsiella pneumoniae, Serratia marcescens and

Pseudomonas aeruginosa

isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital.

Results. In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and

K. pneumoniae

SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since.

Conclusion. We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.
Effects of visual attention modulation on dynamic effective connectivity and visual fixation during own-face viewing in body dysmorphic disorder
Authors: Wong Wan-wa , Rangaprakash D. , Diaz-Fong Joel P. , Rotstein Natalie M. , Hellemann Gerhard S. , Feusner Jamie D.
Published: February 2021

Background

In individuals with body dysmorphic disorder (BDD), selective attention biases and aberrant visual scanning patterns may cause imbalances in global vs. detailed visual processing, contributing to perceptual distortions for appearance. The mechanistic effects of modifying visual attention on brain function in BDD, which may be critical to developing perceptual-based treatments, have not been explored. This study tested the effects of visual-attention modulation on dorsal and ventral visual stream activation and connectivity, and eye behaviors.

Methods

We acquired functional magnetic resonance imaging data in 37 unmedicated adults with BDD and 30 controls. Participants viewed their faces under two conditions: a) unconstrained (naturalistically), and b) holding their gaze on the center of the image (visual-attention modulation), monitored with an eye-tracking camera. We analyzed activation and dynamic effective connectivity in dorsal and ventral visual streams and visual fixation duration.

Results

Visual-attention modulation resulted in longer fixation duration and reduced activation in dorsal and ventral visual streams in both groups compared with naturalistic viewing. Longer fixation duration was associated with greater effective connectivity from V1 to early dorsal visual stream during the second naturalistic viewing, across groups. During naturalistic viewing, there was greater V1 to early dorsal visual stream connectivity after, compared with before, visual-attention modulation.

Conclusions

When viewing one’s face, longer visual fixation may confer greater communication in dorsal visual system, facilitating global/holistic visual processing. The finding that reduction in visual scanning while viewing one’s face results in persistent effects during unconstrained viewing has implications for perceptual retraining treatment design for BDD.
FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system
Authors: Pawlowski Colin , Lenehan Patrick , Puranik Arjun , Agarwal Vineet , Venkatakrishnan AJ , Niesen Michiel J.M. , O’Horo John C. , Virk Abinash , Swift Melanie D. , Badley Andrew D. , Halamka John , Soundararajan Venky
Published: February 2021

Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st2020 and February 8th2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.
Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response
Authors: de Biagi Carlos Alberto Oliveira , Cury Sarah Santiloni , de Pádua Alves Cleidson , Rabhi Nabil , Silva Wilson Araujo , Farmer Stephen R. , Carvalho Robson Francisco , Batista Miguel Luiz
Published: February 2021

Adipose tissue has been classified based on its morphology and function as white, brown, or beige / brite. It plays an essential role as a regulator of systemic metabolism through paracrine and endocrine signals. Recently, multiple adipocyte subtypes have been revealed using RNA sequencing technology, going beyond simply defined morphology but by their cellular origin, adaptation to metabolic stress, and plasticity. Here, we performed an in-depth analysis of publicly available single-nuclei RNAseq from adipose tissue and utilized a workflow template to characterize adipocyte plasticity, heterogeneity, and secretome profiles. The reanalyzed dataset led to the identification of different subtypes of adipocytes including three subpopulations of thermogenic adipocytes and provided a characterization of distinct transcriptional profiles along the adipocyte trajectory under thermogenic challenges. This study provides a useful resource for further investigations regarding mechanisms related to adipocyte plasticity and trans-differentiation.

Highlights

Multidimensional transcriptome analysis at single-nucleus resolution recovers nuclei of cell types in adipose tissue

Adaptative thermogenic response results in 3 distinct mature adipose cell types

Single-nuclei transcriptomic-based secretome analysis reveals adipose cell-type-specific genes

Thein vivotrajectory of adipocyte plasticity for thermogenic response reveals sets of trans-differentiation genes

Graphic Abstract
Statistical determinants of visuomotor adaption along different dimensions during naturalistic 3D reaches
Authors: Ferrea E. , Franke J. , Morel P. , Gail A.
Published: February 2021

Neurorehabilitation in patients suffering from motor deficits relies on relearning or re-adapting motor skills. Yet our understanding of motor learning is based mostly on results from one or two-dimensional experimental paradigms with highly confined movements. Since everyday movements are conducted in three-dimensional space, it is important to further our understanding about the effect that gravitational forces or perceptual anisotropy might or might not have on motor learning along all different dimensions relative to the body. Here we test how well existing concepts of motor learning generalize to movements in 3D. We ask how a subject’s variability in movement planning and sensory perception influences motor adaptation along three different body axes. To extract variability and relate it to adaptation rate, we employed a novel hierarchical two-state space model using Bayesian modeling via Hamiltonian Monte Carlo procedures. Our results show that differences in adaptation rate occur between the coronal, sagittal and horizontal planes and can be explained by the Kalman gain, i.e., a statistically optimal solution integrating planning and sensory information weighted by the inverse of their variability. This indicates that optimal integration theory for error correction holds for 3D movements and explains adaptation rate variation between movements in different planes.
Gene loss during a transition to multicellularity
Authors: Jiménez-Marín Berenice , Rakijas Jessica B. , Tyagi Antariksh , Pandey Aakash , Hanschen Erik R. , Anderson Jaden , Heffel Matthew G. , Platt Thomas G. , Olson Bradley J. S. C.
Published: February 2021

Multicellular evolution is a major transition associated with momentous diversification of multiple lineages and increased developmental complexity. The volvocine algae comprise a valuable system for the study of this transition, as they span from unicellular to undifferentiated and differentiated multicellular morphologies despite their genomes being highly similar, suggesting multicellular evolution requires few genetic changes to undergo dramatic shifts in developmental complexity. Here, the evolutionary dynamics of six volvocine genomes were examined, where a gradual loss of genes was observed in parallel to the co-option of a few key genes. Protein complexes in the six species exhibited a high degree of novel interactions, suggesting that gene loss plays a role in evolutionary novelty. This finding was supported by gene network modeling, where gene loss outpaces gene gain in generating novel stable network states. These results suggest developmental complexity may be driven by gene loss, and not just by gene gain.

Significance Statement

Increased developmental complexity is thought to evolve mainly through genetic innovation and co-option. Comparison of the genomes of the closely related volvocines revealed that despite large changes in developmental complexity their genomes are exhibiting significant gene loss. Further, a burst of gene loss is shown to occur at the transition to undifferentiated multicellularity by gene inactivation and decay. This likely results in changes to protein-protein interactions within the cell, suggesting evolutionary novelty does not always require gene gain. Using empirical and modelling approaches we demonstrate gene loss can more easily produce protein network novelty than gene gain. We propose that gene loss can be a driver of biological innovation, allowing for reconfiguration of gene networks and differential use of existing functional repertoires.
Evolutionary jumps in bacterial GC content
Authors: Mahajan Saurabh , Agashe Deepa
Published: February 2021

Genomic GC content is a fundamental molecular trait linked with many key genomic features such as codon and amino acid use. Across bacteria, GC content is surprisingly diverse and has been studied for many decades; yet its evolution remains incompletely understood. Since it is difficult to observe GC content evolve on laboratory time-scales, phylogenetic comparative approaches are instrumental; but this dimension is rarely studied systematically in the case of bacterial GC content. We applied phylogenetic comparative models to analyse GC content evolution in multiple bacterial groups across two major bacterial phyla. We find that GC content diversifies via a combination of gradual evolution and evolutionary “jumps”. Surprisingly, unlike prior reports that solely focused on reductions in GC, we found a comparable number of jumps with both increased and decreased GC content. Overall, many of the identified jumps occur in lineages beyond the well-studied peculiar examples of endosymbiotic and AT-rich marine bacteria, and do not support the predicted role of oxygen dependence. Our analysis of rapid and large shifts in GC content thus identifies new clades and novel contexts to further understand the ecological and evolutionary drivers of this important genomic trait.