bluuebunny/crossref_metadata_2025 huggingface dataset:
The lacustrine microbial carbonate factory of the successive Lake Bonneville and Great Salt Lake, Utah, USA
Authors: Vennin Emmanuelle , Bouton Anthony , Bourillot Raphaël , Pace Aurélie , Roche Adeline , Brayard Arnaud , Thomazo Christophe , Virgone Aurelien , Gaucher Eric C. , Desaubliaux Guy , Visscher Pieter T.
Published: May 2018

The Bonneville Basin is a continental lacustrine system accommodating extensive microbial carbonate deposits corresponding to two distinct phases: the deep Lake Bonneville (30 000 to 11 500 14C bp) and the shallow Great Salt Lake (since 11 500 14C bp). A characterization of these microbial deposits and their associated sediments provides insights into their spatio‐temporal distribution patterns. The Bonneville phase preferentially displays vertical distribution of the microbial deposits resulting from high‐amplitude lake level variations. Due to the basin physiography, the microbial deposits were restricted to a narrow shoreline belt following Bonneville lake level variations. Carbonate production was more efficient during intervals of relative lake level stability as recorded by the formation of successive terraces. In contrast, the Great Salt Lake microbial deposits showed a great lateral distribution, linked to the modern flat bottom configuration. A low vertical distribution of the microbial deposits was the result of the shallow water depth combined with a low amplitude of lake level fluctuations. These younger microbial deposits display a higher diversity of fabrics and sizes. They are distributed along an extensive ‘shore to lake’ transect on a flat platform in relation to local and progressive accommodation space changes. Microbial deposits are temporally discontinuous throughout the lake history showing longer hiatuses during the Bonneville phase. The main parameters controlling the rate of carbonate production are related to the interaction between physical (kinetics of the mineral precipitation, lake water temperature and runoff), chemical (Ca2+, Mg2+ and HCO3− concentrations, Mg/Ca ratio, dilution and depletion) and/or biological (trophic) factors. The contrast in evolution of Lake Bonneville and Great Salt Lake microbial deposits during their lacustrine history leads to discussions on major chemical and climatic changes during this interval as well as the role of physiography. Furthermore, it provides novel insights into the composition, structure and formation of microbialite‐rich carbonate deposits under freshwater and hypersaline conditions.
A novel HLA variant, HLA‐C*03:376, detected by next generation sequencing
Authors: Pruszak J. , Bernheiden M. , Emmerich F.
Published: May 2018

HLA‐C*03:376 differs from HLA‐C*03:04:01 in exon 6 by a single nucleotide substitution.
Rebuilding
Authors: Osborne Evan
Published: May 2018

Here the analysis turns to questioning the very premises that underlie the virtues of self-regulating social systems. Macro-objections agree that individuals cannot be assumed to be able to do what is best. It is the job of political regulators to take over and facilitate the development of society. Marxist theory in particular viewed history as unfolding inevitably, and so appalling cruelties were inflicted by Marxist governments to steer the revolution forward. The eugenics revolution categorized entire groups of people as genetically inferior, frequently because of their ethnicity. Politics was used in various countries to improve society by reducing births among inferior types. Micro-objections to self-regulation described individuals as incapable of being incented to choose what self-regulation requires. In either case, it is the essential task of political regulators to replace, if not destroy, the outcomes of the choices made under self-regulation.
The Best Way(s) Forward
Authors: Osborne Evan
Published: May 2018

There is good reason to be skeptical of the assumption that political regulation operates with the public interest in mind. Scientific productivity has continued to advance in the past half-century, as has the value and quantity of human expression. The argument in favor of socioeconomic self-regulation is identical to that for the other two systems. Yet recent scholarship suggests declining rates of economic growth in the wealthiest countries most subject to increasing political regulation during this period, while greater reliance on self-regulating economic forces has resulted in dramatic improvement of socioeconomies in the developing world. As political regulation of human expression has declined, literary, artistic, and philosophical achievement have expanded. Guidance is offered for how people should understand social change in their role as citizens and how they should conduct themselves in a world full of short-term instability but tremendous long-term progress.
The Sincerity Edge
Authors: Christina Alexandra , Fort Timothy L.
Published: May 2018

The authors interviewed 22 leading CEOs who explained why ethical leadership is crucial to business, what conduct is most important, and who provided examples of both scandalous and exemplary conduct. Based on these interviews and the author’s own experience as a European corporate director and an American academic, they connect these interviews to a theory of ethical leadership that makes for dynamic businesses. They conclude with 12 concrete actions businesses can take to engage ethical leadership with a central theme that business ethics has its greatest economic payoff when sincerely embracing ethics as a good independent of its instrumental payoff.
Making Good Decisions about Strategy, Ethics, and Leadership
Authors: Alexandra Christina Countess of Frederiksborg , Fort Timothy L.
Published: May 2018

At the heart of good leadership and governance is good decision-making, whether applied to strategy, ethics, marketing, or anything else. Good decisions require being aware of our own cognitive biases, being analytical and methodical and gathering facts, applying the best knowledge we have to date, and listening to our intuitions and sentiments. Drawing from interviews with leading CEOs, this chapter provides a framework for arriving at values-driven decisions and governance.
Primitivism After Its Poststructural Eclipse
Authors: Etherington Ben
Published: May 2018

Chapter 1 focuses on the conceptual and theoretical problems that pertain to literary primitivism. It surveys the breadth of previous scholarship and points out that a comprehensive study that proceeded according to received usage would be hopelessly vast owing to the ahistorical presuppositions that have tended to inform its use. It sets out the terms by which the book redefines the term--especially, that primitivism was an aesthetic project specific to the historical moment when the possibility of primitive experience was perceived to be at the point of obsolescence. Transformed thus into an inherently speculative notion, it fell to the capacities of art to revive and reanimate the remnants of “primitive” (i.e., noncapitalist) social realities. The chapter reviews the previous postmodern generation of scholarship on primitivism, arguing that the historical nature of primitivism was obscured when scholars, employing the methods of poststructuralism, restricted their inquiries to questions of representation.
Primitivism and Philo-primitivism
Authors: Etherington Ben
Published: May 2018

Chapter 2 advances the historical side of the argument by drawing a distinction between “philo-primitivism” and “emphatic primitivism.” It finds that the philo-primitivist ideal of the “noble savage” was the product of earlier periods of European colonial expansion when there yet existed social worlds beyond the perimeter of the capitalist world-system. As the “primitive accumulation” of noncapitalist societies accelerated, so the ideal of the primitive became entirely speculative and utopian. Emphatic primitivism’s emergence coincides with the period that political economists at the time labeled “Imperialism,” a concept explored with reference to the work of Rosa Luxemburg in particular. The chapter ends with a discussion of the notion prevalent at this time that the “primitive” was in fact the product of “civilized” sublimation. Other writers and artists discussed include John Dryden, George Catlin, Charles Darwin, Jean-Jacques Rousseau, Robert Louis Stevenson, Karl Marx, Sigmund Freud, and Friedrich Nietzsche.
The Legislature and the ASEAN Charter
Authors: Rüland Jürgen
Published: May 2018

The chapter shows how as a consequence of democratization the Indonesian legislature became a major stakeholder in Indonesian foreign policymaking. Based on Acharya’s localization theory, it goes on to scrutinize the responses of Indonesian legislators to the external normative challenges during the ASEAN Charter debate. One of the results is that Indonesian legislators expect a reformed ASEAN to promote the democratization of regional governance and increases in public welfare. Yet, unlike NGO representatives, legislators avoided explicit calls for popular empowerment. In sum, legislators, too, did not opt for a wholesale adoption of European concepts of regional integration. They localized democracy aspirations with ancient notions of leadership, organicist ideas, and welfare concepts.
Indonesian Visions of Regionalism: From Yudhoyono to Jokowi
Authors: Rüland Jürgen
Published: May 2018

With the “leadership frame,” the chapter unearths a new interpretive frame of the Charter from 2009 onward, suggesting a gradual return of extant ideas of Indonesian foreign policymaking. The chapter also scrutinizes the internalization of the new EU-inspired ideas of regionalism. The litmus tests were events in which the territorial and economic sovereignty of Indonesia was challenged, such as the disputes with Malaysia over maritime borders and the ASEAN-China Free Trade Area. The response to these events showed that most stakeholders except civil society threw overboard many of the liberal-cosmopolitan values associated with European regional integration. Last, the chapter examines whether this ideational reversal continued under the Jokowi government and suggests that the latter did not abruptly break with the foreign policy of his predecessor. Many of the seemingly new Jokowi policies had their roots in the second term of the Yudhoyono presidency.
Emptied Lands
Authors: Kedar Alexandre , Amara Ahmad , Yiftachel Oren
Published: May 2018

It is commonly claimed by Israeli authorities that Bedouins are trespassers who never acquired property or settlement rights in southern Israel/Palestine. This led to massive dispossession of Bedouins. This book sets to examine state claims by providing, for the first time, a thorough analysis of the legal geography of the Negev. It adopts critical scholarly perspectives, drawing on multidisciplinary sources from geography, law, history and the social sciences. The study defines the “Dead Negev Doctrine (DND)”—a set of legal arguments and practices founded on a manipulative use of Ottoman and British laws through which Israel constructed its own version of “'terra nullius”—the now repealed colonial doctrine denying indigenous land and political rights. The book systematically tests the doctrine, using systematic archival and geographic research, and focusing on key land cases, most notably the al-‘Uqbi claim in ‘Araqib. The analysis reveals that the DND is based on shaky, often distorted, historical and legal grounds, thereby wrongly denying land rights from the majority of the Negev Bedouins. The book then discusses the indigeneity of the Bedouins in the face of persistent state denial. It argues that international law and norms protecting indigenous peoples are highly applicable to the case of Negev Bedouins. The book then offers an overview of state and Bedouin proposals to resolve the dispute. It shows how alternative plans advanced by the Bedouins, based on the concepts of recognition and equality, provide the most promising path to resolve the protracted conflict.
The Land Regime of the Late Ottoman Period
Authors: Kedar Alexandre , Amara Ahmad , Yiftachel Oren
Published: May 2018

This chapter begins to set the historical background for the book by outlining in detail the state of affairs in the Negev during the last period of Ottomans rule in the late nineteenth and early twentieth centuries. Focusing on tribal-state relations, the chapter explores the late Ottoman modes of governance, and traces changing Ottoman policies and practices in the region. More specifically, the chapter addresses the founding of the Beersheba sub-district, and seeks to understand the land regime that existed prior, during and after the Ottoman reforms (Tanzimat), especially the introduction of the 1858 Ottoman Land Code (OLC).
State and Bedouin Policies and Plans
Authors: Kedar Alexandre , Amara Ahmad , Yiftachel Oren
Published: May 2018

Among the most contested facets of the conflict between the state and the Bedouins are land ownership and recognition of 46 “unrecognized” or partly recognized localities. This chapter completes the picture by addressing the question of planning and the Bedouin unrecognized villages. Since 1948, the Israeli government has persistently and forcefully attempted to urbanize the Bedouins and concentrate them in a few urban centers. Such practices involved displacements, house demolitions, and zoning practices that produced an “illegal” geography and “gray spacing” that exposed the Bedouins to constant threat of demolition and eviction. The chapter outlines the various plans, commissions, and development and zoning plans introduced by the government, as well as the alternative plans and visions offered by the Bedouins communities, in an effort to protect their homes, localities and lands. Such alternative planning serves as a foundation for long-term reconciliation and coexistence between settler and indigenous groups.
Introduction
Authors: Leavitt-Alcántara Brianna
Published: May 2018

This chapter introduces the book’s methodology, arguments, and scholarly significance. Most works on women and early modern religion focus on nuns, holy women, or religious “deviants,” and emphasize rising hostility toward female autonomy as officials moved to enclose unmarried women and intensive female religiosity (e.g. mysticism, asceticism). This book takes a different approach and examines ordinary laywomen, particularly the broad population of non-elite women who frequently lived outside of both marriage and convent in colonial Spanish American cities. Through an analysis of approximately 550 wills, as well as a variety of other source materials such as hagiographies, religious chronicles, and ecclesiastical records, this study argues that the complex alliances forged between non-elite single women and the Catholic Church shaped local religion and the spiritual economy, late colonial reform efforts, and post-Independence politics in Guatemala’s capital.
City of Women, City of God
Authors: Leavitt-Alcántara Brianna
Published: May 2018

Chapter 1 examines the hagiography of local holy woman Anna Guerra de Jesús who migrated to Guatemala’s capital in the late seventeenth century. While the early modern Catholic ideal of feminine piety prized enclosure, obedience, and virginity, Anna was neither nun nor virgin, but rather a poor abandoned wife and mother. And although Church decrees clearly required actively religious laywomen to live in cloistered communities, Anna became an independent beata (laywoman who took informal vows) and Jesuit tertiary. This chapter explores Anna’s lived religious experience as a poor migrant and abandoned wife and mother, her engagement with female mysticism and devotional networks, and her alliances with powerful priests and religious orders. It also places Anna’s story within the context of late seventeenth and early eighteenth-century Santiago de Guatemala, particularly urban demographic shifts and social tensions, as well as movements for spiritual renewal and enthusiastic lay female piety.
Sex, Honor, and Devotion
Authors: Leavitt-Alcántara Brianna
Published: May 2018

Chapter 3 traces how non-elite single women navigated their moral status and developed alliances with the Catholic Church in the shifting religious landscape between 1700 and 1770. Although scholars have examined the ways in which elite women in colonial Spanish America took advantage of loopholes and the distance between public honor and private sexual matters, the experiences of non-elite women remain unclear. Wills highlight how laboring unmarried women invoked feminine ideals other than chastity and enclosure through their enthusiastic participation in confraternities and Third Orders, contributions to the spiritual economy as pious benefactors, and complex alliances with local priests. Much as scholars recognize that race in colonial Latin America was a flexible category and individuals might count multiple racial identities simultaneously or change their racial identity over time, these findings illustrate how poor single women took advantage of alternative feminine ideals and claimed moral status within their communities.
The Evolution and Adaptation of Business–Government Relations in Zouping
Authors: Dimitrov Martin K.
Published: May 2018

This chapter analyzes business-government relations in a single Chinese county through the lens of IPR regulation. A focus on Zouping reveals the scope of variation that exists in business-government relations more than two decades after the introduction of policies regarding the separation of business and government. Three different ideal-typical models characterize business-government relations in Zouping: the Maoist model, where state and business are fused; the local developmental state model, where state financial and administrative resources are used to create the best possible environment for business; and the regulatory state model, where the relationship between the state and business is mediated by regulatory agencies, which are independent of the state and approach business as impartial referees. This variation within the same county with regard to IPR enforcement highlights one of the main themes of this volume, namely the coexistence of both continuity and adaptive change in Zouping.
The Role of the Organization Department in Political Selection
Authors: Manion Melanie
Published: May 2018

In Zouping County, as elsewhere in China, the organization department is arguably the most powerful operational department of the communist party committee. This chapter focuses on the crux of that power, which is also the crux of party power: political selection. The county organization department collects information about party and government officials in the course of routine evaluations and non-routine vetting and uses that information to recommend personnel decisions to the party committee. This is a huge responsibility. Reform-era changes have not only increased the challenges for the department but also increased the likelihood that its failure to do the job well will be more easily detected. With few new staff and no major new institutional design, the organization department does many new (and newly required) things, so as to accomplish the core task of political selection that has always been its main charge.
China's ambitious brain science project inches forward
Authors: Normile Dennis
Published: May 2018

Beijing and Shanghai open new research centers ahead of the launch of a 15-year national effort.
Global health shifts to local experts with global partners
Authors: Hoy Anne Q.
Published: May 2018

Local health specialists seek international collaborations to fight health emergencies
Comment on “Plant diversity increases with the strength of negative density dependence at the global scale”
Authors: Hülsmann Lisa , Hartig Florian
Published: May 2018

LaManna
et al
. (Reports, 30 June 2017, p. 1389) claim that subadult trees are proportionally less common at high conspecific adult density (CNDD) and that this effect increases toward the tropics and for rare species. We show that the CNDD-abundance correlation may have arisen from a methodological artifact and that a range of processes can explain the reported latitudinal pattern.
Disparities in science literacy
Authors: Allum Nick , Besley John , Gomez Louis , Brunton-Smith Ian
Published: May 2018

Cognitive and socioeconomic factors don't fully explain gaps
Our inheritance
She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity
Carl Zimmer
Dutton, 2018. 672 pp.
Authors: Meyer Axel
Published: May 2018

A fascinating history of heredity research reveals the field's highs and lows
Illuminating dark depths
Authors: Gibson Peter R. , Burgell Rebecca E.
Published: May 2018

Microelectronic processing and engineered bacteria provide real-time insights into the gut
Comparison of
In Vitro
Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China
Authors: Zong Zhaojing , Jing Wei , Shi Jin , Wen Shu'an , Zhang Tingting , Huo Fengmin , Shang Yuanyuan , Liang Qian , Huang Hairong , Pang Yu
Published: May 2018

Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant
Mycobacterium tuberculosis
. In this study, we compared the
in vitro
activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA,
rplC
, and
rplD
genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240
M. tuberculosis
isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC
90
values for
M. tuberculosis
isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (
P
> 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (
P
= 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by
rplD
that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion,
in vitro
susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within
rplD
that endowed
M. tuberculosis
with linezolid, but not delpazolid, resistance was identified.
Examination of Needle Surface Corrosion in Electroacupuncture
Authors: Zhang Claire Shuiqing , Zhang George Shengxi , Xu Shanqing , Li Bin , Zhang Anthony Lin , Xue Charlie Changli , Xie Yi Min
Published: May 2018

Background

Electroacupuncture (EA) is a modern form of acupuncture therapy where stainless steel acupuncture needles are used as percutaneous electrodes to apply electrical stimulation. The concern about electrolytic corrosion of needles during EA has not been conclusively addressed.

Aim

To examine whether corrosion of stainless steel acupuncture needles occurs after EA to establish the safety profile of this therapy.

Methods

The study comprised four EA sessions on healthy participants mimicking a common clinical practice, with needle surface examinations conducted immediately after each session. Used acupuncture needles that did not undergo electrical stimulation and unused needles taken from the original package were also examined as control comparisons. Two commonly used types of single-use, silicone-coated, stainless steel needles were selected for the experiment. The ES-160 digital acupunctoscope (a charge-balanced electric stimulator) was used to deliver electrical stimulation, and an oscilloscope was used to record the waveforms and electric currents. All needles were sterilised before examination by a scanning electron microscope (SEM), where images of needle tips and shafts were taken for further analysis.

Results and conclusions

32 needles were examined under the SEM. As the main findings, the SEM images showed the surface finish, burr attachments and surface characteristics of needle samples. No evidence of electrolytic corrosion was detected on any needle that underwent electrical stimulation for 30 min delivered by a charge-balanced acupunctoscope in healthy participants. The choice of a charge-balanced acupunctoscope is recommended to avoid any potential corrosion of needles in EA clinical practice.
Multimorbidity in children and youth: a scoping review protocol
Authors: Romano Isabella , Buchan M Claire , Ferro Mark A
Published: May 2018

Introduction

Multimorbidity (co-occurring physical and mental illness) is an important issue for clinicians and researchers with combined efforts aimed at promoting the health and well-being of individuals across the life course. In children and youth, experience of any chronic physical illness leads to a substantial increase in risk for mental illness. As a growing field of interest, research is needed to map the current state of the literature in child and youth multimorbidity in order to identify existing gaps and inform the direction of future investigations.

Methods and analysis

We are proposing the conduct of a scoping review to explore the depth and breadth of existing evidence in the field of child and youth multimorbidity. The scoping review will follow the methodological framework developed by Arksey and O’Malley, and will incorporate additional scoping review recommendations made by Levacet al. A systematic search of the following four key databases will be conducted: (1) PubMed; (2) EMBASE; (3) PsycINFO; and (4) Scopus, using combinations of Medical Subject Headings (MeSH) and Emtree terms. We will also consult grey literature sources and hand-search reference lists of included studies to identify additional studies of relevance. For eligible studies that meet all identified inclusion and exclusion criteria, a data extraction tool will be used to collect and store key study characteristics that will be relevant for collating, summarising and reporting the results of the scoping review. This scoping review also presents a novel use of quality index scoring, which we anticipate will contribute to strengthening the rigour of the scoping review methodology.

Ethics and dissemination

The proposed scoping review does not require ethical approval. Final study results will be disseminated via conference presentations, publication in a peer-reviewed journal and knowledge translation activities with relevant stakeholders.
Nurse education
Authors: Barrett David
Published: May 2018

EBN Perspectives brings together key issues from the commentaries in one of our nursing topic themes.
Nardilysin inhibits pancreatitis and suppresses pancreatic ductal adenocarcinoma initiation in mice
Authors: Ikuta Kozo , Fukuda Akihisa , Ogawa Satoshi , Masuo Kenji , Goto Norihiro , Hiramatsu Yukiko , Tsuda Motoyuki , Kimura Yoshito , Matsumoto Yoshihide , Kimura Yuto , Maruno Takahisa , Kanda Keitaro , Nishi Kiyoto , Takaori Kyoichi , Uemoto Shinji , Takaishi Shigeo , Chiba Tsutomu , Nishi Eiichiro , Seno Hiroshi
Published: May 2018

Objective

Nardilysin (NRDC), a zinc peptidase, exhibits multiple localisation-dependent functions including as an enhancer of ectodomain shedding in the extracellular space and a transcriptional coregulator in the nucleus. In this study, we investigated its functional role in exocrine pancreatic development, homeostasis and the formation of pancreatic ductal adenocarcinoma (PDA).

Design

We analysedPtf1a-Cre; Nrdcflox/floxmice to investigate the impact ofNrdcdeletion. Pancreatic acinar cells were isolated fromNrdcflox/floxmice and infected with adenovirus expressing Cre recombinase to examine the impact ofNrdcinactivation. Global gene expression inNrdc-cKOpancreas was analysed compared with wild-type pancreas by microarray analysis. We also analysedPtf1a-Cre; KrasG12D; Nrdcflox/floxmice to investigate the impact ofNrdcdeletion in the context of oncogenic Kras. A total of 51 human samples of pancreatic intraepithelial lesions (PanIN) and PDA were examined by immunohistochemistry for NRDC.

Results

We found that pancreatic deletion ofNrdcleads to spontaneous chronic pancreatitis concomitant with acinar-to-ductal conversion, increased apoptosis and atrophic pancreas in mice. Acinar-to-ductal conversion was observed mainly through a non-cell autonomous mechanism, and the expression of several chemokines was significantly increased inNrdc-null pancreatic acinar cells. Furthermore, pancreatic deletion ofNrdcdramatically acceleratedKrasG12D-driven PanIN and subsequent PDA formation in mice. These data demonstrate a previously unappreciated anti-inflammatory and tumour suppressive functions of Nrdc in the pancreas in mice. Finally, absence of NRDC expression was observed in a subset of human PanIN and PDA.

Conclusion

Nrdc inhibits pancreatitis and suppresses PDA initiation in mice.
015 Predicting a diagnosis of pathologically confirmed vasculitic neuropathy
Authors: Nathani Dev , Barnett Michael H , Spies Judith , Pollard John , Kiernan Matthew C
Published: May 2018

Introduction

Nerve biopsy remains the gold standard to diagnose vasculitic neuropathy. Conversely, biopsy has imperfect sensitivity and entails risks associated with an invasive procedure. Methods to improve diagnostic accuracy remain important considerations given the severity of the disease, added with the risks associated with subsequent therapy, particularly in ill-defined cases.

Methods

Clinical, laboratory and neurophysiological parameters were analysed for all patients who subsequently underwent biopsy. Nerve and muscle biopsy reports were assigned pathologic categories of definite, probable, possible or absent vasculitis using standard guidelines. Correlations were assessed between pre-biopsy parameters and subsequent diagnosis of definite or probable vasculitic neuropathy (pathologically confirmed vasculitis).

Results

From a cohort of 207 patients who underwent nerve biopsy over 21 months, 70 were suspected of having vasculitic neuropathy prior to biopsy. Of the 70 patients, vasculitis was confirmed as definite (11.4%), probable (15.7%) or possible (10.0%) on neuropathological assessment. The most sensitive parameters for pathologically confirmed vasculitis were the presence of sensorimotor neuropathy (78%) and axonal neuropathy (67%) on nerve conduction studies (NCS) in the overall cohort. Pathologically absent vasculitis was most prevalent in patients with normal NCS (90%), chronic, symmetric symptoms (86%) and demyelinating findings on NCS (79%). The parameters with the strongest associations with pathologically confirmed vasculitis were positive autoantibody serology (50.0% vs 21.1%, p<0.01), anti-neutrophil cytoplasmic antibody (27.3% vs 6.4%, p<0.01), anti-myeloperoxidase antibody (22.7% vs 1.8%, p<0.005) and rheumatoid factor (22.7% vs 2.8%, p<0.005). In patients suspected to have vasculitis, 83.3% of anti-myeloperoxidase antibody positive patients had pathologically confirmed vasculitis. In patients not suspected to have vasculitis, acute symptoms had the strongest association with pathologically confirmed vasculitis (36.4% vs 10.5%, p<0.05).

Conclusion

Specific characteristics of symptoms at the time of presentation, combined with the presence of autoantibodies and neurophysiological abnormalities, were predictive of a tissue diagnosis of vasculitic neuropathy.
017 Paradoxical reaction in tuberculous meningitis: a tertiary referral hospital retrospective experience of concomitant immunosuppression therapy
Authors: Ledingham David , El-Wahsh Shadi , Cappelen-Smith Cecilia , Hodgkinson Suzanne , McDougall Alan , Maley Michael , Cordato Dennis
Published: May 2018

Introduction

Tuberculous meningitis (TBM) accounts for <1% of all tuberculosis (TB) presentations. Paradoxical reactions (PR) in non-HIV patients are a common manifestation of anti-tuberculosis therapy characterised by clinico-radiological deterioration. We report a case series of TBM admissions to our institution, including two cases with corticosteroid-refractory PR who responded to adjuvant cyclosporin.

Methods

Retrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005–2017) with laboratory and/or radiologically confirmed TBM.

Results

Median age 40 (range 22–81 years), 7 males. Eleven patients were of Asia-Pacific origin. All eleven presented with central nervous system manifestations and 1 had preceding miliary TB. Nine patients had extra-cranial TB involvement, including 8 with past or current pulmonary disease. Cerebrospinal fluid (CSF) TB PCR/culture was positive in 10 patients. One patient had multi-resistant TB. PR of TBM developed in 5 patients despite concomitant corticosteroids in 4. Two cases had refractory PR.

Case 1. 22 year old Vietnamese male presented with 6 week history of progressive headache and neck stiffness. CSF demonstrated 61 WCC (75% neutrophils), protein 2.67 g/L (n<0.45), glucose 2.1 mmol/L. Despite concomitant anti-tuberculosis and high-dose corticosteroid treatment, he developed worsening headaches and altered mentation with interval MRI brain increase in size and number of tuberculomas, hydrocephalus, and left thalamic infarction. Cyclosporin was added with gradual improvement and ultimately good outcome.

Case 2. 47 year old Filipino male presented with 3 week history of headache and neck stiffness and 3 day history of fever, dysarthria and diplopia. MRI brain showed basal meningitis, hydrocephalus and left putaminal infarction. CSF demonstrated 245 WCC (35% neutrophils), protein 0.68 g/L, glucose 1.8 mmol/L. Despite concomitant anti-tuberculosis and corticosteroid treatment, the patient developed PR-induced worsening hydrocephalus necessitating ventriculo-peritoneal shunting. Cyclosporin was added with gradual PR resolution.

Conclusion

Our case series highlights the importance of concomitant corticosteroids in TBM and the potential role of cyclosporin in refractory PR.
018 Management of migraine in the australian emergency department
Authors: Gunasekera Lakshini , Sun-Edelstein Christina , Heywood John , Sanders Lauren
Published: May 2018

Introduction

Acute migraine commonly causes significant personal, economic and work-related disability. Australian guidelines recommend treating mild migraine with aspirin and metoclopramide, and moderate-severe migraine with prochlorperazine, chlorpromazine or sumatriptan. Stratified treatment based on severity is preferred to step-wise treatment. Australian data regarding Emergency Department (ED) migraine treatment are scarce. We evaluated prescribing patterns at a Melbourne hospital against national guidelines.

Methods

Retrospective cohort study of migraine (G439 ICD-10-AM) between 2012–2016. Exclusion criteria included migraine without headache, other primary headaches and secondary headaches. Demographic and prescribing data were extracted from medical records. Proportions were calculated with 95% confidence intervals using Wilson’s method. Comparisons were made between groups using Mann-Whitney and Chi-square tests.

Results

Of 214,932 ED presentations, 744 with headache presentation received a G439 diagnosis. Most were female (75%; 558/744), young (mean age 34±13 years) and self-reported migraine history (75%; 558/744). There were 55 different medications prescribed. Paracetamol was more frequently prescribed (52%; 385/744) than aspirin (10.6%; 78/744). Opioid prescription occurred in 46% (345/744), single opioid 36% (267/744),>1 opioid 10% (78/744). Median time-to-discharge was 38 min longer with opioid prescription compared with no opioid (222; IQR 164–309 vs 184; 122–258; p<0.01). Just 6.85% (51/744) received triptans. Other treatments were prochlorperazine (14%; 97/744), metoclopramide (38%; 286/744) and chlorpromazine (44%; 3 25/744). Overall, 25.4% (189/744) received no guideline-recommended medication.

Conclusion

We observed considerable polypharmacy in ED migraine management with inconsistent prescribing patterns. Recommended medications are infrequently used. Opioid use is common and associated with increased time-to-discharge. Failure of ED staff to follow guidelines is unexplained, and requires further investigation.
024 Longitudinal diffusion tensor imaging in the primary progressive aphasias
Authors: Mahoney Colin J , Simpson Ivor JA , Nicholas Jennifer M , Rohrer Jonathan D , Warren Jason D
Published: May 2018

Introduction

Primary progressive aphasia (PPA) is characterised by progressive erosion of the language network, and is most commonly associated with frontotemporal lobar degeneration. Few biomarkers exist for diagnosis and tracking of disease progression in PPA. Novel techniques such as diffusion tensor imaging (DTI) may allow early disease detection and monitoring, as well as improving our understanding of the trajectory of PPA.

Methods

Thirty patients with PPA (13 with non-fluent variant, 11 with semantic variant, 6 with logopenic variant), and 20 age-matched healthy participants were assessed using serial DTI at baseline and on average 1.2 years later. Baseline and follow-up DTI scans were registered using a group-wise approach and a region-of-interest analysis performed for individual white matter tracts. Annualised rates of change for DTI metrics were calculated and compared between groups. Changes in neuro-psychometric scores were correlated with white matter structural changes.

Results

In the non-fluent group, rates of change in fractional anisotropy were most significant within the right and left superior longitudinal fasciculus (right, −5.7%/year, left, −4.3%/year, p<0.001). In the semantic group, change was most significant in right uncinate fasciculus (−14.8%/year, p<0.001). In the logopenic group, change was most significant in only radial diffusivity, within the right inferior longitudinal fasciculus (6.8% per year increase, p<0.05). Using DTI as an outcome measure, sample size estimates for future treatment trials were generally lower across all syndromic groups compared with volumetric MRI.

Conclusion

This study demonstrates the feasibility of longitudinal DTI, identifying rates of disease progression across the spectrum of PPA. Syndrome specific trajectories of disease progression emerged. This highlights the potential use of serial DTI as a disease biomarker in PPA, particular in the design of future treatment trials.
027 Lightning injuries: keraunoparalysis and other neurologic manifestations
Authors: Hooi Wai Foong , Tse Gabrielle , Waterston John
Published: May 2018

Introduction

Lightning is one of the most powerful and spectacular natural phenomena. A flash of lightning can heat the air around it to 27 000 degrees Celsius, 6 times hotter than the surface of the sun. Lightning strikes the earth more than 8 million times per day. It was responsible for more than 2 40 000 injuries per year worldwide. Neurologic complications after lightning strikes are not uncommon. They vary from transient benign symptoms to permanent neurological deficits. We present a case of keraunoparalysis and a literature review of neurologic manifestations of lightning strikes.

Case

A 23 year old man presented with acute paraplegia with complete sensory loss in the lower limbs after being struck by lightning. He also suffered from other significant injuries including mild sensorineural hearing loss in the left ear, right upper lobe pulmonary contusion, rhabdomyolysis (creatine kinase level peaked at 17 867units/L) and bilateral lower limb compartment syndrome requiring emergency fasciotomy. MRI full spine was normal with no evidence of cord lesion. His lower limb neurology improved significantly over 48 hours.

Conclusion

Keraunoparalysis is characterised by transient lower limb weakness that usually improves within hours to days. In patients presenting with paraparesis post lightning strike, it is important to consider the diagnosis of keraunoparalysis to avoid unnecessary surgical procedures. Neuroimaging is crucial to exclude other etiologies such as traumatic cord injuries or bleeding.

References

. Cherington M. Neurologic manifestations of lightning strikes. Neurology2003;60:182–5.

. Ritenour AE, Morton MJ, McManus JG, Barillo DJ, Cancio LC. Lightning injury: A review. Burns2008;34:585–94.

. Kumar A, Srinivas V, Sahu BP. Keraunoparalysis: What a neurosurgeon should know about it?J Craniovertebr Junction Spine2012Jan;3(1):3–6.
038 Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia mimicking systemic lupus erythematosus cerebral vasculitis
Authors: Lubomski Michal , Buckland Michael , Sy Joanne , Wei Heng , Tan Irene , Kane Barry , Spring Penelope J
Published: May 2018

Introduction

We present an unusual case of adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP) mimicking systemic lupus erythematosus (SLE) cerebral vasculitis. ALSP is an autosomal dominant progressive leukodystrophy, associated with mutations in the CSF1R gene, which induce dysregulation of microglia. The case was compiled from records of clinical data, imaging, brain biopsy and genetic studies.

Case

A 56 year old previously high functioning man of Southern Chinese origin was hospitalised with recurrent seizures. He had a prior 4 year history of progressive neuropsychiatric features, and 1 year of cognitive decline and occasional falls. Within the year prior, he had positive SLE serology and a renal biopsy consistent with lupus nephritis treated with steroids, mycophenolate, hydroxyl-chloroquine, and later rituximab due to concerns of evolving cerebral vasculitis on cerebral MRI and SPECT scan with MoCA of 20/30. Examination after seizure therapy revealed hyperreflexia, fine tremor, myoclonus, pseudobulbar affect, ideomotor apraxia and slow, independent gait. RUDAS was 6/30 with perseveration. CSF examination and SLE serology were quiescent. Consecutive brain MRIs showed multiple regions of worsening high T2/FLAIR signal in the corpus callosum and supra-tentorial white matter with persistent restricted diffusion. IV steroids and cyclophosphamide were added. Following treatment unresponsiveness, a frontal lobe brain biopsy demonstrated white matter gliosis with prominent axonal spheroids consistent with a primary leukoencephalopathy, with no inflammation, vasculitis nor infection. Immunotherapy was weaned. Genetic testing confirmed a positive CSF1R mutation (c.2329C>T; p. Arg777Trp in Exon 18). A positive family history of dementia in the patient’s elderly mother overseas was identified. The patient remained mobile but mute, and fatally aspirated 8 months after final presentation.

Conclusion

This report illustrates an unusual presentation of ALSP, initially misdiagnosed as SLE vasculitis. Clinicians should consider an adult onset leukodystrophy and proceed to biopsy and CSF1R gene testing early in suspected ‘refractory cerebral vasculitis’.
040 An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis
Authors: Galazka Andrew , Nolting Axel , Cook Stuart , Leist Thomas , Comi Giancarlo , Montalban Xavier , Hicking Christine , King John , Dangond Fernando
Published: May 2018

Introduction

An independent meta-analysis; Pakpoor et al. Neurol Neuroimmunol Neuroinflamm 2015;2:e158) in Phase III trials (with a 2 year duration) of disease modifying drugs (DMDs) in patients with relapsing multiple sclerosis found no increased rate of malignancy with cladribine tablets (CT) versus other DMD treatments. Data from additional trials involving CT 3.5 mg/kg (CT3.5) and a safety registry (up to 8 years’ follow-up) allow further insights into malignancy risk. Objective is to assess malignancy risk with CT3.5 monotherapy and placebo (PBO) in data from 3 Phase III trials and a registry, and compare the incidence rate with a global database.

Methods

The CT 3.5 population comprised 923 patients (3433 patient-years’ [PY] total exposure time) and the PBO group comprised 641 patients (2026 PY). Individual case reports of malignancies were reviewed by independent, blinded adjudication committee. Standardised incidence ratios (SIR) were calculated using the GLOBOCAN reference population (excluding non-melanoma skin cancers [NMSCs]) and a Danish reference population for NMSC rates.

Results

The incidence per 100 PY of confirmed malignancy was CT3.5 0.293 (95%CI 0.158–0.544) and PBO 0.148 (95%CI 0.048–0.460); the risk difference 95% CI included 0 (−0.166–0.414). The CT 3.5 malignancy SIR was almost identical (0.97, 95% CI 0.44–1.85) to the GLOBOCAN matched reference population. The PBO group SIR was numerically lower (0.48, 95% CI 0.14–1.53). There were no cases of haematological, lymphoproliferative or virus-induced cancers. There was no clustering of specific tumour types, and the incidence of skin cancer was not increased after treatment with CT3.5 versus PBO. The incidence of malignancies with CT3.5 was constant and did not increase over time.

Conclusion

Analysis of malignancy rates in a cohort that includes patients with up to 8 years’ follow-up confirms the Conclusion of the earlier meta-analysis; the incidence of malignancies with CT3.5 is similar to a matched reference population.
047 Creutzfeld-jakob disease with prolonged disease course in two younger patients
Authors: Dhanapalaratnam Roshan , Beran Roy , Buckland Michael , Cappelen-Smith Cecilia
Published: May 2018

Introduction

Sporadic Creuzfeldt-Jakob disease (sCJD) is a rare disease caused by prion proteins and usually presents in the 7th decade of life. sCJD classically presents with a rapidly progressive dementing illness, associated myoclonus and a median time to death of 6 months. Less commonly younger patients are described with a neuropsychiatric presentation and a prolonged disease course. We report two young sCJD patients with neuropsychiatric presentations and slow disease progression admitted to Liverpool Hospital, Sydney (2016–2017).

Case 1 A 48 year old Chinese man presented with a 12 month history of depressive symptoms and insomnia. Over the next 5 months, he developed progressive cognitive impairment, disinhibited behaviour, aggression, paranoia and ataxia of gait. Serial EEG and MRI brain scans, cerebrospinal fluid (CSF) testing for 14–3–3 protein and PRNP gene testing were negative or non-contributory. He progressively became mute, bedbound and died at 24 months from symptom onset. Diagnosis was only confirmed with a limited brain autopsy at post-mortem that revealed severe microvacuolar change, gliosis, neuronal loss and status spongiosus. Anti-prion antibody 12 F10 staining showed a diffuse fine synaptic pattern in the frontal cortex and striatum consistent with sCJD.

Case 2 A 42 year old Afghani man presented with a 36 month history of emotional lability and progressive social withdrawal followed by auditory and visual hallucinations, cognitive impairment and gait ataxia. Screening for vasculitis, infective (including HIV/syphilis) and autoimmune encephalopathies were negative. EEG demonstrated non-specific slowing, without characteristic periodic sharp-wave complexes. MRI brain was initially normal but progress imaging showed bilateral cortical ribboning, caudate nucleus T2-hyperintensity and associated diffusion restriction consistent with sCJD. CSF 14–3–3 protein analysis was positive. The patient died 38 months from symptom onset. Post-mortem examination was not performed.

Conclusions

CJD in younger patients may present as a slowly progressive neuropsychiatric disorder and ante-mortem investigations may remain negative. Post-mortem remains the gold standard for CJD diagnosis.