bluuebunny/crossref_metadata_2025 huggingface dataset:
Promotion
Authors: Smith Daniel M.
Published: January 2019

This chapter evaluates the advantage of dynastic ties in promotion to cabinet. Before 1970, legacy members of parliament—particularly those whose predecessors had served in cabinet—were overrepresented in most cabinets. From 1970 to 1993, seniority rule and factional balancing functioned as informal institutions constraining the choices of LDP prime ministers, and legacy MPs enjoyed no apparent advantage. In the years since electoral reform, legacy MPs are again dramatically overrepresented in LDP cabinets. For those whose predecessors never served in cabinet, this advantage is due in large part to seniority. Legacy MPs with a family history in the cabinet, conversely, enjoy a significant advantage in promotion that cannot be explained simply by seniority. It is likely that the relatives of former cabinet ministers benefit from internal party networks or other informational advantages within the party. The advantage of cabinet legacies is evident in several of the comparative country cases.
The Consequences of Dynastic Politics for Representation
Authors: Smith Daniel M.
Published: January 2019

This chapter considers several potential downstream effects of dynastic politics on the functioning of democracy and the quality of representation, including effects on gender representation, the representational style of candidates, and legislative behavior. There is a clear pattern across democracies and in Japan of a gender bias in dynastic politics. However, this bias tends to decrease over time. An analysis of the policy content of candidate manifestos suggests that dynasties provide some continuity in representation for voters, which may be part of their appeal. There is less evidence that legacy MPs are any more active in the legislature than non-legacy MPs. Although cabinet legacies tend to speak more in plenary sessions of the Diet since electoral reform, there are no other obvious differences in the legislative activity of legacy and non-legacy MPs.
Introduction
Authors: Pula Besnik
Published: January 2019

The reigning image of state socialist economies as they existed during the second half of the twentieth century is that of fully closed, autarchic systems. Today, by a number of measures, including dependence on foreign direct investment (FDI), export specialization, and the dominance of transnational corporations (TNCs) in the local economy, the ex-socialist economies of Central and Eastern Europe are among the most globalized in the world. Was the socialist past merely an obstacle these countries needed to overcome to join the global economy? Or, did socialism instead lay the groundwork for the region’s present-day globalization? ...
The Limits of Autarchy in the Periphery
Authors: Pula Besnik
Published: January 2019

This chapter provides an historical overview of Central and Eastern Europe’s integration into the Soviet economic sphere and its effects on patterns of industrialization and trade. It is organized in four parts. First, the chapter discusses the international context of the early Cold War, economic reconstruction and trade policies, and the formation of Comecon. The chapter then turns to the post-Stalin period, when Soviet leaders begin to increasingly see Comecon’s role as a tool of regional economic integration. It examines the benefits of intra-bloc trade by comparing the region with other state socialist and developing states to demonstrate how membership in Comecon aided in facilitating rapid industrialization. Finally, it discusses the challenges Soviet and Central and East European leaders saw in expanding trade with the West.
Critical Junctures and the Politics of Institutional Adjustment
Authors: Pula Besnik
Published: January 2019

This chapter demonstrates how political factors determined the path of postsocialist development and international market specialization in the 2000s. International market roles of individual economies built upon the cumulative advantages in transnational production Central and Eastern European economies gained during their socialist experience, but it was the political challenge of turning cumulative advantage into a sustained comparative institutional advantage that brought important gains in the capital, technological and skill base of the economy that concerned the politics of reform in the 1990s and 2000s. It was here that the interplay between industrial restructuring and reform of other institutions of the political economy came to matter. The chapter examines these policy patterns to show the divergent specialization of Hungary and Slovakia into an assembly platform, Czech Republic and Slovenia into an intermediate producer, and Bulgaria, Poland, and Romania into combined roles.
Introduction
Authors: Wobick-Segev Sarah
Published: January 2019

Pointing to the larger claims of the book, the introduction argues that the late nineteenth and early twentieth centuries were a key moment in the creation of the Jewish individual--a moment when forms and structures of religious, familial, and communal authority were subsumed under the needs and concerns of the individual. As a result, personal desire increasingly defined the limits and scope of Jewishness, resulting in the creation of voluntary Jewish communities. Critically, the emergence and evolution of the Jewish individual occurred roughly at the same time as another pivotal social and cultural development: Leisure sites, including cafés, restaurants, hotel halls, and sports clubs, were gaining increased popularity in European society as available free time increased. The Introduction explores the relevant historiographic and theoretical debates connected to the spatial turn and highlights how they would become important for the Jewish communities of Berlin, Paris, and St. Petersburg.
Political Science
Authors: Chico Tita
Published: January 2019

Late seventeenth-century natural philosophers inherited the conjunction of politics and science at the core of Francis Bacon’s experimental project. Thomas Sprat’s The History of the Royal Society, Margaret Cavendish’s The Blazing World, and Jonathan Swift’s Gulliver’s Travels use the conventions of literary knowledge to express their scientific-political visions, insisting that natural philosophy cannot be understood apart from the political institutions enabling and enabled by its practice and promulgation. These writers use the experimental imagination to envisage, in turn, civil government, absolutist monarchy, and imperialism. Sprat advances scientific triumphalism and a model for schooling gentlemen into civil society.
Dynamic Response and Nonlinear Characteristics of Spatial Parallel Mechanism With Spherical Clearance Joint
Authors: Xiulong Chen , Yuewen Li , Yonghao Jia
Published: January 2019

Spherical joint is a type of common kinematic pair in spatial parallel mechanism. The existence of spherical joint clearance has many adverse effects on the mechanism. A method of forecasting the dynamic behaviors of spatial parallel mechanism with spherical clearance joint is proposed. The 4-UPS-UPU spatial parallel mechanism with spherical clearance is taken as the research object, the dynamic response, and nonlinear characteristics of the mechanism are studied. The kinematic model and the contact force model of the spherical clearance are established. The dynamic equation of the spatial parallel mechanism with spherical joint clearance is derived by Newton–Euler method. The above-mentioned dynamic equation is solved by using the ODE113 function that is based on a variable order numerical differential algorithm in matlab. The dynamic responses of moving platform with different clearance values are analyzed. The contact force and the center trajectory of the sphere at the spherical joint are obtained. In addition, the phase trajectory, Poincare map, and bifurcation diagram are analyzed, and the nonlinear characteristics of the spherical clearance joint and the moving platform are obtained. By comparing the results, such as the acceleration of moving platform and the contact force, with virtual prototype simulation, the correctness of the dynamic equation of the spatial parallel mechanism with spherical clearance joint and the analysis results are verified. The researches show that the change of clearance value has a great influence on the motion state of spherical clearance joint, and chaos phenomena appears in the clearance joint with the increase in the clearance value. And the impact phenomenon appears between the spherical joint elements, which makes the mechanism generated vibration.
Energy Conversion by Nanomaterial-Based Trapezoidal-Shaped Leg of Thermoelectric Generator Considering Convection Heat Transfer Effect
Authors: Raihan Mohammad Siddique Abu , Kratz Franziska , Mahmud Shohel , Van Heyst Bill
Published: January 2019

Thermoelectric generators (TEGs) can harvest energy without any negative environmental impact using low potential sources, such as waste heat, and subsequently convert that energy into electricity. Different shaped leg geometries and nanostructured thermoelectric materials have been investigated over the last decades in order to improve the thermal efficiency of the TEGs. In this paper, a numerical study on the performance analysis of a nanomaterial-based (i.e., p-type leg composed of BiSbTe nanostructured bulk alloy and n-type leg composed of Bi2Te3 with 0.1 vol % SiC nanoparticles) trapezoidal-shaped leg geometry has been investigated considering the Seebeck effect, Peltier effect, Thomson effect, Fourier heat conduction, and surface to surrounding irreversible heat transfer loss. Different surface convection heat transfer losses (h) are considered to characterize the current output, power output, and thermal efficiency at various hot surface (TH) and cold surface (TC) temperatures. Good agreement has been achieved between the numerical and analytical results. Moreover, current numerical results are compared with previous related works. The designed nanomaterial-based TEG shows better performance in terms of output current and thermal efficiency with the thermal efficiency increasing from 7.3% to 8.7% using nanomaterial instead of traditional thermoelectric materials at h = 0 W/m2K while TH is 500 K and TC is 300 K.
The Anatomage table: Differences in student ratings between initial implementation and established use
Authors: Fyfe Sue , Fyfe Georgina , Dye Danielle , Radley-Crabb Hannah
Published: January 2019

Introduction: Increased student numbers and limited cadaver/prosected materials in health courses at Curtin University have required reviewing the way in which we teach our students in laboratory classes. The Anatomage table, an interactive tablet for viewing life-size anatomical images, was introduced into first-year human biology classes in 2013 to replace cadaver materials. Methods: Two student cohorts were surveyed in 2013 and 2014 on their perception of the usefulness of the Anatomage table and other anatomy resources to their learning. On a scale of 0–100, students were asked to rate a range of anatomy learning tools, including the Anatomage table. Results: Respondents (2013, n = 333; 2014, n = 329) rated video/animations most useful for learning (77.8/100), followed by models (63.9/100), plastinates (58.4/100) and the Anatomage table (42.4/100), a pattern consistent across gender, use of digital devices and cohort year. In 2014, respondents rated the Anatomage table more favourably (42.4/100) than in 2013 (36.9/100) (p = 0.022). The Anatomage table was rated most helpful for understanding relative sizes of organs but least helpful for using correct anatomical terminology. Qualitative data showed that in 2013, students were frustrated by screen-freezing problems and low-quality graphics, issues that were mostly addressed by 2014. Across both years, student comments were positive regarding the 3D aspect, seeing organ sizes and relationships, the slice tool for cross-sections and avoiding the need for cadaver specimens. Students also liked the Anatomage structured activities and pre-set images but wanted more time to explore and less than eight students around the table at any one time. Students felt unprepared for using the Anatomage table, and the single touch capacity was limiting when working in groups. Conclusions: These findings indicate that touch-screen technology needs careful curriculum design and training for both students and staff to optimise its usefulness for learning.
A new species of the genus Adamystis Cunliffe (Acari: Trombidiformes: Adamystidae) from Iran, with a key to the world species
Authors: Paktinat-Saeij Saeid , Ahaniazad Mansoureh , Bagheri Mohammad , Damavandian Mohammad Reza
Published: January 2019

A new species, Adamystis saboorii sp. nov. (Trombidiformes: Prostigmata: Adamystidae) is described based on adult females from Maragheh city, East Azerbaijan Province, Iran. The new species can be distinguished from other species by the following features: three pairs of adoral setae; chelicera with two setae; idiosoma with reticulated dorsal shield; lateral lens-like structures absent, three pairs of aggenital setae (ag1–3) on divided coxisternal shield and two setae (ag4–5) on a large reticulated shield. Also, an identification key to known species of Adamystis is updated.
Government report blasts creator of CRISPR twins
Authors: Normile Dennis
Published: January 2019

He Jiankui loses university job after preliminary findings that he "dodged supervision" and violated regulations.
Bearing witness
Authors: Starr Douglas
Published: January 2019

In the courtroom, physician David Egilman is the scourge of companies he accuses of harming public health and corrupting science.
Mason awardees display benefits of outsider perspectives
Authors: Kimbrell Elana
Published: January 2019

Early-career female researchers in chemistry recognized for connections across scientific disciplines
Characterizing mutagenic effects of recombination through a sequence-level genetic map
Authors: Halldorsson Bjarni V. , Palsson Gunnar , Stefansson Olafur A. , Jonsson Hakon , Hardarson Marteinn T. , Eggertsson Hannes P. , Gunnarsson Bjarni , Oddsson Asmundur , Halldorsson Gisli H. , Zink Florian , Gudjonsson Sigurjon A. , Frigge Michael L. , Thorleifsson Gudmar , Sigurdsson Asgeir , Stacey Simon N. , Sulem Patrick , Masson Gisli , Helgason Agnar , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Stefansson Kari
Published: January 2019

Human recombination and mutation mapped

Genetic recombination is an essential process in generating genetic diversity. Recombination occurs both through the shuffling of maternal and paternal chromosomes and through mutations generated by resolution of the physical breaks necessary for this process. Halldorsson
et al.
sequenced the full genomes of parents and offspring to create a map of human recombination and estimate the relationship with de novo mutations. Interestingly, transcribed regions of the genome were less likely to have crossovers, suggesting that there may be selection to reduce changes in genetic sequences via recombination or mutation in these regions.

Science
, this issue p.
eaau1043
Working together for Amazonia
Authors: Artaxo Paulo
Published: January 2019

This month, President Jair Bolsonaro took office in Brazil. He must now lead a country that is undergoing its worst recession and political divisions in a generation—a daunting time to take up the reins. Unfortunately, his immediate solutions are a threat to the Amazon forest—a resource that most Brazilians want to protect. For this sentiment to continue to flourish, science and its role in policy-making must be strengthened, not reduced. Brazil must keep environmental conservation and sustainability as priorities if it wants solutions that benefit all of its people, as well as the greater Earth ecosystem, for future generations.
Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
Authors: Robertson Gregory T. , Ektnitphong Victoria A. , Scherman Michael S. , McNeil Matthew B. , Dennison Devon , Korkegian Aaron , Smith Anthony J. , Halladay Jason , Carter David S. , Xia Yi , Zhou Yasheen , Choi Wai , Berry Pamela W. , Mao Weimin , Hernandez Vincent , Alley M. R. K. , Parish Tanya , Lenaerts Anne J.
Published: January 2019

AN12855 is a direct, cofactor-independent inhibitor of InhA in
Mycobacterium tuberculosis
. In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid.
Molecular Basis for the Potent Inhibition of the Emerging Carbapenemase VCC-1 by Avibactam
Authors: Mangat Chand S. , Vadlamani Grishma , Holicek Viktor , Chu Mitchell , Larmour Veronica L. C. , Vocadlo David J. , Mulvey Michael R. , Mark Brian L.
Published: January 2019

In 2016, we identified a new class A carbapenemase, VCC-1, in a nontoxigenic
Vibrio cholerae
strain that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1-producing
V. cholerae
isolates were recovered along the German coastline.
Predicting Antibiotic Resistance in Gram-Negative Bacilli from Resistance Genes
Authors: Walker G. Terrance , Quan Julia , Higgins Stephen G. , Toraskar Nikhil , Chang Weizhong , Saeed Alexander , Sapiro Vadim , Pitzer Kelsey , Whitfield Natalie , Lopansri Bert K. , Motyl Mary , Sahm Daniel
Published: January 2019

We developed a rapid high-throughput PCR test and evaluated highly antibiotic-resistant clinical isolates of
Escherichia coli
(
n
 = 2,919),
Klebsiella pneumoniae
(
n
 = 1,974),
Proteus mirabilis
(
n
 = 1,150), and
Pseudomonas aeruginosa
(
n
 = 1,484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), or Oceania (1%) or were of unknown origin (9%).
Large-Scale Identification of AbaR-Type Genomic Islands in Acinetobacter baumannii Reveals Diverse Insertion Sites and Clonal Lineage-Specific Antimicrobial Resistance Gene Profiles
Authors: Bi Dexi , Xie Ruting , Zheng Jiayi , Yang Huiqiong , Zhu Xingchen , Ou Hong-Yu , Wei Qing
Published: January 2019

AbaR-type genomic islands (AbaRs) are important elements responsible for antimicrobial resistance in
Acinetobacter baumannii
. This study performed a large-scale identification of AbaRs to understand their distribution and compositions of antimicrobial resistance genes.
Higher Temperatures Do Not Always Achieve Better Antibiotic Resistance Gene Removal in Anaerobic Digestion of Swine Manure
Authors: Huang Xu , Zheng Jialun , Tian Shaohua , Liu Chaoxiang , Liu Lin , Wei Lili , Fan Hongyong , Zhang Tingfeng , Wang Lei , Zhu Gefu , Xu Kaiqin
Published: January 2019

Antibiotic resistance genes (ARGs) are frequently detected with high abundance in manure-applied soils. Anaerobic digestion is one of widely used processes for animal waste treatment. Thus, it is critical to understand the potential of anaerobic digestion to attenuate ARGs. Although some previous studies recommended thermophilic digestion for ARG removal, they did not get sufficient evidence to support this view. The antibiotics applied to animals are mostly excreted through feces and urine because of incomplete metabolism. It is indispensable to know whether residual antibiotics in manure will hinder ARG attenuation in anaerobic digesters. The significance of our research is in comprehensively understanding the evolution and mechanism of ARGs in anaerobic digestion of swine manure affected by temperature and residual antibiotics, which will allow the development of an ARG elimination strategy before their release into the environment.
Similarities and Differences between Colicin and Filamentous Phage Uptake by Bacterial Cells
Authors: Duché Denis , Houot Laetitia
Published: January 2019

Gram-negative bacteria have evolved a complex envelope to adapt and survive in a broad range of ecological niches. This physical barrier is the first line of defense against noxious compounds and viral particles called bacteriophages. Colicins are a family of bactericidal proteins produced by and toxic to
Escherichia coli
and closely related bacteria. Filamentous phages have a complex structure, composed of at least five capsid proteins assembled in a long thread-shaped particle, that protects the viral DNA. Despite their difference in size and complexity, group A colicins and filamentous phages both parasitize multiprotein complexes of their sensitive host for entry. They first bind to a receptor located at the surface of the target bacteria before specifically recruiting components of the Tol system to cross the outer membrane and find their way through the periplasm. The Tol system is thought to use the proton motive force of the inner membrane to maintain outer membrane integrity during the life cycle of the cell. This review describes the sequential docking mechanisms of group A colicins and filamentous phages during their uptake by their bacterial host, with a specific focus on the translocation step, promoted by interactions with the Tol system.
Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques
Authors: Wang Lin , Teng Jade L. L. , Lau Susanna K. P. , Sridhar Siddharth , Fu Hongwei , Gong Wanyun , Li Manyu , Xu Qieshi , He Yunye , Zhuang Hui , Woo Patrick C. Y. , Wang Ling
Published: January 2019

It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection.
Food-to-Humans Bacterial Transmission
Authors: Antunes Patrícia , Novais Carla , Peixe Luísa
Published: January 2019

Microorganisms vehiculated by food might benefit health, cause minimal change within the equilibrium of the host microbial community or be associated with foodborne diseases. In this chapter we will focus on human pathogenic bacteria for which food is conclusively demonstrated as their transmission mode to human. We will describe the impact of foodborne diseases in public health, the reservoirs of foodborne pathogens (the environment, human and animals), the main bacterial pathogens and food vehicles causing human diseases, and the drivers for the transmission of foodborne diseases related to the food-chain, host or bacteria features. The implication of food-chain (foodborne pathogens and commensals) in the transmission of resistance to antibiotics relevant to the treatment of human infections is also evidenced. The multiplicity and interplay of drivers related to intensification, diversification and globalization of food production, consumer health status, preferences, lifestyles or behaviors, and bacteria adaptation to different challenges (stress tolerance and antimicrobial resistance) from farm to human, make the prevention of bacteria-food-human transmission a modern and continuous challenge. A global One Health approach is mandatory to better understand and minimize the transmission pathways of human pathogens, including multidrug-resistant pathogens and commensals, through food-chain.
Outer Membrane Vesicle-Host Cell Interactions
Authors: Cecil Jessica D. , Sirisaengtaksin Natalie , O’Brien-Simpson Neil M. , Krachler Anne Marie
Published: January 2019

Outer membrane vesicles (OMVs) are nanosized proteoliposomes derived from the outer membrane of Gram-negative bacteria. They are ubiquitously produced both in culture and during infection and are now recognized to play crucial roles during host-microbe interactions. OMVs can transport a broad range of chemically diverse cargoes, including lipids and lipopolysaccharides, membrane-embedded and associated proteins and small molecules, peptidoglycan, and nucleic acids. Particularly, virulence factors such as adhesins and toxins are often enriched in OMVs. Here we discuss a variety of ways in which OMVs facilitate host-microbe interactions, including their contributions to biofilm formation, nutrient scavenging, and modulation of host cell function. We particularly examine recent findings regarding OMV-host cell interactions in the oral cavity and the gastrointestinal tract.
The Remarkable Biomechanical Properties of the Type 1 Chaperone-Usher Pilus: A Structural and Molecular Perspective
Authors: Hospenthal Manuela K. , Waksman Gabriel
Published: January 2019

Chaperone-usher (CU) pili are long, supramolecular protein fibers tethered to the surface of numerous bacterial pathogens. These virulence factors function primarily in bacterial adhesion to host tissues, but they also mediate biofilm formation. Type 1 and P pili of uropathogenic
Escherichia coli
(UPEC) are the two best-studied CU pilus examples, and here we primarily focus on the former. UPEC can be transmitted to the urinary tract by fecal shedding. It can then ascend up the urinary tract and cause disease by invading and colonizing host tissues of the bladder, causing cystitis, and the kidneys, causing pyelonephritis. FimH is the subunit displayed at the tip of type 1 pili and mediates adhesion to mannosylated host cells via a unique catch-bond mechanism. In response to shear forces caused by urine flow, FimH can transition from a low-affinity to high-affinity binding mode. This clever allosteric mechanism allows UPEC cells to remain tightly attached during periods of urine flow, while loosening their grip to allow dissemination through the urinary tract during urine stasis. Moreover, the bulk of a CU pilus is made up of the rod, which can reversibly uncoil in response to urine flow to evenly spread the tensile forces over the entire pilus length. We here explore the novel structural and mechanistic findings relating to the type 1 pilus FimH catch-bond and rod uncoiling and explain how they function together to enable successful attachment, spread, and persistence in the hostile urinary tract.
A Hybrid Secretion System Facilitates Bacterial Sporulation: A Structural Perspective
Authors: Zeytuni Natalie , Strynadka Natalie C.J.
Published: January 2019

Bacteria employ a number of dedicated secretion systems to export proteins to the extracellular environment. Several of these comprise large complexes that assemble in and around the bacterial membrane(s) to form specialized channels through which only selected proteins are actively delivered. Although typically associated with bacterial pathogenicity, a specialized variant of these secretion systems has been proposed to play a central part in bacterial sporulation, a primitive protective process that allows starving cells to form spores that survive in extreme environments. Following asymmetric division, the mother cell engulfs the forespore, leaving it surrounded by two bilayer membranes. During the engulfment process an essential channel apparatus is thought to cross both membranes to create a direct conduit between the mother cell and forespore. At least nine proteins are essential for channel formation, including SpoIIQ under forespore control and the eight SpoIIIA proteins (SpoIIIAA to -AH) under mother cell control. Presumed to form a core channel complex, several of these proteins share similarity with components of Gram-negative bacterial secretion systems, including the type II, III, and IV secretion systems and the flagellum. Based on these similarities it has been suggested that the sporulation channel represents a hybrid, secretion-like transport machinery. Recently, in-depth biochemical and structural characterization of the individual channel components accompanied by
in vivo
studies has further reinforced this model. Here we review and discuss these recent studies and suggest an updated model for the unique sporulation channel apparatus architecture.
Rectal adenocarcinoma: rare metastasis to the optic nerve
Authors: Jamall Omer , Theodoraki Korina , Amin Sepideh , Verity David , Bates Adam
Published: January 2019

We present the first reported case of histologically proven colorectal adenocarcinoma with metastatic spread to the optic nerve. A 49-year-old man, with a known history of rectal adenocarcinoma, presented with progressive loss of vision in his left eye. On presentation, he had no perception to light in his left eye and Snellen acuity of 6/36 in the right eye. Fundus examination showed a left globally swollen optic nerve with a few flame-shaped haemorrhages. A gadolinium-enhanced MRI scan demonstrated abnormal thickening of the anterior and mid-section of the optic nerve with high signal on STIR and postgadolinium enhancement. Optic nerve biopsy confirmed the presence of epithelial adenocarcinoma compatible with metastasis of gut origin. The patient died within 4 months of presentation.
Evaluation of the combined effect of factors influencing bowel preparation and adenoma detection rates in patients undergoing colonoscopy
Authors: Tariq Hassan , Kamal Muhammad Umar , Sapkota Binita , ElShikh Fady , Pirzada Usman Ali , Pullela Nanda , Azam Sara , Zhang Aiyi , Baiomi Ahmed , Abbas Hafsa , Makker Jasbir , Balar Bhavna , Ihimoyan Ariyo , Daniel Myrta , Dev Anil
Published: January 2019

Background

Colonoscopy is a commonly used modality for screening and surveillance of colorectal cancer (CRC). Therefore, it is essential to have adequate bowel preparation (prep) for the procedure which depends on type of bowel regimens, diet before colonoscopy and timing of the procedure.

Aims

The purpose of this study is to analyse the effect of multiple factors on adenoma detection rate (ADR) and prep quality of colonoscopy. This is the also the first study determining outcomes based on various combinations of diet, timing of the procedure and bowel prep regimens.

Methods

This is a retrospective single-centre observational study. Data about diet before procedure, bowel prepprep regimen and timing of the procedure was collected for patients coming for screening colonoscopy.

Results

Patients with split prep had higher good prep rates (73.8% vs 56.2%) and higher ADRs (34.2 % vs 29.9%) as compared with non-split prep. The good prep quality (65.8% vs 62.1%) and ADRs (31.9% vs 31.5%) were comparable in patients who received clear liquid diet as compared with low residue diet. The good results of bowel prep were obtained with split prep with either clear liquids or low residue diet irrespective of the timing of procedure. The poor prep was noticed in patients who underwent procedure in afternoon, with a low restrictive diet and non-split bowel regimen.

Conclusions

The current study adds to our knowledge about the combined effect of multiple variables affecting the bowel prep quality and ADR. It is imperative to opt for the best combination required for colonoscopy, as this will influence the effectiveness of colonoscopies regarding timely cancer detection and prevention.
Synthesising quantitative evidence in systematic reviews of complex health interventions
Authors: Higgins Julian P T , López-López José A , Becker Betsy J , Davies Sarah R , Dawson Sarah , Grimshaw Jeremy M , McGuinness Luke A , Moore Theresa H M , Rehfuess Eva A , Thomas James , Caldwell Deborah M
Published: January 2019

Public health and health service interventions are typically complex: they are multifaceted, with impacts at multiple levels and on multiple stakeholders. Systematic reviews evaluating the effects of complex health interventions can be challenging to conduct. This paper is part of a special series of papers considering these challenges particularly in the context of WHO guideline development. We outline established and innovative methods for synthesising quantitative evidence within a systematic review of a complex intervention, including considerations of the complexity of the system into which the intervention is introduced. We describe methods in three broad areas: non-quantitative approaches, including tabulation, narrative and graphical approaches; standard meta-analysis methods, including meta-regression to investigate study-level moderators of effect; and advanced synthesis methods, in which models allow exploration of intervention components, investigation of both moderators and mediators, examination of mechanisms, and exploration of complexities of the system. We offer guidance on the choice of approach that might be taken by people collating evidence in support of guideline development, and emphasise that the appropriate methods will depend on the purpose of the synthesis, the similarity of the studies included in the review, the level of detail available from the studies, the nature of the results reported in the studies, the expertise of the synthesis team and the resources available.
Is a government-regulated rehabilitation guideline more effective than general practitioner education or preferred-provider rehabilitation in promoting recovery from acute whiplash-associated disorders? A pragmatic randomised controlled trial
Authors: Côté Pierre , Boyle Eleanor , Shearer Heather M , Stupar Maja , Jacobs Craig , Cassidy John David , Carette Simon , van der Velde Gabrielle , Wong Jessica J , Hogg-Johnson Sheilah , Ammendolia Carlo , Hayden Jill Alison , van Tulder Maurits , Frank John W
Published: January 2019

Objective

To evaluate the effectiveness of a government-regulated rehabilitation guideline compared with education and activation by general practitioners, and to a preferred-provider insurance-based rehabilitation programme on self-reported global recovery from acute whiplash-associated disorders (WAD) grade I–II.

Design

Pragmatic randomised clinical trial with blinded outcome assessment.

Setting

Multidisciplinary rehabilitation clinics and general practitioners in Ontario, Canada.

Participants

340 participants with acute WAD grade I and II. Potential participants were sampled from a large automobile insurer when reporting a traffic injury.

Interventions

Participants were randomised to receive one of three protocols: government-regulated rehabilitation guideline, education and activation by general practitioners or a preferred-provider insurance-based rehabilitation.

Primary and secondary outcome measures

Our primary outcome was time to self-reported global recovery. Secondary outcomes included time on insurance benefits, neck pain intensity, whiplash-related disability, health-related quality of life and depressive symptomatology at 6 weeks and 3, 6, 9 and 12 months postinjury.

Results

The median time to self-reported global recovery was 59 days (95% CI 55 to 68) for the government-regulated guideline group, 105 days (95% CI 61 to 126) for the preferred-provider group and 108 days (95% CI 93 to 206) for the general practitioner group; the difference was not statistically significant (Χ2=3.96; 2 df: p=0.138). We found no clinically important differences between groups in secondary outcomes. Post hoc analysis suggests that the general practitioner (hazard rate ratio (HRR)=0.51, 95% CI 0.34 to 0.77) and preferred-provider groups (HRR=0.67, 95% CI 0.46 to 0.96) had slower recovery than the government-regulated guideline group during the first 80 days postinjury. No major adverse events were reported.

Conclusions

Time-to-recovery did not significantly differ across intervention groups. We found no differences between groups with regard to neck-specific outcomes, depression and health-related quality of life.

Trial registration number

NCT00546806.
Adapting health interventions for local fit when scaling-up: a realist review protocol
Authors: Power Jessica , Gilmore Brynne , Vallières Frédérique , Toomey Elaine , Mannan Hasheem , McAuliffe Eilish
Published: January 2019

Introduction

Scaling-up is essential to ensure universal access of effective health interventions. Scaling-up is a complex process, which occurs across diverse systems and contexts with no one-size-fits-all approach. To date, little attention has been paid to the process of scaling-up in how to make adaptations for local fit. The aim of this research is to develop theory on what actions can be used to make adaptations to health interventions for local fit when scaling-up across diverse contexts that will have practical application for implementers involved in scaling-up.

Methods and analysis

Given the complexity of this subject, a realist review methodology was selected. Specifically, realist review emphasises an iterative, non-linear process, whereby the review is refined as it progresses. The identification of how the context may activate mechanisms to achieve outcomes is used to generate theories on what works for whom in what circumstances. This protocol will describe the first completed stage of development of an initial programme theory framework, which identified potential actions, contexts, mechanisms and outcomes that could be used to make adaptations when scaling-up. It will then outline the methods for future stages of the review which will focus on identifying case examples of scale-up and adaptation in practice. This realist review consists of six stages: (i) clarifying scope and development of a theoretical framework, (ii) developing a search strategy, (iii) selection and appraisal, (iv) data extraction, (v) data synthesis and analysis and (vi) further theory refinement with stakeholders.

Ethics and dissemination

This review will develop theory on how adaptations can be made when scaling-up. Findings will be disseminated in a peer-reviewed journal and through stakeholder engagement as part of the research process. Ethical approval has been received through Health Policy and Management/Centre for Global Health Research Ethics Committee of Trinity College Dublin.
Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the context of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial
Authors: Favrais Geraldine , Ursino Moreno , Mouchel Catherine , Boivin Estelle , Jullien Vincent , Zohar Sarah , Saliba Elie
Published: January 2019

Introduction

Therapeutic schedules for treating neonatal seizures remain elusive. First-line treatment with phenobarbital is widely supported but without strong scientific evidence. Levetiracetam (LEV) is an emerging and promising antiepileptic drug (AED). The aim of this phase II trial is to determine the benefits of LEV by applying a strict methodology and to estimate the optimal dose of LEV as a first-line AED to treat seizures in newborns suffering from hypoxic-ischaemic encephalopathy.

Methods and analysis

LEVNEONAT-1 is an open and sequential LEV dose-finding study. The optimal dose is that which is estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy is defined by a seizure burden reduction of 80% after the loading dose. Four increasing dose regimens will be assessed including one loading dose of 30, 40, 50 or 60 mg/kg followed by eight maintenance doses (ie, a quarter of the loading dose) injected every 8 hours. A two-patient cohort will be necessary at each dose level to consider an upper dose level assignment. The maximal sample size expected is 50 participants with a minimum of 24 patients or fewer in the case of a high rate of toxicity. Patients will be recruited in five neonatal intensive care units beginning in October 2017 and continuing for 2 years. In parallel, the LEV pharmacokinetics will be measured five times (ie, 30 min; 4 and 7 hours after the loading dose; 1–3 hours and 12–18 hours after the last maintenance dose).

Ethics and dissemination

Ethics approval has been obtained from the regional ethical committee (2016-R25) and the French Drug Safety Agency (160652A-31). The results will be published in a peer-reviewed journal. The results will also be presented at medical meetings.

Trial registration number

NCT02229123; Pre-results.
Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis
Authors: Peters Ruth , Booth Andrew , Rockwood Kenneth , Peters Jean , D’Este Catherine , Anstey Kaarin J
Published: January 2019

Objective

To systematically review the literature relating to the impact of multiple co-occurring modifiable risk factors for cognitive decline and dementia.

Design

A systematic review and meta-analysis of the literature relating to the impact of co-occurring key risk factors for incident cognitive decline and dementia. All abstracts and full text were screened independently by two reviewers and each article assessed for bias using a standard checklist. A fixed effects meta-analysis was undertaken.

Data sources

Databases Medline, Embase and PsycINFO were searched from 1999 to 2017.

Eligibility criteria

For inclusion articles were required to report longitudinal data from participants free of cognitive decline at baseline, with formal assessment of cognitive function or dementia during follow-up, and an aim to examine the impact of additive or clustered comorbid risk factor burden in with two or more core modifiable risk factors.

Results

Seventy-nine full-text articles were examined. Twenty-two articles (18 studies) were included reporting data on >40 000 participants. Included studies consistently reported an increased risk associated with greater numbers of intraindividual risk factors or unhealthy behaviours and the opposite for healthy or protective behaviours. A meta-analysis of studies with dementia outcomes resulted in a pooled relative risk for dementia of 1.20 (95% CI 1.04 to 1.39) for one risk factor, 1.65 (95% CI 1.40 to 1.94) for two and 2.21 (95% CI 1.78 to 2.73) for three or more, relative to no risk factors. Limitations include dependence on published results and variations in study outcome, cognitive assessment, length of follow-up and definition of risk factor exposure.

Conclusions

The strength of the reported associations, the consistency across studies and the suggestion of a dose response supports a need to keep modifiable risk factor exposure to a minimum and to avoid exposure to additional modifiable risks. Further research is needed to establish whether particular combinations of risk factors confer greater risk than others.

PROSPERO registration number

42016052914.
Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity—a retrospective study
Authors: Shen Yanfei , Huang Xinmei , Zhang Weimin
Published: January 2019

Objective

The role of platelet-to-lymphocyte ratio (PLR) as an indicator of inflammation has been the focus of research recently. We aimed to investigate theprognosticvalue of PLR for sepsis.

Design

A retrospective cohort study.

Setting and participants

Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. Data on 5537 sepsis patients were analysed.

Methods

Logistic regression was used to explore the association between PLR and hospital mortality. Subgroup analyses were performed based on vasopressor use, acute kidney injury (AKI) and a Sequential Organ Failure Assessment (SOFA) score >10.

Results

In the logistic model with linear spline function, a PLR >200 was significantly (OR 1.0002; 95% CI 1.0001 to 1.0004) associated with mortality; the association wasnon-significantfor PLRs ≤200 (OR 0.997; 95% CI 1.19 to 1.67). In the logistic model using the PLR as a design variable, only high PLRs were significantly associated with mortality (OR 1.29; 95% CI 1.09 to 1.53); the association with low PLRs wasnon-significant(OR 1.15; 95% CI 0.96 to 1.38). In the subgroups with vasopressor use, AKI and a SOFA score >10, the association between high PLR and mortality wasnon-significant; this remained significant in the subgroups without vasopressor use (OR 1.39; 95% CI 1.08 to 1.77) and AKI (OR 1.54; 95% CI 1.20 to 1.99) and with a SOFA score ≤10 (OR 1.51; 95% CI 1.17 to 1.94).

Conclusions

High PLRs at admission were associated with an increased risk of mortality. In patients with vasopressor use, AKI or a SOFA score >10, this association wasnon-significant.
Five-year standardised mortality ratios in a cohort of homeless people in Dublin
Authors: Ivers Jo-Hanna , Zgaga Lina , O’Donoghue-Hynes Bernie , Heary Aisling , Gallwey Brian , Barry Joe
Published: January 2019

Objective

To calculate standardised mortality ratios (SMRs) for a cohort of homeless people in the Dublin region over a 5-year period and to examine leading causes of death.

Setting

Homeless services reporting deaths from homeless persons in their care across the Dublin Homeless Region.

Methods

Death data among people who experience homelessness was acquired from the Dublin Region Homeless Executive (2011–2015) and validated from both death certificates and records from the Dublin Coroner’s Office.

Participants

Two hundred and nine deaths were recorded; of these 201 were verified (n=156 males, 77.6%). Deaths that could not be verified by certificate or coroners record were excluded from the study.

Results

SMRs were 3–10 times higher in homeless men and 6–10 times higher in homeless women compared with the general population. Drug and alcohol-related deaths were the leading cause of death, accounting for 38.4% of deaths in homeless individuals. These were followed by circulatory (20%) and respiratory causes (13%).

Conclusion

Mortality rates among homeless persons are exceptionally high. Services and programmes, particularly housing and those targeting overdose and alcoholism, are urgently needed to prevent premature mortality in this vulnerable population.