bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer immunotherapy using checkpoint blockade
Authors: Ribas Antoni , Wolchok Jedd D.
Published: March 2018

The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte–associated protein 4 (CTLA-4) or the programmed cell death 1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the preexistence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long-lasting disease control, yet one-third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
CAR T cell immunotherapy for human cancer
Authors: June Carl H. , O’Connor Roddy S. , Kawalekar Omkar U. , Ghassemi Saba , Milone Michael C.
Published: March 2018

Adoptive T cell transfer (ACT) is a new area of transfusion medicine involving the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory effects. The field has rapidly advanced from a promising form of immuno-oncology in preclinical models to the recent commercial approvals of chimeric antigen receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes opportunities and challenges for entering mainstream oncology that presently face the CAR T field, with a focus on the challenges that have emerged over the past several years.
The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies
Authors: Zitvogel Laurence , Ma Yuting , Raoult Didier , Kroemer Guido , Gajewski Thomas F.
Published: March 2018

The fine line between human health and disease can be driven by the interplay between host and microbial factors. This “metagenome” regulates cancer initiation, progression, and response to therapies. Besides the capacity of distinct microbial species to modulate the pharmacodynamics of chemotherapeutic drugs, symbiosis between epithelial barriers and their microbial ecosystems has a major impact on the local and distant immune system, markedly influencing clinical outcome in cancer patients. Efficacy of cancer immunotherapy with immune checkpoint antibodies can be diminished with administration of antibiotics, and superior efficacy is observed with the presence of specific gut microbes. Future strategies of precision medicine will likely rely on novel diagnostic and therapeutic tools with which to identify and correct defects in the microbiome that compromise therapeutic efficacy.
The threshold for conscious report: Signal loss and response bias in visual and frontal cortex
Authors: van Vugt Bram , Dagnino Bruno , Vartak Devavrat , Safaai Houman , Panzeri Stefano , Dehaene Stanislas , Roelfsema Pieter R.
Published: March 2018

Setting conscious perception alight

What are the neuronal mechanisms that enable conscious perception? Why do some images remain subliminal? Van Vugt
et al.
trained monkeys to detect low-contrast images and compared neuronal activity in brain areas V1, V4, and the dorsolateral prefrontal cortex. Some stimuli made it into consciousness, and others were subliminal depending on their propagation, which can be variable for weak stimuli (see the Perspective by Mashour). Strongly propagated stimuli initiated a state in the higher brain areas called “ignition” that caused information about a brief stimulus to become sustained and broadcasted back through recurrent interactions between many brain areas.

Science
, this issue p.
537
; see also p.
493
Lumping and splitting
Authors: Berg Jeremy
Published: March 2018

Next month, the National Postdoctoral Association will convene its annual meeting
in Cleveland, Ohio, where, among many topics, the matter of how data can inform
policies to improve post-Ph.D. career pathways will be discussed. Many such data
are indeed “out there,” but a major question is whether they are
accessible and usable—which brings me to the value of taxonomies.
Profiling of
PDR1
and
MSH2
in Candida glabrata Bloodstream Isolates from a Multicenter Study in China
Authors: Hou Xin , Xiao Meng , Wang He , Yu Shu-Ying , Zhang Ge , Zhao Yanan , Xu Ying-Chun
Published: March 2018

Among 158
Candida glabrata
bloodstream isolates collected from numerous centers in China, a resistance to fluconazole was seen in 8.9%. Three isolates (1.9%) were resistant to all echinocandins. Multilocus sequence typing (MLST) revealed that sequence type 7 ([ST7] 65.8%) was the most common type, followed by ST3 (7.6%).
PDR1
polymorphisms were associated with the acquisition of fluconazole resistance in
C. glabrata
isolates, while
MSH2
polymorphisms were associated with the STs and microsatellite genotypes, irrespective of fluconazole resistance.
Induction of Genes Encoding Plant Cell Wall-Degrading Carbohydrate-Active Enzymes by Lignocellulose-Derived Monosaccharides and Cellobiose in the White-Rot Fungus Dichomitus squalens
Authors: Casado López Sara , Peng Mao , Issak Tedros Yonatan , Daly Paul , de Vries Ronald P. , Mäkelä Miia R.
Published: March 2018

Fungi can decompose plant biomass into small oligo- and monosaccharides to be used as carbon sources. Some of these small molecules may induce metabolic pathways and the production of extracellular enzymes targeted for degradation of plant cell wall polymers. Despite extensive studies in ascomycete fungi, little is known about the nature of inducers for the lignocellulolytic systems of basidiomycetes. In this study, we analyzed six sugars known to induce the expression of lignocellulolytic genes in ascomycetes for their role as inducers in the basidiomycete white-rot fungus
Dichomitus squalens
using a transcriptomic approach. This identified cellobiose and
l
-rhamnose as the main inducers of cellulolytic and pectinolytic genes, respectively, of
D. squalens
. Our results also identified differences in gene expression patterns between dikaryotic and monokaryotic strains of
D. squalens
cultivated on plant biomass-derived monosaccharides and the disaccharide cellobiose. This suggests that despite conservation of the induction between these two genetic forms of
D. squalens
, the fine-tuning in the gene regulation of lignocellulose conversion is differently organized in these strains.

IMPORTANCE
Wood-decomposing basidiomycete fungi have a major role in the global carbon cycle and are promising candidates for lignocellulosic biorefinery applications. However, information on which components trigger enzyme production is currently lacking, which is crucial for the efficient use of these fungi in biotechnology. In this study, transcriptomes of the white-rot fungus
Dichomitus squalens
from plant biomass-derived monosaccharide and cellobiose cultures were studied to identify compounds that induce the expression of genes involved in plant biomass degradation.
Candida albicans White-Opaque Switching Influences Virulence but Not Mating during Oropharyngeal Candidiasis
Authors: Solis Norma V. , Park Yang-Nim , Swidergall Marc , Daniels Karla J. , Filler Scott G. , Soll David R.
Published: March 2018

The capacity of
Candida albicans
to switch reversibly between the white phenotype and the opaque phenotype is required for the fungus to mate. It also influences virulence during hematogenously disseminated candidiasis. We investigated the roles of the mating type loci (
MTL
) and white-opaque switching in the capacity of
C. albicans
to mate in the oropharynx and cause oropharyngeal candidiasis (OPC). When immunosuppressed mice were orally infected with mating-competent opaque
a/a
and α/α cells either alone or mixed with white cells, no detectable mating occurred, indicating that the mating frequency was less than 1.6 × 10
−6
. Opaque cells were also highly attenuated in virulence; they either were cleared from the oropharynx or switched to the white phenotype during OPC. Although there were strain-to-strain differences in the virulence of white cells, they were consistently more virulent than opaque cells.
In vitro
studies indicated that relative to white cells, opaque cells had decreased capacity to invade and damage oral epithelial cells. The reduced invasion of at least one opaque strain was due to reduced surface expression of the Als3 invasin and inability to activate the epidermal growth factor receptor, which is required to stimulate the epithelial cell endocytic machinery. These results suggest that mating is a rare event during OPC because opaque cells have reduced capacity to invade and damage the epithelial cells of the oral mucosa.
A Critical Region in the FlaA Flagellin Facilitates Filament Formation of the Vibrio cholerae Flagellum
Authors: Echazarreta Mylea A. , Kepple Johnathan L. , Yen Li-Hua , Chen Yue , Klose Karl E.
Published: March 2018

V. cholerae
causes the severe diarrheal disease cholera. Its ability to swim is mediated by rotation of a polar flagellum, and this motility is integral to its ability to cause disease and persist in the environment. The current studies illuminate how one specific flagellin (FlaA) within a multiflagellin structure mediates formation of the flagellar filament, thus allowing
V. cholerae
to swim. This knowledge can lead to safer vaccines and potential therapeutics to inhibit cholera.
Staphylococcus aureus Utilizes Host-Derived Lipoprotein Particles as Sources of Fatty Acids
Authors: Delekta Phillip C. , Shook John C. , Lydic Todd A. , Mulks Martha H. , Hammer Neal D.
Published: March 2018

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a threat to global health. Consequently, much effort has focused on the development of new antimicrobials that target novel aspects of
S. aureus
physiology. Fatty acids are required to maintain cell viability, and bacteria synthesize fatty acids using the type II fatty acid synthesis (FASII) pathway. FASII is significantly different from human fatty acid synthesis, underscoring the therapeutic potential of inhibiting this pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids, bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors uncertain. Importantly, the source(s) of fatty acids available to pathogens within the host environment remains unclear. Fatty acids are transported throughout the body by lipoprotein particles in the form of triglycerides and esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL), represent a potentially rich source of exogenous fatty acids for
S. aureus
during infection. We sought to test the ability of LDLs to serve as a fatty acid source for
S. aureus
and show that cells cultured in the presence of human LDLs demonstrate increased tolerance to the FASII inhibitor triclosan. Using mass spectrometry, we observed that host-derived fatty acids present in the LDLs are incorporated into the staphylococcal membrane and that tolerance to triclosan is facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase. Finally, we demonstrate that human LDLs support the growth of
S. aureus
fatty acid auxotrophs. Together, these results suggest that human lipoprotein particles are a viable source of exogenous fatty acids for
S. aureus
during infection.

IMPORTANCE
Inhibition of bacterial fatty acid synthesis is a promising approach to combating infections caused by
S. aureus
and other human pathogens. However,
S. aureus
incorporates exogenous fatty acids into its phospholipid bilayer. Therefore, the clinical utility of targeting bacterial fatty acid synthesis is debated. Moreover, the fatty acid reservoir(s) exploited by
S. aureus
is not well understood. Human low-density lipoprotein particles represent a particularly abundant
in vivo
source of fatty acids and are present in tissues that
S. aureus
colonizes. Herein, we establish that
S. aureus
is capable of utilizing the fatty acids present in low-density lipoproteins to bypass both chemical and genetic inhibition of fatty acid synthesis. These findings imply that
S. aureus
targets LDLs as a source of fatty acids during pathogenesis.
High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia
Authors: Riley Thomas V. , Collins Deirdre A. , Karunakaran Rina , Kahar Maria Abdul , Adnan Ariza , Hassan Siti Asma , Zainul Nadiah Hanim , Rustam F. R. Mohammed , Wahab Z. Abd , Ramli Ramliza , Lee Yeong Yeh , Hassan Hamimah
Published: March 2018

Accumulating evidence shows a high prevalence of
Clostridium difficile
in Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigated
C. difficile
infection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A or B were performed on diarrheal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates of
C. difficile
characterized by PCR ribotyping and detection of toxin genes. In total, 437 specimens were collected and fecal toxin was detected in 3.0%. A further 16.2% of specimens were GDH positive and toxin negative. After culture, toxigenic strains were isolated from 10.3% and nontoxigenic strains from 12.4% of specimens. The most prevalent PCR ribotypes (RTs) were RT 017 (20.0%) and RT 043 (10.0%). The high prevalence of RT 017 and nontoxigenic strains in Malaysia and in neighboring Thailand and Indonesia suggests that they localize to the region of Southeast Asia, with an implication that they may mediate the burden of CDI in the region.
H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells
Authors: Mazel-Sanchez B. , Boal-Carvalho I. , Silva F. , Dijkman R. , Schmolke M.
Published: March 2018

Highly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans.

IMPORTANCEAquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction factor of the viral polymerase complex HAX-1. Interestingly, we found that human influenza A virus polymerase complexes are already adapted to HAX-1 and do not require this function of PB1-F2. We thus propose that a functional full-length PB1-F2 supports direct transmission of bird viruses into humans.
Acceptability of a parental early warning tool for parents of infants with complex congenital heart disease: a qualitative feasibility study
Authors: Gaskin Kerry Louise , Wray Jo , Barron David J
Published: March 2018

Aim

To explore the acceptability and feasibility of a parental early warning tool, called the Congenital Heart Assessment Tool (CHAT), for parents going home with their infant between first and second stage of surgery for complex congenital heart disease.

Background

Home monitoring programmes were developed to aid early recognition of deterioration in fragile infants between first and second surgical stage. However, this necessitates good discharge preparation to enable parents to develop appropriate knowledge and understanding of signs of deterioration to look for and who to contact.

Design

This was a longitudinal qualitative feasibility study, within a constructivist paradigm. Parents were taught how to use the CHAT before taking their infant home and asked to participate in semistructured interviews at four time points: before discharge (T0), 2 weeks after discharge (T1), 8 weeks after discharge (T2) and after stage 2 surgery (T3). Interviews were transcribed verbatim and thematically analysed.

Setting

One tertiary children’s cardiac centre in the UK.

Subjects

Twelve parents of eight infants who were discharged following first stage cardiac surgery for complex congenital heart disease, between August 2013 and February 2015.

Results

Four main themes emerged: (1) parental preparation and vigilance, (2) usability, (3) mastery, and (4) reassurance and support.

Conclusions

The study highlighted the benefit of appropriately preparing parents before discharge, using the CHAT, to enable identification of normal infant behaviour and to detect signs of clinical deterioration. The study also demonstrated the importance of providing parents with information about when and who to call for management advice and support.
Motivation and main flavour of use, use with nicotine and dual use of electronic cigarettes in Barcelona, Spain: a cross-sectional study
Authors: Bunch Kailey , Fu Marcela , Ballbè Montse , Matilla-Santader Nuria , Lidón-Moyano Cristina , Martin-Sanchez Juan Carlos , Fernandez Esteve , Martínez-Sánchez Jose M
Published: March 2018

Objective

This study seeks to describe current e-cigarette users’ patterns of use including primary motivation for use, dual use, use with nicotine and principal flavour used, according to individuals’ sociodemographic characteristics and conventional tobacco consumption in Barcelona, Spain.

Design, setting and participants

This is a cross-sectional study of adult (≥18) current e-cigarette users of Barcelona (n=600), recruited in 2015. Researchers calculated percentages and ORs with their 95% CIs of users’ e-cigarette use with nicotine, primary motivation for use and preferred flavour. The analyses were stratified by sociodemographic variables including sex, age and level of education and by patterns of e-cigarette use and past and current conventional tobacco use.

Results

The most prevalent motivation for using e-cigarettes was to reduce tobacco smoking (48%, n=288), followed by quitting smoking (39.2%, n=235), and to use e-cigarettes in places where tobacco smoking was prohibited (10.2%, n=61). The most prevalent primary flavour used was tobacco (49%, n=294), followed by fruit (19.5%, n=117). People younger than 25 years old (OR=4.36, 95% CI 1.99 to 9.57) were more likely than older people to use them where smoking cigarettes was prohibited. A greater proportion of those in the youngest age group preferred fruit flavour compared with older individuals (29.3%, n=41).

Conclusions

Younger users of e-cigarettes and non-smokers are more likely to use flavours other than tobacco and to use e-cigarettes mainly for recreational purposes.
A novel inpatient complex pain team: protocol for a mixed-methods evaluation of a single-centre pilot study
Authors: Mordecai Luke , Vindrola-Padros Cecilia , Wood Victoria J , Swart Nicholas , Morris Stephen , Williams Amanda , Curran Natasha , Moonesinghe Ramani
Published: March 2018

Introduction

Complex pain is a debilitating condition that is responsible for low quality of life and significant economic impacts. Although best practice in the treatment of complex pain employs a multidisciplinary team, many patients do not have access to this care, leading to poor outcomes.

Methods and analysis

This study evaluates a novel inpatient complex pain team at a large London teaching hospital. A multidisciplinary pain team comprising specialist doctors, nurses, psychologists and physiotherapists was instituted for inpatients with complex pain who will undergo an intense and bespoke evidence-based programme which will then be integrated into the community. A mixed-methods evaluation will take place and patients will be recruited over the course of 1 year. A qualitative arm will interview 15 staff and 15 patients on recruitment and again 6 months later looking to compare and contrast the new pain team with past experiences of pain management. A quantitative arm will assess clinical outcomes using validated scoring tools. An economic evaluation will seek to evaluate the relative cost of the service by comparing healthcare costs before and after the intervention.

Ethics and dissemination

The study was categorised as a service evaluation, so formal ethical approval was not considered necessary. Participant recruitment began in January 2016 and the 1-year follow-up will end in November 2017. The results of this study will be published in 2018.
Reliability of coded data to identify earliest indications of cognitive decline, cognitive evaluation and Alzheimer’s disease diagnosis: a pilot study in England
Authors: Dell’Agnello Grazia , Desai Urvi , Kirson Noam Y , Wen Jody , Meiselbach Mark K , Reed Catherine C , Belger Mark , Lenox-Smith Alan , Martinez Carlos , Rasmussen Jill
Published: March 2018

Objectives

Evaluate the reliability of using diagnosis codes and prescription data to identify the timing of symptomatic onset, cognitive assessment and diagnosis of Alzheimer’s disease (AD) among patients diagnosed with AD.

Methods

This was a retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD). The study cohort consisted of a random sample of 50 patients with first AD diagnosis in 2010–2013. Additionally, patients were required to have a valid text-field code and a hospital episode or a referral in the 3 years before the first AD diagnosis. The earliest indications of cognitive impairment, cognitive assessment and AD diagnosis were identified using two approaches: (1) using an algorithm based on diagnostic codes and prescription drug information and (2) using information compiled from manual review of both text-based and coded data. The reliability of the code-based algorithm for identifying the earliest dates of the three measures described earlier was evaluated relative to the comprehensive second approach. Additionally, common cognitive assessments (with and without results) were described for both approaches.

Results

The two approaches identified the same first dates of cognitive symptoms in 33 (66%) of the 50 patients, first cognitive assessment in 29 (58%) patients and first AD diagnosis in 43 (86%) patients. Allowing for the dates from the two approaches to be within 30 days, the code-based algorithm’s success rates increased to 74%, 70% and 94%, respectively. Mini-Mental State Examination was the most commonly observed cognitive assessment in both approaches; however, of the 53 tests performed, only 19 results were observed in the coded data.

Conclusions

The code-based algorithm shows promise for identifying the first AD diagnosis. However, the reliability of using coded data to identify earliest indications of cognitive impairment and cognitive assessments is questionable. Additionally, CPRD is not a recommended data source to identify results of cognitive assessments.
Roles played by community cadres to support retention in PMTCT Option B+ in four African countries: a qualitative rapid appraisal
Authors: Besada Donela , Goga Ameena , Daviaud Emmanuelle , Rohde Sarah , Chinkonde Jacqueline Rose , Villeneuve Susie , Clarysse Guy , Raphaely Nika , Okokwu Steve , Tumwesigye Nathan , Daries Nathalie , Doherty Tanya
Published: March 2018

Objectives

To explore the roles of community cadres in improving access to and retention in care for PMTCT (prevent mother-to-child transmission of HIV) services in the context of PMTCT Option B+ treatment scale-up in high burden low-income and lower-middle income countries.

Design/Methods

Qualitative rapid appraisal study design using semistructured in-depth interviews and focus group discussions (FGDs) between 8 June and 31 July 2015.

Setting and participants

Interviews were conducted in the offices of Ministry of Health Staff, Implementing partners, district offices and health facility sites across four low-income and lower-middle income countries: Cote D’Ivoire, Democratic Republic of Congo (DRC), Malawi and Uganda. A range of individual interviews and FGDs with key stakeholders including Ministry of Health employees, Implementation partners, district management teams, facility-based health workers and community cadres. A total number of 18, 28, 31 and 83 individual interviews were conducted in Malawi, Cote d’Ivoire, DRC and Uganda, respectively. A total number of 15, 9, 10 and 16 mixed gender FGDs were undertaken in Malawi, Cote d’Ivoire, DRC and Uganda, respectively.

Results

Community cadres either operated solely in the community, worked from health centres or in combination and their mandates were PMTCT-specific or included general HIV support and other health issues. Community cadres included volunteers, those supported by implementing partners or employed directly by the Ministry of Health. Their complimentary roles along the continuum of HIV care and treatment include demand creation, household mapping of pregnant and lactating women, linkage to care, infant follow-up and adherence and retention support.

Conclusions

Community cadres provide an integral link between communities and health facilities, supporting overstretched health workers in HIV client support and follow-up. However, their role in health systems is neither standardised nor systematic and there is an urgent need to invest in the standardisation of and support to community cadres to maximise potential health impacts.
Risk factors of asthma exacerbation based on asthma severity: a nationwide population-based observational study in South Korea
Authors: Kang Hye-Rim , Song Hyun Jin , Nam Jin Hyun , Hong Sung-Hyun , Yang So-Young , Ju SangEun , Lee Sang Won , Kim Tae-Bum , Kim Hye-Lin , Lee Eui-Kyung
Published: March 2018

Objectives

Asthma exacerbation, associated with many risks factors, can reflect management failure. However, little is known about how risk factors are associated with exacerbation, according to asthma severity. We aimed to investigate differences in risk factors in patients with different asthma severity and evaluate whether risk factors differed between frequent exacerbators and patients with single exacerbation.

Design

Nationwide population-based observational study.

Setting

Korean National Sample Cohort database.

Participants

We included 22 130 adults with asthma diagnoses more than twice (ICD-10 (International Classification of Diseases, Tenth revision) codes J45 and J46) and one prescription for asthma medication from 2010 to 2011.

Outcome measures

Asthma exacerbation was defined as having a corticosteroid (CS) burst characterised by a prescription of high-dose oral CS for ≥3 days or one systemic CS injection, hospitalisation or emergency department visit.

Results

Among severities, history of CS bursts was significantly associated with exacerbation. In mild and moderate asthma, exacerbation was significantly associated with age ≥45 years, being female, gastro-oesophageal reflux disease and chronic rhinitis. High medication possession ratio (MPR≥50%), compared with low MPR (<20%) showed adjusted ORs of 0.828 (95% CI 0.707 to 0.971) and 0.362 (0.185 to 0.708) in moderate and severe asthma, respectively. In severe asthma, compared with mild asthma, only allergic rhinitis and history of hospitalisation were strongly associated with exacerbation. When comparing frequent exacerbators to patients with single exacerbation, age ≥45 years, atopic dermatitis, anxiety and history of CS burst were significant risk factors in mild and moderate asthma, whereas no risk factors were significant in severe asthma.

Conclusions

Different associations between risk factors and asthma exacerbations based on asthma severity suggest that patients with mild asthma require greater attention to their age and comorbidities, whereas those with severe asthma require greater attention to hospitalisation history and drug adherence.
Canadian Child Safety Report Card: a comparison of injury prevention practices across provinces
Authors: Fridman Liraz , Fraser-Thomas Jessica L , Pike Ian , Macpherson Alison K
Published: March 2018

Background

Injury prevention report cards that raise awareness about the preventability of childhood injuries have been published by the European Child Safety Alliance and the WHO. These report cards highlight the variance in injury prevention practices around the world. Policymakers and stakeholders have identified research evidence as an important enabler to the enactment of injury legislation. In Canada, there is currently no childhood injury report card that ranks provinces on injury rates or evidence-based prevention policies.

Methods

Three key measures, with five metrics, were used to compare provinces on childhood injury prevention rates and strategies, including morbidity, mortality and policy indicators over time (2006–2012). Nine provinces were ranked on five metrics: (1) population-based hospitalisation rate/100 000; (2) per cent change in hospitalisation rate/100 000; (3) population-based mortality rate/100 000; (4) per cent change in mortality rate/100 000; (5) evidence-based policy assessment.

Results

Of the nine provinces analysed, British Columbia ranked highest in Canada and Saskatchewan lowest. British Columbia had a morbidity and mortality rate that was close to the Canadian average and decreased over the study period. British Columbia also had a number of injury prevention policies and legislation in place that followed best practice guidelines. Saskatchewan had a higher rate of injury hospitalisation and death; however, Saskatchewan’s rate decreased over time. Saskatchewan had a number of prevention policies in place but had not enacted bicycle helmet legislation.

Conclusions

Future preventative efforts should focus on harmonising policies across all provinces in Canada that reflect evidence-based best practices.
Synthesis and structural characterization of new polyether complexes of germanium(II) and tin(II)
Authors: Secara Alina M. , Binder Justin F. , Swidan Ala’aeddeen , Macdonald Charles L.B.
Published: March 2018

A series of germanium(II) and tin(II) bromide polyether complexes have been synthesized. Specifically, [GeBr([15]crown-5)][GeBr3], [GeBr([18]crown-6)][GeBr3], [GeBr(triglyme)][GeBr3], [GeBr(tetraglyme)][GeBr3], [SnBr([18]crown-6)][SnBr3], [Sn([15]crown-5)2][SnBr3]2, [SnBr(triglyme)][SnBr3], and [SnBr(tetraglyme)][SnBr3] have been fully characterized including by single crystal X-ray diffraction. The synthesis of [GeBr(dibenzo[24]crown-8)][GeBr3] and [GeCl(dibenzo[24]crown-8)][GeCl3] are also reported, along with the crystal structure of the latter’s water adduct, which features a water molecule adjacent to the GeCl+ ion within the cavity of the crown ether.
The extended Einstein–Maxwell-aether-axion model: Exact solutions for axionically controlled pp-wave aether modes
Authors: Balakin Alexander B.
Published: March 2018

The extended Einstein–Maxwell-aether-axion model describes internal interactions inside the system, which contains gravitational, electromagnetic fields, the dynamic unit vector field describing the velocity of an aether, and the pseudoscalar field associated with the axionic dark matter. The specific feature of this model is that the axion field controls the dynamics of the aether through the guiding functions incorporated into Jacobson’s constitutive tensor. Depending on the state of the axion field, these guiding functions can control and switch on or switch off the influence of acceleration, shear, vorticity and expansion of the aether flow on the state of physical system as a whole. We obtain new exact solutions, which possess the pp-wave symmetry, and indicate them by the term pp-wave aether modes in contrast to the pure pp-waves, which cannot propagate in this field conglomerate. These exact solutions describe a specific dynamic state of the pseudoscalar field, which corresponds to one of the minima of the axion potential and switches off the influence of shear and expansion of the aether flow; the model does not impose restrictions on Jacobson’s coupling constants and on the axion mass. Properties of these new exact solutions are discussed.
Froissart bound and self-similarity based models of proton structure functions
Authors: Choudhury D. K. , Saikia Baishali
Published: March 2018

Froissart bound implies that the total proton–proton cross-section (or equivalently proton structure function) cannot rise faster than [Formula: see text]. Compatibility of such behavior with the notion of self-similarity in proton structure function was suggested by us sometime back. In the present work, we generalize and improve it further by considering more recent self-similarity based models of proton structure functions and compare with recent data as well as with the model of Block, Durand, Ha and McKay.
Spatiotemporal Patterns in a Predator–Prey Model with Cross-Diffusion Effect
Authors: Sambath M. , Balachandran K. , Guin L. N.
Published: March 2018

The present research deals with the emergence of spatiotemporal patterns of a two-dimensional (2D) continuous predator–prey system with cross-diffusion effect. First, we work out the critical lines of Hopf and Turing bifurcations of the current model system in a 2D spatial domain by means of bifurcation theory. More specifically, the exact Turing region is specified in a two-parameter space. In effect, by choosing the cross-diffusion coefficient as one of the momentous parameter, we demonstrate that the model system undergoes a sequence of spatiotemporal patterns in a homogeneous environment through diffusion-driven instability. Our results via numerical simulation authenticate that cross-diffusion be able to create stationary patterns which enrich the findings of pattern formation in an ecosystem.
Bifurcation Analysis in a Class of Piecewise Nonlinear Systems with a Nonsmooth Heteroclinic Loop
Authors: Liu Yuanyuan , Li Feng , Dang Pei
Published: March 2018

We consider the bifurcation in a class of piecewise polynomial systems with piecewise polynomial perturbations. The corresponding unperturbed system is supposed to possess an elementary or nilpotent critical point. First, we present 17 cases of possible phase portraits and conditions with at least one nonsmooth periodic orbit for the unperturbed system. Then we focus on the two specific cases with two heteroclinic orbits and investigate the number of limit cycles near the loop by means of the first-order Melnikov function, respectively. Finally, we take a quartic piecewise system with quintic piecewise polynomial perturbation as an example and obtain that there can exist ten limit cycles near the heteroclinic loop.
Negative Feedback Mediated by Fast Inhibitory Autapse Enhances Neuronal Oscillations Near a Hopf Bifurcation Point
Authors: Jia Bing
Published: March 2018

One-parameter and two-parameter bifurcations of the Morris–Lecar (ML) neuron model with and without the fast inhibitory autapse, which is a synapse from a neuron onto itself, are investigated. The ML neuron model without autapse manifests an inverse Hopf bifurcation point from firing to a depolarized resting state with high level of membrane potential, with increasing depolarization current. When a fast inhibitory autapse is introduced, a negative feedback or inhibitory current is applied to the ML model. With increasing conductance of the autapse to middle level, the depolarized resting state near the inverse Hopf bifurcation point can change to oscillation and the parameter region of the oscillation becomes wide, which can be well interpreted by the dynamic responses of the depolarized resting state to the inhibitory current stimulus mediated by the autapse. The enlargement of the parameter region of the oscillation induced by the negative feedback presents a novel viewpoint different from the traditional one that inhibitory synapse often suppresses the neuronal oscillation activities. Furthermore, complex nonlinear dynamics such as the coexisting behaviors and codimension-2 bifurcations including the Bautin and cusp bifurcations are acquired. The relationship between the bifurcations and the depolarization block, a physiological concept that indicates a neuron can enter resting state when receiving the depolarization current, is discussed.
Characterization of the Effectiveness of Several Outranking-Based Multi-Criteria Sorting Methods
Authors: Fernandez Eduardo , Navarro Jorge , Olmedo Rafael
Published: March 2018

ELECTRE TRI-C, ELECTRE TRI-nC and THESEUS are recently proposed outranking-based multi-criteria sorting methods. The effectiveness of each method is here characterized by (i) its capacity for suggesting precise and appropriate assignments, (ii) the probability of suggesting imprecise assignments, and (iii) the probability of suggesting wrong assignments. We are also interested in studying to what extent the effectiveness of the methods is influenced by the number of criteria and categories, the cardinality of the reference set (in case of ELECTRE TRI-nC and THESEUS), and the way in which this set is chosen or populated. Our conclusions are supported by extensive computer experiments. The results underline the importance of (a) the number of reference actions and their distribution per category, (b) the number of criteria, and (c) the way in which the reference set is populated. These results help to identify contexts for which a particular method may be more appropriate.
Innovation and Performance: An Empirical Study of Russian Industrial Companies
Authors: Trachuk Arkady , Linder Natalia
Published: March 2018

The paper investigates the relationship between investment in research and development (R&D), innovation expenses, and productivity of manufacturing companies. These empirical results have shown that innovation investments (1) improve the performance of industrial companies with the elasticity of 0.09; (2) innovation investment has an impact on the performance of the company, and the extent of this impact depends on the value of R&D investment and has a range of elasticity ranging from 0.03 (for low volumes of R&D investment) to 0.16 in high volumes of R&D investment; (3) the relationship between innovation investment and the growth of performance is nonlinear in nature and has a strong positive relationship only after a critical mass of innovation investment has been reached; (4) a significant role in the relationship of innovation investment and productivity is played by the features of the industry in which the company operates (the companies that operate in high-tech industries not only invest more in R&D and innovation but also have a better performance due to research and development); (5) companies of low-tech industries have a negative elasticity of innovation investment and productivity, which is due to the influence of unprofitable innovation investments (appropriability effect), i.e. additional profits from the investment are not significant.
DISTRIBUTIONAL IMPLICATIONS OF A NATIONAL CO2TAX IN THE U.S. ACROSS INCOME CLASSES AND REGIONS: A MULTI-MODEL OVERVIEW
Authors: CARON JUSTIN , COLE JEFFERSON , GOETTLE RICHARD , ONDA CHIKARA , MCFARLAND JAMES , WOOLLACOTT JARED
Published: March 2018

This paper presents a multi-model assessment of the distributional impacts of carbon pricing. A set of harmonized representative CO2taxes and tax revenue recycling schemes is implemented in five large-scale economy-wide general equilibrium models. Recycling schemes include various combinations of uniform transfers to households and labor and capital income tax reductions. Particular focus is put on equity — the distribution of impacts across household incomes — and efficiency, evaluated in terms of household welfare. Despite important differences in the assumptions underlying the models, we find general agreement regarding the ranking of recycling schemes in terms of both efficiency and equity. All models identify a clear trade-off between efficient but regressive capital tax reductions and progressive but costly uniform transfers to households; all agree upon the inferiority of labor tax reductions in terms of welfare efficiency; and all agree that different combinations of capital tax reductions and household transfers can be used to balance efficiency and distributional concerns. A subset of the models go further and find that equity concerns, particularly regarding the impact of the tax on low income households, can be alleviated without sacrificing much of the double-dividend benefits offered by capital tax rebates. There is, however, less agreement regarding the progressivity of CO2taxation net of revenue recycling. Regionally, the models agree that abatement and welfare impacts will vary considerably across regions of the U.S. and generally agree on their broad geographical distribution. There is, however, little agreement regarding the regions which would profit more from the various recycling schemes.
THE ECONOMIC COSTS AND CO-BENEFITS OF CARBON TAXATION: A GENERAL EQUILIBRIUM ASSESSMENT
Authors: WOOLLACOTT JARED
Published: March 2018

I examine the general equilibrium costs of climate policies that levy taxes on carbon dioxide (CO2) emissions in the United States and return the revenue in the form of lump-sum rebates and tax relief over the years 2020 to 2040 using the US regional version of the Applied Dynamic Analysis of the Global Economy (ADAGE-US) forward-looking dynamic Computable General Equilibrium (CGE) model. I approximate the value of co-benefits to these policies that arise from concomitant reductions in nongreenhouse gas (GHG) emissions using the CO-Benefits Risk Assessment model (COBRA). There is significant heterogeneity in costs and co-benefits from climate policies across space and income. Policy costs are generally less than 0[Formula: see text]5% in equivalent variation terms (between a few tens of dollars and several hundred per household, depending on the income quintile), can be fully neutralized for the lowest- quintile households at a modest increase in overall policy cost, and tend to be lower for upper-quintile households in coastal regions. The policy co-benefit values range widely across regions, approximately $150–1250 per household, exceeding the gross cost of the policy for many households, particularly those in the Midwest. Last, I identify a marginal welfare cost of $58[Formula: see text]tCO2 and a marginal co-benefit of $31[Formula: see text]tCO2 at a national level over all households, which implies a required climate benefit of $27[Formula: see text]tCO2 or less to justify the level of abatement achieved by a $25[Formula: see text]tCO2 tax growing at 5%.
EXPLORING THE IMPACTS OF A NATIONAL U.S. CO2 TAX AND REVENUE RECYCLING OPTIONS WITH A COUPLED ELECTRICITY-ECONOMY MODEL
Authors: CARON JUSTIN , COHEN STUART M. , BROWN MAXWELL , REILLY JOHN M.
Published: March 2018

This paper provides a comprehensive exploration of the impacts of economy-wide CO2 taxes in the U.S. simulated using a detailed electric sector model [the National Renewable Energy Laboratory’s Regional Energy Deployment System (ReEDS)] linked with a computable general equilibrium model of the U.S. economy [the Massachusetts Institute of Technology’s U.S. Regional Energy Policy (USREP) model]. We implement various tax trajectories and options for using the revenue collected by the tax and describe their impact on household welfare and its distribution across income levels. Overall, we find that our top-down/bottom-up models affects estimates of the distribution and cost of emission reductions as well as the amount of revenue collected, but that these are mostly insensitive to the way the revenue is recycled. We find that substantial abatement opportunities through fuel switching and renewable penetration in the electricity sector allow the economy to accommodate extensive emissions reductions at relatively low cost. While welfare impacts are largely determined by the choice of revenue recycling scheme, all tax levels and schemes provide net benefits when accounting for the avoided global climate change benefits of emission reductions. Recycling revenue through capital income tax rebates is more efficient than labor income tax rebates or uniform transfers to households. While capital tax rebates substantially reduce the overall costs of emission abatement, they profit high income households the most and are regressive. We more generally identify a clear trade-off between equity and efficiency across the various recycling options. However, we show through a set of hybrid recycling schemes that it is possible to limit inequalities in impacts, particularly those on the lowest income households, at relatively little incremental cost.
Multiple Local Community Detection
Authors: Hollocou Alexandre , Bonald Thomas , Lelarge Marc
Published: March 2018

Community detection is a classical problem in the field of graph mining. We are interested in local community detection where the objective is the recover the communities containing some given set of nodes, called the seed set. While existing approaches typically recover only one community around the seed set, most nodes belong to multiple communities in practice. In this paper, we introduce a new algorithm for detecting multiple local communities, possibly overlapping, by expanding the initial seed set. The new nodes are selected by some local clustering of the graph embedded in a vector space of low dimension. We validate our approach on real graphs, and show that it provides more information than existing algorithms to recover the complex graph structure that appears locally.
Response Time Distribution of a Class of Limited Processor Sharing Queues
Authors: Telek Miklos , Van Houdt Benny
Published: March 2018

Processor sharing queues are often used to study the performance of time-sharing systems. In such systems the total service rate ?(m) depends on the number of jobs m present in the system and there is a limit implemented, called the multi-programming level (MPL), on the number of jobs k that can be served simultaneously. Prior work showed that under highly variable jobs sizes, setting the MPL k beyond the value k = arg maxm ?(m) may reduce the mean response time. In order to study the impact of the MPL k on the response time distribution, we analyse the MAP/PH/LPSk( m) queue. In such a queue jobs arrive according to a Markovian arrival process (MAP), have phase-type (PH) distributed sizes, at most k jobs are processed in parallel and the total service rate depends on the number of jobs being served. Jobs that arrive when there are k or more jobs present are queued. We derive an expression for the Laplace transform of the response time distribution and numerically invert it to study the impact of the MPL k. Numerical results illustrate to what extent increasing k beyond k? increases the quantiles and tail probabilities of the response time distribution. They further demonstrate that for bursty arrivals and larger MPL k values having more variable job sizes may reduce the mean response time.