bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulatory effect of antibiotics on cytokine production by human monocytes in vitro
Authors: Morikawa K , Watabe H , Araake M , Morikawa S
Published: October 2018

Some antimicrobial agents have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. Fosfomycin (FOM) and clarithromycin (CAM) have immunomodulatory activity on human lymphocyte function. In the present study, we examined the effects of FOM and CAM on cytokine synthesis by lipopolysaccharide (LPS)-stimulated human monocytes in comparison with that of dexamethasone in vitro. The three drugs demonstrated positive or negative effects on the synthesis of various cytokines by LPS-primed monocytes. They suppressed the synthesis of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), IL-1 beta, the IL-1 receptor antagonist, and granulocyte-macrophage colony-stimulating factor in a concentration-dependent manner at concentrations between 1.6 and 40 micrograms/ml. On the contrary, the drugs showed different actions on the synthesis of IL-6 and IL-10. Namely, FOM enhanced both IL-6 and IL-10 synthesis, CAM enhanced only IL-10 synthesis, but dexamethasone deeply suppressed the synthesis of both cytokines. These data indicate that antibacterial agents may modify acute-phase inflammatory responses through their effects on cytokine synthesis by monocytes.
Optimizing the Correlation between Results of Testing In Vitro and Therapeutic Outcome In Vivo for Fluconazole by Testing Critical Isolates in a Murine Model of Invasive Candidiasis
Authors: Rex John H. , Nelson Page W. , Paetznick Victor L. , Lozano-Chiu Mario , Espinel-Ingroff A. , Anaissie Elias J.
Published: October 2018

The trailing growth phenomenon seen when determining the susceptibilities of
Candida
isolates to the azole antifungal agents makes consistent endpoint determination difficult, and the M27-A method of the National Committee for Clinical Laboratory Standards addresses this problem by requiring an 80% reduction in growth after 48 h of incubation. For some isolates, however, minor variations of this endpoint criterion can produce up to 128-fold variations in the resulting MIC. To investigate the significance of this effect, isolates of
Candida
that exhibited various forms of trailing growth when tested against fluconazole were identified. The isolates were examined in a murine model of invasive candidiasis and were ranked by their relative response to fluconazole by using both improvement in survival and reduction in fungal burden in the kidney. The resulting rank order of in vivo response did not match the MICs obtained by using the M27-A criterion, and these MICs significantly overestimated the resistance of three of the six isolates tested. However, if the MIC was determined after 24 h of incubation and the endpoint required a less restrictive 50% reduction in growth, MICs which better matched the in vivo response pattern could be obtained. Minor variations in the M27-A endpoint criterion are thus required to optimize the in vitro-in vivo correlation for isolates that demonstrate significant trailing growth when tested against fluconazole.
Overexpression, Purification, and Characterization of the Cloned Metallo-β-Lactamase L1 from
Stenotrophomonas maltophilia
Authors: Crowder Michael W. , Walsh Timothy R. , Banovic Linda , Pettit Margaret , Spencer James
Published: October 2018

The metallo-β-lactamase L1 from
Stenotrophomonas maltophilia
was cloned, overexpressed, and characterized by spectrometric and biochemical techniques. Results of metal analyses were consistent with the cloned enzyme having 2 mol of tightly bound Zn(II) per monomer. Gel filtration chromatography demonstrated that the cloned enzyme exists as a tightly held tetramer with a molecular mass of ca. 115 kDa, and matrix-assisted laser desorption ionization and time-of-flight mass spectrometry indicated a monomeric molecular mass of 28.8 kDa. Steady-state kinetic studies with a number of diverse penicillin and cephalosporin antibiotics demonstrated that L1 effectively hydrolyzes all tested compounds, with
k
cat
/

K
m

values ranging between 0.002 and 5.5 μM
−1
s
−1
. These characteristics of the recombinant enzyme are contrasted to those previously reported for metallo-β-lactamases isolated directly from
S. maltophilia.
Antimicrobial Resistance of 914 Beta-Hemolytic Streptococci Isolated from Pharyngeal Swabs in Spain: Results of a 1-Year (1996–1997) Multicenter Surveillance Study
Authors: Baquero Fernando , García-Rodríguez José Angel , de Lomas Juan García , Aguilar Lorenzo ,   the Spanish Surveillance Group for Respiratory Pathogens
Published: October 2018

A nationwide susceptibility surveillance study of beta-hemolytic streptococcal isolates from pharyngeal swabs obtained in 11 Spanish hospitals between May 1996 and April 1997 against 12 antibiotics was carried out. Of the isolates 86% (786 of 914 isolates) were group A and 8.4% (77 of 914 isolates) were group C. No resistance was found to β-lactam antibiotics, but significant differences (
P
< 0.001) with respect to lack of susceptibility to macrolides were found between groups (27% for group A and 12% for group C) and between seasons (13.2% in summer and 31.7% in winter). Most of these isolates displayed the M phenotype (low-level resistance to erythromycin and susceptibility to clindamycin).
Erythromycin Resistance Genes in Group A Streptococci in Finland
Authors: Kataja Janne , Huovinen Pentti , Skurnik Mikael ,   the Finnish Study Group for Antimicrobial Resistance, Seppälä Helena
Published: October 2018

Streptococcus pyogenes
isolates (group A streptococcus) of different erythromycin resistance phenotypes were collected from all over Finland in 1994 and 1995 and studied; they were evaluated for their susceptibilities to 14 antimicrobial agents (396 isolates) and the presence of different erythromycin resistance genes (45 isolates). The erythromycin-resistant isolates with the macrolide-resistant but lincosamide- and streptogramin B-susceptible phenotype (M phenotype) were further studied for their plasmid contents and the transferability of resistance genes. Resistance to antimicrobial agents other than macrolides, clindamycin, tetracycline, and chloramphenicol was not found. When compared to our previous study performed in 1990, the rate of resistance to tetracycline increased from 10 to 93% among isolates with the inducible resistance (IR) phenotype of macrolide, lincosamide, and streptogramin B (MLS
B
) resistance. Tetracycline resistance was also found among 75% of the MLS
B
-resistant isolates with the constitutive resistance (CR) phenotype. Resistance to chloramphenicol was found for the first time in
S. pyogenes
in Finland; 3% of the isolates with the IR phenotype were resistant. All the chloramphenicol-resistant isolates were also resistant to tetracycline. Detection of erythromycin resistance genes by PCR indicated that, with the exception of one isolate with the CR phenotype, all M-phenotype isolates had the macrolide efflux (
mefA
) gene and all the MLS
B
-resistant isolates had the erythromycin resistance methylase (
ermTR
) gene; the isolate with the CR phenotype contained the
ermB
gene. No plasmid DNA could be isolated from the M-phenotype isolates, but the
mefA
gene was transferred by conjugation.
Cloning, Sequence Analyses, Expression, and Distribution of
ampC-ampR
from
Morganella morganii
Clinical Isolates
Authors: Poirel Laurent , Guibert Michele , Girlich Delphine , Naas Thierry , Nordmann Patrice
Published: October 2018

Shotgun cloning experiments with restriction enzyme-digested genomic DNA from
Morganella morganii
1, which expresses high levels of cephalosporinase, into the pBKCMV cloning vector gave a recombinant plasmid, pPON-1, which encoded four entire genes:
ampC
,
ampR
, an
hybF
family gene, and
orf-1
of unknown function. The deduced AmpC β-lactamase of pI 7.6 shared structural and functional homologies with AmpC from
Citrobacter freundii
,
Escherichia coli
,
Yersinia enterocolitica
,
Enterobacter cloacae
, and
Serratia marcescens
. The overlapping promoter organization of
ampC
and
ampR
, although much shorter in
M. morganii
than in the other enterobacterial species, suggested similar AmpR regulatory properties. The MICs of β-lactams for
E. coli
MC4100 (
ampC
mutant) harboring recombinant plasmid pACYC184 containing either
ampC
and
ampR
(pAC-1) or
ampC
(pAC-2) and induction experiments showed that the
ampC
gene of
M. morganii
1 was repressed in the presence of
ampR
and was activated when a β-lactam inducer was added. Moreover, transformation of
M. morganii
1 or of
E. coli
JRG582 (Δ
ampDE
) harboring
ampC
and
ampR
with a recombinant plasmid containing
ampD
from
E. cloacae
resulted in a decrease in the β-lactam MICs and an inducible phenotype for
M. morganii
1, thus underlining the role of an AmpD-like protein in the regulation of the
M. morganii
cephalosporinase. Fifteen other
M. morganii
clinical isolates with phenotypes of either low-level inducible cephalosporinase expression or high-level constitutive cephalosporinase expression harbored the same
ampC-ampR
organization, with the
hybF
and
orf-1
genes surrounding them; the organization of these genes thus differed from those of
ampC-ampR
genes in
C. freundii
and
E. cloacae
, which are located downstream from the fumarate operon. Finally, an identical AmpC β-lactamase (DHA-1) was recently identified as being plasmid encoded in
Salmonella enteritidis
, and this is confirmatory evidence of a chromosomal origin of the plasmid-mediated cephalosporinases.
A Novel Type of AmpC β-Lactamase, ACC-1, Produced by a
Klebsiella pneumoniae
Strain Causing Nosocomial Pneumonia
Authors: Bauernfeind Adolf , Schneider Ines , Jungwirth Renate , Sahly Hany , Ullmann Uwe
Published: October 2018

A
Klebsiella pneumoniae
strain resistant to oxyimino cephalosporins was cultured from respiratory secretions of a patient suffering from nosocomial pneumonia in Kiel, Germany, in 1997. The isolate harbors a
bla
resistance gene located on a transmissible plasmid. An
Escherichia coli
transconjugant produces a β-lactamase with an isoelectric point of 7.7 and a resistance phenotype characteristic of an AmpC (class 1) β-lactamase except for low MICs of cephamycins. The
bla
gene was cloned and sequenced. It encodes a protein of 386 amino acids with the active site serine of the S-X-X-K motif at position 64, as is characteristic for class C β-lactamases. Multiple alignment of the deduced amino acid sequence with 21 other AmpC β-lactamases demonstrates only very distant homology, reaching at maximum 52.3% identity for the chromosomal AmpC β-lactamase of
Serratia marcescens
SR50. The β-lactamase of
K. pneumoniae
KUS represents a new type of AmpC-class enzyme, for which we propose the designation ACC-1 (Ambler class C-1).
Primary Colonizing
Betaproteobacteriales
Play a Key Role in the Growth of
Legionella pneumophila
in Biofilms on Surfaces Exposed to Drinking Water Treated by Slow Sand Filtration
Authors: van der Kooij Dick , Veenendaal Harm R. , Italiaander Ronald , van der Mark Ed J. , Dignum Marco
Published: October 2018

Proliferation of
L. pneumophila
in premise plumbing poses a public health threat. Extended water treatment using physicochemical and biofiltration processes, including slow sand filtration, at four surface water supplies in The Netherlands reduces the microbial growth potential of the treated water to a minimum level, and the distributed drinking water complies with high quality standards. However, heating of the water in warm tap water installations increases the concentration of easily assimilable organic compounds, thereby promoting biofilm formation and growth of
L. pneumophila
. Prevention of biofilm formation in plumbing systems by maintenance of a disinfectant residual during distribution and/or further natural organic matter (NOM) removal is not feasible in the supplies studied. Temperature management in combination with optimized hydraulics and material selection are therefore essential to prevent growth of
L. pneumophila
in premise plumbing systems. Still, reducing the concentration of biodegradable compounds in drinking water by appropriate water treatment is important for limiting the
Legionella
growth potential.
Behavior of Foodborne Pathogens Listeria monocytogenes and Staphylococcus aureus in Mixed-Species Biofilms Exposed to Biocides
Authors: Oxaran Virginie , Dittmann Karen Kiesbye , Lee Sarah H. I. , Chaul Luíza Toubas , Fernandes de Oliveira Carlos Augusto , Corassin Carlos Humberto , Alves Virgínia Farias , De Martinis Elaine Cristina Pereira , Gram Lone
Published: October 2018

This study demonstrates that foodborne pathogens can be established in mixed-species biofilms and that this can protect them from biocide action. The protection is not due to specific characteristics of the pathogen, here
S. aureus
and
L. monocytogenes
, but likely caused by specific members or associations in the mixed-species biofilm. Biocide treatment and resistance are a challenge for many industries, and biocide efficacy should be tested on microorganisms growing in biofilms, preferably mixed systems, mimicking the application environment.
Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis
Authors: Gralinski Lisa E. , Sheahan Timothy P. , Morrison Thomas E. , Menachery Vineet D. , Jensen Kara , Leist Sarah R. , Whitmore Alan , Heise Mark T. , Baric Ralph S.
Published: October 2018

The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.
Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review
Authors: Matthews Anthony , Stanway Susannah , Farmer Ruth E , Strongman Helen , Thomas Sara , Lyon Alexander R , Smeeth Liam , Bhaskaran Krishnan
Published: October 2018

Objective

To investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer.

Design

Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data sources

Medline and Embase up until June 2018.

Eligibility criteria for selecting studies

Studies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer.

Appraisal and data extraction

Relevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration’s tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies.

Results

26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes.

Conclusion

This review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease outcomes including venous thromboembolism and myocardial infarction, progressing knowledge. Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient’s risk of venous or arterial vascular disease should be an important secondary consideration.

Systematic review registration

Prospero CRD42017065944.
Comparative, cross-sectional study of the format, content and timing of medication safety letters issued in Canada, the USA and the UK
Authors: Bjerre Lise M , Parlow Simon , de Launay David , Hogel Matthew , Black Cody D , Mattison Donald R , Grimshaw Jeremy M , Watson Margaret C
Published: October 2018

Objectives

To assess consistency in the format and content, and overlap of subject and timing, of medication safety letters issued by regulatory health authorities to healthcare providers in Canada, the USA and the UK.

Design

A cross-sectional study comparing medication safety letters issued for the purpose of alerting healthcare providers to newly identified medication problems associated with medications already on the market.

Setting

Online databases operated by Health Canada, the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency were searched to select medication safety letters issued between 1 January 2010 and 31 December 2014. Format, content and timing of each medication safety letter were assessed using an abstraction tool comprising 21 characteristics deemed relevant by consensus of the research team.

Main outcome measures

Main outcome measures included, first, characteristics (format and content) of medication safety letters and second, overlap of subject and release date across countries.

Results

Of 330 medication safety letters identified, 227 dealt with unique issues relating to medications available in all three countries. Of these 227 letters, 21 (9%) medication problems were the subject of letters released in all three countries; 40 (18%) in two countries and 166 (73%) in only one country. Only 13 (62%) of the 21 letters issued in all three countries were released within 6 months of each other.

Conclusions

Significant discrepancies in both the subject and timing of medication safety letters issued by health authorities in three countries (Canada, the USA and the UK) where medical practice is otherwise comparable, raising questions about why, how and when medication problems are identified and communicated to healthcare providers by the authorities. More rapid communication of medication problems and better alignment between authorities could enhance patient safety.
Testing the information-motivation-behavioural skills model of diabetes self-management among Chinese adults with type 2 diabetes: a protocol of a 3-month follow-up study
Authors: Liu Tingting , Wu Dongmei , Wang Jing , Li Changwei , Yang Rumei , Ge Song , Du Yan , Wang Yanyan
Published: October 2018

Introduction

Currently, China leads the world in the number of people with diabetes, making it home to a third of the global diabetic population. Persons with diabetes have to carry out 95% of their self-care. As an important component of diabetes care, diabetes self-management (DSM) is defined as everyday behaviours that persons carry out to control diabetes. Consistent findings have been reported that level of compliance to suggested DSM behaviours is not considered optimal among Chinese adults with type 2 diabetes (T2D). The underlying reasons for suboptimal DSM behaviours among Chinese adults are not well known and no conceptual model has been developed to guide DSM interventions in this population. Although the information-motivation-behavioural skills model has been tested among Chinese adults with T2D, some key components of the original model were not tested. In this proposed study protocol, we will refine and test a culturally tailored model of DSM longitudinally among 250 Chinese adults residing in China.

Methods and analysis

This is a descriptive, repeated-measure study to be conducted at a tertiary hospital in Chengdu, China. A total of 250 adults with T2D will be enrolled and followed for 3 months in this study. Information of multiple domains will be collected, including demographics, diabetes knowledge, health education form, provider-patient communication, health beliefs, social support, diabetes self-efficacy, the medical coping modes, the diabetes self-care, depression, diabetes-dependent quality of life, haemoglobin A1c, blood pressure and blood lipids at baseline and 3-month follow-up. Main analyses comprise linear regression modelling controlling for covariates and structural equation modelling.

Ethics and dissemination

Ethical approval has been obtained through the Fourth People’s Hospital of Chengdu Research Ethics Committee (study approval number 2017017). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media.

Trial registration number

ChiCTR-ROC-17013592.
Do changing medical admissions practices in the UK impact on who is admitted? An interrupted time series analysis
Authors: Fielding Shona , Tiffin Paul Alexander , Greatrix Rachel , Lee Amanda J , Patterson Fiona , Nicholson Sandra , Cleland Jennifer
Published: October 2018

Introduction

Medical admissions must balance two potentially competing missions: to select those who will be successful medical students and clinicians and to increase the diversity of the medical school population and workforce. Many countries address this dilemma by reducing the heavy reliance on prior educational attainment, complementing this with other selection tools. However, evidence to what extent this shift in practice has actually widened access is conflicting.

Aim

To examine if changes in medical school selection processes significantly impact on the composition of the student population.

Design and setting

Observational study of medical students from 18 UK 5-year medical programmes who took the UK Clinical Aptitude Test from 2007 to 2014; detailed analysis on four schools.

Primary outcome

Proportion of admissions to medical school for four target groups (lower socioeconomic classes, non-selective schooling, non-white and male).

Data analysis

Interrupted time-series framework with segmented regression was used to identify the impact of changes in selection practices in relation to invitation to interview to medical school. Four case study medical schools were used looking at admissions within for the four target groups.

Results

There were no obvious changes in the overall proportion of admissions from each target group over the 8-year period, averaging at 3.3% lower socioeconomic group, 51.5% non-selective school, 30.5% non-white and 43.8% male. Each case study school changed their selection practice in decision making for invite to interview during 2007–2014. Yet, this within-school variation made little difference locally, and changes in admission practices did not lead to any discernible change in the demography of those accepted into medical school.

Conclusion

Although our case schools changed their selection procedures, these changes did not lead to any observable differences in their student populations. Increasing the diversity of medical students, and hence the medical profession, may require different, perhaps more radical, approaches to selection.
Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink
Authors: Gamble John-Michael , Chibrikov Eugene , Midodzi William K , Twells Laurie K , Majumdar Sumit R
Published: October 2018

Objectives

To compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents.

Design

Population-based cohort study.

Setting

Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD).

Participants

Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016. Patients with a prior history of depression, self-harm and other serious psychiatric conditions were excluded.

Main outcome measures

The primary study outcome comprised a composite of new-onset depression or self-harm. Unadjusted and adjusted Cox proportional hazards regression was used to quantify the association between incretin-based therapies and depression or self-harm. Deciles of High-Dimensional Propensity Scores and concurrent number of glucose-lowering agents were used to adjust for potential confounding.

Results

We identified new users of 6206 DPP-4i and 22 128 SU in the DPP-4i-cohort, and 501 GLP-1RA and 16 409 SU new users in the GLP-1RA-cohort. The incidence of depression or self-harm was 8.2 vs 11.7 events/1000 person-years in the DPP-4i-cohort and 18.2 vs 13.6 events/1000 person-years in the GLP-1RA-cohort for incretin-based therapies versus SU, respectively. Incretin-based therapies were not associated with an increased or decreased incidence of depression or self-harm compared with SU (DPP-4i-cohort: unadjusted HR 0.70, 95% CI 0.51 to 0.96; adjusted HR 0.80, 95% CI 0.57 to 1.13; GLP-1RA-cohort: unadjusted HR 1.36, 95% CI 0.72 to 2.58; adjusted HR 1.25, 95% CI 0.63 to 2.50). Consistent results were observed for other glucose-lowering comparators including insulin and thiazolidinediones.

Conclusions

Our findings suggest that the two incretin-based therapies are not associated with an increased or decreased risk of depression or self-harm.
Relationship between right-to-left shunt and migraine in patients with epilepsy: a single-centre, cross-sectional study in China
Authors: Zhang Lin , Zhu Xi , Qiu Xiangmiao , Li Yajiao , Chen Yucheng , Wang Hui , He Shixu , Lai Wanlin , Peng Anjiao , Ning Mingming , Chen Lei
Published: October 2018

Objectives

To investigate the relationship between right-to-left shunt and migraine to account for the unexplained high prevalence of migraine in patients with epilepsy.

Design

This is a cross-sectional study. The diagnosis and interview process of patients with migraine was based on the International Classification of Headache Disorders-3 beta in patients with epilepsy. Participants underwent transthoracic echocardiography (TTE) with contrast medium to identify right-to-left shunt. The highest number of microbubbles were recorded in the left atrium before the complete microbubble outflow of the right atrium. A moderate-to-large shunt was defined as the presence of 10 or more microbubbles.

Setting

A single-centre, cross-sectional study in China, 2015–2017.

Participants

Patients with epilepsy.

Primary and secondary outcome measures

The primary outcome measures were the prevalence of migraine, the prevalence of right-to-left shunt in patients with migraine and those without migraine, and the prevalence of migraine in different degrees of shunting.

Results

Three hundred thirty-nine participants with epilepsy who completed TTE were included in the analysis. The overall prevalence of migraine was 23.0%. One-third of the migraineurs had mild right-to-left shunt and one-fifth of the migraineurs had moderate-to-large right-to-left shunt. Patients with mild shunt did not have a higher prevalence of migraine than those without shunt (26.3% vs 18.1%, p=0.102); however, a higher prevalence of migraine was found in patients with moderate-to-large shunt (39.0% vs 18.1%, OR=2.90, 95% CI=1.41 to 5.98, p=0.003). Patients with migraine and patients without migraine had similar prevalence of mild shunt; however, patients with migraine had more moderate-to-large shunt (20.5% vs 9.6%, p=0.002). Right-to-left shunt and female were factors predicting migraine prevalence.

Conclusions

One-fifth of migraineurs were correlated with moderate-to-large right-to-left shunt which could be an underlying cause of migraine in epilepsy.
Effectiveness of a multistate quality improvement campaign in reducing risk of surgical site infections following hip and knee arthroplasty
Authors: Calderwood Michael S , Yokoe Deborah S , Murphy Michael V , DeBartolo Katherine O , Duncan Kathy , Chan Christina , Schneider Eric C , Parry Gareth , Goldmann Don , Huang Susan
Published: October 2018

Background

Quality improvement (QI) campaigns appear to increase use of evidence-based practices, but their effect on health outcomes is less well studied.

Objective

To assess the effect of a multistate QI campaign (Project JOINTS, Joining Organizations IN Tackling SSIs) that used the Institute for Healthcare Improvement’s Rapid Spread Network to promote adoption of evidence-based surgical site infection (SSI) prevention practices.

Methods

We analysed rates of SSI among Medicare beneficiaries undergoing hip and knee arthroplasty during preintervention (May 2010 to April 2011) and postintervention (November 2011 to September 2013) periods in five states included in a multistate trial of the Project JOINTS campaign and five matched comparison states. We used generalised linear mixed effects models and a difference-in-differences approach to estimate changes in SSI outcomes.

Results

125 070 patients underwent hip arthroplasty in 405 hospitals in intervention states, compared with 131 787 in 525 hospitals in comparison states. 170 663 patients underwent knee arthroplasty in 397 hospitals in intervention states, compared with 196 064 in 518 hospitals in comparison states. After the campaign, patients in intervention states had a 15% lower odds of developing hip arthroplasty SSIs (OR=0.85, 95% CI 0.75 to 0.96, p=0.01) and a 12% lower odds of knee arthroplasty SSIs than patients in comparison states (OR=0.88, 95% CI 0.78 to 0.99, p=0.04).

Conclusions

A larger reduction of SSI rates following hip and knee arthroplasty was shown in intervention states than in matched control states.
National hospital mortality surveillance system: a descriptive analysis
Authors: Cecil Elizabeth , Wilkinson Samantha , Bottle Alex , Esmail Aneez , Vincent Charles , Aylin Paul P
Published: October 2018

Objective

To provide a description of the Imperial College Mortality Surveillance System and subsequent investigations by the Care Quality Commission (CQC) in National Health Service (NHS) hospitals receiving mortality alerts.

Background

The mortality surveillance system has generated monthly mortality alerts since 2007, on 122 individual diagnosis and surgical procedure groups, using routinely collected hospital administrative data for all English acute NHS hospital trusts. The CQC, the English national regulator, is notified of each alert. This study describes the findings of CQC investigations of alerting trusts.

Methods

We carried out (1) a descriptive analysis of alerts (2007–2016) and (2) an audit of CQC investigations in a subset of alerts (2011–2013).

Results

Between April 2007 and October 2016, 860 alerts were generated and 76% (654 alerts) were sent to trusts. Alert volumes varied over time (range: 40–101). Septicaemia (except in labour) was the most commonly alerting group (11.5% alerts sent). We reviewed CQC communications in a subset of 204 alerts from 96 trusts. The CQC investigated 75% (154/204) of alerts. In 90% of these pursued alerts, trusts returned evidence of local case note reviews (140/154). These reviews found areas of care that could be improved in 69% (106/154) of alerts. In 25% (38/154) trusts considered that identified failings in care could have impacted on patient outcomes. The CQC investigations resulted in full trust action plans in 77% (118/154) of all pursued alerts.

Conclusion

The mortality surveillance system has generated a large number of alerts since 2007. Quality of care problems were found in 69% of alerts with CQC investigations, and one in four trusts reported that failings in care may have an impact on patient outcomes. Identifying whether mortality alerts are the most efficient means to highlight areas of substandard care will require further investigation.
Balloon remodeling-assisted Woven EndoBridge technique: description and feasibility for complex bifurcation aneurysms
Authors: Mihalea Cristian , Escalard Simon , Caroff Jildaz , Ikka Léon , Rouchaud Aymeric , Da Ros Valerio , Pagiola Igor , Marenco de la Torre Joaquin Jose , Yasuda Thomas , Popa Bogdan Valeriu , Ples Horia , Benachour Nidhal , Ozanne Augustin , Moret Jacques , Spelle Laurent
Published: October 2018

Background

Woven EndoBridge (WEB) deployment remains challenging in aneurysms with a complex shape or orientation.

Objective

To show that embolization of wide-neck bifurcation aneurysms using the WEB device balloon remodeling-assisted technique is a feasible and elegant endovascular solution compared with other techniques, such as balloon remodeling or stent-assisted coiling.

Materials and methods

10 cases (10 aneurysms in 9 patients) of balloon remodeling-assisted WEB treatment of unruptured complex bifurcation aneurysms were treated in our institution and retrospectively analyzed. Details of clinical presentations, technical details, perioperative and postoperative complications, and outcomes were collected. Immediate and long-term angiographic results were also evaluated.

Results

Aneurysms included six middle cerebral artery aneurysms, one anterior communicating artery aneurysm, one posterior communicating artery aneurysm, one basilar artery aneurysm, and one T-shaped carotid aneurysm. Mean dome width was 6.55 mm, mean neck size 4.5 mm, mean height 4.79 mm, and mean dome-to-neck ratio was 1:1.46. Treatment was performed exclusively with the balloon remodeling-assisted WEB technique in all cases. The device was successfully deployed in every case. Periprocedural thromboembolic or hemorrhagic events did not occur. The modified Rankin Scale score at discharge was 0 for all patients. At mid-term or long-term angiographic follow-up, adequate occlusion was observed in 7 aneurysms from 8 controlled cases (87.5%), and one patient (2 aneurysms) did not have angiographic follow-up.

Conclusion

The balloon remodeling-assisted WEB technique seems to be a safe and effective solution for endovascular treatment of unruptured wide-neck bifurcation aneurysms with specific complex anatomy. However, further studies are needed to evaluate the rate of complications and long-term efficacy.
Vertebral body stent augmentation to reconstruct the anterior column in neoplastic extreme osteolysis
Authors: Cianfoni Alessandro , Distefano Daniela , Pravatà Emanuele , Espeli Vittoria , Pesce Gianfranco , Mordasini Pasquale , La Barbera Luigi , Scarone Pietro , Bonaldi Giuseppe
Published: October 2018

Background

Extensive lytic lesions of the vertebral body (VB) increase risk of fracture and instability and require stabilization of the anterior column. Vertebral augmentation is an accepted treatment option, but when osteolysis has extensively destroyed the VB cortical boundaries (a condition herein defined as ‘extreme osteolysis’), the risk of cement leakage and/or insufficient filling is high. Vertebral body stents (VBSs) might allow partial restoration of VB height, cement containment, and reinforcement, but their use in extreme osteolysis has not been investigated.

Objective

To assess retrospectively the feasibility and safety of VBS augmentation in patients with ‘extreme osteolysis’ of the VB.

Methods

We retrospectively analyzed 41 treated vertebrae (from T1 to L5). VB reconstruction was assessed on postprocedure CT images and rated on a qualitative 4-point scale (poor-fair-good-excellent). Clinical and radiological follow-up was performed at 1 month and thereafter at intervals in accordance with oncological protocols.

Results

VBS augmentation was performed at 12 lumbar and 29 thoracic levels, with bilateral VBS in 23/41. VB reconstruction was judged satisfactory (good or excellent) in 37/41 (90%) of levels. Bilateral VBS received higher scores than unilateral (p=0.057, Pearson’s X2). We observed no periprocedural complications. Cement leaks (epidural or foraminal) occurred at 5/41 levels (12.2%) without clinical consequences. Follow-up data were available for 27/29 patients, extending beyond 6 months for 20 patients (7–28 months, mean 15.3 months). VBS implant stability was observed in 40/41 cases (97.5%).

Conclusions

Our results support the use of VBS as a minimally invasive, safe and effective option for reconstructing the anterior column in prominent VB osteolysis.
Selective compromise of hypoplastic posterior communicating artery variants with aneurysms treatable by coil embolization: clinical and radiologic outcomes
Authors: Choi Hyun Ho , Cho Young Dae , Yoo Dong Hyun , Yeon Eung Koo , Lee Jeongjun , Lee Su Hwan , Kang Hyun-Seung , Cho Won-Sang , Kim Jeong Eun , Han Moon Hee
Published: October 2018

Background

Posterior communicating artery (PcoA) compromise may serve as adjunctive treatment in patients with hypoplastic variants of PcoA who undergo coil embolization of PcoA aneurysms. However, procedural safety and the propensity for later recanalization are still unclear.

Objective

To evaluate clinical and radiologic outcomes of coil embolization in this setting, focusing on compromise of PcoA.

Methods

As a retrospective review, we examined 250 patients harboring 291 aneurysms of hypoplastic PcoAs, all consecutively treated by coil embolization between January 2004 and June 2016. PcoA compromise was undertaken in conjunction with 81 of the treated aneurysms (27.8%; incomplete 53; complete 28). Medical records and radiologic data were assessed during extended monitoring.

Results

During the mean follow-up of 33.9±24.6 months (median 36 months), a total of 107 (36.8%) coiled aneurysms showed recanalization (minor 50; major 57). Recanalization rates were as follows: PcoA preservation 40.5% (85/210); incomplete PcoA occlusion 34.0% (18/53); complete PcoA occlusion 14.3% (4/28). Aneurysms >7 mm (HR 3.40; P<0.01), retreatment for recanalization (HR 3.23; P<0.01), and compromise of PcoA (P<0.01) emerged from multivariate analysis as significant risk factors for recanalization. Compared with PcoA preservation, complete PcoA compromise conferred more favorable outcomes (HR 0.160), whereas incomplete compromise of PcoA fell short of statistical significance. Thromboembolic infarction related to PcoA compromise did not occur in any patient.

Conclusion

PcoA compromise in conjunction with coil embolization of PcoA aneurysms appears safe in hypoplastic variants of PcoA, helping to prevent recanalization if complete occlusion is achieved.
The safety and effectiveness of the LVIS stent system for the treatment of wide-necked cerebral aneurysms: final results of the pivotal US LVIS trial
Authors: Fiorella David , Boulos Alan , Turk Aquilla S , Siddiqui Adnan H , Arthur Adam S , Diaz Orlando , Lopes Demetrius K
Published: October 2018

Introduction

The LVIS stent system (LVIS and LVIS Junior) is a self-expanding, retrievable, microstent system indicated for the treatment of wide-necked cerebral aneurysms (WNAs). The present pivotal study was performed to evaluate the safety and effectiveness of this device.

Methods

The US LVIS pivotal trial was a prospective, multicenter, single-arm, interventional study conducted at 21 US centers. The study enrolled 153 adults with WNAs of the anterior and posterior circulations. The study was conducted under good clinical practices and included independent adjudication of all adverse events. The primary effectiveness endpoint was defined as successful aneurysm treatment with the LVIS System as evidenced by complete (100%) aneurysm occlusion at 12 months on conventional angiography without retreatment and without significant (≥50%) stenosis of the treated artery at 12 months as determined by an independent core laboratory. The primary safety endpoint was defined as the rate of stroke or death within 30 days, or ipsilateral stroke or neurologic death with 12 months.

Results

One hundred and fifty-three patients enrolled at 21 investigational sites underwent attempted LVIS-assisted coil embolization. The mean age was 58.3±10.5 years and the majority of the participants (110/153, 71.9%) were female. Fifty-seven aneurysms (57/153, 37.3%) arose from the anterior cerebral artery, 43 (43/153, 28.1%) from the internal carotid artery, 17 (17/153, 11.1%) from the middle cerebral artery, 27 (27/153, 17.6%) from the basilar artery, six (6/153,3.9 %) from the PCA, and two from the vertebral artery. A single aneurysm arose from the superior cerebellar artery. The mean aneurysm dome height was 6.0±2.2 mm and mean width 5.5±2.3 mm. Mean neck width was 4.2±1.4 mm. A total of 22 participants presented for re-treatment of a previously ruptured (>30 days prior to treatment) target aneurysm. The primary effectiveness endpoint was observed in 70.6% (108/153) in the intent to treat population (ITT). Of the evaluable participants with follow-up 12-month angiography, 79.1 % (110/139) demonstrated complete occlusion– 92.1% (128/139) in this population demonstrated ≥95% occlusion and 95% demonstrated ≥90% occlusion (132/139). Eight participants (5.2%, 8/153) had at least one primary safety event in the ITT population.

Conclusion

The LVIS stent system allows safe and highly effective coil embolization of WNAs.

Clinical registration number

NCT01793792.
Ground state energy of mixture of Bose gases
Authors: Michelangeli Alessandro , Nam Phan Thành , Olgiati Alessandro
Published: October 2018

We consider the asymptotic behavior of a system of multi-component trapped bosons, when the total particle number [Formula: see text] becomes large. In the dilute regime, when the interaction potentials have the length scale of order [Formula: see text], we show that the leading order of the ground state energy is captured correctly by the Gross–Pitaevskii energy functional and that the many-body ground state fully condensates on the Gross–Pitaevskii minimizers. In the mean-field regime, when the interaction length scale is [Formula: see text], we are able to verify Bogoliubov’s approximation and obtain the second order expansion of the ground state energy. While such asymptotic results have several precursors in the literature on one-component condensates, the adaptation to the multi-component setting is non-trivial in various respects and the analysis will be presented in detail.
Memristor Emulator Circuit Using Multiple-Output OTA and Its Experimental Results
Authors: Ranjan Rajeev Kumar , Sharma Pankaj Kumar , Sagar  , Raj Niranjan , Kumari Bharti , Khateb Fabian
Published: October 2018

A charge-controlled memristor emulator circuit based on one kind of active device [operational transconductance amplifier (OTA)] using CMOS technology is introduced in this paper. The proposed circuit can be configured in both incremental and decremental types by using a simple switch. The memristor behavior can be electronically tuned by adjusting the transconductance of the OTAs. By changing the value of the capacitor, the pinched hysteresis loop observed in the current versus voltage plane can be held at higher frequencies. The proposed emulator circuit functions well up to 500 kHz. The experiment has been performed using commercially available OTA ICs (CA3080). The experimental demonstration has been carried out for 10, 20 and 120[Formula: see text]kHz. A simple high-pass filter is explained in both configurations to demonstrate the functionality of the proposed memristor emulator. The proposed circuit has been simulated in PSPICE using 0.5-[Formula: see text]m CMOS parameter. The simulated and experimental results validate the theoretical proposition.
Background independence in string theory
Authors: Hohm Olaf
Published: October 2018

I discuss various aspects of background independence in the context of string theory, for which so far we have no manifestly background independent formulation. After reviewing the role of background independence in classical Einstein gravity, I discuss recent results implying that there is a conflict in string theory between manifest background independence and manifest duality invariance when higher-derivative corrections are included. The resolution of this conflict requires the introduction of new gauge degrees of freedom together with an enlarged gauge symmetry. This suggests more generally that a manifestly background independent and duality invariant formulation of string theory requires significantly enhanced gauge symmetries.
Spectroscopies of rod- and pear-shaped nuclei in covariant density functional theory
Authors: Zhao Pengwei , Li Zhipan
Published: October 2018

The spectroscopic properties play a crucial role in understanding the structure of nuclei, in particular, the shape and shape transitions of nuclei. In recent years, the exotic shapes of nuclear systems, such as the rod and pear shapes, have attracted a lot of attention. Covariant density functional theory (CDFT) has become a standard tool for nuclear structure calculations, and it provides a global and accurate description of nuclear ground states and excitations. In the present paper, we briefly review the recent progress in covariant density functional theory (DFT) for spectroscopic properties of the rod- and pear-shaped nuclei with the cranking calculations in a rotating mean field and the collective Hamiltonian method beyond mean field. The novel linear-chain structure of alpha clustering is discussed with the cranking approach, and low lying spectra of pear-shaped nuclei are illustrated with the quadrupole–octupole collective Hamiltonian.
A Situational Method for Creating Shared Understanding on Requirements for an Enterprise Architecture
Authors: Nakakawa Agnes , Van Bommel Patrick , Proper Erik H. A. , Mulder Hans J. B. F.
Published: October 2018

Lack of shared understanding among stakeholders is a commonly cited drawback in enterprise architecture development. Stakeholders need to have shared understanding of requirements and principles for an enterprise architecture, and the extent to which the resultant architecture addresses their concerns. However, existing approaches for enterprise architecture development lack adequate capabilities for managing aspects associated with creating shared understanding among stakeholders. Although such aspects can be largely managed by approaches for collaborative decision making and soft systems thinking, these approaches lack details on the enterprise architecture process and its products. Therefore, this paper explores ways of mutually diminishing these gaps through adopting situational method engineering, to guide the development of a situational method for enabling stakeholders to acquire shared understanding of requirements for an enterprise architecture. The situational method presented herein is a component of a broader method for supporting collaboration between stakeholders and architects during enterprise architecture creation. Although the latter was successfully evaluated in 6 enterprises, it exhibited highest performance scores in two enterprises after it was amended with the situational method. Therefore, this paper also presents key findings from evaluating the situational method in the two agencies that are located in Uganda.