bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Peptide CMA3 Derived from the CA-MA Hybrid Peptide: Antibacterial and Anti-inflammatory Activities with Low Cytotoxicity and Mechanism of Action in Escherichia coli
Authors: Lee Jong-kook , Seo Chang Ho , Luchian Tudor , Park Yoonkyung
Published: November 2015

CA-MA is a hybrid antimicrobial peptide (AMP) derived from two naturally occurring AMPs, cecropin A and magainin 2. CA-MA shows strong antimicrobial activity against Gram-negative and Gram-positive bacteria but also exhibits cytotoxicity toward mammalian cells. Our objective was to identify CA-MA analogues with reduced cytotoxicity by systematic replacement of amino acids with positively charged R groups (His and Lys), aliphatic R groups (Leu), or polar R groups (Glu). Among the CA-MA analogues studied (CMA1 to -6), CMA3 showed the strongest antimicrobial activity, including against drug-resistant
Escherichia coli
and
Pseudomonas aeruginosa
strains isolated from hospital patients. CMA3 appeared to act by inducing pore formation (toroidal model) in the bacterial membrane. In cytotoxicity assays, CMA3 showed little cytotoxicity toward human red blood cells (hRBCs) or HaCaT cells. Additionally, no fluorescence was released from small or giant unilamellar vesicles exposed to 60 μM CMA3 for 80 s, whereas fluorescence was released within 35 s upon exposure to CA-MA. CMA3 also exerted strong lipopolysaccharide (LPS)-neutralizing activity in RAW 264.7 cells, and BALB/c mice exposed to LPS after infection by
Escherichia coli
showed improved survival after administration of one 0.5-mg/kg of body weight or 1-mg/kg dose of CMA3. Finally, in a mouse model of septic shock, CMA3 reduced the levels of proinflammatory factors, including both nitric oxide and white blood cells, and correspondingly reduced lung tissue damage. This study suggests that CMA3 is an antimicrobial/antiendotoxin peptide that could serve as the basis for the development of anti-inflammatory and/or antimicrobial agents with low cytotoxicity.
Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli
Authors: Ho Pak-Leung , Ng Ka-Ying , Lo Wai-U , Law Pierra Y. , Lai Eileen Ling-Yi , Wang Ya , Chow Kin-Hung
Published: November 2015

Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene
oqxAB
and its contribution to nitrofurantoin resistance by using
Escherichia coli
isolates originating from patients with UTI (
n
= 205; collected in 2004 to 2013) and food-producing animals (
n
= 136; collected in 2012 to 2013) in Hong Kong. The
oqxAB
gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the
oqxAB
gene was associated with IS
26
and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of
oqxAB
-positive
E. coli
were diverse. The combination of
oqxAB
and
nfsA
mutations was found to be sufficient for high-level NIT resistance. Curing of
oqxAB
-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 μg/ml to 34.3 μg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with
nfsA
mutations were NIT-S, while 80% (12/15) of isolates without
nfsA
mutations were NIT-S (
P
= 0.015). The presence of plasmid-based
oqxAB
increased the mutation prevention concentration of NIT from 128 μg/ml to 256 μg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated
oqxAB
is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.
Azole Resistance in Aspergillus fumigatus Clinical Isolates from an Italian Culture Collection
Authors: Lazzarini Cristina , Esposto Maria Carmela , Prigitano Anna , Cogliati Massimo , De Lorenzis Gabriella , Tortorano Anna Maria
Published: November 2015

The aims of the study were to investigate the prevalence of azole resistance among
Aspergillus fumigatus
clinical isolates. A total of 533 clinical isolates that had been collected between 1995 and 2006, from 441 patients, were screened. No resistance was detected in isolates collected between 1995 and 1997. Starting in 1998, the resistance rate was 6.9%; a total of 24 patients (6.25%) harbored a resistant isolate. The TR34/L98H substitution was found in 21 of 30 tested isolates.
In Vitro
Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms
Authors: Arendrup Maiken Cavling , Jensen Rasmus Hare , Cuenca-Estrella Manuel
Published: November 2015

ASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity against
Aspergillus
and
Candida glabrata
. We compared its
in vitro
activity against wild-type and azole-resistant
A. fumigatus
and
A. terreus
isolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-type
A. fumigatus
isolates, 24
A. fumigatus
isolates with alterations in CYP51A TR/L98H (5 isolates), M220 (9 isolates), G54 (9 isolates), and HapE (1 isolate), and
A. terreus
isolates (2 wild-type isolates and 1 isolate with an M217I CYP51A alteration), were analyzed. EUCAST E.Def 9.2 and CLSI M38-A2 MIC susceptibility testing was performed. ASP2397 MIC
50
values (in milligrams per liter, with MIC ranges in parentheses) determined by EUCAST and CLSI were 0.5 (0.25 to 1) and 0.25 (0.06 to 0.25) against
A. fumigatus
CYP51A wild-type isolates and were similarly 0.5 (0.125 to >4) and 0.125 (0.06 to >4) against azole-resistant
A. fumigatus
isolates, respectively. These values were comparable to those for amphotericin B, which were 0.25 (0.125 to 0.5) and 0.25 (0.125 to 0.25) against wild-type isolates and 0.25 (0.125 to 1) and 0.25 (0.125 to 1) against isolates with azole resistance mechanisms, respectively. In contrast, MICs for the azole compounds were elevated and highest for itraconazole: >4 (1 to >4) and 4 (0.5 to >4) against isolates with azole resistance mechanisms compared to 0.125 (0.125 to 0.25) and 0.125 (0.06 to 0.25) against wild-type isolates, respectively. ASP2397 was active against
A. terreus
CYP51A wild-type isolates (MIC 0.5 to 1), whereas MICs of both azole and ASP2397 were elevated for the mutant isolate. ASP2397 displayed
in vitro
activity against
A. fumigatus
and
A. terreus
isolates which was independent of the presence or absence of azole target gene resistance mutations in
A. fumigatus
. The findings are promising at a time when azole-resistant
A. fumigatus
is emerging globally.
fosI
Is a New Integron-Associated Gene Cassette Encoding Reduced Susceptibility to Fosfomycin
Authors: Pelegrino Karla de Oliveira , Campos Juliana Coutinho , Sampaio Suely Carlos Ferreira , Lezirovitz Karina , Seco Bruna Mara , Pereira Mayne de Oliveira , Rocha Darlan Augusto da Costa , Jové Thomas , Nicodemo Antonio Carlos , Sampaio Jorge Luiz Mello
Published: November 2015

In this work, we demonstrate that the
fosI
gene encodes a predicted small protein with 134 amino acids and determines reduced susceptibility to fosfomycin. It raised the MIC from 0.125 to 6 μg/ml when the pBRA100 plasmid was introduced into
Escherichia coli
TOP10 and to 16 μg/ml when the gene was cloned into the pBC_SK(−) vector and expressed in
E. coli
TOP10.
Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae
Authors: Ipe Deepak S. , Ben Zakour Nouri L. , Sullivan Matthew J. , Beatson Scott A. , Ulett Kimberly B. , Benjamin William H. , Davies Mark R. , Dando Samantha J. , King Nathan P. , Cripps Allan W. , Schembri Mark A. , Dougan Gordon , Ulett Glen C.
Published: November 2015

Streptococcus agalactiae
causes both symptomatic cystitis and asymptomatic bacteriuria (ABU); however, growth characteristics of
S. agalactiae
in human urine have not previously been reported. Here, we describe a phenotype of robust growth in human urine observed in ABU-causing
S. agalactiae
(ABSA) that was not seen among uropathogenic
S. agalactiae
(UPSA) strains isolated from patients with acute cystitis. In direct competition assays using pooled human urine inoculated with equal numbers of a prototype ABSA strain, designated ABSA 1014, and any one of several UPSA strains, measurement of the percentage of each strain recovered over time showed a markedly superior fitness of ABSA 1014 for urine growth. Comparative phenotype profiling of ABSA 1014 and UPSA strain 807, isolated from a patient with acute cystitis, using metabolic arrays of >2,500 substrates and conditions revealed unique and specific
l
-malic acid catabolism in ABSA 1014 that was absent in UPSA 807. Whole-genome sequencing also revealed divergence in malic enzyme-encoding genes between the strains predicted to impact the activity of the malate metabolic pathway. Comparative growth assays in urine comparing wild-type ABSA and gene-deficient mutants that were functionally inactivated for the malic enzyme metabolic pathway by targeted disruption of the
maeE
or
maeK
gene in ABSA demonstrated attenuated growth of the mutants in normal human urine as well as synthetic human urine containing malic acid. We conclude that some
S. agalactiae
strains can grow in human urine, and this relates in part to malic acid metabolism, which may affect the persistence or progression of
S. agalactiae
ABU.
Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis
Authors: Zimbler Daniel L. , Eddy Justin L. , Schroeder Jay A. , Lathem Wyndham W.
Published: November 2015

Pneumonic plague represents the most severe form of disease caused by
Yersinia pestis
due to its ease of transmission, rapid progression, and high mortality rate. The
Y. pestis
outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by
Y. pestis
in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A
2
activities of Prdx6. In addition, we found that infection with wild-type
Y. pestis
reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with Δ
pla
Y. pestis
, suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or Δ
pla Y. pestis
, Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function
in vitro
and reduce Prdx6 levels
in vivo
, the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague.
Dissecting the Structural Elements for the Activation of β-Ketoacyl-(Acyl Carrier Protein) Reductase from Vibrio cholerae
Authors: Hou Jing , Zheng Heping , Chruszcz Maksymilian , Zimmerman Matthew D. , Shumilin Igor A. , Osinski Tomasz , Demas Matt , Grimshaw Sarah , Minor Wladek
Published: November 2015

β-Ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either the active or inactive conformation. However, the structural elements which enable activation of FabG require further exploration. Here we report the findings of structural, enzymatic, and binding studies of the FabG protein found in the causative agent of cholera,
Vibrio cholerae
(vcFabG). vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between the dimeric and tetrameric states of vcFabG is related to changes in the conformations of the α4/α5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified to be the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loop β4-α4 and loop β5-α5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by binding and enzymatic assays for the corresponding mutants.

IMPORTANCE
This paper describes the results of structural, enzymatic, and binding studies of FabG from
Vibrio cholerae
(vcFabG). In this work, we dissected the structural elements responsible for the activation of vcFabG. The structural information provided here is essential for the development of antibiotics specifically targeting bacterial FabG, especially for the multidrug-resistant strains of
V. cholerae
.
GroEL2 of Mycobacterium tuberculosis Reveals the Importance of Structural Pliability in Chaperonin Function
Authors: Chilukoti Neeraja , Kumar C. M. Santosh , Mande Shekhar C.
Published: November 2015

Intracellular protein folding is mediated by molecular chaperones, the best studied among which are the chaperonins GroEL and GroES. Conformational changes and allosteric transitions between different metastable states are hallmarks of the chaperonin mechanism. These conformational transitions between three structural domains of GroEL are anchored at two hinges. Although hinges are known to be critical for mediating the communication between different domains of GroEL, the relative importance of hinges on GroEL oligomeric assembly, ATPase activity, conformational changes, and functional activity is not fully characterized. We have exploited the inability of
Mycobacterium tuberculosis
GroEL2 to functionally complement an
Escherichia coli
groEL
mutant to address the importance of hinge residues in the GroEL mechanism. Various chimeras of
M. tuberculosis
GroEL2 and
E. coli
GroEL allowed us to understand the role of hinges and dissect the consequences of oligomerization and substrate binding capability on conformational transitions. The present study explains the concomitant conformational changes observed with GroEL hinge variants and is best supported by the normal mode analysis.

IMPORTANCE
Conformational changes and allosteric transitions are hallmarks of the chaperonin mechanism. We have exploited the inability of
M. tuberculosis
GroEL2 to functionally complement a strain of
E. coli
in which
groEL
expression is repressed to address the importance of hinges. The significance of conservation at the hinge regions stands out as a prominent feature of the GroEL mechanism in binding to GroES and substrate polypeptides. The hinge residues play a significant role in the chaperonin activity
in vivo
and
in vitro
.
Management of ulcerative colitis
Authors: Fell John M , Muhammed Rafeeq , Spray Chris , Crook Kay , Russell Richard K ,   BSPGHAN IBD working group
Published: November 2015

Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects.
Clustering of pain and its associations with health in people aged 50 years and older: cross-sectional results from the North Staffordshire Osteoarthritis Project
Authors: Lacey R J , Strauss V Y , Rathod T , Belcher J , Croft P R , Natvig B , Wilkie R , McBeth J
Published: November 2015

Objective

Most pain in patients aged ≥50 years affects multiple sites and yet the predominant mode of presentation is single-site syndromes. The aim of this study was to investigate if pain sites form clusters in this population and if any such clusters are associated with health factors other than pain.

Setting

Six general practices in North Staffordshire, UK.

Design

Cross-sectional, postal questionnaire, study.

Participants

Community-dwelling adults aged ≥50 years registered at the general practices.

Main outcomes measures

Number of pain sites was measured by asking participants to shade sites of pain lasting ≥1 day in the past 4 weeks on a blank body manikin. Health factors measured included anxiety and depression (Hospital and Anxiety Depression Scale), cognitive complaint (Sickness Impact Profile) and sleep. Pain site clustering was investigated using latent class analysis. Association of clusters with health factors, adjusted for age, sex, body mass index and morbidities, was analysed using multinomial regression models.

Results

13 986 participants (adjusted response 70.6%) completed a questionnaire, of whom 12 408 provided complete pain data. Four clusters of participants were identified: (1) low number of pain sites (36.6%), (2) medium number of sites with no back pain (31.5%), (3) medium number of sites with back pain (17.9%) and (4) high number of sites (14.1%). Compared to Cluster 1, other clusters were associated with poor health. The strongest associations (relative risk ratios, 95% CI) were with Cluster 4: depression (per unit change in score) 1.11 (1.08 to 1.14); cognitive complaint 2.60 (2.09 to 3.24); non-restorative sleep 4.60 (3.50 to 6.05).

Conclusions

These results indicate that in a general population aged ≥50 years, pain forms four clusters shaped by two dimensions—number of pain sites (low, medium, high) and, within the medium cluster, the absence or presence of back pain. The usefulness of primary care treatment approaches based on this simple classification should be investigated.
Funding allocation to surgery in low and middle-income countries: a retrospective analysis of contributions from the USA
Authors: Gutnik Lily , Dieleman Joseph , Dare Anna J , Ramos Margarita S , Riviello Robert , Meara John G , Yamey Gavin , Shrime Mark G
Published: November 2015

Objective

The funds available for global surgical delivery, capacity building and research are unknown and presumed to be low. Meanwhile, conditions amenable to surgery are estimated to account for nearly 30% of the global burden of disease. We describe funds given to these efforts from the USA, the world's largest donor nation.

Design

Retrospective database review. US Agency for International Development (USAID), National Institute of Health (NIH), Foundation Center and registered US charitable organisations were searched for financial data on any organisation giving exclusively to surgical care in low and middle income countries (LMICs). For USAID, NIH and Foundation Center all available data for all years were included. The five recent years of financial data per charitable organisation were included. All nominal dollars were adjusted for inflation by converting to 2014 US dollars.

Setting

USA.

Participants

USAID, NIH, Foundation Center, Charitable Organisations.

Primary and secondary outcome measures

Cumulative funds appropriated to global surgery.

Results

22 NIH funded projects (totalling $31.3 million) were identified, primarily related to injury and trauma. Six relevant USAID projects were identified—all obstetric fistula care totalling $438 million. A total of $105 million was given to universities and charitable organisations by US foundations for 12 different surgical specialties. 95 US charitable organisations representing 14 specialties totalled revenue of $2.67 billion and expenditure of $2.5 billion.

Conclusions and relevance

Current funding flows to surgical care in LMICs are poorly understood. US funding predominantly comes from private charitable organisations, is often narrowly focused and does not always reflect local needs or support capacity building. Improving surgical care, and embedding it within national health systems in LMICs, will likely require greater financial investment. Tracking funds targeting surgery helps to quantify and clarify current investments and funding gaps, ensures resources materialise from promises and promotes transparency within global health financing.
Protocol for the design of an instrument to measure preadolescent children's self-report of covert aggression and bullying
Authors: Nelson Helen Jean , Kendall Garth Edward , Burns Sharyn , Schonert-Reichl Kimberly
Published: November 2015

Introduction

Covert bullying in schools is associated with a range of academic, social, emotional and physical health problems. Much research has focused on bullying, but there remains a gap in understanding about covert aggression and how to most accurately and reliably measure children's own reports of this behaviour. This paper reviews relevant literature and outlines a research project that aims to develop a self-report instrument that effectively measures covert aggression and bullying. It is anticipated that this research will result in a standardised instrument that is suitable for exploring preadolescent children's experiences of covert aggressive behaviour. The data collected by the instrument will enhance health and education professionals understanding of covert bullying behaviours and will inform the design and evaluation of interventions.

Methods and analysis

Relational developmental systems theory will guide the design of an online self-report instrument. The first phase of the project will include a critical review of the research literature, focus groups with children aged 8–12 years (grades 4–6) in Perth, Western Australia, and expert review. The instrument will be explored for content and face validity prior to the assessment of convergent and discriminant validity, internal consistency and test-retest reliability.

Ethics and dissemination

The study has been approved by the Curtin University of Human Research Ethics Committee (RDHS-38-15) and by the Executive Principal of the participating school.
Comparison of transient associations of air pollution and AMI hospitalisation in two cities of Alberta, Canada, using a case-crossover design
Authors: Wang Xiaoming , Kindzierski Warren , Kaul Padma
Published: November 2015

Objective

To investigate reproducibility of outcomes for short-term associations between ambient air pollutants and acute myocardial infarction (AMI) hospitalisation in 2 urban populations.

Design

Using a time-stratified design, we conducted independent case-crossover studies of AMI hospitalisation events over the period 1999–2010 in the geographically close and demographically similar cities of Calgary and Edmonton, Alberta, Canada. Patients with his/her first AMI hospitalisation event were linked with air pollution data from the National Ambient Pollution Surveillance database and meteorological data from the National Climatic Data Center database. Patients were further divided into subgroups to examine adjusted pollution effects. Effects of pollution levels with 0–3-day lag were modelled using conditional logistic regression and adjusted for daily average ambient temperature, dew point temperature and wind speed.

Setting

Population-based studies in Calgary/Edmonton.

Participants

12 066/10 562 first-time AMI hospitalisations in Calgary/Edmonton.

Main outcome measures

Association (adjusted OR) between daily ambient air pollution levels and hospitalisation for AMI.

Results

Among 600 potential air pollution effect variables investigated for the Calgary (Edmonton) population, only 1.17% (0.67%) was statistically significant by using the traditional 5% criterion. None of the effect variables were reproduced in the 2 cities, despite their geographic closeness (within 300 km of each other), and demographic and air pollution similarities.

Conclusions

Comparison of independent investigations of the effect of air pollution on risk of AMI hospitalisation in Calgary and Edmonton, Alberta, indicated that none of the air pollutants investigated—CO, NO, NO2, O3and particulate matter (PM2.5)—showed consistent positive associations with increased risk of AMI hospitalisation.
Oxfordshire Women and Their Children's Health (OxWATCH): protocol for a prospective cohort feasibility study
Authors: Harrison S , Petrovic G , Chevassut A , Brook L , Higgins N , Kenworthy Y , Selwood M , Snelgar T , Arnold L , Boardman H , Heneghan C , Leeson P , Redman C , Granne I
Published: November 2015

Introduction

Some specific pregnancy disorders are known to be associated with increased incidence of long-term maternal ill health (eg, gestational diabetes with late onset type 2 diabetes; pre-eclampsia with arterial disease). To what degree these later health conditions are a consequence of the woman's constitution prior to pregnancy rather than pregnancy itself triggering changes in a woman's health is unknown. Additionally, there is little prospective evidence for the impact of pre-pregnancy risk factors on the outcome of pregnancy. To understand the importance of pre-pregnancy health requires the recruitment of women into a long-term cohort study before their first successful pregnancy. The aim of this feasibility study is to test recruitment procedures and acceptability of participation to inform the planning of a future large-scale cohort study.

Methods

The prospective cohort feasibility study will recruit nulliparous women aged 18–40 years. Women will be asked to complete a questionnaire to assess the acceptability of our recruitment and data collection procedures. Baseline biophysical, genetic, socioeconomic, behavioural and psychological assessments will be conducted and samples of blood, urine, saliva and DNA will be collected. Recruitment feasibility and retention rates will be assessed. Women who become pregnant will be recalled for pregnancy and postpregnancy assessments.

Ethics and dissemination

The study protocol was approved by South Central Portsmouth REC (Ref: 12/SC/0492). The findings from the study will be disseminated through peer reviewed journals, national and international conference presentations and public events.

Trial registration number

http://www.clinicaltrials.gov;NCT02419898.
Validity assessment of self-reported medication use by comparing to pharmacy insurance claims
Authors: Fujita Misuzu , Sato Yasunori , Nagashima Kengo , Takahashi Sho , Hata Akira
Published: November 2015

Objectives

In Japan, an annual health check-up and health promotion guidance programme was established in 2008 in accordance with the Act on Assurance of Medical Care for the Elderly. A self-reported questionnaire on medication use is a required item in this programme and has been used widely, but its validity has not been assessed. The aim of this study was to evaluate the validity of this questionnaire by comparing self-reported usage to pharmacy insurance claims.

Setting

This is a population-based validation study. Self-reported medication use for hypertension, diabetes and dyslipidaemia is the evaluated measurement. Data on pharmacy insurance claims are used as a reference standard.

Participants

Participants were 54 712 beneficiaries of the National Health Insurance of Chiba City.

Primary and secondary outcome measures

Sensitivity, specificity and κ statistics of the self-reported medication-use questionnaire for predicting actual prescriptions during 1 month (that of the check-up) and 3 months (that of the check-up and the previous 2 months) were calculated.

Results

Sensitivity and specificity scores of questionnaire data for predicting insurance claims covering 3 months were, respectively, 92.4% (95% CI 91.9 to 92.8) and 86.4% (95% CI 86.0 to 86.7) for hypertension, 82.6% (95% CI 81.1 to 84.0) and 98.5% (95% CI 98.4 to 98.6) for diabetes, and 86.2% (95% CI 85.5 to 86.8) and 91.0% (95% CI 90.8 to 91.3) for dyslipidaemia. Corresponding κ statistics were 70.9% (95% CI 70.1 to 71.7), 77.1% (95% CI 76.2 to 77.9) and 69.8% (95% CI 68.9 to 70.6). The specificity was significantly higher for questionnaire data covering 3 months compared with data covering 1 month for all 3 conditions.

Conclusions

Self-reported questionnaire data on medication use had sufficiently high validity for further analyses. Item responses showed close agreement with actual prescriptions, particularly those covering 3 months.
A qualitative analysis of New Zealand retailers’ responses to standardised packaging legislation and tobacco industry opposition
Authors: Guthrie John , Hoek Janet , Darroch Ella , Wood Zoë
Published: November 2015

Objectives

Many of the approximately 8000 New Zealand retailers selling tobacco are small stores that tobacco companies have represented as victims of policy measures designed to reduce smoking. Despite this depiction, many retailers experience considerable ambivalence in selling tobacco, a product they know harms their customers. We explored how retailers perceived the proposed introduction of standardised (or ‘plain’) packaging and their assessment of arguments made by tobacco companies in submissions on proposed standardised packaging legislation.

Participants

Using qualitative in-depth interviews, we recruited and interviewed 23 retailers of dairies (small convenience stores), small supermarkets, and service stations.

Analyses

Data were analysed using a protocol-driven approach; this stance enabled direct analysis of tobacco companies’ arguments, particularly those purporting to represent retailers’ concerns.

Results

Retailers were concerned about the financial implications of standardised packaging and the effects it may have on their ability to provide rapid and efficient customer service. However, few thought standardised packaging would foster illicit trade or spawn further regulation; most placed public health goals ahead of tobacco companies’ ‘rights’, and many supported government intervention to protect population health.

Conclusions

Retailers held ambivalent views on standardised packaging; while they were concerned about short-term effects on their business, they recognised the harm smoking causes. Policymakers and health researchers could collaborate more effectively with retailers by assisting them to create financially viable roles more compatible with public health objectives.
The effects of a free-weight-based resistance training intervention on pain, squat biomechanics and MRI-defined lumbar fat infiltration and functional cross-sectional area in those with chronic low back
Authors: Welch Neil , Moran Kieran , Antony Joseph , Richter Chris , Marshall Brendan , Coyle Joe , Falvey Eanna , Franklyn-Miller Andrew
Published: November 2015

Background

Low back pain is one of the most prevalent musculoskeletal conditions in the world. Many exercise treatment options exist but few interventions have utilised free-weight resistance training. To investigate the effects of a free-weight-based resistance training intervention on pain and lumbar fat infiltration in those with chronic low back pain.

Methods

Thirty participants entered the study, 11 females (age=39.6±12.4 years, height=164 cm±5.3 cm, body mass=70.9±8.2 kg,) and 19 males (age=39.7±9.7 years, height=179±5.9 cm, body mass=86.6±15.9 kg). A 16-week, progressive, free-weight-based resistance training intervention was used. Participants completed three training sessions per week. Participants completed a Visual Analogue Pain Scale, Oswestry Disability Index and Euro-Qol V2 quality of life measure at baseline and every 4 weeks throughout the study. Three-dimensional kinematic and kinetic measures were used for biomechanical analysis of a bodyweight squat movement. Maximum strength was measured using an isometric mid-thigh pull, and lumbar paraspinal endurance was measured using a Biering-Sorensen test. Lumbar paraspinal fat infiltration was measured preintervention and postintervention using MRIs.

Results

Postintervention pain, disability and quality of life were all significantly improved. In addition, there was a significant reduction in fat infiltration at the L3L4 and L4L5 levels and increase in lumbar extension time to exhaustion of 18%.

Conclusions

A free-weight-based resistance training intervention can be successfully utilised to improve pain, disability and quality of life in those with low back pain.
Diamond: immunohistochemistry versus sequencing inEGFRanalysis of lung adenocarcinomas
Authors: Ragazzi Moira , Tamagnini Ione , Bisagni Alessandra , Cavazza Alberto , Pagano Maria , Baldi Licia , Boni Corrado , Cantile Flavia , Barbieri Fausto , Nicoli Davide , Sartori Giuliana , de Biase Dario , Gardini Giorgio , Rossi Giulio
Published: November 2015

Aims

Identification of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas is the single most important predictor of clinical response and outcome using EGFR tyrosine kinase inhibitors (TKIs).EGFRE746-A750del and L858R mutations are the most common gene alterations, also predicting the best clinical response to TKIs. We evaluated the accuracy of EGFR mutation-specific antibodies in a large cohort of lung adenocarcinomas, with different molecular settings and types of tissue samples.

Methods

300 lung adenocarcinomas diagnosed on cytology (48 cell blocks), biopsy (157 cases) and surgical resections (95 cases) were selected. All cases were investigated for EGFR by sequencing and two mutation-specific antibodies (clone 6B6 for E746-A750del; clone 43B2 for L858R) were tested using an automated immunostainer. Discordant results were investigated by next-generation sequencing (NGS).

Results

Overall sensitivity and specificity of mutant-specific antibodies were 58.6% and 98.0%, respectively, and they increased up to 84% and 100% if only tumours harbouring E746-A750del were considered. In 13 discordant cases, NGS confirmed immunohistochemistry results in eight samples.

Conclusions

TheEGFRmutation-specific antibodies have a fair/good sensitivity and good/high specificity in identifying classic mutations, but they cannot replace molecular tests. The antibodies work equally well on biopsies and cell blocks, possibly permitting a rapid screening in cases with poor material.
Interpretation of the loading–wetting behaviour of compacted soils within the “MPK” framework. Part I: Static compaction
Authors: Islam Tanvirul , Kodikara Jayantha
Published: November 2015

Depending on the state paths, loading–wetting of compacted unsaturated soils can exhibit complex volumetric behaviour, such as swelling, collapse, collapse followed by swelling, swelling followed by collapse, and swelling pressure development. Microscopically, these behaviours arise from complex interactions among applied stresses, air–water pressure deficit or suction at the water menisci, moisture content or degree of saturation in the voids, and the nature of the micro- and macrosoil aggregates of compacted soils that depend on the level of suction. While significant advances have been made in modelling hydromechanical behaviour of compacted unsaturated soils taking these interactions into account, input parameter determination requires advanced testing equipment and the testing processes can be very time-consuming. In 2012, a relatively simple and practical framework within the void ratio – moisture ratio (water volume / solid volume) – net stress space (referred to as the MPK framework) has been proposed by Kodikara to explain–predict these state paths. A desirable feature of this framework is that it identifies a direct link between the well-known compaction curve and the compacted soil constitutive behaviour. This paper presents a comprehensive series of tests on statically compacted soils, the results of which are in close agreement with this framework. Two soil types, namely lightly reactive kaolin and more reactive clay (referred to as Merri Creek soil), were used in the testing. The soils were prepared with different moisture contents from the dry state and statically compacted at constant water content to obtain void ratio – moisture ratio – net stress constitutive surfaces, as well as soil specimens for state path tests. The state path test results of yielding under loading, collapse under wetting, swelling pressure development, and change in yield pressure due to wetting are explained within this framework. In addition, some published data on a silty soil mixture were also analysed, highlighting that the framework is valid, regardless of the degree of reactivity of the soil. Suction was not measured in the authors’ experiments, as it was not required to explain the above state paths according to this framework. However, it is recognised that suction is the conjugate state variable to the moisture content. Therefore, in future experiments, suction will be measured and its role will be fully explained within the framework, adding more generality.
Multiple developmental pathways for range-margin Pinus banksiana forests
Authors: Gill Kyle G. , D’Amato Anthony W. , Fraver Shawn
Published: November 2015

Empirical knowledge of forest structure and development in early successional and range-margin populations is often lacking, limiting our ability to effectively model and manage these forests. Such is the case for jack pine (Pinus banksiana Lamb.) in central Minnesota, USA, where it reaches its southwestern range limit. Our objective was to quantify this population’s historical range of variability of structural conditions and developmental pathways. We collected structural, spatial, and dendrochronological data on 0.25 ha plots from 10 jack pine dominated sites that initiated and developed outside of active management. Our results revealed a broad range of structural characteristics and developmental pathways, including rapid and protracted recruitment windows (5–50 years), with subsequent even- and uneven-aged structures, and random and clumped stem spatial arrangements. As such, these mature, early successional forests often displayed a degree of complexity more typically associated with old-growth forests. Our findings suggest that this population, like other southern range-margin populations with mostly nonserotinous cones, historically followed a variety of stand development pathways and did not solely follow the rapid establishment, even-aged pathway often attributed to this forest type. We suggest that even- and uneven-aged silvicultural systems should be used to reflect this historical range of developmental pathways and to increase resilience and adaptability.
Draft genome sequence of the silver pomfret fish, Pampus argenteus
Authors: AlMomin Sabah , Kumar Vinod , Al-Amad Sami , Al-Hussaini Mohsen , Dashti Talal , Al-Enezi Khaznah , Akbar Abrar
Published: November 2015

Silver pomfret, Pampus argenteus, is a fish species from coastal waters. Despite its high commercial value, this edible fish has not been sequenced. Hence, its genetic and genomic studies have been limited. We report the first draft genome sequence of the silver pomfret obtained using a Next Generation Sequencing (NGS) technology. We assembled 38.7 Gb of nucleotides into scaffolds of 350 Mb with N50 of about 1.5 kb, using high quality paired end reads. These scaffolds represent 63.7% of the estimated silver pomfret genome length. The newly sequenced and assembled genome has 11.06% repetitive DNA regions, and this percentage is comparable to that of the tilapia genome. The genome analysis predicted 16 322 genes. About 91% of these genes showed homology with known proteins. Many gene clusters were annotated to protein and fatty-acid metabolism pathways that may be important in the context of the meat texture and immune system developmental processes. The reference genome can pave the way for the identification of many other genomic features that could improve breeding and population-management strategies, and it can also help characterize the genetic diversity of P. argenteus.
Statement of principles on the return of research results and incidental findings in paediatric research: a multi-site consultative process
Authors: Sénécal Karine , Rahimzadeh Vasiliki , Knoppers Bartha M. , Fernandez Conrad V. , Avard Denise , Sinnett Daniel
Published: November 2015

This paper proposes a set of recommendations for the return of research results and incidental findings in paediatrics. The Network of Applied Genetic Medicine of Quebec spearheaded the initiative to develop the Statement of Principles on the Return of Research Results and Incidental Findings, which was the result of a consultation process with clinical and research experts in the field. To formulate the Statement of Principles, the authors (i) reviewed empirical and grey literature on the return of research results and incidental findings in Europe and Canada, (ii) conducted a qualitative study of stakeholder groups, (iii) developed, and (iv) validated the recommendations through consultations with the stakeholder groups. The Statement of Principles provides a useful disclosure tool for deciding when, and under what circumstances to return research results and incidental findings. It addresses the issue of return of results in genetic research generally, and has also specific principles for various research contexts, including paediatric research. It delineates ethical issues unique to paediatric research, and provides a framework to guide research ethics committees as well as the research community in addressing these issues.
Conformal cylindrically symmetric spacetimes in modified gravity
Authors: Türkog̃lu Murat Metehan , Dog̃ru Melis Ulu
Published: November 2015

We investigate cylindrically symmetric spacetimes in the context of [Formula: see text] gravity. We firstly attain conformal symmetry of the cylindrically symmetric spacetime. We obtain solutions to use features of the conformal symmetry, field equations and their solutions for cylindrically symmetric spacetime filled with various cosmic matters such as vacuum state, perfect fluid, anisotropic fluid, massive scalar field and their combinations. With the vacuum state solutions, we show that source of the spacetime curvature is considered as Casimir effect. Casimir force for given spacetime is found using Wald’s axiomatic analysis. We expose that the Casimir force for Boulware, Hartle–Hawking and Unruh vacuum states could have attractive, repulsive and ineffective features. In the perfect fluid state, we show that matter form of the perfect fluid in given spacetime must only be dark energy. Also, we offer that potential of massive and massless scalar field are developed as an exact solution from the modified field equations. All solutions of field equations for vacuum case, perfect fluid and scalar field give a special [Formula: see text] function convenient to [Formula: see text]-CDM model. In addition to these solutions, we introduce conformal cylindrical symmetric solutions in the cases of different [Formula: see text] models. Finally, geometrical and physical results of the solutions are discussed.
Cosmology from quantum potential in a system of oscillating branes
Authors: Sepehri Alireza
Published: November 2015

Recently, some authors proposed a new mechanism which gets rid of the Big Bang singularity and shows that the age of the universe is infinite. In this paper, we will confirm their results and predict that the universe may expand and contract many N fundamental strings decay to N M0–anti-M0-branes. Then, M0-branes join each other and build a M8-anti-M8 system. This system is unstable, broken and two anti-M4-branes, a compactified M4-brane, a M3-brane in addition to one M0-brane are produced. The M3-brane wraps around the compactified M4-brane and both of them oscillate between two anti-M4-branes. Our universe is located on the M3-brane and interacts with other branes by exchanging the M0-brane and some scalars in transverse directions. By wrapping of M3-brane, the contraction epoch of universe starts and some higher order of derivatives of scalar fields in the relevant action of branes are produced which are responsible for generating the generalized uncertainty principle (GUP). By oscillating the compactified M4-M3-brane and approaching one of anti-M4-branes, one end of M3-brane glues to the anti-M4-brane and other end remains sticking and wrapping around M4-brane. Then, by getting away of the M4-M3 system, M4 rolls, wrapped M3 opens and expansion epoch of universe begins. By closing the M4 to anti-M4, the mass of some scalars become negative and they make a transition to tachyonic phase. To remove these states, M4 rebounds, rolls and M3 wraps around it again. At this stage, expansion branch ends and universe enters a contraction epoch again. This process is repeated many times and universe expands and contracts due to oscillation of branes. We obtain the scale factor of universe in this system and find that its values only at t [Formula: see text] shrinks to zero. Thus, in our method, the Big Bang is replaced by the fundamental string and the age of universe is predicted to be infinite. Also, when tachyonic states disappear at the beginning of expansion branch, some extra energy is produced and leads to an increase in the velocity of opening of M3. In these conditions, our universe, which is located on this brane, expands very fast and experiences an inflation epoch. Finally, by reducing the fields in 11-dimensional M-theory to the fields in four-dimensional universe, we show that our theory matches with quantum field theory prescriptions.
GPUSPH: a Smoothed Particle Hydrodynamics model for the thermal and rheological evolution of lava flows
Authors: Bilotta Giuseppe , Hérault Alexis , Cappello Annalisa , Ganci Gaetana , Del Negro Ciro
Published: November 2015

GPUSPH is a fully three-dimensional model for the simulation of the thermal and rheological evolution of lava flows that relies on the Smoothed Particle Hydrodynamics (SPH) numerical method. Thanks to the Lagrangian, meshless nature of SPH, the model incorporates a more complete physical description of the emplacement process and rheology of lava that considers the free surface, the irregular boundaries represented by the topography, the solidification fronts and the non-Newtonian rheology with temperature-dependent parameters. GPUSPH follows the very general Herschel–Bulkley rheological model, which encompasses Newtonian, power-law and Bingham flow behaviours, with both constant and temperature-dependent parameters, and can thus be used to explore in detail the impact of rheology on the behaviour of lava flows and on their emplacement. To illustrate this possibility, we present some preliminary applications of the model for studying the rheology of lava flows with different constitutive relationships and thermal regimes using the real topography of the Mt Etna volcano.
Design of a Novel Nonlinear Observer to Estimate Sideslip Angle and Tire Forces for Distributed Electric Vehicle
Authors: Song Chuanxue , Xiao Feng , Song Shixin , Li Shaokun , Li Jianhua
Published: November 2015

For four-wheel independently driven (4WD) distributed electric vehicle (DEV), vehicle dynamics control systems such as direct yaw moment control (DYC) can be easily achieved. Accurate estimation of vehicle state variables and uncertain parameters can improve the robustness of vehicle dynamics control system. Various sensors are generally equipped to the acquisition of the vehicle dynamics. For both technical and economic reasons, some fundamental vehicle parameters, such as the sideslip angle and tire-road forces, can hardly be obtained through sensors directly. Therefore, this paper presented a state observer to estimate these variables based on Unscented Kalman Filter (UKF). To improve the accuracy of UKF, measurement noise covariance is also self-adaptive regulated. In addition, a nonlinear dynamics tire model is utilized to improve the accuracy of tire lateral force estimation. The simulation and experiment results show that the proposed observer can provide the precision values of the vehicle state.