bluuebunny/crossref_metadata_2025 huggingface dataset:
The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling
Authors: Best Sonja M.
Published: November 2016

The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection. The most direct and potent viral inhibitor of this pathway is the nonstructural protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses are often quite different, sometimes despite close evolutionary relationships between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also surprising given that the evolution of NS5 is restrained by the requirement to maintain function of two enzymatic activities critical for virus replication, the methyltransferase and RNA-dependent RNA polymerase. This review discusses the different strategies used by flavivirus NS5 to evade the antiviral effects of IFN-I and how this information can be used to better model disease and develop antiviral countermeasures.
Identification of New World Quails Susceptible to Infection with Avian Leukosis Virus Subgroup J
Authors: Plachý Jiří , Reinišová Markéta , Kučerová Dana , Šenigl Filip , Stepanets Volodymyr , Hron Tomáš , Trejbalová Kateřina , Elleder Daniel , Hejnar Jiří
Published: November 2016

The J subgroup of avian leukosis virus (ALV-J) infects domestic chickens, jungle fowl, and turkeys. This virus enters the host cell through a receptor encoded by the
tvj
locus and identified as Na
+
/H
+
exchanger 1. The resistance to avian leukosis virus subgroup J in a great majority of galliform species has been explained by deletions or substitutions of the critical tryptophan 38 in the first extracellular loop of Na
+
/H
+
exchanger 1. Because there are concerns of transspecies virus transmission, we studied natural polymorphisms and susceptibility/resistance in wild galliforms and found the presence of tryptophan 38 in four species of New World quails. The embryo fibroblasts of New World quails are susceptible to infection with avian leukosis virus subgroup J, and the cloned Na
+
/H
+
exchanger 1 confers susceptibility on the otherwise resistant host. New World quails are also susceptible to new avian leukosis virus subgroup J variants but resistant to subgroups A and B and weakly susceptible to subgroups C and D of avian sarcoma/leukosis virus due to obvious defects of the respective receptors. Our results suggest that the avian leukosis virus subgroup J could be transmitted to New World quails and establish a natural reservoir of circulating virus with a potential for further evolution.

IMPORTANCE
Since its spread in broiler chickens in China and Southeast Asia in 2000, ALV-J remains a major enzootic challenge for the poultry industry. Although the virus diversifies rapidly in the poultry, its spillover and circulation in wild bird species has been prevented by the resistance of most species to ALV-J. It is, nevertheless, important to understand the evolution of the virus and its potential host range in wild birds. Because resistance to avian retroviruses is due particularly to receptor incompatibility, we studied Na
+
/H
+
exchanger 1, the receptor for ALV-J. In New World quails, we found a receptor compatible with virus entry, and we confirmed the susceptibilities of four New World quail species
in vitro
. We propose that a prospective molecular epidemiology study be conducted to identify species with the potential to become reservoirs for ALV-J.
Porcine Reproductive and Respiratory Syndrome Virus Antagonizes JAK/STAT3 Signaling via nsp5, Which Induces STAT3 Degradation
Authors: Yang Liping , Wang Rong , Ma Zexu , Xiao Yueqiang , Nan Yuchen , Wang Yu , Lin Shaoli , Zhang Yan-Jin
Published: November 2016

Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic signaling mediator of many cytokines, including interleukin-6 (IL-6) and IL-10. STAT3 is known to play critical roles in cell growth, proliferation, differentiation, immunity and inflammatory responses. The objective of this study was to determine the effect of porcine reproductive and respiratory syndrome virus (PRRSV) infection on the STAT3 signaling since PRRSV induces a weak protective immune response in host animals. We report here that PRRSV infection of MARC-145 cells and primary porcine pulmonary alveolar macrophages led to significant reduction of STAT3 protein level. Several strains of both PRRSV type 1 and type 2 led to a similar reduction of STAT3 protein level but had a minimal effect on its transcripts. The PRRSV-mediated STAT3 reduction was in a dose-dependent manner as the STAT3 level decreased, along with incremental amounts of PRRSV inocula. Further study showed that nonstructural protein 5 (nsp5) of PRRSV induced the STAT3 degradation by increasing its polyubiquitination level and shortening its half-life from 24 h to ∼3.5 h. The C-terminal domain of nsp5 was shown to be required for the STAT3 degradation. Moreover, the STAT3 signaling in the cells transfected with nsp5 plasmid was significantly inhibited. These results indicate that PRRSV antagonizes the STAT3 signaling by accelerating STAT3 degradation via the ubiquitin-proteasomal pathway. This study provides insight into the PRRSV interference with the JAK/STAT3 signaling, leading to perturbation of the host innate and adaptive immune responses.

IMPORTANCE
The typical features of immune responses in PRRSV-infected pigs are delayed onset and low levels of virus neutralizing antibodies, as well as weak cell-mediated immunity. Lymphocyte development and differentiation rely on cytokines, many of which signal through the JAK/STAT signaling pathway to exert their biological effects. Here, we discovered that PRRSV antagonizes the JAK/STAT3 signaling by inducing degradation of STAT3, a master transcription activator involved in multiple cellular processes and the host immune responses. The nsp5 protein of PRRSV is responsible for the accelerated STAT3 degradation. The PRRSV-mediated antagonizing STAT3 could lead to suppression of a broad spectrum of cytokines and growth factors to allow virus replication and spread in host animals. This may be one of the reasons for the PRRSV interference with the innate immunity and its poor elicitation of protective immunity. This finding provides insight into PRRSV pathogenesis and its interference with the host immune responses.
Escherichia coli Sequence Type 131
H
30 Is the Main Driver of Emerging Extended-Spectrum-β-Lactamase-Producing E. coli at a Tertiary Care Center
Authors: Johnson James R. , Johnston Brian , Thuras Paul , Launer Bryn , Sokurenko Evgeni V. , Miller Loren G.
Published: November 2016

The ever-rising prevalence of resistance to first-line antibiotics among clinical
Escherichia coli
isolates leads to worse clinical outcomes and higher health care costs, thereby creating a need to discover its basis so that effective interventions can be developed. We found that the
H
30 subset within
E. coli
sequence type 131 (ST131-
H
30) is currently, and has been since at least 2004, the main
E. coli
lineage contributing to key resistance phenotypes—including extended-spectrum-beta-lactamase (ESBL) production, fluoroquinolone resistance, multidrug resistance, and dual ESBL production-plus-fluoroquinolone resistance—at a United States tertiary care center with a rising prevalence of ESBL-producing
E. coli
isolates. This identifies ST131-
H
30 as a target for diagnostic tests and preventive measures designed to curb the emergence of multidrug-resistant
E. coli
isolates and/or to blunt its clinical impact.
A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome
Authors: Moriel Danilo G. , Tan Lendl , Goh Kelvin G. K. , Phan Minh-Duy , Ipe Deepak S. , Lo Alvin W. , Peters Kate M. , Ulett Glen C. , Beatson Scott A. , Schembri Mark A.
Published: November 2016

E. coli
is a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic
E. coli
strains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of the
E. coli
genome by examining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology approach in combination with proteomics to identify putative broadly protective vaccine antigens. One such antigen was identified that was highly immunogenic and induced protection in a mouse model of bacteremia. Overall, our study provides a genomic and proteomic framework for the selection of novel vaccine antigens that could mediate broad protection against pathogenic
E. coli
.
Bilateral ureteric obstruction during in vitro fertilisation therapy in a patient with complex surgically managed Crohn's disease
Authors: Khoo Christopher Charles , Ahluwalia Nikhil , Grace Jan , Sahai Arun
Published: November 2016

A 37-year-old woman receiving in vitro fertilisation (IVF) treatment presented with lethargy, fevers and anuria. Her background included complex surgically managed Crohn's disease and mild right-sided hydronephrosis (with no evidence of obstruction on MAG3 renogram). On examination, she had a distended abdomen with generalised tenderness. Blood tests revealed an acute kidney injury and confirmed sepsis. She was found to have bilateral ureteric obstruction with worsening of the right-sided hydronephrosis and new-onset left-sided hydronephrosis secondary to bilateral ovarian masses, diagnosed as mild ovarian hyperstimulation syndrome (OHSS). She was initially managed with fluid resuscitation, bilateral nephrostomies, antibiotics and supportive management of mild OHSS. She made a good recovery and was discharged after placement of antegrade stents and removal of nephrostomies. On follow-up, following resolution of ovarian hyperstimulation, she has been diagnosed with a right-sided distal ureteric stricture and is awaiting reconstruction. Her left ureteric stent has been removed.
Risk factors for developing colorectal cancer in Japanese patients with ulcerative colitis: a retrospective observational study—CAPITAL (Cohort and Practice for IBD total management in Kyoto-Shiga Links) study I
Authors: Yoshino Takuya , Nakase Hiroshi , Takagi Tomohisa , Bamba Shigeki , Okuyama Yusuke , Kawamura Takuji , Oki Teruki , Obata Hirozumi , Kawanami Chiharu , Katsushima Shinji , Kusaka Toshihiro , Tsujikawa Tomoyuki , Naito Yuji , Andoh Akira , Kogawa Takafumi
Published: November 2016

Background and Aims

Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient's risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC.

Methods

Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003–2013. We performed a retrospective cohort study of 2137 patients with UC.

Results

In total, 60 lesions of CRC were detected in 43 (2.0%) of 2137 patients. 30 of the 43 patients were male. The median age was 53 years. The median duration of disease was 13 years, and 67.4% of these patients had a disease duration >10 years. Of the 43 patients, 34 (79.1%) had extensive colitis. Primary sclerosing cholangitis was detected in 2 patients (4.7%). The median corticosteroids (CS) dose was 6.4 g, and 4 patients were treated with a total of more than 10 g of CS. 18 of these patients underwent more than 1 year CS treatment. Of all 60 CRC lesions, 43 (71.7%) were located in the distal colon and 35 (58.3%) were of the superficial type. Moreover, the stage of CRC was stage 0 or I in 55.8% of the 43 patients with CRC. Multivariate analysis suggested that extensive colitis could be a risk factor for the development of advanced CRC in patients with UC.

Conclusions

Our findings indicated that male, extensive colitis, long-term duration of UC and family history of CRC, but not concomitant primary sclerosing cholangitis, are important factors for predicting CRC in Japanese patients with UC. Moreover, long-standing extensive colitis might contribute to the progression of CRC. Further studies are required to establish CRC surveillance in Japanese patients with UC.
Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry
Authors: Zhang Xinji , Zhang Yuan , Ye Xiaofei , Guo Xiaojing , Zhang Tianyi , He Jia
Published: November 2016

Objective

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data.

Methods

A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation.

Results

A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor.

Conclusions

Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task.
Effects of culture-sensitive adaptation of patient information material on usefulness in migrants: a multicentre, blinded randomised controlled trial
Authors: Hölzel Lars P , Ries Zivile , Kriston Levente , Dirmaier Jörg , Zill Jördis M , Rummel-Kluge Christine , Niebling Wilhelm , Bermejo Isaac , Härter Martin
Published: November 2016

Objectives

To evaluate the usefulness of culture-sensitive patient information material compared with standard translated material.

Design

Multicentre, double-blind randomised controlled trial.

Setting

37 primary care practices.

Participants

435 adult primary care patients with a migration background with unipolar depressive disorder or non-specific chronic low back pain were randomised. Patients who were unable to read in the language of their respective migration background were excluded. Sufficient data were obtained from 203 women and 106 men. The largest group was of Russian origin (202 patients), followed by those of Turkish (52), Polish (30) and Italian (25) origin.

Interventions

Intervention group: provision of culture-sensitive adapted material. Control group: provision of standard translated material.

Main outcome measures

Primary outcome: patient-rated usefulness (USE) assessed immediately after patients received the material. Secondary outcomes: patient-rated usefulness after 8 weeks and 6 months, symptoms of depression (PHQ-9), back pain (Back Pain Core Set) and quality of life (WHO-5) assessed at all time points.

Results

Usefulness was found to be significantly higher (t=1.708, one-sided p=0.04) in the intervention group (USE-score=65.08, SE=1.43), compared with the control group (61.43, SE=1.63), immediately after patients received the material, in the intention-to-treat analysis, with a mean difference of 3.65 (one-sided 95% lower confidence limit=0.13). No significant differences were found for usefulness at follow-up (p=0.16, p=0.71). No significant effect was found for symptom severity in depression (p=0.95, p=0.66, p=0.58), back pain (p=0.40, p=0.45, p=0.32) or quality of life (p=0.76, p=0.86, p=0.21), either immediately after receiving the material, or at follow-up (8 weeks; 6 months). Patients with a lower level of dominant society immersion benefited substantially and significantly more from the intervention than patients with a high level of immersion (p=0.005).

Conclusion

Cultural adaptation of patient information material provides benefits over high quality translations. Clinicians are encouraged to use culture-sensitive material in their consultations, particularly with low-acculturated patients.

Trial registration number

German Register for Clinical Trials: DRKS00004241, Universal Trial Number: U1111-1135-8043, Results.
Clinical factors associated with initiation of and persistence with ADP receptor-inhibiting oral antiplatelet treatment after acute coronary syndrome: a nationwide cohort study from Finland
Authors: Prami Tuire , Khanfir Houssem , Deleskog Anna , Hasvold Pål , Kytö Ville , Reissell Eeva , Airaksinen Juhani
Published: November 2016

Objectives

To study patient selection for and persistence with ADP receptor-inhibiting oral antiplatelet (OAP) treatment after acute coronary syndrome (ACS).

Design

Observational, retrospective, cohort study linking real-life patient-level register data.

Setting

Nationwide drug usage study using data of patients with ACS discharged from hospitals in Finland.

Participants

The study population consisted of 54 416 patients (aged ≥18 years) following hospital admission for unstable angina pectoris or myocardial infarction during 2009–2013. Patients were classified as either OAP or non-OAP users based on drug purchases within 7 days of discharge.

Outcome measures

Initiation of and a 12-month persistence with OAP medication.

Results

In total, 49% of patients with ACS received OAP treatment after hospital discharge. Women represented 40% of the population, but only 32% of them became OAP users (adjusted OR for initiation compared with men 0.8; p<0.001). Patients not treated with percutaneous coronary intervention (PCI), elderly and patients with dementia/Alzheimer's disease, atrial fibrillation or warfarin treatment were less likely to be treated with OAP. If initiated, they were less likely to complete the recommended 12 months’ medication (adjusted risk increment >38% and p<0.001 for all). The OAP users showed good compliance with immediate initiation (92% within 1 day of discharge) and high mean medication possession rate (99%). Among OAP users, the usage of other secondary prevention drugs after ACS was more common than in non-OAP-treated patients (difference >20 percentage points for each).

Conclusions

Only half of the patients with ACS received guideline-recommended ADP receptor-inhibiting OAP treatment after hospital discharge, suggesting suboptimal treatment practices. Non-PCI-treated patients and patients with increased age, unstable angina, dementia or atrial fibrillation appear to have the highest risk of deficient treatment with OAPs. OAP users, however, showed good compliance during drug usage.
Life-course socioeconomic status and breast and cervical cancer screening: analysis of the WHO's Study on Global Ageing and Adult Health (SAGE)
Authors: Akinyemiju Tomi , Ogunsina Kemi , Sakhuja Swati , Ogbhodo Valentine , Braithwaite Dejana
Published: November 2016

Objectives

Socioeconomic differences in screening have been well documented in upper-income countries; however, few studies have examined socioeconomic status (SES) over the life-course in relation to cancer screening in lower-income and middle-income countries. Here, we examine individual, parental and life-course SES differences in breast and cervical cancer screening among women in India, China, Mexico, Russia and South Africa.

Setting

Data from the WHO's Study on Global Ageing and Adult Health (SAGE) 2007–2008 data were used for survey-weighted multivariable regression analysis. We examined the association between individual, parental and life-course SES in relation to breast and cervical cancer screening using education-based and employment-based measures of SES.

Participants

22 283 women aged 18–65 years, recruited from China, India, Mexico, Russia and South Africa.

Results

Having a college degree (OR 4.18; 95% CI 2.36 to 7.40) increased the odds of breast cancer screening compared with no formal education. Women with higher parental SES were almost 10 times more likely to receive breast cancer screening (OR 9.84; 95% CI 1.75 to 55.5) compared with women with low parental SES. Stable higher life-course (OR 3.07; 95% CI 1.96 to 4.79) increased breast cancer screening by threefold and increased cervical cancer screening by more than fourfold (OR 4.35; 95% CI 2.94 to 6.45); however, declining life-course SES was associated with reduced breast cancer screening (OR 0.26; 95% CI 0.08 to 0.79) compared to low life-course SES.

Conclusions

Higher individual, parental and life-course SES was positively associated with breast and cervical cancer screening, although education-based SES measures were stronger predictors of screening compared with employment-based measures. Improving knowledge of the benefits of cancer screening and integrating cancer screening into routine healthcare practice for low SES women are actionable strategies that may significantly improve screening rates in low-income and middle-income countries.
Co-occurrence and clustering of health conditions at age 11: cross-sectional findings from the Millennium Cohort Study
Authors: Hesketh Kathryn R , Fagg James , Muniz-Terrera Graciela , Bedford Helen , Law Catherine , Hope Steven
Published: November 2016

Objectives

To identify patterns of co-occurrence and clustering of 6 common adverse health conditions in 11-year-old children and explore differences by sociodemographic factors.

Design

Nationally representative prospective cohort study.

Setting

Children born in the UK between 2000 and 2002.

Participants

11 399 11-year-old singleton children for whom data on all 6 health conditions and sociodemographic information were available (complete cases).

Main outcome measures

Prevalence, co-occurrence and clustering of 6 common health conditions: wheeze; eczema; long-standing illness (excluding wheeze and eczema); injury; socioemotional difficulties (measured using Strengths and Difficulties Questionnaire) and unfavourable weight (thin/overweight/obese vs normal).

Results

42.4% of children had 2 or more adverse health conditions (co-occurrence). Co-occurrence was more common in boys and children from lower income households. Latent class analysis identified 6 classes: ‘normative’ (57.4%): ‘atopic burdened’ (14.0%); ‘socioemotional burdened’ (11.0%); ‘unfavourable weight/injury’ (7.7%); ‘eczema/injury’ (6.0%) and ‘eczema/unfavourable weight’ (3.9%). As with co-occurrence, class membership differed by sociodemographic factors: boys, children of mothers with lower educational attainment and children from lower income households were more likely to be in the ‘socioemotional burdened’ class. Children of mothers with higher educational attainment were more likely to be in the ‘normative’ and ‘eczema/unfavourable weight’ classes.

Conclusions

Co-occurrence of adverse health conditions at age 11 is common and is associated with adverse socioeconomic circumstances. Holistic, child focused care, particularly in boys and those in lower income groups, may help to prevent and reduce co-occurrence in later childhood and adolescence.
Menstrual cups and sanitary pads to reduce school attrition, and sexually transmitted and reproductive tract infections: a cluster randomised controlled feasibility study in rural Western Kenya
Authors: Phillips-Howard Penelope A , Nyothach Elizabeth , ter Kuile Feiko O , Omoto Jackton , Wang Duolao , Zeh Clement , Onyango Clayton , Mason Linda , Alexander Kelly T , Odhiambo Frank O , Eleveld Alie , Mohammed Aisha , van Eijk Anna M , Edwards Rhiannon Tudor , Vulule John , Faragher Brian , Laserson Kayla F
Published: November 2016

Objectives

Conduct a feasibility study on the effect of menstrual hygiene on schoolgirls' school and health (reproductive/sexual) outcomes.

Design

3-arm single-site open cluster randomised controlled pilot study.

Setting

30 primary schools in rural western Kenya, within a Health and Demographic Surveillance System.

Participants

Primary schoolgirls 14–16 years, experienced 3 menses, no precluding disability, and resident in the study area.

Interventions

1 insertable menstrual cup, or monthly sanitary pads, against ‘usual practice’ control. All participants received puberty education preintervention, and hand wash soap during intervention. Schools received hand wash soap.

Primary and secondary outcome measures

Primary: school attrition (drop-out, absence); secondary: sexually transmitted infection (STI) (Trichomonas vaginalis,Chlamydia trachomatis,Neisseria gonorrhoea), reproductive tract infection (RTI) (bacterial vaginosis,Candida albicans); safety: toxic shock syndrome, vaginalStaphylococcus aureus.

Results

Of 751 girls enrolled 644 were followed-up for a median of 10.9 months. Cups or pads did not reduce school dropout risk (control=8.0%, cups=11.2%, pads=10.2%). Self-reported absence was rarely reported and not assessable. Prevalence of STIs in the end-of-study survey among controls was 7.7% versus 4.2% in the cups arm (adjusted prevalence ratio (aPR) 0.48, 0.24 to 0.96, p=0.039), 4.5% with pads (aPR=0.62; 0.37 to 1.03, p=0.063), and 4.3% with cups and pads pooled (aPR=0.54, 0.34 to 0.87, p=0.012). RTI prevalence was 21.5%, 28.5% and 26.9% among cup, pad and control arms, 71% of which were bacterial vaginosis, with a prevalence of 14.6%, 19.8% and 20.5%, per arm, respectively. Bacterial vaginosis was less prevalent in the cups (12.9%) compared with pads (20.3%, aPR=0.65, 0.44 to 0.97, p=0.034) and control (19.2%, aPR=0.67, 0.43 to 1.04, p=0.075) arm girls enrolled for 9 months or longer. No adverse events were identified.

Conclusions

Provision of menstrual cups and sanitary pads for ∼1 school-year was associated with a lower STI risk, and cups with a lower bacterial vaginosis risk, but there was no association with school dropout. A large-scale trial on menstrual cups is warranted.

Trial registration

ISRCTN17486946; Results
Burnout prevalence in New Zealand's public hospital senior medical workforce: a cross-sectional mixed methods study
Authors: Chambers Charlotte N L , Frampton Christopher M A , Barclay Murray , McKee Martin
Published: November 2016

Objectives

To explore the prevalence of, and associated factors contributing to burnout among senior doctors and dentists working in the New Zealand's public health system.

Design

Cross-sectional, mixed methods study.

Setting

New Zealand's 20 district health boards (DHBs).

Participants

A total of 1487 of 3740 senior doctors and dentists who are members of the Association of Salaried Medical Specialists working in DHBs were recruited (response rate 40%).

Primary and secondary outcome measures

Gender, age, self-rated health status, vocation and hours of work per week were obtained from an electronic questionnaire. Burnout was measured using the Copenhagen Burnout Inventory. Qualitative data taken from an open-ended comments section was coded using grounded theory and used for contextual data.

Results

The overall prevalence of high personal burnout was 50%. Women aged <40 years had 71% prevalence of high personal burnout. Prevalence of high work-related burnout and patient-related burnout was 42% and 16%, respectively. Those working in emergency medicine and psychiatry had significantly higher mean work-related burnout than other specialties (p<0.001). On multivariate analysis, having fair or poor health status (OR 10.8, 95% CI 6.8 to 17.1), working more than 14 consecutive hours (OR 1.43, 95% CI 1.12 to 1.82) and being a woman (OR 2.14, 95% CI 1.68 to 2.73) were independently associated with high personal and work-related burnout. Personal burnout rates decreased with age (age 30–39 OR 2.86, 95% CI 1.78 to 4.59, age 40–49 OR 2.45, 95% CI 1.70 to 3.55, age 50–59 OR 1.70, 95% CI 1.17 to 2.46, compared with age>60). Qualitative data emphasised intense and unrelenting workloads, under-staffing, onerous on-call duties and frustrations with management as factors contributing to burnout.

Conclusions

High burnout appears prevalent in New Zealand's senior doctors and dentists. Many attribute their feelings of burnout to work conditions. These findings may assist with understanding contributors to burnout and with developing strategies to ameliorate the high burnout found across this cohort.
A pilot study to evaluate the utility of live training (LIVEX) in the operational preparedness of UK military trauma teams
Authors: Smith J E , Withnall R D J , Rickard R F , Lamb D , Sitch A , Hodgetts T J
Published: November 2016

Background

With the end of UK military operations in Iraq and Afghanistan, it is essential that peacetime training of Defence Medical Services (DMS) trauma teams ensures appropriate future preparedness. A new model of pre-deployment training involves placement of formed military trauma teams into civilian trauma centres. This study evaluates the benefit of ‘live training during an exercise period’ (LIVEX) for DMS trauma teams.

Methods

A cross-sectional questionnaire-based survey of participants was conducted. Quantitative data were collected prior to the start and on the final day. Written reports were collected from the coordinators. Thematic analysis was used to identify emergent themes in a supplementary, qualitative analysis.

Results

Each team comprised 13 personnel and results should be interpreted with knowledge of this small sample size. The response rate for both the pre-LIVEX and post-LIVEX questionnaire was 100%. By the end of the week, 89% of participants (n=23) stated LIVEX was an ‘appropriate or very appropriate’ way of preparing for an operational role compared with 40% (n=9) before the exercise (p<0.01). However, completing LIVEX made no difference to participants' personal perception of their own operational preparedness. Thematic analysis suggested greater training benefit for more junior members of the team; from Regulars and Reservists training together; and from two-way exchange of information between DMS and National Health Service medical staffs.

Conclusions

Completing LIVEX made no statistically significant difference to participants' personal perception of their own operational preparedness, but the perception of LIVEX as an appropriate training platform improved significantly after conducting the training exercise.
Thin flexible lithium-ion battery featuring graphite paper based current collectors with enhanced conductivity
Authors: Qu Hang , Hou Jingshan , Tang Yufeng , Semenikhin Oleg , Skorobogatiy Maksim
Published: November 2016

A flexible, lightweight, and high conductivity current collector is the key element that enables fabrication of a high-performance, flexible lithium-ion battery. Here, we report a thin, lightweight, and flexible lithium-ion battery that uses graphite papers deposited with nano-sized metallic layers as the current collector, LiFePO4 and Li4Ti5O12 as the cathode and anode materials, respectively, and a PE membrane soaked in LiPF6 as the separator. Using thin, flexible graphite paper as a substrate for the current collector instead of a rigid, heavy metal foil enables us to demonstrate an ultra-thin lithium-ion battery (total thickness including encapsulation layers of less than 250 μm) that also features a light weight and high flexibility.
Effects of 1,3,5-triphenyl-4,5-dihydro-1H-pyrazole derivatives on cell-cycle and apoptosis in human acute leukemia cell lines
Authors: Santos Bubniak Lorena dos , Gaspar Pâmela Cristina , de Moraes Ana Carolina Rabello , Bigolin Alisson , de Souza Rubia Karine , Buzzi Fátima Campos , Corrêa Rogério , Filho Valdir Cechinel , Bretanha Lizandra Czermainski , Micke Gustavo Amadeu , Nunes Ricardo José , Santos-Silva Maria Cláudia
Published: November 2016

Pyrazoline is an important 5-membered nitrogen heterocycle that has been extensively researched. Ten derivatives were synthesized and tested for antileukemic effects on 2 human acute leukemia cell lines, K562 and Jurkat. The most cytotoxic of these derivatives, compound 21, was chosen for investigation of cytotoxicity mechanisms. The results obtained with selectivity calculations revealed that compound 21 is more selective for acute leukemia (K562 and Jurkat cell lines) than for other tumor cell lines. Moreover, compound 21 was not cytotoxic to normal cell lines, indicating a potential use in clinical tests. Compound 21 caused a significant cell cycle arrest in the S-phase in Jurkat cells and increased the proportion of cells in the sub G0/G1 phase in both cell lines. Cells treated with compound 21 demonstrated morphological changes characteristic of apoptosis in the EB/AO assay, confirmed by externalization of phosphatidylserine by the annexin V – fluorescein isothiocyanate method and by DNA fragmentation. An investigation of cytotoxicity mechanisms suggests the involvement of an intrinsic apoptosis pathway due to mitochondrial damage and an increase in the ratio of mitochondrial Bax/Bcl2. Pyrazoline 21 obeyed Lipinski’s “rule of five” for drug-likeness. Based on these preliminary results, the antileukemic activity of compound 21 makes it a potential anticancer agent.
miR-29b promotes skin wound healing and reduces excessive scar formation by inhibition of the TGF-β1/Smad/CTGF signaling pathway
Authors: Guo Jingdong , Lin Quan , Shao Ying , Rong Li , Zhang Duo
Published: November 2016

The hypertrophic scar is a medical difficulty of humans, which has caused great pain to patients. Here, we investigated the inhibitory effect of miR-29b on scar formation. The scalded model was established in mice and miR-29b mimics or a negative control was subcutaneously injected into the injury skin. Then various molecular biological experiments were performed to assess the effect of miR-29b on scar formation. According to our present study, first, the results demonstrated that miR-29b was down-regulated in thermal injury tissue and miR-29b treatment could promote wound healing, inhibit scar formation, and alleviate histopathological morphologic alteration in scald tissues. Additionally, miR-29b treatment suppressed collagen deposition and fibrotic gene expression in scar tissues. Finally, we found that miR-29b treatment inhibited the TGF-β1/Smad/CTGF signaling pathway. Taken together, our data suggest that miR-29b treatment has an inhibitory effect against scar formation via inhibition of the TGF-β1/Smad/CTGF signaling pathway and may provide a potential molecular basis for future treatments for hypertrophic scars.
Goldstone origin of black hole hair from supertranslations and criticality
Authors: Averin Artem , Dvali Gia , Gomez Cesar , Lüst Dieter
Published: November 2016

Degrees of freedom that carry black hole entropy and hair can be described in the language of Goldstone phenomenon. They represent the pseudo-Goldstone bosons of certain supertranslations, called [Formula: see text]-transformations, that are spontaneously broken by the black hole metric. This breaking gives rise to a tower of Goldstone bosons created by the spontaneously-broken generators that can be labeled by spherical harmonics. Classically, the number of charges is infinite, they have vanishing vacuum expectation values (VEVs) and the corresponding Goldstone modes are gapless. The resulting hair and entropy are infinite, but unresolvable. In quantum theory, the two things happen. The number of legitimate Goldstone modes restricted by requirement of weak-coupling, becomes finite and scales as black hole area in Planck units. The Goldstones generate a tiny gap, controlled by their gravitational coupling. The gap turns out to be equal to the inverse of black hole half-life, [Formula: see text]. Correspondingly, in quantum theory the charges are neither conserved nor vanish, but non-conservation time is set by [Formula: see text]. This picture nicely matches with the idea of a black hole as critical system is composed of many soft gravitons. The [Formula: see text]-Goldstones of geometric picture represent the near-gapless Bogoliubov–Goldstone modes of critical soft-graviton system.
Casimir effect in the Kerr spacetime with quintessence
Authors: Bezerra V. B. , Cunha M. S. , Freitas L. F. F. , Muniz C. R. , Tahim M. O.
Published: November 2016

We calculate the Casimir energy of a massless scalar field in a cavity formed by nearby parallel plates orbiting a rotating spherical body surrounded by quintessence, investigating the influence of the gravitational field on that energy, at zero temperature. This influence includes the effects due to the spacetime dragging caused by the source rotation as well as those ones due to the quintessence. We show that the energy depends on all the involved parameters, as source mass, angular momentum and quintessence state parameter, for any radial coordinate and polar angle. We show that at the north pole the Casimir energy is not influenced by the quintessential matter. At the equatorial plane, when the quintessence is canceled, the result obtained in the literature is recovered. Finally, constraints in the quintessence parameters are obtained from the uncertainty in the current measurements of Casimir effect.
Finite element investigation of the vibrational behavior of concentric multi-walled boron nitride and carbon nanotubes
Authors: Ansari R. , Rouhi S. , Nikkar A.
Published: November 2016

This paper concerns the vibrational behavior of concentric double-walled and triple-walled carbon and boron nitride nanotubes using the finite element method. Armchair and zigzag nanotubes with different lengths and diameters are considered. Moreover, different boundary conditions are applied on the nanotubes. It is observed that in double-walled nanotubes, when the inner and outer layers are respectively from boron nitride and carbon, the frequencies are larger than those in the reverse arrangement. Investigating the effect of diameter on the first 10 natural frequencies of double-walled and triple-walled nanotubes showed that nanotubes with larger diameters possess smaller frequencies. The effect of diameter is more significant for higher modes. Finally, comparisons are made between the vibrational behavior of concentric carbon and boron nitride double-walled and triple-walled nanotubes. Considering the effect of vacancy defect on the vibrational characteristics of the nanotubes revealed that when all of the walls of the nanotubes are defective, the largest diminish occurs for the fundamental natural frequencies.
New optimal asymmetric quantum codes constructed from constacyclic codes
Authors: Xu Gen , Li Ruihu , Guo Luobin , Lü Liangdong
Published: November 2016

In this paper, we propose the construction of asymmetric quantum codes from two families of constacyclic codes over finite field [Formula: see text] of code length [Formula: see text], where for the first family, [Formula: see text] is an odd prime power with the form [Formula: see text] ([Formula: see text] is integer) or [Formula: see text] ([Formula: see text] is integer) and [Formula: see text]; for the second family, [Formula: see text] is an odd prime power with the form [Formula: see text] or [Formula: see text] ([Formula: see text] is integer) and [Formula: see text]. As a result, families of new asymmetric quantum codes [Formula: see text] with [Formula: see text] distance larger than [Formula: see text] are obtained, which are not covered by the asymmetric quantum error-correcting codes (AQECCs) in Refs. 32 and 33 [J.-Z. Chen, J.-P. Li and J. Lin, Int. J. Theor. Phys. 53, 72 (2014); L. Wang and S. Zhu, Int. J. Quantum Inf. 12, 1450017 (2014)] that [Formula: see text]. Also, all the newly obtained asymmetric quantum codes are optimal according to the singleton bound for asymmetric quantum codes.
Pressure variation of melting temperatures of alkali halides
Authors: Arafin Sayyadul , Singh Ram N.
Published: November 2016

The melting temperatures of alkali halides (LiCl, LiF, NaBr, NaCl, NaF, NaI, KBr, KCl, KF, KI, RbBr, RbCl, RbI and CsI) have been evaluated over a wide range of pressures. The solid–liquid transition of alkali halides is of considerable significance due to their huge industrial applications. Our formalism requires a priori knowledge of the bulk modulus and the Grüneisen parameter at ambient conditions to compute [Formula: see text] at high pressures. The computed values are in very good agreement with the available experimental results. The formalism can satisfactorily be used to compute [Formula: see text] at high pressures where the experimental data are scanty. Most of the melting curves ([Formula: see text] versus [Formula: see text]) exhibit nonlinear variation with increasing pressure having curvatures downward and exhibit a maximum in some cases like NaCl, RbBr, RbCl and RbI. The values of [Formula: see text] and [Formula: see text] corresponding to the maxima of the curves are given.
Conservation laws of a perturbed Kaup–Newell equation
Authors: Yang Jing-Yun , Ma Wen-Xiu
Published: November 2016

A new Lax pair is introduced for a perturbed Kaup–Newell equation and used to construct two series of conservation laws through a Riccati equation that a ratio of eigenfunctions satisfies. Both series of conservation laws are defined recursively, and the first two in each series are presented explicitly.
Electromagnetic instability induced by neutrino interaction
Authors: Bhatt Jitesh R. , George Manu
Published: November 2016

We consider the generation and evolution of magnetic field in a primordial plasma at temperature [Formula: see text][Formula: see text]MeV in the presence of asymmetric neutrino background, i.e. the number densities of right-handed and left-handed neutrinos are not the same. Semi-classical equations of motion of a charged fermion are derived using the effective low-energy Lagrangian. We show that the spin degree of freedom of the charged fermion couples with the neutrino background. Using this kinetic equation, we study the collective modes of the plasma. We find that there exist an unstable mode. This instability is closely related with the instability induced by chiral-anomaly in high temperature [Formula: see text][Formula: see text]TeV plasma where right and left-handed electrons are out of equilibrium. We find that at the temperatures below the neutrino decoupling this instability can produce magnetic field in the universe. We discuss cosmological implications of the results.
STUDY ON THE PHOTOINDUCED ELECTRON TRANSFER BETWEEN C60 AND POLY (N-VINYLCARBAZOLE) (PVK) POLYMERS FOR THE PVK/C60 COMPOSITE FILM
Authors: JIANG XIAOHONG , CHI JIANYU , LIU HE , DU ZULIANG
Published: November 2016

The film of poly (N-vinylcarbazole) (PVK) polymers and its composite film of PVK/C[Formula: see text] were prepared successfully by spin-coating method at speed of 1200[Formula: see text]rms for 30[Formula: see text]s. Atomic force microscopy (AFM), UV–Vis absorption spectroscopy and the photoluminescence (PL) were used to investigate the film structure and optoelectronic properties. The PL quench was observed for the PVK/C[Formula: see text] composite film. The current increased near three orders of magnitude under illumination for PVK/C[Formula: see text] composite film comparing with that in the dark through [Formula: see text] measurement, which resulted from the electron transfer from PVK to C[Formula: see text].
EFFECT OF OXYACETYLENE FLAME REMELTING ON WEAR BEHAVIOUR OF SUPERSONIC AIR-PLASMA SPRAYED NiCrBSi/h-BN COMPOSITE COATINGS
Authors: ZHANG N. N. , LIN D. Y. , HE B. , ZHANG G. W. , ZHANG Y. , LI D. Y.
Published: November 2016

NiCrBSi alloy coatings are widely used in wear and corrosion protection at higher temperature. As a primary hard phase forming element, B element can effectively improve the coating hardness. In this study, the low coefficient of friction of BN with three ratios (10%, 20%, and 30%) was added in order to reduce the wear rate and provide additional B element. The NiCrBSi/h-BN composite coatings were successfully prepared on a cast-iron substrate using supersonic air-plasma spray technology. The phase constitution, microstructure characterization, and microhardness of the coatings before and after oxyacetylene flame remelting were investigated by means of scanning electron microscope (SEM), X-ray diffraction, and energy dispersive analysis of X-ray techniques, respectively. The wear resistance of composite coatings was also tested in this paper. It was found that the microstructure was well refined by remelting treatment and this was beneficial for the adherence between the coating and the substrate, which was nearly 33[Formula: see text]MPa. The wear resistance of the NiCrBSi alloy coating was also improved with the increasing component of h-BN in remelted samples. When the h-BN content reached 30%, the friction coefficient decreased to 0.38 for the remelted coating. The effect of the remelting process on the anti-abrasive property and extension of the material’s wear life was quite important.
Development of software and modification of Q-FISH protocol for estimation of individual telomere length in immunopathology
Authors: Barkovskaya M. Sh. , Bogomolov A. G. , Knauer N. Yu. , Rubtsov N. B. , Kozlov V. A.
Published: November 2016

Telomere length is an important indicator of proliferative cell history and potential. Decreasing telomere length in the cells of an immune system can indicate immune aging in immune-mediated and chronic inflammatory diseases. Quantitative fluorescent in situ hybridization (Q-FISH) of a labeled (C3TA[Formula: see text] peptide nucleic acid probe onto fixed metaphase cells followed by digital image microscopy allows the evaluation of telomere length in the arms of individual chromosomes. Computer-assisted analysis of microscopic images can provide quantitative information on the number of telomeric repeats in individual telomeres. We developed new software to estimate telomere length. The MeTeLen software contains new options that can be used to solve some Q-FISH and microscopy problems, including correction of irregular light effects and elimination of background fluorescence. The identification and description of chromosomes and chromosome regions are essential to the Q-FISH technique. To improve the quality of cytogenetic analysis after Q-FISH, we optimized the temperature and time of DNA-denaturation to get better DAPI-banding of metaphase chromosomes. MeTeLen was tested by comparing telomere length estimations for sister chromatids, background fluorescence estimations, and correction of nonuniform light effects. The application of the developed software for analysis of telomere length in patients with rheumatoid arthritis was demonstrated.