bluuebunny/crossref_metadata_2025 huggingface dataset:
Using social norms to encourage healthier eating
Authors: Higgs S. , Liu J. , Collins E. I. M. , Thomas J. M.
Published: February 2019

What and how much people choose to eat is influenced by social context. People tend to use the eating habits of others as a guide to appropriate consumption. This suggests that one way of encouraging healthier eating would be to provide information about the healthy eating choices of others. Research conducted as part of an Economic and Social Research Council‐funded project investigated the effect of providing information about how others eat on the purchase and consumption of vegetables in both laboratory and in field settings (restaurants). In a laboratory‐based study, we found that that while overall vegetable intake was not increased, exposure to a novel ‘liking norm’ message increased the selection and intake of broccoli from a buffet by participants who were low habitual consumers of vegetables. We also found that the liking norm increased broccoli intake even when there was a delay between exposure to the message and selection at the buffet, suggesting that the effects of social message exposure may persist beyond initial exposure. In two online studies and a laboratory study, we found that the effect of exposure to a descriptive social norm message on eating intentions and intake was moderated by the participants’ motivation to identify with the norm referent group. In three intervention studies, exposure to social norm messaging was associated with increased purchases of meals with vegetables in restaurant settings. Taken together, these results suggest that it is feasible to use social norm messages in restaurant settings and they provide information that could be used to implement randomised controlled trials.
Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015–2016
Authors: Makino Nobuko , Nakamura Yosikazu , Yashiro Mayumi , Kosami Koki , Matsubara Yuri , Ae Ryusuke , Aoyama Yasuko , Yanagawa Hiroshi
Published: February 2019

Background

Approximately 50 years have passed since Kawasaki disease (KD) was first reported. The KD nationwide survey began in 1970. Although >360 000 cases have already been reported in Japan, the cause is still unknown. In Japan, the number of patients and incidence rate of KD has continued to increase. It is necessary to examine the trend of the occurrence in the surveillance of KD.

Methods

The nationwide survey of patient incidence in 2015 and 2016 was conducted in 2017, as the 24th nationwide survey of KD. A questionnaire was sent to pediatric departments in hospitals with >100 beds and specialized pediatric hospitals, and was responded to by the attending pediatricians.

Results

The total number of patients in 2 years was 31 595, and the sex ratio (male/female) was 1.34. The incidence rate (/100 000 children aged 0–4 years/year) was 330.2 (371.2 in boys, 287.3 in girls) in 2015, and 309.0 (343.2 in boys, 273.2 in girls) in 2016. The number of patients by month peaked in January. The age‐specific incidence rate according to sex was highest in children between 9 and 11 months of age, after which the incidence rate gradually decreased with advancing age.

Conclusions

We summarize the most recent nationwide survey of KD and consider the change in the epidemiologic picture.
Successful hematopoietic stem cell transplantation from an HLA‐mismatched parent for engraftment failure after unrelated cord blood transplantation in patients with juvenile myelomonocytic leukemia: Report of two cases
Authors: Akahane Koshi , Watanabe Atsushi , Furuichi Yoshiyuki , Somazu Shinpei , Oshiro Hiroko , Goi Kumiko , Sakashita Kazuo , Muramatsu Hideki , Hama Asahito , Takahashi Yoshiyuki , Koike Kenichi , Kojima Seiji , Sugita Kanji , Inukai Takeshi
Published: February 2019

JMML is an aggressive hematopoietic malignancy of early childhood, and allogeneic HSCT is the only curative treatment for this disease. Umbilical cord blood is one of donor sources for HSCT in JMML patients who do not have an HLA‐compatible relative, but engraftment failure remains a major problem. Here, we report two cases of JMML who were successfully rescued by HSCT from an HLA‐mismatched parent after development of primary engraftment failure following unrelated CBT. Both patients had severe splenomegaly and underwent unrelated CBT from an HLA‐mismatched donor. Immediately after diagnosis of engraftment failure, both patients underwent HSCT from their parent. For the second HSCT, we used RIC regimens consisting of FLU, CY, and a low dose of rabbit ATG with or without TBI and additionally administered ETP considering their persistent severe splenomegaly. Both patients achieved engraftment without severe treatment‐related adverse effects. After engraftment of second HSCT, their splenomegaly was rapidly regressed, and both patients showed no sign of relapse for over 4 years. These observations demonstrate that HSCT from an HLA‐mismatched parent could be a feasible salvage treatment for primary engraftment failure in JMML patients.
Intelligence as a predictor of social mobility in Estonia
Authors: Anni Kätlin , Mõttus René
Published: February 2019

The purpose of this study was to explore how individual and environmental predictors of intergenerational social mobility intersect in rarely studied post‐communist developing society of Estonia. We used a contemporary cross‐sectional dataset (n = 759) to assess the influence of cognitive ability and parental socioeconomic status to the participants’ educational and occupational attainment. Our results indicated that cognitive ability and one's own educational level mediated the association of parental socioeconomic status with one's own occupational success. Analysis of separate components of cognitive ability indicated that verbal ability had the highest influence on occupational status. We concluded that both individual‐level and environmental factors have a predictive effect on educational and occupational attainment.
The novel HLA‐C*08:80 allele identified by full‐length sequencing of the HLA region
Authors: Cheng Bochen , Mo Xiaodong , Feng Qian , Fang Mingyan
Published: February 2019

A novel allele HLA‐C*08:80 differs from HLA‐C*08:01:01:01 by one nucleotide substitution at position 142.
Analysis of the blood donor behaviours: 9 years’ experience of Turkish Red Crescent in blood donor management practice
Authors: Ulger Dervis , Çelik İbrahim , Ulukanligil Mustafa , Hafizoglu Nurettin , Kinik Kerem , Yilmaz Fatma Meric
Published: February 2019

Objectives

The Turkish Red Crescent has been the responsible body and created the national blood banking system in Turkey. In this study, we aimed to share the 9 years’ experience of the Turkish Red Crescent in blood donor management practice for a better understanding of donors’ motivations which might improve the ability of a blood bank to provide a more robust blood supply.

Materials and Methods

Blood Banking Information Management System of Turkish Red Crescent allows to follow the donor behaviours throughout in the country. In this study, donors who are registered in the Turkish Red Crescent system were evaluated according to the DOMAINE (Donor Management IN Europe) definitions in terms of donor populations and donor behaviours. The improvement of blood donor numbers and the change of behaviours with time is analysed and discussed.

Results

While 24% of the total blood donors in 2009 were regular donors, the number of regular donors increased over the years to 41% in 2017 with the help of donor acquisition programmes. However, it is observed that 1 106 351 of the donors registered in the Turkish Red Crescent system (13%) are silent donors and 4 269 909 persons (49·7%) are inactive donors (As of 10 March 2018).

Conclusion

Classification and analysis of blood donors in the system helps to create incentives to increase the number of regular blood donors. Good donor management can be achieved by classifying donors using DOMAINE definitions and developing new strategies with appropriate donor management programmes.
Polar gap after cementless total hip replacement in dogs
Authors: Liska William D. , Israel Sarah K. , Poteet Brian A.
Published: February 2019

Objective

To determine the incidence and outcomes of total hip replacements with polar gaps in dogs.

Study design

Retrospective case series.

Animals

One hundred fifty‐five client‐owned dogs.

Methods

Serial postoperative and follow‐up digital orthogonal radiographs of 200 hips in 155 dogs that underwent consecutive index total hip replacement (THR) were examined for the presence of polar gaps. Length and depth of polar gaps were measured and monitored on serial radiographs.

Results

A polar gap was identified in at least 1 zone in 136 (68%) of the ventral‐dorsal (VD) radiographs and in 80 (40%) of the lateral radiographs obtained immediately after surgery. Gaps were more common in zones 2 and 5, measuring ≤1 mm in depth in 94 hips on the VD and in 78 hips on the lateral views. No gaps were radiographically visible after 5 weeks postsurgery. No continuous interface radiolucency or lysis was detected, and none of the THR required revision because of loosening.

Conclusion

Polar gaps were identified on the majority of radiographs immediately after THR in our clinical setting and all resolved without complications.

Clinical significance

Recognition and incidence of postoperative polar gaps after THR may vary among surgeons. Gaps do not warrant clinical intervention.
Water Resources Accounting and Nigeria’s Economic Advancement
Authors: Omodero Cordelia Onyinyechi , Uche Belonwu Azubike - Joseph , Ogbonnaya Amah Kalu
Published: February 2019

Water resources accounting is presently a universal challenge due to the high rate of water contamination and other discharges that put nations at risk of water scarcity if precautionary measures are not taken on time. All needed government interventions to reduce the risk of water scarcity is dependent on the extent of water resource accountability available in the country. This paper examines the contribution of water resources accounting to Nigeria’s economic advancement. The data employed span from 1981-2017 and have been collected from the CBN Statistical Bulletin, 2017 edition. Ordinary Least Squares technique is used to analyze the date and the result indicates that water resources accounted for, have strong and significant positive impact on the RGDP. The findings also reveal that water resources are estimated to contribute a total of 72.6% variation in the RGDP between the periods from 1981 to 2017 in Nigeria. Therefore, the study recommends sufficient training and empowerment for all agencies responsible for data gathering of water resources. This will enhance quality water resources’ accountability. Policy makers should encourage all forms of water resources accountability and management to sustain the economy by liaising with international bodies and getting updates on global best practices in this area.
Human circadian phase–response curves for exercise
Authors: Youngstedt Shawn D. , Elliott Jeffrey A. , Kripke Daniel F.
Published: February 2019

Key points

Exercise elicits circadian phase‐shifting effects, but additional information is needed.

The phase–response curve describing the magnitude and direction of circadian rhythm phase shifts, depending on the time of the zeigeber (time cue) stimulus, is the most fundamental chronobiological tool for alleviating circadian misalignment and related morbidity.

Fifty‐one older and 48 young adults followed a circadian rhythms measurement protocol for up to 5.5 days, and performed 1 h of moderate treadmill exercise for 3 consecutive days at one of eight times of the day/night.

Temporal changes in the phase of 6‐sulphatoxymelatonin (aMT6s) were measured from evening onset, cosine acrophase, morning offset and duration of excretion. Significant phase–response curves were established for aMT6 onset and acrophase with large phase delays from 7:00 pm to 10:00 pm and large phase advances at both 7:00 am and from 1:00 pm to 4:00 pm. Delays or advances would be desired, for example, for adjustment to westward or eastward air travel, respectively.

Along with known synergism with bright light, the above PRCs with a second phase advance region (afternoon) could support both practical and clinical applications.

Although bright light is regarded as the primary circadian zeitgeber, its limitations support exploring alternative zeitgebers. Exercise elicits significant circadian phase‐shifting effects, but fundamental information regarding these effects is needed. The primary aim of the present study was to establish phase–response curves (PRCs) documenting the size and direction of phase shifts in relation to the circadian time of exercise. Aerobically fit older (n = 51; 59–75 years) and young adults (n = 48; 18–30 years) followed a 90 min laboratory ultrashort sleep–wake cycle (60 min wake/30 min sleep) for up to 5½ days. At the same clock time on three consecutive days, each participant performed 60 min of moderate treadmill exercise (65–75% of heart rate reserve) at one of eight times of day/night. To describe PRCs, phase shifts were measured for the cosine‐fitted acrophase of urinary 6‐sulphatoxymelatonin (aMT6s), as well as for the evening rise, morning decline and change in duration of aMT6s excretion. Significant PRCs were found for aMT6s acrophase, onset and duration, with peak phase advances corresponding to clock times of 7:00 am and from 1:00 pm to 4:00 pm, delays from 7:00 pm to 10:00 pm, and minimal shifts around 4:00 pm and 2:00 am. There were no significant age or sex differences. The amplitudes of the aMT6s onset and acrophase PRCs are comparable to expectations for bright light of equal duration. The phase advance to afternoon exercise and the exercise‐induced PRC for change in aMT6s duration are novel findings. The results support further research exploring additive phase‐shifting effects of bright light and exercise and health benefits.
A New Vascular System Highly Efficient in the Storage and Transport of Healing Agent for Self-Healing Wind Turbine Blades
Authors: Shen Rulin , Amano Ryoichi S. , Lewinski Giovanni , Matt Arun Kumar Koralagundi
Published: February 2019

Self-healing wind turbine blades offer a substantial offset for costly blade repairs and failures. We discuss the efforts made to optimize the self-healing properties of wind turbine blades and provide a new system to maximize this offset. Copper wire coated by paraffin wax was embedded into fiber-reinforced polymer (FRP) samples incorporated with Grubbs' first-generation catalyst. The wires were extracted from cured samples to create cavities that were then injected with the healing agent, dicyclopentadiene (DCPD). Upon sample failure, the DCPD and catalyst react to form a thermosetting polymer to heal any crack propagation. Three-point bending flexural tests were performed to obtain the maximum flexural strengths of the FRP samples before and after recovery. Using those results, a hierarchy of various vascular network configurations was derived. To evaluate the healing system's effect in a real-life application, a prototype wind turbine was fabricated and wind tunnel testing was conducted. Using ultraviolet (UV) dye, storage and transport processes of the healing agent were observed. After 24 h of curing time, Raman spectroscopy was performed. The UV dye showed dispersion into the failure zone, and the Raman spectra showed the DCPD was polymerized to polydicyclopentadiene (PDCPD). Both the flexural and wind tunnel test samples were able to heal successfully, proving the validity of the process.
Thermal Design and Analysis of a Solid-State Grid-Tied Thermal Energy Storage for Hybrid Compressed Air Energy Storage Systems
Authors: Hakamian Khashayar , Anderson Kevin R. , Shafahi Maryam , Lakeh Reza Baghaei
Published: February 2019

Power overgeneration by renewable sources combined with less dispatchable conventional power plants introduces the power grid to a new challenge, i.e., instability. The stability of the power grid requires constant balance between generation and demand. A well-known solution to power overgeneration is grid-scale energy storage. Compressed air energy storage (CAES) has been utilized for grid-scale energy storage for a few decades. However, conventional diabatic CAES systems are difficult and expensive to construct and maintain due to their high-pressure operating condition. Hybrid compressed air energy storage (HCAES) systems are introduced as a new variant of old CAES technology to reduce the cost of energy storage using compressed air. The HCAES system split the received power from the grid into two subsystems. A portion of the power is used to compress air, as done in conventional CAES systems. The rest of the electric power is converted to heat in a high-temperature thermal energy storage (TES) component using Joule heating. A computational approach was adopted to investigate the performance of the proposed TES system during a full charge/storage/discharge cycle. It was shown that the proposed design can be used to receive 200 kW of power from the grid for 6 h without overheating the resistive heaters. The discharge computations show that the proposed geometry of the TES, along with a control strategy for the flow rate, can provide a 74-kW microturbine of the HCAES with the minimum required temperature, i.e., 1144 K at 0.6 kg/s of air flow rate for 6 h.
Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its oncogenic potential
Authors: Bandekar Sumit J. , Arang Nadia , Tully Ena S. , Tang Brittany A. , Barton Brenna L. , Li Sheng , Gutkind J. Silvio , Tesmer John J. G.
Published: February 2019

Structural analysis of the RhoGEF Trio reveals modes of its activation in patients with cancer.
Expansion of Vancomycin-Resistant
Enterococcus faecium
in an Academic Tertiary Hospital in Southwest Germany: a Large-Scale Whole-Genome-Based Outbreak Investigation
Authors: Liese Jan , Schüle Leonard , Oberhettinger Philipp , Tschörner Leonie , Nguyen Tran , Dörfel Daniela , Vogel Wichard , Marschal Matthias , Autenrieth Ingo , Willmann Matthias , Peter Silke
Published: February 2019

Vancomycin-resistant
Enterococcus faecium
(VREfm) is a frequent cause of nosocomial outbreaks. In the second half of 2015, a sharp increase in the incidence of VREfm was observed at our university medical center.
Emergence of Parechovirus A4 Central Nervous System Infections among Infants in Kansas City, Missouri, USA
Authors: Sasidharan A. , Harrison C. J. , Banerjee D. , Selvarangan R.
Published: February 2019

Among known parechovirus (PeV) types infecting humans, PeV-A3 (formerly HPeV3) and PeV-A1 (formerly HPeV1) are associated with pediatric central nervous system (CNS) infections. The prevalence of PeV-A3 among hospitalized infants with sepsis-like illness and viral CNS infection is well described; however, the contribution of PeV-A4 to infant CNS infection is relatively unexplored.
Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3
Authors: Lian Xue , Bao Chenyi , Li Xueqi , Zhang Xunhai , Chen Hongjun , Jung Yong-Sam , Qian Yingjuan
Published: February 2019

MDV is used as a biomedical model to study virus-induced lymphoma due to the similar genomic structures and physiological characteristics of MDV and human herpesviruses. Upon infection, MDV induces DNA damage, which may activate the DDR pathway. The DDR pathway has a dual impact on viruses because it manipulates repair and recombination factors to facilitate viral replication and also initiates antiviral action by regulating other signaling pathways. Many DNA viruses evolve to manipulate the DDR pathway to promote virus replication. In this study, we identified a mechanism used by MDV to inhibit ATR-Chk1 pathways. ATR is a cellular kinase that responds to broken single-stranded DNA, which has been less studied in MDV infection. Our results suggest that MDV infection activates STAT3 to disable the ATR-Chk1 pathway, which is conducive to viral replication. This finding provides new insight into the role of STAT3 in interrupting the ATR-Chk1 pathway during MDV replication.
Genome Sequence Announcement of Lactobacillus vaginalis LMG S-26419, Isolated from a Healthy Woman
Authors: Puglisi Edoardo , Galletti Serena , Sagheddu Valeria , Elli Marina
Published: February 2019

The
Lactobacillus vaginalis
LMG S-26419 strain, also named CBA-L88 (BV2), was isolated at the AAT-Advanced Analytical Technologies laboratories from a vaginal swab obtained from a healthy woman. The total genome size is 1,806,242 bp with a G+C content of 40.6%.
Atypical testicular pain
Authors: Bedi Nishant , Rahimi Muhammad Naim Che , Menzies Sarah , Kalsi Jas
Published: February 2019

Testicular tuberculosis (TB) is rare, and, because of this, the lack of pathognomonic clinical features and its tendency to mimic other commoner conditions, the diagnosis is frequently delayed or may be missed. In this case, the initial clinical presentation was typical for bacterial epididymo-orchitis in a 38-year-old man. When the patient failed to improve with standard treatment including broadening of antibiotics, the diagnosis was re-considered because some unusual signs suggested testicular malignancy or lymphoma. Further, history-taking and subsequent cross-sectional imaging with CT/MRI identified co-existent pulmonary nodularity, thoracic and abdominal lymphadenopathy and bony changes that, together, raised the suspicion of TB.Mycobacterium tuberculosiswas confirmed on DNA-based testing of the hydrocele fluid, although standard acid-fast bacilli culture was negative. This case prompted a review of the literature to explore the optimal steps in the investigation and diagnosis of this rare disease.
Acute adrenal failure: a potentially fatal consequence of an adulterated herbal remedy
Authors: Sensi Harminder , Buch Harit , Ford Loretta , Gama Rousseau
Published: February 2019

Herbal remedies adulterated with glucocorticoids can cause Cushing’s syndrome. We report a severe presentation of a ‘herbal remedy’ adulterated with glucocorticoids; causing a potentially fatal adrenal crisis precipitated by acute illness. Investigations were consistent with adrenal suppression and confirmed, after tablet analysis, to be due to a ‘herbal remedy’ containing synthetic betamethasone/dexamethasone. This case highlights the need for clinical vigilance and patient education about the potential risks associated with the use of unlicensed treatments and the role of tablet analysis in routine biochemistry.
Costs and effects of higher turnover of nurses and Aboriginal health practitioners and higher use of short-term nurses in remote Australian primary care services: an observational cohort study
Authors: Zhao Yuejen , Russell Deborah Jane , Guthridge Steven , Ramjan Mark , Jones Michael P , Humphreys John S , Wakerman John
Published: February 2019

Objectives

To compare the costs and effects of higher turnover of resident nurses and Aboriginal health practitioners and higher use of agency-employed nurses in remote primary care (PC) services and quantify associations between staffing patterns and health outcomes in remote PC clinics in the Northern Territory (NT) of Australia.

Design

Observational cohort study, using hospital admission, financial and payroll data for the period 2013–2015.

Setting

53 NT Government run PC clinics in remote communities.

Outcome measures

Incremental cost-effectiveness ratios were calculated for higher compared with lower turnover and higher compared with lower use of agency-employed nurses. Costs comprised PC, travel and hospitalisation costs. Effect measures were total hospitalisations and years of life lost per 1000 person-months. Multiple regression was performed to investigate associations between overall health costs and turnover rates and use of agency-employed nurses, after adjusting for key confounders.

Results

Higher turnover was associated with significantly higher hospitalisation rates (p<0.001) and higher average health costs (p=0.002) than lower turnover. Lower turnover was always more cost-effective. Average costs were significantly (p<0.001) higher when higher proportions of agency-employed nurses were employed. The probability that lower use of agency-employed nurses was more cost-effective was 0.84. Halving turnover and reducing use of a short-term workforce have the potential to save $32 million annually in the NT.

Conclusion

High turnover of health staff is costly and associated with poorer health outcomes for Aboriginal peoples living in remote communities. High reliance on agency nurses is also very likely to be cost-ineffective. Investment in a coordinated range of workforce strategies that support recruitment and retention of resident nurses and Aboriginal health practitioners in remote clinics is needed to stabilise the workforce, minimise the risks of high staff turnover and over-reliance on agency nurses and thereby significantly reduce expenditure and improve health outcomes.
Development and external validation of new nomograms by adding ECG changes (ST depression or tall T wave) and age to conventional scoring systems to improve the predictive capacity in patients with subarachnoid haemorrhage: a retrospective, observational study in Korea
Authors: Hong Ju young , You Je Sung , Kim Min Joung , Lee Hye Sun , Park Yoo Seok , Chung Sung Phil , Park Incheol
Published: February 2019

Objectives

To develop new nomograms by adding ECG changes (ST depression or tall T wave) and age to three conventional scoring systems, namely, World Federation of Neurosurgical Societies (WFNS) scale, Hunt and Hess (HH) system and Fisher scale, that can predict prognosis in patients with subarachnoid haemorrhage (SAH) using our preliminary research results and to perform external validation of the three new nomograms.

Design

Retrospective, observational study

Setting

Emergency departments (ED) of two university-affiliated tertiary hospital between January 2009 and March 2015.

Participants

Adult patients with SAH were enrolled. Exclusion criteria were age <19 years, no baseline ECG, cardiac arrest on arrival, traumatic SAH, referral from other hospital and referral to other hospitals from the ED.

Primary outcome measures

The 6 month prognosis was assessed using the Glasgow Outcome Scale (GOS). We defined a poor outcome as a GOS score of 1, 2 or 3.

Results

A total of 202 patients were included for analysis. From the preliminary study, age, ECG changes (ST depression or tall T wave), and three conventional scoring systems were selected to predict prognosis in patients with SAH using multi-variable logistic regression. We developed simplified nomograms using these variables. Discrimination of the developed nomograms including WFNS scale, HH system and Fisher scale was superior to those of WFNS scale, HH system and Fisher scale (0.912 vs 0.813; p<0.001, 0.913 vs 0.826; p<0.001, and 0.885 vs 0.746; p<0.001, respectively). The calibration plots showed excellent agreement. In the external validation, the discrimination of the newly developed nomograms incorporating the three scoring systems was also good, with an area under the receiver-operating characteristic curve value of 0.809, 0.812 and 0.772, respectively.

Conclusions

We developed and externally validated new nomograms using only three independent variables. Our new nomograms were superior to the WFNS scale, HH systems, and Fisher scale in predicting prognosis and are readily available.
Protocol for a systematic literature review and network meta-analysis of the clinical benefit of inhaled maintenance therapies in chronic obstructive pulmonary disease
Authors: Lewis Adam , Axson Eleanor L , Potts James , Tarnowska Renelle , Vioix Helene , Quint Jennifer K
Published: February 2019

Introduction

Chronic obstructive pulmonary disease (COPD) exacerbations progress the course of disease and impair lung function. Inhaled maintenance therapy reduces exacerbations. It is not yet established which inhaled therapy combination is best to reduce exacerbations, lung function decline and symptom burden.

Methods and analysis

MEDLINE, EMBASE and the Cochrane Library will be searched for articles between January 2011 and May 2018 using a pre-specified search strategy. Conference proceedings will be searched. Systematic reviews (with or without meta-analysis), randomised controlled trials (RCTs), cohort studies and case controlled studies comparing six interventions comprising different combinations of long-acting bronchodilators and inhaled corticosteroids in unison or on their own. The primary outcome is the reduction in moderate-to-severe exacerbations. Secondary outcomes include: lung function, quality of life, mortality and other adverse events. Titles and abstracts will screened by the primary researcher. A second reviewer will repeat this on a proportion of records. The Population, Intervention, Comparator, Outcomes and Study framework will be used for data extraction. A network meta-analyses of outcomes from RCTs and real-world evidence will be integrated if feasible. The 95% credible interval will be used to assess the statistical significance of each summary effect. Ranking of interventions will be based on their surface under cumulative ranking area.

Ethics and dissemination

COPD exacerbations are burdensome to patients. We aim to report results that provide clinicians with a more informed choice of which inhaled therapy combinations are best to reduce exacerbations, improve disease burden and reduce lung function and exercise capacity decline, compared with the potential harms, in certain populations with COPD.

PROSPERO registration number

CRD42018088013.
Cardiovascular, antidepressant and immunosuppressive drug use in relation to risk of cutaneous melanoma: a protocol for a prospective case–control study
Authors: Berge Leon Alexander Mclaren , Andreassen Bettina Kulle , Stenehjem Jo Steinson , Larsen Inger Kristin , Furu Kari , Juzeniene Asta , Roscher Ingrid , Heir Trond , Green Adele , Veierød Marit Bragelien , Robsahm Trude Eid
Published: February 2019

Introduction

The incidence of cutaneous melanoma (hereafter melanoma) has increased dramatically among fair-skinned populations worldwide. In Norway, melanoma is the most rapidly growing type of cancer, with a 47% increase among women and 57% among men in 2000–2016. Intermittent ultraviolet exposure early in life and phenotypic characteristics like a fair complexion, freckles and nevi are established risk factors, yet the aetiology of melanoma is multifactorial. Certain prescription drugs may have carcinogenic side effects on the risk of melanoma. Some cardiovascular, antidepressant and immunosuppressive drugs can influence certain biological processes that modulate photosensitivity and immunoregulation. We aim to study whether these drugs are related to melanoma risk.

Methods and analysis

A population-based matched case–control study will be conducted using nation-wide registry data. Cases will consist of all first primary, histologically verified melanoma cases diagnosed between 2007 and 2015 identified in the Cancer Registry of Norway (14 000 cases). Ten melanoma-free controls per case (on date of case melanoma diagnosis) will be matched based on sex and year of birth from the National Registry of Norway. For the period 2004—2015, and by using the unique personal identification numbers assigned to all Norwegian citizens, the case–control data set will be linked to the Norwegian Prescription Database for information on drugs dispensed prior to the melanoma diagnosis, and to the Medical Birth Registry of Norway for data regarding the number of child births. Conditional logistic regression will be used to estimate associations between drug use and melanoma risk, taking potential confounding factors into account.

Ethics and dissemination

The project is approved by the Regional Committee for Medical Research Ethics in Norway and by the Norwegian Data Protection Authority. The study is funded by the Southeastern Norway Regional Health Authority. Results will be published in peer-reviewed journals and disseminated further through scientific conferences, news media and relevant patient interest groups.
Secreted frizzled-related protein 5 suppresses aggressive phenotype and reverses docetaxel resistance in prostate cancer
Authors: Xu Qiang , Lü Zhong , Wang Xugang , Zhu Qingxian , Wu Haoran
Published: February 2019

Secreted frizzled-related protein 5 (SFRP5) has been reported to be downregulated in prostate cancer. However, its biological role in this malignancy has not been clarified yet. In the present study, we performed SFRP5 overexpression experiments to determine its function in prostate cancer cell growth, invasion, tumorigenesis, and docetaxel sensitivity. Our results showed that overexpression of SFRP5 significantly suppressed the proliferation and colony formation of PC-3 and DU-145 cells, compared with vector-transfected control cells. SFRP5 overexpression arrested PC-3 and DU-145 cells at G0/G1 phase and induced apoptosis. Transwell invasion assay revealed that ectopic expression of SFRP5 inhibited the invasion of PC-3 cells. Overexpression of SFRP5 resensitized docetaxel-resistant PC-3 and DU-145 cells to docetaxel, which was coupled with increased apoptosis. Mechanistically, SFRP5 overexpression blocked β-catenin nuclear translocation and transcriptional activity. In vivo studies confirmed that overexpression of SFRP5 significantly suppressed the growth of PC-3 xenograft tumors. SFRP5-transfected xenograft tumors showed a reduction in the percentage of Ki-67-positive proliferating cells and an increase in terminal deoxynucleotidyl transferasebiotin-dUTP nick end labeling-positive cells. These data suggest that SFRP5 overexpression suppresses the aggressive phenotype of prostate cancer cells and overcomes docetaxel resistance through inactivation of β-catenin signaling. Therefore, delivery of SFRP5 may offer therapeutic benefits in the treatment of prostate cancer.
General surgical training for Operation Trenton
Authors: Khan Mansoor
Published: February 2019

The UK military commitment to United Nations operations has led to a new challenge in identifying and developing skill sets required for humanitarian operations. The last two decades have concentrated on kinetic operations, with haemorrhage control being the main driver. The austere location and prolonged evacuation timelines have led to identifying management strategies of conditions that would previously have been evacuated to higher echelons of care. The Defence Medical Services have a multifaceted approach to training military personnel for operations, varying from regular exposure to high-acuity trauma and general surgery within their host NHS Trust, to validated training platforms that evolve continually to address the training needs demanded by differing fields of conflict.
L-sepiapterin restores SLE serum-induced markers of endothelial function in endothelial cells
Authors: Jones Buie Joy N , Pleasant Jenkins Dorea , Muise-Helmericks Robin , Oates Jim C
Published: February 2019

Objective

SLE serves as an independent risk factor` for endothelial dysfunction (ED) not explained by Framingham risk factors. We sought to understand the development of SLE-induced ED on a cellular level in order to develop strategies aimed at reversing cellular abnormalities. This study assessed the impact of SLE patient serum on endothelial nitric oxide synthase (eNOS), nitric oxide (NO) production and functional changes in the cell.

Methods

Human umbilical vein endothelial cells (HUVECs) cultured in serum of either SLE (n=25) or healthy patients (n=14) or endothelial basal medium 2 (EBM-2) culture media supplemented with fetal bovine serum with or without L-sepiapterin were used for our studies. We applied the fluorescent probe DAF-FM diacetate for intracellular NO detection using flow cytometry. Total RNA isolates were analysed using reverse transcription PCR for eNOS mRNA expression. Oxygen consumption rate was determined using seahorse analysis. Neutrophil adhesion and migration were determined using a calcein AM microscopy assay.

Results

The mRNA expression of eNOS was increased in SLE cultured HUVECs compared with healthy control (p<0.05). The SLE eNOS mRNA level correlated with SLE patient age (p=0.008); however, this trend was not observed with healthy patients. SLE serum reduced NO production in HUVECs compared with EBM-2 cultured cells (p<0.05). Co-treatment of endothelial cells with L-sepiapterin preserved HUVEC capacity to produce NO in SLE conditions (p<0.01). SLE serum enhanced neutrophil migration (p<0.01) but not neutrophil adhesion compared with healthy controls. The bioenergetic health index was not different.

Conclusions

SLE likely causes disruption of endothelial cell eNOS function and NO modulated pathways.
Investigation of behavior of footings over rigid inclusion-reinforced soft soil: experimental and numerical approaches
Authors: Pham Hung V. , Briançon Laurent , Dias Daniel , Racinais Jérôme
Published: February 2019

The aim of this study is to investigate the behavior of a footing lying directly upon a rigid inclusion-reinforced soft soil. Both experimental and numerical approaches were conducted. The studied cases include single rigid inclusion tests, a footing over nonrigid inclusion-reinforced soil, and a footing over rigid inclusion-reinforced soil. The vertical loading tests on single rigid inclusions and the footing over unreinforced soil showed the behavior of the multi-layered soil, thus allowing for the determination of soil parameters for the numerical analyses. The tests on the footing over reinforced soil were, furthermore, carried out with different loading cases (centered and eccentric vertical loads and horizontal loads). Special attention was paid to the influence of the complex loading cases on the footing over a reinforced soil system by the measurement of the inclusion head pressure, the vertical and lateral footing settlements, and the lateral inclusion displacements. The measured pressure on the inclusion seemed to increase linearly with the vertical loading on the footing. A good agreement between the numerical analysis results and measurement data has been found for the loading phases while underprediction appears for a few loading cycles, probably due to the simplified soil constitutive model adopted.
Contributions of Rho-kinase and AMP-related kinase signaling pathways to responses mediated by endothelium-derived contracting factors in diabetic rat aorta
Authors: Balcilar Cennet , Ozakca-Gunduz Isil , Altan V. Melih
Published: February 2019

Diabetes-induced endothelial damage leads to vascular dysfunction. The current study investigated the effects of short-term (4-week) streptozotocin (STZ)-induced diabetes on responses mediated by endothelium-derived contracting factors (EDCFs) as well as possible contributions of Rho-kinase and AMP-activated kinase (AMPK) signaling pathways. The effects of STZ-diabetes on vascular function were examined in isolated thoracic aorta preparations of 30-week-old rats (n = 27). The diabetes-associated changes in vascular function were studied with calcium ionophore A23187, acetylcholine, Rho-kinase inhibitor Y27632 ((R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride), and AMPK activator AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside). The phosphorylation of acetyl-CoA carboxylase, AMPK, and phospholamban and the protein levels of sarcoplasmic/endoplasmic Ca2+-ATPase 2 (SERCA2) and Rho-associated protein kinase (ROCKII) were measured in aortic preparations. Although the acetylcholine-mediated relaxation responses were preserved in 4-week STZ-induced diabetes, the increased activation of the Rho-kinase pathway was demonstrated via twofold enhancement in A23187-mediated contractile responses and significantly augmented protein levels of ROCKII. The AICAR-activated AMPK-mediated relaxation response was also augmented ∼4-fold in diabetic rats, without any alteration in phospholamban phosphorylation; further, this relaxation response suppressed A23187-mediated contraction in both groups. Diabetic rats showed an increase in AICAR-induced AMPK-mediated vasorelaxation and a 2.5-fold elevation of phosphorylated AMPK levels. These results indicate a possible compensation between hyperglycemia-induced endothelium-dependent hypercontractility and AMPK-mediated vasorelaxation in diabetes.
Effect of component volume ratio on the absorption spectra of Ag@Fe3O4 core–shell nanoparticles
Authors: Zhang Weichun , Fan Jiyu
Published: February 2019

In this paper, we study the absorption efficiency spectra and electric field distribution of Ag nanoparticles enveloped with [Formula: see text] nanoshell by applying the discrete dipole approximation theory. Three kinds of [Formula: see text] core–shell nanoparticles (NPs) structural variables, including the same core with different shell thickness, the same outer shell with different core radius, and the same size of total radius have been discussed in detail. The simulated results show that the localized surface plasmon resonance (LSPR) peak wavelength of NPs is linearly proportional with the volume fraction of the shell, regardless of the outer shell material property and one structural variable. Compared to the plasmon resonance peak of the Ag nanoparticles, the LSPR shift of the NPs is dependent on both the total particles size and the outer [Formula: see text] shell thickness. The electric field around the surface of NPs becomes weaker under the same damping when the core radius decreases. Based on the plasmonic characteristics revealed in this study, it is suggested that it would provide some key guidances for designing the future NPs structural variables for a broad range of plasmon applications.
Impurity effects in Debye–Waller factors of bcc crystals based on anharmonic correlated Einstein model
Authors: Vuong Dinh Quoc , Hung Nguyen Van
Published: February 2019

Impurity effects in Debye–Waller factors (DWFs) describing thermodynamic properties of bcc impure crystals included in X-ray absorption fine structure (XAFS) have been studied based on the anharmonic correlated Einstein model. The impurity is obtained by replacing absorber of host element by an atom of doping element. Analytical expressions of DWFs presented in terms of cumulant expansion up to the third-order and thermal expansion coefficient of impure crystals have been derived. Anharmonic effective potential of impure crystal includes interactions of absorber and backscatterer atoms with their first shell near neighbors. Morse potential is assumed to describe single-pair atomic interaction. The obtained expressions for impure crystal can also be used for calculating the considered XAFS quantities of pure material based on replacing all data of the doping atoms by those of pure host element. The advantage of using the anharmonic effective potential is shown by its possibility of defining the difference of XAFS quantities between the two inverse doping processes, which cannot be obtained by using the single-pair potential. Numerical results are found to be in good agreement with experiment for the impure Fe doped by Mo or inversely for Mo doped by Fe, as well as for pure Fe and Mo.
How Good Can Single-Particle Cryo-EM Become? What Remains Before It Approaches Its Physical Limits?
Authors: Glaeser Robert M.
Published: February 2019

Impressive though the achievements of single-particle cryo–electron microscopy are today, a substantial gap still remains between what is currently accomplished and what is theoretically possible. As is reviewed here, twofold or more improvements are possible as regards ( a) the detective quantum efficiency of cameras at high resolution, ( b) converting phase modulations to intensity modulations in the image, and ( c) recovering the full amount of high-resolution signal in the presence of beam-induced motion of the specimen. In addition, potential for improvement is reviewed for other topics such as optimal choice of electron energy, use of aberration correctors, and quantum metrology. With the help of such improvements, it does not seem to be too much to imagine that determining the structural basis for every aspect of catalytic control, signaling, and regulation, in any type of cell of interest, could easily be accelerated fivefold or more.
Cellular senescence in the lung across the age spectrum
Authors: Parikh Pavan , Wicher Sarah , Khandalavala Karl , Pabelick Christina M. , Britt Rodney D. , Prakash Y. S.
Published: February 2019

Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors, and remodeling proteins (senescence-associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis, and proliferation, while hindering tissue repair and regeneration. While the role of senescence and the contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, or pulmonary fibrosis. In this review, we introduce concepts of cellular senescence, the mechanisms involved in the induction of senescence, and the SASP portfolio that are relevant to lung cells, presenting the potential contribution of senescent cells and SASP to inflammation, hypercontractility, and remodeling/fibrosis: aspects critical to a range of lung diseases. The potential to blunt lung disease by targeting senescent cells using a novel class of drugs (senolytics) is discussed. Potential areas for future research on cellular senescence in the lung are identified.
Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3)
Authors: Cabrera Sandra , Maciel Mariana , Hernández-Barrientos Daniel , Calyeca Jazmín , Gaxiola Miguel , Selman Moisés , Pardo Annie
Published: February 2019

Matrix metalloprotease 13 (MMP13) deficiency in pulmonary fibrosis has described contradictory phenotypes on inflammatory and fibrotic responses after lung injury, and its role during lung fibrosis resolution is still undefined. MMP13 has been considered the main collagenase in rodents, and the remodeling of fibrillar collagen is widely attributed to the action of this enzyme. In this study we aimed to explore the role of MMP13 during lung fibrosis progression and resolution. Lung fibrosis was induced by intratracheal instillation, and inflammatory, fibrotic, and resolution stages were evaluated in Mmp13-null and wild-type (WT) mice. Bronchoalveolar lavage fluid was taken for cytokine array analysis and activity of gelatinases. Our results showed that MMP13 is upregulated mainly during two stages after lung injury, inflammation and resolution of fibrosis, and it is mainly expressed by alveolar and interstitial macrophages. Mmp13-null mice exhibited more extensive inflammation at 7 days after bleomycin treatment, and it was characterized by increased macrophage infiltration and significant alterations in proinflammatory cytokines. We also documented that Mmp13-deficient mice experienced more severe and prolonged lung fibrosis compared with WT mice. Delayed resolution in Mmp13-deficient lungs was characterized by a decreased overall collagenolytic activity and persistent fibrotic foci associated with emphysema-like areas. Together, our findings indicate that MMP13 plays an antifibrotic role and its activity is crucial in lung repair and restoration of tissue integrity during fibrosis resolution.