bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenetics of inhaled long‐acting beta2‐agonists in asthma: A systematic review
Authors: Slob Elise M. A. , Vijverberg Susanne J. H. , Palmer Colin N. A. , Zazuli Zulfan , Farzan Niloufar , Oliveri Nadia M. B. , Pijnenburg Mariëlle W. , Koppelman Gerard H. , Maitland‐van der Zee Anke H.
Published: July 2018

Background

Long‐acting beta2‐agonists (LABA) are recommended in asthma therapy; however, not all asthma patients respond well to LABA. We performed a systematic review on genetic variants associated with LABA response in patients with asthma.

Methods

Articles published until April 2017 were searched by two authors using PubMed and EMBASE. Pharmacogenetic studies in patients with asthma and LABA response as an outcome were included.

Results

In total, 33 studies were included in this systematic review; eight focused on children (n = 6051). Nineteen studies were clinical trials, while 14 were observational studies. Studies used different outcomes to define LABA response, for example, lung function measurements (FEV1, PEF, MMEF, FVC), exacerbations, quality of life, and asthma symptoms. Most studies (n = 30) focused on the ADRB2 gene, encoding the beta2‐adrenergic receptor. Thirty studies (n = 14 874) addressed ADRB2 rs1042713, 7 ADRB2 rs1042714 (n = 1629), and 3 ADRB2 rs1800888 (n = 1892). The association of ADRB2 rs1042713 and rs1800888 with LABA response heterogeneity was successfully replicated. Other variants were only studied in three studies but not replicated. One study focused on the ADCY9 gene. Five studies and a meta‐analysis found an increased risk of exacerbations in pediatrics using LABA carrying one or two A alleles (OR 1.52 [1.17; 1.99]). These results were not confirmed in adults.

Conclusions

ADRB2 rs1042713 variant is most consistently associated with response to LABA in children but not adults. To assess the clinical value of ADRB2 rs1042713 in children with asthma using LABA, a randomized clinical trial with well‐defined outcomes is needed.
Interspecific compatibility barriers, development of interspecific hybrids through embryo rescue and lineage ofTrifolium alexandrinum(Egyptian clover)—important tropical forage legume
Authors: Malaviya Devendra R. , Roy Ajoy K. , Kaushal Pankaj , Chakraborti Mridul , Yadav Aradhana , Khare Ambica , Dhir Richa , Khairnar Dushyant , George Ginu Percis
Published: July 2018

Genetic improvement ofTrifolium alexandrinumL. is hampered because of narrow genetic base and lack of interspecies compatibility information. The study was envisaged to understand the interspecies incompatibility and the affinity betweenT. alexandrinumand 22 species of the genus representing different sections and to develop interspecific crosses. Development of interspecific hybrids withT. resupinatum, T. lappaceum, T. subterraneum, T. vesiculosumandT. echinatum,through embryo rescue, revealed their affinity withT. alexandrinum. Failure of pollen germination or restricted pollen tube growth showed its distant relatedness withT. clypeatum, T. balansae, T. purpureum, T. leucanthum, T. hirtum, T. pilulareandT. hybridum. Pollen tubes reached up to ovule among the crosses withT. alpestre, T. repensandT. nigrescens,whereas it travelled up to ovary among the crosses withT. angustifolium, T. grandiflorumandT. dasyurumindicating need of manipulation to overcome barrier. Thus, incompatibility ofT. alexandrinumwith manyTrifoliumspecies could be overcome through embryo rescue with intensive crossing. Egyptian clover ecotype ‘Fahli’ was more compatible with other species than ‘Mescavi’.
Characterization of broad‐spectrum resistance to Soybean mosaic virus in soybean [Glycine max (L.) Merr.] cultivar ‘RN‐9’
Authors: Ren Rui , Yin Jinlong , Zheng Huanfang , Wang Tao , Liu Shichao , Karthikeyan Adhimoolam , Yang Qinghua , Gao Le , Zhi Haijian , Li Kai
Published: July 2018

Soybean mosaic virus (SMV) can cause serious yield losses in soybean. Soybean cultivar ‘RN‐9’ is resistant to 15 of 21 SMV strains. To well‐characterize this invaluable broad‐spectrum SMV‐resistance, populations (F1, F2 and F2:3) derived from resistant (R) × susceptible (S) and R × R crosses were tested for SMV‐SC18 resistance. Genetic analysis revealed that SC18 resistance in ‘RN‐9’ plus two elite SMV‐resistant genotypes (‘Qihuang No.1’ and ‘Kefeng No.1’) are controlled by independently single dominant genes. Linkage analysis showed that the resistance of ‘RN‐9’ to SMV strains SC10, SC14, SC15 and SC18 is controlled by more than one gene(s). Moreover, Rsc10‐r and Rsc18‐r were both positioned between the two simple sequence repeats markers Satt286 and Satt277, while Rsc14‐r was fine‐mapped in 136.8‐kb genomic region containing sixteen genes, flanked by BARCSOYSSR_06_0786 and BARCSOYSSR_06_0790 at genetic distances of 3.79 and 4.14 cM, respectively. Allelic sequence comparison showed that Cytochrome P450‐encoding genes (Glyma.06g176000 and Glyma.06g176100) likely confer the resistance to SC14 in ‘RN‐9’. Our results would facilitate the breeding of broad‐spectrum and durable SMV resistance in soybeans.
Carbon and oxygen isotope fractionations in tree rings reveal interactions between cambial phenology and seasonal climate
Authors: Belmecheri Soumaya , Wright William E. , Szejner Paul , Morino Kiyomi A. , Monson Russell K.
Published: July 2018

We developed novel approaches for using the isotope composition of tree‐ring subdivisions to study seasonal dynamics in tree–climate relations. Across a 30‐year time series, the δ13C and δ18O values of the earlywood (EW) cellulose in the annual rings of Pinus ponderosa reflected relatively high intrinsic water‐use efficiencies and high evaporative fractionation of 18O/16O, respectively, compared with the false latewood (FLW), summerwood (SW), and latewood (LW) subdivisions. This result is counterintuitive, given the spring origins of the EW source water and midsummer origins of the FLW, SW, and LW. With the use of the Craig–Gordon (CG), isotope‐climate model revealed that the isotope ratios in all of the ring subdivision are explained by the existence of seasonal lags, lasting several weeks, between the initial formation of tracheids and the production of cellulosic secondary cell walls during maturation. In contrast to some past studies, modification of the CG model according to conventional methods to account for mixing of needle water between fractionated and nonfractionated sources did not improve the accuracy of predictions. Our results reveal new potential in the use of tree‐ring isotopes to reconstruct past intra‐annual tree–climate relations if lags in cambial phenology are reconciled with isotope ratio observations and included in theoretical treatments.
Outcome of treosulfan‐based reduced‐toxicity conditioning regimens for HSCT in high‐risk patients with primary immune deficiencies
Authors: Haskoloğlu Şule , Köstel Bal Sevgi , İslamoğlu Candan , Altun Demet , Kendirli Tanıl , Doğu Esin Figen , İkincioğulları Aydan
Published: July 2018

Introduction

HSCT is the curative therapeutic option in PIDs. Due to the increase in survival rates, reduced‐toxicity conditioning regimens with treosulfan have become another alternative. The purpose of this retrospective study was to analyze the outcome of treosulfan‐based conditioning before HSCT for patients with PID.

Method

A total of 15 patients that received a treosulfan‐based conditioning regimen for HSCT were recruited. Type of diagnosis, donor and stem cell source, pretransplant organ damage, infections, engraftment, chimerism, and transplant‐related toxicities were analyzed.

Results

At a median follow‐up time of 32 months, the overall survival was 86.7%. Following HSCT, 14 of 15 patients had engraftment, with 86.7% of the cohort having full‐donor chimerism. The most common toxicity was seen on the skin (53.3%). Acute GVHD and chronic GVHD were documented in 53% and 20% of the study population, respectively. Although the cohort consisted of patients with pretransplant liver damage, SOS manifestations were documented in 20%.

Conclusion

Treosulfan‐based conditioning regimens before HSCT are associated with lower toxicity compared to myeloablative regimens, are safe, and have high engraftment rates with full‐donor chimerism in patients having PID, regardless of the specified genetic diagnosis and donor type.
Transcatheter stenting of superior vena cava obstruction after pediatric heart transplantation: A single‐center experience assessing risk factors and outcomes
Authors: Salavitabar Arash , Flyer Jonathan N. , Torres Alejandro J. , Richmond Marc E. , Crystal Matthew A. , Turner Mariel E. , Chai Paul , Zuckerman Warren A.
Published: July 2018

Transcatheter stent implantation for SVC obstruction following OHT has been well described, particularly in pediatric patients. This study describes a large single‐center pediatric heart transplant experience that investigates the risk factors for SVC stenosis requiring stent implantation and its associated outcomes. All pediatric OHTs between January 1, 2000, and December 12, 2016, were examined for risk factors. Twelve of 349 (3.4%) OHTs required SVC stent implantation. Patients who required stents were younger (2.5 years vs 10.0 years, P = 0.0097), weighed less (8.6 kg vs 26.0 kg, P = 0.0024), and were more likely to have had CHD (83% vs 32%, P = 0.001) or previous SCPA (58% vs 18%, P = 0.002). Bicaval anastomosis was not associated with subsequent SVC stent implantation. Symptoms included SVC syndrome and chylous effusions. All 12 patients had evidence of significant SVC obstruction by both echocardiographic Doppler interrogation and transcatheter angiography. There were no acute procedural complications; however, reinterventions were common (four of 12 patients) and occurred at a mean of 5.7 ± 3.6 months poststent implantation. In conclusion, transcatheter SVC stent implantation is safe and effective after OHT. There were significant associations between SVC stent implantation and younger age, smaller weight, CHD, and history of SCPA, but not with bicaval anastomosis or donor‐recipient weight ratio.
Hypoxia and the group VII ethylene response transcription factor HRE2 promote adventitious root elongation inArabidopsis
Authors: Eysholdt‐Derzsó E. , Sauter M.
Published: July 2018

Soil water‐logging and flooding are common environmental stress conditions that can impair plant fitness. Roots are the first organs to be confronted with reduced oxygen tension as a result of flooding. While anatomical and morphological adaptations of roots are extensively studied, the root system architecture is only now becoming a focus of flooding research. Adventitious root (AR) formation shifts the root system higher up the plant, thereby facilitating supply with oxygen, and thus improving root and plant survival.

We usedArabidopsisknockout mutants and overexpressors of ERFVII transcription factors to study their role in AR formation under hypoxic conditions and in response to ethylene.

Results show that ethylene inhibits AR formation. Hypoxia mainly promotes AR elongation rather than formation mediated by ERFVII transcription factors, as indicated by reduced AR elongation inerfVIIseedlings. Overexpression of HRE2 induces AR elongation to the same degree as hypoxia, while ethylene overrides HRE2‐induced AR elongation.

The ERFVII transcription factors promote establishment of an AR system that is under negative control by ethylene. Inhibition of growth of the main root system and promotion of AR elongation under hypoxia strengthens the root system in upper soil layers where oxygen shortage may last for shorter time periods.
Disease state changes and safety of long‐term donepezil hydrochloride administration in patients with Alzheimer's disease: Japan‐Great Outcome of Long‐term trial with Donepezil (J‐GOLD)
Authors: Arai Heii , Hashimoto Naoyuki , Sumitomo Kenta , Takase Takao , Ishii Mika
Published: July 2018

Background

A long‐term, large‐scale study of donepezil hydrochloride in patients with Alzheimer's disease (AD) was conducted. Previously, two interim reports were published during this study. We have now completed the study and herein present our analysis of the final results.

Methods

The subjects of this study included AD patients who received the drug for the first time (newly treated patients), as well as AD patients who were already receiving the drug at the start of the study (continuously treated patients). The observation period was 48 months. Changes in cognitive function and severity of dementia associated with the drug administration and its safety were assessed.

Results

Cognitive function decreased significantly after 24 months in newly treated patients and after 6 months in continuously treated patients, compared with baseline. The percentages of patients whose dementia severity improved or remained the same compared with baseline were 59.27% at 48 months in the newly treated patients and 57.09% at 48 months in the continuously treated patients. There were no major safety problems with the drug.

Conclusions

We conducted a large‐scale study of AD patients in Japan. Here, we present our analysis of the final results and describe current clinical practice with the drug, changes in cognitive function and dementia severity associated with long‐term administration of the drug, and the drug's safety.
The monocyte locomotion inhibitory factor inhibits the expression of inflammation‐induced cytokines following experimental contusion in rat tibia
Authors: Rojas‐Dotor Sara , Araujo‐Monsalvo Víctor Manuel , Sánchez‐Rojas Marco Julio , Domínguez‐Hernández Víctor Manuel
Published: July 2018

Entamoeba histolityca produces the monocyte locomotion inhibitory factor (MLIF), a pentapeptide with powerful anti‐inflammatory properties. MLIF may regulate trauma‐induced inflammation through the effects it exerts directly or indirectly on immune cells, modulating the production and/or expression of the cytokines involved in the inflammatory processes that occur after damage. The aim of the present study was to evaluate the effect of MLIF on production of pro/anti‐inflammatory cytokines after contusion in the rat tibia. Fifty‐four Wistar rats were subjected to controlled contusion with a special guillotine‐type device, and 36 rats were injected with MLIF or tenoxicam into the tibia. Eighteen animals received saline; the animals were sacrificed 24 or 48 hours after injection. Cytokine mRNA and protein production were determined by reverse transcriptase‐polymerase chain reaction (RT‐PCR), immunofluorescence, and hematoxylin‐eosin staining was performed to visualize cellular infiltration in the rats’ injured tissue. Expression levels of the cytokines interferon gamma (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6) and transforming growth factor‐beta (TGF‐β) mRNA were inhibited significantly by MLIF at 24 hours post‐contusion. MLIF significantly increased the expression levels of IL‐10 at 24 hours compared with tenoxicam or the control group. These changes were associated with a significant decrease in protein production levels of TNF‐α, IFN‐γ, IL‐6 and TGF‐β at 24 hours. Histological evaluation showed the presence of infiltration by neutrophils, monocytes and leucocytes in control tissues. This infiltration was decreased after MLIF administration, and intense infiltration was observed in tenoxicam‐treated group. MLIF inhibited the expression of pro‐inflammatory cytokines and increased the expression of anti‐inflammatory cytokine IL‐10.
The performance of the Australian welfare system in a time of neoliberal economic reform
Authors: Tapper Alan
Published: July 2018

“Neoliberalism”, both as a body of theory and as a set of policies and practices, is commonly seen as unsympathetic, even antagonistic, to the welfare state. In the period from the mid‐1980s to the global financial crisis of 2007–08, Australia underwent very considerable “neoliberal” economic policy reform. What happened to the Australian welfare system and to Australia's socioeconomic egalitarianism in this period? To shed light on that question three kinds of trend are tracked. The first is household taxes and social expenditure in both cash and kind, using fiscal incidence analysis where the main metric is “net benefits”. The second is economic inequality, as measured by the distribution of incomes and wealth. The third is the performance of the labor market, as measured by earned incomes and unemployment rates. The article concludes with an attempt to integrate the evidence collected from these three sources. The general conclusion is that the Australian welfare system did not follow the pessimists' predictions. The welfare system grew in size and redistributive quantum. Wage levels rose strongly, while unemployment rates fell. Overall, income inequality increased to a small extent, though mainly before the full economic reform process was in place, while wealth inequality changed little.
A formula for a two‐dice horse race
Authors: Meyer Joerg
Published: July 2018

A formula is derived for a ‘two‐dice horse race’, in which two ordinary dice are thrown repeatedly and each time the sum of the scores determines which horse (numbered 2 to 12) moves forward one space.

This paper answers a question posed in a former Teaching Statistics article, and demonstrates the value of simulation.
Inferential statistics made fun: stories that boxes of ‘100 paper clips’ can tell
Authors: Roy Sudipta
Published: July 2018

The natural experiment proposed in this article extracts three stories from boxes of “100 paper clips”. The activity requires students to apply three lessons from inferential statistics, starting with a hypothesis test and including confidence intervals as well as tolerance intervals.
Is Global Management of Anti-Global Warming Policies at All Feasible?
Authors: Lane Jan-Erik
Published: July 2018

Climate and earth scientists now predicting abrupt climate change never ask the social sciences whether large scale policy-making and international coordination, like the COP21 project, is all feasible. The message from policy analysis is that rational decision-making is a myth, as there is bound to be mistakes, confusion and opportunism in policy implementation. Is it better for each state to develop its own climate policy – the resilience option? However, when looking at energy planning by core states, one finds little of decarbonisation. Only Uruguay has good preparation for global warming. Abrupt climate change threatens numerous tipping points towards Hawking irreversibility. But the social sciences are skeptical about large scale policy implementation based upon comprehensively rational decision-making.
A Second-Order Scheme for Nonlinear Fractional Oscillators Based on Newmark-β Algorithm
Authors: Liu Q. X. , Liu J. K. , Chen Y. M.
Published: July 2018

This paper presents an accurate and efficient hybrid solution method, based on Newmark-β algorithm, for solving nonlinear oscillators containing fractional derivatives (FDs) of arbitrary order. Basically, this method employs a quadrature method and the Newmark-β algorithm to handle FDs and integer derivatives, respectively. To reduce the computational burden, the proposed approach provides a strategy to avoid nonlinear algebraic equations arising routinely in the Newmark-β algorithm. Numerical results show that the presented method has second-order accuracy. Importantly, it can be applied to both linear and nonlinear oscillators with FDs of arbitrary order, without losing any precision and efficiency.
Bayesian inference for the ultrasonic characterization of rigid porous materials using reflected waves by the first interface
Authors: Roncen R. , Fellah Z. E. A. , Simon F. , Piot E. , Fellah M. , Ogam E. , Depollier C.
Published: July 2018

The purpose of this paper is to present a method for the ultrasonic characterization of air-saturated porous media, by solving the inverse problem using only the reflected waves from the first interface to infer the porosity, the tortuosity, and the viscous and thermal characteristic lengths. The solution of the inverse problem relies on the use of different reflected pressure signals obtained under multiple obliquely incident waves, in the time domain. In this paper, the authors propose to solve the inverse problem numerically with a first level Bayesian inference method, summarizing the authors' knowledge on the inferred parameters in the form of posterior probability densities, exploring these densities using a Markov-Chain Monte-Carlo approach. Despite their low sensitivity to the reflection coefficient, it is still possible to extract the knowledge of the viscous and thermal characteristic lengths, allowing the simultaneous determination of all the physical parameters involved in the expression of the reflection operator. To further constrain the problem and guide the inference, the knowledge of a particular incident angle is used at one's advantage in order to more precisely define the thermal length, by effectively yielding a statistical relationship between tortuosity and characteristic length ratio.
Improving competing voices segregation for hearing impaired listeners using a low-latency deep neural network algorithm
Authors: Bramsløw Lars , Naithani Gaurav , Hafez Atefeh , Barker Tom , Pontoppidan Niels Henrik , Virtanen Tuomas
Published: July 2018

Hearing aid users are challenged in listening situations with noise and especially speech-on-speech situations with two or more competing voices. Specifically, the task of attending to and segregating two competing voices is particularly hard, unlike for normal-hearing listeners, as shown in a small sub-experiment. In the main experiment, the competing voices benefit of a deep neural network (DNN) based stream segregation enhancement algorithm was tested on hearing-impaired listeners. A mixture of two voices was separated using a DNN and presented to the two ears as individual streams and tested for word score. Compared to the unseparated mixture, there was a 13%-point benefit from the separation, while attending to both voices. If only one output was selected as in a traditional target-masker scenario, a larger benefit of 37%-points was found. The results agreed well with objective metrics and show that for hearing-impaired listeners, DNNs have a large potential for improving stream segregation and speech intelligibility in difficult scenarios with two equally important targets without any prior selection of a primary target stream. An even higher benefit can be obtained if the user can select the preferred target via remote control.
Plasticity reveals hidden resistance to extinction under climate change in the global hotspot of salamander diversity
Authors: Riddell Eric A. , Odom Jonathan P. , Damm Jason D. , Sears Michael W.
Published: July 2018

Integrating physiological and behavioral plasticity into climate change models markedly reduces predicted extinction risk.
BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance
Authors: Matsushita Takashi , Kobayashi Tadahiro , Mizumaki Kie , Kano Miyu , Sawada Tomoyo , Tennichi Momoko , Okamura Ai , Hamaguchi Yasuhito , Iwakura Yoichiro , Hasegawa Minoru , Fujimoto Manabu , Takehara Kazuhiko
Published: July 2018

IL-6–producing effector B cells play a pathogenic role, while IL-10–producing regulatory B cells play a protective role in a scleroderma model.
Establishment of environmentally sensitive DNA methylation states in the very early human embryo
Authors: Kessler Noah J. , Waterland Robert A. , Prentice Andrew M. , Silver Matt J.
Published: July 2018

We have tracked DNA methylation dynamics at metastable epialleles across multiple developmental stages in the early human embryo.
Small Regulatory RNAs in the Enterobacterial Response to Envelope Damage and Oxidative Stress
Authors: Fröhlich Kathrin S. , Gottesman Susan
Published: July 2018

The ability of bacteria to thrive in diverse habitats and to adapt to ever-changing environmental conditions relies on the rapid and stringent modulation of gene expression. It has become evident in the past decade that small regulatory RNAs (sRNAs) are central components of networks controlling the bacterial responses to stress. Functioning at the posttranscriptional level, sRNAs base-pair with cognate mRNAs to alter translation, stability, or both to either repress or activate the targeted transcripts; the RNA chaperone Hfq participates in stabilizing sRNAs and in promoting pairing between target and sRNA. In particular, sRNAs act at the heart of crucial stress responses, including those dedicated to overcoming membrane damage and oxidative stress, discussed here. The bacterial cell envelope is the outermost protective barrier against the environment and thus is constantly monitored and remodeled. Here, we review the integration of sRNAs into the complex networks of several major envelope stress responses of Gram-negative bacteria, including the RpoE (σ
E
), Cpx, and Rcs regulons. Oxidative stress, caused by bacterial respiratory activity or induced by toxic molecules, can lead to significant damage of cellular components. In
Escherichia coli
and related bacteria, sRNAs also contribute significantly to the function of the RpoS (σ
S
)-dependent general stress response as well as the specific OxyR- and SoxR/S-mediated responses to oxidative damage. Their activities in gene regulation and crosstalk to other stress-induced regulons are highlighted.
GOAL study: clinical and non-clinical predictive factors for achieving glycemic control in people with type 2 diabetes in real clinical practice
Authors: Al Mansari Abdulqawi , Obeid Youssef , Islam Najmul , Fariduddin Mohammed , Hassoun Ahmed , Djaballah Khier , Malek Mojtaba , Dicker Dror , Chaudhury Tirthankar
Published: July 2018

Objective

The American Diabetes Association and the European Association for the Study of Diabetes guidelines recommend to individualize treatment targets/strategies in inadequately controlled patients by lifestyle management and glucose-lowering drugs to decrease the burden of diabetes-related complications. This real-world practice study aimed to assess predictive factors for achieving the glycemic hemoglobin A1c (HbA1c) at 6 months as targeted by the treating physician in adults with type 2 diabetes who required initiation of basal insulin, initiation of bolus insulin, or modification from basal or premixed insulin to new insulin regimen containing insulin glargine and/or insulin glulisine. 

Research design and methods

This was an international, multicenter, observational survey with 12-month follow-up time in adults with type 2 diabetes inadequately controlled conducted in 10 developing countries. 

Results

Overall, 2704 patients (mean age: 54.6 years, body mass index: 28.7 kg/m2; Caucasian: 46.1%, type 2 diabetes duration: 10.1 years) with poor glycemic control (mean HbA1c: 9.7% (83 mmol/mol), fasting blood glucose: 196.8 mg/dL) were eligible. At 6 months, advanced age, Caucasian ethnicity, shorter type 2 diabetes duration (>10 vs 1 year, p<0.0001), lower baseline HbA1c (≥ 8.5% vs <7%, p<0.0001) and no intake of oral antidiabetic drug (OAD) (none vs 2, p=0.02) were predictive factors for achieving glycemic goal as targeted by the treating physician. Absolute changes in the mean HbA1c of −1.7% and −2% were observed from baseline to 6 and 12 months, respectively. 

Conclusions

Along with some well-known predictive factors, this study suggested that early insulin regimen treatment initiation and/or intensification allowed patients to promote glycemic control.
Gaps in health behaviours and use of preventive services between patients with diabetes and the general population: a population-based cross-sectional study
Authors: Shin Hyun-Young , Park Sohee , Park Sang Min
Published: July 2018

Objectives

Although both the prevalence and treatment rate of diabetes have increased, the degree of adherence to healthy behaviours by patients with diabetes has not yet been comprehensively evaluated. This study examines the differences in health management and mental health status according to diabetes status and awareness of that diagnosis.

Methods

This was a cross-sectional study of 14 655 people using data from the Korean National Health and Nutrition Examination Study 2010–2012, which used sampling weights. Multiple logistic regression analyses were used to compare health-risk behaviours, preventive healthcare utilisation and mental health status according to diabetes diagnosis and awareness of the disease.

Results

Compared with people without diabetes, people with diabetes had comparably worse smoking status (adjusted OR (aOR) 1.09, 95% CI 0.92 to 1.30), insufficient physical activity (aOR 1.09, 95% CI 0.95 to 1.24) and were less likely to receive cancer screenings and regular health check-ups (aOR 0.75, 95% CI 0.66 to 0.85). Furthermore, compared with people unaware of their diabetes, people aware of their diabetes had lower odds of physical inactivity (aOR 0.66, 95% CI 0.45 to 0.99) and greater odds of receiving colon cancer screening (aOR 1.55, 95% CI 1.17 to 2.05) and influenza vaccination (aOR 1.56, 95% CI 1.15 to 2.11).

Conclusions

People with diabetes were no better in terms of health behaviours and preventive healthcare utilisation than those who were without diabetes. Further efforts and political attention to ensure the delivery of quality care for people with diabetes are needed.
Using smartphone-based virtual patients to assess the quality of primary healthcare in rural China: protocol for a prospective multicentre study
Authors: Liao Jing , Chen Yaolong , Cai Yiyuan , Zhan Nan , Sylvia Sean , Hanson Kara , Wang Hong , Wasserheit Judith N , Gong Wenjie , Zhou Zhongliang , Pan Jay , Wang Xiaohui , Tang Chengxiang , Zhou Wei , Xu Dong
Published: July 2018

Introduction

Valid and low-cost quality assessment tools examining care quality are not readily available. The unannounced standardised patient (USP), the gold standard for assessing quality, is costly to implement while the validity of clinical vignettes, as a low-cost alternative, has been challenged. Computerised virtual patients (VPs) create high-fidelity and interactive simulations of doctor-patient encounters which can be easily implemented via smartphone at low marginal cost. Our study aims to develop and validate smartphone-based VP as a quality assessment tool for primary care, compared with USP.

Methods and analysis

The study will be implemented in primary health centres (PHCs) in rural areas of seven Chinese provinces, and physicians practicing at township health centres and village clinics will be our study population. The development of VPs involves three steps: (1) identifying 10 VP cases that can best represent rural PHCs’ work, (2) designing each case by a case-specific development team and (3) developing corresponding quality scoring criteria. After being externally reviewed for content validity, these VP cases will be implemented on a smartphone-based platform and will be tested for feasibility and face validity. This smartphone-based VP tool will then be validated for its criterion validity against USP and its reliability (ie, internal consistency and stability), with 1260 VP/USP-clinician encounters across the seven study provinces for all 10 VP cases.

Ethics and dissemination

Sun Yat-sen University: No. 2017-007. Study findings will be published and tools developed will be freely available to low-income and middle-income countries for research purposes.
Schistosoma Mansoni Antigen Sm-p80: Prophylactic Efficacy using TLR4 Agonist Vaccine Adjuvant Glucopyranosyl Lipid A-Alum in Murine and Non-Human Primate Models
Authors: Zhang Weidong , Ahmad Gul , Molehin Adebayo J , Torben Workineh , Le Loc , Kim Eunjee , Lazarus Samra , Siddiqui Arif J , Carter Darrick , Siddiqui Afzal A
Published: July 2018

Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading candidate for a schistosomiasis vaccine. The prophylactic and antifecundity efficacy of Sm-p80 has been tested in three animal models (mouse, hamster and baboon) using a multitude of vaccine formulations and approaches. In our continual effort to enhance the vaccine efficacy, in this study, we have utilized the adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum) with recombinant Sm-p80. The rSm-p80+GLA-Alum immunization regimen provided 33.33%–53.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons. Robust Sm-p80-specific immunoglobulin (Ig)G, IgG1, IgG2a and IgM responses were observed in all immunized animals. The rSm-p80+GLA-Alum coadministration induced a mix of T-helper (Th) cells (Th1, Th2 and Th17) responses as determined via the release of interleukin (IL)-2, IL-4, IL-18, IL-21, IL-22 and interferon-γ.
Szegö kernel asymptotic expansion on strongly pseudoconvex CR manifolds with S1 action
Authors: Herrmann Hendrik , Hsiao Chin-Yu , Li Xiaoshan
Published: July 2018

Let [Formula: see text] be a compact connected strongly pseudoconvex Cauchy–Riemann (CR) manifold of real dimension [Formula: see text] with a transversal CR [Formula: see text] action on [Formula: see text]. We establish an asymptotic expansion for the [Formula: see text]th Fourier component of the Szegö kernel function as [Formula: see text], where the expansion involves a contribution in terms of a distance function from lower dimensional strata of the [Formula: see text] action. We also obtain explicit formulas for the first three coefficients of the expansion.
The influence of positive news on rumor spreading in social networks with scale-free characteristics
Authors: Luo Yongcong , Ma Jing
Published: July 2018

We explore the impact of positive news on rumor spreading in this paper. It is a fact that most of the rumors related to hot events or emergencies can be propagated rapidly on the hotbed of online social networks. In Chinese words, it is better to divert rather than block. Therefore, we propose the spreading model [Formula: see text] in which positive news is a good factor to guide rumor spreading. Based on transition probability method, we have got the spreading parameters of the [Formula: see text] model by running the rumor spreading process in online social networks with scale-free characteristics. The results give a good proof that improving the activity of the positive news spreader [Formula: see text] derived from the [Formula: see text] model can guide and restrain the spreading speed of rumor smoothly.
An HVS Inspired Robust Non-blind Watermarking Scheme in YCbCr Color Space
Authors: Roy Aniket , Maiti Arpan Kumar , Ghosh Kuntal
Published: July 2018

Digital Watermarking is an important tool for copyright protection. A good quality watermarking scheme should provide both perceptual transparency as well as robustness against attacks. Many efficient schemes exist for grayscale image watermarking, but relatively less attention has been paid to watermarking for color images. Moreover, the existing works do not provide adequate justification for the possible choice of color space. In this paper, justification is provided for the choice of YCbCr color space for watermark embedding. A human visual system (HVS)-inspired image-adaptive non-blind watermarking scheme in the YCbCr space has subsequently been proposed. This new algorithm has been referred to as the Additive Embedding Scheme (AES). It comprises of a modified watermarking strength parameter ([Formula: see text]), in combination with the discrete wavelet transform and singular value decomposition (DWT-SVD). Experimental results demonstrate that the proposed watermarking scheme in YCbCr color space provides better perceptual quality as well as robustness against attacks as compared to existing schemes. We have further improvised the aforementioned scheme to come up with a Multiplicative Embedding Scheme (MES) for additional robustness against a special type of attack, viz. the Singular Value Exchange Attack.
An Analysis of CNN Feature Extractor Based on KL Divergence
Authors: Zhang Jinpeng , Zhang Jinming
Published: July 2018

Convolutional neural networks (CNNs) have brought in exciting progress in many computer vision tasks. But the feature extraction process executed by CNN still keeps a black box to us, and we have not fully understood its working mechanism. In this paper, we propose a method to evaluate CNN features and further to analyze the CNN feature extractor, which is inspired by Bayes Classification Theory and KL divergence (KLD). Experiments have shown that CNN can promote feature discrimativeness by gradually increasing the intra-class KLD, and meanwhile promote feature robustness by gradually decreasing the inner-class KLD during training. Experiments also reveal that, with the deepening of network, CNN can gradually improve separability information density in feature space and encode much more separability information into the final feature vectors.
Pascal finite polynomial automorphisms
Authors: Adamus Elżbieta , Bogdan Paweł , Crespo Teresa , Hajto Zbigniew
Published: July 2018

The class of Pascal finite polynomial automorphisms is a subclass of the class of locally finite ones allowing a more effective approach. In characteristic zero, a Pascal finite automorphism is the exponential map of a locally nilpotent derivation. However, Pascal finite automorphisms are defined in any characteristic, and therefore constitute a generalization of exponential automorphisms to positive characteristic. In this paper, we prove several properties of Pascal finite automorphisms. We obtain in particular that the Pascal finite property is stable under taking powers but not under composition. This leads us to formulate a generalization of the exponential generators conjecture to arbitrary characteristic.
Advances on the development of the detection system of C-BORD’s rapidly relocatable tagged neutron inspection
Authors: Pino Felix , Fontana Cristiano Lino , Lunardon Marcello , Stevanato Luca , Sada Cinzia , Carnera Alberto , Soramel Francesca , Moretto Sandra , Nebbia Giancarlo , Sardet Alix , Carasco Cedric , Perot Bertrand , Sannie Guillaume , Iovene Alessandro , Tintori Carlo , Sibczynski Pawel , Swiderski Lukasz , Grodzicki Krystian , Moszynski Marek
Published: July 2018

The European H2020 project entitled “effective container inspection at border control point” (C-BORD) focuses on the development and in-situ tests of a comprehensive, cost-effective solution for the generalized non-intrusive inspection (NII) of containers and large-volume freight at the European Union border. The opening procedures of suspect containers are time consuming and expensive for economical and safety reasons; therefore, to reduce such operations, the C-BORD project aims to develop a set of technologies that can improve the quality of NII. Among these techniques, a tagged neutron inspection system is being developed in the C-BORD project. It will be a second-line defense system, to be used on sealed containers to detect explosives, illicit drugs, and chemical agents in suspect voxels (elementary volume units). This method employs a beam of tagged neutrons and a set of NaI(Tl) and LaBr[Formula: see text](Ce) scintillators, which will be used to detect prompt gamma rays produced by the neutron interactions. Here we report the advances on the development of the C-BORD’s rapidly relocatable tagged neutron inspection system, in particular the comprehensive characterization of the NaI(Tl) and LaBr[Formula: see text](Ce) gamma detectors (time and energy resolutions, high-count-rate behavior), the digital analysis for time-coincidence measurements and the data acquisition system (DAQ).
A Learning-Based Thermal-Sensitive Power Optimization Approach for Optical NoCs
Authors: Zhang Zhe , Ye Yaoyao
Published: July 2018

Optical networks-on-chip (NoCs) based on silicon photonics have been proposed as emerging on-chip communication architectures for chip multiprocessors with large core counts. However, due to the thermal sensitivity of optical devices used in optical NoCs, on-chip temperature variations cause significant thermal-induced optical power loss, which would counteract the power advantages of optical NoCs. To tackle this problem, in this work, we propose a learning-based thermal-sensitive power optimization approach for mesh- or torus-based optical NoCs in the presence of temperature variations. The key techniques proposed include an initial device-setting and thermal-tuning mechanism that is a device-level optimization technique, and a learning-based thermal-sensitive adaptive routing algorithm that is a network-level optimization technique. Simulation results of an 8x8 mesh-based optical NoC show that the proposed initial device-setting and thermal-tuning mechanism confines the worst-case thermal-induced optical energy consumption to be on the order of tens of pJ/bit, by avoiding significant thermal-induced optical power loss caused by temperature-dependent wavelength shifts. Besides, it shows that the learning-based thermal-sensitive adaptive routing algorithm is able to find an optimal path with the minimum estimated thermal-induced optical power consumption for each communication pair. The proposed routing has a greater space for optimization, especially for applications with more long-distance traffic.
A Study of Complex Deep Learning Networks on High-Performance, Neuromorphic, and Quantum Computers
Authors: Potok Thomas E. , Schuman Catherine , Young Steven , Patton Robert , Spedalieri Federico , Liu Jeremy , Yao Ke-Thia , Rose Garrett , Chakma Gangotree
Published: July 2018

Current deep learning approaches have been very successful using convolutional neural networks trained on large graphical-processing-unit-based computers. Three limitations of this approach are that (1) they are based on a simple layered network topology, i.e., highly connected layers, without intra-layer connections; (2) the networks are manually configured to achieve optimal results, and (3) the implementation of the network model is expensive in both cost and power. In this article, we evaluate deep learning models using three different computing architectures to address these problems: quantum computing to train complex topologies, high performance computing to automatically determine network topology, and neuromorphic computing for a low-power hardware implementation. We use the MNIST dataset for our experiment, due to input size limitations of current quantum computers. Our results show the feasibility of using the three architectures in tandem to address the above deep learning limitations. We show that a quantum computer can find high quality values of intra-layer connection weights in a tractable time as the complexity of the network increases, a high performance computer can find optimal layer-based topologies, and a neuromorphic computer can represent the complex topology and weights derived from the other architectures in low power memristive hardware.
Evaluating Model Performance in Evolutionary Biology
Authors: Brown Jeremy M. , Thomson Robert C.
Published: July 2018

Many fields of evolutionary biology now depend on stochastic mathematical models. These models are valuable for their ability to formalize predictions in the face of uncertainty and provide a quantitative framework for testing hypotheses. However, no mathematical model will fully capture biological complexity. Instead, these models attempt to capture the important features of biological systems using relatively simple mathematical principles. These simplifications can allow us to focus on differences that are meaningful, while ignoring those that are not. However, simplification also requires assumptions, and to the extent that these are wrong, so is our ability to predict or compare. Here, we discuss approaches for evaluating the performance of evolutionary models in light of their assumptions by comparing them against reality. We highlight general approaches, how they are applied, and remaining opportunities. Absolute tests of fit, even when not explicitly framed as such, are fundamental to progress in understanding evolution.
Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer
Authors: Hunyor Imre , Cook Kristina M.
Published: July 2018

Obstructive sleep apnea (OSA) is common and linked to a variety of poor health outcomes. A key modulator of this disease is nocturnal intermittent hypoxia. There is striking epidemiological evidence that patients with OSA have higher rates of cancer and cancer mortality. Small-animal models demonstrate an important role for systemic intermittent hypoxia in tumor growth and metastasis, yet the underlying mechanisms are poorly understood. Emerging data indicate that intermittent hypoxia activates the hypoxic response and inflammatory pathways in a manner distinct from chronic hypoxia. However, there is significant heterogeneity in published methods for modeling hypoxic conditions, which are often lacking in physiological relevance. This is particularly important for studying key transcriptional mediators of the hypoxic and inflammatory responses such as hypoxia-inducible factor (HIF) and NF-κB. The relationship between HIF, the molecular clock, and circadian rhythm may also contribute to cancer risk in OSA. Building accurate in vitro models of intermittent hypoxia reflective of OSA is challenging but necessary to better elucidate underlying molecular pathways.
Impact of age on the development of fatigue during large and small muscle mass exercise
Authors: Weavil Joshua C. , Hureau Thomas J. , Thurston Taylor S. , Sidhu Simranjit K. , Garten Ryan S. , Nelson Ashley D. , McNeil Chris J. , Richardson Russell S. , Amann Markus
Published: July 2018

To examine the impact of aging on neuromuscular fatigue following cycling (CYC; large active muscle mass) and single-leg knee-extension (KE; small active muscle mass) exercise, 8 young (25 ± 4 years) and older (72 ± 6 years) participants performed CYC and KE to task failure at a given relative intensity (80% of peak power output). The young also matched CYC and KE workload and duration of the old (iso-work comparison). Peripheral and central fatigue were quantified via pre-/postexercise decreases in quadriceps twitch torque (∆Qtw, electrical femoral nerve stimulation) and voluntary activation (∆VA). Although young performed 77% and 33% more work during CYC and KE, respectively, time to task failure in both modalities was similar to the old (~9.5 min; P > 0.2). The resulting ΔQtw was also similar between groups (CYC ~40%, KE ~55%; P > 0.3); however, ∆VA was, in both modalities, approximately double in the young (CYC ~6%, KE ~9%; P < 0.05). While causing substantial peripheral and central fatigue in both exercise modalities in the old, ∆Qtw in the iso-work comparison was not significant (CYC; P = 0.2), or ~50% lower (KE; P < 0.05) in the young, with no central fatigue in either modality ( P > 0.4). Based on iso-work comparisons, healthy aging impairs fatigue resistance during aerobic exercise. Furthermore, comparisons of fatigue following exercise at a given relative intensity mask the age-related difference observed following exercise performed at the same workload. Finally, although active muscle mass has little influence on the age-related difference in the rate of fatigue at a given relative intensity, it substantially impacts the comparison during exercise at a given absolute intensity.