bluuebunny/crossref_metadata_2025 huggingface dataset:
Planning for the future: Modelling daily emergency department presentations in an Australian capital city
Authors: McAllan Fern J , Egerton‐Warburton Diana , O'Reilly Gerard , Weiland Tracey J , Jelinek George A
Published: March 2019

Objective

To describe and model a decade of ED presentations in metropolitan Melbourne, Australia, from July 2000 to June 2010 and to validate the model of ED presentations by testing the model's performance in forecasting the subsequent 2 year period of daily presentations, from July 2010 to June 2012.

Methods

Retrospective analyses of prospectively collected data sourced from the Victorian Emergency Minimum Dataset were performed and included 13 public hospitals. Time series modelling involved unobserved components modelling and forward selection of variables using incidence rate ratios. Forecasting with the model and validation were performed using the 2 year period up to June 2012. Model performance was calculated using the mean average percentage error.

Results

A total of 7 031 242 patient presentations occurred to the sample metropolitan EDs in the 12 year study period. An absolute increase in mean daily ED presentations of 81.3% was observed. Presentations increased on Sunday and Monday incidence rate ratio of 1.10 (95% CI 1.08–1.11, P < 0.05). No monthly or seasonal pattern was evident. Public holidays were associated with increased presentations, incidence rate ratio of 1.11 (95% CI 1.08–1.15, P < 0.05). The model with the best goodness‐of‐fit and Wald χ2 value included Sunday–Monday (vs Tuesday–Saturday), public holidays, the trend of gradual increase over time and a stochastic (random white noise) cycle. The mean average percentage error for the 2 year forecast period was 3.6%.

Conclusion

We have produced and validated a model for predicting daily ED presentations across a major city. Even though ED presentations are multifactorial, city‐wide daily presentations are predictable and explained by a small number of variables. The model will have implications for future health planning.
Emerging next‐generation robotic colonoscopy systems towards painless colonoscopy
Authors: Yeung Chung‐Kwong , Cheung Jo LK , Sreedhar Biji
Published: March 2019

Advances in the field of robotics have allowed modern technology to be integrated into medicine and that can minimize patients suffering from the side effects that are inherent to procedures for improving their quality of life. Conventional devices that are used for colonoscopies are rigid and require a high level of expertise from endoscopists to perform the procedure. Advances in robot‐assisted colonoscopic systems now produce softer, more slender, automated designs that no longer require the operator to use forceful pushing to advance the colonoscope inside the colon, reducing risks to the patient of perforation and pain. It is challenging to reprocess these scopes for reuse as the materials used can be damaged during decontamination, leading to the possible risks of cross‐infection by pathogenic microorganisms when reused by patients. An ideal solution is to eliminate these contamination risks to patients by adopting sterile, single‐use scopes straight from the manufacturer's package to the patient.

With this idea in mind, emerging developments that push the boundaries in this area will benefit patients and encourage the public to participate in and adhere better to colonoscopy screening to reduce the development of colorectal cancer. Thus, in light of these concerns and challenges, to encourage patients undergoing colorectal screening to comply with colonoscopy procedures that they are less invasive, changes in the design and materials are necessary. One of the more promising technological advances in this area is the advent of robotic colonoscopy.
The impact of endoscopic ultrasound in preoperative evaluation for ampullary adenomas
Authors: Peng Chun Yan , Lv Ying , Shen Shan Shan , Wang Lei , Ding Xi Wei , Zou Xiao Ping
Published: March 2019

Objective

We aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in assessing locoregionally and determining therapeutic options for ampullary adenomas and the related factors.

Methods

Patients undergoing EUS and surgical or endoscopic resection for biopsy‐proven ampullary adenomas between 2009 and 2016 were retrospectively analyzed. The depth of tumor invasion, intraductal extension, and regional lymph node staging evaluated by EUS were compared with post‐treatment pathological findings.

Results

Altogether 120 patients were enrolled in this study. The overall accuracy for EUS in T staging was 81.7%. The sensitivity and specificity of EUS for T staging were 93.9%, 45.5% for adenoma and T1, 50.0% and 96.5% for T2, 66.7% and 97.4% for T3, 50.0% and 97.5% for T4 lesions, respectively. The sensitivity, specificity, and accuracy of EUS for the diagnosis of any intraductal extension were 89.5%, 86.1%, and 86.7%, respectively. The overall accuracy of EUS for regional lymph node staging was 75.0%. The sensitivity and specificity of EUS for diagnosing N1 were 62.5% and 87.5%. By multivariate analysis no factors were found to be independently associated with EUS accuracy for tumor invasive depth. However, small lesion size (≤15 mm) and dilated duct were associated with an overestimation in intraductal extension.

Conclusion

EUS may be a useful diagnostic tool for selecting endoscopic or surgical treatment for ampullary adenomas.
Novel bioactive natural products from bacteria via bioprospecting, genome mining and metabolic engineering
Authors: Sekurova Olga N. , Schneider Olha , Zotchev Sergey B.
Published: March 2019

For over seven decades, bacteria served as a valuable source of bioactive natural products some of which were eventually developed into drugs to treat infections, cancer and immune system‐related diseases. Traditionally, novel compounds produced by bacteria were discovered via conventional bioprospecting based on isolation of potential producers and screening their extracts in a variety of bioassays. Over time, most of the natural products identifiable by this approach were discovered, and the pipeline for new drugs based on bacterially produced metabolites started to run dry. This mini‐review highlights recent developments in bacterial bioprospecting for novel compounds that are based on several out‐of‐the‐box approaches, including the following: (i) targeting bacterial species previously unknown to produce any bioactive natural products, (ii) exploring non‐traditional environmental niches and methods for isolation of bacteria and (iii) various types of ‘genome mining’ aimed at unravelling genetic potential of bacteria to produce secondary metabolites. All these approaches have already yielded a number of novel bioactive compounds and, if used wisely, will soon revitalize drug discovery pipeline based on bacterial natural products.
Rock Mass Characteristics in Beishan, A Preselected Area for China's High‐Level Radioactive Waste Disposal
Authors: WEI Xiang , GUO Ying , CHENG Hanlie , MENG Xiangdong , CHENG Mingqian , YANG Ting , XU Chunmei
Published: March 2019

Geological and hydrological characteristics, joint geometric features, rock physical and mechanical properties and rock mass quality are studied in the Beishan area, preselected for China's high‐level radioactive waste (HLW) disposal engineering. A comprehensive survey method is developed to study joint geometric features in the outcrop and samples from borehole BS06 into the Xinchang rock mass were tested. The optimal joint sets are determined by rose diagrams and equal‐area lower hemisphere plots of joint poles. Results show that: 1) the distribution of joint occurrence obeys a normal distribution, while the distribution of joint spacing obeys a negative exponential distribution; 2) concentric circular and tangent circular sampling windows are applied to study the trace length and the trace midpoint density. Results indicate that tangent circular sampling window is more stable and reasonable; 3) Beishan granite shows high density, low porosity and high strength based on many laboratory tests and the physical properties and mechanical properties are closely related; and 4) a synthesis index, Joint Structure Rating (JSR), is applied to evaluate the quality of rock mass. Through the research results of rock mass characteristics, the Xinchang rock mass in the Beishan preselected area has the favorable conditions for China's HLW disposal repository site.
Drug Order in Rapid Sequence Intubation
Authors: Driver Brian E. , Klein Lauren R. , Prekker Matthew E. , Cole Jon B. , Satpathy Rajesh , Kartha Gautham , Robinson Aaron , Miner James R. , Reardon Robert F.
Published: March 2019

Background

The optimal order of drug administration (sedative first vs. neuromuscular blocking agent first) in rapid sequence intubation (RSI) is debated.

Objective

We sought to determine if RSI drug order was associated with the time elapsed from administration of the first RSI drug to the end of a successful first intubation attempt.

Methods

We conducted a planned secondary analysis of a randomized trial of adult ED patients undergoing emergency orotracheal intubation that demonstrated higher first‐attempt success with bougie use compared to a tracheal tube + stylet. Drug choice, dose, and the order of sedative and neuromuscular blocking agent were not stipulated. We analyzed trial patients who received both a sedative and a neuromuscular blocking agent within 30 seconds of each other who were intubated successfully on the first attempt. The primary outcome was the time elapsed from complete administration of the first RSI drug to the end of the first intubation attempt, a surrogate outcome for apnea time. We performed a multivariable analysis using a mixed‐effects generalized linear model.

Results

Of 757 original trial patients, 562 patients (74%) met criteria for analysis; 153 received the sedative agent first, and 409 received the neuromuscular blocking agent first. Administration of the neuromuscular blocking agent before the sedative agent was associated with a reduction in time from RSI administration to the end of intubation attempt of 6 seconds (95% confidence interval = 0 to 11 sec).

Conclusion

Administration of either the neuromuscular blocking or the sedative agent first are both acceptable. Administering the neuromuscular blocking agent first may result in modestly faster time to intubation. For now, it is reasonable for physicians to continue performing RSI in the way they are most comfortable with. If future research determines that the order of medication administration is not associated with awareness of neuromuscular blockade, administration of the neuromuscular blocking agent first may be a logical default administration method to attempt to minimize apnea time during intubation.
Do Social Rights Affect Social Outcomes?
Authors: Bjørnskov Christian , Mchangama Jacob
Published: March 2019

While the United Nations and NGOs are pushing for global judicialization of economic, social, and cultural rights (ESCRs), little is known of their consequences. We provide evidence of the effects of introducing three types of ESCRs into the constitution: the rights to education, health, and social security. Employing a large panel covering annual data from 160 countries in the period 1960–2010, we find no robust evidence of positive effects of ESCRs. We do, however, document adverse medium‐term effects on education, inflation, and civil rights.
Inflammatory endotypes in COPD
Authors: Barnes Peter J.
Published: March 2019

Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid‐resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes. Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs. However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL‐5 has been detected, anti‐IL‐5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines.
Neural inertia and differences between loss of and recovery from consciousness during total intravenous anaesthesia: a narrative review
Authors: Sepúlveda P. O. , Tapia L. F. , Monsalves S.
Published: March 2019

Most anaesthetists using target‐controlled infusion systems will have observed that the calculated effect‐site concentration at loss of consciousness is usually higher than the concentration at emergence. Inertia is the ability of biological systems to keep a functional state at rest or in activity and is an active process of resistance to change in state. Hysteresis is a phenomenon whereby the value of a physical property lags behind changes in the effect that is causing it and this is also seen in anaesthesia pharmacology. Recently, a phenomenon called neuronal inertia has been proposed when trying to explain the resistance observed to changes in consciousness induced by general anaesthesia, independent of drug kinetics. This review discusses the existence of this phenomenon and the conceptual and practical impact it may have on induction and recovery from general anaesthesia.
Opposing effects of 25‐hydroxy‐ and 1α,25‐dihydroxy‐vitamin D3 on pro‐cachectic cytokine‐and cancer conditioned medium‐induced atrophy in C2C12 myotubes
Authors: Sustova Hana , De Feudis Marilisa , Reano Simone , Alves Teixeira Maraiza , Valle Ilaria , Zaggia Ivan , Agosti Emanuela , Prodam Flavia , Filigheddu Nicoletta
Published: March 2019

Aim

Loss of skeletal muscle is one of the main features of cancer cachexia. Vitamin D (VD) deficiency is associated with impairment of muscle mass and performance and is highly prevalent in cachectic patients; therefore, VD supplementation has been proposed to counteract cancer cachexia‐associated muscle loss. However, in both cachectic cancer patients and tumour‐bearing animals, VD supplementation led to disappointing results, urging the need for a better understanding of VD activity on skeletal muscle.

Methods

Cancer‐associated muscle wasting was reproduced in vitro by treating C2C12 myotubes with cancer cell conditioned medium, a combination of TNF‐α and IFNγ or IL‐6 pro‐cachectic cytokines. The biological effects and mechanisms of action of 1,25‐dihydroxy VD (1,25 VD) and its precursor 25‐hydroxy VD (25 VD) on myotubes were explored.

Results

We demonstrated that only 25 VD was able to protect from atrophy by activating Akt signalling, inducing protein synthesis, and stimulating the autophagic flux, while 1,25 VD had an atrophic activity per se, increasing FoxO3 levels, inducing the expression of atrogenes, and blocking the autophagic flux. Furthermore, we showed that the contrasting activities of these VD metabolites on C2C12 myotubes depend on a differential induction of VD‐24‐hydroxylase and transformation of VD metabolites in pro‐atrophic 24‐hydroxylated products, as silencing of VD‐24‐hydroxylase reduced the atrophic activity of 1,25 VD.

Conclusions

Altogether these data might explain the lack of efficacy of VD treatment in vivo for the protection of muscle mass in cancer.
The effectiveness of intelligent tutoring systems on K‐12 students' reading comprehension: A meta‐analysis
Authors: Xu Zhihong , Wijekumar Kausalai (Kay) , Ramirez Gilbert , Hu Xueyan , Irey Robin
Published: March 2019

This meta‐analysis examined the effectiveness of improving reading comprehension for students in K‐12 classrooms using intelligent tutoring systems (ITSs), a computer‐based learning environment that provides customizable and immediate feedback to the learner. Nineteen studies from 13 publications incorporating approximately 10 000 students were included in the final analysis; using robust variance estimation to account for statistical dependencies, the 19 studies yielded 88 effect size estimates. The meta‐analysis indicated that the overall random effect size of ITSs on reading comprehension was 0.60 (using a mix of standardized and researcher‐designed measures) with a 95% confidence interval 0.36 to 0.85 (p < 0.001). This review confirms previous studies comparing ITSs to human tutoring: ITSs produced a small effect size when compared to human tutoring (0.20, 0.02–0.38, p = 0.036, n = 21). All comparisons to human tutoring used standardized measures. This review also found that ITSs produced a larger effect size on reading comprehension when compared to traditional instruction (0.86) for mixed measures and (0.26) for standardized measures. These findings may be of interest to practitioners and policy makers seeking to improve reading comprehension using consistent and accessible ITSs. Recommendations for researchers include conducting studies to understand the difference between traditional and updated versions of ITSs and employing valid and reliable standardized tests and researcher‐designed measures.
C‐type lectin domain family 5, member A (CLEC5A, MDL‐1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling
Authors: Fan Hong‐Wei , Ni Qi , Fan Ya‐Ni , Ma Zhi‐Xiang , Li Ying‐Bin
Published: March 2019

Objectives

Glioblastoma is the most common malignant glioma of all brain tumours. It is difficult to treat because of its poor response to chemotherapy and radiotherapy and high recurrence rate after treatment. The aetiology of glioblastoma is a result of disorders of multiple factors. Depending on cell signal transduction, these glioblastoma‐associated factors lead to cell proliferation, differentiation and apoptosis. Therefore, investigation of the potential factors which involved in the development of glioblastoma could provide a new target for the treatment of glioblastoma.

Materials and methods

We analysed the transcript expression of CLEC5A in glioblastoma by accessing The Cancer Genome Atlas (TCGA). qRT‐PCR was performed to detect the RNA expression of genes in cells and tissues, and Western blot was used to measure the protein levels (Cyclin D1, Bcl‐2, BAX, PCNA, MMP2, MMP9, Akt and Akt phosphorylation) in tissues and cells. Cell proliferation, migration, invasion, cycle and apoptosis were measured by CCK‐8, transwell and flow cytometry assays, respectively. Ki67 level and lung metastasis were determined by immunochemistry and H&E staining.

Results

In this study, we found that CLEC5A was highly upregulated in glioblastoma compared to normal brain tissues, which had an opposite relation with the overall patient survival. Downregulation of CLEC5A could inhibit cell proliferation, migration and invasion via promoting apoptosis and G1 arrest. In contrast, overexpression of CLEC5A stimulated cell proliferation, migration and invasion. In addition, we found that CLEC5A level was positively correlated with Akt phosphorylation level. Akt inhibitor or agonist could reverse the modulation effects of CLEC5A in glioblastoma. Moreover, In vivo results suggested that inhibition of CLEC5A significantly reduced tumour size, weight, cell proliferation ability and lung metastasis via inhibition of phosphorylation Akt.

Conclusion

Both in vitro and in vivo evidences supported that CLEC5A was involved in glioblastoma pathogenesis via regulation of PI3K/Akt pathway. Thus, CLEC5A might serve as a potential therapeutic target in the treatment of glioblastoma in the future.
Ethics and neurodisability: the power of one life
Authors: Cass Hilary
Published: March 2019

Video Podcast: https://www.youtube.com/watch?v=1ALPdA7HFjg&feature=youtu.be
How large is Vietnam's informal economy?
Authors: Hoa Nguyen Thai
Published: March 2019

The purpose of this article is to estimate the size of the informal economy in Vietnam, describe its development from 1995 to 2015, and assess the country's potential tax loss from this activity. The MIMIC model indicates that the informal economy accounts for between 15 per cent and 27 per cent of GDP. The informal economy has grown sharply in Vietnam since 2007, while its size has decreased in other comparable nations. Potential tax revenue lost annually amounts to between 3.3 per cent and 5 per cent of gross domestic product.
Left ventricular end‐diastolic strain rate recovered in hypothyroidism following levothyroxine replacement therapy: A strain rate imaging study
Authors: Kong Ling‐Yun , Gao Xia , Ding Xue‐Yan , Wang Guang , Liu Fang
Published: March 2019

Background

This study aimed to explore the impact of overt hypothyroidism on diastolic left ventricular (LV) deformation and the effect of levothyroxine therapy using 2‐dimensional speckle‐tracking echocardiography (STE) strain rate (SR) imaging.

Methods

Forty‐seven newly diagnosed hypothyroidic patients and 51 controls were prospectively enrolled. All participants underwent comprehensive 2‐dimensional echocardiography. Besides the recently recommended parameters of LV diastolic function, strain imaging for LV systolic global longitudinal strain (GLS), and diastolic SR imaging at isovolumic relaxation period (SRivr), early (SRe) and late (SRa) diastole were assessed. Repeated echocardiography in hypothyroidic patients was made 6 months after the euthyroidic state was achieved.

Results

Hypothyroidic patients had a lower ejection fraction (EF) than the controls (68.6 ± 5.2% vs 71.5 ± 4.0%, P = 0.002) but all within normal range (57%–80% and 64%–79%, respectively). No difference in the ratio of early mitral flow (E) to early diastolic septal or lateral myocardial motion velocity (e′) was found (both P > 0.05), but significant difference was identified for SRa (0.85 ± 0.17 [/s] vs 1.00 ± 0.17 [/s], P = 0.000) and GLS (−20.8 ± 3.2% vs −23.6 ± 2.3%, P = 0.000). Upon follow‐up, LV SRa (1.01 ± 0.20 [/s], P = 0.99 vs control) normalized when GLS (−21.6 ± 3.1%, P = 0.004 vs control) remained worse than the controls.

Conclusion

This study demonstrates subtle LV diastolic impairment in untreated hypothyroidic patients using SR imaging, which normalizes with short‐term therapy and predates GLS.
DISCOUNT PRICING
Authors: Armstrong Mark , Chen Yongmin
Published: March 2019

We investigate the practice of framing a price as a discount from an earlier price, with information such as “was $200, now $100.” We discuss two reasons why a discounted price—rather than a merely low price—can make a consumer more willing to purchase. First, a high initial price can indicate the seller has chosen to supply a high‐quality product. Second, when a seller with limited stock runs a clearance sale, later consumers infer that unsold stock has higher expected quality when its initial price was higher. We also suggest a behavioral explanation, which is that consumers with reference‐dependence preferences are more likely to buy if they perceive the price as a bargain relative to the earlier price. Discount pricing is therefore an effective marketing technique, and a seller may wish to deceive potential customers by offering a false discount. The welfare effects of regulation to prevent fictitious pricing are subtle, with potential unintended consequences, and depend on whether consumers are sophisticated or naive. (JELD18, D42, D83, L15, M31)
IL‐35 ameliorates collagen‐induced arthritis by promoting TNF‐α‐induced apoptosis of synovial fibroblasts and stimulating M2 macrophages polarization
Authors: Peng Mingzheng , Qiang Lei , Xu Yan , Li Cuidi , Li Tao , Wang Jinwu
Published: March 2019

Synovitis, the chronic inflammation of the synovial membranes, is a hallmark of rheumatoid arthritis, a chronic disease with profound impact on human health. Recently, interleukin‐35 (IL‐35), a new member of the IL‐12 family, was identified as an anti‐inflammatory and immunosuppressive cytokine and was shown to ameliorate collagen‐induced arthritis (CIA) in mice. However, the mechanism by which IL‐35 alleviates CIA remains unknown. In this study, we investigated the effect of IL‐35 on the CIA microenvironment and, specifically, the tumor necrosis factor alpha (TNF‐α)‐induced macrophage inflammatory response and apoptosis of fibroblast‐like synoviocytes (FLSs). Firstly, using RT‐PCR, western blot, and flow cytometry, we found that IL‐35 suppressed TNF‐α‐induced inflammatory responses by down‐regulating iNOS and COX‐2 in peripheral blood monocyte‐derived macrophages. IL‐35 also activated alternative M2 macrophage polarization, as determined by evaluation of CCR7 and CD206 expression. Moreover, we showed that IL‐35 enhanced TNF‐α‐induced FLS apoptosis. Using a panel of immunohistochemical and immunofluorescence analyses in a CIA model established in 18 DBA/1J mice, we demonstrated that IL‐35 promotes synoviocyte apoptosis and alternative activation of macrophages to alleviate arthritis in vivo. Taken together, our results show that IL‐35 promotes TNF‐α‐induced FLS apoptosis and modulates M2 macrophage polarization to ameliorate CIA inflammation both in vitro and in vivo.
Strength and fatigue strength of a similar Ti‐6Al‐2Sn‐4Zr‐2Mo‐0.1Si linear friction welded joint
Authors: García Juan Manuel , Morgeneyer Thilo F.
Published: March 2019

Strengths for monotonic and cyclic loadings of similar overmatching Ti‐6Al‐2Sn‐4Zr‐2Mo‐0.1Si (Ti6242) linear friction welds (LFW) were studied and compared with the parent material (PM) behaviour. Non‐destructive synchrotron observations revealed the presence of pores in the weld interface. The weld centre zone (WCZ) showed a higher strength leading to lower macroscopic ductility of the cross‐weld samples. Local strain and normalized strain rate have been assessed by stereo digital image correlation (DIC) and revealed an early plastic activity at yielding in the vicinity of the WCZ attributed to residual stresses. For the target life, the fatigue strength was slightly reduced but compromised by a strong scatter. Indeed, an internal fish‐eye fatigue crack initiation was found on an unexpected dendritic defect that was very different from the PM microstructure and the known martensitic α′ in the WCZ. The dendritic defect was linked to surface contamination prior to welding and led to melting.
Multiaxial fatigue life calculation model for components in rolling‐sliding line contact with application to gears
Authors: Basan Robert , Marohnić Tea
Published: March 2019

Important components such as gears, rollers, or bearings operate in rolling‐sliding contact loading conditions. Determination of their fatigue lives remains a challenging task due to complex states of stress and strain in the contact region, as well as complex contact conditions such as variable loading amplitude and complex geometry of contact. A mathematical model of rolling‐sliding line contact combined with a multiaxial fatigue life calculation model based on the Fatemi‐Socie critical plane crack initiation criterion is proposed. The developed model was applied to gears' teeth in mesh and compared with fatigue lives of gears reported in the literature. Good agreement was determined confirming the validity of the proposed model. A further advantage is obtaining locations of initiated cracks and the orientation of critical plane(s), which can subsequently be used for the estimation of crack shapes in initial phases of their growth and the damage type that they can be expected to develop into.
Effect of forage species and ensiling conditions on silage composition and quality and the feed choice behaviour of goats
Authors: Scherer Rebecca , Gerlach Katrin , Taubert Johannes , Adolph Stephanie , Weiß Kirsten , Südekum Karl‐Heinz
Published: March 2019

The hypothesis was that forage species and ensiling conditions have an impact on the formation of biogenic amines and the feed choice of goats in short‐term preference trials. At ensiling, lucerne (Medicago sativa L., first cut), red clover (Trifolium pratense L., first cut) and Italian ryegrass (Lolium multiflorum Lam., second cut) were treated differently to obtain a range of fermentation qualities. Six treatments of each forage species were prepared and included different dry‐matter concentrations, chemical and biological silage additives, and additions of soil. Silages were sampled for chemical analyses (proximate constituents, fermentation products and other volatile compounds, crude protein fractions and biogenic amines) and stored anaerobically in vacuum‐sealed plastic bags for use in preference trials (one trial for each forage species) with Saanen‐type wethers (n = 8 or 6). Each possible two‐way combination of the six silage treatments and a standard hay (n = 21 combinations) was offered for ad libitum intake for 3 hr. Data were analysed using multidimensional scaling, analysis of variance and correlation analysis between silage characteristics and dry‐matter intake (DMI). For each forage species, fermentation characteristics and crude protein fractions revealed only small differences among treatments. Although the degree of proteolysis, as measured by non‐protein nitrogen, of all silages was high, biogenic amine and butyric acid concentrations were low. The different treatments apparently had no direct influence on the formation of biogenic amines and feed choice. The preference behaviour within one forage species was strongly divergent, but DMI rankings of the three species were very similar.
GÜNTER GRASS’ HUNDEJAHRE: EIN BEITRAG ZUR ERINNERUNGSKULTUR IN DER BUNDESREPUBLIK DER SECHZIGER JAHRE
Authors: Hahn Hans‐Joachim
Published: March 2019

This study considers Grass's Hundejahre as the most important contribution towards the establishment of a cultural memory in the Federal Republic of the 1960s. A brief introduction discusses the concept of ‘Erinnerungskultur’ with reference to international research on memory culture, suggesting that a persistent focus on the Holocaust would neglect important aspects evident in earlier documents in German literature and culture which may have brought about these crimes. My discussion of the ‘Holocaust’ in this novel places less emphasis on the victims than on the collaborators in the crimes and their self‐satisfied lives in post‐war Germany. The portrayal of violence and ‘Mitläufer’ compliance become central aspects, with the ‘Kleinbürger’ mentality featuring as a significant component of the German mindset. By coalescing different time scales, Grass revitalises the past and enhances its relevance for the reader. An ‘Aesthetics of Obscenity’ is employed as a means of illustrating unspeakable Nazi crimes, while fairy‐tale elements and satirical fantasy (the scarecrow ballet) serve as forms of alienation, tasking the reader with unravelling their significance. Compared to the formalism evident in post‐war German literary criticism, Hundejahre must be seen as an eminent contribution to German memory culture which contributed to bringing the debate in Germany closer to international trends.
The association of overhydration with chronic inflammation in chronic maintenance hemodiafiltration patients
Authors: Zsom Lajos , Faludi Mária , Fülöp Tibor , Dossabhoy Neville R. , Rosivall László , Tapolyai Mihály B.
Published: March 2019

Introduction: Achieving euvolemia is one of the major challenges when treating end‐stage renal disease (ESRD) patients receiving maintenance renal replacement therapy. Fluid overload is recognized as an independent predictor of mortality in ESRD, but its association with chronic inflammation is less well explored especially in chronic maintenance hemodiafiltration.

Methods: We performed a cross‐sectional study of 87 prevalent ESRD patients receiving chronic maintenance hemodiafiltration (vintage 66.5 ± 57.1 months) with bioimpedance analysis to characterize the degree of percent overhydration (OH%). We also compared the levels of inflammatory markers, including C‐reactive protein (CRP), serum albumin, neutrophil/lymphocyte ratio (NLR), and hemoglobin red cell distribution width (RDW) for the overhydrated (OH% ≥ 15%) versus euvolemic (OH% < 15%) groups. Linear regression analysis was performed to explore relationships between the degree of OH and inflammatory indicators.

Findings: The cohort represented an all‐European population with a mean age of 60.9 ± 14.7 years and prevalence of diabetes mellitus of 27%. The entire cohort's OH% was 14.9% ± 5.1% (range −11.1% to 39.0%); further, the <15% group of patients’ OH% was 8.0% ± 8.5% versus 20.9% ± 5.1% in the OH% ≥ 15% group (P < 0.0001). Forty‐seven patients (53%) were overhydrated by traditional criteria (OH% ≥15%) and 20 patients (23%) were severely overhydrated (OH% > 20%). The euvolemic (OH% <15%) versus severely overhydrated (OH% > 20%) groups had significant differences in markers of inflammation: CRP (9.8 ± 10.6 vs. 21.5 ± 21.6 mg/L, P < 0.006), serum albumin (37.6 ± 02.9 vs. 34.5 ± 5.3 g/L, P < 0.004), and NLR (3.06 ± 1.25 vs. 3.92 ± 2.04; P < 0.004). On linear regression, significant correlations were found between OH% and CRP (r = 0.2899, P < 0.006), serum albumin (r = −0.3670; P < 0.0005), RDW (r = 0.2992; P < 0.005), and NLR (r = 0.2900; P < 0.006).

Discussion: In a prevalent hemodiafiltration cohort, OH was common and correlated with several inflammatory markers.
Applicability of quantitative polymerase chain reaction (qPCR) assays for common bean authentication in processed food
Authors: Venturelli Gustavo Luiz , Bischoff Joana Laura , Scariot Mirella Christine , Rossi Gabriela Barbosa , Arisi Ana Carolina Maisonnave
Published: March 2019

Food authentication by quantitative polymerase chain reaction (qPCR) methods assures food quality. The aim was to evaluate three qPCR assays for DNA quantification after heat processing of common bean grains, genus‐specific FAS assay for Phaseolus, species‐specific LEC assay for common bean (Phaseolus vulgaris) and genetically modified (GM) event‐specific FGM assay for Embrapa 5.1 event GM common bean. FAS assay showed high stability among Phaseolus genus samples. Common bean grains were heat‐treated in autoclave (at 120 °C for 15–60 min) and target DNA copy number decreased as processing time increased. Even with DNA degradation, qPCR assays were capable to detect low DNA quantity, and the limit of detection was 100 copy number. Mean efficiency value of FGM assay was 92% in the presence of background DNA. Background DNA did not cause any interference, and 0.39% of GM material can be detected. These qPCR assays are able to quantify common bean in processed food.
Functional characterization of ultraspiracle in Leptinotarsa decemlineata using RNA interference assay
Authors: Xu Q.‐Y. , Deng P. , Li A. , Zhang Q. , Mu L.‐L. , Fu K.‐Y. , Guo W.‐C. , Li G.‐Q.
Published: March 2019

A heterodimer of ultraspiracle (USP) and ecdysone receptor (EcR) mediates 20‐hydroxyecdysone (20E) signalling cascade to regulate insect moulting and metamorphosis. However, at least two questions remain to be addressed in terms of the molecular importance of USP in insect species. First, is USP involved in both regulation of ecdysteroidogenesis and mediation of 20E signalling in non‐drosophilid insects, as in Drosophila melanogaster? Second, does USP play any role in larval metamorphosis except as the partner of heterodimeric receptor to activate the downstream 20E signalling genes? In this paper, we found that RNA interference (RNAi) of LdUSP in the final (fourth) instar larvae reduced the messenger RNA levels of four ecdysteroidogenesis genes (Ldspo, Ldphm, Lddib and Ldsad) and 20E titre, and repressed the expression of five 20E signal genes (EcRA, HR3, HR4, E74 and E75) in Leptinotarsa decemlineata. The LdUSP RNAi larvae remained as prepupae, with developing antennae, legs and discs of forewings and hindwings. Dietary supplement with 20E restored the expression of the five 20E signal genes, but only partially alleviated the decreased pupation rate in LdUSP RNAi beetles. Knockdown of LdUSP at the penultimate (third) instar larvae did not affect third–fourth instar moulting. However, silencing LdUSP caused similar but less severe impairments on pupation. Accordingly, we propose that USP is undoubtedly necessary for ecdysteroidogenesis, for mediation of 20E signalling and for initiation of metamorphosis in L. decemlineata.
Malocclusion in children and adolescents with Down syndrome: A systematic review and meta‐analysis
Authors: Doriguêtto Paulo Victor T. , Carrada Camila F. , Scalioni Flávia A. R. , Abreu Lucas G. , Devito Karina L. , Paiva Saul M. , Ribeiro Rosangela A.
Published: March 2019

Background

Previous studies have shown a high prevalence of malocclusion in people with Down syndrome (DS) compared to individuals without DS, but no systematic review to summarize the evidence on this topic has been performed thus far.

Aim

To evaluate whether children/adolescents with DS are more affected by malocclusion than those without DS.

Design

A search was performed in seven electronic databases. The quality of the included studies was assessed using the Newcastle‐Ottawa Scale. The strength of the evidence from the selected studies was evaluated by the Grading of Recommendations Assessment, Development and Evaluation system.

Results

Eleven publications were included in the systematic review and eight were meta‐analysed. The meta‐analysis showed that malocclusion was more prevalent in children/adolescents with DS for Angle Class III (risk difference [RD] = 0.40; confidence interval [CI] = 0.33, 0.46), posterior crossbite (risk ratio [RR] = 3.09; CI = 2.02, 4.73), anterior crossbite (RR = 2.18; CI = 1.41, 3.39), and anterior open bite (RD = 0.21; CI = 0.06, 0.36).

Conclusion

The occurrence of malocclusion was higher in children/adolescents with DS compared to individuals without the syndrome. The strength of the evidence of the studies analysed, however, was considered moderate and low.
Moving Up or Falling Behind? Gender, Promotions, and Wages in Canada
Authors: Javdani Mohsen , McGee Andrew
Published: March 2019

We estimate that Canadian women working full time are 1.8 percentage points less likely to be promoted, receive fewer promotions, and experience 2.8 percent less wage growth following promotions than similar men. Significant “family gaps” exist among women. Women without children are less likely to have been promoted than similar men but experience similar wage growth following promotions, while women with children are as likely to have been promoted but experience less wage growth following promotions. Weekly hours and overtime hours explain significant fractions of these gender gaps. Though not precisely estimated, gender gaps in promotions also exist among part‐time workers.
Improvement of quality factor of SrTiO3 dielectric ceramics with high dielectric constant using Sm2O3
Authors: Luo Ting , Shan Xinxuan , Zhao Jingwei , Feng Hengheng , Zhang Qi , Yu Hongtao , Liu Jingsong
Published: March 2019

The ceramics with the formula of Sr1−xSm2x/3TiO3 (x = 0‐0.5) were prepared by conventional ceramic process. A single phase of SrTiO3‐type with cubic perovskite structure was found companied with a decrease in crystal volume when x < 0.5, which was confirmed by X‐ray diffraction results and Rietveld refine. At the level of x = 0.5, the sample consisted of two phases of SrTiO3‐type and Sm2Ti2O7. Raman spectra were used to confirm the change of vibration to explain the variation in microwave dielectric properties. The dielectric constant decreased, the quality factor increased, and the temperature coefficient shifted negatively, when the x value increased from 0 to 0.4. When the x value located between 0.3 and 0.4, the ceramics exhibited high dielectric constant of 140‐152, high quality factor (>6000).
Subtypes of overtime work and nurses’ fatigue, mental status, and work engagement: A latent class analysis of Japanese hospital nurses
Authors: Watanabe Mayumi , Yamauchi Keita
Published: March 2019

Aims

To clarify the subgroups of overtime work motivations and to determine how fatigue, mental status, and work engagement differ among the subgroups.

Design

Cross‐sectional.

Methods

Questionnaires were distributed to 1,075 full‐time nurses working in four hospitals in Japan from October 2015 ‐ February 2016. Nurses were categorized into subgroups of overtime work motivation by latent class analysis. An analysis of covariance was conducted to examine how fatigue, mental status, and work engagement differ among subgroups.

Results/Findings

We identified five types of overtime workers differing greatly in fatigue, mental status, and work engagement.

Conclusions

Even when nurses worked approximately the same work hours, the difference in motivation corresponded to different degrees of fatigue, mental status, and work engagement. When introducing policies to reduce overtime work, managers should consider the different groups of overtime workers, as effective measures may differ.
An unusual ectopic ventricular rhythm in a young woman
Authors: Sternick Eduardo B. , Lokhandwala Yash , Wellens Hein J. J.
Published: March 2019

A case of a 22‐year‐old young pregnant woman with palpitations and near syncope is presented. Holter monitoring showed very frequent premature beats and runs of wide complex tachycardia, refractory to antiarrhythmic drugs. Electrophysiologic evaluation disclosed spontaneous automatism arising in an atriofascicular pathway. Differential diagnosis is discussed.
C‐reactive protein and incident hypertension in a worksite population of Japanese men
Authors: Kansui Yasuo , Matsumura Kiyoshi , Morinaga Yuki , Inoue Minako , Kiyohara Kanako , Ohta Yuko , Goto Kenichi , Ohtsubo Toshio , Ooboshi Hiroaki , Kitazono Takanari
Published: March 2019

Inflammation plays a key role in the pathogenesis of cardiovascular diseases via the development of atherosclerosis. Here, we evaluated the impact of serum C‐reactive protein (CRP) and the white blood cell (WBC) count on the risk of hypertension in middle‐aged Japanese men at a work site. We evaluated a total of 2991 Japanese male workers without hypertension who ranged in age from 18 to 64 years (mean age 40.4 ± 0.2 years) at a worksite in 2010. The hazard ratio (HR) for incident hypertension was estimated according to quartile levels of serum high‐sensitivity CRP (hs‐CRP) or WBC count. These men were followed up for 5 years from 2010 to 2015. During the follow‐up period, 579 (19.4%) subjects developed hypertension. In a multivariable analysis, the risk of incident hypertension was significantly increased with higher hs‐CRP levels: HR 1.00 (reference) for the lowest quartile, 1.39 (1.04‐1.85) for the 2nd quartile, 1.46 (1.08‐1.98) for the 3rd quartile, and 1.57 (1.17‐2.11) for the highest quartile. In contrast, the WBC count was not associated with a greater risk of incident hypertension after multivariable adjustment. These findings suggest that higher levels of serum hs‐CRP, but not the WBC count, are associated with the future incidence of hypertension in middle‐aged Japanese men.
Increase in the nuclear localization of PTEN by the Toxoplasma GRA16 protein and subsequent induction of p53‐dependent apoptosis and anticancer effect
Authors: Kim Sang‐Gyun , Seo Seung‐Hwan , Shin Ji‐Hun , Yang Jung‐Pyo , Lee Sang Hyung , Shin Eun‐Hee
Published: March 2019

This study investigated the efficacy of Toxoplasma GRA16, which binds to herpes virus‐associated ubiquitin‐specific protease (HAUSP), in anticancer treatment, and whether the expression of GRA16 in genetically modified hepatocellular carcinoma (HCC) cells (GRA16‐p53‐wild HepG2 and GRA16‐p53‐null Hep3B) regulates PTEN because alterations in phosphatase and tensin homologue (PTEN) and p53 are vital in liver carcinogenesis and the abnormal p53 gene appears in HCC. For this purpose, we established the GRA16 cell lines using the pBABE retrovirus system, assessed the detailed mechanism of PTEN regulation in vitro and established the anticancer effect in xenograft mice. Our study showed that cell proliferation, antiapoptotic factors, p‐AKT/AKT ratio, cell migration and invasive activity were decreased in GRA16‐stable HepG2 cells. Conversely, the apoptotic factors PTEN and p53 and apoptotic cells were elevated in GRA16‐stable HepG2 cells but not in Hep3B cells. The change in MDM2 was inconspicuous in both HepG2 and Hep3B; however, the PTEN level was remarkably elevated in HepG2 but not in Hep3B. HAUSP‐bound GRA16 preferentially increased p53 stabilization by the nuclear localization of PTEN rather than MDM2‐dependent mechanisms. These molecular changes appeared to correlate with the decreased tumour mass in GRA16‐stable‐HepG2 cell‐xenograft nude mice. This study establishes that GRA16 is a HAUSP inhibitor that targets the nuclear localization of PTEN and induces the anticancer effect in a p53‐dependent manner. The efficacy of GRA16 could be newly highlighted in HCC treatment in a p53‐dependent manner.
Comprehensive medication reviews by ward‐based pharmacists in Swedish hospitals: What does the patient have to say?
Authors: Kempen Thomas G.H. , Kälvemark Amanda , Gillespie Ulrika , Stewart Derek
Published: March 2019

Rationale, aims, and objectives

Inappropriate medication prescribing and use amongst older patients is a major patient safety and health care problem. To promote appropriate medication prescribing and use, comprehensive medication reviews (CMRs) by ward‐based pharmacists, including follow‐up telephone calls after hospital discharge, have been conducted in older patients in the context of a randomized controlled trial (RCT). One of the key actors in a CMR is the patient. To support the understanding of the effects of CMRs on patients' health outcomes and improve clinical practice, knowledge about the patient perspective is needed. We therefore aimed to explore older patients' experiences with, and views on, hospital‐initiated CMRs and follow‐up telephone calls by ward‐based clinical pharmacists within an RCT.

Methods

We conducted in‐depth semi‐structured interviews with 15 patients (66‐94 years) and carers from four hospitals in Sweden. Discussion topics included communication, information, decision‐making, and effects on the patient. Interviews took place after discharge, were audio‐recorded, transcribed verbatim, and thematically analysed using a framework approach.

Results

In general, patients' experiences and views were positive. Seven key themes were identified: (a) feeling of being taken care of and heterogenous health effects; (b) the pharmacist is competent; (c) despite the unclear role of pharmacists, their involvement is appreciated; (d) patients rely on health care professionals for decision‐making; (e) importance of being informed, but receiving and retaining information is problematic; (f) time, location, and other factors influencing the effectiveness of CMRs; and (g) generic substitution is a problem.

Conclusions

Older patients generally have positive experiences with and views on CMRs and follow‐up telephone calls. However, some factors, like the unclear role of the ward‐based pharmacist and problems with receiving and retaining information, may negatively impact the effectiveness of these interventions. Future initiatives on hospital‐initiated CMRs by clinical pharmacists should address these negative factors and utilize the positive views.