bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences between experts and novices when reading with navigational table of contents
Authors: Lu Quan , Zhang Jiyue , Chen Jing , Li Ji
Published: January 2018

Purpose

The purpose of this paper is to examine the difference between experts and novices when reading with navigational table of contents (N-TOC). Experts refer to readers with high level of domain knowledge; novices refer to readers with low level of domain knowledge.

Design/methodology/approach

The authors performed a controlled experiment of three reading tasks (including fact finding task, partial understanding task, and full-text understanding task) on an N-TOC system for 35 post-graduates of Wuhan University who have rich experience in reading with N-TOC. Participants’ domain knowledge was measured by pre-experiment questionnaires; reading performance data including score, time, navigation use, and evaluation of N-TOC were collected.

Findings

The results showed that there was significant difference in neither navigation use nor participants’ evaluation, but domain experts performed significantly better in both score and time of all tasks than domain novices, which revealed an “illusion of control” phenomenon that rich experience in reading with N-TOC enabled domain novices to achieve the same performance as domain experts. In addition, this research found that N-TOC was not suitable for domain novices to solve full-text understanding task because of “cognitive overload” phenomenon.

Originality/value

This study makes a good contribution to the literature on the effect of domain knowledge on reading performance during N-TOC reading and how to provide better digital reading service in the field of library science and information science.
The genome and microbiome of a dikaryotic fungus (Inocybe terrigena, Inocybaceae) revealed by metagenomics
Authors: Bahram Mohammad , Vanderpool Dan , Pent Mari , Hiltunen Markus , Ryberg Martin
Published: January 2018

Recent advances in molecular methods have increased our understanding of various fungal symbioses. However, little is known about genomic and microbiome features of most uncultured symbiotic fungal clades. Here, we analysed the genome and microbiome of Inocybaceae (Agaricales, Basidiomycota), a largely uncultured ectomycorrhizal clade known to form symbiotic associations with a wide variety of plant species. We used metagenomic sequencing and assembly of dikaryotic fruiting‐body tissues from Inocybe terrigena (Fr.) Kuyper, to classify fungal and bacterial genomic sequences, and obtained a nearly complete fungal genome containing 93% of core eukaryotic genes. Comparative genomics reveals that I. terrigena is more similar to ectomycorrhizal and brown rot fungi than to white rot fungi. The reduction in lignin degradation capacity has been independent from and significantly faster than in closely related ectomycorrhizal clades supporting that ectomycorrhizal symbiosis evolved independently in Inocybe. The microbiome of I. terrigena fruiting‐bodies includes bacteria with known symbiotic functions in other fungal and non‐fungal host environments, suggesting potential symbiotic functions of these bacteria in fungal tissues regardless of habitat conditions. Our study demonstrates the usefulness of direct metagenomics analysis of fruiting‐body tissues for characterizing fungal genomes and microbiome.
Relative stability of ploidy in a marine Synechococcus across various growth conditions
Authors: Perez‐Sepulveda Blanca , Pitt Frances , N'Guyen An N. , Ratin Morgane , Garczarek Laurence , Millard Andrew , Scanlan David J.
Published: January 2018

Marine picocyanobacteria of the genus Synechococcus are ubiquitous phototrophs in oceanic systems. Consistent with these organisms occupying vast tracts of the nutrient impoverished ocean, most marine Synechococcus so far studied are monoploid, i.e., contain a single chromosome copy. The exception is the oligoploid strain Synechococcus sp. WH7803, which on average possesses around 4 chromosome copies. Here, we set out to understand the role of resource availability (through nutrient deplete growth) and physical stressors (UV, exposure to low and high temperature) in regulating ploidy level in this strain. Using qPCR to assay ploidy status we demonstrate the relative stability of chromosome copy number in Synechococcus sp. WH7803. Such robustness in maintaining an oligoploid status even under nutrient and physical stress is indicative of a fundamental role, perhaps facilitating recombination of damaged DNA regions as a result of prolonged exposure to oxidative stress, or allowing added flexibility in gene expression via possessing multiple alleles.
Has Abenomics Succeeded in Raising Japan's Inward Foreign Direct Investment?
Authors: Hoshi Takeo
Published: January 2018

Japan is known to have an exceptionally low level of inward foreign direct investment (FDI). The promotion of inward FDI is one of the policy goals of Abenomics structural reforms. This present paper studies the accumulation of Japan's inward FDI stock during the first 3 years of Abenomics (2012–2015), and finds no evidence that Japan's inward FDI stock increased more than the trend before Abenomics started would have predicted. A comparison of the main policies for promoting inward FDI that have been implemented to the real and perceived impediments to inward FDI reveals that it may be advisable to shift the emphasis of the policy to address more regulatory and administrative issues and to reduce the cost of doing business in Japan.
Cardiovascular complications after non‐cardiac surgery
Authors: Sellers D. , Srinivas C. , Djaiani G.
Published: January 2018

Cardiac complications are common after non‐cardiac surgery. Peri‐operative myocardial infarction occurs in 3% of patients undergoing major surgery. Recently, however, our understanding of the epidemiology of these cardiac events has broadened to include myocardial injury after non‐cardiac surgery, diagnosed by an asymptomatic troponin rise, which also carries a poor prognosis. We review the causation of myocardial injury after non‐cardiac surgery, with potential for prevention and treatment, based on currently available international guidelines and landmark studies. Postoperative arrhythmias are also a frequent cause of morbidity, with atrial fibrillation and QT‐prolongation having specific relevance to the peri‐operative period. Postoperative systolic heart failure is rare outside of myocardial infarction or cardiac surgery, but the impact of pre‐operative diastolic dysfunction and its ability to cause postoperative heart failure is increasingly recognised. The latest evidence regarding diastolic dysfunction and the impact on non‐cardiac surgery are examined to help guide fluid management for the non‐cardiac anaesthetist.
Spinal cord injury arising in anaesthesia practice
Authors: Hewson D. W. , Bedforth N. M. , Hardman J. G.
Published: January 2018

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury – vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis – will be discussed in turn. For each condition, we draw attention to practical, evidence‐based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia.
Adverse drug reactions
Authors: Patton K. , Borshoff D. C.
Published: January 2018

Adverse drug reactions are a cause of significant morbidity and mortality to patients and a source of financial burden to the healthcare system. Of the wide spectrum of adverse drug reactions, the most concerning to the anaesthetist remain anaphylaxis and malignant hyperthermia. Although the incidence of anaphylaxis under anaesthesia is difficult to ascertain, it occurs commonly enough that most anaesthetists will manage at least one case in their career. The wide range of drugs given in the peri‐operative period and the variable presentation in the anaesthetised patient can delay diagnosis and treatment, and adversely affect outcome. Furthermore, despite improvements in testing, causative drugs can still be difficult to identify, as adverse reactions may be mediated by mechanisms other than IgE activation. With an increase in the reporting of anaphylaxis to newer anaesthetic drugs such as sugammadex, combined with change over the recent decades in the most likely causative peri‐operative agents, it is imperative anaesthetists remain up to date on recent developments. In addition, they should be vigilant to patient characteristics, including pharmacogenetic variations that may predispose to adverse drug reactions, in order to help minimise risks of a reaction. The severity of adverse drug reactions to peri‐operative drugs means morbidity and mortality remain high.
Influence of CYP2D6,CYP3A4,CYP3A5 and ABCB1 Polymorphisms on Pharmacokinetics and Safety of Aripiprazole in Healthy Volunteers
Authors: Belmonte Carmen , Ochoa Dolores , Román Manuel , Saiz‐Rodríguez Miriam , Wojnicz Aneta , Gómez‐Sánchez Clara Isabel , Martín‐Vílchez Samuel , Abad‐Santos Francisco
Published: January 2018

The aim of this study was to investigate the effect of polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A4 and CYP3A5 enzymes and in P‐glycoprotein (P‐gp) on the pharmacokinetics and safety of aripiprazole and, its active metabolite, dehydro‐aripiprazole, in 148 healthy volunteers from six bioequivalence trials receiving a single oral dose of aripiprazole. The plasma concentrations of both analytes were measured by LC‐MS/MS. CYP2D6 (*3,*4,*5,*6,*7,*9 and copy number variations), CYP3A4 (*20 and *22), CYP3A5*3 and C3435T, C1236T and G2677T/A in ABCB1 gene were determined. As the number of active CYP2D6 alleles decreased, AUC0−t, Cmax and t1/2 of aripiprazole were higher and clearance of aripiprazole, AUC0−t of dehydro‐aripiprazole and ratio dehydro‐aripiprazole/aripiprazole were lower. AUC0−t of aripiprazole of poor metabolizer (PM) subjects was increased by 50% compared to extensive metabolizers (EM), and AUC0−t of dehydro‐aripiprazole was decreased by 33%. ABCB1 1236TT subjects had a lower clearance of aripiprazole (p = 0.023) and AUC0−t (p = 0.039) and Cmax of dehydro‐aripiprazole (p = 0.036) compared to C/C. CYP3A5*3/*3 subjects had a 10% lower ratio dehydro‐aripiprazole/aripiprazole than *1/*3 (p = 0.019). Adverse drug reactions (ADRs) had a directly proportional relationship with AUC0−t of aripiprazole (p = 0.001), especially nausea/vomiting, which were more common in women (p = 0.005). Women and CYP3A5*1/*1 subjects showed more often dizziness (p = 0.034; p = 0.009). Pharmacokinetics of aripiprazole is affected by CYP2D6 phenotype but also by sex and C1236T (ABCB1 gene), while dehydro‐aripiprazole pharmacokinetics is affected by CYP2D6 and C1236T. The ratio dehydro‐aripiprazole/aripiprazole was influenced by CYP2D6 phenotype and CYP3A5*3. Concentrations of aripiprazole, sex, CYP3A5*3 and CYP2D6 were involved in the development of ADRs.
Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: A systematic review and meta‐analysis
Authors: Thompson William , Russell Ginny , Baragwanath Genevieve , Matthews Justin , Vaidya Bijay , Thompson‐Coon Jo
Published: January 2018

Background

In the last 2 decades, several studies have examined the association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children and shown conflicting results.

Aim

This systematic review aimed to assess the evidence for an association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children. We also sought to assess whether levothyroxine treatment for maternal thyroid hormone insufficiency improves child neurodevelopment outcomes.

Methods

We performed systematic literature searches in MEDLINE, EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit, Grey Source and Open Grey (latest search: March 2017). We also conducted targeted web searching and performed forwards and backwards citation chasing. Meta‐analyses of eligible studies were carried out using the random‐effects model.

Results

We identified 39 eligible articles (37 observational studies and 2 randomized controlled trials [RCT]). Meta‐analysis showed that maternal subclinical hypothyroidism and hypothyroxinaemia are associated with indicators of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04, respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not associated with attention deficit hyperactivity disorder, and their effect on the risk of autism in offspring was unclear. Meta‐analysis of RCTs showed no evidence that levothyroxine treatment for maternal hypothyroxinaemia or subclinical hypothyroidism reduces the incidence of low intelligence quotient in offspring.

Limitations

Although studies were generally of good quality, there was evidence of heterogeneity between the included observational studies (I2 72%‐79%).

Conclusion

Maternal hypothyroxinaemia and subclinical hypothyroidism may be associated with intellectual disability in offspring. Currently, there is no evidence that levothyroxine treatment, when initiated 8‐ to 20‐week gestation (mostly between 12 and 17 weeks), for mild maternal thyroid hormone insufficiency during pregnancy reduces intellectual disability in offspring.
Children's Acquisition of the English Past‐Tense: Evidence for a Single‐Route Account From Novel Verb Production Data
Authors: Blything Ryan P. , Ambridge Ben , Lieven Elena V.M.
Published: January 2018

This study adjudicates between two opposing accounts of morphological productivity, using English past‐tense as its test case. The single‐route model (e.g., Bybee & Moder, ) posits that both regular and irregular past‐tense forms are generated by analogy across stored exemplars in associative memory. In contrast, the dual‐route model (e.g., Prasada & Pinker, ) posits that regular inflection requires use of a formal “add ‐ed” rule that does not require analogy across regular past‐tense forms. Children (aged 3–4; 5–6; 6–7; 9–10) saw animations of an animal performing a novel action described with a novel verb (e.g., gezz; chake). Past‐tense forms of novel verbs were elicited by prompting the child to describe what the animal “did yesterday.” Collapsing across age group (since no interaction was observed), the likelihood of a verb being produced in regular past‐tense form (e.g., gezzed; chaked) was positively associated with the verb's similarity to existing regular verbs, consistent with the single‐route model only. Results indicate that children's acquisition of the English past‐tense is best explained by a single‐route analogical mechanism that does not incorporate a role for formal rules.
Importance of phosphoinositide binding by human β‐defensin 3 for Akt‐dependent cytokine induction
Authors: Phan Thanh Kha , Lay Fung T , Hulett Mark D
Published: January 2018

Host defense peptides (HDPs) are well‐characterized for their antimicrobial activities but also variously display potent immunomodulatory effects. Human β‐defensin 3 (HBD‐3) belongs to a well‐known HDP family known as defensins and is able to induce leukocyte chemotactic recruitment, leukocyte activation/maturation, proinflammatory cytokine release, and co‐stimulatory marker expression. HBD‐3‐stimulated cytokine induction is NF‐κB‐dependent and was initially suggested to act via G protein‐coupled C‐C chemokine receptor phospholipase C (PLC) and/or Toll‐like receptor signaling. Subsequent pharmacological inhibition, however, revealed that NF‐κB activation by HBD‐3 is receptor‐independent and instead involves the phosphoinositide 3‐kinase (PI3K)‐protein kinase B (Akt) pathway, the mechanism of which remains undetermined. Recently, we have shown that HBD‐3 can enter mammalian cells and bind to inner membrane phosphoinositide 4,5‐bisphosphate [PI(4,5)P2], an important second lipid messenger of PLC and PI3K‐Akt pathways. In this study, we report that the interaction of HBD‐3 with PI(4,5)P2 is important for PI3K‐Akt‐NF‐κΒ‐mediated induction of tumor necrosis factor and interleukin‐6. These data provide insights into the mechanism of immunomodulation by HBD‐3, and more generally, highlight the complex multifaceted signaling roles of HDPs in innate defense. Furthermore, it is suggested that the proposed mode of action may be conserved in other HDPs.
The T‐cell fingerprint of MALT1 paracaspase revealed by selective inhibition
Authors: Bardet Maureen , Unterreiner Adeline , Malinverni Claire , Lafossas Frédérique , Vedrine Corinne , Boesch Danielle , Kolb Yeter , Kaiser Daniel , Glück Anton , Schneider Martin A , Katopodis Andreas , Renatus Martin , Simic Oliver , Schlapbach Achim , Quancard Jean , Régnier Catherine H , Bold Guido , Pissot‐Soldermann Carole , Carballido José M , Kovarik Jiri , Calzascia Thomas , Bornancin Frédéric
Published: January 2018

Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is essential for immune responses triggered by antigen receptors but the contribution of its paracaspase activity is not fully understood. Here, we studied how MALT1 proteolytic function regulates T‐cell activation and fate after engagement of the T‐cell receptor pathway. We show that MLT‐827, a potent and selective MALT1 paracaspase inhibitor, does not prevent the initial phase of T‐cell activation, in contrast to the pan‐protein kinase C inhibitor AEB071. However, MLT‐827 strongly impacted cell expansion after activation. We demonstrate this is the consequence of profound inhibition of IL‐2 production as well as reduced expression of the IL‐2 receptor alpha subunit (CD25), resulting from defective canonical NF‐κB activation and accelerated mRNA turnover mechanisms. Accordingly, MLT‐827 revealed a unique transcriptional fingerprint of MALT1 protease activity, providing evidence for broad control of T‐cell signaling pathways. Altogether, this first report with a potent and selective inhibitor elucidates how MALT1 paracaspase activity integrates several T‐cell activation pathways and indirectly controls gamma‐chain receptor dependent survival, to impact on T‐cell expansion.
Heterogeneous effects of M‐CSF isoforms on the progression of MLL‐AF9 leukemia
Authors: Wang Rong , Feng Wenli , Yang Feifei , Yang Xiao , Wang Lina , Chen Chong , Hu Yuting , Ren Qian , Zheng Guoguang
Published: January 2018

Macrophage colony‐stimulating factor (M‐CSF) regulates both malignant cells and microenvironmental cells. Its splicing isoforms show functional heterogeneity. However, their roles on leukemia have not been well established. Here, the expression of total M‐CSF in patients with hematopoietic malignancies was analyzed. The roles of M‐CSF isoforms on the progression of acute myeloid leukemia (AML) were studied by establishing MLL‐AF9‐induced mouse AML models with high level membrane‐bound M‐CSF (mM‐CSF) or soluble M‐CSF (sM‐CSF). Total M‐CSF was highly expressed in myeloid leukemia patients. Furthermore, mM‐CSF but not sM‐CSF prolonged the survival of leukemia mice. While sM‐CSF was more potent to promote proliferation and self‐renew, mM‐CSF was more potent to promote differentiation. Moreover, isoforms had different effects on leukemia‐associated macrophages (LAMs) though they both increase monocytes/macrophages by growth‐promoting and recruitment effects. In addition, mM‐CSF promoted specific phagocytosis of leukemia cells by LAMs. RNA‐seq analysis revealed that mM‐CSF enhanced phagocytosis‐associated genes and activated oxidative phosphorylation and metabolism pathway. These results highlight heterogeneous effects of M‐CSF isoforms on AML progression and the mechanisms of mM‐CSF, that is, intrinsically promoting AML cell differentiation and extrinsically enhancing infiltration of macrophages and phagocytosis by macrophages, which may provide potential clues for clinical diagnosis and therapy.
Does Interindustry and Intraindustry Information Help Predict Financial Distress?
Authors: Lin Hsiou‐Wei William , Wu Ruei‐Shian , Lo Huai‐Chun
Published: January 2018

This study investigates whether and how the accounting ratios of peer firms within the same industry (the industry peers) or firms within the industry of their customers (the downstream peers) help improve the predictability of sample firm financial distress. We document that the Z‐score factors of the companies with high correlation in stock returns help predict financial distress. The results show that accounting‐based ratios of the industry peers and the downstream peers enhance the accuracy of early warnings of financial distress, especially when prior returns of peer firms are highly correlated with the sample firm.
Spatio‐temporal dynamics in maturation and spawning of Patagonian toothfish Dissostichus eleginoides on the sub‐Antarctic Kerguelen Plateau
Authors: Yates P. , Ziegler P. , Welsford D. , McIvor J. , Farmer B. , Woodcock E.
Published: January 2018

This study investigated maturation and spawning of Patagonian toothfish Dissostichus eleginoides in the Heard Island and McDonald Islands (HIMI) fishery on the Kerguelen Plateau in the Indian Sector of the Southern Ocean based on gonads and otoliths collected between 2004 and 2015 and using histological analyses and calibration of macroscopic staging criteria. Dissostichus eleginoides at HIMI spawn throughout the austral late autumn and winter months of May–August and spawning activity is concentrated on slopes along the west and south of the plateau around HIMI at depths of 1500–1900 m. Comparison between histological analyses and macroscopic gonad staging indicated that many fish that had spawned, as indicated by the presence of post‐ovulatory follicles, returned to a resting stage which was macroscopically indistinguishable from maturing fish. Furthermore, the occurrence of females of all size classes with low gonado‐somatic index and low macroscopic gonad stage during the spawning season suggested that a proportion of mature females did not spawn every year. Age‐at‐maturity estimates, based on the assumption that fish of macroscopic stages ≥2 were mature, decreased between the 2004–2009 and 2010–2015 periods for both sexes. The magnitude of this temporal variation in age at maturity, however, varied between gear types and fishing depths and variable sampling regimes probably influenced these variations. This study highlights the importance of correct interpretation of macroscopic gonad stages and understanding the influence of fishery operations on estimations of life‐history parameters.
Expression of CD163 in hereditary gingival fibromatosis: A possible association with TGF‐β1
Authors: Hazzaa Hala H. , Gouda Ossama M. , Kamal Naglaa M. , Ali Shereen Abdel Moula , El Shiekh Marwa A. M. , Tawfik Marwa M.
Published: January 2018

Background

Although several studies have discussed some of the molecular and cellular changes associated with hereditary gingival fibromatosis (HGF), its pathogenesis is still largely unclear. This study was directed to detect and outline the degree of relationship between the immunophenotyped macrophages (M2) expressing CD163 and TGF‐β1 in patients with gingival overgrowth due to HGF.

Methods

Biopsies from 20 patients suffering from HGF and 20 normal control subjects were harvested, histologically and immunohistochemically stained then, analyzed and statistically compared and correlated for CD163 immunoexpression and TGF‐β1.

Results

All HGF specimens expressed TGF‐β1 by most of the connective tissue fibroblasts, with statistically high significant mean of area % (2.61 ± 0.41) compared to normal controls (0.11 ± 0.06; P = .001). All control specimens revealed negligible CD163 immunostaining of the few inflammatory cells found with a mean area of % (0.69 ± 0.12), while the specimens of HGF cases showed statistically significant higher CD163 expression (3.39 ± 0.75) at (P = .007). A statistically significant higher mean % of M2 cells expressing CD163 in relation to the total number of the inflammatory cells was revealed in HGF (34.46 ± 2.04) compared to the control group (16.36 ± 2.39; P‐value ≤ .05). Moderate correlation between CD163 and TGF‐β1 was detected in HGF (r = .451; P‐value < .05).

Conclusions

CD163 and TGF‐β1 were clearly expressed in HGF cases compared to healthy control patients, with significant correlation. In HGF, the increase in CD 163‐positive cells was specific and not dependent on the chronic gingival inflammation.
Effects of deficiency and surplus dietary threonine on reproductive performance of primiparous pregnant gilts
Authors: Shi M. , Liu T. , Li T. , Wang H. , Yuan T. , Li D. , Wang J.
Published: January 2018

Dietary threonine imbalance is known to impair reproductive performances of gestating sows, but the underlying mechanisms are largely unknown. In this study, effects of deficiency and surplus dietary threonine during gestation on reproductive performance, serum metabolites and hormones concentration, and colostral nutrient and immunoglobulin contents of primiparous sows were investigated. Ninety primiparous pregnant gilts were assigned to one of the three dietary treatments with different standardized ileal digestible threonine/lysine ratios at 0.59, 0.72 and 0.85, which represented deficient (DT), adequate (AT) and surplus (ST) dietary threonine concentration respectively. Maternal body weight gain from day 80–110 of gestation was highest (p < .05) for gilts fed AT than for gilts fed DT or ST. On days 30 and 110, serum threonine concentration increases in a dose‐dependent manner with the increasing of dietary threonine concentration in (p < .01), serum urea nitrogen concentration was lower (p < .01) in gilts fed AT than DT or ST, and serum insulin‐like growth factor‐I (IGF‐I) was lowest (p < .05) for gilts fed DT. On day 110, gilts fed AT had lower serum progesterone concentration but higher concentrations of serum prolactin (p < .05) compared to DT and ST. Concentration of colostral immunoglobulin A and G from gilts fed DT was lower (p < .05) compared with gilts fed AT or ST. In conclusion, gilts with the adequate threonine intake were more able to conserve dietary amino acids to support foetal and maternal tissue gain. Deficient or ST threonine intake may induce a delay in changes in progesterone and prolactin concentrations during the prepartum period impeding the transition from pregnancy to lactation.
Daclatasvir and reduced‐dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min
Authors: Goel Amit , Bhadauria Dharmendra S , Kaul Anupma , Verma Prashant , Mehrotra Mayank , Gupta Amit , Sharma Raj K , Rai Praveer , Aggarwal Rakesh
Published: January 2018

Aim

Sofosbuvir is a key agent for HCV treatment. It is not recommended for patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 mL/min. We report real‐life experience of treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half‐daily dose of sofosbuvir.

Methods

Adults patients who (i) had eGFR<30 mL/min and detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA based regimens were included. All patients were treated with daily doses of daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12 weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or on immunosuppressive drugs. The end‐points of the study were: (i) 12 weeks of follow‐up after treatment completion, (ii) treatment discontinuation, or (iii) death or loss to follow‐up.

Results

Thirty‐six (88%) among 41 included patients (median [range] age: 48 [19–75] years; 25 [61%] male; genotype 1/3/4 were 17/ 22/2; cirrhosis 5) completed the treatment, two discontinued and three died during treatment. On an intention‐to‐treat basis, HCV RNA were undetectable at 4 weeks of treatment, treatment completion and after 12 weeks of follow‐up in 40/41 (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had a relapse.

Conclusions

Daclatasvir and half‐daily dose of sofosbuvir was effective against genotype 1 and 3 HCV infection in patients with eGFR <30 mL/min. This combination could be a pangenotypic treatment option for such patients.
Aboveground herbivory induced jasmonates disproportionately reduce plant reproductive potential by facilitating root nematode infestation
Authors: Machado Ricardo A.R. , Arce Carla C.M. , McClure Michael A. , Baldwin Ian T. , Erb Matthias
Published: January 2018

Different plant feeders, including insects and parasitic nematodes, can influence each other by triggering systemic changes in their shared host plants. In most cases, however, the underlying mechanisms are unclear, and the consequences for plant fitness are not well understood. We studied the interaction between leaf feeding Manduca sexta caterpillars and root parasitic nematodes in Nicotiana attenuata. Simulated M. sexta attack increased the abundance of root parasitic nematodes in the field and facilitated Meloidogyne incognita reproduction in the glasshouse. Intact jasmonate biosynthesis was found to be required for both effects. Flower counts revealed that the jasmonate‐dependent facilitation of nematode infestation following simulated leaf attack reduces the plant's reproductive potential to a greater degree than would be expected from the additive effects of the individual stresses. This work reveals that jasmonates mediate the interaction between a leaf herbivore and root parasitic nematodes and illustrates how plant‐mediated interactions can alter plant's reproductive potential. The selection pressure resulting from the demonstrated fitness effects is likely to influence the evolution of plant defense traits in nature.
“Post‐Truth,” “Alternative Facts” and “Fakenomics”
Authors: Keeton Gavin
Published: January 2018

South African companies are accused of hoarding profits to accumulate large amounts of “idle” cash, as well as of being the perpetrators of massive illegal capital flight. This paper argues that much of the claimed corporate cash is either offshore or belongs to banks. It reminds that bank deposits increase when companies borrow, not when they retain profits. It shows, too, that measures of massive capital flight actually reflect data errors. Exaggerating, through faulty methodology the extent to which companies have cash or may be involved in illegal capital flight is unhelpful. It exacerbates already‐fraught government‐business relations, and complicates the search for solutions to South Africa's economic problems.
Current and Military‐Specific Gender Minority Stress Factors and Their Relationship with Suicide Ideation in Transgender Veterans
Authors: Tucker Raymond P. , Testa Rylan J. , Reger Mark A. , Simpson Tracy L. , Shipherd Jillian C. , Lehavot Keren
Published: January 2018

Research suggests the prevalence of suicide ideation and suicide attempts in the transgender veteran community may be upwards of 20 times higher than nontransgender veterans, who are known to be at increased risk than the general US population. This study aimed to understand the potential influence of external and internal minority stress experienced during and after military service on past‐year and recent suicide ideation in a sample of 201 transgender veterans. Nonparametric bootstrapping analyses indicated past‐year transgender‐specific discrimination and rejection (external minority stress) indirectly predicted frequency of both past‐year and past 2‐week suicide ideation through past‐year shame related to gender identity (internal minority stress). This result was significant when controlling for symptoms of depression and demographics. Similar patterns emerged when examining relationships among military external and internal minority stress on suicide outcomes. These results suggest that attempts to reduce both the experience and impact of minority stressors related to gender identity during and after military service may be an important avenue for suicide prevention.
Translating international HIV treatment guidelines into local priorities in Indonesia
Authors: Tromp Noor , Prawiranegara Rozar , Siregar Adiatma , Wisaksana Rudi , Pinxten Lucas , Pinxten Juul , Lesmana Putra Arry , Kurnia Sunjaya Deni , Jansen Maarten , Hontelez Jan , Maurits Scott , Maharani Febrina , Bijlmakers Leon , Baltussen Rob
Published: January 2018

Objective

International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV‐infected individuals and establish local‐level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical guidance is provided for such priority‐setting processes. Evidence‐informed deliberative processes (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant social values with rational decision‐making informed by evidence on these values. This study reports on the first‐time implementation and evaluation of an EDP in HIV control, organised to support the AIDS Commission in West Java province, Indonesia, in the development of its strategic plan for 2014–2018.

Methods

Under the responsibility of the provincial AIDS Commission, an EDP was implemented to select priority interventions using six steps: (i) situational analysis; (ii) formation of a multistakeholder Consultation Panel; (iii) selection of criteria; (iv) identification and assessment of interventions’ performance; (v) deliberation; and (vi) selection of funding and implementing institutions. An independent researcher conducted in‐depth interviews (n = 21) with panel members to evaluate the process.

Results

The Consultation Panel included 23 stakeholders. They identified 50 interventions and these were evaluated against four criteria: impact on the epidemic, stigma reduction, cost‐effectiveness and universal coverage. After a deliberative discussion, the Consultation Panel prioritised a combination of several treatment, prevention and mitigation interventions.

Conclusion

The EDP improved both stakeholder involvement and the evidence base for the strategic planning process. EDPs fill an important gap which international guidelines and current tools for strategic planning in HIV control leave unaddressed.
GM‐CSF ameliorates microvascular barrier integrity via pericyte‐derived Ang‐1 in wound healing
Authors: Yan Min , Hu Yange , Yao Min , Bao Shisan , Fang Yong
Published: January 2018

Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound‐area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony‐stimulating factor (GM‐CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM‐CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM‐CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full‐thickness skin wound mouse model after GM‐CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co‐culture system using a FITC‐Dextran permeability assay. To identify the source of angiopoietin‐1 (Ang‐1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang‐1 on GM‐CSF maintaining microvascular stabilization, Ang‐1 siRNA was applied to inhibit Ang‐1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM‐CSF treatment in mouse wound sites. GM‐CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang‐1 protein level that was derived by perictye. Furthermore, applications of siRNAAng‐1 inhibited GM‐CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM‐CSF ameliorates microvascular barrier integrity via pericyte‐derived Ang‐1 during wound healing.
Affordable Uncertainty Quantification for Industrial Problems: Application to Aero-Engine Fans
Authors: Ghisu Tiziano , Shahpar Shahrokh
Published: January 2018

Uncertainty quantification (UQ) is an increasingly important area of research. As components and systems become more efficient and optimized, the impact of uncertain parameters is likely to become critical. It is fundamental to consider the impact of these uncertainties as early as possible during the design process, with the aim of producing more robust designs (less sensitive to the presence of uncertainties). The cost of UQ with high-fidelity simulations becomes therefore of fundamental importance. This work makes use of least-squares approximations in the context of appropriately selected polynomial chaos (PC) bases. An efficient technique based on QR column pivoting has been employed to reduce the number of evaluations required to construct the approximation, demonstrating the superiority of the method with respect to full-tensor quadrature (FTQ) and sparse-grid quadrature (SGQ). Orthonormal polynomials used for the PC expansion are calculated numerically based on the given uncertainty distribution, making the approach optimal for any type of input uncertainty. The approach is used to quantify the variability in the performance of two large bypass-ratio jet engine fans in the presence of shape uncertainty due to possible manufacturing processes. The impacts of shape uncertainty on the two geometries are compared, and sensitivities to the location of the blade shape variability are extracted. The mechanisms at the origin of the change in performance are analyzed in detail, as well as the differences between the two configurations.
Nodal Unsteady Inverse Elastohydrodynamic Lubrication: Axisymmetric Normal Approach
Authors: Booker J. F. , Boedo S.
Published: January 2018

An “inverse” formulation is described for general problems of unsteady elastohydrodynamic lubrication (EHL). Spatial discretization gives an explicit initial-value ordinary differential equation (ODE) problem with (interior) nodal film thicknesses as state variables. Numerical results are compared with published experimental results for normal approach of a spherical surface to an elastic foundation.
On the Singularity Theory Applied in Rail Vehicle Bifurcation Problem
Authors: Dong Hao , Zhao Bin , Xie Jianhua
Published: January 2018

The application of Hopf bifurcation is essential to rail vehicle dynamics because it corresponds to the linear critical speed. In engineering, researchers always wonder which vehicle parameters are sensitive to it. With the nonlinear singularity theory's development, it has been widely applied in many other engineering areas. This paper mainly studies the singularity theory applied in nonlinear rail vehicle dynamics. First, the bifurcation norm forms of wheelset and bogie system are, respectively, deduced. Then the universal unfolding is obtained and the influences of perturbation on bifurcation are investigated. By the analysis of a simple bar-spring system, the relationship between the unfolding and original perturbation parameters can be found. But this may be difficult to calculate for the case in vehicle system because of higher degrees-of-freedom (DOFs) and indicate that can explain the influence of all possible parameters perturbations on vehicle bifurcation.
A Before-and-After Study of the Effectiveness of an Antimicrobial Stewardship Program in Critical Care
Authors: Álvarez-Lerma Francisco , Grau Santiago , Echeverría-Esnal Daniel , Martínez-Alonso Montserrat , Gracia-Arnillas María Pilar , Horcajada Juan Pablo , Masclans Juan Ramón
Published: January 2018

We evaluated the use of antimicrobials expressed as defined daily doses (DDDs) per 1,000 patient days and days of therapy (DOT) per 100 occupied bed-days in a intensive care unit (ICU) of a general hospital in Barcelona, Spain, before and after implementation of an antimicrobial stewardship (AMS) program (2007 to 2010 versus 2011 to 2015). The quarterly costs of antimicrobials used in the ICU and its weight in the overall hospital costs of antimicrobials were calculated. The effect of the applied AMS program on DDDs and DOT time series data was analyzed by means of intervention time series analysis. A total of 5,002 patients were included (1,971 for the first [before] period and 3,031 for the second [after] period). The percentage of patients treated with one or more antimicrobials decreased from 88.6 to 77.2% (
P
< 0.001). DDDs decreased from 246.8 to 192.3 (mean difference, −54.5;
P
= 0.001) and DOT from 66.7 to 54.6 (mean difference, −12.1;
P
= 0.066). The mean cost per trimester decreased from €115,543 to €73,477 (mean difference, −42,065.4 euros;
P
< 0.001), and the percentage of ICU antimicrobials cost with respect to the total cost of hospital antimicrobials decreased from 28.5 to 22.8% (mean difference, −5.59;
P
= 0.023). Implementation of an AMS program in the ICU was associated with a marked reduction in the use of antimicrobials, with cost savings close to one million euros since its implementation. An AMS program can have a significant impact on optimizing antimicrobial use in critical care practice.
The ‘Buntsandstein’ gas play of the Horn Graben (German and Danish offshore): dry well analysis and remaining hydrocarbon potential
Authors: Kilhams Ben , Stevanovic Snezana , Nicolai Carlo
Published: January 2018

An analysis of the Lower Triassic ‘Buntsandstein’ gas play in the underexplored Mesozoic rift system of the German–Danish Horn Graben is presented. Dry hole information from four well penetrations is analysed alongside the development of a 3D basin model. It is demonstrated that the dry holes do not preclude the existence of a working hydrocarbon system. Reservoir and seal elements are present, although details of quality and distribution are uncertain. Carboniferous coal preservation is likely, in a limited area, within the graben and can be constrained through seismic mapping. Vertical gas migration through the Zechstein interval is considered likely due to a large thickness variability (driven by halokinesis and facies changes). The overlap of peak gas-expulsion timing and halokinetic movements make rollover/turtle-back traps risky in terms of breaching or underfill. Dry wells in Denmark are explained by a combination of this relative timing and uncertainty over longer distance migration. This play analysis demonstrates a general agreement with previously published 1D basin models with respect to gas-expulsion timing. However, in contrast to published examples, it is shown that the Zechstein interval can allow for vertical gas migration. Considerable uncertainty in parameters, such as depth conversion, amount of erosion and migration paths, are recognized. Exploration opportunities remain, albeit relatively high risk, in the German area of the graben both in the ‘Buntsandstein’ play and at other stratigraphic levels.
Variability Bugs in Highly Configurable Systems
Authors: Abal Iago , Melo Jean , Stănciulescu Ştefan , Brabrand Claus , Ribeiro Márcio , Wąsowski Andrzej
Published: January 2018

Variability-sensitive verification pursues effective analysis of the exponentially many variants of a program family. Several variability-aware techniques have been proposed, but researchers still lack examples of concrete bugs induced by variability, occurring in real large-scale systems. A collection of real world bugs is needed to evaluate tool implementations of variability-sensitive analyses by testing them on real bugs. We present a qualitative study of 98 diverse variability bugs (i.e., bugs that occur in some variants and not in others) collected from bug-fixing commits in the Linux, Apache, BusyBox, and Marlin repositories. We analyze each of the bugs, and record the results in a database. For each bug, we create a self-contained simplified version and a simplified patch, in order to help researchers who are not experts on these subject studies to understand them, so that they can use these bugs for evaluation of their tools. In addition, we provide single-function versions of the bugs, which are useful for evaluating intra-procedural analyses. A web-based user interface for the database allows to conveniently browse and visualize the collection of bugs. Our study provides insights into the nature and occurrence of variability bugs in four highly-configurable systems implemented in C/C++, and shows in what ways variability hinders comprehension and the uncovering of software bugs.
Shadow Symbolic Execution with Java PathFinder
Authors: Noller Yannic , Nguyen Hoang Lam , Tang Minxing , Kehrer Timo
Published: January 2018

Regression testing ensures that a software system when it evolves still performs correctly and that the changes introduce no unintended side-effects. However, the creation of regression test cases that show divergent behavior needs a lot of effort. A solutionis the idea of shadow symbolic execution, originally implemented based on KLEE for programs written in C, which takes a unified version of the old and the new program and performs symbolic execution guided by concrete values to explore the changed behavior. In this work, we apply the idea of shadow symbolic execution to Java programs and, hence, provide an extension of the Java PathFinder (JPF) project to perform shadow symbolic execution on Java bytecode. The extension has been applied on several subjects from the JPF test classes where it successfully generated test inputs that expose divergences relevant for regression testing.
A Centralized Platform of Open Government Data as Support to Applications in the Smart Cities Context
Authors: Vieira Ianegitz , Alvaro Alexandre
Published: January 2018

Purpose - This article aims to present the design, implementation and validation of an Open Government Data Platform.

Design/methodology/approach - The development of the work took place in 4 steps: survey of the state of the art of literature; design of the open government data platform; implementation and testing of the platform; and, finally, experimental validation with a group of students of a Brazilian university.

Findings - Through the validations of the platform can be noted advantages with respect to the productivity gain for the development of solutions, in the context of Smart Cities, using the proposed platform.

Research limitations/implications - The experiment was developed in a controlled manner in the context of a Brazilian university. In addition, there is a need to capture more data from other town hall to store on the platform.

Originality/value - The centralized storage of open government data is a tool that enables the decision-making of public managers as well as the beginning of the transformation of the present cities to a smart city.