bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing genome-wide association study results from different measurements of an underlying phenotype
Authors: Gage Joseph L. , Natalia de Leon , Murray Clayton
Published: May 2018

Increasing popularity of high-throughput phenotyping technologies, such as image-based phenotyping, offer novel ways for quantifying plant growth and morphology. These new methods can be more or less accurate and precise than traditional, manual measurements. Many large-scale phenotyping efforts are conducted to enable genome-wide association studies (GWAS), but it is unclear exactly how alternative methods of phenotyping will affect GWAS results. In this study we simulate phenotypes that are controlled by the same set of causal loci but have differing heritability, similar to two different measurements of the same morphological character. We then perform GWAS with the simulated traits and create receiver operating characteristic (ROC) curves from the results. The areas under the ROC curves (AUCs) provide a metric that allows direct comparisons of GWAS results from different simulated traits. We use this framework to evaluate the effects of heritability and the number of causative loci on the AUCs of simulated traits; we also test the differences between AUCs of traits with differing heritability. We find that both increasing the number of causative loci and decreasing the heritability reduce a trait’s AUC. We also find that when two traits are controlled by a greater number of causative loci, they are more likely to have significantly different AUCs as the difference between their heritabilities increases. These results provide a framework for deciding between competing phenotyping strategies when the ultimate goal is to generate and use phenotype-genotype associations from GWAS.
Waves of Maturation and Senescence in Micro-Structural MRI Markers of Human Cortical Myelination over the Lifespan
Authors: Grydeland Håkon , Vértes Petra E. , Váša František , Romero-Garcia Rafael , Whitaker Kirstie , Alexander-Bloch Aaron F. , Bjørnerud Atle , Patel Ameera X. , Sedervicius Donatas , Tamnes Christian K. , Westlye Lars T. , White Simon R. , Walhovd Kristine B. , Fjell Anders M. , Bullmore Edward T.
Published: May 2018

Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8-85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of 7 cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30s but there was a second wave reaching stability in the 50s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.
Multiple-scattering effects in SAXS and XPCS measurements in the ultra-small-angle region
Authors: Semeraro Enrico F. , Möller Johannes , Narayanan Theyencheri
Published: May 2018

An experimental study of the influence of multiple-scattering events on data acquired by small-angle X-ray scattering (SAXS) and X-ray photon correlation spectroscopy (XPCS) techniques in the ultra-small-angle range is presented. Both techniques rely on the single-scattering assumption and any deviation may lead to erroneous interpretation of structural and dynamical results. Typical effects of multiple scattering on measured static and dynamic scattering from model colloidal suspensions are presented, and it is demonstrated that the same information content as in a single-scattering experiment can be extracted after applying appropriate corrections. The perturbations induced by multiple scattering on resolution, photon statistics and speckle visibility are evaluated and the required optimal experimental conditions are discussed. In many cases, multiple scattering might be tolerable to a certain extent, especially if any shortcomings are outweighed by beneficial effects from counting statistics, acquisition time and signal-to-background ratio. The presented study may help to optimize future experiments and serve as a guide for data evaluation for this type of system.
Fairness in franchisor–franchisee relationship: an integrative perspective
Authors: Shaikh Ateeque , Sharma Dheeraj , Vijayalakshmi Akshaya , Yadav Rama Shankar
Published: May 2018

Purpose

This paper aims to elucidate and extend the concept of power and fairness in the context of franchisor–franchisee relationship.

Design/methodology/approach

On the basis of Dul and Hak’s (2007) recommendations, the conceptual model is developed from closely related domains (e.g. channel relationship) using pertinent theories. On the basis of this comprehensive analysis, new propositions about fairness in a franchisee–franchisor context are drawn. The primary purpose of this research is to conceptually and theoretically further the understanding of antecedents and consequences of fairness in a franchisor–franchisee relationship context by proffering a framework. Finally, this study examines the concept of fairness of its antecedents and moderators that have received scant attention in the context of franchising research.

Findings

This study contends that non-coercive power is perceived fairly. Also, coercive power that is legitimate is perceived fairly. However, coercive power that is illegitimate can be detrimental to relationships between franchisee and franchisor. Furthermore, a franchisee who perceives the relationship to be fair is likely to place more trust in relationship, is more satisfied with relationship and is less likely to be opportunistic. Finally, the study contends that these relationship outcomes are dependent on the franchisee’s personality traits.

Research limitations/implications

One major limitation of this study is that the propositions have not been empirically tested. However, this paper cites several business cases that have been used to support the propositions proffered in the study. Our conceptual model supported by previous theoretical findings and industry cases suggests that it is important to focus on social dimensions along with economic costs of a franchisor–franchisee relationship. Future researchers may empirically examine the relationships posited in this study by using the primary industry data.

Originality/value

This paper takes a comprehensive view of various social constructs affecting a franchisor–franchisee relationship. It also highlights the role of individual personality factors in a franchisor–franchisee relationship, extends prior work on relational dimensions from channels to the franchising context and provides managerial conclusions.
Mutations in mevalonate pathway genes in patients with familial or sporadic porokeratosis
Authors: Leng Yunji , Yan Lulu , Feng Hongquan , Chen Chen , Wang Shusen , Luo Yang , Cao Lihua
Published: May 2018

Porokeratosis comprises heterogeneous keratinization disorders that are characterized by one or more atrophic patches surrounded by a ridge‐like cornoid lamella. In this study, we evaluated seven families affected by porokeratosis and five sporadic patients of the disease in a Chinese population. We performed Sanger sequencing of exons and flanking intron–exon boundaries of mevalonate pathway genes (MVD, MVK, PMVK and FDPS) and of SLC17A9. In five familial and three sporadic patients, we detected six variations, including four novel mutations (MVD c.1A>G; p.Met1?, c.916G>A; p.Ala306Thr, c.1013+1G>A, and PMVK c.65A>G; p.Lys22Arg) and two recurrent mutations (MVD c.746T>C; p.Phe249Ser, and MVK c.1028T>C; p.Leu343Pro). We then applied I‐TASSER and iGEMDOCK to assess these variants for probable functional impacts. The findings of this study extend the mutation spectrum of porokeratosis and provide further evidence for the genetic basis of this disease.
Travel time computations using a compact eikonal equation for vertical transverse isotropic media
Authors: Moghaddam Peyman , Khajavi Reza , Keers Henk
Published: May 2018

Eikonal solvers often have stability problems if the velocity model is mildly heterogeneous. We derive a stable and compact form of the eikonal equation for P‐wave propagation in vertical transverse isotropic media. The obtained formulation is more compact than other formulations and therefore computationally attractive. We implemented ray shooting for this new equation through a Hamiltonian formalism. Ray tracing based on this new equation is tested on both simple as well as more realistic mildly heterogeneous velocity models. We show through examples that the new equation gives travel times that coincide with the travel time picks from wave equation modelling for anisotropic wave propagation.
Study on sterol fraction of commercial brands of milk, yoghurt and butter sold in Iranian market and chemometric data analysis
Authors: Sadeghi Naficeh , Rostami Akram , Taghavianpour Alale , Jafari‐Semnani Sourena , Torabi Parisa , Pourjabar Zeinab , Hajimahmoodi Mannan
Published: May 2018

A gas chromatographic procedure for analysis of sterols was developed to detect possible addition of vegetable oils to milk, yoghurt and butter samples. The method involved fat extraction, saponification, hexane extraction, silylation of sterols and then analysis by gas chromatography. The sterol content of 102 samples of milk, yoghurt and butter was determined. Phytosterol content higher than 5% of total sterol was observed in four samples of milk and yoghurt. Principal component analysis showed that there was a direct relationship between the level of phytosterols and fat percentage in yoghurt samples. The described method is accurate and reliable enough to be employed regularly in food quality laboratories.
Determination of the relationship between oxalate degradation and exopolysaccharide production by different Lactobacillus probiotic strains
Authors: Sönmez Şule , Önal Darilmaz Derya , Beyatli Yavuz
Published: May 2018

The aim of this study was to evaluate the protective effects of exopolysaccharide (EPS) production on resistance to gastrointestinal digestive conditions and oxalate by probiotic strains of the species Lactobacillus rhamnosus, Lactobacillus fermentum and Lactobacillus brevis. The oxalate‐degrading ability of the strains was determined using an enzymatic assay. The correlation between oxalate degradation rate and EPS production was not significant (P > 0.05); however, the high‐EPS‐producing L. fermentumIP5 and L. brevisYG7 strains showed high oxalate‐degrading activity, whereas the low‐EPS‐producing strain L. fermentumBP5 demonstrated low oxalate‐degrading activity. The present findings suggest that dietary supplementation with the probiotic strain L. fermentumIP5 could be a promising strategy for the prevention of oxalate stone disease.
Observational pre–post study showed that a quality improvement project reduced paediatric antibiotic prescribing rates in primary care
Authors: Di Mario Simona , Gagliotti Carlo , Buttazzi Rossella , Cisbani Luca , Di Girolamo Chiara , Brambilla Antonio , Moro Maria Luisa ,   the regional working group “Progetto ProBA‐Progetto Bambini e Antibiotici‐2014”
Published: May 2018

Aim

This study assessed the effectiveness of a quality improvement project that aimed to promote more considered antibiotic prescribing in paediatric primary care.

Method

This was an observational pre–post study that used patient‐level prescribing data from the Emilia‐Romagna region of Italy to monitor indicators from 2005 to 2016. Multilevel interventions and activities were started in 2007 and these included developing guidelines and updates, disseminating evidence, audits and feedback, public information campaigns, engaging health managers and performance incentives. The primary outcomes were total antibiotic prescription rates for children aged 0–13 years and the rates for specific drugs.

Results

The intervention was associated with a significant reduction in the antibiotic prescribing rate, from 1307 per 1000 children in 2005 to 881 prescriptions in 2016 (p for trend <0.001), and a significant increase in the ratio of amoxicillin to amoxicillin–clavulanic acid, from 0.6 to 1.1 (p for trend = 0.001). Prescriptions of other second‐choice antibiotics also declined significantly. In contrast, antibiotic prescribing rates remained high in the rest of Italy.

Conclusion

The intervention was effective in promoting a more considered use of antibiotic in paediatric primary care in an Italian region. Further studies are needed to confirm its effectiveness in other settings.
High prevalence and low spontaneous eradication rate of Helicobacter pylori infection among schoolchildren aged 7–12 years
Authors: Zhou Ying , Ye Ziqing , Huang Jie , Huang Ying , Yan Weili , Zhang Yi
Published: May 2018

Aim

Helicobacter pylori infections mainly occur during childhood and may cause chronic diseases and persist for life unless they are treated. The aim of this study was to identify the prevalence and infection status of H. pylori infection among schoolchildren.

Methods

We conducted a cross‐sectional study of 867 children (52% male) aged 7–12 years in a primary school in the Minhang District of Shanghai, China, in 2014, and a one‐year follow‐up study of 352 subjects. The 13C‐urea breath test was used to identify the H. pylori infection at baseline and one year later. A parental questionnaire provided information regarding the children's socioeconomic status and household environment.

Results

The overall prevalence of the H. pylori infection was 24.1% (209/867), with a 95% confidence interval of 21.3% to 27.0%. The one‐year follow‐up study of 352 subjects found that 33.5% were positive for the infection at baseline and 66.5% were negative. We found that 27.1% of the positive cases recovered and 8.9% of the negative cases acquired the infection during the year. The spontaneous eradication rate was only 2.9% over the one‐year period.

Conclusion

The prevalence of the H. pylori infection among Chinese schoolchildren aged 7–12 was high and spontaneous eradication was low.
Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders
Authors: Gill P. A. , van Zelm M. C. , Muir J. G. , Gibson P. R.
Published: May 2018

Background

Butyrate, propionate and acetate are short chain fatty acids (SCFA), important for maintaining a healthy colon and are considered as protective in colorectal carcinogenesis. However, they may also regulate immune responses and the composition of the intestinal microbiota. Consequently, their importance in a variety of chronic inflammatory diseases is emerging.

Aims

To review the physiology and metabolism of SCFA in humans, cellular and molecular mechanisms by which SCFA may act in health and disease, and approaches for therapeutic delivery of SCFA.

Methods

A PubMed literature search was conducted for clinical and pre‐clinical studies using search terms: ‘dietary fibre’, short‐chain fatty acids’, ‘acetate’, ‘propionate’, ‘butyrate’, ‘inflammation’, ‘immune’, ‘gastrointestinal’, ‘metabolism’.

Results

A wide range of pre‐clinical evidence supports roles for SCFA as modulators of not only colonic function, but also multiple inflammatory and metabolic processes. SCFA are implicated in many autoimmune, allergic and metabolic diseases. However, translating effects of SCFA from animal studies to human disease is limited by physiological and dietary differences and by the challenge of delivering sufficient amounts of SCFA to the target sites that include the colon and the systemic circulation. Development of novel targeted approaches for colonic delivery, combined with postbiotic supplementation, may represent desirable strategies to achieve adequate targeted SCFA delivery.

Conclusions

There is a large array of potential disease‐modulating effects of SCFA. Adequate targeted delivery to the sites of action is the main limitation of such application. The ongoing development and evaluation of novel delivery techniques offer potential for translating promise to therapeutic benefit.
Futility of current urine salbutamol doping control
Authors: Heuberger Jules A. A. C. , van Dijkman Sven C. , Cohen Adam F.
Published: May 2018

Aims

Salbutamol is used in the management of obstructive bronchospasm, including that of some elite athletes. It is claimed that high salbutamol (oral) doses may also have an anabolic effect. Therefore, inhalation of salbutamol is restricted by the World Anti‐Doping Agency (WADA) to a maximal daily dose. Urine is tested for violations, but recent cases have resulted in a debate regarding the validity of this approach. It was our aim to determine whether current approaches are sufficiently able to differentiate approved usage from violations.

Methods

We extracted pharmacokinetic parameters from literature for salbutamol and its sulphated metabolite. From these parameters, a semi‐physiological pharmacokinetic model of inhaled and orally administered salbutamol was synthesized, validated against literature data, and used to perform clinical trial simulations (n = 1000) of possible urine concentrations over time resulting from WADA‐allowed and oral unacceptable dosages.

Results

The synthesized model was able to predict the literature data well. Simulations showed a very large range of salbutamol concentrations, with a significant portion of virtual subjects (15.4%) exceeding the WADA threshold limit of 1000 ng ml−1 at 1 h post‐dose.

Conclusions

The observed large variability in urine concentrations indicates that determining the administered dose from a single untimed urine sample is not feasible. The current threshold inadvertently leads to incorrect assumptions of violation, whereas many violations will go unnoticed, especially when samples are taken long after drug administration. These issues, combined with the dubious assertion of its anabolic effect, leads us to conclude that the large effort involved in testing should be reconsidered.
The opioid oxycodone use‐dependently inhibits the cardiac sodium channel NaV1.5
Authors: Meents Jannis E , Juhasz Krisztina , Stölzle‐Feix Sonja , Peuckmann‐Post Vera , Rolke Roman , Lampert Angelika
Published: May 2018

Background and Purpose

Oxycodone is a potent semi‐synthetic opioid that is commonly used for the treatment of severe acute and chronic pain. However, treatment with oxycodone can lead to cardiac electrical changes, such as long QT syndrome, potentially inducing sudden cardiac arrest. Here, we investigate whether the cardiac side effects of oxycodone can be explained by modulation of the cardiac Nav1.5 sodium channel.

Experimental Approach

Heterologously expressed human Nav1.5, Nav1.7 (HEK293 cells) or Nav1.8 channels (mouse N1E‐115 cells) were used for whole‐cell patch‐clamp electrophysiology. A variety of voltage‐clamp protocols were used to test the effect of oxycodone on different channel gating modalities. Human stem cell‐derived cardiomyocytes were used to measure the effect of oxycodone on cardiomyocyte beating.

Key Results

Oxycodone inhibited Nav1.5 channels, concentration and use‐dependently, with an IC50 of 483 μM. In addition, oxycodone slows recovery of Nav1.5 channels from fast inactivation and increases slow inactivation. At high concentrations, these effects lead to a reduced beat rate in cardiomyocytes and to arrhythmia. In contrast, no such effects could be observed on Nav1.7 or Nav1.8 channels.

Conclusions and Implications

Oxycodone leads to an accumulation of Nav1.5 channels in inactivated states, with a slow time course. Although the concentrations needed to elicit cardiac arrhythmias in vitro are relatively high, some patients under long‐term treatment with oxycodone as well as drug abusers and addicts might suffer from severe cardiac side effects induced by the slowly developing effects of oxycodone on Nav1.5 channels.
A novel cross‐species inhibitor to study the function of CatSper Ca2+ channels in sperm
Authors: Rennhack Andreas , Schiffer Christian , Brenker Christoph , Fridman Dmitry , Nitao Elis T , Cheng Yi‐Min , Tamburrino Lara , Balbach Melanie , Stölting Gabriel , Berger Thomas K , Kierzek Michelina , Alvarez Luis , Wachten Dagmar , Zeng Xu‐Hui , Baldi Elisabetta , Publicover Stephen J , Kaupp U Benjamin , Strünker Timo
Published: May 2018

Background and Purpose

Sperm from many species share the sperm‐specific Ca2+ channel CatSper that controls the intracellular Ca2+ concentration and, thereby, the swimming behaviour. A growing body of evidence suggests that the mechanisms controlling the activity of CatSper and its role during fertilization differ among species. A lack of suitable pharmacological tools has hampered the elucidation of the function of CatSper. Known inhibitors of CatSper exhibit considerable side effects and also inhibit Slo3, the principal K+ channel of mammalian sperm. The compound RU1968 was reported to suppress Ca2+ signaling in human sperm by an unknown mechanism. Here, we examined the action of RU1968 on CatSper in sperm from humans, mice, and sea urchins.

Experimental Approach

We resynthesized RU1968 and studied its action on sperm from humans, mice, and the sea urchin Arbacia punctulata by Ca2+ fluorimetry, single‐cell Ca2+ imaging, electrophysiology, opto‐chemistry, and motility analysis.

Key Results

RU1968 inhibited CatSper in sperm from invertebrates and mammals. The compound lacked toxic side effects in human sperm, did not affect mouse Slo3, and inhibited human Slo3 with about 15‐fold lower potency than CatSper. Moreover, in human sperm, RU1968 mimicked CatSper dysfunction and suppressed motility responses evoked by progesterone, an oviductal steroid known to activate CatSper. Finally, RU1968 abolished CatSper‐mediated chemotactic navigation in sea urchin sperm.

Conclusion and Implications

We propose RU1968 as a novel tool to elucidate the function of CatSper channels in sperm across species.
On‐the‐job‐search, wage dispersion and trade liberalization
Authors: Rodrigue Joel , Tsuyuhara Kunio
Published: May 2018

This paper builds a dynamic, general equilibrium, open economy model that allows for ex ante homogeneous workers to experience different wage growth before and after trade liberalization. Key features of our model include a product market composed of heterogeneous firms and a labour market characterized by directed, on‐the‐job‐search and dynamic contracts. We characterize the complementarity of these two sources of wage dispersion in an open economy setting where trade liberalization affects the endogenous equilibrium set of producers and the structure of wages. We find that worker job‐to‐job transitions, through on‐the‐job search, increases the impact of trade liberalization on wage dispersion by 4%.

Recherche d’emploi en cours d’emploi, dispersion des salaires et libéralisation du commerce. Ce mémoire construit un modèle dynamique d’équilibre général d’une économie ouverte qui permet à des travailleurs ex ante homogènes de faire l’expérience de croissance différente des salaires avant et après la libéralisation du commerce. Les caractéristiques importantes du modèle incluent un marché du produit composé de firmes hétérogènes et un marché du travail caractérisé par une recherche dirigée d’emploi en cours d’emploi et des contrats de salaires dynamiques. On caractérise la complémentarité de ces deux sources de dispersion des salaires dans une économie ouverte où la libéralisation du commerce affecte l’équilibre endogène de l’ensemble des producteurs et la structure des salaires. On découvre que les transitions d’emploi à emploi des travailleurs, via la recherche d’emploi en cours d’emploi, accroîssent l’impact de la libéralisation du commerce sur la dispersion des salaires de 4 %.
One‐pot synthesis and antiproliferative activity of novel double‐modified derivatives of the polyether ionophore monensin A
Authors: Klejborowska Greta , Maj Ewa , Wietrzyk Joanna , Stefańska Joanna , Huczyński Adam
Published: May 2018

Monensin A (MON) is a polyether ionophore antibiotic, which shows a wide spectrum of biological activity. New MON derivatives such as double‐modified ester‐carbonates and double‐modified amide‐carbonates were obtained by a new and efficient one‐pot synthesis with triphosgene as the activating reagent and the respective alcohol or amine. All new derivatives were tested for their antiproliferative activity against two drug‐sensitive (MES‐SA, LoVo) and two drug‐resistant (MES‐SA/DX5, LoVo/DX) cancer cell lines, and were also studied for their antimicrobial activity against different Staphylococcus aureus and Staphylococcus epidermidis bacterial strains. For the first time, the activity of MON and its derivatives against MES‐SA and MES‐SA/DX5 were evaluated.
Discovery of 4 exonic and 1 intergenic novel susceptibility loci for leprosy
Authors: Wang Z. , Mi Z. , Wang H. , Sun L. , Yu G. , Fu X. , Wang C. , Bao F. , Yue Z. , Zhao Q. , Wang N. , Cheng X. , Liu H. , Zhang F.
Published: May 2018

Seven new risk coding variants have been identified through an exome‐wide association study (EWAS), which studied the contributions of protein‐coding variants to leprosy susceptibility. But some potential susceptibility loci were not studied in the previous EWAS study because of the project consideration. Seventeen unstudied potential susceptibility loci of the previous EWAS were validated in 3169 cases and 9814 controls in this study. Four disease‐associated exonic loci were identified: rs671 in ALDH2 (P = 2.0 × 10−20, odds ratio [OR] = 1.35), rs13259978 in SLC7A2 (P = 1.74 × 10−8, OR = 1.28), rs925368 in GIT2 (P = 9.18 × 10−17, OR = 1.44), and rs75680863 in TCN2 (P = 8.37 × 10−21, OR = 0.74). Potentially implicating ZFP36L1 as a new susceptibility gene, 1 intergenic single nucleotide polymorphism (SNP), rs1465788 (P = 7.81 × 10−6, OR = 0.88), was also suggested to be associated with leprosy. A luciferase reporter assay showed that the rs1465788 risk allele notably decreased the transcription activity of the flanking sequence. These findings suggest the possible involvement of lipid metabolism, NF‐κB homeostasis and macrophage antimicrobial pathways in leprosy pathogenesis.
Modulation of forebrain function by nucleus incertus and relaxin‐3/RXFP3 signaling
Authors: Olucha‐Bordonau Francisco E. , Albert‐Gascó Héctor , Ros‐Bernal Francisco , Rytova Valeria , Ong‐Pålsson Emma K. E. , Ma Sherie , Sánchez‐Pérez Ana M. , Gundlach Andrew L.
Published: May 2018

The nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin‐3, which acts via the Gi/o‐protein‐coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin‐3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory. This range of actions corresponds to a likely impact of NI/(relaxin‐3) projections on multiple integrated circuits, but makes it difficult to draw conclusions about a generalized function for this network. This review will focus on the key physiological process of oscillatory theta rhythm and the neural circuits that promote it during behavioral activation, highlighting the ability of NI and relaxin‐3/RXFP3 signaling systems to modulate these circuits. A better understanding of these mechanisms may provide a way to therapeutically adjust malfunction of forebrain activity present in several pathological conditions.
Investigating cumulative effects across ecological scales
Authors: Hodgson Emma E. , Halpern Benjamin S.
Published: May 2018

Species, habitats, and ecosystems are increasingly exposed to multiple anthropogenic stressors, fueling a rapidly expanding research program to understand the cumulative impacts of these environmental modifications. Since the 1970s, a growing set of methods has been developed through two parallel, sometimes connected, streams of research within the applied and academic realms to assess cumulative effects. Past reviews of cumulative effects assessment (CEA) methods focused on approaches used by practitioners. Academic research has developed several distinct and novel approaches to conducting CEA. Understanding the suite of methods that exist will help practitioners and academics better address various ecological foci (physiological responses, population impacts, ecosystem impacts) and ecological complexities (synergistic effects, impacts across space and time). We reviewed 6 categories of methods (experimental, meta‐analysis, single‐species modeling, mapping, qualitative modeling, and multispecies modeling) and examined the ability of those methods to address different levels of complexity. We focused on research gaps and emerging priorities. We found that no single method assessed impacts across the 4 ecological foci and 6 ecological complexities considered. We propose that methods can be used in combination to improve understanding such that multimodel inference can provide a suite of comparable outputs, mapping methods can help prioritize localized models or experimental gaps, and future experiments can be paired from the outset with models they will inform.
Impact on clinical follow‐up of the Milan System for salivary gland cytology: A comparison with a traditional diagnostic classification
Authors: Layfield L. J. , Baloch Z. W. , Hirschowitz S. L. , Rossi E. D.
Published: May 2018

Introduction

No universally accepted classification exists for salivary gland FNA. The proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers a uniform classification with management recommendations. We compared FNA diagnoses from a prior study with specific diagnoses with corresponding MSRSGC diagnoses.

Methods

One‐hundred and sixty‐four cases from a prior cytological study with histological follow‐up were re‐reviewed by one of the authors and assigned to one of the MSRSGC categories. The original and MSRSCG diagnoses were compared, as were follow‐up recommendations.

Results

The MSRSGC system classified 29 specimens as non‐diagnostic (seven histologically shown to be benign salivary gland, two non‐mucinous cysts, 14 sialadenitis, one pleomorphic adenoma, one haemangioma, one lymphoma, one adenoid cystic carcinoma, one squamous carcinoma and one benign lymphoid proliferation). The original study diagnosed these lesions as: seven benign cysts, 15 benign salivary gland tissue, one benign neoplasm and two insufficient for diagnosis. In seven cases, MSRSGC disagreed with original diagnoses and surgical resection showed lesions where optimal follow‐up was more consistent with original cytological diagnosis. In 10 cases with disagreement, the MSRSGC was associated with a more appropriate follow‐up based on the surgical diagnosis. Malignancy risks for the Milan categories were: non‐diagnostic (12%), non‐neoplastic (5%), atypia of undetermined significance (19%), neoplasm, benign (5%), neoplasm (40%), suspicious for malignancy (60%) and malignant (93%).

Conclusion

MSRSGC was comparable with the original reported diagnoses in the majority of cases. Both systems had high accuracy for distinguishing benign from malignant lesions and both were associated with appropriate follow‐up in most cases.
Blood glucose reduction by diabetic drugs with minimal hypoglycaemia risk for cardiovascular outcomes: Evidence from meta‐regression analysis of randomized controlled trials
Authors: Huang Chi‐Jung , Wang Wei‐Ting , Sung Shih‐Hsien , Chen Chen‐Huan , Lip Gregory Y. H. , Cheng Hao‐Min , Chiang Chern‐En
Published: May 2018

Aims

To investigate the effects of blood glucose control with antihyperglycaemic agents with minimal hypoglycaemia risk on cardiovascular outcomes in patients with type 2 diabetes (T2D).

Materials and methods

Randomized controlled trials (RCTs) comparing the relative efficacy and safety of antidiabetic drugs with less hypoglycaemia risk were comprehensively researched in MEDLINE, Embase and the Cochrane Library up to January 27, 2018. Mixed‐effects meta‐regression analysis was conducted to explore the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse cardiovascular events (MACE), myocardial infarction, stroke, cardiovascular death, all‐cause death, and hospitalization for heart failure.

Results

Ten RCTs comprising 92 400 participants with T2D were included and provided information on 9773 MACE during a median follow‐up of 2.6 years. The mean HbA1c concentration was 0.42% lower (range, 0.27%‐0.86%) for participants given antihyperglycaemic agents than those given placebo. The meta‐regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value, −0.39 to −0.55; P < 0.02) even after adjusting for possible confounding factors including age, sex, baseline HbA1c, duration of follow‐up, difference in achieved systolic blood pressure, difference in achieved body weight, and risk difference in hypoglycaemia. Lowering HbA1c by 1% conferred a significant risk reduction of 30% (95% confidence interval, 17%‐40%) for MACE. By contrast, the meta‐regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P > 0.74).

Conclusions

Compared with placebo, newer T2D agents with less hypoglycaemic hazard significantly reduced the risk of MACE. The MACE reduction appears to be associated with HbA1c reduction in a linear relationship.
Leaning Against the Wind: Debt Financing in the Face of Adversity
Authors: Brennan Michael J. , Kraft Holger
Published: May 2018

We offer evidence of a new stylized feature of corporate financing decisions: the tendency of managers to rely more on debt financing when earnings prospects are poor. We term this “leaning against the wind” and consider three possible explanations: market timing, precautionary financing, and “making the numbers.” We find no evidence in favor of the first two hypotheses, and provisionally accept the making the numbers hypothesis that managers who are under pressure due to unrealistically optimistic earnings expectations by analysts and deteriorating real opportunities will rely more heavily on debt financing to boost earnings per share and return on equity.
Causes of reduced leaf‐level photosynthesis during strong El Niño drought in a Central Amazon forest
Authors: Santos Victor Alexandre Hardt Ferreira dos , Ferreira Marciel José , Rodrigues João Victor Figueiredo Cardoso , Garcia Maquelle Neves , Ceron João Vitor Barbosa , Nelson Bruce Walker , Saleska Scott Reid
Published: May 2018

Sustained drought and concomitant high temperature may reduce photosynthesis and cause tree mortality. Possible causes of reduced photosynthesis include stomatal closure and biochemical inhibition, but their relative roles are unknown in Amazon trees during strong drought events. We assessed the effects of the recent (2015) strong El Niño drought on leaf‐level photosynthesis of Central Amazon trees via these two mechanisms. Through four seasons of 2015, we measured leaf gas exchange, chlorophyll a fluorescence parameters, chlorophyll concentration, and nutrient content in leaves of 57 upper canopy and understory trees of a lowland terra firme forest on well‐drained infertile oxisol. Photosynthesis decreased 28% in the upper canopy and 17% in understory trees during the extreme dry season of 2015, relative to other 2015 seasons and was also lower than the climatically normal dry season of the following non‐El Niño year. Photosynthesis reduction under extreme drought and high temperature in the 2015 dry season was related only to stomatal closure in both upper canopy and understory trees, and not to chlorophyll a fluorescence parameters, chlorophyll, or leaf nutrient concentration. The distinction is important because stomatal closure is a transient regulatory response that can reverse when water becomes available, whereas the other responses reflect more permanent changes or damage to the photosynthetic apparatus. Photosynthesis decrease due to stomatal closure during the 2015 extreme dry season was followed 2 months later by an increase in photosynthesis as rains returned, indicating a margin of resilience to one‐off extreme climatic events in Amazonian forests.
Spatial scale dependence of factors driving climate regulation services in the Americas
Authors: Serna‐Chavez Hector M. , Kissling W. Daniel , Veen Lourens E. , Swenson Nathan G. , van Bodegom Peter M.
Published: May 2018

Aim

A key hypothesis in macroecology is that the relative importance of factors driving ecological phenomena changes with spatial scale. However, studies on ecosystem services usually ignore this. Here, we test how the importance of factors related to climate regulation services varies with spatial extent (i.e., area of assessment) and how covariation among factors affects scale dependencies.

Location

The Americas.

Time period

Present.

Major taxa studied

Plants.

Methods

We combined a multi‐model inference framework with variance partitioning to quantify the importance of factors that could potentially influence climate regulation services (i.e., albedo, evapotranspiration and primary productivity). We quantified abiotic (climate, soil, heterogeneity in soils/topography), biotic (open vegetation, forest area and biomass, plant functional traits) and anthropogenic (forest fragmentation, managed vegetation, non‐vegetated surfaces) conditions and tested their importance in relation to climate regulation services at spatial extents ranging from 9 × 103 to 1 × 106 km2.

Results

We found that the importance of abiotic factors in relation to climate regulation services increases with spatial extent. However, we found no evidence for a change from primarily biotically to abiotically driven climate regulation services with increasing spatial extent. All spatial extent dependencies were heavily influenced by covariation between abiotic, biotic and anthropogenic factors. After accounting for covariation, we found a primacy of abiotic factors as drivers of climate regulation services across spatial extents. Biotic and anthropogenic factors were less important than abiotic factors, and their independent effects were conserved across spatial extents.

Main conclusions

Our results show that the relative importance of abiotic factors related to climate regulation services depends on spatial extent. Biotic and anthropogenic factors are less important for climate regulation services than abiotic factors, and this hierarchy is scale invariant. Our findings suggest that spatial extent dependence needs to be quantified and assessed in climate‐change mitigation projects that focus on ecosystem services.
The development of central venous thrombosis in hemodialyzed patients is associated with catheter tip depth and localization
Authors: Premuzic Vedran , Perkov Drazen , Smiljanic Ranko
Published: May 2018

Introduction: The aim of our work was to analyze the incidence of tunneled hemodialysis catheters‐related thrombosis in hemodialyzed patients depending on catheter tip depth and position and to evaluate the impact of other established risk factors responsible for development of central venous thrombosis.

Methods: The presence of central vein thrombosis, location, and the depth of the catheter tip was reviewed by two experienced radiologists. All patients with suspected central venous thrombosis had factor V Leiden, lupus anticoagulant, and cardiolipin antibodies checked (acIgM and acIgG) and were evaluated with cat‐scan venography.

Findings: A total of 68 tunneled hemodialysis catheters were analyzed with CT venography for central venous thrombosis. There were no signs of central venous thrombosis when catheter tips were placed in the right atrium. There was significantly higher number of catheter tips located on the vein wall than located centrally in patients with central venous thrombosis. Higher percentage of central venous thrombosis, smaller number of tips placed in the right atrium, higher values of IgM cardiolipin antibodies, and higher number of patients with positive factor V Leiden mutation were found in group of patients with catheter tips located on vein wall.

Discussion: Higher incidence of central venous thrombosis in patients with the catheter tip placed on the vein wall is a consequence of a catheter tip depth proximal of the right atrium. Increased factor V Leiden mutation and acIgM values in these patients should be observed as a result of the vein stasis caused by inappropriate catheter tip depth and localization.
Standardized extract of wild apple fruit in alkyl‐polyglucoside‐based cosmetic cream – estimation of stability, safety, antioxidant activity and efficiency
Authors: Stojiljković D. , Tadić V. , Stanković M. , Roganović S. , Arsić I.
Published: May 2018

Objective

The aim of this study was in vitro and in vivo characterization of cosmetic cream with 6% of wild apple fruit water extract, containing 3.5% of alpha‐hydroxyacids‐AHAs and polyphenolic compounds, stabilized by biodegradable alkyl‐polyglucoside emulsifiers.

Methods

In vitro characterization of cream included organoleptic and physico‐chemical (pH values and electrical conductivity) analysis, antioxidant activity‐AA estimation (using DPPH test) during 180 days of storage at 22 ± 2°C and determination of cosmetic active substances content‐AHAs (using HPLC analysis). In vivo estimation of skin irritation potential after creams application under occlusion during 24 h was investigated employing the biophysical methods on 12 healthy volunteers; hydration efficiency, transepidermal water loss‐TEWL, skin pH, erythema‐EI and melanin index‐MI on 10 healthy volunteers after 28 days of cream application and bleaching efficiency on 10 healthy volunteers after 7 days of cream application after artificially induced skin hyperpigmentation.

Results

Investigated cosmetic cream was pale beige colour, odourless, semi‐solid consistency and homogeneous, with pH values of 6.53 ± 0.14, electrical conductivity above 50 μS cm−1 and AA of 24.96%RSC after preparation and these characteristics were stable during investigated period. In vivo measurements revealed the absence of skin irritation after cream application under occlusion, which was part of its safety profile. Increase in skin hydration after 14 days of cream application was 17.28 ± 12.23 and after 28 days 21.19 ± 7.59. In addition, in performed experiment, TEWL and skin pH values during cream application remained unchanged. Cream application after artificial hyperpigmentation induced decrease in MI (∆MI after 7 days was −45.30 ± 18.55).

Conclusion

Formulated cosmetic cream with 6% of standardized wild apple fruit water extract and stabilized by biodegradable alkyl‐polyglucoside emulsifiers demonstrated good stability, acceptable level of in vitro antioxidant activity, absence of skin irritation after cream application under occlusion and positive effects of cream on human skin after application (hydrating and bleaching effects). All mentioned properties make the cream suitable for possible usage as cosmetic product for preventing the skin damages caused by oxidative stress, for moisturizing the dry skin and bleaching of skin hyperpigmentation.
Utility of photoplethysmography for heart rate estimation among inpatients
Authors: Koshy Anoop N. , Sajeev Jithin K. , Nerlekar Nitesh , Brown Adam J. , Rajakariar Kevin , Zureik Mark , Wong Michael C. , Roberts Louise , Street Maryann , Cooke Jennifer , Teh Andrew W.
Published: May 2018

The accuracy of photoplethysmography (PPG) for heart rate (HR) estimation in cardiac arrhythmia is unknown. PPG‐HR was evaluated in 112 hospitalised inpatients (cardiac arrhythmias (n = 60), sinus rhythm (n = 52)) using a continuous electrocardiogram monitoring as a reference standard. Strong agreement was observed in sinus rhythm HR < 100 and atrial flutter (bias 1 beat), modest agreement in sinus tachycardia (bias 24 beats) and complete heart block (bias −6 beats) and weak agreement with significant HR underestimation was seen in atrial fibrillation (bias 23 beats). Routine utilisation of PPG for HR estimation may delay early recognition of clinical deterioration in certain arrhythmias and sinus tachycardia.
Seafood‐borne parasitic diseases in Australia: are they rare or underdiagnosed?
Authors: Shamsi Shokoofeh , Sheorey Harsha
Published: May 2018

Australia is a multicultural country surrounded by water where seafood is regularly consumed. Literature suggests that some popular edible fish sold in fish markets may be infected with parasites transmissible to humans (notably, anisakids and other helminths); however the number of reported human cases due to these parasites is low. In this article we critically review topical publications to understand whether the low number of human infection is due to lack of expertise in Australia to identify and diagnose accurately seafood‐borne parasitic infections. The risk these parasites pose to humans may be underestimated due to: (i) errors or inability of diagnosing these infections, primarily due to less sensitive and specific serological tests and misidentifying parasites without a taxonomist in the diagnostic team; and (ii) medical practitioners not being aware of these parasites or not considering them in the differential diagnosis even in patients with history of regular raw or undercooked seafood consumption.
Predicting student performance in a blended MOOC
Authors: Conijn R. , Van den Beemt A. , Cuijpers P.
Published: May 2018

Predicting student performance is a major tool in learning analytics. This study aims to identify how different measures of massive open online course (MOOC) data can be used to identify points of improvement in MOOCs. In the context of MOOCs, student performance is often defined as course completion. However, students could have other learning objectives than MOOC completion. Therefore, we define student performance as obtaining personal learning objective(s). This study examines a subsample of students in a graduate‐level blended MOOC who shared on‐campus course completion as a learning objective. Aggregated activity frequencies, specific course item frequencies, and order of activities were analysed to predict student performance using correlations, multiple regressions, and process mining. All aggregated MOOC activity frequencies related positively to on‐campus exam grade. However, this relation is less clear when controlling for past performance. In total, 65% of the specific course items showed significant correlations with final exam grade. Students who passed the course spread their learning over more days compared with students who failed. Little difference was found in the order of activities within the MOOC between students who passed and who failed. The results are combined with course evaluations to identify points of improvement within the MOOC.