bluuebunny/crossref_metadata_2025 huggingface dataset:
Brexit and Cherry Picking: Who’s Afraid of the Big Bad Wolf?
Authors: Tangermann Stefan
Published: August 2018

In my view, Brexit is a tragedy, for both the UK and the EU‐27, in both political and economic terms. Negotiations on future trade relations between the UK and the EU‐27 should at least aim at minimising the economic harm. Unfortunately the attitude of the EU‐27 revealed so far in the Brexit negotiations does not appear to point in that direction. The philosophy behind the negotiating stance of the EU‐27 seems to aim at punishing the UK for its decision to exit the Union. The EU‐27 have enforced a sequence of items to be negotiated that is not logical. Rather than seeking to maximise mutual benefit, the EU‐27 appear to see trade with the UK as a zero‐sum game. EU‐27 representatives reproach the UK time and again for ‘cherry picking’, negating the fact that trade negotiations have always been based on a request and offer approach. The argument, advanced by the EU‐27, that the four freedoms of the Single Market are indivisible lacks economic logic. Trade is a (partial) substitute for free movement of workers. Even if not all elements of the Single Market can be agreed with the UK, implementing as many of them as possible would make good economic sense.
Globalisation, Corruption and Women Empowerment
Authors: Dutta Meghna
Published: August 2018

The paper studies how well‐being of women is impacted by the interaction of prevalent corruption levels with the forces of globalisation. Given that corruption disproportionately affect women and girls as they generally start from low level of endowments on most socio‐economic aspects, it tests if the benefits of trade and investment linkages, information flows and political globalisation gets nullified by public sector corruption thereby actually reducing women's well‐being across seventy countries. Two‐stage least square estimates as well as GMM estimates confirm that higher levels of existing corruption can interact with trade linkages and capital mobility between countries to unambiguously reduce women empowerment. Sample split regressions show that the effect of the intensity of corruption remains significant in all cases and inversely affects women empowerment. The results are robust to alternate measures of corruption.
Native fly parasites are the principal cause of nestling mortality in endangered Tasmanian pardalotes
Authors: Edworthy A. B. , Langmore N. E. , Heinsohn R.
Published: August 2018

Established host–parasite interactions at an evolutionary equilibrium are not predicted to result in host population decline. However, parasites may become a major threat to host species weakened by other factors such as habitat degradation or loss of genetic diversity in small populations. We investigate an unusually virulent Tasmanian ectoparasite,Passeromyia longicornis, in its long‐term hosts, the endangered forty‐spotted pardalote (Pardalotus quadragintus) and striated pardalote (Pardalotus striatus) in southeastern Tasmania, Australia. We conducted a parasite elimination experiment to determine the net effect of parasites on forty‐spotted pardalote nestling mortality, and monitored nestling parasite load and mortality in forty‐spotted and striated pardalote nestlings during two breeding seasons (Aug–Jan, 2013–2015).Passeromyia longicornislarvae killed 81% of all forty‐spotted pardalotes nestlings. Across 2 years, forty‐spotted pardalotes fledged fewer nestlings (18%) than sympatric striated pardalotes (26%), and this difference was generated by a combination of higher parasite load and virulence in forty‐spotted pardalote nests. These results show that native ectoparasites can cause substantial and potentially unsustainable mortality in their hosts.
Standardised guidelines and reference networks for treating neuroinflammatory conditions in children are lacking
Authors: Bjerin Olof , Wickström Ronny
Published: August 2018

Aim

To investigate whether local or national guidelines are used in treating neuroinflammatory conditions in children and if there is a perceived need for more guidelines and forums of cooperation.

Methods

A web‐based questionnaire sent to all university hospitals in the Nordic countries (n = 21) between March and July 2015.

Results

All 21 centres replied to the survey. Markers of neuronal or glial damage and markers of inflammation were used at varying rates. Neuronal antibodies were used at all sites except two. Only three hospitals collaborated with their laboratories in developing new assays for biomarkers. Although most centres used some form of guideline for neuroinflammatory conditions, no single disease had a guideline prevalence over 60%. For some diagnoses, access to guidelines was as low as 10%. Standardised follow‐up programs were lacking in 50–95%. A clear majority of the centres perceived a need for more guidelines. Also, forums of cooperation were few. However, there was a great interest in developing paediatric neuroinflammatory guidelines and to create platforms for further consensus work and discussion.

Conclusion

There is a need for developing treatment guidelines within the field of paediatric neuroinflammation to aid in clinical decision‐making, and to establish forums of cooperation.
Enriching the concept of vulnerability in research ethics: An integrative and functional account
Authors: Racine Eric , Bracken‐Roche Dearbhail
Published: August 2018

The concept of vulnerability is widely used in research ethics to signal attention to participants who require special protections in research. However, this concept is vague and under‐theorized. There is also growing concern that the dominant categorical approach to vulnerability (as exemplified by research ethics regulations and guidelines delineating vulnerable groups) is ethically problematic because of its assumptions about groups of people and is, in fact, not very guiding. An agreed‐upon strategy is to move from categorical towards analytical approaches (focused on analyzing types and sources of vulnerability) to vulnerability. Beyond this agreement, however, scholars have been advancing competing accounts of vulnerability without consensus about its appropriate operationalization in research ethics. Based on previous debates, we propose that a comprehensive account of vulnerability for research ethics must include four components: definition, normative justifications, application, and implications. Concluding that no existing accounts integrate these components in a functional (i.e., practically applicable) manner, we propose an integrative and functional account of vulnerability inspired by pragmatist theory and enriched by bioethics literature. Using an example of research on deep brain stimulation for treatment‐resistant depression, we illustrate how the integrative‐functional account can guide the analysis of vulnerability in research within a pragmatist, evidence‐based approach to research ethics. While ultimately there are concerns to be addressed in existing research ethics guidelines on vulnerability, the integrative‐functional account can serve as an analytic tool to help researchers, research ethics boards, and other relevant actors fill in the gaps in the current landscape of research ethics governance.
In vitro gametogenesis: The end of egg donation?
Authors: Carter‐Walshaw Sarah
Published: August 2018

This paper explores whether egg donation could still be ethically justified if in vitro gametogenesis (IVG) became reliable and safe. In order to do this, issues and concerns that might inform a patient’s reasoning in choosing to use donor eggs instead of IVG are explored and assessed. It is concluded that egg donation would only be ethically justified in a narrow range of special cases given the (hypothetical) availability of IVG treatment and, further, that egg donation could itself be replaced by donation through IVG techniques. Two possible criticisms of this position are then considered: Ones based on respect for patient wishes, and on loss of donor benefit. It is concluded that whilst neither argument constitutes a strong enough reason to continue with programmes of egg donation, egg‐sharing programmes could still be permitted come the advent of IVG; these could then provide a morally acceptable source of “natural” donor eggs.
Strategic Dilemmas: How Managers Use HR Practices to Meet Multiple Goals
Authors: Lee Jae Eun , Batt Rosemary , Moynihan Lisa M.
Published: August 2018

Contrary to the classic assumptions in the business and human resource (HR) strategy literatures, real‐world organizations often pursue multiple and potentially contradictory performance goals. They may adopt ‘hybrid’ strategies to maximize both differentiation and low cost — leading middle managers to face dilemmas in how to achieve different goals using the same HR practices. We link employee‐level surveys of HR practices to establishment‐level data on service quality, labour efficiency and profitability to examine the effects of HR practices on these outcomes. We find that establishments with greater use of high involvement practices have significantly higher service quality, which mediates the relationship between HR practices and profitability. Findings for labour efficiency are positive, but generally not significant. These findings also have implications for the quality of jobs.
OLFM4, LY6D and S100A7 as potent markers for distant metastasis in estrogen receptor‐positive breast carcinoma
Authors: Mayama Akifumi , Takagi Kiyoshi , Suzuki Hiroyoshi , Sato Ai , Onodera Yoshiaki , Miki Yasuhiro , Sakurai Minako , Watanabe Takanori , Sakamoto Kazuhiro , Yoshida Ryuichi , Ishida Takanori , Sasano Hironobu , Suzuki Takashi
Published: August 2018

Metastatic breast cancer is a highly lethal disease, and it is very important to evaluate the biomarkers associated with distant metastasis. However, molecular features of distant metastasis remain largely unknown in breast cancer. Estrogens play an important role in the progression of breast cancer and the majority of stage IV breast carcinomas express estrogen receptor (ER). Therefore, in this study, we examined molecular markers associated with distant metastasis in ER‐positive breast carcinoma by microarray and immunohistochemistry. When we examined the gene expression profile of ER‐positive stage IV breast carcinoma tissues (n = 7) comparing ER‐positive stage I‐III cases (n = 11) by microarray analysis, we newly identified OLFM4, LY6D and S100A7, which were closely associated with the distant metastasis. Subsequently, we performed immunohistochemistry for OLFM4, LY6D and S100A7 in 168 ER‐positive breast carcinomas. OLFM4, LY6D and S100A7 immunoreactivities were significantly associated with stage, pathological T factor, distant metastasis and Ki67 status in the ER‐positive breast carcinomas. Moreover, these immunoreactivities were significantly associated with a worse prognostic factor for distant metastasis‐free and breast cancer‐specific survival in ER‐positive stage I‐III breast cancer patients. However, when we performed immunohistochemistry for OLFM4, LY6D and S100A7 in 40 ER‐negative breast carcinomas, these immunoreactivities were not generally associated with the clinicopathological factors examined, including distant metastasis and prognosis of patients, in this study. These results suggest that OLFM4, LY6D and S100A7 immunoreactivity are associated with an aggressive phenotype of ER‐positive breast carcinoma, and these are potent markers for distant metastasis of ER‐positive breast cancer patients.
Neoadjuvant chemotherapy with docetaxel, nedaplatin, and fluorouracil for resectable esophageal cancer: A phase II study
Authors: Ohnuma Hiroyuki , Sato Yasushi , Hayasaka Naotaka , Matsuno Teppei , Fujita Chisa , Sato Masanori , Osuga Takahiro , Hirakawa Masahiro , Miyanishi Koji , Sagawa Tamotsu , Fujikawa Koshi , Ohi Motoh , Okagawa Yutaka , Tsuji Yasushi , Hirayama Michiaki , Ito Tatsuya , Nobuoka Takayuki , Takemasa Ichiro , Kobune Masayoshi , Kato Junji
Published: August 2018

Cisplatin plus 5‐fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5‐fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib‐III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 8, and a continuous infusion of 5‐fluorouracil (400 mg/m2/day) on days 1‐5 and 8‐12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end‐point was the completion rate of the protocol treatment. Twenty‐eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty‐five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment‐related deaths and major surgical complications did not occur. Estimated 2‐year progression‐free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305).
Machine learning in major depression: From classification to treatment outcome prediction
Authors: Gao Shuang , Calhoun Vince D. , Sui Jing
Published: August 2018

Aims

Major depression disorder (MDD) is the single greatest cause of disability and morbidity, and affects about 10% of the population worldwide. Currently, there are no clinically useful diagnostic biomarkers that are able to confirm a diagnosis of MDD from bipolar disorder (BD) in the early depressive episode. Therefore, exploring translational biomarkers of mood disorders based on machine learning is in pressing need, though it is challenging, but with great potential to improve our understanding of these disorders.

Discussions

In this study, we review popular machine‐learning methods used for brain imaging classification and predictions, and provide an overview of studies, specifically for MDD, that have used magnetic resonance imaging data to either (a) classify MDDs from controls or other mood disorders or (b) investigate treatment outcome predictors for individual patients. Finally, challenges, future directions, and potential limitations related to MDD biomarker identification are also discussed, with a goal of offering a comprehensive overview that may help readers to better understand the applications of neuroimaging data mining in depression.

Conclusions

We hope such efforts may highlight the need for an urgently needed paradigm shift in treatment, to guide personalized optimal clinical care.
Development and the effects of extended parenting in the cold‐breeding burying beetle Nicrophorus sayi
Authors: Benowitz Kyle M. , Amukamara Ashley U. , Mckinney Elizabeth C. , Moore Allen J.
Published: August 2018

1. Burying beetles (Nicrophorus spp.) provide an excellent model system to test predictions about the relationships between environment, life‐history and behaviour. All species in the genus display similar natural histories, breeding on vertebrate carcasses and providing parental care to developing offspring. However, variations in other aspects of species' ecologies provide a rich framework to examine the evolution of parental behaviours and other traits.

2. One little‐studied species, N. sayi, breeds in substantially colder temperatures than its congeners, creating a potentially harsh environment for offspring. Here, we examined the timing of reproductive and developmental events in this species, and also investigated the effects of removing parents on offspring performance.

3. We find that development is not only extremely slow in this species, but it is also delayed even in comparison to other burying beetles reared at similar temperatures. However, the presence of parents reduces the time that offspring take to leave the carcass. This decrease in development time does not appear to result in a trade‐off with mortality or body size.

4. From these results, we suggest that very slow development may be advantageous when living in a particularly cold environment. Additionally, one role of extended parental care may be to assist offspring in dealing with these harsh conditions, and to mitigate the potentially negative consequences of adopting such a slow life‐history strategy.
Elites and the expansion of education in nineteenth‐century Sweden
Authors: Andersson Jens , Berger Thor
Published: August 2018

A large literature emphasizes that elite capture of political institutions hampered the spread of mass schooling in the nineteenth and twentieth century. We collect new data on investments in elementary education and the distribution of voting rights for more than 2,000 local governments in nineteenth‐century Sweden and document that educational expenditure was higher where the distribution of political power was more unequal. In particular, areas governed by local landed elites—even those where a single landowner had de jure dictatorial powers—invested substantially more in mass schooling relative to areas where political power was more widely shared, or where it lay in the hands of capitalist elites. Our findings lend quantitative support to an earlier literature produced by economic and social historians which argues that landed elites advanced mass schooling as part of their historical role as patrons of the local community and as a response to the increasing proletarianization of the rural population, while also furthering our understanding of how Sweden maintained a high level of human capital despite its low level of economic development and restricted franchise in the nineteenth century.
The Perils of Gender Beliefs for Men Leaders as Change Agents for Gender Equality
Authors: Humbert Anne Laure , Kelan Elisabeth , van den Brink Marieke
Published: August 2018

This article examines the potentially damaging role that gender beliefs can play in hindering women's equal representation in leadership positions. Based on a secondary analysis of a large‐scale EU‐wide survey (Eurobarometer 76.1), the article shows that essentialist gender beliefs lower support for equality interventions such as quotas or targets, particularly among men as leaders. The results show that discriminatory gender beliefs partially mediate this relationship and produce a more negative effect among men leaders. The paper contributes to understanding the role essentialist gender beliefs often lay the groundwork for gender discriminatory beliefs. Those in turn hinder support for effective gender equality measures. Gender essentialist beliefs can be held by everyone but are more prevalent among men leaders. We conclude that greater gender balance in leadership cannot be achieved without tackling underlying gender beliefs, particularly among men leaders since they are called upon to enact change. We thereby argue that simply asking for men to become change agents for gender equality is not an effective strategy if underlying gender beliefs are left unchallenged.
How friends with money affect corporate cash policies? The international evidence
Authors: Javakhadze David , Rajkovic Tijana
Published: August 2018

We examine the association between managerial social capital and the cash flow sensitivity of cash in an international setting. We find that social capital reduces the marginal propensity to save cash out of cash flows. This association is stronger for more financially constrained firms, firms with high hedging needs, and firms with more uncertain cash flows. The effect of social capital is partially moderated by the extent of legal protection standards and financial development. We also show that social capital matters for valuation. These findings are robust to alternative model specifications, alternative variable measurement, and tests for endogeneity.
Knowledge discovery using maximization of the spread of influence in an expert system
Authors: Tselykh Alexander , Tselykh Larisa , Vasilev Vladislav , Barkovskii Simon
Published: August 2018

The problem of knowledge acquisition (KA) and the automation of this process is a bottleneck of expert systems (ESs) and remains a topical issue. The present study is an attempt to develop an ES in which inference attributes are formed on the basis of automated discovery of tacit knowledge. The structure of the KA module provides an opportunity to discover new knowledge from the cognitive representations of domain models. The algorithmic processing mechanism consists of three blocks: cluster analysis, influence analysis, and modelling of the equivalent graph. In the proposed expert system based on effective controls, a method of finding influences that highlights the main characteristics of the system is presented. These parameters are used as attributes for the further development of the rule base, expertise, or independent use in decision‐making. A qualitative decrease in user subjectivity is achieved using this algorithm and through elimination of the knowledge engineer from the cycle of KA, which transforms it into a discovery knowledge cycle. Quality assurance of the knowledge base is achieved using three approaches: system presentation, mathematical support, and automation.
Pharmacologic Prevention of Migraine: A Narrative Review of the State of the Art in 2018
Authors: Loder Elizabeth , Rizzoli Paul
Published: August 2018

This paper describes current non‐antibody pharmacologic approaches to the prevention of migraine in adults. Preventive therapy should be considered for patients with migraine who routinely have more than 6 headache days per month or in other special circumstances. Choices for preventive therapy are based on patient preferences about side effects and evidence of efficacy. The evidence level and commonly used doses for selected categories of migraine preventive medication are reviewed, including antiepileptic drugs, antihypertensive drugs, and antidepressants. Propranolol, timolol, topiramate, and divalproex sodium are approved for migraine prevention by the US FDA. OnabotulinumtoxinA is approved for prevention of chronic migraine. Several off‐label drugs, especially lisinopril, candesartan, and amitriptyline also have good evidence of benefit. The spectrum of response to preventive therapy varies; in general, complete cessation of headaches is uncommon, although there are “super‐responders” to every therapy, as illustrated by patient reports of dramatic responses to treatment. Preventive treatment should be started at a low dose and doses increased slowly until therapeutic benefit is achieved or side effects preclude continued use.
Intonation Plays a Role in Language Discrimination by Infants
Authors: Chong Adam J. , Vicenik Chad , Sundara Megha
Published: August 2018

Previous research on infant language discrimination has focused primarily on the role of prosody, specifically rhythmic timing cues. This, however, ignores the potentially useful role that intonation, another aspect of prosody, might play in aiding discrimination. In this article, we investigated how and when American English‐learning infants discriminate between prosodically similar languages, specifically American English and German, focusing on the role of intonation in infant language discrimination. We found that the ability to distinguish American English and German develops between 5 and 7 months. However, 7‐month‐olds failed to discriminate the two languages when the natural pitch variation was replaced by a monotone. Thus, intonation is necessary for infants’ discrimination of American English and German. Based on these results, we argue for a greater role of intonation in supporting language discrimination by infants.
“Differential risk of hospitalization among single virus infections causing influenza‐like illnesses”
Authors: Ortiz‐Hernández Ana A. , Nishimura Katherine K. , Noyola Daniel E. , Moreno‐Espinosa Sarbelio , Gamiño Ana , Galindo‐Fraga Arturo , Valdéz Vázquez Rafael , Magaña Aquino Martín , Ramirez‐Venegas Alejandra , Valdés Salgado Raydel , Andrade‐Platas Diana , Estevez‐Jimenéz Juliana , Ruiz‐Palacios Guillermo M. , Guerrero Maria Lourdes , Beigel John , Smolskis Mary C. , Hunsberger Sally , Freimanis‐Hence Laura , Llamosas‐Gallardo Beatriz ,   the Mexico Emerging Infectious Diseases Clinical Research Network (La Red)
Published: August 2018

Background

Acute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza‐like illness (ILI).

Methods

Data from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza.

Results

A total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively).

Conclusions

Children presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.
Effects of surface initial condition on aqueous corrosion of glass—A study with a model nuclear waste glass
Authors: Liu Hongshen , Ngo Dien , Ren Mengguo , Du Jincheng , Kim Seong H.
Published: August 2018

Being a nonequilibrium material, the structure of glass varies with the sample history. Thus, the initial surface condition of a glass can vary with the preparation condition and have a large impact on its reactivity. This paper shows that the aqueous corrosion behavior of international simple glass (ISG) varies depending on the initial surface state. The ISG glass samples were prepared as‐polished‐only and polished‐then‐annealed and they were immersed in aqueous solution saturated with soluble SiO2 at 30°C (modeling a mild condition) and at 90°C (modeling a severe condition). Molecular dynamics simulations were performed to obtain coordination numbers of network formers of ISG to assist oxygen speciation calculations. The surface structures of as‐prepared and corroded ISG samples were analyzed using various imaging and spectroscopic techniques. Among these analyses, only the oxygen speciation with x‐ray photoelectron spectroscopy showed discernable differences between two uncorroded surfaces with different preparation histories; all other methods could not differentiate the surface preparation history before aqueous corrosion. Such minor difference in chemical structures was found to have a profound impact on corrosion behaviors in the mild condition. In the harsh condition, the surface history dependence was not as drastic as the corrosion in the mild condition. The analysis results of the corroded surfaces suggested that the thickness and structure of the alteration layer formed on ISG in aqueous corrosion can vary with the initial surface state.
Learning performance and cognitive load in mobile learning: Impact of interaction complexity
Authors: Wang Cixiao , Fang Ting , Miao Rong
Published: August 2018

In the increasing pervasiveness of today's digital society, mobile devices are changing the face of education. Students can interact with mobile devices in context‐aware environment. This paper presents a mobile application based on expert system (Plant‐E) for students to acquire knowledge about plant classification by answering decision‐making questions. In order to study effectiveness of Plant‐E and cognitive load of students who experience different kinds of interaction in learning process, another mobile application (Plant‐G) only providing information pages of plants was developed. A quasi‐experiment was conducted with three classes of 137 seventh graders. The three classes, Class A with 46 students using Plant‐E in campus, Class B with 44 students using Plant‐G in campus, and Class C with 47 students using Plant‐G in a traditional classroom, constitute three groups with different interaction complexity. The research conducted pretest, posttest, and delayed test to evaluate learning performance of students in three classes and used a questionnaire to investigate their perceptions and attitudes towards proposed system. Results show that interaction complexity has an impact on students' learning performance and mental effort in mobile learning; the higher the interaction complexity is, the higher mental effort and the better learning performance in mobile learning will be.
Notch pathway activation enhances cardiosphere in vitro expansion
Authors: Secco Ilaria , Barile Lucio , Torrini Consuelo , Zentilin Lorena , Vassalli Giuseppe , Giacca Mauro , Collesi Chiara
Published: August 2018

Cardiospheres (CSps) are self‐assembling clusters of a heterogeneous population of poorly differentiated cells outgrowing from in vitro cultured cardiac explants. Scanty information is available on the molecular pathways regulating CSp growth and their differentiation potential towards cardiac and vascular lineages. Here we report that Notch1 stimulates a massive increase in both CSp number and size, inducing a peculiar gene expression programme leading to a cardiovascular molecular signature. These effects were further enhanced using Adeno‐Associated Virus (AAV)‐based gene transfer of activated Notch1‐intracellular domain (N1‐ICD) or soluble‐Jagged1 (sJ1) ligand to CSp‐forming cells. A peculiar effect was exploited by selected pro‐proliferating miRNAs: hsa‐miR‐590‐3p induced a cardiovascular gene expression programme, while hsa‐miR‐199a‐3p acted as the most potent stimulus for the activation of the Notch pathway, thus showing that, unlike in adult cardiomyocytes, these miRNAs involve Notch signalling activation in CSps. Our results identify Notch1 as a crucial regulator of CSp growth and differentiation along the vascular lineage, raising the attracting possibility that forced activation of this pathway might be exploited to promote in vitro CSp expansion as a tool for toxicology screening and cell‐free therapeutic strategies.
Should sulfonylurea be discontinued or maintained at the lowest dose when starting ipragliflozin? A multicenter observational study in Japanese patients with type 2 diabetes
Authors: Takahashi Kiyohiko , Cho Kyu Yong , Nakamura Akinobu , Miya Aika , Miyoshi Arina , Yamamoto Chiho , Nomoto Hiroshi , Niwa Hirokatsu , Takahashi Kiyohito , Manda Naoki , Kurihara Yoshio , Aoki Shin , Ito Yoichi M , Atsumi Tatsuya , Miyoshi Hideaki
Published: August 2018

Aims/Introduction

We investigated the difference in efficacy and safety between discontinuation and maintaining of sulfonylurea when adding a sodium–glucose cotransporter 2 inhibitor.

Materials and Methods

In the present multicenter, prospective observational study, 200 patients with type 2 diabetes treated with sulfonylurea and with a need to add ipragliflozin were enrolled and divided into two groups: discontinued sulfonylurea (Discontinuation group) or maintained sulfonylurea, but at the lowest dose (Low‐dose group) when adding ipragliflozin. We compared the two groups after 24 weeks using propensity score matching to adjust for differences between the groups.

Results

In the matched cohort (58 patients in each group), baseline characteristics of both groups were balanced. The primary outcome of the proportion of patients with non‐exacerbation in glycated hemoglobin after 24 weeks was 91.4% in the Low‐dose group and 75.9% in the Discontinuation group, a significant difference (P = 0.024). However, bodyweight was significantly decreased in the Discontinuation group compared with the Low‐dose group (−4.4 ± 2.1 kg vs −2.9 ± 1.9 kg, P < 0.01). Similarly, liver enzyme improvement was more predominant in the Discontinuation group. A logistic regression analysis showed that high‐density lipoprotein cholesterol, age and sulfonylurea dose were independent factors associated with non‐exacerbation of glycated hemoglobin in the Discontinuation group.

Conclusions

The purpose of using ipragliflozin should be considered when making the decision to discontinue or maintain sulfonylurea at the lowest dose. Furthermore, low high‐density lipoprotein cholesterol level, low dose of sulfonylurea and younger age were possible markers to not show worsening of glycemic control by discontinuing sulfonylurea.
Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus: A focus on hypoglycemia
Authors: Fukuda Masahiro , Doi Kunihiro , Sugawara Masahiro , Mochizuki Koichi
Published: August 2018

Aims/Introduction

To investigate the efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus, with a focus on hypoglycemia.

Materials and Methods

Type 2 diabetes mellitus patients who started sitagliptin therapy and were followed for 52 weeks were enrolled in the Impact of Sitagliptin on Diabetes Mellitus in Japanese Elderly Patients study. The frequency of hypoglycemia and knowledge of hypoglycemia were analyzed using a questionnaire.

Results

In total, 5,130 patients (aged 73.8 ± 6.1 years) were analyzed. A significant reduction in glycated hemoglobin (−0.7 ± 1.1%, P < 0.001) and glycoalbumin levels (−2.2 ± 3.8%, P < 0.001) was observed at week 52. The percentage of patients with hypoglycemia did not increase from the baseline (3.3%) to week 52 (2.8%) of sitagliptin administration. Hypoglycemia incidence was significantly higher for combination therapy with insulin (odds ratio 17.75, P < 0.001) or sulfonylurea (odds ratio 2.22, P < 0.001). The increase in sitagliptin dose for combination therapy with antidiabetic drug(s) increased the percentage of patients with hypoglycemia (5.6% in sitagliptin increased subgroup, 2.4% in sitagliptin maintained subgroup, P < 0.01). The awareness of hypoglycemia symptoms and attitude to carry glucose as a countermeasure to prevent hypoglycemia increased during the study.

Conclusions

Sitagliptin did not increase the percentage of patients with hypoglycemia among elderly patients with type 2 diabetes mellitus. However, hypoglycemia occurred more frequently in add‐on therapy to sulfonylurea or when the sitagliptin dose was increased in combination therapy, showing that sitagliptin should be used with caution.
Robotic dispensing improves patient safety, inventory management, and staff satisfaction in an outpatient hospital pharmacy
Authors: Rodriguez‐Gonzalez Carmen Guadalupe , Herranz‐Alonso Ana , Escudero‐Vilaplana Vicente , Ais‐Larisgoitia Maria Aranzazu , Iglesias‐Peinado Irene , Sanjurjo‐Saez Maria
Published: August 2018

Rationale, aims and objectives

Implementation of robotic systems in outpatient hospital pharmacies is uncommon. Other than cost, 1 of the barriers to widespread adoption is the lack of definitive evidence that this technology actually reduces dispensing errors and improves inventory management.

Objective

To identify the frequency of medication dispensing errors before and after the implementation of a robotic original pack dispensing system in an outpatient hospital pharmacy and to analyse the impact of this system on the quality of stock management and staff satisfaction.

Methods

A prospective before‐and‐after medication error study was performed using a disguised observation technique. Several indicators of stock management and staff satisfaction were monitored.

Drugs were dispensed manually by technicians using a barcode‐controlled system (preimplementation phase) or the dispensing robot ROWA Vmax (ARX) (postimplementation phase). As not all drugs could be handled by the robot, residual manual dispensing was also used.

Results

The dispensing error rate was reduced from 1.31% of prescriptions (43/3284) to 0.63% (19/3004) (relative risk reduction [RRR], 51.7%; 95% CI, 17.3% to 71.8%). The error rate decreased up to 0.12% (3/2496) (RRR, 90.8%; 95% CI, 70.4% to 97.1%) if errors during residual manual dispensing were excluded. The stock‐out ratio was reduced from 0.85% to 0.17% (RRR, 80.5%; 95% CI, 49.5% to 92.5%). Daily staff time (median) in stock management was reduced by 59.3% (from 1 hour 36 minutes to 39 minutes). High level of staff satisfaction with this technology was achieved, although it was slightly higher in the group of pharmacists compared to technicians (8.63 ± 0.7 vs 7.78 ± 0.7, P = .046).

Conclusion

The implementation of a robotic original pack dispensing system substantially decreased the rate of dispensing errors and optimized stock management. Minimizing the number of drugs out of the dispensing robot is critical when attempting to maximize the benefits of its implementation.
Fungal diversity and frequency carried by housefly (Musca domesticaL.) and their relation with stored grains in rural areas of Pakistan
Authors: Abid Muhammad , Chohan Sobia , Akram Shazia , Shah Rizwan M. , Hussain Sabir , Binyameen Muhammad , Shad Sarfraz A. , Perveen Rashida
Published: August 2018

Housefly (Musca domesticaL.) contaminates food by transferring microbes. Fungi carried by houseflies cause postharvest losses by food spoilage produce mycotoxins and spread various infectious diseases in human beings and animals. This study was planned to determine the diversity and frequency of fungal species carried by houseflies and their relation with stored grains. Houseflies in the vicinity of stored wheat and rice grains were collected from the rural areas of four districts of Pakistan. Overall, 897, 631, and 687 fungal species were isolated from houseflies, rice, and wheat grains, respectively.AspergillusandFusariumspecies followed byAlternariaandPenicilliumspecies were found dominant in houseflies, rice, and wheat grains. Correlation analyses revealed a significant association between most of the fungal species isolated from houseflies, wheat, and rice grains. The study concludes that a strong correlation of fungi exists between stored grains and houseflies around the unhygienic storage places.

Practical applications

It is highly important to understand the role of houseflies in spreading various fungal species to stored grains, particularly in our persisting rural grain storage system. Our study is first of its kind in which we have studied the correlation of fungal diversity and abundance between houseflies, wheat, and rice grains stored in the same vicinity/place/house. Our findings show a strong correlation in fungal diversity and abundance, isolated from flies and stored grains. This study demonstrates the role of houseflies in the dispersal of various fungal species to contaminate the stored grains. Therefore, appropriate measures should be taken to control the houseflies or their entrance to store houses. There is a strong need to give awareness and improve the grain storage system in houses, especially in rural areas, by food regulating authorities.
Use of the Antenatal Risk Questionnaire to Assess Psychosocial Risk Factors Associated with Risk for Postpartum Depression: A Pilot Study
Authors: Ruyak Sharon L. , Qeadan Fares
Published: August 2018

Introduction

Postpartum depression is the most common complication of childbirth. The purpose of this pilot study was to examine use of the Antenatal Risk Questionnaire (ANRQ) to assess psychosocial risk factors associated with increased risk for the development of symptoms of postpartum depression.

Methods

This study was a prospective investigation of women during the third trimester of pregnancy. Women were recruited from a high‐volume collaborative obstetric and midwifery practice in a large academic tertiary‐care hospital. Participants were enrolled during their third trimesters of pregnancy and studied through 6 weeks postpartum. Surveys were completed for psychosocial risk (ANRQ), perceived stress, and symptoms of depression. Bivariate analysis was conducted and multiple regression analysis was performed to examine the effects of the predictor variables on the outcome variable, symptoms of depression at 6 weeks postpartum.

Results

Thirty‐five women participated in the study. Prenatal ANRQ scores, Perceived Stress Scale (PSS) scores, and Edinburgh Postnatal Depression Scale (EPDS) scores were significantly correlated with EPDS scores at 6 weeks postpartum. In the multiple regression analysis, the prenatal ANRQ score was a significant predictor of the postpartum EPDS score, whereas the prenatal PSS and EPDS scores were not significant. This regression model explained 57% of the variance in symptoms of depression at 6 weeks postpartum.

Discussion

Key past and present psychosocial risk factors experienced by women (measured by the prenatal ANRQ) were a significant predictor of postpartum depressive symptoms. In light of our results, use of the ANRQ in clinical practice warrants further exploration.
Network meta‐analysis comparing iFR versus FFR versus coronary angiography to drive coronary revascularization
Authors: Verardi Roberto , Fioravanti Francesco , Barbero Umberto , Conrotto Federico , Omedè Pierluigi , Montefusco Antonio , Moretti Claudio , D'Amico Maurizio , Rinaldi Mauro , Escaned Javier , D'Ascenzo Fabrizio
Published: August 2018

Aims

Instantaneous free‐wave ratio (iFR) has been recently demonstrated non‐inferior to fractional flow reserve (FFR) to drive coronary revascularization; however, no study has compared iFR versus coronary angiography (CA). We performed a network meta‐analysis to evaluate efficacy and safety of iFR‐ versus CA‐guided strategy.

Methods and Results

We searched for randomized trials and studies with propensity score matching in The Cochrane Collaboration Central Register of Controlled Trials, EMBASE, and MEDLINE/Pubmed. CA, FFR, and iFR were the three competitive arms, MACE (a composite endpoint of death, myocardial infarction [MI], and target vessel revascularization [TVR]) was the primary endpoint, while its single components the secondary ones. Subgroup analysis was performed for patients presenting with stable coronary artery disease. Eight studies were selected: 4126 patients were evaluated with FFR, 2160 with iFR, and 2214 with CA, acute coronary syndrome (ACS) was the most frequent admission diagnosis. After 12 months, rates of MACE and all‐cause death did not differ between groups (respectively OR 1.04 and OR 0.86 for iFR vs FFR). Both FFR and iFR reduced TVR compared to CA (respectively OR 0.68 and OR 0.70). In patients with stable CAD both FFR and iFR reduced risk of subsequent MI compared to CA (respectively OR 0.66 and OR 0.79).

Conclusion

Compared to CA alone, both FFR and iFR are safe and effective in guiding coronary revascularization at 12 months. In patients with stable CAD, both FFR and iFR‐guided revascularization reduce the risk of subsequent MI at 12 months.
Evaluation of the pungency intensity and time‐related aspects of Chinese Zanthoxylum bungeanum based on human sensation
Authors: Zhang Lu‐Lu , Xu Shan‐Shan , Shi Bo‐Lin , Wang Hou‐Yin , Liu Long‐Yun , Zhong Kui , Zhao Lei , Chen Zhong‐Xiu
Published: August 2018

In this study, the intensity of pungency and the time‐related aspects of nine samples of Zanthoxylum bungeanum from nine different provinces of China were determined, first via Scoville Pungency Units (SPU), then quantitative descriptive analysis, time intensity (TI), and temporal dominance sensation (TDS). The SPU of samples was determined as ranging from 38,000 to 460,000. Furthermore, the intensities of tingling, vibrating, salivating, burning, astringency, numbing, and bitterness in high‐performing SPU samples (measured at more than 150,000) were found to be much higher than in low SPU samples (less than 150,000). In this paper, TI results showed that the high area under the curve (AUC), high intensity of maximum (Imax) and long duration time (Ttot) in high SPU samples were more than 13,482.91, 42.05, and 900 s, respectively, while these values were as low as 4,201.06, 16.61, and 700 s, respectively, in the low SPU samples. TDS results demonstrated that the sequence of appearance of the dominant sensations in the oral cavity were similar for the different samples. It is especially noteworthy that the duration of the dominant sensations of vibrating, salivating, burning, and numbing were significantly higher in the high as opposed to the low pungency intensity samples.

Practical applications

Chinese Zanthoxylum bungeanum has been used decades as a culinary spice and condiment within the catering and food industry. Sensory intensity and temporal changes in odor and flavor throughout the process of consumption are an integral part of the way in which humans perceive the sensory characteristics of food, and this quality thus merits further research. Knowledge regarding the pungency intensity and time‐related aspects of Chinese Z. bungeanum based on human sensation will not only benefit new methods for pungency evaluation, but also provide a scientific basis for flavor design, development of pungent food products, quality control, and consumer choice evaluations. High‐tech products based on Z. bungeanum from different geographical origins may also be developed according to their pungency characteristics.
Public policy, dynamic status preferences, and wealth inequality
Authors: Dioikitopoulos Evangelos V. , Turnovsky Stephen J. , Wendner Ronald
Published: August 2018

This paper studies the effect of productive government spending (taxation) on aggregate savings behavior and its consequences for the dynamics of wealth inequality, taking into consideration key behavioral changes that occur during the process of economic development. Substantial empirical evidence suggests that during this process agents' preferences toward status (positional consumption) evolves according to the average wealth of the society. The sources of wealth include private capital and productive public capital, the latter financed by a distortionary income tax. This dynamic status effect impacts peoples' responses to tax policy in ways which contrast with those of the standard neoclassical model. Specifically, we find that in response to an increase in the income tax, in economies with a strong (weak) enough dynamic status effect, savings and inequality increase (decrease). Incorporating the behavioral changes to fiscal policy expands the set of mechanisms available to explain the observed variations of savings and wealth distribution dynamics that cannot be attributed to technological or other structural factors.