bluuebunny/crossref_metadata_2025 huggingface dataset:
Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment–Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials
Authors: Cahn Pedro , Madero Juan Sierra , Arribas José R. , Antinori Andrea , Ortiz Roberto , Clarke Amanda E. , Hung Chien-Ching , Rockstroh Jürgen K. , Girard Pierre-Marie , Sievers Jörg , Man Choy Y. , Urbaityte Rimgaile , Brandon Daisy J. , Underwood Mark , Tenorio Allan R. , Pappa Keith A. , Wynne Brian , Gartland Martin , Aboud Michael , van Wyk Jean , Smith Kimberly Y.
Published: December 2019

Background:

The 2-drug regimen dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL in treatment-naive adults in the 48-week primary analysis of the GEMINI trials. We present results from the prespecified 96-week secondary analyses.

Setting:

One hundred eighty-seven centers in 21 countries.

Methods:

GEMINI-1 and GEMINI-2 are identical, double-blind phase III studies. Participants with screening HIV-1 RNA ≤500,000 copies/mL were randomized 1:1 to once-daily dolutegravir + lamivudine or dolutegravir + tenofovir disoproxil fumarate/emtricitabine.

Results:

At week 96, dolutegravir + lamivudine (N = 716) was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (N = 717) in achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm; −10% noninferiority margin) in the pooled analysis (proportion of responders, 86.0% vs 89.5%, respectively; adjusted treatment difference [95% CI], −3.4% [−6.7 to 0.0007]), GEMINI-1 (−4.9% [−9.8 to 0.03]), and GEMINI-2 (−1.8% [−6.4 to 2.7]). Proportions of participants in the HIV-1 RNA ≥50 copies/mL Snapshot category were largely unchanged from week 48 to 96. Eleven participants taking dolutegravir + lamivudine and 7 taking dolutegravir + tenofovir disoproxil fumarate/emtricitabine met confirmed virologic withdrawal criteria through week 96; none had treatment-emergent resistance mutations. Dolutegravir + lamivudine had a lower rate of drug-related adverse events than dolutegravir + tenofovir disoproxil fumarate/emtricitabine (19.6% vs 25.0%; relative risk ratio, 0.78; 95% CI: 0.64 to 0.95). Renal and bone biomarker changes favored dolutegravir + lamivudine.

Conclusions:

Consistent with 48-week data, dolutegravir + lamivudine demonstrated long-term, noninferior efficacy vs dolutegravir + tenofovir disoproxil fumarate/emtricitabine without increased risk of treatment-emergent resistance, supporting its use in treatment-naive HIV-1–infected individuals.
Memantine treatment prevents okadaic acid induced neurotoxicity at the systemic and molecular levels
Authors: Dashniani Manana G. , Chighladze Mariam R. , Solomonia Revaz O. , Burjanadze Maia A. , Kandashvili Manana , Chkhikvishvili Nino C. , Beselia Gela V. , Kruashvili Lali B.
Published: December 2019

The present study was designed to investigate the effects of okadaic acid intracerebroventricular (ICV) injection on memory function and expression level of α7 subunit of nicotinic acetylcholine receptor (nAChR) and NR2B subunit of NMDA glutamate receptors in the hippocampus, as well as effect of the antidementic drug memantine on okadaic acid induced changes at systemic and molecular levels in rats. Okadaic acid was dissolved in artificial cerebrospinal fluid (aCSF) and injected ICV 200 ng/10 μl. Vehicle control received 10 μl of aCSF ICV bilaterally. Control and okadaic acid injected rats were divided into two subgroups: treated i.p. with saline or memantine (5 mg/kg daily for 13 days starting from the day of okadaic acid injection). Rats were trained in the dual-solution plus-maze task that can be solved by using place or response strategies. The Western immunoblotting was used to determine relative amount of hippocampal receptors protein levels. Obtained data revealed that okadaic acid ICV injected rats were severely impaired at acquiring the place version of the maze accompanied by significant decline in hippocampal α7 subunit of nACh receptors protein levels. Memantine treatment can prevent okadaic acid induced impairment of hippocampal-dependent spatial memory and accompanied by modulation of the expression level of α7 subunit of nACh and NR2B subunit of NMDA receptors in the hippocampus. Thus, our results support the presumption that α7 nACh receptors may play an important role in the cognitive enhancer effects of memantine and emphasize the role of cholinergic–glutamatergic interactions in memory.
Frankia soli sp. nov., an actinobacterium isolated from soil beneath Ceanothus jepsonii
Authors: Gtari Maher , Ghodhbane-Gtari Faten , Nouioui Imen
Published: December 2019

Actinobacterial strain CjT was directly isolated from soil beneath Ceanothus jepsonii growing in the USA. The strain formed cell structures typical of the genus

Frankia

including extensive hyphae, vesicles and sporangia, and it effectively nodulated members of the actinorhizal Colletieae, Elaeagnaceae and Myricaceae. The whole-cell hydrolysate of strain CjT was rich in meso-diaminopimelic acid and galactose, glucose, mannose, xylose, ribose and a trace of rhamnose. Tbe polar lipid profile contained phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol and glycophospholipid. The menaquinone was predominantly MK-9(H4). The fatty acid profile predominantly consisted of C17 : 1ω8c, iso-C16 : 0, C15:0, C16 : 0 and C17 : 0. A multilocus sequence analysis phylogeny based on atp1, ftsZ, dnaK, gyrA and secA gene sequences positioned the strain within Elaeagnaceae- and Colletieae﻿-nodulating species together with

Frankia elaeagni

DSM 46783T,

Frankia discariae

DSM 46785T and

Frankia irregularis

DSM 45899T. Pairwise 16S rRNA gene sequence similarities showed that strain CjT was most closely related to

F. discariae

DSM 46785T (99.78 %) while their digital DNA–DNA hybridization value was 41.1 %. Based on the overall analyses, strain CjT (=DSM 100623T=CECT 9041T) warrants classification as the type strain of a novel species, for which the name Frankia soli sp. nov. is proposed.
Situating the Left-Lateralized Language Network in the Broader Organization of Multiple Specialized Large-Scale Distributed Networks
Authors: Braga Rodrigo M. , DiNicola Lauren M. , Buckner Randy L.
Published: December 2019

Using procedures optimized to explore network organization within the individual, the topography of a candidate language network was characterized and situated within the broader context of adjacent networks. The candidate network was first identified using functional connectivity and replicated across individuals, datasets, acquisition tasks, and analytic methods. In addition to classical language regions near to perisylvian cortex and temporal pole, additional regions were observed in dorsal posterior cingulate, midcingulate, anterior superior frontal and inferior temporal cortex. The candidate network was selectively activated when processing meaningful (as contrast to non-word) sentences, while spatially adjacent networks showed minimal or even decreased activity. Examined in relation to adjacent networks, the topography of the language network was found to parallel the motif of other association networks including the transmodal association networks linked to theory of mind and episodic remembering (often collectively called the default network). The several networks contained juxtaposed regions in multiple association zones. Outside of these juxtaposed higher-order networks, we further noted a distinct frontotemporal network situated between language regions and a frontal orofacial motor region and a temporal auditory region. A possibility is that these functionally-related sensorimotor regions might anchor specialization of neighboring association regions that develop into the language network. What is most striking is that the canonical language network appears to be just one of multiple similarly organized, differentially specialized distributed networks that populate the evolutionarily expanded zones of human association cortex.
Examining the relationships between phenotypic plasticity and local environments with genomic structural equation models
Authors: Campbell Malachy T. , Yu Haipeng , Momen Mehdi , Morota Gota
Published: December 2019

Environmental association analyses (EAA) seek to identify genetic variants associated with local adaptation by regressing local environmental conditions at collection sites on genome-wide polymorphisms. The rationale is that environmental conditions impose selective pressure on trait(s), and these traits are regulated in part by variation at a genomic level. Here, we present an alternative multivariate genomic approach that can be utilized when both phenotypic and environmental data are available for the population. This framework utilizes Bayesian networks (BN) to elucidate interdependancies between local environmental conditions and empirical phenotypes, and jointly estimates the direct and indirect genetic covariances between empirical phenotypes and environmental conditions using a mixed-effects structural equation model (SEM). Direct genomic covariance between empirical phenotypes and environmental conditions may provide insight into whether QTL that affect adaptation to an environmental gradient also affects the observed phenotype. To demonstrate the utility of this approach, we leveraged two existing datasets consisting of 55 climate variables for 1,130Arabidopsisaccessions and empirical phenotypes for fitness and phenology collected on 515 accessions in two common garden locations in Europe. BN showed that plasticity for fitness and phenology was highly dependant on local environmental conditions. Moreover, genomic SEM revealed relatively high positive genomic correlation between plasticity in fitness and environmental variables that describe the favorability of the local environment for plant growth, indicating the presence of common QTL or independent QTL that are tightly linked. We believe the frameworks presented in this manuscript can provide new insights into the genetic basis of local adaptation.
Track-Control, an automatic video-based real-time closed-loop behavioral control toolbox
Authors: Zhang Guang-Wei , Shen Li , Li Zhong , Tao Huizhong W. , Zhang Li I.
Published: December 2019

Approaches of optogenetic manipulation of neuronal activity have boosted our understanding of the functional architecture of brain circuits underlying various behaviors. In the meantime, rapid development in computer vision greatly accelerates the automation of behavioral analysis. Real-time and event-triggered interference is often necessary for establishing a tight correlation between neuronal activity and behavioral outcome. However, it is time consuming and easily causes variations when performed manually by experimenters. Here, we describe our Track-Control toolbox, a fully automated system with real-time object detection and low latency closed-loop hardware feedback. We demonstrate that the toolbox can be applied in a broad spectrum of behavioral assays commonly used in the neuroscience field, including open field, plus maze, Morris water maze, real-time place preference, social interaction, and sensory-induced defensive behavior tests. The Track-Control toolbox has proved an efficient and easy-to-use method with excellent flexibility for functional extension. Moreover, the toolbox is free, open source, graphic processing unit (GPU)-independent, and compatible across operating system (OS) platforms. Each lab can easily integrate Track-Control into their existing systems to achieve automation.
The DNA end-binding protein Ku associates with human telomeres primarily via protein-protein interactions
Authors: Sukumar Ann T. , Williams Christopher L. , Jones Celina Y. , Asik Elif , Morris Danna K. , Baldan Alessandro , Indiviglio Sandra M. , Chiodi Ilaria , Mondello Chiara , Bertuch Alison A.
Published: December 2019

The Ku heterodimer (Ku70/Ku80) binds DNA ends with high affinity but without sequence specificity and, upon binding ends created by double-stranded breaks (DSBs), initiates canonical nonhomologous end-joining (c-NHEJ). Ku also localizes to functional telomeres where its c-NHEJ activity is inhibited. Interestingly, Ku has been co-opted at telomeres across species, where it performs varied telomeric functions. In humans, Ku is essential for its role in telomere maintenance, but how it associates with human telomeres is not known. Analysis of Ku’s telomere association in different populations of cen3tel cells, which had a wide range of average telomere lengths, supported Ku’s localization at human telomeres primarily via protein-protein interaction. We also found that the Ku70 and Ku80 α5 helices, which are on opposing sides of the heterodimer and were previously implicated inSaccharomyces cerevisiaeKu’s NHEJ and telomeric functions, respectively, participated in Ku’s telomere association in human cells. While the Ku70 α5 mutant showed increased interaction with TRF2, the Ku80 α5 mutant was not impacted for TRF2 association. Interestingly, residues altered to impair Ku’s DNA end-binding function were also involved in TRF2 interaction and telomere association. Overall, our results suggest protein-protein interactions as the primary mode by which Ku associates with human telomeres.
Sustained virome diversity in Antarctic penguins and their ticks: geographical connectedness and no evidence for low pathogen pressure
Authors: Wille Michelle , Harvey Erin , Shi Mang , Gonzalez-Acuña Daniel , Holmes Edward C. , Hurt Aeron C.
Published: December 2019

Despite its isolation and extreme climate, Antarctica is home to diverse fauna and associated microorganisms. It has been proposed that the most iconic Antarctic animal, the penguin, experiences low pathogen pressure, accounting for their disease susceptibility in foreign environments. However, there is a limited understanding of virome diversity in Antarctic species, the extent of in situ virus evolution, or how it relates to that in other geographic regions. To test the idea that penguins have limited microbial diversity we determined the viromes of three species of penguins and their ticks sampled on the Antarctic peninsula. Using total RNA-Sequencing we identified 107 viral species, comprising likely penguin associated viruses (n = 13), penguin diet and microbiome associated viruses (n = 82) and tick viruses (n = 8), two of which may have the potential to infect penguins. Notably, the level of virome diversity revealed in penguins is comparable to that seen in Australian waterbirds, including many of the same viral families. These data therefore reject the theory that penguins are subject to lower pathogen pressure. The repeated detection of specific viruses in Antarctic penguins also suggests that rather than being simply spill-over hosts, these animals may act as key virus reservoirs.
Wwc2is a novel cell division regulator during preimplantation mouse embryo lineage formation and oogenesis
Authors: Virnicchi Giorgio , Bora Pablo , Gahurová Lenka , Šušor Andrej , Bruce Alexander W.
Published: December 2019

Formation of a mature and hatching mouse blastocyst marks the end of the preimplantation development, whereby regulated cell cleavages culminate in the formation of three distinct lineages. We report dysregulated expression ofWwc2, an ill-characterised paralog of the Hippo-signalling activatorKibra/Wwc1, is specifically associated with cell autonomous deficits in embryo cell number and cell division abnormalities, typified by imbalanced daughter cell chromatin segregation. Division phenotypes are also observed during mouse oocyte meiotic maturation, asWwc2dysregulation blocks progression to the fertilisation competent stage of meiosis II metaphase arrest, characterised by spindle defects and failed Aurora-A kinase (AURKA) activation. Such cell division defects, each occurring in the absence of centrosomes, are fully reversible by expression of recombinant HA-epitope tagged WWC2, restoring activated oocyte AURKA levels. Additionally, clonal dysregulation implicatesWwc2in maintaining the pluripotent late blastocyst stage epiblast lineage. Thus,Wwc2is a novel regulator of meiotic and early mitotic cell divisions, and mouse blastocyst cell-fate.
ThePseudomonas aeruginosalectin LecB causes integrin internalization to facilitate crawling of bacteria underneath host cells
Authors: Thuenauer Roland , Landi Alessia , Trefzer Anne , Altmann Silke , Wehrum Sarah , Eierhoff Thorsten , Diedrich Britta , Dengjel Jörn , Nyström Alexander , Imberty Anne , Römer Winfried
Published: December 2019

The opportunistic bacteriumPseudomonas aeruginosaproduces the fucose-specific lectin LecB, which has been identified as virulence factor. LecB has a tetrameric structure with four opposing binding sites and has been shown to act as crosslinker. Here, we demonstrate that LecB strongly binds to the glycosylated moieties of β1-integrins on the basolateral plasma membrane of epithelial cells and caused rapid integrin endocytosis. Whereas internalized integrins were degraded via a lysosomal pathway, washout of LecB restored integrin cell surface localization, thus indicating a specific and direct action of LecB on integrins to bring about their endocytosis. Interestingly, LecB was able to trigger uptake of active and inactive β1-integrins and also of complete α3β1-integrin - laminin complexes. We provide a mechanistic explanation for this unique endocytic process by showing that LecB has the additional ability to recognize fucose-bearing glycosphingolipids and caused the formation of membrane invaginations on giant unilamellar vesicles. In cells, LecB recruited integrins to these invaginations by crosslinking integrins and glycosphingolipids. In epithelial wound healing assays, LecB specifically cleared integrins from the surface of cells located at the wound edge and blocked cell migration and wound healing in a dose-dependent manner. Moreover, the wild typeP. aeruginosastrain PAO1 was able to loosen cell-substrate adhesion in order to crawl underneath exposed cells, whereas knockout of LecB significantly reduced crawling events. Based on these results we suggest that LecB has a role in disseminating bacteria along the cell - basement membrane interface.

Importance

Pseudomonas aeruginosais a ubiquitous environmental bacterium that is one of the leading causes for nosocomial infections.P. aeruginosais able to switch between planktonic, intracellular, and biofilm-based lifestyles, which allows it to evade the immune system as well as antibiotic treatment. Hence, alternatives to antibiotic treatment are urgently required to combatP. aeruginosainfections. Lectins, like the fucose-specific LecB, are promising targets, because removal of LecB resulted in decreased virulence in mouse models. Currently, several research groups are developing LecB inhibitors. However, the role of LecB in host-pathogen interaction is not well understood. The significance of our research is in identifying cellular mechanisms how LecB facilitatesP. aeruginosainfection: We introduce LecB as new member to the list of bacterial molecules that bind integrins and show thatP. aeruginosacan efficiently move forward underneath attached epithelial cells by loosening cell - basement membrane attachment in a LecB-dependent manner.
Fitness Functions Determine Optimal Parental Allocation: Redefining Trivers–Willard Theory
Authors: Choi Jibeom , Roh Hyungmin , Lee Sang-im , Kwon Hee-Dae , Kang Myungjoo , Jablonski Piotr G
Published: December 2019

According to Trivers-Willard theory1, females in a good condition should carry more male offspring to maximize their fitness while should carry more females in a poor condition. Diverse theoretical and empirical studies has been performed to verify the validity of this claim2,3. Some portion of the empirical observations, however, exhibited contrary outcome to Trivers-Willard theory4. To resolve this problem, we computationally and mathematically show in here that reversed Trivers-Willard theory actually could be the outcome of the parental fitness optimization. In our models with identical fitness functions, we found that selective equitable care is optimal, and the number of the cared offspring should monotonically increase with maternal condition (or expendable parental investment). In some of our models with two distinguished male and female fitness functions, optimizations results were congruent with the conventional Trivers-Willard theory. In other models of ours, contrary to Trivers-Willard theory, it was optimal to invest in males when maternal condition was low. The results along with our hypothesis can explain the empirical observations that were previously thought to be the counterexample of Trivers-Willard theory. We propose that Trivers-Willard theory should be interpreted in multidimensional way, and more elaborate empirical data need to be collected to verify such propositions.
Leaf chemical defences and insect herbivory in oak: accounting for canopy position unravels marked genetic relatedness effects
Authors: Valdés-Correcher Elena , Bourdin Audrey , González-Martínez Santiago C. , Moreira Xoaquín , Galmán Andrea , Castagneyrol Bastien , Hampe Arndt
Published: December 2019

Background and Aims

Highly controlled experiments revealed that plant genetic diversity and relatedness can shape herbivore communities and patterns of herbivory. Evidence from the field is scarce and inconsistent. We assessed whether a genetic signal underlying herbivory can be detected in oak forest stands when accounting for variation at smaller (within-tree) and larger (among-stand) scales.

Methods

We tested relationships between tree genetic relatedness, leaf chemical defences and insect herbivory at different canopy layers in 240 trees from 15 Pedunculate oak (Quercus robur) forest stands and partitioned sources of variability in herbivory and defences among stands, individuals, and branches.

Key Results

Leaf defences, insect herbivory, and their relationship differed systematically between the upper and the lower tree canopy. When accounting for this canopy effect, the variation explained by tree genetic relatedness rose from 2.8 to 34.1 % for herbivory and from 7.1 to 13.8 % for leaf defences. The effect was driven by markedly stronger relationships in the upper canopy.

Conclusions

Our findings illustrate that properly accounting for other sources of variation acting at different scales can reveal potentially relevant effects of the host plant genotype on patterns of leaf chemical defences and associated insect herbivory in natural tree populations.
Systematic genome editing of the genes on zebrafish Chromosome 1 by CRISPR/Cas9
Authors: Sun Yonghua , Zhang Bo , Luo Lingfei , Shi De-Li , Wang Han , Cui Zongbin , Huang Honghui , Cao Ying , Shu Xiaodong , Zhang Wenqing , Zhou Jianfeng , Li Yun , Du Jiulin , Zhao Qingshun , Chen Jun , Zhong Hanbing , Zhong Tao P. , Li Li , Xiong Jing-Wei , Peng Jinrong , Xiao Wuhan , Zhang Jian , Yao Jihua , Yin Zhan , Mo Xianming , Peng Gang , Zhu Jun , Chen Yan , Zhou Yong , Liu Dong , Pan Weijun , Zhang Yiyue , Ruan Hua , Liu Feng , Zhu Zuoyan , Meng Anming , The ZAKOC Consortium
Published: December 2019

Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes. Meanwhile, by high-throughput bioinformatics analysis, we found that sequence features play pivotal roles in effective gRNA targeting at specific genes of interest, while the success rate of gene targeting positively correlates with GC content of the target sites. Moreover, we found that nearly one-fourth of all mutants are related to human diseases, and several representative CRISPR/Cas9-generated mutants are described here. Furthermore, we tried to identify the underlying mechanisms leading to distinct phenotypes between genetic mutants and antisense morpholino-mediated knockdown embryos. Altogether, this work has generated the first chromosome-wide collection of zebrafish genetic mutants by the CRISPR/Cas9 technology, which will serve as a valuable resource for the community, and our bioinformatics analysis also provides some useful guidance to design gene-specific gRNAs for successful gene editing.
An original framework for strategic technology development of small manufacturing enterprises in emerging economies
Authors: Nanda Tarun , Gupta Himanshu , Singh Tejinder P. , Kusi-Sarpong Simonov , Jabbour Chiappetta Jose Charbel , Cherri Adriana
Published: December 2019

Purpose

Technology and knowledge have become the buzzwords of the new millennium. Technological changes and demanding customers are creating a more knowledge intensive, turbulent, complex and uncertain environment. Organizations, which are able to continually build faster and cheaper new strategic assets than their competitors, create long-term competitive advantages. Thus, the growth of companies is directly associated with innovativeness and technological development, especially for small organizations that are more vulnerable to dynamic changes in market place. Organizations need a strategic framework that can help them to achieve the goal of technology development and competitiveness. The purpose of this paper is to develop such strategic framework for small organizations for their technology development and, hence, survival in marketplace.

Design/methodology/approach

Options field methodology, options profile methodology, analytic hierarchy process (AHP) and fuzzy set theory are utilized to generate various options and profiles to propose a conceptual framework for technology development.

Findings

The results from the study showed that “mixed approach,” “strategic simulation approach” and the “regulatory environment approach,” in this order, emerged as the top three important options for the strategic technological development of small manufacturing enterprises.

Originality/value

This result can provide an original and more accurate implementation pathway toward technological innovative development in emerging economies. The proposed framework can provide valuable guidelines and recommendations to practicing managers and analysts for policy development to promote innovative and technological developments.
Numerical study on instantaneous radial force of a centrifugal pump for different working conditions
Authors: Jia Xiaoqi , Yuan Sheng , Zhu Zuchao , Cui Baoling
Published: December 2019

Purpose

Instantaneous radial force induced from unsteady flow will intensify vibration noise of the centrifugal pump, especially under off-design working conditions, which will affect safety reliability of pump operation in severe cases. This paper aims to conduct unsteady numerical computation on one centrifugal pump; thus, unsteady fluid radial force upon the impeller and volute is obtained, so as to study the evolution law of instantaneous radial force, the internal relationship between radial force and pressure pulsation, the relationship among each composition of radial force that the impeller received and the influence of leakage rate of front and back chamber on radial force.

Design/methodology/approach

The unsteady numerical simulation with SST k-ω turbulence model was carried out for a low specific-speed centrifugal pump using computational fluid dynamics codes FLUENT. The performance tests and pressure tests were conducted by a closed loop system. The performance curves and the pressure distribution from numerical simulation agree with that of the experiment conducted. The unsteady pressure distributions and the instantaneous radial forces induced from unsteady flow were analyzed under different flow rates. Contribution degrees of three components of the radial force on the impeller and the relation between the radial force and leakage rate were analyzed.

Findings

Radial force on the volute and pressure pulsation on the volute wall have the same distribution tendency, but in contrast to the distribution trend of the radial force on the impeller. In the component of radial force that the impeller received, radial force on the blade accounts for the main position. With the decrease of flow rate, ratio of the radial force on front and back casings will be increased; under large flow rate, vortex and flow blockage at volute section will enhance the pressure and radial force fluctuation greatly, and the pulsation degree may be much more intense than that of a smaller flow rate.

Originality/value

This paper revealed the relation of the radial force and the pressure pulsation. Meanwhile, contribution degrees of three components of the radial force on the impeller under different working conditions as well as the relation between the radial force and leakage rate of front and rear chambers were analyzed.
Consumer adoption of smartphone fitness apps: an extended UTAUT2 perspective
Authors: Dhiman Neeraj , Arora Neelika , Dogra Nikita , Gupta Anil
Published: December 2019

Purpose

The purpose of this paper is to examine the determinants of user adoption of smartphone fitness apps in context of an emerging economy.

Design/methodology/approach

The present study uses the extended unified theory of acceptance and use of technology (UTAUT2) as the base model along with two additional constructs, i.e. self-efficacy and personal innovativeness. The data collection was done through an online survey, wherein a total of 324 valid responses were obtained for the statistical analysis. All the hypothesized relationships were tested through partial least square structural equation modelling (PLS-SEM) using an open source programming language and software environment, i.e. R Software along with plspm-package.

Findings

Significant predictors of smartphone fitness app adoption intention include effort expectancy, social influence, perceived value, habit and personal innovativeness. Further, this study confirms significant relationship between personal innovativeness and habit, self-efficacy and effort expectancy and effort expectancy and performance expectation. This study reveals that personal innovativeness is the strongest predictor of behavioural intention. Contrary to the expectations, factors like performance expectancy, facilitating conditions and hedonic motivation did not influence behavioural intention.

Practical implications

This study gives significant clues to app developers that can drastically influence the adoption of fitness apps. The findings suggest that marketers should focus on users with high personal innovativeness that can further act as role models and significantly influence their social circle. Interestingly, the findings suggest that fitness apps, as compared to other apps, should not emphasize much on the hedonic value of their offerings.

Originality/value

This study is one of the few studies to examine the adoption of smartphone fitness apps in an emerging economy context by using extended version of UTAUT2 model. Further, this study shows how new endogenous and exogenous variables (i.e. self-efficacy and personal innovativeness) contribute to better explanatory power of the UTAUT2 framework.
Between trust and control in R&D alliances
Authors: Henttonen Kaisa , Hurmelinna-Laukkanen Pia , Blomqvist Kirsimarja
Published: December 2019

Purpose

Trust and control through contracting have been juxtaposed in many studies addressing interorganizational collaboration and knowledge exchange. In this study, the authors move from the opposite ends of a continuum between trust as an attitude and control exercised through formal contracts toward the center of the continuum where trust and contracting start to show similar features. The authors ask how trust in its analytical form and control gained through establishing informal protection for knowledge assets affect the innovation and market performance of firms engaged in research and development (R&D) alliances.

Design/methodology/approach

The authors examine the existing literature and conduct a quantitative empirical study to answer the research question.

Findings

The authors find, first, that controlling an organization’s own knowledge assets in R&D alliances with informal means of protection can be more effective than a strategy of controlling the alliance through formal contracts. Second, the authors find that an analytical audit of partner trustworthiness, and especially partner capabilities and goodwill can be more effective than trust as an attitude.

Research limitations/implications

The findings support softening the sharp distinction between trust and control and provide evidence on the relevance of highlighting the firm point of view in knowledge management in R&D alliance governance.

Originality/value

The study adds to the existing understanding of trust and control in R&D alliance governance. Specifically, the authors turn the focus from interorganizational governance to intra-organizational knowledge management measures, and particularly toward how a focal actor can take an analytical approach to evaluate partner trustworthiness and use informal control in protecting its own knowledge assets. Consequently, this study also provides a plausible explanation for the contradictory findings in studies that examine the relationship between trust and control. The study indicates that depending on the specific nature of trust and control, they can be either a complement or a supplement factors: the extreme forms of trust and control are notably different from those forms that share similar features.
Well data mapping validation
Authors: Krilov D. , Krylova M.
Published: December 2019

Some key geologic data can only be obtained from wells. This article provides original technology concerning the geological mapping validation of complex anomalous zones based on information obtained from irregular or sparse drilling. Only complex non‐unique cases of geologic characteristics delineation (i.e. characterized by multiple solutions) are considered here. Representative groups of multiple mapping solutions (i.e. essential variations in anomaly zones delineation in terms of size and location) are analysed in order to optimize and verify the mapping parameters. Minor interpolation discrepancies not influencing the geologic interpretation, for example, resulting from specificities of different interpolation techniques or insignificant mapping procedure corrections, are neglected. The mapping error can be quantitatively assessed by the cross validation error analysis. Maps can be optimized by the proper choice of the interpolation algorithm and data filtering. Using trial‐and‐error schema, interpolation and filtering options are tested and mapping errors are compared. Single assessments or selective tests of the mapping accuracy often cannot lead to the best solution. The optimization procedure can be used for mapping verification, accuracy assessment and mapping parameter optimization. It may also be used to find an optimal balance between the mapping accuracy and the resolution by interpolants (i.e. initial well data) test processing. The interpolation algorithms used here are most technologically fit for a check comparison – not as a substitution of the existing mapping technologies. After positive mapping validation, a common procedure of interpolation can be started. Franke's theoretical work on scattered data interpolation and Krilov's smart averaging interpolation tests were used here to substantiate the well data mapping validation technology. The authors tried not to delve deep into the theory and interpolation testing details using due references and concentrating on the technology procedure and algorithm description.
Zygotic splitting following embryo biopsy: a cohort study of 207 697 single‐embryo transfers following IVF treatment
Authors: Kamath MS , Antonisamy B , Sunkara SK
Published: December 2019

Objective

To evaluate the risk of monozygotic splitting with embryo biopsy during in vitro fertilisation (IVF).

Design

A cohort study.

Setting

Anonymised assisted reproductive technology national data from the Human Fertilisation and Embryology Authority, UK.

Population

Women undergoing single‐embryo transfer (SET) following either pre‐implantation genetic testing (PGT) involving embryo biopsy or IVF without PGT.

Methods

Data on women undergoing SET either following PGT and non‐PGT IVF treatment in 2000–2016 were analysed to compare the risk of zygotic splitting and monozygotic twining. Logistic regression analysis was performed adjusting for potential confounders.

Main outcomes

Monozygotic spitting, monozygotic twin birth.

Results

Data comprising a total of 207 697 SET cycles (4544 following PGT and 203 153 following non‐PGT IVF) were analysed. The live birth rate per embryo transfer was 31.9% (95% confidence interval [CI] 30.5–33.2%) following PGT and 26.9% (95% CI 26.7–27.1%) following non‐PGT IVF. The incidence of zygotic splitting following PGT was 2.4% (95% CI 1.7–3.3%) versus 1.5% (95% CI 1.4–1.6%) following non‐PGT IVF. There was a significantly higher risk of zygotic splitting with PGT versus non‐PGT IVF cycles (odds ratio [OR] 1.64, 95% CI 1.19–2.27). The higher risk of zygotic splitting with PGT cycles remained significant after adjusting for potential confounders (adjusted OR 1.51, 95% CI 1.06–2.15).

Conclusions

The present study demonstrated an increased risk of monozygotic splitting with embryo biopsy. Given the current sparse literature, it is important to accumulate further evidence to validate the findings.

Tweetable abstract

A likely increased risk of monozygotic splitting following embryo biopsy.
Do people want a ‘fairer’ electoral system? An experimental study in four countries
Authors: PLESCIA CAROLINA , BLAIS ANDRÉ , HÖGSTRÖM JOHN
Published: December 2019

When judging how ‘fair’ voting rules are, a fundamental criterion used by both scholars and politicians is their ability or inability to produce proportional results – that is, the extent parties’ seat distribution after the elections accurately reflects their vote shares. How about citizens? Do citizens care about how proportional the outcome is? Or do they judge the outcome solely on the basis of how well (or poorly) their party performed? Taking advantage of a uniquely designed survey experiment, this article investigates the causal effect of proportionality on voter support for voting rules in four countries: Austria, England, Ireland and Sweden. The results show that proportionality drives support for the voting rules not above, but beyond party performance. There is little cross‐country variation, which suggests that proportionality is appreciated in different contexts with little status quo bias. These findings have important implications for our understanding of the causal mechanisms linking electoral rules to voter support.
Dynamic determination of functional liver capacity with the LiMAx test in post‐cardiac arrest patients undergoing targeted temperature management—A prospective trial
Authors: Nee Jens , Schroeder Tim , Vornholt Florian , Schaeuble Julian , Leithner Christoph , Stockmann Martin , Storm Christian
Published: December 2019

Background

Transiently increased transaminases is a common finding after cardiac arrest but little is known about the functional liver capacity (LiMAx) during the post‐cardiac arrest syndrome and treatment in the intensive care unit (ICU). The aim of this trial was to evaluate liver function capacity in post‐cardiac arrest survivors undergoing targeted temperature management (TTM) in ICU.

Methods

Thirty‐two post‐cardiac arrest survivors were prospectively included with all patients undergoing TTM at 33°C for 24 hours. Blood samples were collected, and LiMAx testing was performed at days 1, 2, 5, and 10 post‐cardiac arrest. LiMAx is a non‐invasive, in vivo, dynamic breath test determining cytochrome P450 1A2 (CYP1A2) capacity using intravenous (IV) 13C‐methacetin, thus reflecting maximum liver function capacity. Static liver parameters were determined and compared to LiMAx values.

Results

A typical pattern of transiently, mildly increased transaminases was demonstrated without fulfilling the criteria for hypoxic hepatitis (HH). CYP1A2 activity was reduced with slow normalization over 10 days (lowest median 48 hours after cardiac arrest: 228.5 (25‐75 percentile 105.2‐301.7 μg/kg/h, P < .05). Parameters reflecting the liver synthetic function were not impaired, as assessed by, in standard laboratory testing.

Conclusion

Liver functional capacity is impaired in patients after cardiac arrest undergoing TTM at 33°C. More data are needed to determine if liver functional capacity may add relevant information, especially in the context of pharmacotherapy, to individualize post‐cardiac arrest care.
Assessment of platelet function after discontinuation of ticagrelor
Authors: Söderberg Martin , Holm Manne , Gupta Anil
Published: December 2019

Background

Patients presenting with acute coronary syndromes (ACS) are often treated by percutaneous coronary intervention (PCI) with insertion of coronary artery stents and a majority receive dual antiplatelet therapy (DAPT), usually a combination of a COX‐1 inhibitor (aspirin) and a P2Y12 inhibitor (eg ticagrelor). Not seldom the question arises as to when DAPT should be discontinued prior to interventional surgery. This study was done with the primary aim of investigating thrombocyte function immediately prior to and after discontinuation of ticagrelor.

Materials and methods

In this prospective, longitudinal, observational study including 24 patients, venous blood was obtained from patients on day 0, before stopping maintenance dose of 90 mg ticagrelor twice daily, and then on days 1, 3, 5, and 8, after discontinuation. Samples were analyzed using Multiplate® and VerifyNow®.

Results

Prior to urgent surgery platelet aggregation >30 aggregation units (Multiplate®) and >208 P2Y12 reaction units (VerifyNow®) have been shown to correlate with reduced risk of peri‐ and postoperative bleeding risk. On day 3 after ticagrelor discontinuation, 100% (P = .016) and 67% (P=<.001) of patients had reached these levels on Multiplate® and VerifyNow®, respectively. On day 5, the corresponding figures were 100% (P = .016) and 78% (P=<.001).

Conclusion

Discontinuation of ticagrelor for 3 days resulted in return of adequate platelet function in all patients on Multiplate® and in a majority of patients on VerifyNow®, indicating a lower bleeding risk. A bedside test for platelet function may be considered if time to anticipated surgery is less than 5 days after ticagrelor discontinuation.
Ceramides affect alcohol consumption and depressive‐like and anxiety‐like behavior in a brain region‐ and ceramide species‐specific way in male mice
Authors: Zoicas Iulia , Huber Sabine E. , Kalinichenko Liubov S. , Gulbins Erich , Müller Christian P. , Kornhuber Johannes
Published: December 2019

Depression and alcohol dependence are associated with increased plasma ceramide concentrations in humans. Pharmacological increase in C16 ceramide concentrations in the dorsal hippocampus (DH) induced a depressive‐like phenotype in naïve mice. However, the effects of C16 ceramide on alcohol consumption and anxiety‐like behavior as well as the behavioral effects of other ceramide species are yet unknown. Therefore, we investigated whether repeated infusion of ceramides with different fatty acid chain lengths (C8, C16, and C20) into the DH and the basolateral amygdala (BLA) alter alcohol consumption, emotional behavior, and tissue monoamine levels. Our results revealed that C16, but not C8 and C20, ceramide altered alcohol drinking and emotional behavior in a brain region–specific way without altering tissue noradrenaline, dopamine, and serotonin levels in the prefrontal cortex, ventral striatum, and dorsal mesencephalon. In more detail, C16 ceramide increased alcohol consumption when infused into the BLA, but not when infused into the DH. Furthermore, C16 ceramide induced a depressive‐like phenotype when infused into the DH, but a predominantly anxiogenic‐like phenotype (in a non‐social, but not a social context) when infused into the BLA. In turn, alcohol drinking normalized C16 ceramide‐induced depressive‐like and anxiogenic‐like phenotypes. This study demonstrates a complex ceramide species‐specific and brain region‐specific modulation of alcohol consumption and emotional behavior in mice and provides the framework for future studies investigating the involvement of distinct ceramide species in the regulation of emotional behavior.
Predictive value of oxidative stress testing in semen for sperm DNA fragmentation assessed by sperm chromatin dispersion test
Authors: Elbardisi Haitham , Finelli Renata , Agarwal Ashok , Majzoub Ahmad , Henkel Ralf , Arafa Mohamed
Published: December 2019

Background

Although standard semen analysis is a cornerstone of male infertility investiation, it has significant limitations. Seminal oxidative stress and DNA damage have shown potential to better predict male fertility potential and provide improved diagnostic and management strategies.

Objective

The aim of this study was to investigate whether seminal oxidation‐reduction potential (ORP), a new parameter to measure oxidative stress directly, can accurately predict the percentage of sperm DNA fragmentation (SDF) and thereby serve as a surrogate marker in the evaluation of male infertility.

Materials and methods

ORP was evaluated in 3968 patients using the MiOXSYS system and SDF in 1147 patients using the Halosperm G2 test kit. Both parameters were analyzed in 1068 patients, along with seminal analysis, according to WHO guidelines 2010 (5th edition).

Results

SDF correlated positively with seminal ORP normalized for sperm concentration (n = 1068; r = .218; P < .0001) as well as with ORP normalized for the motile sperm concentration (motORP; n = 1068; r = .387; P < .0001). MotORP can significantly (P < .0001) better predict SDF than ORP normalized for the sperm concentration (area under the curve (AUC): 0.719 vs 0.623) (specificity: 71.5%; sensitivity: 61.9%; PPV: 47.1%; NPV: 82.1%). Moreover, motORP can significantly (P < .0001) better predict (AUC: 0.826 vs 0.771) normozoospermia with high sensitivity (82.75%) and specificity (68.5%).

Discussion

Unlike other oxidative stress (OS) markers, ORP provides a global vision of the redox balance in semen. Moreover, SDF can also be induced by mechanisms different from OS, which could explain why its predictive power was low. The higher predictive power of motORP reflects the impact of seminal ROS on motility rather than inherent DNA breaks present in immature and aborted apoptotic spermatozoa.

Conclusion

The evaluation of motORP seems a more promising parameter than ORP normalized for sperm concentration for the prediction of SDF and normozoospermia. However, even if ORP and SDF are inter‐related, they measure independent sperm functions and one test cannot replace the other in the evaluation of sperm function defects.