bluuebunny/crossref_metadata_2025 huggingface dataset:
Data access as a big competitive advantage: evidence from China's car-hailing platforms
Authors: Huang Lei , Zhao Yandong , He Guangxi , Lu Yangxu , Zhang Juanjuan , Wu Peiyi
Published: November 2020

Purpose

The online platform is one of the essential components of the platform economy that is constructed by a large scale of the personal data resource. However, accurate empirical test of the competition structure of the data-driven online platform is still less. This research is trying to reveal market allocation structure of the personal data resource of China's car-hailing platforms competition by the empirical data analysis.

Design/methodology/approach

This research is applying the social network analysis by R packages, which include k-core decomposition and multilevel community detection from the data connectedness via the decompilation and the examination of the application programming interface of terminal applications.

Findings

This research has found that the car-hailing platforms, which establish more constant personal data connectedness and connectivity with social media platforms, are taking the competitive market advantage within the sample network. Data access discrimination is a complementary method of market power in China's car-hailing industry.

Research limitations/implications

This research offers a new perspective on the analysis of the multi-sided market from the personal data resource allocation mechanism of the car-hailing platform. However, the measurement of the data connectedness requires more empirical industry data.

Practical implications

This research reveals the competition structure that relies on personal data resource allocation mechanism. It offers empirical evidence for governance, which is considered as the critical issue of big data research, by reviewing the nature of the data network.

Social implications

It also reveals the data convergence process of the social system and the technological system.

Originality/value

This research offers a new research method for the real-time regulation of the car-hailing platform.
Sales technology and salespeople’s ambidexterity: an ecosystem approach
Authors: Giovannetti Marta , Cardinali Silvio , Sharma Piyush
Published: November 2020

Purpose

This paper aims to explore the impact of salespeople’s goal orientation and self-regulatory mode on their performance through sales ambidexterity and sales technology infusion (STI) using a sales technology ecosystem approach.

Design/methodology/approach

This paper adopts a qualitative methodology, through in-depth interviews with salespeople from a diverse range of industries, age profiles and contexts, to explore the narratives and original meanings related to their goal orientation, self-regulatory mode, ambidexterity, STI and performance.

Findings

Sceptics are salespeople who may fear or hesitate to fully use the sales technology, whereas enthusiasts are ambidextrous salespeople with high STI, who are more open to change and able to face uncertainty, regardless of the differences in their background in terms of industry, age and experience.

Practical implications

STI may be influenced by individual factors, such as the salesperson’s goal orientation and self-regulatory mode. Hence, sales organizations should try to foster and facilitate further STI and sales ambidexterity, which are key to achieving positive outcomes in today’s technology-intensive sales settings.

Originality/value

This paper extends the current literature on sales technology and sales ambidexterity within a sales technology ecosystem perspective and provides new insight on the combined impact of these variables on the salesperson’s performance.
Motivations and consumption practices of fostered idol fans: a self-determination theory approach
Authors: Zhao Shuguang , Wu Xuan
Published: November 2020

Purpose

“Fostered idols” refer to entertainment idols and young stars-in-the-making who begin their careers as amateurs. Today, the fostered idol model has become increasingly popular in China, and fans demonstrate incredible consumption power. Despite the booming market, little is known about this phenomenon. Therefore, this study aims to explore fans’ motivations and consumption practices from the consumer’s perspective within the framework of self-determination theory.

Design/methodology/approach

In all 20 in-depth interviews with fostered idol fans were conducted through online phone calls. The interviews were recorded, transcribed and subsequently analysed using a grounded approach.

Findings

The results indicate that fans’ consumption practices are motivated both intrinsically and extrinsically. Intrinsic motivation includes sensory pleasure while extrinsic motivations are composed of a sense of being needed and a sense of success. Extrinsic motivations play a dominant role and reflect the needs of relatedness and competence. Additionally, consumption practices are found to be consistent with motivations.

Research limitations/implications

The results show the crucial role of psychological satisfaction experienced by fans in the consumption of the fostered idol and highlight the importance of a relatedness- and competence-supportive environment to secure fans’ persistent consumption and loyalty.

Originality/value

This study focuses on fans of fostered idols that has not been explored in existing studies and offers valuable insights regarding the similarities and differences between fan consumption in China and other Asian countries. The results will inform marketing practitioners for the development of effective strategies and business decisions.
Green brand communication, brand prominence and self–brand connection
Authors: Lin Jialing (Catherine) , Zhou Zhimin , Leckie Civilai
Published: November 2020

Purpose

This study aims to empirically investigate how green transparency and green competence enhancement can promote consumer behavioral outcomes (i.e. green brand loyalty and resistance to negative information regarding green brands) through green brand attachment (i.e., self–green brand connection and green brand prominence). It further explores these hypothesized relationships across brands of physical products and services.

Design/methodology/approach

Data were collected using an online survey from 826 Chinese consumers. Structural equation modeling is used to test the proposed conceptual model.

Findings

Our results demonstrate that green transparency and green competence enhancement positively affect consumer green brand attachment (i.e. self–green brand connection and green brand prominence) which subsequently influence consumers’ loyalty toward green brands and their resistance to negative information. Finally, the development of green brand attachment across brands of products and services is found to be different.

Research limitations/implications

Extending the conceptual model to other cultural contexts is suggested. Using the experimental design to examine other boundary conditions is recommended.

Practical implications

This study provides recommendations for marketers, especially brand managers, to facilitate green brand communications to strengthen consumer–brand relationships.

Originality/value

This study extends past research by examining two types of green brand attachment via a cognitive schema lens. Also, it shows the internal cognitive process by which green brand communications potentially promote consumer behavioral outcomes through green brand attachment. Lastly, it highlights differences in the development of green brand loyalty and consumer resistance to negative information across brands of products and services.
Dynamic resource allocation between exploration and exploitation
Authors: Kunieda Yosuke , Takashima Katsuyoshi
Published: November 2020

Purpose

This study aims to clarify how companies should manage exploration and exploitation in the long term, and particularly whether companies should dynamically change their resource allocation related to exploration and exploitation activities.

Design/methodology/approach

To demonstrate the effect of shifts in focus between exploration and exploitation on financial performance and market evaluation, an empirical examination was conducted using secondary panel data for Japanese manufacturers from 2000 to 2014, which was analyzed by fixed-effect estimation with a control function approach considering the problem of endogeneity.

Findings

The empirical results suggest that companies should change their resource allocation related to exploration and exploitation in the long term. Long-term focus shifts between exploration and exploitation activities enhance not only future financial performance (return on assets and return on sales), but also future market evaluations (Tobin’s Q).

Research limitations/implications

This paper showed a pathway connecting technological knowledge searches to the company’s future performance. With reference to the discussion of existing research, it remains unclear what kind of management is required for company activities related to exploration and exploitation. This study showed that companies can improve their profitability and market evaluations by changing their resource allocation for exploration and exploitation activities over time.

Originality/value

While most research on exploration and exploitation is from a static perspective, this study simultaneously incorporated focus balance and focus shifts into the empirical model and thereby examined exploration and exploitation from a dynamic perspective. Even when considering the effects of balancing exploration and exploitation, this study confirmed that organizational vacillation will improve financial performance and market evaluation.
Adaptive trait syndromes along multiple economic spectra define cold and warm adapted ecotypes in a widely distributed foundation tree species
Authors: Blasini Davis E. , Koepke Dan F. , Grady Kevin C. , Allan Gerard J. , Gehring Catherine A. , Whitham Thomas G. , Cushman Samuel A. , Hultine Kevin R.
Published: November 2020

The coordination of traits from individual organs to whole plants is under strong selection because of environmental constraints on resource acquisition and use. However, the tight coordination of traits may provide underlying mechanisms of how locally adapted plant populations can become maladapted because of climate change.

To better understand local adaptation in intraspecific trait coordination, we studied trait variability in the widely distributed foundation tree species, Populus fremontii using a common garden near the mid‐elevational point of this species distribution. We examined 28 traits encompassing four spectra: phenology, leaf economic spectrum (LES), whole‐tree architecture (Corner's Rule) and wood economic spectrum (WES).

Based on adaptive syndrome theory, we hypothesized that trait expression would be coordinated among and within trait spectra, reflecting local adaptation to either exposure to freeze‐thaw conditions in genotypes sourced from high‐elevation populations or exposure to extreme thermal stress in genotypes sourced from low‐elevation populations.

High‐elevation genotypes expressed traits within the phenology and WES that limit frost exposure and tissue damage. Specifically, genotypes sourced from high elevations had later mean budburst, earlier mean budset, higher wood densities, higher bark fractions and smaller xylem vessels than their low‐elevation counterparts. Conversely, genotypes sourced from low elevations expressed traits within the LES that prioritized hydraulic efficiency and canopy thermal regulation to cope with extreme heat exposure, including 40% smaller leaf areas, 67% higher stomatal densities and 34% higher mean theoretical maximum stomatal conductance. Low‐elevation genotypes also expressed a lower stomatal control over leaf water potentials that subsequently dropped to pressures that could induce hydraulic failure.

Synthesis. Our results suggest that Populus fremontii expresses a high degree of coordination across multiple trait spectra to adapt to local climate constraints on photosynthetic gas exchange, growth and survival. These results, therefore, increase our mechanistic understanding of local adaptation and the potential effects of climate change that in turn, improves our capacity to identify genotypes that are best suited for future restoration efforts.
Cu(II) nonspecifically binding chromate reductase NfoR promotes Cr(VI) reduction
Authors: Han Huawen , Zheng Yuanzhang , Zhou Tuoyu , Liu Pu , Li Xiangkai
Published: November 2020

Cu(II)‐enhanced microbial Cr(VI) reduction is common in the environment, yet its mechanism is unknown. The specific activity of chromate reductase, NfoR, from Staphylococcus aureus sp. LZ‐01 was augmented 1.5‐fold by Cu(II). Isothermal titration calorimetry and spectral data show that Cu(II) binds to NfoR nonspecifically. Further, Cu(II) stimulates the nitrobenzene reduction of NfoR, indicating that Cu(II) promotes electron transfer. The crystal structure of NfoR in complex with CuSO4 (1.46 Å) was determined. The overall structure of NfoR‐Cu(II) complex is a dimer that covalently binds with FMN and Cu(II)‐binding pocket is located at the interface of the NfoR dimer. Structural superposition revealed that NfoR resembles the structure of class II chromate reductase. Site‐directed mutagenesis revealed that Leu46 and Phe123 were involved in NADH binding, whereas Trp70 and Ser45 were the key residues for nitrobenzene binding. Furthermore, His100 and Asp171 were preferential affinity sites for Cu(II) and that Cys163 is an active site for FMN binding. Attenuation reductase activity in C163S can be partially restored to 54% wild type by increasing Cu(II) concentration. Partial restoration indicates dual‐channel electron transfer of NfoR via Cu(II) and FMN. We propose a catalytic mechanism for Cu(II)‐enhanced NfoR activity in which Cu(I) is formed transiently. Together, the current results provide an insight on Cu (II)‐induced enhancement and benefit of Cr(VI) bioremediation.
Host–microbiota interactions and responses to grass carp reovirus infection in Ctenopharyngodon idellus
Authors: Xiao Fanshu , Liao Lanjie , Xu Qiaoqing , He Zhili , Xiao Tiaoyi , Wang Jianjun , Huang Jie , Yu Yuhe , Wu Bo , Yan Qingyun
Published: November 2020

Gut microbiota could facilitate host to defense diseases, but fish–microbiota interactions during viral infection and the underlying mechanism are poorly understood. We examined interactions and responses of gut microbiota to grass carp reovirus (GCRV) infection in Ctenopharyngodon idellus, which is the most important aquaculture fish worldwide. We found that GCRV infection group with serious haemorrhagic symptoms (G7s) showed considerably different gut microbiota, especially with an abnormally high abundance of gram‐negative anaerobic Cetobacterium somerae. It also showed the lowest (p < 0.05) alpha‐diversity but with much higher ecological process of homogenizing dispersal (28.8%), confirming a dysbiosis of the gut microbiota after viral infection. Interestingly, signaling pathways of NOD‐like receptors (NLRs), toll‐like receptors (TLRs), and lipopolysaccharide (LPS) stimulation genes were significantly (q‐value < 0.01) enriched in G7s, which also significantly (p < 0.01) correlated with the core gut microbial genera of Cetobacterium and Acinetobacter. The results suggested that an expansion of C. somerae initiated by GCRV could aggravate host inflammatory reactions through the LPS‐related NLRs and TLRs pathways. This study advances our understanding of the interplay between fish immunity and gut microbiota challenged by viruses; it also sheds new insights for ecological defense of fish diseases with the help of gut microbiota.
Archetypes and the ‘Impoverished Genome’ argument: updates from evolutionary genetics
Authors: Goodwyn Erik
Published: November 2020

Throughout his career, Jung felt the psyche had ‘ancestral layers’ that contained elements of an individual’s species history, and clinical experience has shown that this idea can be an aid to psychological healing and emotional well‐being. Thus, some later thinkers have attempted to link such theoretical constructs to the genome, as Jung had little knowledge of genetics in his day. But in the early 2000s, genome studies suggested that the genome might contain too little content to be capable of encoding symbolic information. This opinion gave rise to an oft‐repeated ‘impoverished genome’ argument, i.e. that the genome could not provide a significant contribution to the collective unconscious, prompting theorists to propose other sources for it, or to argue that it doesn’t exist. Today, however, developments in evolutionary neurogenetics calls the impoverished genome argument into question for a number of independent reasons. These developments re‐open the idea that the genome may be worth reconsidering as the biological substrate for the collective unconscious.
Hosting certain facultative symbionts modulates the phenoloxidase activity and immune response of the pea aphid Acyrthosiphon pisum
Authors: Luo Chen , Belghazi Maya , Schmitz Antonin , Lemauf Séverine , Desneux Nicolas , Simon Jean‐Christophe , Poirié Marylène , Gatti Jean‐Luc
Published: November 2020

The pea aphid Acyrthosiphon pisum hosts different facultative symbionts (FS) which provide it with various benefits, such as tolerance to heat or protection against natural enemies (e.g., fungi, parasitoid wasps). Here, we investigated whether and how the presence of certain FS could affect phenoloxidase (PO) activity, a key component of insect innate immunity, under normal and stressed conditions. For this, we used clones of A. pisum of different genetic backgrounds (LL01, YR2 and T3‐8V1) lacking FS or harboring one or two (Regiella insecticola, Hamiltonella defensa, Serratia symbiotica + Rickettsiella viridis). Gene expression and proteomics analyses of the aphid hemolymph indicated that the two A. pisum POs, PPO1 and PPO2, are expressed and translated into proteins. The level of PPO genes expression as well as the amount of PPO proteins and phenoloxidase activity in the hemolymph depended on both the aphid genotype and FS species. In particular, H. defensa and R. insecticola, but not S. symbiotica + R. viridis, caused a sharp decrease in PO activity by interfering with both transcription and translation. The microinjection of different types of stressors (yeast, Escherichia coli, latex beads) in the YR2 lines hosting different symbionts affected the survival rate of aphids and, in most cases, also decreased the expression of PPO genes after 24 h. The amount and activity of PPO proteins varied according to the type of FS and stressor, without clear corresponding changes in gene expression. These data demonstrate that the presence of certain FS influences an important component of pea aphid immunity.
Is being barefoot, wearing shoes and physical activity associated with knee osteoarthritis pain flares? Data from a usually barefoot Sri Lankan cohort
Authors: Atukorala Inoshi , Pathmeswaran Arunasalam , Batuwita Nishamani , Rajapaksha Nimesha , Ratnasiri Vishmi , Wijayaratne Lalith , De Silva Monika , Chang Thashi , Zhang Yuqing , Hunter David John
Published: November 2020

Aim

To identify the association between hours of being barefoot/wearing footwear, physical activity (PA) and knee osteoarthritis pain flares (KOAF).

Methods

Persons with a diagnosis of knee osteoarthritis, who reported previous KOAF, were followed up in a 3 months long telephone‐based case‐crossover study. Exposures to risk factors were assessed every 10 days and whenever the participants experienced a KOAF. Conditional logistic regression examined associations of KOAF with following: hours of being barefoot/using footwear and PA performed (P < .05).

Results

There were 260 persons recruited, of whom 183 continued longitudinal follow up. Of them, 120 persons had at least one valid KOAF and control period. Participants were female (90%) with mean (SD) age and body mass index of 59.9 (7.0) years, 28.0 (5.0) kg/m2 respectively. Participants were barefoot for a mean duration of 12.7 hours (SD 4.6) and used footwear for 5.1 (SD 4.7) hours daily; 99% wore heel heights <2.5 cm. Duration of being barefoot, 1 and 2 days before, demonstrated reduced multivariate odds of KOAF (odds ratio [OR] = 0.85; 95% CI 0.80‐0.90). Moderate PA performed 1, 2 days prior was associated with a significantly increased risk of KOAF (multivariate OR 4.29; 2.52‐7.30 and OR 3.36; 2.01‐5.61). Similarly, hours of using footwear 1 and 2 days before flare demonstrated increased odds of KOAF (OR 1.15; 1.07‐1.23 and 1.10; 1.03‐1.18).

Conclusions

Increased duration of being barefoot 1 to 2 days before is associated with reduced risk of KOAF. Performing moderate PA 1 to 2 days before was associated with an increased risk of KOAF.
Rising Powers, UN Security Council Reform, and the Failure of Rhetorical Coercion
Authors: Binder Martin , Heupel Monika
Published: November 2020

Despite repeated calls for reform, the UN Security Council has as yet resisted to satisfy the demands of a group of rising powers – Brazil, Germany, India, and Japan (G4) – for a permanent seat. We focus on one strategy of institutional adaptation to power shifts mentioned in the introductory article to this special issue and examine why the G4’s rhetorical coercion strategy has failed to resonate with the Council’s permanent members and the wider UN membership. Looking at the key debate on Security Council reform in the General Assembly in 2005, we examine the justifications the G4 have offered to support their proposal and whether these have been accepted as legitimate by UN member states. We show that the G4’s rhetorical coercion strategy has failed to resonate with the targeted audience because the G4 have justified their demand strongly in terms of how their material contributions would enhance the UN’s performance. In contrast, the G4’s opponents provided justifications predominantly based on fair and democratic procedures, generating higher levels of expressed support. The importance of procedural fairness is consistent with findings in social psychology and challenges the prominent argument that performance is the main path to legitimacy for international institutions.
Informal IGOs as Mediators of Power Shifts
Authors: Vabulas Felicity , Snidal Duncan
Published: November 2020

In an era defined by shifting distributions of power, states are not only pushing for change in formal international organizations, they are increasingly using informal intergovernmental organizations (IIGOs) to mediate change. Why and how do states use IIGOs – institutions without a treaty or secretariat – to manage global power shifts? IIGOs are useful for states on both sides of the power shift. Established powers use IIGOs for system management through ‘collaboration’ and strengthening the ‘hegemonic consensus’ to preserve their institutional privileges while adapting to changing power realities. Rising powers use IIGOs to redistribute through ‘power bargaining’ and ‘rhetorical coercion’ to strengthen their institutional roles without overly disrupting the current order. Established and rising powers also work together to use IIGOs for integrative strategies including ‘cooptation’ and ‘principled persuasion’, creating a mutually beneficial solution that accommodates both increased demands but also mounting responsibilities. IIGOs help states manage power transitions by providing flexible institutional arrangements that facilitate bargaining without freezing outcomes in permanent institutions while the power distribution evolves. We provide case vignettes of the G7 (system management) in the early phase of a power shift, BRICS (redistributive strategies) in the middle phase, and the G20 (integrative strategies) in the later phase.
RNF213 gene mutation in circulating tumor DNA detected by targeted next‐generation sequencing in the assisted discrimination of early‐stage lung cancer from pulmonary nodules
Authors: Jiang Ning , Zhou Jie , Zhang Wenhao , Li Peichao , Liu Yu , Shi Hubo , Zhang Chengke , Wang Yunshan , Zhou Chengjun , Peng Chuanliang , Zhang Weiquan , Hao Yingtao , Sun Qifeng , Li Yuliang , Zhao Xiaogang
Published: November 2020

Background

To distinguish early‐stage lung cancer from benign disease in pulmonary nodules, especially lesions with ground‐glass opacity (GGO), we assessed gene mutations of ctDNA in peripheral blood using targeted next‐generation sequencing (NGS).

Methods

Single pulmonary nodule patients without mediastinal lymph nodes and symptoms that were hard to diagnose by chest CT and lung cancer biomarker measurement in multiple medical centers were enrolled into the study. All patients accepted minimally invasive surgery but refused preoperative biopsy. Gene mutations in preoperative blood samples were detected by targeted NGS. Mutations with significant differences between lung tumors and benign lesions, as grouped by postoperative pathology, were screened. Protein expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood.

Results

In the training set, the RNF213, KMT2D, CSMD3 and LRP1B genes were mutated more frequently in early‐stage lung cancer (27 cases) than in benign nodules (15 cases) (P < 0.05). High expression of the RNF213 gene in lung cancers and low expression in benign diseases were seen by immunohistochemistry. The RNF213 gene was mutated in 25% of lung cancer samples in the validation set of 28 samples and showed high specificity (100%). In GGO patients, RNF213 was mutated more frequently in early‐stage lung cancer compared to benign diseases (P < 0.05).

Conclusions

RNF213 gene mutations were observed more frequently in early‐stage lung cancer, but not in benign nodules. Mutation of the RNF213 gene in peripheral blood may be a high specificity biomarker for the assisted early diagnosis of lung cancer in pulmonary nodules.

Key points

Significant findings of the study: In peripheral venous blood and tumor tissue, RNF213 gene mutated more frequently in lung cancer than benign pulmonary nodules.

What this study adds: Detection mutation of the RNF213 gene in peripheral blood may be a high specificity method for the assisted early diagnosis of lung cancer in pulmonary nodules.
Routinely collected data and patient‐centred research in anaesthesia and peri‐operative care: a narrative review
Authors: Armstrong R. A. , Mouton R. , Hinchliffe R. J.
Published: November 2020

Randomised controlled trials are the gold standard in clinical research, but remain rare due to their expense and a perceived lack of ‘real‐world’ applicability. At the same time, there has been an exponential increase in routinely collected data which presents opportunities for audit, quality improvement, adverse event reporting and more efficient clinical research. Registry‐based research benefits from reduced cost, large sample size and real‐world applicability, with methodological developments, particularly registry‐based randomised controlled trials and causal inference techniques, showing promise. Limitations include data quality and validity, the need for data linkage, the restrictions of fixed data fields, regulatory barriers, and privacy and security concerns. However, the principal factor hampering current efforts is a lack of anaesthesia‐specific datasets in the UK and the fact that most surgical registries do not collect any anaesthetic data. This presents an opportunity for anaesthetists, through enhanced engagement and collaboration, to influence and improve the design of these datasets and increase the value and volume of data collected. Better datasets, coupled with a growing appreciation of new analysis methodologies, would allow significant progress towards realising the potential of routinely collected data for patient benefit. At the same time, work should begin on the development of a minimum dataset for anaesthesia to underpin new data sharing networks and, ideally, a national registry of anaesthesia.
Population pharmacokinetics of vancomycin in patients with external ventricular drain‐associated ventriculitis
Authors: Jalusic Kris Oliver , Hempel Georg , Arnemann Philip‐Helge , Spiekermann Christina , Kampmeier Tim‐Gerald , Ertmer Christian , Gastine Silke , Hessler Michael
Published: November 2020

Background

To determine the distribution of vancomycin into the cerebrospinal fluid (CSF) in patients with external ventricular drain (EVD)‐associated ventriculitis, the pharmacokinetics of vancomycin were evaluated and covariate relationships explored.

Methods

For the population pharmacokinetic model patients were recruited in a neurocritical care unit at the University Hospital of Muenster in the period between January 2014 and June 2015. All patients had a clinical evidence of EVD‐associated ventriculitis. Population pharmacokinetic analysis of vancomycin was performed using NONMEM.

Results

A total of 184 blood and 133 CSF samples were collected from 29 patients. The final population pharmacokinetic model is a three‐compartment model with linear elimination. Creatinine clearance (ClCr) and CSF‐lactate were detected as significant covariates, showing that the total vancomycin plasma clearance (Cl) depends on ClCrand furthermore the clearance (Cldif) between the central and CSF compartment correlates with CSF lactate concentration. Based on the final model, the following values were estimated by NONMEM: Cl = 5.15 L/h,Q(intercompartmental clearance) = 3.31 L/h, Cldif = 0.0031 L/h,Vcentral = 42.1 L,VCSF = 0.32 L and the value ofVperipheralwas fixed to 86.2 L. With the developed pharmacokinetic model, area under the curve (AUC) values as well as CSF trough levels were simulated.

Conclusion

Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation (derived from the CSF lactate concentration) and renal function (derived from ClCr).
Ocrelizumab in relapsing and primary progressive multiple sclerosis: Pharmacokinetic and pharmacodynamic analyses of OPERA I, OPERA II and ORATORIO
Authors: Gibiansky Ekaterina , Petry Claire , Mercier Francois , Günther Andreas , Herman Ann , Kappos Ludwig , Hauser Stephen , Yamamoto Yumi , Wang Qing , Model Fabian , Kletzl Heidemarie
Published: November 2020

Aims

Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20‐positive B cells and is indicated for treatment of patients with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS). The pharmacokinetics and pharmacodynamics of ocrelizumab in patients with RMS or PPMS were assessed.

Methods

A population pharmacokinetic model was developed based on data from the Phase II study and the Phase III studies OPERA I and OPERA II in patients with RMS. Data from the ORATORIO Phase III study in patients with PPMS became available after model finalization and was used for external model evaluation.

Results

The ocrelizumab serum concentrationvstime course was accurately described by a 2‐compartment model with time‐dependent clearance. Body weight was found to be the main covariate. The area under the concentration–time curve over the dosing interval was estimated to be 26% higher for patients with RMS weighing <60 kg and 21% lower for patients weighing >90 kg when compared with the 60–90 kg group. The terminal half‐life of ocrelizumab was estimated as 26 days. The extent of B‐cell depletion in blood, as the pharmacodynamic marker, was greater with increasing ocrelizumab exposure.

Conclusion

The pharmacokinetics of ocrelizumab was described with pharmacokinetic parameters typical for an immunoglobulin G1 monoclonal antibody, with body weight as the main covariate. The pharmacokinetics and B‐cell depletion in blood were comparable across the RMS and PPMS trials, and the extent of blood B‐cell depletion was greater with higher exposure.
Review: Inflammation and anxiety‐based disorders in children and adolescents – a systematic review and meta‐analysis
Authors: Parsons Chelsea , Roberts Rachel , Mills Natalie T.
Published: November 2020

Background

Anxiety‐based disorders are common and are often chronic with an onset during childhood or adolescence. An emerging literature has examined the role of inflammation in these disorders by measuring blood concentrations of inflammatory markers such as cytokines, C‐reactive protein (CRP) and immune markers such as white blood cell counts. However, existing results are inconsistent, with available meta‐analyses only including adult populations. We believe this is the first systematic review and meta‐analysis to investigate these inconsistencies among the population of children and adolescents.

Methods

A systematic search of five electronic databases was conducted to identify studies which compared inflammatory markers between individuals with an anxiety‐based disorder and healthy controls. Study quality was assessed, and pooled effect sizes (Hedges’ g) were calculated using random‐effects meta‐analyses.

Results

Nine independent studies were identified. The combined meta‐analysis of 16 cytokines and CRP was approaching significance; however, no significant between‐group difference was observed for meta‐analyses of individual inflammatory or immune markers. Heterogeneity was high, and quality assessments identified important limitations; primarily, small sample sizes and a lack of control over confounding variables.

Conclusions

Although no significant effects were observed, the small number of included studies and limitations in study or reporting quality render these findings provisional. Research in this area has the potential for important clinical implications in relation to therapeutic interventions. Important recommendations for further research are put forth.
A Developmental Perspective on Children With Incarcerated Parents
Authors: Poehlmann‐Tynan Julie , Turney Kristin
Published: November 2020

Parental incarceration is a socially relevant topic with substantial implications for children, yet it is understudied by child development scholars. About 2.6 million U.S. children currently have a parent who is incarcerated, and by age 14, one in 14 U.S. children experiences a resident parent leaving for jail or prison. In this developmentally oriented review, we summarize research on associations between parental incarceration and child well‐being, and suggest areas where developmental scientists can contribute. While most analyses of large population‐based U.S., datasets have found that experiencing paternal incarceration typically has detrimental implications for child well‐being, especially as children grow older, analyses of maternal incarceration have yielded less consistent findings. Longitudinal population‐based developmental studies focusing on parental incarceration, especially early in life through adulthood, are urgently needed to answer basic questions, clarify mixed findings, inform policies, and develop interventions for vulnerable children.
Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients
Authors: Song Danyu , Dai Yi , Chen Xiaoyu , Fu Xiaona , Chang Xingzhi , Wang Ning , Zhang Cheng , Yan Chuanzhu , Zheng Hong , Wu Liwen , Jiang Li , Hua Ying , Yang Haipo , Wang Zhiqiang , Dai Tingjun , Zhu Wenhua , Han Chunxi , Yuan Yun , Kobayashi Kazuhiro , Toda Tatsushi , Xiong Hui
Published: November 2020

Dystroglycanopathy is a group of muscular dystrophies with deficient glycosylation of alpha‐dystroglycan (α‐DG). We recruited patients from 36 tertiary academic hospitals in China. In total, 143 patients with genetically diagnosed dystroglycanopathy were enrolled. Of these, limb girdle muscular dystrophy was the most common initial diagnosis (83 patients) and Walker‐Warburg syndrome was the least common (1 patient). In 143 patients, mutations in FKRP gene were the most prevalent (62 patients), followed by POMT2, POMT1 (16), POMGNT1, ISPD (14), FKTN, GMPPB, B3GALNT2, DPM3, and DAG1. Several frequent mutations were identified in FKRP, POMT1, POMGNT1, ISPD, and FKTN genes. Many of these were founder mutations. Patients with FKRP mutations tended to have milder phenotypes, while those with mutations in POMGNT1 genes had more severe phenotypes. Mental retardation was a clinical feature associated with mutations of POMT1 gene. Detailed clinical data of 83 patients followed up in Peking University First Hospital were further analyzed. Our clinical and genetic analysis of a large cohort of Chinese patients with dystroglycanopathy expanded the genotype variation and clinical spectrum of congenital muscular dystrophies.
The Bariatric Interprofessional Psychosocial Assessment of Suitability Scale predicts binge eating, quality of life and weight regain following bariatric surgery
Authors: Atwood Molly E. , Cassin Stephanie E. , Rajaratnam Thiyake , Hawa Raed , Sockalingam Sanjeev
Published: November 2020

Presurgical psychosocial evaluations are an important component of bariatric care; yet, bariatric programs vary widely in their assessment and interpretation of psychosocial risk. There is a need for validated clinical tools that help to standardize and streamline the assessment of variables relevant to surgical outcomes. The present study contributes to the validation of the Bariatric Interprofessional Psychosocial Assessment of Suitability Scale (BIPASS), a novel presurgical psychosocial evaluation tool, by: (a) examining the psychometric properties and optimal cutoff score, and; (b) examining the ability of the BIPASS tool to predict outcomes 1 and 2 years postsurgery, including weight regain, quality of life, psychiatric symptoms and adherence to postsurgical follow‐up appointments. The BIPASS was applied retrospectively to the charts of 179 consecutively referred patients to a metropolitan bariatric surgery programme. Internal consistency for the BIPASS was acceptable, and interrater reliability was excellent. Higher BIPASS scores predicted higher binge eating symptomatology and lower mental health‐related quality of life at 1 year postsurgery, and weight regain at 2 years (all P < .01). The BIPASS did not predict adherence to postsurgical follow‐up appointments. Findings suggest that the BIPASS can be used to identify patients at increased risk of disordered eating, poor quality of life and weight regain early in the postsurgical course, thereby facilitating patient education and appropriate interventions.
The majority of people with type 1 diabetes and multiple daily insulin injections benefit from using continuous glucose monitoring: An analysis based on the GOLD randomized trial (GOLD‐5)
Authors: Ólafsdóttir Arndís F. , Bolinder Jan , Heise Tim , Polonsky William , Ekelund Magnus , Wijkman Magnus , Pivodic Aldina , Ahlén Elsa , Schwarcz Erik , Nyström Thomas , Hellman Jarl , Hirsch Irl B. , Lind Marcus
Published: November 2020

Aim

To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections.

Materials and Methods

We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements.

Results

Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = −0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self‐measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire.

Conclusion

The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision‐makers for reimbursement and diabetes guidelines.
Clinical sequencing yield in epilepsy, autism spectrum disorder, and intellectual disability: A systematic review and meta‐analysis
Authors: Stefanski Arthur , Calle‐López Yamile , Leu Costin , Pérez‐Palma Eduardo , Pestana‐Knight Elia , Lal Dennis
Published: November 2020

Objective

Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta‐analysis and systematic review of the success rate (diagnostic yield) of clinical sequencing through next‐generation sequencing (NGS) across NDDs. We compare the genetic testing yield across NDD subtypes and sequencing technology.

Methods

We performed a systematic review of the PubMed literature until May 2020. We included clinical sequencing studies that utilized NGS in individuals with epilepsy, autism spectrum disorder (ASD), or intellectual disability (ID). Data were extracted, reviewed, and categorized according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Two investigators performed clinical evaluation and grouping following the International League Against Epilepsy (ILAE) guidelines. Pooled rates of the diagnostic yield and 95% confidence intervals were estimated with a random‐effects model.

Results

We identified 103 studies (epilepsy, N = 72; ASD, N = 14; ID, N = 21) across 32,331 individuals. Targeted gene panel sequencing was used in 73, and exome sequencing in 36 cohorts. Given highly selected patient cohorts, the diagnostic yield was 17.1% for ASD, 24% for epilepsy, and 28.2% for ID (23.7% overall). The highest diagnostic yield for epilepsy subtypes was observed in individuals with ID (27.9%) and early onset seizures (36.8%). The diagnostic yield for exome sequencing was higher than for panel sequencing, even though not statistically significant (27.2% vs 22.6%, P = .071). We observed that clinical sequencing studies are performed predominantly in countries with a high Inequality‐adjusted Human Development Index (IHDI) (countries with sequencing studies: IHDI median = 0.84, interquartile range [IQR] = 0.09 vs countries without sequencing studies: IHDI median = 0.56, IQR = 0.3). No studies from Africa, India, or Latin America were identified, indicating potential barriers to genetic testing.

Significance

This meta‐analysis and systematic review provides a comprehensive overview of clinical sequencing studies of NDDs and will help guide policymaking and steer decision‐making in patient management.
Great tits (Parus major) adequately respond to both allopatric combinatorial mobbing calls and their isolated parts
Authors: Salis Ambre , Léna Jean‐Paul , Lengagne Thierry
Published: November 2020

When mobbing a predator, birds often produce specific mobbing calls that are efficient in recruiting both conspecifics and heterospecifics. Recent studies on Parids have demonstrated that these mobbing calls are in fact a combination of two distinct calls—first, introductory notes eliciting vigilance in the receiver, then broadband frequency notes (D notes) triggering approach. Debates on a parallel between human syntax and this form of combination have emerged. The degree to which this combinatoriality is perceived in heterospecific communication may shed light onto the relative complexity of such combinatoriality. In this study, our aim was to determine whether European great tits (Parus major) appropriately responded to mobbing calls (and their isolated parts) of an allopatric species, the black‐capped chickadee (Poecile atricapillus), a North‐American species which produces similar combinatorial mobbing calls. In addition, we tested whether the behavioural response to complete mobbing sequences was different than the simple sum of its two constituents. As we hypothesized, great tits behaved differently when hearing the two isolated calls or the complete mobbing sequence: they produced calls and displayed excitement signs only towards the complete mobbing sequence. Moreover, great tits responded to the introductory and D notes by respectively scanning and approaching, and to the complete sequence by mobbing. Our results altogether support the emerging hypothesis of semantic compositionality in Parids, although the present study does not definitively demonstrate the existence of this cognitive process in the great tit.
Latitudinal variation in plant defence against herbivory in a marine foundation species does not follow a linear pattern: The importance of resource availability
Authors: Hernán Gema , Ortega María J. , Henderson Jeremy , Alós Josep , Boyer Katharyn , Cimon Stephanie , Combes Vincent , Cusson Mathieu , Hereu Clara M. , Hessing‐Lewis Margot , Hovel Kevin , Jorgensen Pablo , Kiriakopolos Stephanie , Kollars Nicole , O´Connor Mary I. , Olsen Jeanine , Reynolds Pamela L. , Ruesink Jennifer , Voigt Erin , Tomas Fiona
Published: November 2020

Aim

Studies on latitudinal patterns in plant defence have traditionally overlooked the potential effect that resource availability may have in shaping plant defence. Likewise, latitudinal patterns of tolerance traits have rarely been studied, yet they can be a critical component of plant defence. Therefore, the aim of our study was to examine latitudinal variation in the production of tolerance and resistance traits against herbivory along a latitudinal range and a natural gradient of resource availability from upwelling conditions.

Location

North America (Canada, USA, Mexico).

Time period

Summer months of 2015.

Major taxa used

The seagrass Zostera marina.

Methods

We conducted experiments simulating macroherbivore (e.g., bird, fish) damage on the seagrass Z. marina at 10 sites across the Eastern Pacific coast (Canada–Mexico) and Quebec and analysed several traits related to resistance and tolerance strategies against herbivory. In addition, we examined the effects of potential seagrass changes in defence strategies by performing a series of feeding experiments with mesoherbivores in a subset of sites.

Results

We found that eelgrass resistance defences did not follow a linear latitudinal pattern but rather followed a bell‐shaped curve which correlated with bottom‐up control. In sites with higher nutrient availability, plants allocated resources to tolerance strategies and had lower resistance traits. Furthermore, seagrasses did not respond linearly to increased herbivory pressure; while they tolerated moderate levels of herbivory, they underwent a significant reduction in tolerance and resistance under high herbivory levels, which also made them more susceptible to consumers in feeding experiments.

Main conclusions

Our results highlight the importance that nutrient availability has in shaping latitudinal patterns of plant defence against herbivory and show how these defences may not respond linearly to increased herbivory pressure in seagrasses.