bluuebunny/crossref_metadata_2025 huggingface dataset:
Confidential genetic testing and electronic health records: A survey of current practices among Huntington disease testing centers
Authors: Eno Celeste C. , Barton Stacey K. , Dorrani Naghmeh , Cederbaum Stephen D. , Deignan Joshua L. , Grody Wayne W.
Published: November 2019

Background

Clinical care teams providing presymptomatic genetic testing often employ advanced confidentiality practices for documentation and result storage. However, patient requests for increased confidentiality may be in conflict with the legal obligations of medical providers to document patient care activities in the electronic health record (EHR). Huntington disease presents a representative case study for investigating the ways centers currently balance the requirements of EHRs with the privacy demands of patients seeking presymptomatic genetic testing.

Methods

We surveyed 23 HD centers (53% response rate) regarding their use of the EHR for presymptomatic HD testing.

Results

Our survey revealed that clinical care teams and laboratories have each developed their own practices, which are cumbersome and often include EHR avoidance. We found that a majority of HD care teams record appointments in the EHR (91%), often using vague notes. Approximately half of the care teams (52%) keep presymptomatic results of out of the EHR.

Conclusion

As genetic knowledge grows, linking more genes to late‐onset conditions, institutions will benefit from having professional recommendations to guide development of policies for EHR documentation of presymptomatic genetic results. Policies must be sensitive to the ethical differences and patient demands for presymptomatic genetic testing compared to those undergoing confirmatory genetic testing.
Identification of a five‐mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor
Authors: Lin Xiao‐Dan , Wu Yu‐Peng , Chen Shao‐Hao , Sun Xiong‐Lin , Ke Zhi‐Bin , Chen Dong‐Ning , Li Xiao‐Dong , Lin Yun‐Zhi , Wei Yong , Zheng Qing‐Shui , Xu Ning , Xue Xue‐Yi
Published: November 2019

Background

The aim of this study was to generate a prognostic model to predict survival outcome in pediatric Wilms tumor (WT).

Methods

The data including mRNA expression and clinical information of pediatric WT patients were downloaded from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. The differentially expressed genes were identified and a prognostic signature of pediatric WT was generated according to the results of univariate and multivariate Cox analysis. Receiver operating characteristic (ROC) curve was used to evaluate the five‐mRNA signature in pediatric Wilms tumor patients. Bootstrap test with 500 times was used to perform the internal validation.

Results

We identified 6,964 differentially expressed mRNAs associated with pediatric WT, including 3,190 downregulated mRNAs and 3,774 up‐regulated mRNAs. Univariate and multivariate Cox analysis identified five mRNAs (SPRY1, SPIN4, MAP7D3, C10orf71, and SPAG11A) to establish a predictive model. The risk score formula is as follows: Risk score = 0.3036*SPIN4 + 0.8576*MAP7D3 −0.1548*C10orf71 −0.7335*SPRY1 −0.2654*SPAG11A. The pediatric WT patients were divided into low‐risk group and high‐risk group based on the median risk score (value = 1.1503). The receiver operating characteristic (ROC) curve analysis revealed good performance of the 5‐mRNA prognostic model (the area under the curve [AUC] was 0.821). Bootstrap test (Bootstrap resampling times = 500) was used to perform the internal validation and revealed that the AUC was 0.822. REACTOME, KEGG, and BIOCARTA pathway analyses demonstrated that these survival‐related genes were mainly enriched in ErbB2 and ErbB3 signaling pathways, and calcium signaling pathway.

Conclusion

The five‐mRNA signature can predict the prognosis of patients with pediatric WT. It has significant implication in the understanding of therapeutic targets for pediatric WT patients. However, further study is needed to validate this five‐mRNA signature and uncover more novel diagnostic or prognostic mRNAs candidates in pediatric WT patients.
Existence of the periodic solution to the nematic liquid crystal equations in weighted Sobolev spaces
Authors: Guo Boling , Qin Guoquan
Published: November 2019

This paper is concerned with the time‐periodic solution to the simplified incompressible nematic liquid crystal equation. We prove the existence of the time‐periodic solution of this equation with small external forces g1 and g2, satisfying the T‐periodic conditions gj(t)=gj(t+T) for j=1,2 in weighted Sobolev spaces.
Characterization and modeling of the reverse behavior of a vertical power MOSFET
Authors: Yan Lixi , Li Tianyu , Kallfass Ingmar
Published: November 2019

In this work, the static and dynamic reverse behavior of a vertical structure Si power MOSFET is characterized. The BSIM3 model is adopted and extended to describe the channel current considering asymmetric channel behavior caused by the vertical structure. The diffusion capacitance of the body diode is analyzed, which is critical for the reverse recovery behavior but currently not precisely defined in power MOSFET models. To accurately depict the reverse recovery current, two diode models with diffusion capacitance definitions based on the solution of different methods are built into the MOSFET model and their performance is compared. The result shows that to describe the reverse recovery of the body diode for smaller current range simulation, the stored charge model is recommended, but when scalability is necessary, the carrier distribution model is more suitable.
Pattern reconfigurable Yagi‐Uda antenna with seven switchable beams for WiMAX application
Authors: Gaya Sagiru , Hussain Rifaqat , Sharawi Mohammad S. , Attia Hussein
Published: November 2019

In this paper, a pattern reconfigurable printed Yagi‐Uda antenna with linear polarization is presented. The proposed design consists of three parts, including a driving element centered between two other parasitic elements. To achieve pattern reconfigurability, the approach of Yagi‐Uda configuration is employed, where the positions of the director and reflector are exchanged using PIN diodes. The proposed antenna employing six PIN diodes is designed to radiate the main beam at seven scanning angles (−60°, −40°, −20°, 0°, 20°, 40°, and 60°). The beam tilt depends on the size of the antenna's partial ground plane. The proposed design is simple in structure realized on a single substrate board of dimensions 75 × 70 mm2. The measured peak directivity obtained at various scanning angles is about 6.5 dB. The simulated and measured results are in good agreement. The proposed reconfigurable antenna is suitable for WiMAX applications operating around the frequency of 3.6 GHz.
Electronic intracavitary brachytherapy quality management based on risk analysis: The report of AAPM TG 182
Authors: Thomadsen Bruce R. , Biggs Peter J. , Cardarelli Gene A. , Chu James C. H. , Cormack Robert A. , Feng Wenzheng , Heaton H. Thompson , Hiatt Jessica R. , Law Jonathan N. , Limmer Jeffery P. , Ouhib Zoubir , Pai Sujatha , Pillai Sushakumari , Ringor Michael R. , Rivard Mark J. , Waldron Timothy J. , Caldwell Barrett S. , Holt Randall W. , Pike Tina L. , Safigholi Habib , Stacey Christopher , Weigand Frank
Published: November 2019

Purpose

The purpose of this study was to provide guidance on quality management for electronic brachytherapy.

Materials and Methods

The task group used the risk‐assessment approach of Task Group 100 of the American Association of Physicists in Medicine. Because the quality management program for a device is intimately tied to the procedure in which it is used, the task group first designed quality interventions for intracavitary brachytherapy for both commercial electronic brachytherapy units in the setting of accelerated partial‐breast irradiation. To demonstrate the methodology to extend an existing risk analysis for a different application, the task group modified the analysis for the case of post‐hysterectomy, vaginal cuff irradiation for one of the devices.

Results

The analysis illustrated how the TG‐100 methodology can lead to interventions to reduce risks and improve quality for each unit and procedure addressed.

Conclusion

This report provides a model to guide facilities establishing a quality management program for electronic brachytherapy.
Differential association between S100A4 levels and insulin resistance in prepubertal children and adult subjects with clinically severe obesity
Authors: Taxerås Siri D. , Galán María , Campderros Laura , Piquer‐Garcia Irene , Pellitero Silvia , Martínez Eva , Puig Rocío , Lucena Icíar , Tarascó Jordi , Moreno Pau , Balibrea José , Bel Joan , Murillo Marta , Martínez María , Ramon‐Krauel Marta , Puig‐Domingo Manel , Villarroya Francesc , Lerin Carles , Sánchez‐Infantes David
Published: November 2019

Objectives

S100A4 has been recently identified as an adipokine associated with insulin resistance (IR) in adult subjects with obesity. However, no data about its levels in children with obesity and only a few approaches regarding its potential mechanism of action have been reported. To obtain a deeper understanding of the role of S100A4 in obesity, (a) S100A4 levels were measured in prepubertal children and adult subjects with and without obesity and studied the relationship with IR and (b) the effects of S100A4 in cultured human adipocytes and vascular smooth muscle cells (VSMCs) were determined.

Methods

Sixty‐five children (50 with obesity, age 9.0 ±1.1 years and 15 normal weight, age 8.4 ±0.8 years) and fifty‐nine adults (43 with severe obesity, age 46 ±11 years and 16 normal weight, age 45 ±9 years) were included. Blood from children and adults and adipose tissue samples from adults were obtained and analysed. Human adipocytes and VSMC were incubated with S100A4 to evaluate their response to this adipokine.

Results

Circulating S100A4 levels were increased in both children (P = .002) and adults (P < .001) with obesity compared with their normal‐weight controls. In subjects with obesity, S100A4 levels were associated with homeostatic model assessment‐insulin resistance (HOMA‐IR) in adults (βstd = .42, P = .008) but not in children (βstd = .12, P = .356). Human adipocytes were not sensitive to S100A4, while incubation with this adipokine significantly reduced inflammatory markers in VSMC.

Conclusions

Our human data demonstrate that higher S100A4 levels are a marker of IR in adults with obesity but not in prepubertal children. Furthermore, the in vitro results suggest that S100A4 might exert an anti‐inflammatory effect. Further studies will be necessary to determine whether S100A4 can be a therapeutic target for obesity.
Psychosocial interventions for informal caregivers of lung cancer patients: A systematic review
Authors: Kedia Satish K. , Collins Andy , Dillon Patrick J. , Akkus Cem , Ward Kenneth D. , Jackson Bianca M.
Published: November 2019

Objective

Caregivers of patients with lung cancer often face physical, emotional, and financial distress, which not only negatively affects the caregivers' mental health and quality of life but may also impact patients' well‐being. The purpose of this systematic review is to examine the content, delivery, and efficacy of psychosocial interventions targeting caregivers of lung cancer patients.

Methods

Studies included in this systematic review assessed psychosocial interventions for caregivers of lung cancer patients that were published in English between January 2009 and December 2017. These interventions focused on burden, mental health, quality of life, self‐efficacy, and/or coping as outcome measures. CINAHL, PubMed, PsycInfo, Science Direct, and Web of Science databases were searched using the terms (lung cancer OR lung neoplasms OR thoracic cancer) AND (caregiver OR caregiving) AND (intervention OR program) to systematically review the relevant literature on this topic.

Results

From the 22 studies included in this systematic review, interventions were classified into four categories: communication‐based interventions, coping skills training interventions, multicomponent interventions, and stress reduction interventions. The majority of the interventions (especially communication‐based and multicomponent) led to improvement, albeit not always statistically significant, in one or more outcomes; however, the most frequently reported improvements included, burden, distress, anxiety, depression, overall quality of life, self‐efficacy, and coping abilities.

Conclusions

The unmet needs of informal caregivers of lung cancer patients have a significant impact on their mental health and quality of life, but this burden can be alleviated by psychosocial interventions that offer appropriate support, education, and resources.
Undergraduate training in breaking bad news: A continuation study exploring the patient perspective
Authors: Carrard Valerie , Bourquin Céline , Stiefel Friedrich , Schmid Mast Marianne , Berney Alexandre
Published: November 2019

Objective

This paper reports on the continuation of an initial study that demonstrated the effectiveness, as rated by experts, of an undergraduate training in breaking bad news (BBN) using simulated patient (SP) and individual feedback. The current study aimed to further explore whether such an individualized training approach also has positive effects from the perspective of the patient, using the analogue patient (AP) methodology.

Methods

A subsample of 180 videotaped interviews with SPs were selected from the existing data set (N = 332), consisting of 60 pre‐ and post‐training interviews of students benefiting from the individualized approach (intervention group) and 60 post‐training interviews of students having small‐group SP training and collective supervision (comparison group). Sixty‐eight APs—healthy untrained observers—were asked to view the videotaped interviews while “putting themselves in the patient's shoes” and evaluate satisfaction, trust, liking, and the competence of medical students.

Results

The intervention group students improved significantly from pre‐ to post‐training on several dimensions evaluated by the APs: patient satisfaction, trust in the student, liking of the student, and perceived medical competence. Increased AP satisfaction was related to different changes in students' communication behavior between pre‐ and post‐training: increase in positive talk, emotional responsiveness, biomedical and psychosocial information, and biomedical counseling. There was no significant between‐group difference at post‐training.

Conclusions

AP evaluation showed significant improvement between pre‐ and post‐training. This result provides additional and complementary evidence of the positive effects of individualized training in BBN from the AP perspective, a proxy of (real) patients.
A critical literature review of dyadic web‐based interventions to support cancer patients and their caregivers, and directions for future research
Authors: Luo Xingjuan , Gao Lihong , Li Jieyu , Lin Yi , Zhao Jie , Li Qiuping
Published: November 2019

Objective

With the rapid development of the Internet, e‐health interventions are becoming popular and are showing positive impacts. Cancer affects not only patients but also their caregivers, leading to a recognition that cancer patient–caregiver dyads cope with cancer as a unit rather than as individuals. The objectives of this paper are to explore web‐based interventions for cancer patient–caregiver dyads coping with cancer from the aspects of intervention content, delivery format, outcome measurements, and outcomes and to provide recommendations on developing patient‐caregiver dyadic web‐based interventions for future research.

Methods

Literature focused on cancer patient–caregiver dyadic web‐based interventions, published in English or Chinese from the launch of five databases (CINAHL, PsycINFO, EMBase, Medline, Science Citation Index Expanded) to April 2019, was systematically searched. Manual searching through the references of full‐text articles was also conducted.

Results

Of a total of 812 articles, 17 articles met the inclusion criteria. The content of these web‐based dyadic interventions mainly included information support, communication and support, skills‐building, and psycho‐education. These web‐based interventions reported a small to large positive impact on patients with cancer and their caregivers in terms of physical health (d = 0.17‐0.75), psychological health (d = 0.04‐0.80), overall quality of life (d = 0.20‐0.68), and dyadic relationship (d = 0.30‐0.95).

Conclusions

Web‐based dyadic interventions can be designed for tailored content, which benefits both patients and their caregivers. Future research on cancer patient–caregiver web‐based interventions should be conducted in diverse cultures.
Mode transition and plasma characteristics of nanosecond pulse gas–liquid discharge: Effect of grounding configuration
Authors: Wang Sen , Yang De‐Zheng , Zhou Rusen , Zhou Renwu , Fang Zhi , Wang Wenchun , Ostrikov Kostya (Ken)
Published: November 2019

Transitions between the streamer and spark modes affect the stability of gas–liquid discharges, limiting their practical applications, while the nature of such transitions is poorly understood. Here we clarify the often neglected effect of a dielectric on the gas–liquid discharge stability, using direct and indirect grounding configurations. Discharge modes and plasma characteristics in these two configurations are investigated. The discharge appears in a transient spark mode in the direct grounding while in a streamer mode in the indirect case. It is shown that the dielectric significantly improves the discharge stability. The gas temperature and electron density in the transient spark are 380 K and 1017/cm3 with a 30 kV pulse voltage, respectively, which are higher than those in the streamer mode.
ConSurf‐DB: An accessible repository for the evolutionary conservation patterns of the majority of PDB proteins
Authors: Ben Chorin Adi , Masrati Gal , Kessel Amit , Narunsky Aya , Sprinzak Josef , Lahav Shlomtzion , Ashkenazy Haim , Ben‐Tal Nir
Published: November 2019

Patterns observed by examining the evolutionary relationships among proteins of common origin can reveal the structural and functional importance of specific residue positions. In particular, amino acids that are highly conserved (i.e., their positions evolve at a slower rate than other positions) are particularly likely to be of biological importance, for example, for ligand binding. ConSurf is a bioinformatics tool for accurately estimating the evolutionary rate of each position in a protein family. Here we introduce a new release of ConSurf‐DB, a database of precalculated ConSurf evolutionary conservation profiles for proteins of known structure. ConSurf‐DB provides high‐accuracy estimates of the evolutionary rates of the amino acids in each protein. A reliable estimate of a query protein's evolutionary rates depends on having a sufficiently large number of effective homologues (i.e., nonredundant yet sufficiently similar). With current sequence data, ConSurf‐DB covers 82% of the PDB proteins. It will be updated on a regular basis to ensure that coverage remains high—and that it might even increase. Much effort was dedicated to improving the user experience. The repository is available at https://consurfdb.tau.ac.il/.

Broader audience

By comparing a protein to other proteins of similar origin, it is possible to determine the extent to which each amino acid position in the protein evolved slowly or rapidly. A protein's evolutionary profile can provide valuable insights: For example, amino acid positions that are highly conserved (i.e., evolved slowly) are particularly likely to be of structural and/or functional importance, for example, for ligand binding and catalysis. We introduce here a new and improved version of ConSurf‐DB, a continually updated database that provides precalculated evolutionary profiles of proteins with known structure.
A reliability‐based fatigue design for mechanical components under material variability
Authors: Du Weiqi , Wang Yongqin , Luo Yuanxin
Published: November 2019

The mechanical components subjected cyclic load unusually fail due to fatigue. The traditional deterministic design method still has the risk of failure while the safety factor method sometimes is overconservative and uneconomic. In this study, reliability‐based design optimization is applied in structural design of components under low cycle fatigue. A constitutive model (Jiang and Sehitoglu model) was written into user‐defined material subroutine of finite element software to make simulation more accurate. In addition, an adaptive least squares support vector machines (LS‐SVM)‐based response surface method is employed to improve the efficiency of design process. After constructing the implicit life model, a hybrid directional step method is employed to implement the performance measure approach. Finally, a simple case (thickness optimization for cantilever tube) is used to demonstrate the whole procedure of proposed design procedure.
Interannual variation in spawning success of striped bass (Morone saxatilis) in the Saint John River, New Brunswick
Authors: Andrews Samuel N. , Linnansaari Tommi , Leblanc Nathalie , Pavey Scott A. , Curry R. Allen
Published: November 2019

Barriers such as dams have been cited as a serious threat to striped bass survival, especially when they affect or impede migration and access to spawning grounds. On the Saint John River, New Brunswick, the installation of the large Mactaquac Dam in the immediate vicinity of a historic striped bass spawning location was suspected to have caused the arrest of striped bass reproduction and the collapse of the native striped bass population. In 2014, juvenile striped bass of confirmed Saint John River origin were documented in the river for the first time since 1979. In the current study, we examined juveniles from 6 years of sampling to determine corresponding years of successful recruitment. We also tracked adult striped bass matching the ancestry of native Saint John River juveniles to determine the timing and location of spawning. Over 5 years, we observed an annual upstream migration by adult striped bass to historic spawning areas near Fredericton, identified a dominant year class of Saint John River origin juveniles reproduced in 2013, and linked the apparent successful production of year classes to definable discharge conditions, that is, extended periods of sustained flow >36 hr downstream from the Mactaquac Dam. The results of this study suggest important first management actions towards recovering and sustaining the re‐discovered striped bass population in the Saint John River, New Brunswick.
Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells
Authors: Chow Lyndah , Johnson Valerie , Impastato Renata , Coy Jonathan , Strumpf Alyssa , Dow Steven
Published: November 2019

Mesenchymal stem cells (MSC) have been shown to improve wound healing and suppress inflammatory immune responses. Newer research also indicates that MSC exhibit antimicrobial activity, although the mechanisms underlying this activity have not been fully elucidated. Therefore, we conducted in vitro and in vivo studies to examine the ability of resting and activated MSC to kill bacteria, including multidrug resistant strains. We investigated direct bacterial killing mechanisms and the interaction of MSC with host innate immune responses to infection. In addition, the activity of MSC against chronic bacterial infections was investigated in a mouse biofilm infection model. We found that MSC exhibited high levels of spontaneous direct bactericidal activity in vitro. Moreover, soluble factors secreted by MSC inhibited Staphylococcus aureus biofilm formation in vitro and disrupted the growth of established biofilms. Secreted factors from MSC also elicited synergistic killing of drug-resistant bacteria when combined with several major classes of antibiotics. Other studies demonstrated interactions of activated MSC with host innate immune responses, including triggering of neutrophil extracellular trap formation and increased phagocytosis of bacteria. Finally, activated MSC administered systemically to mice with established S. aureus biofilm infections significantly reduced bacterial numbers at the wound site and improved wound healing when combined with antibiotic therapy. These results indicate that MSC generate multiple direct and indirect, immunologically mediated antimicrobial activities that combine to help eliminate chronic bacterial infections when the cells are administered therapeutically.

Significance statement This study investigated the antimicrobial properties of human mesenchymal stem cells (MSC) and extends the results of previous studies by describing both the direct antimicrobial activity of MSC and the indirect antimicrobial effects mediated via interaction with host innate immune cells. This article describes in detail how MSC secreted factors augment the antimicrobial activity of nearly all classes of conventional antibiotics examined, including generating enhanced activity against drug-resistant strains of Staphylococcus aureus. This study with human MSC serves to bridge previous studies and suggests the utility of systemic delivery of activated MSC for treatment of chronic drug-resistant infection in human patients, in a scalable and clinically applicable manner.
Autologous cord blood cell infusion in preterm neonates safely reduces respiratory support duration and potentially preterm complications
Authors: Ren Zhuxiao , Xu Fang , Zhang Xiaoling , Zhang Chunyi , Miao Jiayu , Xia Xin , Kang Mengmeng , Wei Wei , Ma Tianbao , Zhang Qi , Lu Lijuan , Wen Jiying , Liu Guocheng , Liu Kaiyan , Wang Qi , Yang Jie
Published: November 2019

Preterm birth and its complications are the leading cause of neonatal death. The main underlying pathological mechanisms for preterm complications are disruption of the normal maturation processes within the target tissues, interrupted by premature birth. Cord blood, as a new and convenient source of stem cells, may provide new, promising options for preventing preterm complications. This prospective, nonrandomized placebo controlled study aimed at investigating the effect of autologous cord blood mononuclear cells (ACBMNC) for preventing preterm associated complications. Preterm infants less than 35 weeks gestational age were assigned to receive ACBMNC (5 × 107 cells/kg) intravenous or normal saline within 8 hours after birth. Preterm complication rates were compared between two groups to demonstrate the effect of ACBMNC infusion in reducing preterm complications. Fifteen preterm infants received ACBMNC infusion, and 16 infants were assigned to the control group. There were no significant differences when comparing mortality and preterm complication rates before discharge. However, ACBMNC infusion demonstrated significant decreases in duration of mechanical ventilation (3.2 days vs 6.41 days, P = .028) and oxygen therapy (5.33 days vs 11.31 days, P = .047). ACBMNC infusion was effective in reducing respiratory support duration in very preterm infants. Due to the limited number of patients enrolled, powered randomized controlled trials are needed to better define its efficacy.

Significance statement The results from this prospective nonrandomized study found that autologous cord blood cells infusion substantially reduced the duration of mechanical ventilation and oxygen supplement. Fewer preterm complications were observed in the cord blood cell infusion group, although there was no significant difference. Preterm birth complications are the first major direct cause of neonatal death, and no curative therapies are available to alleviate the symptoms of preterm complications. Stem cells as a treatment provides regrowth to their underdeveloped organs and therefore could improve the outcomes of preterm infants by adding more stem/progenitor cells. This may be helpful to prevent preterm complications.
Confidence interval estimation for the changepoint of treatment stratification in the presence of a qualitative covariate‐treatment interaction
Authors: Haller Bernhard , Mansmann Ulrich , Dobler Dennis , Ulm Kurt , Hapfelmeier Alexander
Published: November 2019

The goal in stratified medicine is to administer the “best” treatment to a patient. Not all patients might benefit from the same treatment; the choice of best treatment can depend on certain patient characteristics. In this article, it is assumed that a time‐to‐event outcome is considered as a patient‐relevant outcome and a qualitative interaction between a continuous covariate and treatment exists, ie, that patients with different values of one specific covariate should be treated differently. We suggest and investigate different methods for confidence interval estimation for the covariate value, where the treatment recommendation should be changed based on data collected in a randomized clinical trial. An adaptation of Fieller's theorem, the delta method, and different bootstrap approaches (normal, percentile‐based, wild bootstrap) are investigated and compared in a simulation study. Extensions to multivariable problems are presented and evaluated. We observed appropriate confidence interval coverage following Fieller's theorem irrespective of sample size but at the cost of very wide or even infinite confidence intervals. The delta method and the wild bootstrap approach provided the smallest intervals but inadequate coverage for small to moderate event numbers, also depending on the location of the true changepoint. For the percentile‐based bootstrap, wide intervals were observed, and it was slightly conservative regarding coverage, whereas the normal bootstrap did not provide acceptable results for many scenarios. The described methods were also applied to data from a randomized clinical trial comparing two treatments for patients with symptomatic, severe carotid artery stenosis, considering patient's age as predictive marker.
Unwelcome voices: The gender bias‐mitigating potential of unconventionality
Authors: Parker Owen , Mui Rachel , Titus Varkey
Published: November 2019

Research Summary

Substantial evidence indicates that leaders are perceived through a lens of gender bias, but what mitigates such bias remains underexplored. Examining men and women in creative, project‐based leadership roles, we integrate insights from role congruity and gender bias literatures to predict how project unconventionality and leader gender affect external perceptions of project quality. We argue that prejudice against female leaders is strongest for conventional projects due to the established presence of male‐centric prototypical projects which induce bias, but that project unconventionality weakens this bias by distancing the project from these male‐centric prototypes. We find support for this using a sample of 1,414 films by 32 major film studios (1990–2014) across three measures of perceived quality: moviegoer ratings, critic ratings, and film awards.

Managerial Summary

Despite recent strides in gender equality, women are still highly underrepresented in leadership positions across all kinds of organizations. This is partly because society still views women as “less fit for leadership,” and this both prevents the appointment of female leaders and damages audience perceptions of the few projects that women do lead. Surprisingly, we know little about how to address this bias. In this study, we predict that in terms of how audiences rate the quality of a project, “unconventional” projects are less susceptible to gender bias. After examining 1,414 feature films from 32 major studios, we find that whether audiences rate a female‐directed film poorly depends on its conventionality—conventional films favor male directors, while unconventional films favor female directors.
Immune Checkpoint Blockade Mediated by a Small‐Molecule Nanoinhibitor Targeting the PD‐1/PD‐L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer
Authors: Zhang Rui , Zhu Zhiyan , Lv Hongying , Li Futian , Sun Shuqing , Li Juan , Lee Chun‐Sing
Published: November 2019

Targeting programmed cell death protein 1 (PD‐1)/programmed death ligand 1 (PD‐L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol‐Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS‐202 is a small‐molecule inhibitor of the PD‐1/PD‐L1 interaction that is developed by BMS. Transfer of BMS‐202 NPs to 4T1 tumor‐bearing mice results in markedly slower tumor growth to the same degree as treatment with anti‐PD‐L1 monoclonal antibody (α‐PD‐L1). Consistently, the combination of Ce6 NPs with BMS‐202 NPs or α‐PD‐L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen‐specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS‐202 NPs are able to attack spreading metastatic lung tumors and offer immune‐memory protection to prevent tumor relapse. These results indicate that BMS‐202 NPs possess effects similar to α‐PD‐L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS‐202 NPs.
Modelling “Occident/Orient” duality and migration process with mobile agents
Authors: M'hamdi Ahmed , Sfa Fatima‐Ezahra , Nemiche Mohamed , Hachimi El Idrissi Saida , Pla‐López Rafael
Published: November 2019

The history of the evolution of human societies up to the present day has been marked by large‐scale collective migrations as well as by a clear duality between a West dominated by individualistic social behaviours and an East dominated by collective social behaviours. Only, at the end of the 20th century, the two lines of evolution converge towards a capitalist globalization.

The main objective of this work is to build an agent‐based model from the mathematical model of Rafael Pla‐López in order to simulate the social evolution of an artificial society. The simulations of our model make it possible to understand the collective migration process and different lines of social evolution such as Occident/Orient duality. This model can serve as a virtual laboratory to understand the processes involved in human social evolution and explore different trajectories of human social evolution.
Improvement of moving least squares transformation in distance cartogram construction
Authors: Miura Takeshi , Tajima Katsubumi
Published: November 2019

Distance cartograms are deformed maps in which the distance of each of the preselected point pairs in the geographic map is changed in step with a specified value. They are constructed through two steps: locating the points included in the preselected pairs, and locating other points. A technique of moving least squares transformation is used in the second step. In this letter, the above technique is improved to maintain homeomorphism in the cartogram. The weight function used in the transformation is modified. Experimental results show the effectiveness of the proposed approach. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Assessing the impact of R&D policy on PV market development: The case of South Korea
Authors: Ha Yoon‐Hee , Byrne John , Lee Hae‐Seok , Lee Ye‐Jin , Kim Dong‐Hwan
Published: November 2019

The purpose of this article is to examine the Korean photovoltaic (PV) R&D strategy and its effectiveness in helping Korean manufacturer competitiveness. The article reviewed the Korean government's PV R&D funding from 2008 to 2017 and investigated the technology readiness levels of 298 R&D projects funded by the Korean government during the same period. It is found that the Korean government followed a two‐track approach of nurturing commercialization technology to cope with rapid growth and volatility in the current global market. The effects of government support for market‐ready and next‐generation technologies in order to position the country in today's competition and to prepare it for “first mover” opportunities in emerging markets are considered. During 2008–2017, Korean manufacturers maintained a 7% of market share. Module prices, which were more than USD 6 per watt in 2000, fell to less than USD 1 in 2017. From a technical point of view, silicon‐based modules have achieved world‐class status in their efficiency. Performance of the country's nonsilicon technologies reached nearly 90% of the world's best nonsilicon products in the early 2010s, but recently, next‐generation technology development is lagging. Despite Korean PV industry's achievements, it is unclear whether Korean government PV R&D strategy affected competitiveness. Since 2013, the Korean government has sharply cut PV R&D funding. Early growth may have been affected by government support, but recent growth may be driven by corporate strategies. A significantly higher level of R&D funding may be needed for Korea's next‐generation technologies to capture “first mover” status.

This article is categorized under:

Energy and Climate > Economics and Policy

Photovoltaics > Economics and Policy

Energy Policy and Planning > Economics and Policy
Network architecture and regulatory logic in neural crest development
Authors: Hovland Austin S. , Rothstein Megan , Simoes‐Costa Marcos
Published: November 2019

The neural crest is an ectodermal cell population that gives rise to over 30 cell types during vertebrate embryogenesis. These stem cells are formed at the border of the developing central nervous system and undergo extensive migration before differentiating into components of multiple tissues and organs. Neural crest formation and differentiation is a multistep process, as these cells transition through sequential regulatory states before adopting their adult phenotype. Such changes are governed by a complex gene regulatory network (GRN) that integrates environmental and cell‐intrinsic inputs to regulate cell identity. Studies of neural crest cells in a variety of vertebrate models have elucidated the function and regulation of dozens of the molecular players that are part of this network. The neural crest GRN has served as a platform to explore the molecular control of multipotency, cell differentiation, and the evolution of vertebrates. In this review, we employ this genetic program as a stepping‐stone to explore the architecture and the regulatory principles of developmental GRNs. We also discuss how modern genomic approaches can further expand our understanding of genetic networks in this system and others.

This article is categorized under:

Physiology > Mammalian Physiology in Health and Disease

Biological Mechanisms > Cell Fates

Developmental Biology > Lineages

Models of Systems Properties and Processes > Cellular Models
Semiclassical correlators in Jackiw-Teitelboim gravity
Authors: Bulycheva Ksenia
Published: November 2019

Abstract

In the semiclassical approximation to JT gravity, we find two-point and four- point correlators of heavy operators. To do so, we introduce a massive particle in the bulk and compute its action with gravitational backreaction. In Euclidean signature, the two- point function has a finite limit at large distances. In real time, we find that the thermal two-point function approaches an exponentially small value ∼ exp(−N) at long time. We also find that after a period of exponential decay, the out of time ordered four-point function approaches an exponentially small value as well.
Critical point in a holographic defect field theory
Authors: Filev Veselin G. , Rashkov R. C.
Published: November 2019

Abstract

We study a holographic gauge theory dual to the D3/D5 intersection. We consider a pure gauge B-field flux through the internal two-sphere wrapped by the probe D5-brane, which corresponds to a non-commutative configuration of adjoint scalars. There is a domain wall separating the theory into regions with different ranks of the adjoint group. At zero temperature the theory is supersymmetric and at finite temperature there is a critical point of a second order phase transition. We study the corresponding critical exponents and find that the second derivatives of the free energy, with respect to the bare mass and the magnetic field, diverge with a critical exponent of −2/3.
Bisimulation and Coinduction Enhancements: A Historical Perspective
Authors: Pous Damien , Sangiorgi Davide
Published: November 2019

Bisimulation is an instance of coinduction. Both bisimulation and coinduction are today widely used, in many areas of Computer Science, as well as outside Computer Science. Over, roughly, the last 25 years, enhancements of the principles and methods related to bisimulation and coinduction (i.e., techniques to make proofs shorter and simpler) have become a research topic on its own. In the paper the origins and the developments of the topic are reviewed.
The incompatibility of local economic prosperity and migrants’ social integration: evidence from the Netherlands
Authors: Wang Zhiling
Published: November 2019

This paper investigates the effects of the conditions of local labour markets on the social networks of immigrants, with an emphasis on co-ethnic contact and contact with people native to the locality. This study focuses on the case of immigrants in the Netherlands. For this case, I derived and empirically tested a job and residential search model. I found that a high job arrival rate and large wage differences between the ethnic labour market and the host labour market both correlate with immigrants developing stronger co-ethnic networks and weaker native networks as well as with immigrants choosing to live in more ethnically concentrated areas. These findings suggest that local economic prosperity does not necessarily beget social integration: in this case study, immigrants spontaneously assimilated less into the host society during a good economic period.
Extended steep ramp test normative values for 19–24-year-old healthy active young adults
Authors: Werkman M. S. , Bongers B. C. , Blatter T. , Takken T. , Wittink H.
Published: November 2019

Purpose

To extend currently available sex and age-specific normative values in children and adolescents for the peak work rate (WRpeak) attained at the steep ramp test (SRT) to healthy active young adults.

Methods

Healthy male and female participants aged between 19 and 24 years were recruited. After screening and anthropometric measurements, participants performed a SRT on a cycle ergometer (increments of 25 W/10 s), monitoring and recording SRT-WRpeak, heart rate (HR), and blood pressure (BP) at rest and directly after peak exercise.

Results

Fifty-seven participants (31 males and 26 females; median age of 21.3 years) volunteered and were tested. Anthropometrics, resting BP and lung function were all within normal ranges. Ninety-three percent of the participants attained a peak HR (HRpeak) > 80% of predicted (mean HRpeak 87 ± 5% of predicted). No differences were found in resting and peak exercise variables between females and males, except for absolute SRT-WRpeak (350 W [Q1: 306; Q3: 371] and 487 W [Q1: 450; Q3: 517], respectively) and SRT-WRpeak normalized for body mass (relative SRT-WRpeak; 5.4 ± 0.5 and 6.2 ± 0.6 W/kg, respectively). Low-to-moderate correlations (ρ [0.02–0.71]) were observed between SRT-WRpeak and anthropometric variables for females and males separately. Extended reference curves (8–24-year-old subjects) for SRT performance show different trends between male and female subjects when modelled against age, body height, and body mass.

Conclusions

The present study provides sex-, age-, body height-, and body mass-related normative values (presented as reference centiles) for absolute and relative SRT performance throughout childhood and early adulthood.
Improved metabolic control using glucose monitoring systems leads to improvement in vibration perception thresholds in type 1 diabetes patients
Authors: Dahlin Lars B. , Elgzyri Targ , Löndahl Magnus , Ekman Linnéa , Lindholm Eero
Published: November 2019

Aims

Few studies have examined how improved metabolic control might influence vibration perception thresholds (VPTs). The aim of this study was to evaluate if improved HbA1c can influence vibration thresholds in adults with type 1 diabetes (T1DM).

Methods

VPTs were investigated at six frequencies (4–125 Hz) using VibroSense Meter in the sole of the foot at two occasions in 159 T1DM patients, at the heads of the first and fifth metatarsal bones, i.e. MTH1 and MTH5, respectively. The participants were divided into three groups: group A: HbA1c improved by more than 1 mmol/mol (n = 95), group B: HbA1c deteriorated by more than 1 mmol/mol (n = 48) and group C: HbA1c unchanged (± 1 mmol/mol) (n = 16) compared to baseline.

Results

In group A, the mean z-score, reflecting the combined effect of all VPTs, improved being lower at the follow-up than at the baseline [0.2 (− 0.3 to 1.2) vs. −0.1 (− 0.7 to 0.8), p = 0.00002]. VPTs improved at 4 and 64 Hz at both MTH1 (metatarsal head 1) and MTH5. The VPTs at 125 Hz frequency improved at MTH5, but not at MTH1. No significant differences were seen in group B or group C.

Conclusions

Lower HbA1c and lower VPTs in T1DM patients were associated with improved VPT, suggesting a reversible effect on nerve function by improved metabolic control.
Drug-related problems among hospitalized patients with COPD in mainland China
Authors: Li Qin , Qu Hui Jun , Lv Dan , Yeh Ming-Kung , Sun Shusen , Li Ling , Liao Yun
Published: November 2019

BackgroundData are lacking about the extent of drug-related problems in hospitalized patients with COPD in China.ObjectiveIdentify types and causes of drug-related problems and assess interventions performed by pharmacists.SettingStudy was conducted in an academic teaching hospital in Shanghai, China.MethodBetween June 2017 and July 2018, 393 patients admitted to hospital for acute exacerbation of COPD hospitalized were enrolled. Patient demographics and clinical characteristics were collected. The drug-related problems and interventions were recorded and analyzed based on the Pharmaceutical Care Network Europe (PCNE)-DRP V 8.02 classification.Main outcome measuresThe number, types, causes, interventions, and outcomes of the problems were analyzed.ResultsA total of 640 DRPs, with 763 corresponding causes, were identified for 393 patients. “Treatment safety P2” was the most common type of problem (54.2%; 347/640), and the most common causes were “drug selection C1” (24.2%; 185/763), “dose selection C3” (21.5%; 164/763) and “treatment duration C4” (17.7%; 135/763). Antibiotics, corticosteroids, and proton pump inhibitors were the three primary medication classes associated with DRPs. Patients, hospitalized for more than eight days, taking ten or more drugs or having renal dysfunctions were more likely to have drug-related problems. Pharmacists totally proposed 1557 interventions to address the problems. Most interventions (91.0%; 1418/1557) were accepted, and 91.6% of the problems were solved.ConclusionThe prevalence of drug-related problems among the studied COPD patients was high. Pharmacists can have an important role in addressing the problems and optimizing the safety and effectiveness of therapies for hospitalized COPD patients.