bluuebunny/crossref_metadata_2025 huggingface dataset:
SLAC T-510: Experimental validation of particle-level simulations of radio emission from particle cascades
Authors: Mulrey K.
Published: September 2019

The SLAC T-510 experiment was designed to measure radio emission from particle cascades in a controlled laboratory setting and compare measurements with predictions from particle-level simulations. An electron beam incident upon a dense dielectric target produced a particle cascade in the presence of a strong magnetic field. We previously reported the agreement between data and simulations within systematic uncertainties, the largest being the reflection of radio emission within the target. A follow-up experiment has since been carried out to characterize the reflections and include them in simulations. In this contribution we report these new results. The uncertainties in the experiment are greatly reduced, and the features in the observed emission are well understood.
Execution and analysis of classic neural network algorithms when they are implemented in embedded systems
Authors: Jair Martínez López Alfonso , Raúl Pale Suarez José , Tinoco Varela David
Published: September 2019

Many algorithms related to neural networks are used in a large number of applications, most of them implemented on computational equipment that have great processing and storage capacities, however, new communication schemes such as the Internet of Things, need that neural algorithms can be executed from small electronic devices, devices that do not have large storage or processing capacities, but they can function as intelligent control centres for the different "things" connected to the Internet.

Currently, there are various electronic devices that allow generating low-cost intelligent technology projects that permit interaction within the Internet of things, such as the Arduino UNO, Tiva-C, and BeagleBone development boards. In this project, we present the analysis of the Perceptron, ADALINE and Hopfield neural network algorithms, when they are executed within the three mentioned development boards, in order to define the best tool to be utilized when using such neural schemes and few data are processed. Economic cost, temporary response and technical capabilities of electronic devices have been evaluated.
Risk analysis of the soft targets according to the methodology
Authors: Zimek Ondřej
Published: September 2019

The article deals with the fact that religiously motivated terrorism has become more common in Europe, and more than 50% of the attacks have been focused on so-called Soft Targets. The purpose of this paper is to make a risk analysis of a particular Soft Target by the Ministry of the Interior methodology. The Tax Office of the Zlin region was chosen as a Soft Target. Auxiliary tables – Likelihood and Impact are necessary for this methodology. Performing an attack, Place of attack, and Time of attack are very important too. The Degree of Threat is determined as the product of Total Likelihood and Total Impact. Risk analysis shows that the highest risk factor is the possibility of a bomb attack that could happen inside the building during the daily working time. The risk analysis should help to find weaknesses of the soft targets, and the security managers should take precautions to reduce the risk.
The automated system for bandsaw blade properties measurement
Authors: Sysala Tomas , Stuchlík Karel , Neumann Petr
Published: September 2019

The article describes the bandsaw blade properties innovative method design and realization. The introduction contens individual bandsaw parts description, including their important parameters overview. The innovative methods design delineation follows. The constructed device based on our design minimizes the human error influence. Moreover, it is collecting and archiving measured data. The article covers also the design and software realization. In the end, some measured data examples are stated.
Data Assimilation Method, its Application and Stability
Authors: Belyaev Konstantin , Kuleshov Andrey , Smirnov Ilya , Tuchkova Natalia
Published: September 2019

The authors data assimilation method, namely, generalized Kalman filter (GKF) method, its application and stability is considered. The problem of stability of a dynamic system with data assimilation formulated for a sequence of random variables forming a Markov chain is considered. The stability formulation for this problem is suggested as the problem of the convergence of the corresponding Markov chain when the number of its members goes to infinity. Necessary and sufficient conditions of this convergence are proved. A number of numerical experiments with the specific dynamic system, namely with the ocean model circulation HYCOM and the GKF method are conducted and discussed. The stability of the GKF method was proofed.
Mir kann nicht geholfen werden
Authors: Schild Sarah
Published: September 2019

Im dritten Teil unserer Serie geht es um einen depressiven Patienten, der als
provokant, leicht aufbrausend und zänkisch gilt. Er fühlt sich allein, weil er
denkt, dass ihm niemand helfen kann. Lesen Sie, wie das Pflegeteam es schafft,
mithilfe der systemischen Fallbesprechung neue Perspektiven für sich und den
Patienten zu entwickeln.
Glioblastoma Multiforme and Genetic Mutations: The Issue Is Not Over Yet. An Overview of the Current Literature
Authors: Montemurro Nicola
Published: September 2019

Background and Objective Glioblastoma multiforme (GBM) is still a deadly disease with a poor prognosis and high mortality, despite the discovery of new biomarkers and new innovative targeted therapies. The role of genetic mutations in GBM is still not at all clear; however, molecular markers are an integral part of tumor assessment in modern neuro-oncology.

Material and Methods We performed a Medline search for the key words “glioblastoma,” “glioblastoma multiforme,” and “genetic” or “genetics” from 1990 to the present, finding an exponential increase in the number of published articles, especially in the past 7 years.

Results The understanding of molecular subtypes of gliomas recently led to a revision of the World Health Organization classification criteria for these tumors, introducing the concept of primary and secondary GBMs based on genetic alterations and gene or protein expression profiles. Some of these genetic alterations are currently believed to have clinical significance and are more related to secondary GBMs: TP53 mutations, detectable in the early stages of secondary GBM (found in 65%), isocitrate dehydrogenase 1/2 mutations (50% of secondary GBMs), and also O6-methylguanine-DNA methyltransferase promoter methylation (75% of secondary GBMs).

Conclusion From the introduction of the first standard of care (SOC) established in 2005 in patients with a new diagnosis of GBM, a great number of trials have been conducted to improve the actual SOC, but the real turning point has never been achieved or is yet to come. Surgical gross total resection, with at least one more reoperation, radiation therapy plus concomitant and adjuvant temozolomide chemotherapy currently remains the current SOC for patients with GBM.
Effect of hydrostatic pressure on superconductivity of MgB2
Authors: Gerbi Zeleke Deressa , Singh Pooran
Published: September 2019

The effect of hydrostatic pressure on superconductivity of hexagonal bulk MgB2 was investigated using the first-principles calculations. The calculations were performed based on the density functional theory employing the very recently developed EPW code incorporated in Quantum ESPRESSO computational package. The phonon density of states (PhDOS), isotropic Eliashberg function α2F(ω), the superconducting gap along real and imaginary frequency axes, the electron-phonon coupling constant λ, and the superconducting critical temperature Tc were computed within the general framework of Eliashberg formalism. The results show that hydrostatic pressure enhances superconductivity of the material. At equilibrium, where the hydrostatic pressure of the system is almost zero, the calculated Tc value is 35.67 K. It is relatively nearer to the experimental value of 39 K. The slight underestimation is attributed to the LDA-DFT approximation employed. This value is enhanced to around 95 K at hydrostatic pressure of 6500 kbar and then starts to decrease slowly. We emphasize that our approach to lattice strain engineering, with the target of enhancing Tc as demonstrated in this work, can be applied to various strain-engineering problems in other functional materials.
SEMG-based multifeatures and predictive model for knee-joint-angle estimation
Authors: Yang Chen , Xi Xugang , Chen Sijia , Miran Seyed M. , Hua Xian , Luo Zhizeng
Published: September 2019

Surface electromyography (sEMG) signals are commonly used in activity monitoring and rehabilitation training as they reflect effectively the motor intentions of users. This study proposed a new sEMG-based multifeature extraction and predictive model to predict knee-joint angle from multichannel sEMG. Six channels of sEMG from relevant muscles were recorded, and knee-joint angles were sampled simultaneously for six kinds of knee-joint movement models. The root–mean–square (RMS), wavelet coefficients (WC), and permutation entropy (PE) as features of sEMG were extracted. The back propagation neural network, generalized regression neural network, and least-square support vector regression machine (LS-SVR) were used as predictive models. To validate the effectiveness of the sEMG features and predictive models, twelve subjects without neural or musculoskeletal deficits participated in the experiment. Six kinds of knee-joint movement models at different speeds and different loads were respectively conducted by the subjects. Results revealed that the combination of the three features (RMS, WC, and PE) and LS-SVR performed well for the knee-joint-angle of all kinds of leg motions. The RMS error for all kinds of leg motions was <7.7°. The estimation results of joint motion state would be used to rehabilitation robot or functional electrical stimulation for active rehabilitation of spinal cord injury patients or stroke patients.
Genetic and nongenetic factors associated with the fate of maiden ewe lambs: slaughtered without ever lambing versus retained for breeding1
Authors: McHugh Noirin , Pabiou Thierry , McDermott Kevin , Wall Eamon , Berry Donagh P
Published: September 2019

The decision on which ewe lamb to retain versus which to sell is likely to vary by producer based on personal preference. What is not known, however, is if any commonality exists among producers in the characteristics of ewe lambs that influence their eventual fate. The objective of the present study was to determine what genetic and nongenetic factors associate with the fate of maiden ewe lambs. The fate of each ewe lamb born in the present study was defined as either subsequently: 1) having lambed in the flock, or 2) was slaughtered without any recorded lambing event. A total of 9,705 ewe lamb records from 41 crossbred flocks were used. The logit of the odds of the ewe lamb being retained for lambing was modeled using logistic regression. Variance components were then estimated for the binary trait representing the fate of the ewe lamb using animal linear and threshold mixed models. The genetic correlations between fate of the ewe lamb and preweaning, weaning, or postweaning liveweight were also estimated. From the edited data set, 45% of ewe lambs born entered the mature flock as ewes. Ewe lambs reared as singles, with greater levels of heterosis but lower levels of recombination loss, born to dams that lambed for the first time as hoggets, with greater breed proportion of the Belclare, Suffolk, Texel, and Llyen breeds were more likely (P < 0.001) to eventually lamb in the flock than be slaughtered without ever lambing. Irrespective of the age of the animal when weighed, heavier ewe lambs were more likely to eventually lamb (P < 0.001). The genetic SD and direct heritability of fate of the ewe lamb estimated in the univariate linear model was 26.58 percentage units and 0.31 (SE = 0.03), respectively; the heritability was 0.30 when estimated using the threshold model. The corresponding direct heritability of fate of the ewe lamb estimated in the bivariate analyses with liveweight ranged from 0.29 (SE = 0.03; preweaning weight) to 0.35 (SE = 0.04; postweaning weight). The genetic correlations estimated between fate of the ewe lamb and the liveweight traits were weak to moderate but strengthened as the age of the ewe lamb at weighing increased. Results from this study provide an understanding of the factors producers consider when selecting females for retention versus slaughter which may form useful parameters in the development of a decision support tool to identify suitable ewe lambs for retention.
Pediatric Physical Therapists' Use of the Congenital Muscular Torticollis Clinical Practice Guidelines: A Qualitative Implementation Study
Authors: Nixon-Cave Kim , Kaplan Sandra , Dole Robin , Schreiber Joseph
Published: September 2019

Purpose:

This study is a follow-up to the quantitative survey to examine the perceptions of pediatric physical therapists (PTs) on the application of the 2013 Congenital Muscular Torticollis Clinical Practice Guideline (CMT CPG).

Method:

Qualitative semi-structured telephone interviews were completed. Interview questions focused on how the guidelines influenced practice, facilitators and barriers to implementation, and knowledge translation activities.

Results:

Thirteen pediatric PTs from a variety of practice settings participated. Positive perceptions about the CMT CPG included the use of flow charts, synthesized literature in one place, and validation of examination and intervention approaches. Negative perceptions included its length and that approaches without published evidence were not addressed. Three major themes were identified: knowledge and evidence for practice, education of clinicians, and the CPG structure and components that influenced practice.

Conclusions:

The CMT CPG provided a number of benefits. Recommendations for future enhancement and development are provided.
Cell-to-cell variability in AMPK activation reveals autonomous cycles in cellular energy balance
Authors: Kosaisawe Nont , Sparta Breanne , Pargett Michael , Teragawa Carolyn , Albeck John G.
Published: September 2019

Cellular metabolism can be reconfigured to balance nutrient processing (catabolism) and cellular demands (anabolism). However, the kinetics of reconfiguration within individual mammalian cells, and heterogeneity between cells, have remained unexplored. Using live-cell imaging, we investigate the kinetics of bioenergetic adaptation in individual cells. In response to acute inhibition of oxidative phosphorylation, AMPK substrates are phosphorylated bimodally, identifying cells in different underlying states of anabolism and catabolism. Manipulation of glycolysis, insulin/Akt signaling, or protein synthesis shifts the distribution of these states. Long-term lineage analysis confirms that this cellular energy balance cycles over time within individual cells, independently of the cell division cycle. We further demonstrate that AMPK inhibits the ERK and mTOR cell growth signaling pathways specifically when anabolism is in excess. Our results reveal dynamic fluctuations of energetic balance, establish distinct time scales of cellular energetic control, and open opportunities for more precise prediction and control of cellular metabolic functions.
Are new rural ventures different from new urban ones? An exploratory analysis of businesses located in Portuguese incubators and science parks
Authors: Pato Lúcia , Teixeira Aurora A.C.
Published: September 2019

Purpose

Considering the differences between rural and urban spaces, through the theoretical framework developed, the purpose of this paper is to uncover and rationalize the differences between rural and urban new ventures in terms of the environment surrounding the new venture, their general characteristics (e.g. sector, size) and export/economic performance.

Design/methodology/approach

The theoretical framework is empirically assessed resorting to exploratory statistical analysis based on data collected from a questionnaire survey responded by 408 new ventures headquartered in Portuguese business incubators and science parks. The data collected were treated with the Software Package for the Social Sciences.

Findings

The results evidence that rural and urban new ventures differ in terms of generic characteristics, namely sector, size and collaborators’ human capital. Additionally, they differ concerning export and economic performance as well in relation to the perception of the municipality support.

Research limitations/implications

Albeit the present study is mainly exploratory, it constitutes a stepping stone for future research into the differences between rural and urban new ventures regarding their export and economic performance determinants.

Originality/value

The present study innovatively contributes to uncover the role of rural and urban context in entrepreneurship and adds to the scanty empirical literature in the area.
Information Retrieval in Food Science Research II: Accounting for Relevance When Evaluating Database Performance
Authors: Urhan Tuba Karaarslan , Rempel Hannah Gascho , Meunier‐Goddik Lisbeth , Penner Michael H.
Published: September 2019

The impetus for this study is the limited amount of information on performance characteristics of food science–encompassing online bibliographic databases. Database usage is an important element in modern research because a comprehensive understanding of current knowledge is essential for effective, unbiased hypothesis formulation and testing. Six databases commonly recommended by academic libraries for information retrieval in the food sciences (Academic Search Premier [ASP], Agricultural Online Access [AGRICOLA], CAB Direct, Food Science and Technology Abstracts [FSTA], PubMed, and Web of Science [WoS]) were compared in a case study based on the research topic “in vitro bile acid binding properties of dietary lignin.” A complex string of search terms was used for citation retrieval, and predetermined inclusion/exclusion criteria were used to determine the relevancy of retrieved articles. Searching WoS and CAB Direct returned the greatest number of relevant articles, followed closely by FSTA, PubMed, and AGRICOLA. FSTA and AGRICOLA returned the highest ratios of relevant‐to‐irrelevant articles, followed closely by CAB Direct. None of the databases, when used alone, recovered all of the relevant articles identified in the study; WoS indexed the highest percentage of relevant articles identified (WoS = 10; total = 19). WoS also had the highest number of relevant articles that were unique to any one database. The thoroughness of searching the complete group of databases was tested by comparison of retrieved citations with those found in relevant review articles, revealing the need for testing overall inclusivity.

Practical Application

Comprehensive online information retrieval is the most efficient means of accessing current knowledge. Awareness of current knowledge is essential for effective, unbiased decision making in private sector and academic/government‐based research endeavors. Thus, online database usage is an essential element of modern food science research. This paper provides tangible examples of the performance characteristics of online bibliographic databases commonly recommended for information retrieval in the food sciences. The paper is written so as to aid the reader in making decisions with respect to database usage for the recovery of topic‐relevant peer‐reviewed articles germane to their area of research.
Psychometric evaluation of the Chinese version of the Fonseca anamnestic index for temporomandibular disorders
Authors: Zhang Min‐juan , Yap Adrian U‐Jin , Lei Jie , Fu Kai‐Yuan
Published: September 2019

Background

The Fonseca anamnestic index (FAI) offers a simple, low‐cost, patient‐reported method for screening temporomandibular disorders (TMDs).

Objectives

This study described the development of the Chinese version of the FAI (FAI‐C) and examined its reliability and validity when compared to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD).

Methods

The FAI‐C was created by translation and cross‐cultural adaptation of the English instrument following international guidelines. Psychometric evaluation of the FAI‐C was carried out on a sample of 613 patients with TMDs and 57 controls. Reliability of the FAI‐C was determined by means of internal consistency and test‐retest methods while validity was ascertained by criterion‐related validity. Criterion validity was examined via Cohen's kappa, sensitivity and specificity when compared with DC/TMD Axis I diagnoses.

Results

Cronbach's alpha value (internal consistency) for total FAI‐C score was 0.669, and intra‐class correlation coefficient (ICC) value (test‐retest reliability) was 0.823. For criterion validity, kappa coefficient value was 0.633 while sensitivity and specificity was 95.9% and 71.9%, respectively.

Conclusion

The Chinese version of the FAI demonstrated acceptable reliability and good validity. The FAI‐C could thus be used as an instrument for screening TMDs in Chinese literate populations.
Unraveling independent origins of two tetraploid Achillea species by amplicon sequencing
Authors: Wan Jun‐Nan , Guo Yan‐Ping , Rao Guang‐Yuan
Published: September 2019

Allopolyploidy is a significant mechanism of plant speciation, and many allopolyploid species have arisen recurrently. However, the probability that allopolyploidization between the same two parental species could lead to the origin of different taxa has received little attention. Here we used a new progenitor‐specific amplicon sequencing method to demonstrate the independent origins of two yarrow species, Achillea alpina L. and Achillea wilsoniana Heimerl ex Hand.‐Mazz., through allotetraploidy from the same diploid progenitor species pair, Achillea acuminata (Ledeb.) Sch. Bip. and Achillea asiatica Serg. Based on the sequences of 17 nuclear genes from 21 wild populations of the four Achillea species investigated, a clear view of genetic structure and demographic history was obtained with each species. Significant genetic differentiation was evident between the two tetraploid species. Two genetically distinguishable groups were detected within one of the progenitor, A. acuminata, and ancestors belonging to those two groups contributed to the two tetraploid species. Excluding fixed heterozygosity, we detected extremely low genetic diversity in many populations of both tetraploid species. Approximate Bayesian computation indicated that both tetraploid species originated before the Last Glacial Maximum, and nearly all diploid lineages went through population declines after the allopolyploidization events. Our study indicates that independent allopolyploidization events between the same Achillea parental species have generated two genetically and ecologically distinct taxa.
Coccidioidomycosis: Medical and Spatio-Temporal Perspectives
Authors: Sarafoglou Nikias , Laniado-Laborin Rafael , Kafatos Menas
Published: September 2019

Coccidioidomycosis (CM) is a disease of major public health importance due to the challenges in its diagnosis and treatment. To understand CM requires the attributes of a multidisciplinary network analysis to appreciate the complexity of the medical, the environmental and the social issues involved: public health, public policy, geology, atmospheric science, agronomy, social sciences and finally humanities, all which provide insight into this population transformation.In section 1 of this paper, we describe the CM-epidemiology, the clinical features, the diagnosis and finally the treatment.In section 2, we highlight the most important contributions and controversies in the history of the CM-research by using scientometric or bibliometric evaluations of research that are based on Garfield’s work (Garfield.library.upenn.edu) on the propagation of scientific thinking.
Interaction of a normally-incident plane wave with a nonlinear poroelastic fracture
Authors: Nakagawa Seiji , Pride Steven R. , Nihei Kurt T.
Published: September 2019

While it has been recognized that a large amplitude incident wave upon a dry fracture can exhibit nonlinear seismic wave scattering due to its stress-dependent mechanical compliance, the impact of pore fluid in the fracture and a fluid-filled poroelastic background medium—features common for fractures in the Earth—are not well understood. As a first step toward an understanding of the nonlinear poroelastic response of elastic waves in fractured media, analytical approximate formulas are used for the amplitude and phase of a normally incident plane wave using a perturbation method, assuming a fluid-filled, highly compliant nonlinear interface embedded in a linear poroelastic solid. The stress-closure behavior of the fracture is modeled by nonlinear, poroelastic displacement-discontinuity boundary conditions (a linear–slip interface). The theory predicts that the static (“Direct current,” or DC) and higher-order-harmonic waves produced by the nonlinear scattering can be greatly reduced by the presence of fluid in the fracture. This, however, depends upon a number of parameters, including fracture compliance, fluid properties (compressibility and viscosity), and the permeability of the background medium, as well as environmental parameters such as the initial fluid pressure and stress acting on the fracture. The static effect produces low-frequency fluid pressure pulses when a finite-duration wave is incident upon the fracture—behavior unique to fluid-filled fractures within a poroelastic medium.
Does Performance Calibration Generalize Across Sport Tasks? A Multiexperiment Study in Physical Education
Authors: Kolovelonis Athanasios , Goudas Marios
Published: September 2019

Three experiments examined students’ calibration in physical education in relation to task characteristics. Participants in the 3 experiments were 388 students. Calibration accuracy and bias were calculated based on students’ predicted and actual performance in tests including variations of a sport task (basketball shooting) and tasks from different sports (basketball and soccer). An overconfidence effect was found in all experiments, and evidence regarding the hard–easy effect emerged. High compared with low performers were more accurate, and some variations with respect to gender also emerged. The magnitude of calibration error was similar across tasks, whereas approximately half of the students were consistent in the direction of calibration (most of them were overestimators). Results are discussed with reference to theoretical and empirical evidence associated with performance calibration and self-regulated learning in physical education. Methodological issues, practical implications, and future directions are also discussed.
Can earlier BCG vaccination reduce early infant mortality? Study protocol for a cluster randomised trial in Guinea-Bissau
Authors: Thysen Sanne M , Jensen Aksel Karl Georg , Rodrigues Amabelia , Borges Igualdino da Silva , Aaby Peter , Benn Christine , Fisker Ane
Published: September 2019

Introduction

The BCG vaccine is designed to protect against tuberculosis, but the vaccine may have broader effects. In 2014, the Strategic Advisory Group of Experts on Immunization reviewed the literature on non-specific effects of BCG, and concluded that the evidence was consistent with beneficial non-specific effects and requested further randomised trials.

Methods and analyses

Within the Bandim Health Project’s urban and rural health and demographic surveillance systems, we will conduct a cluster-randomised trial in six suburban districts and 55 rural villages. Infants are enrolled at a home visit before 72 hours of life. In intervention clusters, children are vaccinated with BCG and oral polio vaccine (OPV). In control clusters, the caregivers are informed about vaccination opportunities. Using Cox-proportional hazards models, we will test whether BCG and OPV provided at a single home visit can reduce early infant mortality up to 60 days.

The trial was initiated with a pilot study in Biombo region in June 2015. The trial was scaled up to full study including Oio and Cacheu regions in July 2016. The trial was expanded to include the urban study area in July 2017.

Ethics and dissemination

BCG vaccination is delayed in many low-income settings. WHO-recommended home visits are resource demanding and vaccines are not part of the recommendation. Utilising the home visits to provide BCG and OPV may provide countries with a further incentive to introduce a single home visit. In countries, where home visits are already in place, vaccines can easily be added to reduce early infant mortality. The trial is approved by the Guinean Ethical Committee (Reference number: 0016/CNES/INASA/2015) and the Danish Ethics Committee has given its consultative approval. The results of the trial will be published in international peer-reviewed journals.

Trial registration number

NCT02504203; Pre-results.
Rationale and population-based prospective cohort protocol for the disadvantaged populations at risk of decline in eGFR (CO-DEGREE)
Authors: Gonzalez-Quiroz Marvin , Nitsch Dorothea , Hamilton Sophie , O'Callaghan Gordo Cristina , Saran Rajiv , Glaser Jason , Correa-Rotter Ricardo , Jakobsson Kristina , Singh Ajay , Gunawardena Nalika , Levin Adeera , Remuzzi Giuseppe , Caplin Ben , Pearce Neil
Published: September 2019

Introduction

A recently recognised form of chronic kidney disease (CKD) of unknown origin (CKDu) is afflicting communities, mostly in rural areas in several regions of the world. Prevalence studies are being conducted in a number of countries, using a standardised protocol, to estimate the distribution of estimated glomerular filtration rate (eGFR), and thus identify communities with a high prevalence of reduced glomerular filtration rate (GFR). In this paper, we propose a standardised minimum protocol for cohort studies in high-risk communities aimed at investigating the incidence of, and risk factors for, early kidney dysfunction.

Methods and analysis

This generic cohort protocol provides the information to establish a prospective population-based cohort study in low-income settings with a high prevalence of CKDu. This involves a baseline survey that included key elements from the DEGREE survey (eg, using the previously published DEGREE methodology) of a population-representative sample, and subsequent follow-up visits in young adults (without a pre-existing diagnosis of CKD (eGFR<60 mL/min/1.73m2), proteinuria or risk factors for CKD at baseline) over several years. Each visit involves a core questionnaire, and collection and storage of biological samples. Local capacity to measure serum creatinine will be required so that immediate feedback on kidney function can be provided to participants. After completion of follow-up, repeat measures of creatinine should be conducted in a central laboratory, using reference standards traceable to isotope dilution mass spectrometry (IDMS) quality control material to quantify the main outcome of eGFR decline over time, alongside a description of the early evolution of disease and risk factors for eGFR decline.

Ethics and dissemination

Ethical approval will be obtained by local researchers, and participants will provide informed consent before the study commences. Participants will typically receive feedback and advice on their laboratory results, and referral to a local health system where appropriate.
Cohort profile: the clinical ‘Psoriasis in Adolescents’ (PIA) cohort in Denmark
Authors: Blegvad Christoffer , Andersen Anne-Marie Nybo , Groot Jonathan , Zachariae Claus , Skov Lone
Published: September 2019

Purpose

Psoriasis is a chronic inflammatory skin disease that frequently debuts in childhood and adolescence. We wished to determine environmental and genetic risk factors for the development of psoriasis in children and adolescents, as well as to investigate debut type, trigger factors, course of disease, nature and influence of stress related to both child and family and risk factors for comorbidity. The ‘Psoriasis in Adolescents’ (PIA) cohort will provide data on the relationship between psoriasis and, respectively, genetic disposition, early-life exposures, quality of life and comorbidity.

Participants

The PIA cohort is nested in the large general population Danish National Birth Cohort (DNBC). We invited 390 adolescents with psoriasis and corresponding maternally predisposed and non-predisposed controls. Participants underwent an interview and a clinical examination consisting of a skin inspection and physical measurements including blood sampling and microbiological swabs. Additionally, four self-administered questionnaires on physical and mental health were completed.

Findings to date

The final PIA cohort consists of 81 adolescents with psoriasis, 110 parentally predisposed and 124 non-predisposed psoriasis-free adolescents. The validity of the maternally reported psoriasis status from the DNBC was found to be low on clinical examination (47.5%). In contrast, the self-reported psoriasis status of the DNBC mothers was clinically confirmed in 80.8% of the cases.

Future plans

The PIA cohort offers the possibility of assessing the clinical characteristics, course of psoriasis and development of comorbidities in adolescents with clinically confirmed disease from a general population. Comparison with predisposed and non-predisposed controls is possible and genetic analyses are scheduled. We plan to invite the participants for a follow-up in 5–10 years. Furthermore, we plan to include newly diagnosed adolescents with psoriasis from the 18-year DNBC follow-up. All information is linkable on the individual level with data from the DNBC and nationwide registries in Denmark.
Dynamics of a Neural Circuit that Mediates Social and Nonsocial Behaviors
Authors: Hurtado-López Julián , Ramirez-Moreno David Fernando
Published: September 2019

We describe a neural network model of the mouse amygdala and hypothalamus that is able to support competitive interactions between social and grooming behaviors, as well as basic findings about how these behaviors are modulated by light stimulation. The model is built on attractor network dynamics and involves mutual inhibition among different populations of neurons. Simulation results are found to be consistent with some experimental observations such as scalable control of social behaviors and opponent control of social and nonsocial behaviors. Bifurcation analysis is applied in order to understand the dynamical basis of state transitions and to show the dynamics emergent from the model. We conclude that this study also provides some mechanistic insights of behavioral state transitions.
Sirtuin6 (SIRT6) Promotes the EMT of Hepatocellular Carcinoma by Stimulating Autophagic Degradation of E-Cadherin
Authors: Han Li Li , Jia Lijun , Wu Fei , Huang Chen
Published: September 2019

EMT is a pivotal mechanism involved in tumor metastasis, which is the leading cause of poor prognosis for hepatocellular carcinoma (HCC). Sirtuin family members function as NAD+-dependent deacetylases that are essential for tumor metastasis and epithelial–mesenchymal transition (EMT). However, no causal association has been established between Sirtuin6 (SIRT6) and HCC metastasis. SIRT6 expression pattern and its association with HCC metastasis were investigated by informatic analysis, and verified by qRT-PCR and immunochemistry in HCC tissues. Transwell assay, qRT-PCR, and immunofluorescence assay were utilized to assess the effects of SIRT6 on metastasis and E-cadherin expression in vitro and in vivo. Immunoprecipitation assay was performed to observe whether SIRT6 deacetylated Beclin-1 in HCC cells. Immunofluorescence assay and inhibitor treatment rescue experiments were used to clarify the mechanism by which SIRT6 facilitated EMT and metastasis. SIRT6 upregulation was quite prevalent in HCC tissues and closely correlated with worse overall survival, disease-relapse free survival, and HCC metastasis. Furthermore, SIRT6 promoted HCC cell migration, invasion, and EMT. Mechanistically, we found that SIRT6 deacetylated Beclin-1 in HCC cells and this event led to the promotion of the autophagic degradation of E-cadherin. Noticeably, E-cadherin degradation and invasion, migration induced by SIRT6 overexpression could be rescued by dual mutation of Beclin-1 (inhibition of acetylation), CQ (autophagy inhibitor), and knockdown of Atg7. In addition, SIRT6 promoted N-cadherin and Vimentin expression via deacetylating FOXO3a in HCC. These results established a relationship between SIRT6 and HCC EMT and further elucidated the mechanisms underlying HCC metastasis, helping provide a promising approach for the treatment of HCC.

Implications:

Inhibiting SIRT6 represents a potential therapeutic approach to suppress HCC metastasis partially through reduction of autophagic degradation of E-cadherin.
Distinct Roles for BET Family Members in Estrogen Receptor α Enhancer Function and Gene Regulation in Breast Cancer Cells
Authors: Murakami Shino , Li Rui , Nagari Anusha , Chae Minho , Camacho Cristel V. , Kraus W. Lee
Published: September 2019

The bromodomain family member proteins (BRD; BET proteins) are key coregulators for estrogen receptor alpha (ERα)-mediated transcriptional enhancers. The use of BRD-selective inhibitors has gained much attention as a potential treatment for various solid tumors, including ER-positive breast cancers. However, the roles of individual BET family members have largely remained unexplored. Here, we describe the role of BRDs in estrogen (E2)-dependent gene expression in ERα-positive breast cancer cells. We observed that chemical inhibition of BET family proteins with JQ1 impairs E2-regulated gene expression and growth in breast cancer cells. In addition, RNAi-mediated depletion of each BET family member (BRDs 2, 3, and 4) revealed partially redundant roles at ERα enhancers and for target gene transcription. Furthermore, we found a unique role of BRD3 as a molecular sensor of total BET family protein levels and activity through compensatory control of its own protein levels. Finally, we observed that BRD3 is recruited to a subset of ERα-binding sites (ERBS) that are enriched for active enhancer features, located in clusters of ERBSs likely functioning as “super enhancers,” and associated with highly E2-responsive genes. Collectively, our results illustrate a critical and specific role for BET family members in ERα-dependent gene transcription.

Implications:

BRD3 is recruited to and controls the activity of a subset ERα transcriptional enhancers, providing a therapeutic opportunity to target BRD3 with BET inhibitors in ERα-positive breast cancers.
Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
Authors: Chiasakul Thita , De Jesus Elizabeth , Tong Jiayi , Chen Yong , Crowther Mark , Garcia David , Chai‐Adisaksopha Chatree , Messé Steven R. , Cuker Adam
Published: September 2019

Background

Inherited thrombophilias are well‐established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial ischemic stroke, remains uncertain. We aimed to evaluate the association between inherited thrombophilia (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency) and risk of arterial ischemic stroke in adults.

Methods and Results

We searched PubMed,
EMBASE
, and Cochrane Library Databases from inception to December 31, 2018. We included case‐control or cohort studies of adults reporting the prevalence of inherited thrombophilias in those with arterial ischemic stroke and subjects without arterial ischemic stroke. Two reviewers (T.C., E.D.) independently searched the literature and extracted data. Pooled odds ratios (
OR
s) and 95%
CI
s were calculated using random‐effects model. We identified 68 eligible studies, which collectively enrolled 11 916 stroke patients and 96 057 controls. The number of studies reporting factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency were 56, 45, 15, 17, and 12, respectively. Compared with controls, patients with arterial ischemic stroke were significantly more likely to have the following inherited thrombophilias: factor V Leiden (
OR
, 1.25; 95%
CI
, 1.08–1.44; I
2
=0%), prothrombin G20210A mutation (
OR
, 1.48; 95%
CI
, 1.22–1.80; I
2
=0%), protein C deficiency (
OR
, 2.13; 95%
CI
, 1.16–3.90; I
2
=0%), and protein S deficiency (
OR
, 2.26; 95%
CI
, 1.34–3.80; I
2
=8.8%). Statistical significance was not reached for antithrombin deficiency (
OR
, 1.25; 95%
CI
, 0.58–2.67; I
2
=8.8%).

Conclusions

Inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency) are associated with an increased risk of arterial ischemic stroke in adults. The implications of these findings with respect to clinical management of patients with ischemic stroke require further investigation.
Plasma Androgen Receptor Copy Number Status at Emergence of Metastatic Castration-Resistant Prostate Cancer: A Pooled Multicohort Analysis
Authors: Jayaram Anuradha , Wingate Anna , Wetterskog Daniel , Conteduca Vincenza , Khalaf Daniel , Sharabiani Mansour Taghavi Azar , Calabrò Fabio , Barwell Lorraine , Feyerabend Susan , Grande Enrique , Martinez-Carrasco Alberto , Font Albert , Berruti Alfredo , Sternberg Cora N. , Jones Rob , Lefresne Florence , Lahaye Marjolein , Thomas Shibu , Joshi Shilpy , Shen Dong , Ricci Deborah , Gormley Michael , Merseburger Axel S. , Tombal Bertrand , Annala Matti , Chi Kim N. , De Giorgi Ugo , Gonzalez-Billalabeitia Enrique , Wyatt Alexander W. , Attard Gerhardt
Published: September 2019

PURPOSE

Increases in androgen receptor ( AR) copy number (CN) can be detected in plasma DNA when patients develop metastatic castration-resistant prostate cancer. We aim to evaluate the association between AR CN as a continuous variable and clinical outcome.

PATIENTS AND METHODS

PCR2023 was an international, multi-institution, open-label, phase II study of abiraterone acetate plus prednisolone (AAP) or abiraterone acetate plus dexamethasone that included plasma AR assessment as a predefined exploratory secondary end point. Plasma AR CN data (ClinicalTrials.gov identifier: NCT01867710 ) from this study (n = 133) were pooled with data from the following three other cohorts: cohort A, which was treated with either AAP or enzalutamide (n = 73); the PREMIERE trial (ClinicalTrials.gov identifier: NCT02288936 ) of biomarkers for enzalutamide (n = 94); and a phase II trial from British Columbia (ClinicalTrials.gov identifier: NCT02125357 ) that randomly assigned men to either AAP or enzalutamide (n = 201). The primary outcome measures for the biomarker analysis were overall survival and progression-free survival.

RESULTS

Using multivariable fractional polynomials analysis using Cox regression models, a nonlinear relationship between plasma AR CN and outcome was identified for overall survival, where initially for small incremental gains in CN there was a large added hazard ratio that plateaued at higher CN. The CN cut point associated with the highest local hazard ratio was 1.92. A similar nonlinear association was observed with progression-free survival. In an exploratory analysis of PCR2023, the time from start of long-term androgen-deprivation therapy to start of AAP or abiraterone acetate plus dexamethasone was significantly shorter in patients with plasma AR CN of 1.92 or greater than patients with plasma AR CN of less than 1.92 (43 v 130 weeks, respectively; P = .005). This was confirmed in cohort A ( P = .003), the PREMIERE cohort ( P = .03), and the British Colombia cohort ( P = .003).

CONCLUSION

Patients with metastatic castration-resistant prostate cancer can be dichotomized by a plasma AR CN cut point of 1.92. Plasma AR CN value of 1.92 or greater identifies aggressive disease that is poorly responsive to AR targeting and is associated with a prior short response to primary androgen-deprivation therapy.
Comparison of human population receptive field estimates between scanners and the effect of temporal filtering
Authors: Morgan Catherine , Schwarzkopf D. Samuel
Published: September 2019

Background: Population receptive field (pRF) analysis with functional magnetic resonance imaging (fMRI) is an increasingly popular method for mapping visual field representations and estimating the spatial selectivity of voxels in human visual cortex. However, the multitude of experimental setups and processing methods used makes comparisons of results between studies difficult.

Methods: Here, we compared pRF maps acquired in the same three individuals using comparable scanning parameters on a 1.5 and a 3 Tesla scanner located in two different countries. We also tested the effect of low-pass filtering of the time series on pRF estimates.

Results: As expected, the signal-to-noise ratio for the 3 Tesla data was superior; critically, however, estimates of pRF size and cortical magnification did not reveal any systematic differences between the sites. Unsurprisingly, low-pass filtering enhanced goodness-of-fit, presumably by removing high-frequency noise. However, there was no substantial increase in the number of voxels containing meaningful retinotopic signals after low-pass filtering. Importantly, filtering also increased estimates of pRF size in the early visual areas which could substantially skew interpretations of spatial tuning properties.

Conclusion: Our results therefore suggest that pRF estimates are generally comparable between scanners of different field strengths, but temporal filtering should be used with caution.
The Anonymous’ Commentary on Plato’s Theatetus and a Middle-Platonic Theory of Knowledge
Authors: Matoso Renato
Published: September 2019

In this paper, I defend that the historiographical category of eclecticism is a correct way to describe the epistemology and the exegetical activity of the Anonymous commentator on Plato’s Theaetetus. In addition, I show that the interpretation of the platonic philosophy presented in this text not only presupposes an eclectic philosophical attitude, but also offers a conscious defense of a positive and philosophically relevant form of eclecticism. By eclecticism, I understand a method of inquiry based on the deliberate use of hypotheses and arguments from different philosophical traditions. My claim is that Anon. intends to lay ground of his way of doing philosophy by attributing it to Plato and the platonic tradition. In doing so, Anon. provides us with a positive understanding of eclecticism as a legitimate methodology of philosophical investigation.
Physical Education and Physical Activity Policies as Described on California Charter School Websites
Authors: Kahan David , McKenzie Thomas L.
Published: September 2019

Objectives: Nearly all US schools have a website that enables them to inform about and promote physical activity (PA) and physical education (PE). We performed a cross-sectional content analysis of California (state with the most charters) elementary charter school websites'
PA/PE content. Methods: We analyzed data (N = 520 schools) using descriptive statistics and cross tabulations to identify associations among school characteristics and the mentioning of PE, PE curriculum, PE teacher, recess, interscholastic sport, and other extracurricular PA. Results:
Over a third (39%) of websites did not mention providing either PA or PE opportunities at all. Only 30.6% of websites mentioned PE (mandated by state education code to be delivered for 200 min/10 days to students in grades 1-6). Websites also infrequently mentioned Fitnessgram scores (36.5%),
required by state education code to be reported for 5th graders, as well as recess (30.2%), other extracurricular PA (20.4%), and interscholastic sport (16.5%). Conclusions: Schools did not use the full potential of their websites to inform constituents about PA or to promote it on
campus. Deficient schools should expand the PE/PA content information available on their websites and be held accountable for such by their parent school district..