bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal reduction of tuberous sclerosis complex 1 expression in astrocytes and neurons causes seizures in an age‐dependent manner
Authors: Zou Jia , Zhang Bo , Gutmann David H. , Wong Michael
Published: October 2017

Objective

Epilepsy is one of the most prominent symptoms of tuberous sclerosis complex (TSC), a genetic disorder, and may be related to developmental defects resulting from impaired TSC1 or TSC2 gene function in astrocytes and neurons. Inactivation of the Tsc1 gene driven by a glial‐fibrillary acidic protein (GFAP) promoter during embryonic brain development leads to widespread pathologic effects on astrocytes and neurons, culminating in severe, progressive epilepsy in mice (Tsc1GFAP‐Cre mice). However, the developmental timing and cellular specificity relevant to epileptogenesis in this model has not been well defined. The present study evaluates the effect of postnatal Tsc1 gene inactivation on pathologic features of astrocytes and neurons and development of epilepsy.

Methods

An inducible Tsc1 knock‐out mouse was created utilizing a tamoxifen‐driven GFAP‐CreER line (Tsc1GFAP‐CreER mice) with TSC1 reduction induced postnatally at 2 and 6 weeks of age, and compared to conventional Tsc1GFAP‐Cre mice with prenatal TSC1 reduction. Western blotting, immunohistochemistry, histology, and video–electroencephalography (EEG) assessed mechanistic target of rapamycin (mTOR) pathway activation, astrogliosis, neuronal organization, and spontaneous seizures, respectively.

Results

Tsc1 gene inactivation at 2 weeks of age was sufficient to cause astrogliosis and mild epilepsy in Tsc1GFAP‐CreER mice, but the phenotype was much less severe than that observed with prenatal Tsc1 gene inactivation in Tsc1GFAP‐Cre mice. Both astrocytes and neurons were affected by prenatal and postnatal Tsc1 gene activation to a degree similar to the severity of epilepsy, suggesting that both cellular types may contribute to epileptogenesis.

Significance

These findings support a model in which the developmental timing of TSC1 loss dictates the severity of neuronal and glial abnormalities and resulting epilepsy.
Body composition measurement in young children using quantitative magnetic resonance: a comparison with air displacement plethysmography
Authors: Chen L.‐W. , Tint M.‐T. , Fortier M. V. , Aris I. M. , Shek L. P.‐C. , Tan K. H. , Rajadurai V. S. , Gluckman P. D. , Chong Y.‐S. , Godfrey K. M. , Kramer M. S. , Henry C. J. , Yap F. , Lee Y. S.
Published: October 2017

Background

Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited.

Objective

We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi‐ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years).

Methods

Agreements between QMR‐based and ADP‐based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland–Altman plot analyses. Analyses were stratified for the child's sex.

Results

Substantial agreement was observed between QMR‐based and ADP‐based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland–Altman analysis similarly revealed that QMR‐based fat mass were (mean difference [95% limits of agreement]) −0.5 (−2.1 to +1.1) kg lower than ADP‐based fat mass and QMR‐based FMI were −0.4 (−1.8 to +0.9) kg/m2 lower than ADP‐based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys.

Conclusions

QMR‐based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP‐based measures in young Asian children.
Why Facts are not enough in the Fight against Fake News
Authors: Tarran Brian
Published: October 2017

With trust in traditional sources of news and information in decline, journalists, academics and policy experts discuss ways to halt the spread of misinformation. Brian Tarran listens in
Cancer: Misfortune or Carelessness?
Authors: Treasure Peter
Published: October 2017

Public debate about the cause of cancer often falls between two extremes: either there's nothing you can do about it, or it's all your fault. But the game of roulette offers a more nuanced way to think about the disease, writes Peter Treasure
The Great Migration: A Graphics Novel
Authors: Andrews RJ , Wainer Howard
Published: October 2017

RJ Andrews and Howard Wainer imagine a collaboration between W. E. B. Du Bois and C. J. Minard, charting the relocation of African-Americans from the southern United States in the century after emancipation
The Remarkable Life of Frances Wood
Authors: Cole Tim
Published: October 2017

A chemist and medical statistician of the early twentieth century, Frances Wood achieved much in her tragically short lifetime. Tim Cole tells her story
Graphical Interpretations of Data: Walking the Line
Authors: Reese R. Allan
Published: October 2017

R. Allan Reese continues his series on the dos and don'ts of data design with some advice on the best ways of presenting lines of “best fit”
Post-Truth Publications
Authors: Shah Hetan
Published: October 2017

Hetan Shah reviews three timely books on the same urgent topic
Transparent polycrystalline nanoceramics consisting of triclinic Al2SiO5 kyanite and Al2O3 corundum
Authors: Gaida Nico A. , Nishiyama Norimasa , Masuno Atsunobu , Schürmann Ulrich , Giehl Christopher , Beermann Oliver , Ohfuji Hiroaki , Bednarcik Jozef , Kulik Eleonora , Holzheid Astrid , Irifune Tetsuo , Kienle Lorenz
Published: October 2017

Transparent polycrystalline nanoceramics consisting of triclinic Al2SiO5 kyanite (91.4 vol%) and Al2O3 corundum (8.6 vol%) were fabricated at 10 GPa and 1200‐1400°C. These materials were obtained by direct conversion from Al2O3‐SiO2 glasses fabricated using the aerodynamic levitation technique. The material obtained at 10 GPa and 1200°C shows the highest optical transparency with a real in‐line transmission value of 78% at a wavelength of 645 nm and a sample‐thickness of 0.8 mm. This sample shows equigranular texture with an average grain size of 34 ± 13 nm. The optical transparency increases with decreasing mean grain size of the constituent phases. The relationship between real in‐line transmission and grain size is well explained by a grain‐boundary scattering model based on a classical theory.
Sintering dense boron carbide without grain growth under high pressure
Authors: Liu Lixin , Li Xuhai , He Qiang , Xu Liang , Cao Xiuxia , Peng Xusheng , Meng Chuanmin , Wang Wenqiang , Zhu Wenjun , Wang Yuan
Published: October 2017

Traditionally, densification and grain growth are two competing processes in sintering of ceramics. To improve the density, while limiting grain growth at the same time, an ultrahigh pressure (>1 GPa) is employed here and results in plastic deformation as the dominant densification mechanism during the sintering process. In this way, fully dense boron carbide (B4C) structural ceramics without grain growth is prepared under the pressure of 4.5 GPa at low temperature of 1300°C in 5 minutes, while showing excellent mechanical properties such as Vickers hardness of 38.04 GPa, Young's modulus of 487.7 GPa, and fracture toughness of 3.87 MPa·m1/2. This study should also facilitate the development of other structural ceramics for practical applications.
The Science of Salt: A regularly updated systematic review of the implementation of salt reduction interventions (September 2016–February 2017)
Authors: Johnson Claire , Santos Joseph A. , McKenzie Briar , Thout Sudhir Raj , Trieu Kathy , McLean Rachael , Petersen Kristina S. , Campbell Norm R.C. , Webster Jacqui
Published: October 2017

This periodic review aims to identify, summarize, and appraise studies relating to the implementation of salt reduction strategies that were published between September 2016 and February 2017. A total of 41 studies were included as relevant to the design, assessment, and implementation of salt reduction strategies, and a detailed appraisal was conducted on the seven studies that evaluated the impact of salt reduction strategies. Of these, three were national studies or included large populations and four were conducted in communities with small participant sample sizes. Each study used a different strategy for reducing salt intake varying from category‐specific sodium targets for packaged food to use of a low‐sodium salt substitute to behavior change interventions. Four studies found statistically significant decreases in dietary salt intake and one study showed statistically significant decreases in mean sodium density of packaged food products. Four of the seven studies used either spot or 24‐hour urine samples to measure dietary salt intake and five were conducted in East or Southeast Asia—two of which were in low‐ and middle‐income countries. Study quality varied among the seven studies and all except one had one or more risks related to bias.
School‐Based Health Centers and Adolescent Substance Use: Moderating Effects of Race/Ethnicity and Socioeconomic Status
Authors: Bersamin Melina , Paschall Mallie J. , Fisher Deborah A.
Published: October 2017

ABSTRACT

BACKGROUND

School‐based health centers (SBHCs) have been associated with many positive health and academic outcomes. The current study extends previous research and examines possible differences in the association between SBHC exposure and adolescent alcohol, tobacco, and other drug use by race/ethnicity, sex, and socioeconomic status (SES).

METHODS

California Healthy Kids Survey data from 504 traditional high schools in California were linked with publicly available data on SBHCs and school demographics. Multilevel logistic regression analyses were conducted controlling for school and individual characteristics.

RESULTS

Significant interactions suggest that SBHC exposure was inversely associated with past 30‐day alcohol use, binge drinking, and cigarette and e‐cigarette use among African American youth and negatively associated with cigarette and marijuana use among Asian youth, relative to whites. There was also a significant interaction between SBHC exposure and parent education for past 30‐day alcohol use and binge drinking. No significant sex interactions were observed.

CONCLUSIONS

SBHC exposure appears to be inversely related to substance use among youth in some ethnic minority groups and youth of lower SES. This may have implications regarding SBHC placement and investment. Additional research is necessary to understand the mechanisms through which SBHCs may influence adolescent substance use and other health behaviors.
Robust Improvements on Reasoning Performance Following Discussion in Japan
Authors: Boku Mariko , Yama Hiroshi , Mercier Hugo
Published: October 2017

Group discussion significantly improves performance on intellective problems. However, most experiments have been conducted in Western cultures. Cross‐cultural psychology suggests that members of Eastern cultures might be less likely to benefit from group discussion. One experiment in Japan suggested that this was not the case, but this experiment suffered from some limitations. To address these limitations, Japanese participants were asked to solve an intellective task four times: individually (pre‐test), in small discussion groups (test), individually again (transfer task, post‐test), and individually after a delay (delayed post‐test). The results revealed a robust improvement during group discussion. Groups in which at least one member had found the correct answer individually agreed on it during the discussion. Moreover, and in contrast with results obtained in Western cultures, most groups with no such member also found the correct answer. The gains obtained during discussion were maintained in the transfer tasks. This result provides further evidence that the improvement of reasoning performance in group discussion is a universal phenomenon, and provides support for the practice of collaborative learning in Japan.
Comparison of Four Artificial Light Technologies for Indoor Aquaponic Production of Swiss Chard, Beta vulgaris, and Kale, Brassica oleracea
Authors: Oliver Luke P. , Coyle Shawn D. , Bright Leigh A. , Shultz R. Charles , Hager Janelle V. , Tidwell James H.
Published: October 2017

To date, most aquaponic research has been conducted outdoors in tropical climates or in greenhouses in subtropical climates. For more northerly latitudes, aquaponic production will require supplemental light in greenhouses or insulated buildings. Two separate 3‐wk growth trials were conducted to evaluate the effects of four different lighting technologies on the growth of Swiss chard, Beta vulgaris (Trial 1) and kale, Brassica oleracea (Trial 2) in aquaponic systems. Light technologies evaluated included fluorescent (FLO), metal halide (MH), induction (IND), and light‐emitting diode (LED). Four 1175‐L systems were used with all four light types represented in each system in a complete block design. Juvenile Nile tilapia, Oreochromis niloticus (241 g) were stocked in each system and fed a floating 32% protein diet at a rate of 60 g/m2 of plant grow space per day. In Trial 1, Swiss chard plants grown under LED lights for 3 wk achieved significantly higher (P ≤ 0.05) average individual weights (117.7 g), higher production per unit of area (3535 g/m2), and higher production per unit of energy (32.3 g/m2/kwh) than Swiss chard grown under the other three light types, which did not differ significantly (P > 0.05) from each other. In Trial 2, kale grown under LED lights achieved significantly higher (P ≤ 0.05) average individual weights (102.9 g), higher production per unit of area (2136.6 g/m), and higher production per unit of energy (381.5 g/m2/kwh) than kale grown under the other three light types, which did not differ significantly (P > 0.05). The results of the two trials are in agreement and indicate that LED lights were superior to MH, FLO, and IND lights in terms of absolute plant growth as well as growth per unit of energy consumed.
Competitive devaluations in commodity‐based economies: Colombia and the Pacific Alliance Group
Authors: Caporale Guglielmo Maria , Costamagna Rodrigo , Rossini Gustavo
Published: October 2017

This paper investigates whether there is an S‐curve in Colombia using bilateral and disaggregated quarterly data for the period 1991 to 2014. More precisely, the short‐run effects of a depreciation on the trade balance (TB) are analyzed in 27 industries covered by the Pacific Alliance Group free trade agreement. The S‐curve found in sectors representing 30 percent of total industrial production suggests that in these cases competitive devaluations have a positive effect on the TB in the short run. Our findings have important policy implications: since only large competitive devaluations can restore TB equilibrium, industrial restructuring would appear to be a more sensible strategy, though this cannot be achieved in the short run and is instead a medium‐ to long‐term goal.
Have money and credit data releases helped markets to predict the interest rate decisions of the European Central Bank?
Authors: Jung Alexander
Published: October 2017

This paper examines whether money and credit data releases by the European Central Bank (ECB) have provided markets with additional clues about the future course of its monetary policy. It conducts a novel econometric approach, as suggested by El‐Shagi and Jung (Eur J Polit Econ 39:222–234, 2015), based on a combination of an Ordered Probit model explaining future policy rate changes (sample 2000–2014) and the Vuong test for model selection. Overall, our empirical results support the view that information contained in money and credit aggregates is used by markets when assessing forthcoming interest changes of the ECB.
The fiscal and human costs of immigrant detention and deportation in the United States
Authors: Patler Caitlin , Golash‐Boza Tanya Maria
Published: October 2017

An extensive body of literature has analyzed the individual impacts and collateral consequences of mass incarceration. However, few studies explore the consequences of a parallel and overlapping system: mass immigration detention and deportation. The last 30 years witnessed a dramatic increase in the number of noncitizens detained in and deported from the United States. Individuals detained under immigration laws are held pending adjudication, often mandatorily, and without many basic constitutional protections. Immigrant detention and deportation impose severe burdens on immigrants and their households and levy significant costs to society—financially, as well as in terms of social capital and community well‐being. Chiefly due to the difficulty in accessing noncitizens in the process of detention and deportation, this system has largely escaped sociological inquiry. This article provides a background for understanding the growth and consequences of detention and deportation in the United States. It reviews the literature on these immigration law enforcement programs and suggests topical and methodological directions for future research.
The healthy donor effect impacts self‐reported physical and mental health – results from the Danish Blood Donor Study (DBDS)
Authors: Rigas A. S. , Skytthe A. , Erikstrup C. , Rostgaard K. , Petersen M. S. , Hjalgrim H. , Ullum H. , Kyvik K. O. , Pedersen O. B.
Published: October 2017

Aims

This study aimed at quantifying the healthy donor effect by comparing self‐perceived mental and physical health between blood donors and non‐donors.

Background

In theory, the selection process known as the healthy donor effect should result in better self‐perceived, health‐related quality of life in donors than in non‐donors.

Methods

The Short Form‐12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified by sex and age group intervals. Outcome variables were the mental component score (MCS) and the physical component score (PCS).

Results

A total of 28 982 and 36 913 participants from the DTR and the DBDS, respectively, were included in this study. Younger donors had higher MCS than non‐donors, whereas MCS was only marginally high in older donors compared with non‐donors. In contrast, PCS was almost similar for both young donors and non‐donors. With the increase in age, non‐donors had lower PCS than donors.

Conclusions

Two selection patterns were revealed. Among young individuals, better self‐perceived mental health was associated with a blood donor. With the increase in age, better self‐perceived physical health was associated with blood donation.
The Guarantees of the Human Rights of the Defendant in the Law System in Kosovo
Authors: Podvorica Armend , Rakaj Adelina
Published: October 2017

The paper "The guarantees of the human rights of the defendant in the law system in Kosovo" aims to treat the access of the Republic of Kosovo in the delivery of constitutional guarantees and legal guarantees to protect the defendant in the criminal procedure. Within these guarantees, special emphasis is placed on the judicious acts in force that provide these guarantees in the Republic of Kosovo. A special analysis with regard to this paper is dedicated to the Convention for the Protection of Human Rights and Fundamental Freedoms (ECHR), the practice of European Court of Human Rights (ECtHR), the Constitution of the Republic of Kosovo and the Criminal Procedure Code of Kosovo (CPCK). The analysis of those acts clarifies that the guarantees of the Legal System in Kosovo coincide with the rights of the defendant. Another dimension that finds space within the paper is the practical implementation of the guarantees provided by the aforementioned acts in terms of the rights of the defendant. The role of the Constitutional Court in the Republic of Kosovo in the past and now has been mainly analyzed in the formation of the constitutional and international guarantees, applicable in Kosovo concerning the rights of the defendant in the criminal procedure.
Estimación de la huella ecológica del minifundio en la vereda Pasquilla, Bogotá – Colombia
Authors: Valero Vargas Rafael Ernesto , Beltrán Vargas Julio Eduardo
Published: October 2017

En la actualidad el país no cuenta con un instrumento de gestión ambiental que permita estimar la huella ecológica provocada por las actividades agropecuarias de los minifundios, lo que restringe la formulación de políticas públicas locales de desarrollo agropecuario. En 2014, se midió la huella ecológica de 27 minifundios en la vereda Pasquilla de Bogotá, Cundinamarca, Colombia. La información provino de los productores y fue complementada con revisiones secundarias de las publicaciones del sector agropecuario. En hectáreas globales, la huella ecológica per cápita coincidió con una cifra de 1,89, valor que fue desagregado en 0,67 para el cultivo de la papa (Solanum tuberosum); 0,22 para el manejo del pasto kikuyo (Pennisetum clandestinum); 0,37 para los bosques, y 0,38 para el consumo de energía eléctrica. En suma, el balance ecológico mostró un déficit de 0,59 hectáreas globales.
La resistencia como entramado del Lugar: el caso de la “gente de los médanos” (Las Aguadas, Argentina)
Authors: Szmulewicz Melisa , Liscovsky Iris Josefina
Published: October 2017

En Argentina, las problemáticas ambientales están íntimamente relacionadas con la reorganización del territorio que se ha desarrollado con base en procesos que competen al dominio de la tierra. Para comprender las posibles consecuencias de dichos fenómenos se estudia el caso de la comunidad de origen mapuche de Las Aguadas mediante un análisis del lugar. Desde esta mirada multidimensional y superadora de la dualidad sociedad-naturaleza se indagan las dinámicas que se desarrollan en el espacio vivido mediante metodologías cualitativas. Se identifican la pertenencia, el sentido de comunidad y el trabajo como dimensiones articuladas que definen al lugar, reconociéndole un manejo integral. Este manejo responde a circunstancias regionales en las que pueblos y naturalezas protegen historias y gestan resistencias para resguardar sus modos de vivir. El estudio permite reconocer el espacio socionatural vivido como la base para comprender las actuales problemáticas ambientales.
Hacer florecer al desierto: Análisis sobre la intensidad de uso de los recursos hídricos subterráneos y superficiales en Chihuahua, México
Authors: Manzanares Rivera José Luis
Published: October 2017

En México, los efectos de las prácticas agrícolas especializadas sobre los recursos hídricos son objeto de atención creciente. El estado de Chihuahua representa un caso de interés, por la presencia de desarrollos agrícolas altamente especializados que dependen de la extracción de agua subterránea. Adicionalmente, en el estado se localiza el río Conchos, principal tributario mexicano del río Bravo en la frontera con Estados Unidos. El trabajo estima la intensidad de uso de los recursos hídricos por acuífero con base en información georreferenciada y aplica el enfoque metodológico de caudal ecológico para el río Conchos, a partir de registros hidrométricos en el periodo 1947-2011.
La noción de resiliencia en el análisis de las dinámicas territoriales rurales: una aproximación al concepto mediante un enfoque territorial
Authors: Sánchez-Zamora Pedro , Gallardo-Cobos Rosa , Ceña-Delgado Felisa
Published: October 2017

En el ámbito rural, el concepto de resiliencia se ha venido aplicando desde la perspectiva de los sistemas socioecológicos y el desarrollo sostenible. Sin embargo, este concepto todavía no ha sido ampliamente utilizado en el ámbito rural con enfoque territorial. Este trabajo tiene como objetivo avanzar en la conceptualización de la resiliencia territorial, desde una perspectiva espacial, evolutiva y dinámica. Para ello, se toma como punto de partida la resiliencia de los sistemas socioecológicos y la resiliencia comunitaria, y se analizan dentro del marco interpretativo del concepto de territorio y las dinámicas territoriales rurales.
¿Contribuyen las prácticas agroecológicas a la sustentabilidad en la Agricultura Familiar de Montaña? El caso de Curarrehue, región de la Araucanía, Chile.
Authors: Fuentes Acuña Nicolas Ricardo , Marchant Carla
Published: October 2017

La sustentabilidad de la agricultura familiar (AF) ha cobrado interés en el actual escenario de cambio ambiental global. En este contexto, los sistemas agrícolas de montaña son uno de los menos estudiados, a pesar que permiten el manejo predial manteniendo prácticas tradicionales. La investigación analiza mediante la metodología MESMIS, el grado de sustentabilidad de predios de AF con enfoque agroecológico y convencional, con el fin de visibilizar el aporte de la AF con enfoque agroecológico a la sustentabilidad predial en territorios de montaña, en particular el caso de Curarrehue, en la Araucanía Andina Chilena. Los resultados muestran que la utilización de prácticas agroecológicas, basadas en los conocimientos locales, son mecanismos que permiten un mejor desempeño de las unidades familiares en los ámbitos ambiental, económico y social.
Impactos socioeconómicos del cambio climático en América Latina y el Caribe: 2020-2045
Authors: Rodríguez De Luque Jesús José , Gonzalez Rodríguez Carlos Eduardo , Gourdji Sharon , Mason-D’Croz Daniel , Obando Bonilla Diego , Mesa Diez Jeison , Prager Steven D
Published: October 2017

En América Latina y el Caribe (ALC), el arroz, el trigo, el maíz, el frijol y la soya juegan un papel importante debido a sus aportes a la economía y a la seguridad alimentaria. Dada la existencia de evidencia que señala que a nivel mundial se presentarían cambios en el clima en el mediano plazo, en el presente texto se evalúan los impactos socioeconómicos que habría a niveles de ALC si no fueran implementadas medidas de adaptación. Con este fin, se realiza una integración entre modelos climáticos, de cultivos y económicos. Los resultados muestran que los crecimientos de las producciones de maíz y frijol caerían de manera importante en Nicaragua, El Salvador, Guatemala, Honduras, Colombia, Venezuela y Brasil, y los del arroz y trigo presentarían importantes disminuciones en Brasil, Argentina y Uruguay. Finalmente, se encuentra que el cambio climático tiene la capacidad de frenar parte de los avances en materia de seguridad alimentaria en la región, debido a sus efectos negativos sobre la disponibilidad de alimentos.
Increased weight gain by C-section: Functional significance of the primordial microbiome
Authors: Martinez Keith A. , Devlin Joseph C. , Lacher Corey R. , Yin Yue , Cai Yi , Wang Jincheng , Dominguez-Bello Maria G.
Published: October 2017

Mice born by C-section developed increased body weight and lacked microbiota developmental changes observed in control mice.
Cold, clear view of molecules nets chemistry prize
Authors: Service Robert F. , Stokstad Erik
Published: October 2017

Cryo-EM nears sharpness of x-ray crystallography.
Evolution accelerated when life set foot on land
Authors: Pennisi Elizabeth
Published: October 2017

Opportunities of terrestrial living sped innovation.
A future on fire
Firestorm
Edward Struzik
Island Press, 2017. 264 pp.
Authors: Kramer H. Anu
Published: October 2017

Climate change and conservative forest management may mean bigger and more frequent wildfires
Life, death, and antibodies
Authors: Bryant Vanessa L. , Hodgkin Philip D.
Published: October 2017

The search for high-affinity antibodies by B cells leaves a trail of molecular destruction
Robotics for space and marine sciences
Authors: Jacobstein Neil , Bellingham James , Yang Guang-Zhong
Published: October 2017

Harsh space and ocean environments push the limits of sensing, control, and manipulation of robotic systems.
Papers of note in
Science
356
(6342)
Authors: VanHook Annalisa M.
Published: October 2017

This week’s articles explore the structural basis for nitrate sensing in bacteria, the importance of attenuating healing responses to reduce fibrosis and allergy, and the recruitment of chromatin silencing factors in X chromosome inactivation.
Papers of note in
Nature
546
(7657)
Authors: VanHook Annalisa M.
Published: October 2017

This week’s articles highlight an unusual mechanism for switching off GPCR signaling; the structural basis of activation of the GLP-1 receptor; a critical role for the B cell receptor in some lymphoma cells; and how cancer cells exploit nutrient sensing and acquisition pathways.
Papers of note in
Science
356
(6343)
Authors: VanHook Annalisa M.
Published: October 2017

This week’s articles describe a mechanism by which starvation primes a cellular nutrient-sensing system for activation upon refeeding; microRNAs that control pain sensitivity; and the lasting effects of early life stress on the likelihood of developing depression.
Papers of note in
Science Translational Medicine
9
(394)
Authors: Ferrarelli Leslie K.
Published: October 2017

This week’s articles describe how broccoli can combat type 2 diabetes, how monocytes contribute to the failure of organ transplant grafts, and how to more durably treat RET- or KRAS-driven lung cancer.
Eccentric implants stand alone
Authors: Jewell Christopher M.
Published: October 2017

Controlling antibiotic drug clustering in replacement joint material provides a single-step strategy to clear infection while maintaining the mechanical strength needed for load bearing.
Development of a High-Throughput Respiratory Syncytial Virus Fluorescent Focus-Based Microneutralization Assay
Authors: Shambaugh Cindy , Azshirvani Sarieh , Yu Li , Pache Jared , Lambert Stacie L. , Zuo Fengrong , Esser Mark T.
Published: October 2017

Neutralizing antibodies specific for respiratory syncytial virus (RSV) represent a major protective mechanism against RSV infection, as demonstrated by the efficacy of the immune-prophylactic monoclonal antibody palivizumab in preventing RSV-associated lower respiratory tract infections in premature infants. Accordingly, the RSV neutralization assay has become a key functional method to assess the neutralizing activity of serum antibodies in preclinical animal models, epidemiology studies, and clinical trials. In this study, we qualified a 24-h, fluorescent focus-based microneutralization (RSVA FFA-MN) method that requires no medium exchange or pre- or postinfection processing to detect green fluorescent protein-expressing RSV strain A2 (RSVA-GFP)-infected cells, using a high-content imaging system for automated image acquisition and focus enumeration. The RSVA FFA-MN method was shown to be sensitive, with a limit of detection (LOD) and limit of quantitation (LOQ) of 1:10, or 3.32 log
2
; linear over a range of 4.27 to 9.65 log
2
50% inhibitory concentration (IC
50
); and precise, with intra- and interassay coefficients of variation of <21%. This precision allowed the choice of a statistically justified 3-fold-rise seroresponse cutoff criterion. The repeatability and robustness of this method were demonstrated by including a pooled human serum sample in every assay as a positive control (PC). Over 3 years of testing between two laboratories, this PC generated data falling within 2.5 standard deviations of the mean 98.7% of the time (
n
= 1,720). This high-throughput and reliable RSV microneutralization assay has proven useful for testing sera from preclinical vaccine candidate evaluation studies, epidemiology studies, and both pediatric and adult vaccine clinical trials.
Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after Natural Infection with Influenza A Viruses
Authors: Changsom Don , Jiang Li , Lerdsamran Hatairat , Iamsirithaworn Sopon , Kitphati Rungrueng , Pooruk Phisanu , Auewarakul Prasert , Puthavathana Pilaipan
Published: October 2017

The kinetics, longevity, and breadth of antibodies to influenza virus neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A virus (IAV) H5N1 infection survivors and from patients infected with the 2009 pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA) segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1) (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens. These serum/plasma samples were also investigated by microneutralization (MN) and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI) antibodies against N1 NA of both homologous and heterologous viruses were observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease onset, but an increase in titer was not observed in serum samples obtained late in infection. On the other hand, an increase in seroconversion rate with the HI assay was observed in the follow-up series of sera obtained on days 7, 14, 28, and 90 after infection. The study also showed that NI antibodies are broadly reactive, while MN and HI antibodies are more strain specific.
HIV-1 gp120 and Modified Vaccinia Virus Ankara (MVA) gp140 Boost Immunogens Increase Immunogenicity of a DNA/MVA HIV-1 Vaccine
Authors: Shen Xiaoying , Basu Rahul , Sawant Sheetal , Beaumont David , Kwa Sue Fen , LaBranche Celia , Seaton Kelly E. , Yates Nicole L. , Montefiori David C. , Ferrari Guido , Wyatt Linda S. , Moss Bernard , Alam S. Munir , Haynes Barton F. , Tomaras Georgia D. , Robinson Harriet L.
Published: October 2017

An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia virus Ankara (MVA) expressing HIV-1 Env on virus-like particles. In this study, we evaluated whether the addition of a gp120 protein in alum or MVA-expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime-MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26, and 40. Both boost immunogens enhanced the breadth of HIV-1 gp120 and V1V2 responses, antibody-dependent cellular cytotoxicity (ADCC), and low-titer tier 1B and tier 2 neutralizing antibody responses. However, there were differences in antibody kinetics, linear epitope specificity, and CD4 T cell responses between the groups. The gp120 protein boost elicited earlier and higher peak responses, whereas the MVAgp140 boost resulted in improved antibody durability and comparable peak responses after the final immunization. Linear V3 specific IgG responses were particularly enhanced by the gp120 boost, whereas the MVAgp140 boost also enhanced responses to linear C5 and C2.2 epitopes. Interestingly, gp120, but not the MVAgp140 boost, increased peak CD4+T cell responses. Thus, both gp120 and MVAgp140 can augment potential protection of a DNA/MVA vaccine by enhancing gp120 and V1/V2 antibody responses, whereas potential protection by gp120, but not MVAgp140 boosts, may be further impacted by increased CD4+T cell responses.

IMPORTANCEPrior immune correlate analyses with humans and nonhuman primates revealed the importance of antibody responses in preventing HIV-1 infection. A DNA prime-modified vaccinia virus Ankara (MVA) boost vaccine has proven to be potent in eliciting antibody responses. Here we explore the ability of boosts with recombinant gp120 protein or MVA-expressed gp140 to enhance antibody responses elicited by the GOVX-B11 DNA prime-MVA boost vaccine. We found that both types of immunogen boosts enhanced potentially protective antibody responses, whereas the gp120 protein boosts also increased CD4+T cell responses. Our data provide important information for HIV vaccine designs that aim for effective and balanced humoral and T cell responses.
Varicella-Zoster Virus Expresses Multiple Small Noncoding RNAs
Authors: Markus Amos , Golani Linoy , Ojha Nishant Kumar , Borodiansky-Shteinberg Tatiana , Kinchington Paul R. , Goldstein Ronald S.
Published: October 2017

Many herpesviruses express small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), that may play roles in regulating lytic and latent infections. None have yet been reported in varicella-zoster virus (VZV; also known as human herpesvirus 3 [HHV-3]). Here we analyzed next-generation sequencing (NGS) data for small RNAs in VZV-infected fibroblasts and human embryonic stem cell-derived (hESC) neurons. Two independent bioinformatics analyses identified more than 20 VZV-encoded 20- to 24-nucleotide RNAs, some of which are predicted to have stem-loop precursors potentially representing miRNAs. These sequences are perfectly conserved between viruses from three clades of VZV. One NGS-identified sequence common to both bioinformatics analyses mapped to the repeat regions of the VZV genome, upstream of the predicted promoter of the immediate early gene open reading frame 63 (ORF63). This miRNA candidate was detected in each of 3 independent biological repetitions of NGS of RNA from fibroblasts and neurons productively infected with VZV using TaqMan quantitative PCR (qPCR). Importantly, transfected synthetic RNA oligonucleotides antagonistic to the miRNA candidate significantly enhanced VZV plaque growth rates. The presence of 6 additional small noncoding RNAs was also verified by TaqMan qPCR in productively infected fibroblasts and ARPE19 cells. Our results show VZV, like other human herpesviruses, encodes several sncRNAs and miRNAs, and some may regulate infection of host cells.

IMPORTANCE
Varicella-zoster virus is an important human pathogen, with herpes zoster being a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNAs) are recognized as important actors in modulating gene expression, and this study demonstrates the first reported VZV-encoded sncRNAs. Many are clustered to a small genomic region, as seen in other human herpesviruses. At least one VZV sncRNA was expressed in productive infection of neurons and fibroblasts that is likely to reduce viral replication. Since sncRNAs have been suggested to be potential targets for antiviral therapies, identification of these molecules in VZV may provide a new direction for development of treatments for painful herpes zoster.
STANDING Collaboration: a study protocol for developing clinical standards
Authors: Wiles Louise K , Hibbert Peter D , Stephens Jacqueline H , Coiera Enrico , Westbrook Johanna , Braithwaite Jeffrey , Day Ric O , Hillman Ken M , Runciman William B
Published: October 2017

Introduction

Despite widespread availability of clinical practice guidelines (CPGs), considerable gaps continue between the care that is recommended (‘appropriate care’) and the care provided. Problems with current CPGs are commonly cited as barriers to providing ’appropriate care'.

Our study aims to develop and test an alternative method to keep CPGs accessible and up to date. This method aims to mitigate existing problems by using a single process to develop clinical standards (embodied in clinical indicators) collaboratively with researchers, healthcare professionals, patients and consumers. A transparent and inclusive online curated (purpose-designed, custom-built, wiki-type) system will use an ongoing and iterative documentation process to facilitate synthesis of up-to-date information and make available its provenance. All participants are required to declare conflicts of interest. This protocol describes three phases: engagement of relevant stakeholders; design of a process to develop clinical standards (embodied in indicators) for ‘appropriate care’ for common medical conditions; and evaluation of our processes, products and feasibility.

Methods and analysis

A modified e-Delphi process will be used to gain consensus on ‘appropriate care’ for a range of common medical conditions. Clinical standards and indicators will be developed through searches of national and international guidelines, and formulated with explicit criteria for inclusion, exclusion, time frame and setting. Healthcare professionals and consumers will review the indicators via the wiki-based modified e-Delphi process. Reviewers will declare conflicts of interest which will be recorded and managed according to an established protocol. The provenance of all indicators and suggestions included or excluded will be logged from indicator inception to finalisation. A mixed-methods formative evaluation of our research methodology will be undertaken.

Ethics and dissemination

Human Research Ethics Committee approval has been received from the University of South Australia. We will submit the results of the study to relevant journals and offer national and international presentations.
Is an opportunistic primary care-based intervention for non-responders to bowel screening feasible and acceptable? A mixed-methods feasibility study in Scotland
Authors: Calanzani Natalia , Cavers Debbie , Vojt Gabriele , Orbell Sheina , Steele Robert J C , Brownlee Linda , Smith Steve , Patnick Julietta , Weller David , Campbell Christine
Published: October 2017

Objectives

We aimed to test whether a brief, opportunistic intervention in general practice was a feasible and acceptable way to engage with bowel screening non-responders.

Design

This was a feasibility study testing an intervention which comprised a brief conversation during routine consultation, provision of a patient leaflet and instructions to request a replacement faecal occult blood test kit. A mixed-methods approach to evaluation was adopted. Data were collected from proformas completed after each intervention, from the Bowel Screening Centre database and from questionnaires. Semi-structured interviews were carried out. We used descriptive statistics, content and framework analysis to determine intervention feasibility and acceptability.

Participants

Bowel screening non-responders (as defined by the Scottish Bowel Screening Centre) and primary care professionals working in five general practices in Lothian, Scotland.

Primary and secondary outcome measures

Several predefined feasibility parameters were assessed, including numbers of patients engaging in conversation, requesting a replacement kit and returning it, and willingness of primary care professionals to deliver the intervention.

Results

The intervention was offered to 258 patients in five general practices: 220 (87.0%) engaged with the intervention, 60 (23.3%) requested a new kit, 22 (8.5%) kits were completed and returned. Interviews and questionnaires suggest that the intervention was feasible, acceptable and consistent with an existing health prevention agenda. Reported challenges referred to work-related pressures, time constraints and practice priorities.

Conclusions

This intervention was acceptable and resulted in a modest increase in non-responders participating in bowel screening, although outlined challenges may affect sustained implementation. The strategy is also aligned with the increasing role of primary care in promoting bowel screening.
Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis — coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial
Authors: Kim Chi-Hoon , Han Jung-Kyu , Yang Han-Mo , Park Kyung Woo , Lee Hae-Young , Kang Hyun-Jae , Koo Bon-Kwon , Lee Namho , Cha Tae-Joon , Yang Tae-Hyun , Jeong Myung-Ho , Yoon Myeong-Ho , Lee Seung Uk , Lee Seung Jin , Kim Jin Won , Cho Jin-Man , Han Kyu-Rock , Pyun Wook Bum , Kim Hyo-Soo
Published: October 2017

Introduction

We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies.

Methods and analysis

The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2×2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding.

Ethic approval and dissemination

All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers.

Trial registration number

NCT02601157; Pre-results.
Effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed type 1 diabetes: protocol of a randomised controlled trial
Authors: Groele Lidia , Szajewska Hania , Szypowska Agnieszka
Published: October 2017

Introduction

Recent evidence has demonstrated that, among other factors, dysbiosis (imbalances in the composition and function of the gut microbiota) may be relevant in the development of type 1 diabetes (T1D). Thus, gut microbiota may be a target for improving outcomes in subjects with T1D. The aim of the study is to examine the effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed T1D.

Methods and analysis

A total of 96 children aged 8 to 17 years with newly diagnosed T1D, confirmed by clinical history and the presence of at least one positive autoantibody, will be enrolled in a double-blind, randomised, placebo-controlled trial in which they will receiveL. rhamnosusGG andB. lactisBb12 at a dose of 109colony-forming units or an identically appearing placebo, orally, once daily, for 6 months. The follow-up will be for 12 months. The primary outcome measures will be the area under the curve of the C-peptide level during 2-hour responses to a mixed meal.

Ethics and dissemination

The Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences.

Trial registration number

NCT03032354; Pre-results.