bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrostatic deflector studies using small-scale prototype electrodes
Authors: Grigoryev K. , Rathmann F. , Stahl A. , Ströher H.
Published: April 2019

The search for electric dipole moments of particles in storage rings requires the development of dedicated electrostatic deflector elements. The JEDI prototype-ring design consists of more than 50 electric deflectors of 1 m length with 60 mm spacing between the plates with electric fields of 10 MV m−1. This paper presents studies of scaled-down uncoated prototype electrodes with 10 mm radius made of stainless steel. The electric field at electrode gap distances from 1 mm to 0.05 mm increased from 15 to 90 MV m−1. In future investigations, we will study different materials and coatings at similar electrode spacings. Preparations are also underway to study large deflector elements.
Molecular polarizability in open ensemble simulations of aqueous nanoconfinements under electric field
Authors: Moučka F. , Zamfir S. , Bratko D. , Luzar A.
Published: April 2019

Molecular polarization at aqueous interfaces involves fast degrees of freedom that are often averaged-out in atomistic-modeling approaches. The resulting effective interactions depend on a specific environment, making explicit account of molecular polarizability particularly important in solutions with pronounced anisotropic perturbations, including solid/liquid interfaces and external fields. Our work concerns polarizability effects in nanoscale confinements under electric field, open to an unperturbed bulk environment. We model aqueous molecules and ions in hydrophobic pores using the Gaussian-charge-on-spring BK3-AH representation. This involves nontrivial methodology developments in expanded ensemble Monte Carlo simulations for open systems with long-ranged multibody interactions and necessitates further improvements for efficient modeling of polarizable ions. Structural differences between fixed-charge and polarizable models were captured in molecular dynamics simulations for a set of closed systems. Our open ensemble results with the BK3 model in neat-aqueous systems capture the ∼10% reduction of molecular dipoles within the surface layer near the hydrophobic pore walls in analogy to reported quantum mechanical calculations at water/vapor interfaces. The polarizability affects the interfacial dielectric behavior and weakens the electric-field dependence of water absorption at pragmatically relevant porosities. We observe moderate changes in thermodynamic properties and atom and charged-site spatial distributions; the Gaussian distribution of mobile charges on water and ions in the polarizable model shifts the density amplitudes and blurs the charge-layering effects associated with increased ion absorption. The use of polarizable force field indicates an enhanced response of interfacial ion distributions to applied electric field, a feature potentially important for in silico modeling of electric double layer capacitors.
Temperature sensitivity and short-term memory in electroforming-free low power carbon memristors
Authors: Murdoch B. J. , Raeber T. J. , Zhao Z. C. , McKenzie D. R. , McCulloch D. G. , Partridge J. G.
Published: April 2019

We report temperature dependent electrical characteristics of two-terminal Ag/a-COx/ta-C/Pt memristors. In these asymmetric devices, defects at the Ag/a-COx interface are passivated by oxygen. This alleviates Fermi level pinning and hence increases the height of the Schottky barrier formed at the interface. Electric-field-induced detrapping of electrons from sp2-related defects in the ta-C causes the observed resistive switching. This occurs entirely in the insulating regime, i.e., with conductance ≪ 2e2/h, enabling ultralow power resistive switching (∼6 nW). Nonlinear temperature dependent ON/OFF ratios and short-term memory characteristics (governed by thermal detrapping kinetics) suggest suitability for temporal neuromorphic computing and sensing applications.
Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration
Authors: Li Dongqing , Kular Lara , Vij Manika , Herter Eva K. , Li Xi , Wang Aoxue , Chu Tongbin , Toma Maria-Alexandra , Zhang Letian , Liapi Eleni , Mota Ana , Blomqvist Lennart , Sérézal Irène Gallais , Rollman Ola , Wikstrom Jakob D. , Bienko Magda , Berglund David , Ståhle Mona , Sommar Pehr , Jagodic Maja , Landén Ning Xu
Published: April 2019

An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed “wound and keratinocyte migration-associated lncRNA 1” (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds.
The crystal structure of dGTPase reveals the molecular basis of dGTP selectivity
Authors: Barnes Christopher O. , Wu Ying , Song Jinhu , Lin Guowu , Baxter Elizabeth L. , Brewster Aaron S. , Nagarajan V. , Holmes Andrew , Soltis S. Michael , Sauter Nicholas K. , Ahn Jinwoo , Cohen Aina E. , Calero Guillermo
Published: April 2019

Deoxynucleotide triphosphohydrolases (dNTPases) play a critical role in cellular survival and DNA replication through the proper maintenance of cellular dNTP pools. While the vast majority of these enzymes display broad activity toward canonical dNTPs, such as the dNTPase SAMHD1 that blocks reverse transcription of retroviruses in macrophages by maintaining dNTP pools at low levels,Escherichia coli(Ec)-dGTPase is the only known enzyme that specifically hydrolyzes dGTP. However, the mechanism behind dGTP selectivity is unclear. Here we present the free-, ligand (dGTP)- and inhibitor (GTP)-bound structures of hexamericEc-dGTPase, including an X-ray free-electron laser structure of the freeEc-dGTPase enzyme to 3.2 Å. To obtain this structure, we developed a method that applied UV-fluorescence microscopy, video analysis, and highly automated goniometer-based instrumentation to map and rapidly position individual crystals randomly located on fixed target holders, resulting in the highest indexing rates observed for a serial femtosecond crystallography experiment. Our structures show a highly dynamic active site where conformational changes are coupled to substrate (dGTP), but not inhibitor binding, since GTP locks dGTPase in its apo- form. Moreover, despite no sequence homology,Ec-dGTPase and SAMHD1 share similar active-site and HD motif architectures; however,Ec-dGTPase residues at the end of the substrate-binding pocket mimic Watson–Crick interactions providing guanine base specificity, while a 7-Å cleft separates SAMHD1 residues from dNTP bases, abolishing nucleotide-type discrimination. Furthermore, the structures shed light on the mechanism by which long distance binding (25 Å) of single-stranded DNA in an allosteric site primes the active site by conformationally “opening” a tyrosine gate allowing enhanced substrate binding.
Nanoscale imaging reveals miRNA-mediated control of functional states of dendritic spines
Authors: Park Ikbum , Kim Hyun Jin , Kim Youngkyu , Hwang Hye Sung , Kasai Haruo , Kim Joung-Hun , Park Joon Won
Published: April 2019

Significance

Although synaptic plasticity is intimately controlled by synthesis of transmitter receptors and regulatory proteins, it remains largely unknown how synthesis and distribution of synaptic proteins could be modulated at the specific synapses. microRNAs (miRNAs) such as miR-134 could adjust synapse development and plasticity due to their regulatory functions for a distinct set of proteins. We developed an imaging method for in situ microRNAs mediated by atomic force microscopy (AFM), which revealed that miR-134s are enriched at nearby dendritic shafts and necks of spines. Notably, the abundance of miR-134s varied among distinct spine types, and their amounts were inversely correlated with maturity and functional states of individual spines. The functional impact of miR-134s would represent a molecular means of miRNAs, dynamically tuning synaptic connectivity and plasticity.
Linguistic inferences without words
Authors: Tieu Lyn , Schlenker Philippe , Chemla Emmanuel
Published: April 2019

Contemporary semantics has uncovered a sophisticated typology of linguistic inferences, characterized by their conversational status and their behavior in complex sentences. This typology is usually thought to be specific to language and in part lexically encoded in the meanings of words. We argue that it is neither. Using a method involving “composite” utterances that include normal words alongside novel nonlinguistic iconic representations (gestures and animations), we observe successful “one-shot learning” of linguistic meanings, with four of the main inference types (implicatures, presuppositions, supplements, homogeneity) replicated with gestures and animations. The results suggest a deeper cognitive source for the inferential typology than usually thought: Domain-general cognitive algorithms productively divide both linguistic and nonlinguistic information along familiar parts of the linguistic typology.
Genome-wide CRISPR screen for Zika virus resistance in human neural cells
Authors: Li Yun , Muffat Julien , Omer Javed Attya , Keys Heather R. , Lungjangwa Tenzin , Bosch Irene , Khan Mehreen , Virgilio Maria C. , Gehrke Lee , Sabatini David M. , Jaenisch Rudolf
Published: April 2019

Significance

Zika virus (ZIKV) is a neurotropic and neurovirulent arbovirus that has severe detrimental impact on the developing human fetal brain. We used a genome-wide CRISPR-Cas9 knockout screen to identify ZIKV host genes in human neural progenitors. The screen identified host factors involved in heparan sulfation, endocytosis, endoplasmic reticulum processing, Golgi function, and interferon activity. Our findings provide insights into host-dependent mechanisms for ZIKV infection in the highly vulnerable human neural progenitor cells and identify molecular targets for potential therapeutic intervention.
Overlooked roles of DNA damage and maternal age in generating human germline mutations
Authors: Gao Ziyue , Moorjani Priya , Sasani Thomas A. , Pedersen Brent S. , Quinlan Aaron R. , Jorde Lynn B. , Amster Guy , Przeworski Molly
Published: April 2019

Significance

More than three-fourths of human germline mutations are paternal in origin and their total number increases with the father’s age at conception. These observations are thought to support the textbook view that germline point mutations stem mostly from DNA replication errors. Analyzing large germline mutation datasets for humans, we find that this understanding cannot explain the observed patterns of new mutations. Instead, we show that the male mutation bias is not driven by spermatogenesis. We further find evidence that a substantial fraction of mutations are not replicative in origin and uncover a potential effect of a mother’s age on the number of mutations that happen early in the development of the embryo.
Toward personalized cognitive diagnostics of at-genetic-risk Alzheimer’s disease
Authors: Coughlan Gillian , Coutrot Antoine , Khondoker Mizanur , Minihane Anne-Marie , Spiers Hugo , Hornberger Michael
Published: April 2019

Spatial navigation is emerging as a critical factor in identifying preclinical Alzheimer’s disease (AD). However, the impact of interindividual navigation ability and demographic risk factors (e.g., APOE, age, and sex) on spatial navigation make it difficult to identify persons “at high risk” of AD in the preclinical stages. In the current study, we use spatial navigation big data (
n
= 27,108) from the Sea Hero Quest (SHQ) game to overcome these challenges by investigating whether big data can be used to benchmark a highly phenotyped healthy aging laboratory cohort into high- vs. low-risk persons based on their genetic (APOE) and demographic (sex, age, and educational attainment) risk factors. Our results replicate previous findings in APOE ε4 carriers, indicative of grid cell coding errors in the entorhinal cortex, the initial brain region affected by AD pathophysiology. We also show that although baseline navigation ability differs between men and women, sex does not interact with the APOE genotype to influence the manifestation of AD-related spatial disturbance. Most importantly, we demonstrate that such high-risk preclinical cases can be reliably distinguished from low-risk participants using big-data spatial navigation benchmarks. By contrast, participants were undistinguishable on neuropsychological episodic memory tests. Taken together, we present evidence to suggest that, in the future, SHQ normative benchmark data can be used to more accurately classify spatial impairments in at-high-risk of AD healthy participants at a more individual level, therefore providing the steppingstone for individualized diagnostics and outcome measures of cognitive symptoms in preclinical AD.
Coulomb anti-blockade in a Rydberg gas
Authors: Bounds A D , Jackson N C , Hanley R K , Bridge E M , Huillery P , Jones M P A
Published: April 2019

We perform a comprehensive investigation of the coupling between a Rydberg-dressed atomic gas and an ultra-cold plasma (UCP). Using simultaneous time-resolved measurements of both neutral atoms and ions, we show that plasma formation occurs via a Coulomb anti-blockade mechanism, in which background ions DC Stark shift nearby atoms into resonance at specific distances. The result is a highly correlated growth of the Rydberg population that shares some similarities with that previously observed for van der Waals interactions. We show that a rate equation model that couples the laser-driven Rydberg gas to the UCP via a Coulomb anti-blockade mechanism accurately reproduces both the plasma formation and its subsequent decay. Using long-lived high angular momentum states as a probe, we also find evidence of a crossover from Coulomb anti-blockade to Coulomb blockade at high density. As well as shedding light on loss mechanisms in Rydberg-dressed gases, our results open new ways to create low-entropy states in UCPs.
Quantification of solute deuterium in titanium deuteride by atom probe tomography with both laser pulsing and high-voltage pulsing: influence of the surface electric field
Authors: Chang Y H , Mouton I , Stephenson L , Ashton M , Zhang G K , Szczpaniak A , Lu W J , Ponge D , Raabe D , Gault B
Published: April 2019

Atom probe tomography (APT) has been increasingly used to investigate hydrogen embrittlement in metals due to its unique capacity for direct imaging of H atoms interacting with microstructural features. The quantitativeness of hydrogen measurements by APT is yet to be established in views of erroneous compositional measurements of bulk hydrides and the influence of spurious hydrogen, e.g. residual gas inside the analysis chamber. Here, we analyzed titanium deuteride (approx. 65.0 at%–66.6 at% D) in lieu of hydride to minimize the overlap with residual gas, both with laser pulsing and high-voltage (HV) pulsing. Strategies were deployed to prevent H pick-up during specimen fabrication, including preparing specimens at cryogenic temperature. The measured composition of deuterium by APT with laser pulsing decreases significantly with the applied laser pulse energy, which is interpreted with regards to the strength of the corresponding surface electrostatic field, as assessed by the evolution of charge-state ratio. In contrast, compositional analyses with HV pulsing are roughly independent of the applied experimental parameters, although approx. 15 at%–20 at% off the nominal composition. Aided by plotting paired mass-to-charge correlations, the mechanisms of composition bias in both pulsing modes are discussed. A special emphasis is placed on the local variations of the measured composition as a function of the local electric field across the specimen’s surface, which is not uniform due to asymmetric heat distribution related to the localized laser absorption and the faceted nature of surface caused by the crystallographic structure. Our investigations demonstrate the challenges of quantitative analysis of solute deuterium by APT but nevertheless provide insight to achieving the best possible experimental protocol.
Weighted estimates for one-sided martingale transforms
Authors: Chen Wei , Han Rui , Lacey Michael
Published: April 2019

Let
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper T f equals sigma-summation Underscript upper I Endscripts epsilon Subscript upper I Baseline mathematical left-angle f comma h Subscript upper I Sub Superscript plus Subscript Baseline mathematical right-angle h Subscript upper I Sub Superscript minus">

T
f
=

∑

I

ε
I

⟨
f
,

h

I
+

⟩

h

I
−

Tf =\sum _{I} \varepsilon _I \langle f,h_{I^+}\rangle h_{I^-}

. Here,

|

ε
I

|
=
1

\lvert \varepsilon _I\rvert =1

, and

h
J

h_J

is the Haar function defined on dyadic interval

J
J

. We show that, for instance,
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar upper T double-vertical-bar Subscript upper L squared left-parenthesis w right-parenthesis right-arrow upper L squared left-parenthesis w right-parenthesis Baseline less-than-or-equivalent-to left-bracket w right-bracket Subscript upper A 2 Sub Superscript plus Subscript Baseline period">

‖
T

‖

L

2

(
w
)
→

L

2

(
w
)

≲
[
w

]

A
2

+

.

\begin{equation*} \lVert T \rVert _{L ^{2} (w) \to L ^{2} (w)} \lesssim [w] _{A_2 ^{+}} . \end{equation*}

Above, we use the one-sided

A
2

A_2

characteristic for the weight

w
w

. This is an instance of a one-sided

A
2

A_2

conjecture. Our proof of this fact is difficult, as the very quick known proofs of the

A
2

A_2

theorem do not seem to apply in the one-sided setting.
Better safe than sorry: spider societies mitigate risk by prioritizing caution
Authors: Wright Colin M , Lichtenstein James L L , Luscuskie Lauren P , Montgomery Graham A , Pinter-Wollman Noa , Pruitt Jonathan N
Published: April 2019

A major benefit of living in a group is the ability to learn from others. We investigated how spider societies learn and respond to important information when that information is held by the majority or by single influential or generic individuals. We found that groups adopted a “better safe than sorry” strategy and exhibited caution when the group or any individual, regardless of their presumed social influence, had been previously exposed to danger.
Graphical data mining of cancer mechanisms with SEMA
Authors: Solmaz Mustafa , Lane Adam , Gonen Bilal , Akmamedova Ogulsheker , Gunes Mehmet H , Komurov Kakajan
Published: April 2019

Motivation

An important goal of cancer genomics initiatives is to provide the research community with the resources for the unbiased query of cancer mechanisms. Several excellent web platforms have been developed to enable the visual analyses of molecular alterations in cancers from these datasets. However, there are few tools to allow the researchers to mine these resources for mechanisms of cancer processes and their functional interactions in an intuitive unbiased manner.

Results

To address this need, we developed SEMA, a web platform for building and testing of models of cancer mechanisms from large multidimensional cancer genomics datasets. Unlike the existing tools for the analyses and query of these resources, SEMA is explicitly designed to enable exploratory and confirmatory analyses of complex cancer mechanisms through a suite of intuitive visual and statistical functionalities. Here, we present a case study of the functional mechanisms of TP53-mediated tumor suppression in various cancers, using SEMA, and identify its role in the regulation of cell cycle progression, DNA repair and signal transduction in different cancers.

SEMA is a first-in-its-class web application designed to allow visual data mining and hypothesis testing from the multidimensional cancer datasets. The web application, an extensive tutorial and several video screencasts with case studies are freely available for academic use at https://sema.research.cchmc.org/.

Availability and implementation

SEMA is freely available at https://sema.research.cchmc.org. The web site also contains a detailed Tutorial (also in Supplementary Information), and a link to the YouTube channel for video screencasts of analyses, including the analyses presented here. The Shiny and JavaScript source codes have been deposited to GitHub: https://github.com/msolmazm/sema.

Supplementary information

Supplementary data are available at Bioinformatics online.
Habitat Type Influences Danaus plexippus (Lepidoptera: Nymphalidae) Oviposition and Egg Survival on Asclepias syriaca (Gentianales: Apocynaceae)
Authors: Myers Andrew , Bahlai Christie A , Landis Douglas A
Published: April 2019

As agricultural practices intensify, species once common in agricultural landscapes are declining in abundance. One such species is the monarch butterfly (Danaus plexippus L.), whose eastern North American population has decreased approximately 80% during the past 20 yr. One hypothesis explaining the monarch’s decline is reduced breeding habitat via loss of common milkweed (Asclepias syriaca L.) from agricultural landscapes in the north central United States due to the adoption of herbicide-tolerant row crops. Current efforts to enhance monarch breeding habitat primarily involve restoring milkweed in perennial grasslands. However, prior surveys found fewer monarch eggs on common milkweed in grassland versus crop habitats, indicating potential preference for oviposition in row crop habitats, or alternatively, greater egg loss to predation in grasslands. We tested these alternative mechanisms by measuring oviposition and egg predation on potted A. syriaca host plants. Our study revealed that habitat context influences both monarch oviposition preference and egg predation rates and that these patterns vary by year. We found higher monarch egg predation rates during the first 24 h after exposure and that much of the predation occurs at night. Overall, we documented up to 90% egg mortality over 72 h in perennial grasslands, while predation rates in corn were lower (10–30% mortality) and more consistent between years. These findings demonstrate that weekly monarch egg surveys are too infrequent to distinguish oviposition habitat preferences from losses due to egg predation and suggest that monarch restoration efforts need to provide both attractive and safe habitats for monarch reproduction.
Guidance for the Evaluation of Tuberculosis Diagnostics That Meet the World Health Organization (WHO) Target Product Profiles: An Introduction to WHO Process and Study Design Principles
Authors: Denkinger Claudia M , Schumacher Samuel G , Gilpin Christopher , Korobitsyn Alexei , Wells William A , Pai Madhukar , Leeflang Mariska , Steingart Karen R , Bulterys Michelle , Schünemann Holger , Glaziou Philippe , Weyer Karin
Published: April 2019

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions.

This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs.

By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with TB.
Development and application of a high throughput natural language processing architecture to convert all clinical documents in a clinical data warehouse into standardized medical vocabularies
Authors: Afshar Majid , Dligach Dmitriy , Sharma Brihat , Cai Xiaoyuan , Boyda Jason , Birch Steven , Valdez Daniel , Zelisko Suzan , Joyce Cara , Modave François , Price Ron
Published: April 2019

Objective

Natural language processing (NLP) engines such as the clinical Text Analysis and Knowledge Extraction System are a solution for processing notes for research, but optimizing their performance for a clinical data warehouse remains a challenge. We aim to develop a high throughput NLP architecture using the clinical Text Analysis and Knowledge Extraction System and present a predictive model use case.

Materials and Methods

The CDW was comprised of 1 103 038 patients across 10 years. The architecture was constructed using the Hadoop data repository for source data and 3 large-scale symmetric processing servers for NLP. Each named entity mention in a clinical document was mapped to the Unified Medical Language System concept unique identifier (CUI).

Results

The NLP architecture processed 83 867 802 clinical documents in 13.33 days and produced 37 721 886 606 CUIs across 8 standardized medical vocabularies. Performance of the architecture exceeded 500 000 documents per hour across 30 parallel instances of the clinical Text Analysis and Knowledge Extraction System including 10 instances dedicated to documents greater than 20 000 bytes. In a use–case example for predicting 30-day hospital readmission, a CUI-based model had similar discrimination to n-grams with an area under the curve receiver operating characteristic of 0.75 (95% CI, 0.74–0.76).

Discussion and Conclusion

Our health system’s high throughput NLP architecture may serve as a benchmark for large-scale clinical research using a CUI-based approach.
The Galician Paradigm? Post-war Voices of German-Speaking Polish Jewish Survivors1
Authors: Aleksiun Natalia
Published: April 2019

This paper examines the experience of Galician-Jewish survivors who were fluent in German and who had developed close ties to German culture before the Second World War. It suggests that looking through the German linguistic lens highlights the multilayered nature of Jewish cultural identity in Galicia and offers an important critical tool with which to understand the distinct ways in which Galician Jews experienced the Holocaust. Using personal accounts, this article analyzes the ways in which complex cultural biographies of Galician Jews shaped their identities as eastern European Jews, Polish citizens, and Holocaust survivors. On the basis of testimonies included in early accounts for the Jewish historical commissions, statements by Jewish witnesses in post-war trials, oral interviews, and memoirs, this article discusses the ways in which Galician Jews remembered their relationship with German culture and how their complex cultural identity shaped their personal trajectories after the liberation.
Simulations and difficult problems
Authors: Hoover David L
Published: April 2019

An authorship attribution investigation ideally begins with a well-defined set of possible authors and an adequate number of firmly attributed roughly contemporaneous long texts in the same genre by those authors. Many significant or intriguing problems, however, suffer from deficiencies or limitations that reduce the effectiveness or validity of some kinds of analysis and make others impossible. These problematic situations can be approached by creating simulations that are designed to overcome or mitigate the difficulties of the problems. The results of the simulations can be used to suggest at least tentative solutions. Here, simulations are used to investigate four difficult problems. One involves fewer and shorter texts than would be ideal–texts that are also chronologically earlier than the known texts by the target author. The second involves too small a number of well attributed texts by the authors in question, and initial uncertainty about the genres of the texts, the number of authors involved, and their genders. The third is a tricky case of co-authorship with only relatively vague and uncertain evidence about the nature and extent of each author’s contribution; here simulations with sections of well-attributed texts by the two authors are used to test Rolling Classify. The fourth addresses the sparsity of well-attributed and confidently-dated Early Modern plays, using simulations to evaluate Brian Vickers’ rare n-gram approach to the attribution of such plays.
Shifting Our Perspective
Authors: Greenberg Lyn R.
Published: April 2019

This chapter discusses the importance of placing interventions for court-involved families within the context of the developmental tasks children need to master and the multiple systems they interact with. There is a wealth of research and professional literature addressing the risks to children at the center of legal conflict, and many areas of psychology provide evidence-based or evidence-informed models for assisting children with the resilience and coping abilities they will need to adjust successfully. The importance of evidence-informed decision-making is described, along with conceptual models for service planning and considering relevant literature. The association of abilities to eventual adjustment makes it critical that these issues be addressed promptly, even before the parents’ conflict is resolved. Approaches for integrating systemic perspective with coping strategies are discussed.
Behavioral Interventions
Authors: Helbig Kate A. , Wright Sarah J. , Derieux James R. , Schrieber Stefanie R. , Radley Keith C.
Published: April 2019

Behavior does not occur in a vacuum—there are many environmental factors and events that contribute to the occurrence of behavior. When developing an intervention to address the behavior of students, it is critical to first consider the events in close temporal proximity to the behavior of interest. In this chapter, the authors discuss antecedent-behavior-consequent relations and how to effectively modify behavior in one of three ways: manipulating antecedents to behavior, altering the consequences of a behavior, and teaching replacement or alternative forms of the behavior. Further, the chapter provides a review of principles of operant conditioning: positive reinforcement, negative reinforcement, positive punishment, and negative punishment. Finally, the chapter provides an overview of key instructional strategies, such as imitation training, chaining, and shaping.
A Practitioner’s Guide to Understanding the Evidence
Authors: Davis John L.
Published: April 2019

A critical element in bridging the research to practice gap is by enhancing practitioner’s ability to identify evidence-based practices. The term evidence-based refers to any practice, intervention, or strategy that is derived from or informed by empirical or data based research. The evidence-based practice model of intervention and decision-making is an approach where practitioners make recommendations based on high-quality research evidence to support the needs of students and teachers to effect positive change. The chapter describes the history of the evidence-based practice movement with respect to educational policy. Next, an overview of empirical research is provided. The description of empirical research includes various types of research designs utilized in school settings (e.g., single-case design, group design) and accompanying quality indicators. The chapter also provides a discussion of the relative strengths of single-case design in identifying evidence-based practice. Finally, the chapter describes the use of resources that practitioners may consult when determining the empirical basis for intervention strategies.
Peer-Mediated Interventions
Authors: Dart Evan H. , McKinley Lauren E. , Helbig Kate A.
Published: April 2019

Peer-mediated interventions reduce teacher implementation demand by capitalizing on the abundance of students within school settings who may be trained to function as interventionists. Recent meta-analyses have identified peer-mediated interventions as empirically based for addressing challenging behaviors in students. This chapter describes various types of peer-mediated interventions that may be utilized to address student behavior. Specifically, peer management and peer modeling are introduced and described in order to provide practitioners with alternative behavior intervention options within Tier II of an MTSS framework. Additionally, this chapter provides practitioners with a framework for identifying student interventionists and describes practical and ethical issues that are unique to peer-mediated behavioral interventions.
Irritability in Mood and Anxiety Disorders
Authors: Vidal-Ribas Belil Pablo , Stringaris Argyris
Published: April 2019

Irritability is common in children and adolescents presenting with mood and anxiety disorders and was recently introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a diagnostic category under the name of disruptive mood dysregulation disorder (DMDD). The aim of this chapter is to describe the distinct phenomenology, epidemiology, and correlates of irritability in the context of bipolar disorder, DMDD, depression, and anxiety disorders. The course of irritability is episodic in bipolar disorder and depression and is commonly accompanied by elated and depressed mood, respectively. In contrast, the irritability seen in DMDD is chronic and recurrent. In anxiety disorders, the experience of irritability is usually related to the presence of the feared situation. Regardless of these differences, irritability seems to be associated with higher rates of comorbidity and greater functional impairment and may need attention in its own right.
Rehabilitating and (Re-)Training the Injured Brain
Authors: Raz Amir , Rabipour Sheida
Published: April 2019

“Rehabilitating and (Re-)Training the Injured Brain” features approaches to brain training that aim to rehabilitate or remediate cognitive functions in acquired brain injury. It looks at the different approaches based on the type of injury and any additional benefits that may occur. The chapter sketches out methods to restore typical function by activating or stimulating relevant neural networks. Such techniques may help to overcome challenges related to rehabilitation using tools such as neural imaging and non-invasive stimulation. The focus of this chapter is on scientific research and empirical findings, but historical and cultural contexts that shroud these technological and clinical developments are also highlighted.
Molecular Evolution in Large Steps—Codon Substitutions under Positive Selection
Authors: Chen Qingjian , He Ziwen , Lan Ao , Shen Xu , Wen Haijun , Wu Chung-I
Published: April 2019

Molecular evolution is believed to proceed in small steps. The step size can be defined by a distance reflecting physico-chemical disparities between amino acid (AA) pairs that can be exchanged by single 1-bp mutations. We show that AA substitution rates are strongly and negatively correlated with this distance but only when positive selection is relatively weak. We use the McDonald and Kreitman test to separate the influences of positive and negative selection. While negative selection is indeed stronger on AA substitutions generating larger changes in chemical properties of AAs, positive selection operates by different rules. For 65 of the 75 possible pairs, positive selection is comparable in strength regardless of AA distance. However, the ten pairs under the strongest positive selection all exhibit large leaps in chemical properties. Five of the ten pairs are shared between Drosophila and Hominoids, thus hinting at a common but modest biochemical basis of adaptation across taxa. The hypothesis that adaptive changes often take large functional steps will need to be extensively tested. If validated, molecular models will need to better integrate positive and negative selection in the search for adaptive signal.
Increased mortality risk associated with serum sodium variations and borderline hypo- and hypernatremia in hospitalized adults
Authors: Thongprayoon Charat , Cheungpasitporn Wisit , Yap John Q , Qian Qi
Published: April 2019

Background

This study aimed to evaluate short-term and long-term mortalities in a cohort of unselected hospitalized patients with serum sodium concentration ([Na+]) variations within and outside of reference range.

Methods

All adult patients admitted to the Mayo Clinic, Rochester, MN, USA from January 2011 to December 2013 (n = 147358) were retrospectively screened. Unique patients admitted during the study period were examined. The main exposure was serum [Na+] variation. Outcome measures were hospital and 1-year all-cause mortalities.

Results

A total of 60944 patients, mean age 63 ± 17 years, were studied. On admission, 17% (n = 10066) and 1.4% (n = 852) had hypo- and hypernatremia, respectively. During the hospital stay, 11044 and 4128 developed hypo- and hypernatremia, respectively, accounting for 52.3 and 82.9% of the total hypo- and hypernatremic patients. Serum [Na+] variations of ≥6 mEq/L occurred in 40.6% (n = 24 740) of the 60 944 patients and were significantly associated with hospital and 1-year mortalities after adjusting potential confounders (including demographics, comorbidities, estimated glomerular filtration rate, admission serum [Na+], number of [Na+] measurements and length of hospital stay). Adjusted odds ratios for hospital and 1-year mortalities increased with increasing [Na+] variations in a dose-dependent manner, from 1.47 to 5.48 (all 95% confidence intervals >1.0). Moreover, in fully adjusted models, [Na+] variations (≥6 mEq/L) within the reference range (135–145 mEq/L) or borderline hypo- or hypernatremia (133–137 and 143–147 mEq/L, respectively) compared with 138–142 mEq/L were associated with increased hospital and 1-year mortalities.

Conclusion

In hospitalized adults, [Na+] fluctuation (≥6 mEq/L) irrespective of admission [Na+] and borderline hypo- or hypernatremia are independent predictors of progressively increasing short- and long-term mortality burdens.
Inequality and its discontents
Authors: Nolan Brian , Valenzuela Luis
Published: April 2019

Inequality in the distribution of income and wealth has come to the fore as a core concern across the industrialized world. Here we examine what has happened to income inequality across the rich countries in recent decades. We discuss the range of factors that appear to be driving inequality upwards, notably the role of technological change, globalization, and national institutions and policies. We look at how rising inequality might undermine economic growth and squeeze the middle, and assess the extent to which it has actually done so. We assess whether rising inequality is associated with worsening outcomes and inequalities across various social domains. Finally, we review emerging evidence on the role that rising inequality may be playing in the ‘revolt of the angry’ and rise of populism.
Explaining local variation in referrals from health services to children’s social care in England 2013–16: a study using ‘children in need’ administrative data
Authors: Emmott E H , Mc Grath-Lone L , Harron K , Woodman J
Published: April 2019

Background

Referral rates from Health service to Children’s Social Care (CSC) services vary across England. In 2019, the National Audit Office (re)iterated the urgent need to understand the drivers of such variation.

Methods

Using administrative data (Children in Need Census, 2013–16), we calculated annual referral rates from Health to CSC services (Health referral rate) by Local Authority (LA) areas. We used multilevel linear regression to investigate the relationship between age-adjusted Health referral rates and local need (demand factors) and local practice/systems (supply factors). We present a tool to compare unadjusted and adjusted LA rates.

Results

There was high LA variation in Health referral rates, particularly for infants (mean = 29.0/1000 children < 1 y; range = 6.5–101.8; sd = 12.4). LA variation persisted after age-adjustment. Child poverty (local need) and overall referral rate (local practice/systems) explained 60% of variation in age-adjusted Health referral rates. Overall referral rate was the strongest predictor. Adjusted referral rates were substantially different from unadjusted rates. After adjustment, 57.7% of LAs had higher/lower Health referral rates than expected.

Conclusions

While higher levels of local need are associated with higher Health referrals, some areas have high Health referrals irrespective of local need. Our tool demonstrates the benefits of using adjusted rates to compare LAs.
Association of smokeless tobacco and cerebrovascular accident: a systematic review and meta-analysis of global data
Authors: Gupta R , Gupta S , Sharma S , Sinha D N , Mehrotra R
Published: April 2019

Background

The association of smokeless tobacco (SLT) with stroke has been dealt with in only a few reviews. The present meta-analysis aims to present the updated comprehensive summary risk of stroke in adult SLT users along with sub group analysis.

Methods

A systematic literature search for articles evaluating risk of stroke in SLT users was conducted. The study characteristics and risk estimates were extracted independently by two authors (RG and SG). Random-effect model was used to estimate the summary relative risks.

Results

The overall risk of stroke in SLT users was found to be significantly higher (1.17, 95% CI 1.04–1.30) compared to non-users, especially for users in Southeast Asian region. The results remained unchanged even after strict adjustment for smoking (1.18, 95% CI 1.04–1.32). SLT users had 1.34 times or 13.4% higher risk of fatal stroke, though risk of nonfatal stroke was not enhanced. Significantly higher risk of stroke was seen in users of chewing tobacco (1.35, 95% CI 1.20–1.50) in comparison to non-chewers. Gender-based analysis showed enhanced risk of fatal stroke in both male and female users. SLT-attributable fraction of fatal stroke was highest for India at 14.8%.

Conclusion

The significant higher risk of stroke with SLT use, even after adjustment for smoking, emphasizes the imperative need to include SLT cessation advice for control and prevention of stroke.
Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder
Authors: Sterpenich Virginie , Vidal Sonia , Hofmeister Jeremy , Michalopoulos Giorgio , Bancila Victor , Warrot Delphine , Dayer Alexandre , Desseilles Martin , Aubry Jean-Michel , Kosel Markus , Schwartz Sophie , Vutskits Laszlo
Published: April 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression.

Methods

Ten adult patients with a Montgomery–Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients’ performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration.

Results

A significant correlation (R
2 = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area.

Conclusions

Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.
What is the Status? A Systematic Review of Nutritional Status Research in Total Joint Arthroplasty
Authors: Carli Alberto V. , Polascik Breanna A. , Stelmaszczyk Kelly , Haas Steven B.
Published: April 2019

Malnutrition has been previously associated with impaired wound healing, slower locomotion, and poorer outcomes following elective surgery. Although academic societies dedicated to perioperative recovery have published evidence-based guidelines for malnutrition, no consensus exists within orthopedics for screening and treating malnutrition in patients undergoing total joint arthroplasty (TJA). Following PRISMA guidelines, we performed a systematic review to determine: (1) how is malnutrition defined; (2) what is the prevalence of malnutrition among patients with TJA; (3) what perioperative complications are associated with malnutrition; (4) what strategies are successful in managing malnourished patients with TJA. Eight hundred ninety-five articles were identified in the literature, with 53 fulfilling criteria for analysis. Albumin <3.5 g/dL was the most commonly used parameter to define malnutrition. Total lymphocyte count (<1500 cell/mm3) and vitamin D (<20 to <12 ng/mL) were the second most commonly used parameters. Prevalence of malnutrition tended to be under 15% of primary patients with TJA in studies with over 10,000 patients. Morbidly obese patients and patients undergoing revision TJA were found to have significantly higher rates of malnutrition. Significant associations were found with malnutrition before TJA and higher rates of postoperative length of stay, readmission, reoperation, surgical site infection, and mortality. Malnutrition and obesity were not consistently found to have a synergistic effect on complication rates. To date, no formal preoperative treatments of malnourished patients with TJA have been studied. Protein supplementation has been shown to reduced length of stay in 3 TJA studies, but supplementation strategies varied and study patients were well nourished.