bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic memory with a switchable reference layer
Authors: Khvalkovskiy A. V. , Mikhailov A. P. , Leshchiner D. R. , Apalkov D.
Published: October 2018

Spin-Transfer-Torque Magnetic Random Access Memory (STT-MRAM) is a memory which has bit cells made of magnetic tunnel junctions (MTJs), which comprise a storage switchable magnetic layer (“free layer”) and, typically, one thin insulating barrier and one stable magnetic layer providing reference spin polarization for read and write operations (“reference layer”). STT-MRAM may compete with conventional dynamic and static RAM on technological nodes below 22 nm, if its switching current is reduced. This goal may be achieved for MTJ, which has two insulating barriers and reference layers. Building such a double-barrier MTJ, however, faces tremendous material challenges. In this work, a new double-barrier MTJ design with a switchable reference layer is introduced. We show that its efficiency is similar to its counterpart with stable reference layers, but it is much easier to be built.
Effect of boron addition in modulating the optoelectronic properties of undoped and Al-doped ZnO thin films
Authors: Singh Ajay , Panda Emila
Published: October 2018

Designing a transparent conductor for specific applications may require fundamental understanding of its microstructure and thus correlated optoelectronic properties with respect to a number of experimental parameters. To this end, the present study introduced varying concentrations of boron into the undoped and the Al-doped ZnO films by using co-deposition route in RF magnetron sputtering on soda lime glass substrates. A wide range of experimental techniques are then used to characterize these films. The films are found to demonstrate a high optical transparency of >83% and showed blue shift as a result of boron doping with Eg being as high as 3.98 eV. For the B3+-doped ZnO films, an increase in carrier concentration with increasing boron content is related to the cumulative effects of increased boron substitution in the zinc lattice positions and an increase in the intrinsic shallow donor level defects, caused by zinc interstitials and oxygen vacancies. An inverse effect is seen for the (B3+, Al3+)-doped ZnO films with increasing boron introduction, caused by reduced Al substitution in zinc lattice positions because of higher B–O bond strength as well as reduced doping efficiencies of B3+ and/or Al3+ ions due to decreasing crystallinity in these films. Finally, very high boron content in both these films is found to develop B2O3 and/or B7O phases, thereby not contributing entirely to the carrier generation and also reducing the carrier mobility of these films.
Passive bistatic radar using digital video broadcasting–terrestrial receivers as general-purpose software-defined radio receivers
Authors: Feng Weike , Friedt Jean-Michel , Cherniak Grigory , Sato Motoyuki
Published: October 2018

We investigate the use of low-cost digital video broadcasting-terrestrial (DVB-T) receivers as general-purpose software-defined radio (SDR) receivers for passive bistatic radar (PBR) applications. Two DVB-T receivers are synchronized using a common clock to perform coherent measurements. By exploiting the direct-path signal in the surveillance channel, we use the cross-correlation process to estimate the time offset between the data streams of reference and surveillance channels caused by the universal serial bus communication. We demonstrate the detection of static and moving targets as well as short-range targets, including a landing airplane at 8 km, multiple ships with different velocities, and vehicles within 20 m from the receiver acquiring at a 2 MHz bandwidth, by using Japan’s Integrated Services Digital Broadcasting Terrestrial digital TeleVision (TV) signal broadcast. We also propose to improve the range resolution of the designed PBR system by combining multiple SDR receivers tuned to different carrier frequencies. The designed system and proposed method can be used for various applications, such as airplane navigation, harbor protection, and traffic density monitoring.
Electronic structure and intramolecular interactions in three methoxyphenol isomers
Authors: Islam Shawkat , Ganesan Aravindhan , Auchettl Rebecca , Plekan Oksana , Acres Robert G. , Wang Feng , Prince Kevin C.
Published: October 2018

Electronic structures and intramolecular interactions of three methoxyphenol positional isomers and their rotamers have been studied using core X-ray photoelectron spectroscopy and quantum mechanical calculations. The structural calculations are benchmarked against published calculations of enthalpy of formation and rotational constants, and published experimental data. The good agreement obtained confirms the accuracy of the results. A single rotamer of each isomer was then selected and the C 1s photoelectron spectra calculated and compared with experiment. Good agreement is obtained, and the calculations were extended to investigate the effects of conformation. For 3-methoxyphenol, the difference in the C 1s binding energy of the conformers is small, <0.15 eV. For 2-methoxyphenol, whose ground state includes an OH⋯OCH3 hydrogen bond, the higher energy rotamers show the largest shifts for the methyl carbon atom, whereas the ring carbon bonded to OH hardly shifts The theoretical differences in core level energies of the two rotamers of 4-MP are still smaller, <0.05 eV. By comparing calculations neglecting or including final state relaxation upon ionization, the relaxation energy of the phenyl carbons in all isomers is found to be ∼0.5 eV, while that of the methyl groups is ∼1.3 eV.
Temperature- and doping-dependent nanoscale Schottky barrier height at the Au/Nb:SrTiO3 interface
Authors: Buzio R. , Gerbi A. , Bellingeri E. , Marré D.
Published: October 2018

We use ballistic electron emission microscopy to investigate prototypical Au/Nb-doped SrTiO3 (NSTO) Schottky barrier diodes for different temperatures and doping levels. To this end, ultrathin Au overlayers are thermally evaporated onto TiO2-terminated NSTO single crystal substrates. We show that at room temperature, regardless of the nominal doping, rectification is controlled by a spatially inhomogeneous Schottky barrier height (SBH), which varies on a length scale of tens of nanometers according to a Gaussian distribution with a mean value of 1.29–1.34 eV and the standard deviation in the range of 80–100 meV. At lower temperatures, however, doping effects become relevant. In particular, junctions with a low Nb content of 0.01 and 0.05 wt. % show an ∼300 meV decrease in the mean SBH from room temperature to 80 K, which can be explained by an electrostatic analysis assuming a temperature-dependent dielectric permittivity for NSTO. In contrast, this model fails to predict the weaker temperature dependence of SBH for junctions based on 0.5 wt. % NSTO. Our nanoscale investigation demands to reassess conventional models for the NSTO polarizability in high-intensity electric fields. Furthermore, it contributes to the comprehension and prediction of transport in metal/SrTiO3 junctions and devices.
Long noncoding RNA
SYISL
regulates myogenesis by interacting with polycomb repressive complex 2
Authors: Jin Jian Jun , Lv Wei , Xia Pan , Xu Zai Yan , Zheng An Dai , Wang Xiao Jing , Wang Shan Shan , Zeng Rui , Luo Hong Mei , Li Guo Liang , Zuo Bo
Published: October 2018

Significance

While numerous long noncoding RNAs (lncRNAs) have been identified in muscle, most of their roles in myogenesis remain unclear, and many more lncRNAs have yet to be identified. In this study, we identified an intronic lncRNA,
SYISL
(
SYNPO2
intron sense-overlapping lncRNA), which is highly expressed in muscle and interacts directly with polycomb repressive complex 2 (PRC2) to repress muscle development. The results reveal that
SYISL
acts as a regulatory RNA in PRC2-mediated myogenesis.
Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis
Authors: Krishnan Siddharth , Prise Ian E. , Wemyss Kelly , Schenck Louis P. , Bridgeman Hayley M. , McClure Flora A. , Zangerle-Murray Tamsin , O’Boyle Conor , Barbera Thomas A. , Mahmood Faiza , Bowdish Dawn M. E. , Zaiss Dietmar M. W. , Grainger John R. , Konkel Joanne E.
Published: October 2018

γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of
tcrδ
−/−
mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis.
Notch2-dependent DC2s mediate splenic germinal center responses
Authors: Briseño Carlos G. , Satpathy Ansuman T. , Davidson Jesse T. , Ferris Stephen T. , Durai Vivek , Bagadia Prachi , O’Connor Kevin W. , Theisen Derek J. , Murphy Theresa L. , Murphy Kenneth M.
Published: October 2018

CD4
+
T follicular helper (T
FH
) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for
Notch2
-dependent cDC2s, but not
Batf3
-dependent cDC1s or
Klf4
-dependent cDC2s, in promoting T
FH
and GC B cell formation in response to sheep red blood cells and inactivated
Listeria monocytogenes
. This effect was mediated independent of
Il2ra
and several
Notch2
-dependent genes expressed in cDC2s, including
Stat4
and
Havcr2
. Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation of MHC class II-restricted antigens, limiting the strength of CD4 T cell activation. Together, these results demonstrate a nonredundant role for the
Notch2
-dependent cDC2 subset in supporting humoral immune responses.
Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1
Authors: Li Yang , Fu Tian-Min , Lu Alvin , Witt Kristen , Ruan Jianbin , Shen Chen , Wu Hao
Published: October 2018

Significance

Inflammasomes are cytosolic protein complexes that detect the presence of pathogens and damages to elicit immune responses, and dysregulation in inflammasome signaling is associated with many human diseases. As the unified downstream effector of canonical inflammasomes, caspase-1 is recruited though CARD–CARD interactions with the adaptor proteins ASC or NLRC4. We have determined the cryo-EM structures of ASC CARD and NLRC4 CARD filaments. Using multidisciplinary methods, we reveal a common mechanism of caspase-1 CARD nucleation, assembly, and activation by equivalent assembly patterns in ASC and NLRC4. Collectively, our data provide insights into inflammasome assembly and activation and afford structural platforms for modulating these CARD–CARD interactions in potential therapeutic applications.
Dimensions of variation across Internet registers
Authors: Berber Sardinha Tony
Published: October 2018

This paper presents a study that sought to identify the dimensions of variation underlying a corpus of Internet texts, usingBiber’s (1988)multi-dimensional (MD) analysis framework. The corpus was compiled following the method proposed byBiber (1993), according to which the size of each register subcorpus should be determined based on the linguistic variation across the texts. The corpus was tagged using theBiber Taggerand the features were counted and submitted to a factor analysis, which suggested three factors. The factors were interpreted as three dimensions of variation: involved, interactive discourse versus informational focus; expression of stance: interactional evidentiality; and expression of stance: interactional affect. The amount of register variation captured by the register distinctions on the dimensions ranged from 8.7% to 57.1%. Dimension 1 corroborate the oral/involved versus literate/informational distinction defined in previous MD studies of non-Internet registers, whereas Dimensions 2 and 3 highlight the important role played by stance in social media.
State-led security responses and violent extremism: a comparative analysis of Libya, Egypt and Tunisia
Authors: Ardovini Lucia
Published: October 2018

This article investigates the link between the deterioration of state-society relations and the increase in state-sponsored violence in the MENA region in the aftermath of the Arab Uprisings. It does so to address the question of whether state-led security responses are directly related to the perceived proliferation of violent extremism networks. Relying on the comparative analysis of Libya, Egypt and Tunisia, the article argues that together with the escalation of security responses, worsening socio-economic conditions and the recurrent imposition of Emergency Laws indeed lead to the proliferation of violent extremism networks.
Genomic index selection provides a pragmatic framework for setting and refining multi-objective breeding targets in Miscanthus
Authors: Slavov Gancho T , Davey Christopher L , Bosch Maurice , Robson Paul R H , Donnison Iain S , Mackay Ian J
Published: October 2018

Background

Miscanthus has potential as a biomass crop but the development of varieties that are consistently superior to the natural hybrid M. × giganteus has been challenging, presumably because of strong G × E interactions and poor knowledge of the complex genetic architectures of traits underlying biomass productivity and climatic adaptation. While linkage and association mapping studies are starting to generate long lists of candidate regions and even individual genes, it seems unlikely that this information can be translated into effective marker-assisted selection for the needs of breeding programmes. Genomic selection has emerged as a viable alternative, and prediction accuracies are moderate across a range of phenological and morphometric traits in Miscanthus, though relatively low for biomass yield per se.

Methods

We have previously proposed a combination of index selection and genomic prediction as a way of overcoming the limitations imposed by the inherent complexity of biomass yield. Here we extend this approach and illustrate its potential to achieve multiple breeding targets simultaneously, in the absence of a priori knowledge about their relative economic importance, while also monitoring correlated selection responses for non-target traits. We evaluate two hypothetical scenarios of increasing biomass yield by 20 % within a single round of selection. In the first scenario, this is achieved in combination with delaying flowering by 44 d (roughly 20 %), whereas, in the second, increased yield is targeted jointly with reduced lignin (–5 %) and increased cellulose (+5 %) content, relative to current average levels in the breeding population.

Key Results

In both scenarios, the objectives were achieved efficiently (selection intensities corresponding to keeping the best 20 and 4 % of genotypes, respectively). However, the outcomes were strikingly different in terms of correlated responses, and the relative economic values (i.e. value per unit of change in each trait compared with that for biomass yield) of secondary traits included in selection indices varied considerably.

Conclusions

Although these calculations rely on multiple assumptions, they highlight the need to evaluate breeding objectives and explicitly consider correlated responses in silico, prior to committing extensive resources. The proposed approach is broadly applicable for this purpose and can readily incorporate high-throughput phenotyping data as part of integrated breeding platforms.
Microglial phenotypes in the human epileptic temporal lobe
Authors: Morin-Brureau Mélanie , Milior Giampaolo , Royer Juliette , Chali Farah , Le Duigou Caroline , Savary Etienne , Blugeon Corinne , Jourdren Laurent , Akbar David , Dupont Sophie , Navarro Vincent , Baulac Michel , Bielle Franck , Mathon Bertrand , Clemenceau Stéphane , Miles Richard
Published: October 2018

Using transcriptomics, anatomical studies, imaging and ELISA, Morin-Brureau et al. examine microglia in patients with temporal lobe epilepsies. In highly sclerotic regions such as CA1, the anti-inflammatory cytokine IL-10 regulates microglial phenotype. Seizures induce a transient microglial phenotype associated with secretion of inflammatory cytokines including human CXCL8.
PiGx: reproducible genomics analysis pipelines with GNU Guix
Authors: Wurmus Ricardo , Uyar Bora , Osberg Brendan , Franke Vedran , Gosdschan Alexander , Wreczycka Katarzyna , Ronen Jonathan , Akalin Altuna
Published: October 2018

In bioinformatics, as well as other computationally intensive research fields, there is a need for workflows that can reliably produce consistent output, from known sources, independent of the software environment or configuration settings of the machine on which they are executed. Indeed, this is essential for controlled comparison between different observations and for the wider dissemination of workflows. However, providing this type of reproducibility and traceability is often complicated by the need to accommodate the myriad dependencies included in a larger body of software, each of which generally comes in various versions. Moreover, in many fields (bioinformatics being a prime example), these versions are subject to continual change due to rapidly evolving technologies, further complicating problems related to reproducibility. Here, we propose a principled approach for building analysis pipelines and managing their dependencies with GNU Guix. As a case study to demonstrate the utility of our approach, we present a set of highly reproducible pipelines called PiGx for the analysis of RNA sequencing, chromatin immunoprecipitation sequencing, bisulfite-treated DNA sequencing, and single-cell resolution RNA sequencing. All pipelines process raw experimental data and generate reports containing publication-ready plots and figures, with interactive report elements and standard observables. Users may install these highly reproducible packages and apply them to their own datasets without any special computational expertise beyond the use of the command line. We hope such a toolkit will provide immediate benefit to laboratory workers wishing to process their own datasets or bioinformaticians seeking to automate all, or parts of, their analyses. In the long term, we hope our approach to reproducibility will serve as a blueprint for reproducible workflows in other areas. Our pipelines, along with their corresponding documentation and sample reports, are available at http://bioinformatics.mdc-berlin.de/pigx
Helicobacter pylori induces intracellular galectin-8 aggregation around damaged lysosomes within gastric epithelial cells in a host O-glycan-dependent manner
Authors: Li Fang-Yen , Weng I-Chun , Lin Chun-Hung , Kao Mou-Chieh , Wu Ming-Shiang , Chen Huan-Yuan , Liu Fu-Tong
Published: October 2018

Galectin-8, a beta-galactoside-binding lectin, is upregulated in the gastric tissues of rhesus macaques infected with Helicobacter pylori. In this study, we found that H. pylori infection triggers intracellular galectin-8 aggregation in human-derived AGS gastric epithelial cells, and that these aggregates colocalize with lysosomes. Notably, this aggregation is markedly reduced following the attenuation of host O-glycan processing. This indicates that H. pylori infection induces lysosomal damage, which in turn results in the accumulation of cytosolic galectin-8 around damaged lysosomes through the recognition of exposed vacuolar host O-glycans. H. pylori-induced galectin-8 aggregates also colocalize with autophagosomes, and galectin-8 ablation reduces the activation of autophagy by H. pylori. This suggests that galectin-8 aggregates may enhance autophagy activity in infected cells. We also observed that both autophagy and NDP52, an autophagy adapter, contribute to the augmentation of galectin-8 aggregation by H. pylori. Additionally, vacuolating cytotoxin A, a secreted H. pylori cytotoxin, may contribute to the increased galectin-8 aggregation and elevated autophagy response in infected cells. Collectively, these results suggest that H. pylori promotes intracellular galectin-8 aggregation, and that galectin-8 aggregation and autophagy may reciprocally regulate each other during infection.
Explaining Mechanisms That Influence Smoke-Free Implementation at the Local Level: A Realist Review of Smoking Bans
Authors: Mlinarić Martin , Hoffmann Laura , Kunst Anton E , Schreuders Michael , Willemsen Marc C , Moor Irene , Richter Matthias
Published: October 2018

Introduction

While studies have been undertaken to understand the adoption of outdoor and indoor smoking bans, not much is known about why implementation of smoke-free (SF) environments differs at local levels. As most European countries remain at the level of indoor bans, we aim to translate existing evidence into practical recommendations on how to improve SF (outdoor) implementation within European municipalities.

Methods

We applied six methodological steps of a realist review consistent with the RAMESES publication standards for realist syntheses. Literature search was conducted in PubMed/MEDLINE and Web of Science. In total, 3829 references were screened, of which 43 were synthesized. Studies dating from 2004 to 2015 with rigor evidence of SF implementation at the local level were selected. Implementation outcomes were SF enforcement, monitoring, nonsmoking compliance, and public support in cities.

Results

The explanatory realist framework links four innovation stages with three context-mechanism-outcome (CMO)configurations. We identified “triggering trust,” “increasing priorities,” and “limiting opposing interests” as underlying mechanisms, when (1) establishing, (2) developing, (3) contesting, and (4) implementing local smoking bans. The CMO propositions (CMOs) support practical recommendations, such as (1) providing authorities with local data when establishing and developing bans, (2) developing long-term strategies and implementing state-funded SF programs to prioritize sustained enforcement, and (3) limiting opposing interests through the use of the child protection frame.

Conclusions

This is the first realist review on the implementation of SF enviroments at the local level. The process-oriented theory explains how and why CMOs determine SF development in cities and municipalities from planning until implementation.

Implications

In 2015, only 16% of the world’s population lived under the jurisdiction of comprehensive SF laws. The findings of this realist review are useful to implement WHO goals of the Framework Convention on Tobacco Control (FCTC) and specifically SF environments at more local levels and to adjust them to specific contextual circumstances. This paper unpacks three mechanisms that could be triggered by SF strategies developed at local levels and that can result in improved policy implementation. Such evidence is needed to enhance SF strategies at the level of cities and municipalities and to achieve WHO “Healthy Cities Network” objectives.
E-cigarette Usage Is Associated With Increased Past-12-Month Quit Attempts and Successful Smoking Cessation in Two US Population–Based Surveys
Authors: Johnson Linda , Ma Yinjiao , Fisher Sherri L , Ramsey Alex T , Chen Li-Shiun , Hartz Sarah M , Culverhouse Robert C , Grucza Richard A , Saccone Nancy L , Baker Timothy B , Bierut Laura J
Published: October 2018

Introduction

We examined past-12-month quit attempts and smoking cessation from 2006 to 2016 while accounting for demographic shifts in the US population. In addition, we sought to understand whether the current use of electronic cigarettes was associated with a change in past-12-month quit attempts and successful smoking cessation at the population level.

Methods

We analyzed data from 25- to 44-year-olds from the National Health Interview Survey (NHIS) from 2006 to 2016 (N = 26,354) and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS) in 2006–2007, 2010–2011, and 2014–2015 (N = 33,627). Data on e-cigarette use were available in the 2014–2016 NHIS and 2014–2015 TUS-CPS surveys.

Results

Past-12-month quit attempts and smoking cessation increased in recent years compared with 2006. Current e-cigarette use was associated with higher quit attempts (adjusted odds ratio [aOR] = 2.29, 95% confidence interval [CI] = 1.87 to 2.81, p < .001) and greater smoking cessation (aOR = 1.64, 95% CI = 1.21 to 2.21, p = .001) in the NHIS. Multivariable logistic regression of the TUS-CPS data showed that current e-cigarette use was similarly significantly associated with increased past-12-month quit attempts and smoking cessation. Significant interactions were found for smoking frequency (everyday and some-day smoking) and current e-cigarette use for both outcomes (p < .0001) with the strongest positive effects seen in everyday smokers.

Conclusions

Compared with 2006, past-12-month quit attempts and smoking cessation increased among adults aged 25–44 in recent years. Current e-cigarette use was associated with increased past-12-month quit attempts and successful smoking cessation among established smokers. These findings are relevant to future tobacco policy decisions.

Implications

E-cigarettes were introduced into the US market over the past decade. During this period, past-12-month quit attempts and smoking cessation have increased among US adults aged 25–44. These trends are inconsistent with the hypothesis that e-cigarette use is delaying quit attempts and leading to decreased smoking cessation. In contrast, current e-cigarette use was associated with significantly higher past-12-month quit attempts and past-12-month cessation. These findings suggest that e-cigarette use contributes to a reduction in combustible cigarette use among established smokers.
Single-Screw Fixation Compared With Double Screw Fixation for Treatment of Medial Malleolar Fractures: A Prospective Randomized Trial
Authors: Buckley Richard , Kwek Ernest , Duffy Paul , Korley Robert , Puloski Shannon , Buckley Andrew , Martin Ryan , Rydberg Moller Emilia , Schneider Prism
Published: October 2018

Objectives:

To determine whether single or double screw (DS) fixation of medial malleolar fractures results in better long-term health outcomes.

Design:

Randomized clinical trial; sealed envelope technique.

Setting:

Level 1 Trauma Hospital at University of Calgary, Canada.

Patients:

One hundred forty patients were randomized to receive either 1 or 2 screws to reduce a medial malleolar fracture. Thirteen patients were excluded because of loss to follow-up (n = 127).

Intervention:

Surgical fixation of the medial malleolar fracture was performed using 1 or 2 stainless steel screws.

Main Outcome Measurements:

Primary outcome was comparison of physical functioning summary score on Short Form 36 questionnaires between patients in the 2 groups. Secondary objectives were to compare the Ankle Hindfoot Scale and operating room time. Clinical and radiographic assessment occurred at the time of injury and 2, 6 weeks, 3, 6, 12, and 24 months postoperatively.

Results:

Fourteen patients crossed over from the DS group to the single screw (SS) group based on intraoperative decisions by the surgeon (fragment too small for 2 screws), leaving the SS (n = 75) and DS groups (n = 52). There was no difference in the operating room time, SF36, or Ankle Hindfoot Scale at all follow-up time points.

Conclusions:

SS medial malleolar fixation provides an equally safe and effective method of fracture care as compared to DS fixation. Twenty percent of patients receiving 2 screws can be expected to crossover to receive SS fixation as a safer alternative.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Magnitude and Pace of Improvement in Performance of Hospitals Treating Mechanically Ventilated Children in the United States: Analysis From Two National Databases
Authors: Gupta Punkaj , Gossett Jeffrey M. , Rettiganti Mallikarjuna
Published: October 2018

Objectives:

To use two national databases to quantify the pace and magnitude of improvement in hospital performance (as measured by mortality) across hospitals caring for critically ill children in the United States.

Design:

We used empirical Bayes shrinkage estimators to obtain shrinkage estimators of observed/expected mortality ratios for each hospital assuming a Gamma Poisson posterior distribution. Revised mortality rates for each hospital were obtained from the shrunken incidence ratios.

Setting:

Pediatric Health Information System participating hospital and Kids’ Inpatient Database participating hospital.

Patients:

Patients less than or equal to 18 years old who received invasive mechanical ventilation during their hospital stay at a Pediatric Health Information System participating hospital (2005–2015) or a Kids’ Inpatient Database participating hospital (1997–2012) were included.

Interventions:

None.

Measurements and Main Results:

A total of 486,838 patients from 48 Pediatric Health Information System hospitals and 798,840 patients from 947 Kids’ Inpatient Database hospitals were included. For the Pediatric Health Information System hospitals, the median shrunken adjusted mortality decreased from 11.66% in 2005 to 7.11% in 2015; for the Kids’ Inpatient Database hospitals, it decreased from 5.79% in 1997 to 3.86% in 2012. By 2015, more than 95% of the Pediatric Health Information System hospitals performed better than or as well as the best 25% of the hospitals in 2005. By 2012, 33.7% of Kids’ Inpatient Database hospitals performed better than or as well as the best 25% of the hospitals in 1997.

Conclusions:

This study provides insight into the magnitude of improvement in patient mortality in hospitals caring for critically ill children in the United States. This study quantifies hospital performance in pediatric critical care over time, and it provides benchmarks against which individual hospitals can assess their own performance. In future pediatric epidemiologic studies, we should identify outcomes other than mortality to quantify improvement in hospital performance.
Variation in Case-Mix Adjusted Unplanned Pediatric Cardiac ICU Readmission Rates*
Authors: Smith Andrew H. , Anand Vijay , Banerjee Mousumi , Bates Katherine E. , Brunetti Marissa A. , Cooper David S. , Lehrich Jessica , Mistry Kshitij P. , Pasquali Sara K. , Shin Andrew Y. , Tabbutt Sarah , Gaies Michael
Published: October 2018

Objectives:

To identify modifiable factors leading to unplanned readmission and characterize differences in adjusted unplanned readmission rates across hospitals.

Design:

Retrospective cohort study using prospectively collected clinical registry data

Setting:

Pediatric Cardiac Critical Care Consortium clinical registry.

Patients:

Patients admitted to a pediatric cardiac ICU at Pediatric Cardiac Critical Care Consortium hospitals.

Interventions:

None.

Measurements and Main Results:

We examined pediatric cardiac ICU encounters in the Pediatric Cardiac Critical Care Consortium registry from October 2013 to March 2016. The primary outcomes were early (< 48 hr from pediatric cardiac ICU transfer) and late (2–7 d) unplanned readmission. Generalized logit models identified independent predictors of unplanned readmission. We then calculated observed-to-expected ratios of unplanned readmission and identified higher-than or lower-than-expected unplanned readmission rates for those with an observed-to-expected ratios greater than or less than 1, respectively, and a 95% CI that did not cross 1. Of 11,301 pediatric cardiac ICU encounters (16 hospitals), 62% were surgical, and 18% were neonates. There were 175 (1.6%) early unplanned readmission, and 300 (2.7%) late unplanned readmission, most commonly for respiratory (31%), or cardiac (28%) indications. In multivariable analysis, unique modifiable factors were associated with unplanned readmission. Although shorter time between discontinuation of vasoactive infusions and pediatric cardiac ICU transfer was associated with early unplanned readmission, nighttime discharge was independently associated with a greater likelihood of late unplanned readmission. Two hospitals had lower-than-expected unplanned readmission in both the early and late categories, whereas two other hospitals were higher-than-expected in both.

Conclusions:

This analysis demonstrated time from discontinuation of critical care therapies to pediatric cardiac ICU transfer as a significant, modifiable predictor of unplanned readmission. We identified two hospitals with lower-than-expected adjusted rates of both early and late unplanned readmission, suggesting that their systems are well designed to prevent unplanned readmission. This offers the possibility of disseminating best practices to other hospitals through collaborative learning.
Innate immune cell infiltration in melanoma metastases affects survival and is associated with BRAFV600E mutation status
Authors: Dabrosin Nina , Sloth Juul Karen , Bæhr Georgsen Jeanette , Andrup Simon , Schmidt Henrik , Steiniche Torben , Heide Øllegaard Trine , Bønnelykke Behrndtz Louise
Published: October 2018

Little is known about the infiltrative pattern of innate immune cells in primary melanoma compared with their paired metastases and in BRAFV600E-mutated tumors. Therefore, our aim was to characterize the inflammatory microenvironment in primary ulcerated and nonulcerated melanomas and paired metastases, to investigate the relation between inflammation and BRAFV600E mutation in primary melanoma and paired metastases, and to evaluate the effect of the analyzed biomarkers on melanoma-specific survival. A total of 385 primary tumors and 96 paired metastases were stained with immunohistochemistry for BRAFV600E, CD163+ macrophages, CD123+ plasmacytoid dendritic cells, CD66b+ neutrophils, and E-cadherin and estimated using objective computer-assisted image analysis. BRAFV600E was semiquantitatively scored as either present or absent. In metastases of nonulcerated melanomas, we observed higher neutrophil (P=0.02) and macrophage (P=0.01) numbers. In the metastases of ulcerated melanomas, we found a higher number of macrophages (P<0.0001). Increase in the neutrophil numbers in the metastases was associated with poor patient survival after first relapse (hazard ratio=1.19, 95% confidence interval: 1.03–1.38, P=0.02). BRAFV600E-positive primary tumors (P=0.02) and metastases (P=0.01) exhibited increased plasmacytoid dendritic cell numbers compared with BRAFV600E-negative tumors. Lastly, primary melanomas in men had higher neutrophil numbers than women (P≤0.0001), and men had worse melanoma-specific survival (hazard ratio=1.52, 95% confidence interval: 1.04–2.21, P=0.03). Our data show that melanoma metastases are densely infiltrated with neutrophils, which affects survival. Our results also highlight the importance of recognizing the presence of inflammatory cells in the metastases as a prognostic marker, and that they may potentially be used to improve the precision of immunotherapy and BRAFV600E targeted therapy.
Young Children With Gender Nonconforming Behaviors and Preferences
Authors: Reilly Marie , Desousa Vanessa , Garza-Flores Alexandra , Perrin Ellen C.
Published: October 2018

Background:

There is growing awareness and exposure in both the medical community and the lay media about the characteristics and complex needs of individuals who believe that their gender identity does not match their birth sex. Despite research and lay publications about teens with gender dysphoria and those who identify as transgender, little guidance is available regarding young (prepubertal) children with questions about their gender identity. Although many terms are used to describe these children, we have chosen to describe them as “gender nonconforming” (GNC).

Objective:

Primary care and developmental-behavioral pediatric providers are often the first professionals with whom young gender nonconforming children and their families discuss their concerns about their emerging gender identity. It is important, therefore, that pediatric providers be knowledgeable about the dilemmas, conflicts, and choices that are typical of these children and their families to guide them appropriately.

Overview:

In this special article, we present observations, informed by clinical experience, an emerging body of research, and a developmental-behavioral pediatric framework, of the complex needs of prepubertal gender nonconforming children and their families and an approach to their care. The article begins by outlining the cognitive and biological bases for gender identity development, as well as the natural history of gender nonconforming preferences and behaviors. It then sets the context for understanding the care of GNC children as an area in which developmentally sophisticated providers can play a crucial role in support of the complex developmental patterns and need for advocacy in multiple settings among these children.
Appropriate evaluation of postmenopausal bleeding
Authors: Goldstein Steven R.
Published: October 2018

In clinical practice, although only 3% to 7% of women with postmenopausal bleeding (PMB) will ultimately be found to have cancer, it is the clinician's responsibility to ensure that endometrial cancer is not present. The diagnostic evaluation of PMB has evolved greatly. This Practice Pearl addresses the appropriate evaluation of women with PMB.
Low pretreatment serum concentration of vitamin D at breast cancer diagnosis in postmenopausal women
Authors: Machado Murilo Renato Matos , de Sousa Almeida-Filho Benedito , De Luca Vespoli Heloisa , Schmitt Eneida Boteon , Nahas-Neto Jorge , Nahas Eliana A.P.
Published: October 2018

Objective:

The aim of the study was to evaluate the rate of and risk factors for low pretreatment vitamin D (VitD) levels in postmenopausal breast cancer (BC) women, compared with postmenopausal women without BC.

Methods:

A cross-sectional clinical study was conducted to compare 209 women with BC (case group) to 418 women without BC (control group), age range: 45 to 75 years. The case group consisted of women diagnosed with BC, amenorrhea ≥12 months, aged ≥45 years, without use of medication or clinical conditions that might interfere with VitD levels. The control group consisted of women with amenorrhea ≥12 months, aged ≥45 years, without BC. The groups were matched for age and time since menopause, at a case: control ratio of 1:2. Serum 25-hydroxyvitamin-D [25(OH)D] concentration was measured in all women 10 to 20 days after BC diagnosis and before the proposed treatment. Serum levels ≥30 ng/mL were defined as sufficient. The Student'sttest or gamma distribution, χ2test, and logistic regression (odds ratio, OR) were used for statistical analysis.

Results:

The BC group had a higher body mass index (BMI) and higher percentage of obesity than the control group (57.4% vs 40.2%,P < 0.0001). In addition, rates of insufficient (20-29 ng/mL) and deficient (<20 ng/mL) 25(OH)D levels were higher in BC patients than in controls (55.6% vs 49.3%,P = 0.039 and 26.2% vs 20.3%,P = 0.018), respectively. In risk analysis (adjusted for age, time since menopause, and BMI), BC patients had a 1.5-fold higher risk of developing low VitD levels (OR = 1.52, 95% CI, 1.04-2.22,P = 0.029) than women without BC.

Conclusions:

Postmenopausal women had an increased risk of VitD deficiency at the time of BC diagnosis, associated with a higher rate of obesity, than women of the same age group without cancer.
Adaptation and translation of the menopause-specific Utian Quality of Life (UQOL) scale to Yoruba language using middle-aged women attending a clinic in Nigeria
Authors: Aberi Obalowu Ismaila , Okebunor Odeigah Louis , Moradeyo Alabi Kola , Ademola Ayinmode Babatunde , Utian Wulf H.
Published: October 2018

Objective:

The main objective of the study is to translate and adapt the menopause-specific Utian Quality of Life (UQOL) scale to Yoruba, an indigenous Nigerian language, using middle-aged women attending a Family Medicine clinic in Nigeria.

Methods:

A total of 322 middle-aged Nigerian women at various menopausal stages were recruited for the study. Their menopausal status was categorized using the Monash Women's Health Program Menopausal Staging Algorithm into pre-, peri-, and postmenopausal groups. The UQOL Yoruba version (YUQOL), Menopause Rating Scale (MRS), and a semistructured sociodemographic questionnaire were interviewer-administered to the women. The collected data were analyzed using IBM SPSS version 21 software.

Results:

The overall scale and the four subscales of YUQOL all had acceptable internal consistency scores; they also demonstrated good construct and criterion validities, except the YUQOL sexual subscale had poor convergent validity (average variance extracted = 0.23).

Conclusions:

This study has validated the YUQOL as a psychometrically sound research instrument for measuring menopause-specific QOL among women undergoing menopausal transition. Its sexual subscale would, however, need to be further tested, preferably in sexually active menopausal women to fully confirm its true psychometric property.
Effect of high-intensity interval training on body composition and inflammatory markers in obese postmenopausal women: a randomized controlled trial
Authors: Nunes Paulo R.P. , Martins Fernanda M. , Souza Aletéia P. , Carneiro Marcelo A.S. , Orsatti Claudio L. , Michelin Márcia A. , Murta Eddie F.C. , de Oliveira Erick P. , Orsatti Fábio L.
Published: October 2018

Objectives:

This study tested whether high-intensity interval training is a time-efficient strategy for improving visceral adiposity tissue and inflammatory markers in obese postmenopausal women when compared with combined training. Moreover, we tested whether change in visceral adiposity tissue is associated with alterations in these inflammatory markers.

Methods:

Postmenopausal women were randomized in two groups: combined training (n = 13) and high-intensity interval training (n = 13). The combined training group performed 60 minutes of walking at 70% of maximum heart rate and resistance exercises at 70% of one repetition maximum. The high-intensity interval training group performed 28 minutes of high-intensity exercises (> 80% of maximum heart rate). Both groups trained three times a week for 12 weeks. Body composition and inflammatory markers were analyzed with dual-energy x-ray absorptiometry scanning and enzyme-linked immunosorbent assay, respectively.

Results:

All groups reduced body fat percentage (P = 0.026), visceral adiposity tissue (P = 0.027), leptin (P = 0.043), and increased interleukin (IL)-1 receptor antagonist (
P
 < 0.01). The high-intensity interval training group reduced visceral adiposity tissue (P = 0.021) in a greater magnitude and increased interleukin-6 (P = 0.037) level when compared with the combined training group. Moreover, the visceral adiposity tissue changes explained the changes in IL-6 (56%; P = 0.002) only in the high-intensity interval training group.

Conclusions:

These results suggest that high-intensity interval training is a time-efficient strategy for improving visceral adiposity tissue and inflammatory markers in obese postmenopausal women. Moreover, we observed that serum cytokine changes, at least in part, depend on visceral adiposity tissue alterations.
The Outpatient DIEP: Safety and Viability following a Modified Recovery Protocol
Authors: Martinez Carlos A. , Reis Scott M. , Rednam Rukmini , Boutros Sean G.
Published: October 2018

Background:

Breast reconstruction with autologous tissue is considered the current state-of-the-art choice following mastectomies, and the deep inferior epigastric perforator (DIEP) flap is often among the favored techniques. Commonly referred to patients as a combination between a tummy tuck and a breast augmentation, it significantly differs by the required expertise and long hospital stays. We present a series attesting to the feasibility and effectiveness of performing this type of reconstruction in an outpatient setting following our recovery protocol.

Methods:

Patients undergoing DIEP flap breast reconstruction followed a recovery protocol that included intraoperative local anesthesia, microfascial incision technique for DIEP harvest, double venous system drainage technique, rib and chest muscle preservation, and prophylactic anticoagulation agents.

Results:

Fourteen patients totaling 27 flaps underwent breast reconstruction following our protocol. All patients were discharged within the initial 23 hours, and no take-backs, partial, or total flap failures were recorded. A case of abdominal incision breakdown was seen in 1 patient during a postoperative visit, without evidence of frank infection. No further complications were observed in the 12-week average observation period.

Conclusion:

With the proper use of a microfascial incision, complemented by rib sparing and appropriate use of injectable anesthetics, routine breast reconstructions with the DIEP flap can be safely performed in an outpatient setting with discharge in the 23-hour window.
Endoscopic Sinus Surgery Associated with Rhinoseptoplasty: A Case-control Study
Authors: Marchica Paolo , Bassetto Franco , Vindigni Vincenzo , Galici Roberto , Dispenza Francesco , Gallina Salvatore , Speciale Riccardo
Published: October 2018

Objective:

To examine the difference between outcomes in the administration of concurrent endoscopic sinus surgery (ESS), septoplasty (SP), and rhinoplasty (RP) and concurrent ESS and SP in 1 single surgical session.

Methods:

Patients who underwent concurrent ESS and SP from September 2004 to July 2015 were identified. Furthermore, patients among them who underwent functional primary RP were selected. Subjects who had been administered concurrent ESS, SP, and RP (primary RP) were matched for sex, age, sinonasal surgical procedures for treatment of chronic rhinosinusitis with patients underwent concurrent ESS and SP, used as control subjects. A literature review was performed to find previous articles describing results of concurrent procedures among ESS, SP, and RP.

Results:

Twenty subjects, who underwent concurrent ESS, SP, and RP, were compared with a matched control group made of 20 patients who underwent concurrent ESS and SP, evaluating different postoperative outcomes (postoperative complications, postoperative improvement of respiratory symptoms, persistence of chronic rhinosinusitis symptoms 6 months to 1 year postoperative, need of revision surgery, satisfaction of the patient). ObtainedPvalues showed that there was no statistically significant difference (P> 0.05) as regards the different outcomes, except for postoperative complications, increased because of the invasiveness proper of RP (P< 0.05).

Conclusions:

Therefore, execution of concurrent ESS, SP, and RP seems to be safe and effective, and additional RP does not modify postoperative outcomes of concurrent ESS and SP except for a little increase of postoperative complications, even if most of them had low impact on result of procedures.