bluuebunny/crossref_metadata_2025 huggingface dataset:
MetS Risk Score: A Clear Scoring Model to Predict a 3-Year Risk for Metabolic Syndrome
Authors: Zou Tian-Tian , Zhou Yu-Jie , Zhou Xiao-Dong , Liu Wen-Yue , Van Poucke Sven , Wu Wen-Jun , Zheng Ji-Na , Gu Xue-Mei , Zhang Dong-Chu , Zheng Ming-Hua , Pan Xiao-Yan
Published: September 2018

Although several risk factors for metabolic syndrome (MetS) have been reported, there are few clinical scores that predict its incidence. Therefore, we created and validated a risk score for prediction of 3-year risk for MetS. Three-year follow-up data of 4395 initially MetS-free subjects, enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. Subjects at enrollment were randomly divided into the training and the validation cohort. Univariate and multivariate logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. The predictive performance of the model was tested by computing the area under the receiver operating characteristic curve (AUROC). Four independent predictors were chosen to construct the MetS risk score, including BMI (HR=1.906, 95% CI: 1.040–1.155), FPG (HR=1.507, 95% CI: 1.305–1.741), DBP (HR=1.061, 95% CI: 1.002–1.031), HDL-C (HR=0.539, 95% CI: 0.303–0.959). The model was created as –1.5 to 4 points, which demonstrated a considerable discrimination both in the training cohort (AUROC=0.674) and validation cohort (AUROC=0.690). Comparison of the observed with the estimated incidence of MetS revealed satisfactory precision. We developed and validated the MetS risk score with 4 risk factors to predict 3-year risk of MetS, useful for assessing the individual risk for MetS in medical practice.
Recent Applications of α-Carbonyl Sulfoxonium Ylides in Rhodium- and Iridium-Catalyzed C–H Functionalizations
Authors: Cheng Jiang , Wu Xiaopeng , Sun Song , Yu Jin-Tao
Published: September 2018

Sulfoxonium ylides are a special type of sulfur ylides that serve as new C1 or C2 synthons recently developed for use in C–H functionalization to access acylmethylated or cyclized compounds through the formation of metal carbene species. Many excellent works have reported the syntheses of various useful skeletons from these versatile synthons. These developments have not previously been completely investigated or reviewed. In this review, we summarize recent advances in the use of α-carbonyl sulfoxonium ylides in C–H functionalizations, including ortho-C–H acylmethylation reactions and ortho-C–H activation/cyclization reactions.

Table of Contents

1 Introduction

2
Ortho-C–H Acylmethylation Reactions

3
Ortho-C–H Activation/Cyclization Reactions

3.1
Ortho-C–H Activation/Cyclization of Anilines and Enamines

3.2
Ortho-C–H Activation/Cyclization of Azobenzenes

3.3
Ortho-C–H Activation/Cyclization of N-Methoxybenzamide

3.4
Ortho-C–H Activation/Cyclization of Imines

3.5
Ortho-C–H Activation/Cyclization of N-Azoloimines

3.6
Ortho-C–H Activation/Cyclization of Benzoylacetonitriles

3.7
Ortho-C–H Activation/Cyclization of Benzoyl Sulfoxonium Ylides

4 Conclusion
On the smoothness of the critical sets of the cylinder at spatial infinity in vacuum spacetimes
Authors: Paetz Tim-Torben
Published: September 2018

We analyze the appearance of logarithmic terms at the critical sets of Friedrich’s cylinder representation of spatial infinity. It is shown that if the radiation field vanishes at all orders at the critical sets, no logarithmic terms are produced in the formal expansions. Conversely, it is proved that, under the additional hypothesis that the spacetime has constant (ADM) mass aspect and vanishing dual (ADM) mass aspect [by which we mean the limit of the Bondi (dual) mass aspect on ℐ to the critical set], this condition is also necessary for a spacetime to admit a smooth conformal representation at the critical sets.
Crystal and electronic structural changes during annealing in severely deformed Si containing metastable phases formed by high-pressure torsion
Authors: Ikoma Yoshifumi , Chon Bumsoo , Yamasaki Terumasa , Takahashi Kazutoshi , Saito Katsuhiko , Guo Qixin , Horita Zenji
Published: September 2018

Single crystalline p- and n-type Si(100) wafers were severely deformed by high-pressure torsion (HPT) under a nominal pressure of 24 GPa. The HPT-processed samples consisted of metastable phases of body-centered-cubic Si-III and rhombohedral Si-XII, as well as diamond-cubic Si-I and amorphous phases. The photoemission spectroscopy using synchrotron radiation revealed that the valence band edge of the HPT-processed p- and n-type Si samples was located at ∼0.3 eV. Successive annealing in vacuum up to 200 °C led to the valence-band edge shift by ∼0.4 eV for both p- and n-type Si, and the disappearance of Si-III and Si-XII. These results indicated that the Si-III and Si-XII phases in the HPT-processed samples have smaller band gap than that of Si-I, and suggested that the valence-band edge shift after annealing is due to the mixture of Si-I and Si-IV phases in addition to the mid-gap pinning of the Fermi level.
Development of a spectroscopic diagnostic tool for electric field measurements in IShTAR (Ion cyclotron Sheath Test ARrangement)
Authors: Kostic A. , Dux R. , Crombé K. , Nikiforov A. , Ochoukov R. , Shesterikov I. , Martin E. H. , Noterdaeme J.-M.
Published: September 2018

IShTAR, Ion cyclotron Sheath Test ARrangement, is a linear device dedicated to the investigation of the edge plasma–ICRF (Ion Cyclotron Range of Frequencies) antenna interactions in tokamak edge-like conditions and serves as a platform for a diagnostic development for measuring the electric fields in the vicinity of ICRF antennas. We present here our progress in the development of an optical emission spectroscopy method for measuring the electric fields which concentrates on the changes in the helium spectral line profiles introduced by the external electrical field, i.e., the Stark effect. To be able to fully control the operating parameters, at the first stage of the study, the measurements are conducted on a planar electrode installed in the centre of the plasma column in IShTAR’s helicon plasma source. At the second stage, the measurements are performed in the vicinity of IShTAR’s ICRF antenna.
Bimolecular multistage diffusion-influenced chemical reactions proceeding from different sites in solutions. I. Rate constants
Authors: Doktorov Alexander B.
Published: September 2018

General matrix algebraic equations for calculating rate constants of multistage diffusion-influenced reactions (involving bimolecular exchange reactions as elementary stages) in liquid solutions that proceed from different active sites in the immediate vicinity of the contact of reactants have been obtained on the basis of the kinematic approximation developed by the authors earlier. The equations make it possible to express rate constants of any multistage multisite bimolecular reaction between non-identical reactants in terms of the defined reaction constants and stationary Green functions averaged over reaction sites and completely determined by molecular motion of reactants or their molecular groups. The asymptotic behavior of these rate constants as they attain their steady-state values on completion of the transient stage is established. It is shown that it coincides with the corresponding exact time asymptote. Calculations are made with some specific two-stage (three-channel) bimolecular reactions as an example.
Surface plasmon resonances in a branched silver nanorod
Authors: Fujiyoshi Yoshifumi , Kurata Hiroki
Published: September 2018

The properties of surface plasmon-polariton (SPP) resonance modes were investigated in a branched silver nanorod consisting of two nanorods using high energy resolution electron energy-loss spectroscopy (EELS) combined with scanning transmission electron microscopy. The experimental EELS maps of the SPP excitation showed a specific distribution depending on the resonance mode. The analytical formulas of the EELS signal and the resonance conditions for SPP resonance in the branched nanorod were derived by expanding the method reported for a one-dimensional straight resonator, and these were applied to interpret the experimental results. The SPP resonance in the branched nanorod can be attributed to Fabry-Perot type resonance that propagates in any of the three different resonance paths. It was also demonstrated that the modes of SPP resonance are changed by the position of the crossing point in the branched structure, which indicates that the combination of the lengths of the respective branches can be used to control the propagation path and the resonance energy of SPP waves in branched structures.
An angular-resolved multi-channel Thomson parabola spectrometer for laser-driven ion measurement
Authors: Zhang Yihang , Zhang Zhe , Zhu Baojun , Jiang Weiman , Cheng Lei , Zhao Lei , Zhang Xiaopeng , Zhao Xu , Yuan Xiaohui , Tong Bowei , Zhong Jiayong , He Shukai , Lu Feng , Wu Yuchi , Zhou Weimin , Zhang Faqiang , Zhou Kainan , Xie Na , Huang Zheng , Gu Yuqiu , Weng Suming , Xu Miaohua , Li Yingjun , Li Yutong
Published: September 2018

A multi-channel Thomson parabola spectrometer was designed and employed to diagnose ion beams driven by intense laser pulses. Angular-resolved energy spectra for different ion species can be measured in a single shot. It contains parallel dipole magnets and wedged electrodes to fit ion dispersion of different charge-to-mass ratios. The diameter and separation of the entrance pinhole channels were designed properly to provide sufficient resolution and avoid overlapping of dispersed ion beams. To obtain a precise energy spectral resolving, three-dimensional distributions of the electric and magnetic fields were simulated. Experimental measurement of energy-dependent angular distributions of target normal sheath accelerated protons and deuterons was demonstrated. This novel compact design provides a comprehensive characterization for ion beams.
New software protocols for enabling laboratory based temporal CT
Authors: Gajjar Parmesh , Jørgensen Jakob S. , Godinho Jose R. A. , Johnson Chris G. , Ramsey Andrew , Withers Philip J.
Published: September 2018

Temporal micro-computed tomography (CT) allows the non-destructive quantification of processes that are evolving over time in 3D. Despite the increasing popularity of temporal CT, the practical implementation and optimisation can be difficult. Here, we present new software protocols that enable temporal CT using commercial laboratory CT systems. The first protocol drastically reduces the need for periodic intervention when making time-lapse experiments, allowing a large number of tomograms to be collected automatically. The automated scanning at regular intervals needed for uninterrupted time-lapse CT is demonstrated by analysing the germination of a mung bean (vigna radiata), whilst the synchronisation with an in situ rig required for interrupted time-lapse CT is highlighted using a shear cell to observe granular segregation. The second protocol uses golden-ratio angular sampling with an iterative reconstruction scheme and allows the number of projections in a reconstruction to be changed as sample evolution occurs. This overcomes the limitation of the need to know a priori what the best time window for each scan is. The protocol is evaluated by studying barite precipitation within a porous column, allowing a comparison of spatial and temporal resolution of reconstructions with different numbers of projections. Both of the protocols presented here have great potential for wider application, including, but not limited to, in situ mechanical testing, following battery degradation and chemical reactions.
Analysis of flame curvature evolution in a turbulent premixed bluff body burner
Authors: Cifuentes Luis , Dopazo Cesar , Sandeep Anurag , Chakraborty Nilanjan , Kempf Andreas
Published: September 2018

The physical mechanisms responsible for flame curvature evolution of a methane-air premixed flame attached to a bluff-body burner have been investigated using a high-fidelity flame-resolved three-dimensional simulation database. The contributions to the mean curvature generation due to the fluid flow motion and due to a combination of flow and flame propagation induced strain rates have been analyzed in detail and dominant contributions in different zones (reactants, flame, and products) of the flame have been identified. The effect of fluid flow on the mean curvature evolution is important on the unburned gas side, whereas the flame propagation dominates the mean curvature evolution in the reaction region and toward the hot products. The statistical contributions of the mean curvature transport equation have been analyzed in terms of the iso-scalar surface geometry, characterized by the mean and Gauss curvatures. This information has subsequently been used to provide physical insights into the dominant mechanisms of curvature evolution for different flame topologies.
Superior electromigration resistance of a microsized solder interconnection containing a single-Sn grain
Authors: Zhu Wenhui , Yang Hanjie , Chen Zhuo
Published: September 2018

With solder interconnections downsizing to the micrometer scale in integrated circuit packaging, the microstructural nonuniformity generated by the limited number of β-Sn grains is expected to have a significant influence on joint stability when subjected to electromigration. Using electron backscattered diffraction for direct observations, this study investigated the microstructural evolution of solder joints under current stressing. When a joint consists of multiple Sn grains, the grain boundaries that traverse the joint provide fast electromigration paths for Cu, causing severe intermetallic compound growth accompanied by grain rotation due to tensile stress, whereas significantly higher electromigration resistance is observed in a single-grain joint. This strong influence of the number of Sn grains indicates that, unlike the situation in large-sized joints, electromigration through grain boundaries is more significant than electromigration through a crystal lattice in joint degradation at the micrometer scale.
Temperature dependent piezoelectric anisotropy in tetragonal 0.63Pb(Mg1/3Nb2/3)-0.37PbTiO3 single crystal
Authors: Zheng Limei , Jing Yujia , Lu Xiaoyan , Li Shiyang , Yang Liya , Lü Weiming , Cao Wenwu
Published: September 2018

In this work, we studied the temperature-dependent effective piezoelectric coefficient d33* along the arbitrary direction of a tetragonal 0.63Pb(Mg1/3Nb2/3)-0.37PbTiO3 single crystal. Results show that the crystal changes from a rotator ferroelectrics with the maximum d33* occurring along the nonpolar direction to a extender type with maximum piezoelectricity along [001]C. Two polymorphic phase transitions, orthorhombic-tetragonal and tetragonal-cubic, greatly influence the PS dynamics, leading to the change of d33* anisotropy with temperature. The [011]C oriented crystals possess both improved piezoelectricity and high thermal stability, hence are the best choice for practical applications.
Acceptor doping of β-Ga2O3 by Mg and N ion implantations
Authors: Wong Man Hoi , Lin Chia-Hung , Kuramata Akito , Yamakoshi Shigenobu , Murakami Hisashi , Kumagai Yoshinao , Higashiwaki Masataka
Published: September 2018

Deep acceptor doping of β-Ga2O3 with Mg and N was demonstrated by implantation of the impurity ions into n-type bulk substrates. Systematic physical and electrical characterizations were performed to demonstrate recovery of the implantation-damaged crystals and electrical activation of the dopant atoms by thermal annealing at 1000–1200 °C in an N2 atmosphere. N was found to exhibit much lower thermal diffusivity than Mg, thus enabling the use of higher annealing temperatures to maximize N activation efficiency without significantly altering the impurity profile. Consequently, an n-Ga2O3/Ga2O3:N/n-Ga2O3 structure was capable of sustaining a much larger voltage across its end terminals than its Mg-doped counterpart. The development of an ion implantation technology for acceptor doping of β-Ga2O3 creates unique opportunities for designing and engineering a variety of high-voltage β-Ga2O3 devices.
Addition of several tannin extracts to modulate fermentation of barley meal under intensive ruminant feeding conditions simulated in vitro by incubating at pH 6.0–6.2
Authors: Amanzougarene Z. , Yuste S. , Fondevila M.
Published: September 2018

The potential use of tannin extracts from quebracho (QCT), grape (GCT), chestnut (CHT) and oak (OHT) included at 10, 20 or 30 mg/g to modulate rumen fermentation of concentrates was studied in three 24-h in vitro incubation runs, with barley grain as reference substrate and simulating high concentrate feeding conditions by adjusting pH at 6.2. Incubation pH at 8 and 24 h ranged from 6.14 to 6.18 and from 5.94 to 6.00, respectively. Gas production from barley alone (CTL) was linearly reduced with CHT (P < 0.05 up to 6 h; P < 0.10 from 8 to 18 h), OHT (P < 0.05 up to 12 h; P < 0.10 from 18 h), GCT (P < 0.05 from 2 to 24 h) and QCT (P < 0.10 up to 6 h), but a quadratic trend (P < 0.10) was also detected on GCT. The effect of GCT was highest and that of CHT lowest. Similarly, dry matter disappearance after 24 h showed a linear decrease with all tannin sources (P < 0.05), being lower with GCT than with QCT and CHT (P < 0.05). All tannin sources linearly increased (P < 0.05) molar butyrate proportion from CTL, at the expense of propionate proportion in GCT (P < 0.01) and CHT (P < 0.10). Except for the linear effect of chestnut on barley fermentation, all sources already reached their maximum level of response at their first level of inclusion (10 mg/g), especially with GCT. Qualitatively, tannins did not largely affect pH or other environmental parameters, except for an increase in butyrate proportion.
Phylogenetic approach to recover integration dates of latent HIV sequences within-host
Authors: Jones Bradley R. , Kinloch Natalie N. , Horacsek Joshua , Ganase Bruce , Harris Marianne , Harrigan P. Richard , Jones R. Brad , Brockman Mark A. , Joy Jeffrey B. , Poon Art F. Y. , Brumme Zabrina L.
Published: September 2018

Given that HIV evolution and latent reservoir establishment occur continually within-host, and that latently infected cells can persist long-term, the HIV reservoir should comprise a genetically heterogeneous archive recapitulating within-host HIV evolution. However, this has yet to be conclusively demonstrated, in part due to the challenges of reconstructing within-host reservoir establishment dynamics over long timescales. We developed a phylogenetic framework to reconstruct the integration dates of individual latent HIV lineages. The framework first involves inference and rooting of a maximum-likelihood phylogeny relating plasma HIV RNA sequences serially sampled before the initiation of suppressive antiretroviral therapy, along with putative latent sequences sampled thereafter. A linear model relating root-to-tip distances of plasma HIV RNA sequences to their sampling dates is used to convert root-to-tip distances of putative latent lineages to their establishment (integration) dates. Reconstruction of the ages of putative latent sequences sampled from chronically HIV-infected individuals up to 10 y following initiation of suppressive therapy revealed a genetically heterogeneous reservoir that recapitulated HIV’s within-host evolutionary history. Reservoir sequences were interspersed throughout multiple within-host lineages, with the oldest dating to >20 y before sampling; historic genetic bottleneck events were also recorded therein. Notably, plasma HIV RNA sequences isolated from a viremia blip in an individual receiving otherwise suppressive therapy were highly genetically diverse and spanned a 20-y age range, suggestive of spontaneous in vivo HIV reactivation from a large latently infected cell pool. Our framework for reservoir dating provides a potentially powerful addition to the HIV persistence research toolkit.
Wetting controls of droplet formation in step emulsification
Authors: Eggersdorfer Maximilian L. , Seybold Hansjörg , Ofner Alessandro , Weitz David A. , Studart André R.
Published: September 2018

Significance

Step emulsification is one of the few methods that enables upscaled production of droplets with a monodispersity desired for many industrial processes. However, the physical mechanisms of the droplet formation process are poorly understood. We study the droplet breakup by experiments and simulations and find a simple theory predicting the transition from dripping to jetting and the minimal contact angle of
α
= 2π/3 = 120° for which droplets form. These results have important consequences for the development and design of novel microfluidic systems and reactors that address the growing demand for tools to manipulate fluids at the submillimeter scale.
Genetic screen identifies adaptive aneuploidy as a key mediator of ER stress resistance in yeast
Authors: Beaupere Carine , Dinatto Leticia , Wasko Brian M. , Chen Rosalyn B. , VanValkenburg Lauren , Kiflezghi Michael G. , Lee Mitchell B. , Promislow Daniel E. L. , Dang Weiwei , Kaeberlein Matt , Labunskyy Vyacheslav M.
Published: September 2018

Significance

In eukaryotes, about one-third of all proteins are folded in the endoplasmic reticulum (ER). When protein folding demand exceeds capacity of the ER, the unfolded protein response (UPR) is activated to counteract ER stress. However, the mechanisms of adaptation to ER stress are not restricted to the UPR. Here, we report that gain of chromosome II in yeast allows adaptation of cells to protein misfolding. We narrowed down the effect of chromosome II duplication to three genes, which promote ER stress resistance independently of the UPR. Overexpression of these genes was sufficient to protect cells from ER stress and led to the elimination of aneuploidy. Thus, aneuploidy can serve as an important genome adaptation protecting cells against ER stress.
Clinical and veterinary trypanocidal benzoxaboroles target CPSF3
Authors: Wall Richard J. , Rico Eva , Lukac Iva , Zuccotto Fabio , Elg Sara , Gilbert Ian H. , Freund Yvonne , Alley M. R. K. , Field Mark C. , Wyllie Susan , Horn David
Published: September 2018

African trypanosomes cause lethal and neglected tropical diseases, known as sleeping sickness in humans and nagana in animals. Current therapies are limited, but fortunately, promising therapies are in advanced clinical and veterinary development, including acoziborole (AN5568 or SCYX-7158) and AN11736, respectively. These benzoxaboroles will likely be key to the World Health Organization’s target of disease control by 2030. Their mode of action was previously unknown. We have developed a high-coverage overexpression library and use it here to explore drug mode of action in
Trypanosoma brucei
. Initially, an inhibitor with a known target was used to select for drug resistance and to test massive parallel library screening and genome-wide mapping; this effectively identified the known target and validated the approach. Subsequently, the overexpression screening approach was used to identify the target of the benzoxaboroles, Cleavage and Polyadenylation Specificity Factor 3 (CPSF3, Tb927.4.1340). We validated the CPSF3 endonuclease as the target, using independent overexpression strains. Knockdown provided genetic validation of CPSF3 as essential, and GFP tagging confirmed the expected nuclear localization. Molecular docking and CRISPR-Cas9-based editing demonstrated how acoziborole can specifically block the active site and mRNA processing by parasite, but not host CPSF3. Thus, our findings provide both genetic and chemical validation for CPSF3 as an important drug target in trypanosomes and reveal inhibition of mRNA maturation as the mode of action of the trypanocidal benzoxaboroles. Understanding the mechanism of action of benzoxaborole-based therapies can assist development of improved therapies, as well as the prediction and monitoring of resistance, if or when it arises.
Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex
Authors: Chowdhury Saikat , Otomo Chinatsu , Leitner Alexander , Ohashi Kazuto , Aebersold Ruedi , Lander Gabriel C. , Otomo Takanori
Published: September 2018

Autophagy is an enigmatic cellular process in which double-membrane compartments, called “autophagosomes, form de novo adjacent to the endoplasmic reticulum (ER) and package cytoplasmic contents for delivery to lysosomes. Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the PI3P-enriched ER–phagophore junction. We combined single-particle electron microscopy, chemical cross-linking coupled with mass spectrometry, and biochemical analyses to characterize human ATG2A in complex with the PI3P effector WIPI4. ATG2A is a rod-shaped protein that can bridge neighboring vesicles through interactions at each of its tips. WIPI4 binds to one of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle to another PI3P-free vesicle. These data suggest that the ATG2A-WIPI4 complex mediates ER–phagophore association and/or tethers vesicles to the ER–phagophore junction, establishing the required organization for phagophore expansion via the transfer of lipid membranes from the ER and/or the vesicles to the phagophore.
Sinking deltas: trapped in a dual lock-in of technology and institutions
Authors: Seijger Chris , Ellen Gerald Jan , Janssen Stephanie , Verheijen Esther , Erkens Gilles
Published: September 2018

In delta areas, flood protection structures and large-scale land reclamation are preferential water management strategies to cultivate soft delta soils. Over the past decades, river embankments, upstream dams, land reclamation, and groundwater use have intensified, and increasingly contribute to subsidence. In addition, the influence of institutions implementing these strategies has strengthened as they have acquired technical skills, knowledge, and vast financial resources. Sinking deltas are therefore trapped in a dual lock-in as dominating technology and institutions act as constraints to moving into a more long-term sustainable direction. Nine factors for the lock-in are introduced and illustrated for delta regions in Asia, Europe, and the US. To gain a better understanding of what researchers and practitioners can do to address the dual lock-in, a practical case is presented of Gouda, a Dutch subsiding city in search of more sustainable strategies and institutions. The paper ends with three steps to change the configuration of a dual lock-in: (1) getting to know the lock-in; (2) temporarily bypassing it; and (3) constituting a new, more sustainable lock-in. These steps should be further investigated in action-oriented research programmes with local experts, and targeted to policy processes and human behaviour in the sinking deltas.
Innovation paradoxes: a review and typology of explanations
Authors: Fragkandreas Thanos
Published: September 2018

The concept of innovation paradoxes refers to a family of anomalous observations demonstrating that relatively high or outstanding innovation efforts lead to either insignificant or undesirable outcomes. While researchers have long been busy studying the nature and causes of innovation paradoxes, they have yet to assess the fruits of their research efforts. This paper addresses this neglect, in particular by identifying and reviewing the literature of two innovation paradoxes – the European innovation paradox and the Swedish innovation paradox. The findings show that research on both paradoxes has proceeded along similar lines, leading to the development of a working explanatory typology of innovation paradoxes. The paper ends with a discussion of key observations, findings and suggestions.
Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1
Authors: Liu Xian-Dong , Zhu Xiao-Na , Halford Michael M. , Xu Tian-Le , Henkemeyer Mark , Xu Nan-Jie
Published: September 2018

Neuronal connections are initiated by axon targeting to form synapses. However, how the maturation of axon terminals is modulated through interacting with postsynaptic elements remains elusive. In this study, we find that ligand of Numb protein X 1 (Lnx1), a postsynaptic PDZ protein expressed in hippocampal CA3 pyramidal neurons, is essential for mossy fiber (MF) axon targeting during the postnatal period. Lnx1 deletion causes defective synaptic arrangement that leads to aberrant presynaptic terminals. We further identify EphB receptors as novel Lnx1-binding proteins to form a multiprotein complex that is stabilized on the CA3 neuron membrane through preventing proteasome activity. EphB1 and EphB2 are independently required to transduce distinct signals controlling MF pruning and targeting for precise DG-CA3 synapse formation. Furthermore, constitutively active EphB2 kinase rescues structure of the wired MF terminals in Lnx1 mutant mice. Our data thus define a retrograde trans-synaptic regulation required for integration of post- and presynaptic structure that participates in building hippocampal neural circuits during the adolescence period.
A note on a two-weight estimate for the dyadic square function
Authors: Kakaroumpas Spyridon
Published: September 2018

We show that the two-weight estimate for the dyadic square function proved by Lacey–Li is sharp.
A joint central limit theorem for the sum-of-digits function, and asymptotic divisibility of Catalan-like sequences
Authors: Drmota Michael , Krattenthaler Christian
Published: September 2018

We prove a central limit theorem for the joint distribution of

s
q

(

A
j

n
)

s_q(A_jn)

,

1
≤
j
≤
d

1\le j \le d

, where

s
q

s_q

denotes the sum-of-digits function in base 

q
q

and the

A
j

A_j

’s are positive integers relatively prime to 

q
q

. We do this in fact within the framework of quasi-additive functions. As an application, we show that most elements of “Catalan-like” sequences—by which we mean integer sequences defined by products/quotients of factorials—are divisible by any given positive integer.
Intraseason Waning of Influenza Vaccine Effectiveness
Authors: Ray G Thomas , Lewis Ned , Klein Nicola P , Daley Matthew F , Wang Shirley V , Kulldorff Martin , Fireman Bruce
Published: September 2018

Background

In the United States, it is recommended that healthcare providers offer influenza vaccination by October, if possible. However, if the vaccine’s effectiveness soon begins to wane, the optimal time for vaccination may be somewhat later. We examined whether the effectiveness of influenza vaccine wanes during the influenza season with increasing time since vaccination.

Methods

We identified persons who were vaccinated with inactivated influenza vaccine from 1 September 2010 to 31 March 2017 and who were subsequently tested for influenza and respiratory syncytial virus (RSV) by a polymerase chain reaction test. Test-confirmed influenza was the primary outcome and days-since-vaccination was the predictor of interest in conditional logistic regression. Models were adjusted for age and conditioned on calendar day and geographic area. RSV was used as a negative-control outcome.

Results

Compared with persons vaccinated 14 to 41 days prior to being tested, persons vaccinated 42 to 69 days prior to being tested had 1.32 (95% confidence interval [CI], 1.11 to 1.55) times the odds of testing positive for any influenza. The odds ratio (OR) increased linearly by approximately 16% for each additional 28 days since vaccination. The OR was 2.06 (95% CI, 1.69 to 2.51) for persons vaccinated 154 or more days prior to being tested. No evidence of waning was found for RSV.

Conclusions

Our results suggest that effectiveness of inactivated influenza vaccine wanes during the course of a single season. These results may lead to reconsideration of the optimal timing of seasonal influenza vaccination.
Motherhood as Identity: African Refugee Single Mothers Working the Intersections
Authors: Grant Julian , Guerin Pauline B
Published: September 2018

We explored the strategies that refugee single mothers used to manage socio-emotional, physical and economic challenges of raising children during resettlement in a Western country. Ethnographic case studies of 10 families and 12 focus groups were conducted. Bourdieu’s theory of social relations informed the primary analysis. Intersectionality was adopted as a secondary analysis, attending to the agency and empowerment experienced by the participants. Motherhood was identified as a key gendered capability important for the development of capital. Within motherhood, five core themes were identified, including ‘loneliness and sadness’, ‘not enough money’, ‘racism’, ‘struggle for education’ and ‘striving to connect’. Findings suggest the importance of a feminism that legitimizes motherhood as identity with attendant intersections of race, class and gender. Further, the theoretical link between motherhood as a capability and development of capital suggests that investment in structural resources could improve capability and outcomes for refugee mothers and children.
Supratotal Resection of Residual Clival Chordoma With Combined Endoscopic Endonasal and Contralateral Transmaxillary Approaches: 2-Dimensional Operative Video
Authors: Lavigne Philippe , Wang Eric W , Fernandez-Miranda Juan C
Published: September 2018

The optimal treatment for skull base chordomas is gross total resection followed by radiotherapy and not radiation of partially resected tumors. Supratotal resection, defined as removal beyond all involved bone and dura, is ideal but difficult to achieve.

 In this video, we present the case of a 37-yr-old man with new onset of progressive cranial nerve sixth palsy and a skull base lesion compatible with clival chordoma. He underwent partial surgical resection at an outside institution via transcranial approach, with significant tumor residual at the clivus, dorsum sella, posterior clinoids, and petrous apex, extensive dural invasion, and intradural extension with attachment to the basilar artery and its long perforating branches.

 Supratotal surgical resection was achieved using an endoscopic endonasal transclival approach, ipsilateral transpteryoid approach to the foramen lacerum for carotid artery mobilization, bilateral interdural transcavernous approach with posterior clinoidectomies, and con-tralateral transmaxillary approach to the petrous apex. Reconstruction was performed in a multilayer fashion with fascia lata and fat grafts, extended nasoseptal flap, a lumbar drainage for 3 d. No cerebrospinal fluid leak occurred, and the abducens nerve palsy significantly improved at 3-mo follow-up. Proton therapy is planned.

 Recent advances in endoscopic endonasal surgery allow for very high rates of complete and even supratotal resection despite the challenging location. A long learning curve to acquire the technical skills and complex surgical anatomy is required to decrease complication rates and achieve maximal resection in chordomas. Reoperations are more challenging and risky; therefore, first attempt should have curative intent.

 The patient signed informed consent including the use of photographic and video material for educational or academic purposes
Determinants of under-5 mortality in Burkina Faso
Authors: Bado Aristide Romaric , Susuman A Sathiya
Published: September 2018

Background

The aim of this article is to determine the factors associated with under-5 mortality and their evolution from 1993 to 2010 and to analyse the contributors of socioeconomic inequalities in mortality of children under-5 years during the same period.

Data and methods

The data used in this study were derived from the four rounds of Demographic and Health Survey (DHS) conducted in Burkina Faso in 1993, 1998 and 2010. Concentration measurement, logistics regression and Oaxaca–Blinder decomposition method were used to analyse data.

Results

Multivariate analysis revealed that being the first child (odds ratio = 1.8 for 1993, 1.7 for 1998, 1.2 for 2003 and 1.3 for 2010) or a twin (odds ratio = 4.5 for 1993, 2.8 for 1998, 2.7 for 2003 and 4.8 for 2010) were also significantly associated with the probability of dying. The variable (parity) was the main contributor to the part of the inequality due to differences in group characteristics and that would be due to the fact that women from poor households have greater parity compared to those from rich households.

Conclusion

For a reduction in mortality and inequalities related to mortality, the implementation of actions in favour of poor households and promotion of family planning programmes for birth spacing will be required.
Ethical Use of Student Profiles to Predict and Prevent Development of Depression Symptoms During Medical School
Authors: Gengoux Grace W. , Roberts Laura Weiss
Published: September 2018

Research investigations have repeatedly shown that medical school can be a period of high stress and deteriorating mental health for many students. There is a critical need for systematic guidance on how to personalize prevention and treatment programming to help those students at highest risk. The authors of this Invited Commentary respond to the report by Dyrbye and colleagues, published in this issue of Academic Medicine, that proposes a prognostic index to predict risk of developing depression symptoms in medical students. The commentary authors applaud Dyrbye and her coauthors for their innovative approach; their findings provide substantial insights relevant to the critical goal of enhancing medical student well-being. However, evidence indicates that students who identify as members of racial, ethnic, sexual, and/or gender minority groups are at heightened risk of depression, so any program that profiles students in relation to their mental health symptoms must be proactive in ensuring that its efforts do not perpetuate stigma, marginalization, and discrimination for these underrepresented and potentially vulnerable groups. The commentary authors suggest practices for ethically implementing recommended wellness programs while maintaining an inclusive learning environment that respects personal privacy and incorporates transparent consent practices.
Seizure Identification by Critical Care Providers Using Quantitative Electroencephalography
Authors: Lalgudi Ganesan Saptharishi , Stewart Craig P. , Atenafu Eshetu G. , Sharma Rohit , Guerguerian Anne-Marie , Hutchison James S. , Hahn Cecil D.
Published: September 2018

Objectives:

To compare the performance of critical care providers with that of electroencephalography experts in identifying seizures using quantitative electroencephalography display tools.

Design:

Diagnostic accuracy comparison among healthcare provider groups.

Setting:

Multispecialty quaternary children’s hospital in Canada.

Subjects:

ICU fellows, ICU nurses, neurophysiologists, and electroencephalography technologists.

Intervention:

Two-hour standardized one-on-one training, followed by a supervised individual review of 27 continuous electroencephalography recordings with the task of identifying individual seizures on eight-channel amplitude-integrated electroencephalography and color density spectral array displays.

Measurements and Main Results:

Each participant reviewed 27 continuous electroencephalograms comprising 487 hours of recording containing a total of 553 seizures. Performance for seizure identification was compared among groups using a nested model analysis with adjustment for interparticipant variability within groups and collinearity among recordings. Using amplitude-integrated electroencephalography, sensitivity for seizure identification was comparable among ICU fellows (83.8%), ICU nurses (73.1%), and neurophysiologists (81.5%) but lower among electroencephalographic technologists (66.7%) (p = 0.003). Using color density spectral array, sensitivity was comparable among ICU fellows (82.4%), ICU nurses (88.2%), neurophysiologists (83.3%), and electroencephalographic technologists (73.3%) (p = 0.09). Daily false-positive rates were also comparable among ICU fellows (2.8 for amplitude-integrated electroencephalography, 7.7 for color density spectral array), ICU nurses (4.2, 7.1), neurophysiologists (1.2, 1.5), and electroencephalographic technologists (0, 0) (p = 0.41 for amplitude-integrated electroencephalography; p = 0.13 for color density spectral array). However, performance varied greatly across individual electroencephalogram recordings. Professional background generally played a greater role in determining performance than individual skill or electroencephalogram recording characteristics.

Conclusions:

Following standardized training, critical care providers and electroencephalography experts displayed similar performance for identifying individual seizures using both amplitude-integrated electroencephalography and color density spectral array displays. Although these quantitative electroencephalographic trends show promise as a tool for bedside seizure screening by critical care providers, these findings require confirmation in a real-world ICU environment and in daily clinical use.
Development of a Boston Treatment Program for Youth at Clinical High Risk for Psychosis: Center for Early Detection, Assessment, and Response to Risk (CEDAR)
Authors: Friedman-Yakoobian Michelle S. , West Michelle L. , Woodberry Kristen A. , O’Donovan Keira E. , Zimmet Suzannah V. , Gnong-Granato Andréa , Giuliano Anthony J. , Guyer Margaret E. , Rodenhiser-Hill Janine , Keshavan Matcheri S. , Seidman Larry J.
Published: September 2018

Over the past two decades, increasing attention has been given to the importance of early intervention for psychosis. This article describes the development of the Center for Early Detection, Assessment and Response to Risk (CEDAR), which focuses on early identification and treatment of youth at clinical high risk for psychosis. There are relatively few models in the United States for such programs, and we present our developmental story, focusing mainly on the CEDAR Clinic, as a case study of how such a program can develop. We describe the rationale, infrastructure, and services provided at the CEDAR Clinic, and present some descriptive data from the CEDAR Clinic through 2016. A case example is provided to illustrate treatment at CEDAR. We hope that the cultural history of our program’s development is informative for clinicians and policy makers as one model of how to build an early intervention service. We believe that this article is timely in view of the growing momentum in the United States for developing programs for intervening as early as possible for youth at clinical high risk for psychosis.
Why Do We Need a New Clinical Practice Guideline for Moderate to Severe Traumatic Brain Injury?
Authors: Swaine Bonnie , Bayley Mark Theodore , Marshall Shawn , Kua Ailene , Marier-Deschênes Pascale , Allaire Anne-Sophie , Kagan Corinne , Truchon Catherine , Janzen Shannon , Teasell Robert , Lamontagne Marie-Eve
Published: September 2018

Objective:

Clinical practice guidelines (CPGs) aim to improve quality and consistency of healthcare services. A Canadian group of researchers, clinicians, and policy makers developed/adapted a CPG for rehabilitation post–moderate to severe traumatic brain injury (MSTBI) to respond to end users' needs in acute care and rehabilitation settings.

Methods:

The rigorous CPG development process began assessing needs and expectations of end users, then appraised existing CPGs, and, during a consensus conference, produced fundamental and priority recommendations. We also surveyed end users' perceptions of implementation gaps to determine future implementation strategies to optimize adherence to the CPG.

Results:

The unique bilingual (French and English) CPG consists of 266 recommendations (of which 126 are new recommendations), addressing top priorities for MSTBI, rationale, process indicators, and implementations tools (eg, algorithms and benchmarks).

Conclusion:

The novel approach of consulting and working with end users to develop a CPG for MSTBI should influence knowledge uptake for clinicians wanting to provide evidence-based care.
A Phenotype of Primary Open-angle Glaucoma With Systemic Vasospasm
Authors: Alizadeh Reza , Vickers Laura , Hirunpatravong Pradtana , Romero Pablo , Lin Mark C. , Sharifipour Farideh , Caprioli Joseph
Published: September 2018

Purpose:

Primary open-angle glaucoma (POAG) patients constitute a heterogenous group. Identification of phenotypic subtypes among these patients may provide a deeper understanding of the disease and aid associations with genotypes. We describe a phenotype of POAG patients associated with a constellation of systemic disorders; patients with this phenotype seem to be vulnerable to optic nerve damage at low intraocular pressures.

Materials and Methods:

In this retrospective study, we evaluated the medical records of active Jules Stein Eye Institute glaucoma patients from January 1996 to 2017 and included subjects with POAG, acquired pits of the optic nerve (APON), and at least one of the following: systolic blood pressure persistently ≤100 mm Hg, history of migraine headaches or migraine variant, and the Raynaud syndrome.

Results:

Of 87 patients (125 eyes) with APON, 37 patients (55 eyes) met the study criteria. In total, 34 patients were female (92%). The median age at the time of diagnosis was 55 years. Nineteen patients (73%) had low systolic blood pressures, same number had Raynaud syndrome, and 25 (68%) had a history of migraine.

Conclusions:

We describe a POAG subtype with APON and systemic vascular instability, predominantly female in their sixth decade of life who demonstrate progressive glaucomatous visual field damage at low intraocular pressure. We suggest that this clinical picture represents an important phenotype of POAG, and that identification and further study of it will help guide diagnosis and development of individualized treatments.
Association of Patient-reported Experiences and Surgical Outcomes Among Group Practices
Authors: Liu Jason B. , Pusic Andrea L. , Gibbons Christopher J. , Opelka Frank G. , Sage Jill S. , Thompson Vanessa M. , Ko Clifford Y. , Hall Bruce L. , Temple Larissa K.
Published: September 2018

Objective:

The aim of the study was to determine the association of patient-reported experiences (PREs) and risk-adjusted surgical outcomes among group practices.

Background:

The Centers for Medicare and Medicaid Services required large group practices to submit PREs data for successful participation in the Physician Quality Reporting System (PQRS) using the Consumer Assessment of Healthcare Providers and Systems for PQRS survey. Whether these PREs data correlate with perioperative outcomes remains ill defined.

Methods:

Operations between January 1, 2014 and December 31, 2016 in the American College of Surgeons’ National Surgical Quality Improvement Program registry were merged with 2015 Consumer Assessment of Healthcare Providers and Systems for PQRS survey data. Hierarchical logistic models were constructed to estimate associations between 7 subscales and 1 composite score of PREs and 30-day morbidity, unplanned readmission, and unplanned reoperation, separately, while adjusting for patient- and procedure mix.

Results:

Among 328 group practices identified, patients reported their experiences with clinician communication the highest (mean ± standard deviation, 82.66 ± 3.10), and with attention to medication cost the lowest (25.96 ± 5.14). The mean composite score was 61.08 (±6.66). On multivariable analyses, better PREs scores regarding medication cost, between-visit communication, and the composite score of experience were each associated with 4% decreased odds of morbidity [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92–0.99], readmission (OR 0.96, 95% CI 0.93–0.99), and reoperation (OR 0.96, 95% CI 0.93–0.99), respectively. In sensitivity analyses, better between-visit communication remained significantly associated with fewer readmissions.

Conclusions:

In these data, patients’ report of better between-visit communication was associated with fewer readmissions. More sensitive, surgery-specific PRE assessments may reveal additional unique insights for improving the quality of surgical care.