bluuebunny/crossref_metadata_2025 huggingface dataset:
Erfolgreiche Zelltherapie mit virusspezifischen T-Zellen vom HLA-teilkompatiblen Drittspender bei disseminierter Adenovirusinfektion früh nach allogener Stammzelltransplantation
Authors: Kafa Kinan , Tischer Sabine , Heuft Hans-Gert , Blasczyk Rainer , Priesner Christoph , Klusmann Jan-Henning , Eiz-Vesper Britta , Maecker-Kolhoff Britta
Published: November 2018

Adenovirusinfektionen (AdV-Infektionen) nach pädiatrischer hämatopoetischer Stammzelltransplantation sind häufig und treten in 10 – 20% aller allogenen Transplantationen auf (bis 30% der T-Zell-depletierten Transplantationen). Sie sind mit einer hohen Rate an Morbidität und Mortalität verbunden. Da die antivirale Therapie nur virostatisch wirkt und durch erhebliche Toxizität eine limitierende Behandlungsoption darstellt, ist die virusspezifische T-Zell-Therapie als sichere und gut verträgliche komplikationsarme Option sehr attraktiv. Unsere 4-jährige Patientin entwickelte 3 Wochen nach allogener hämatopoetischer Transplantation vom 10/10 HLA-passenden Registerspender eine disseminierte AdV-Infektion (Enteritis, persistierendes Fieber, Sepsis). Eine antivirale Therapie mit Cidofovir zeigte eine gute Wirksamkeit, musste aber wegen erheblicher Nephrotoxizität abgebrochen werden. Unter einer Überbrückungstherapie bis zur geplanten Gabe AdV-spezifischer T-Zellen mit Brincidofovir (BCV) stabilisierte sich die AdV-Last im Blut, blieb aber signifikant hoch. AdV-spezifische T-Zellen der HLA-haploidenten Mutter wurden nach Stimulation mit AdV-Hexon-Peptid-Gemisch über Interferon-γ-Zytokinsekretion (Interferon-γ: IFN-γ) und immunmagnetische Separation aufgereinigt und einmalig in einem Frischpräparat mit einer Dosis von 2,5 × 104 CD3+-Zellen/kg Körpergewicht verabreicht. Die Anwendung verlief komplikationslos und führte zu einer schnellen Elimination des Virus im Blut (ca. nach 2 Wochen). Nahezu zeitgleich (ca. 3 Wochen nach der AdV-spezifischen T-Zell-Gabe) konnten erstmals AdV-spezifische T-Zellen im Patientenblut nachgewiesen werden. Der adoptive Transfer AdV-spezifischer T-Zellen vom HLA-teilpassenden Familienspender als „Third-Party-Spender“ stellt eine rasch verfügbare und wenig toxische Behandlungsoption für Patienten mit refraktärer AdV-Erkrankung dar.
Real-time signal processing for sub-THz range grating-based distributed fiber sensing
Authors: Yao Zheyi , Wei Tao , Hefferman Gerald , Ren Kan
Published: November 2018

Distributed optical fiber sensors are an increasingly utilized method of gathering distributed strain and temperature data. However, the large amount of data they generate presents a challenge that limits their use in real-time, in situ applications. This article describes a parallel and pipelined computing architecture that accelerates the signal-processing speed of sub-terahertz fiber sensor arrays, maintaining high spatial resolution while allowing for expanded use of real-time sensing and control applications. The computing architecture described was successfully implemented in a field programmable gate array chip. The signal processing for the entire array takes only 12 system clock cycles. In addition, this design removes the necessity of storing any raw or intermediate data.
Connecting post-pulsing electrical and microstructural features in GeTe-based inline phase change switches
Authors: King Matthew R. , El-Hinnawy Nabil , Borodulin Pavel , Ezis Andy , Luu Vivien , Salmon Mike , Gu Jitty , Nichols Doyle T. , Dickey Elizabeth , Maria Jon-Paul , Young Robert M.
Published: November 2018

Plan view scanning transmission electron microscopy was used to investigate the microstructural connections to device resistance in inline phase change switch devices. It was revealed that massive structural changes occur in GeTe during switching, most notably the formation of an assembly of voids along the device centerline and large GeTe grains on either side of an “active region.” Restructuring of this variety was tied to changes in ON-state resistance with increasing pulse number, where initially porous and fine-grained (10-20 nm) GeTe was converted to large crystalline domains comprising the majority of the RF gap (400-700 nm). A phenomenological model for this microstructure is presented in which the OFF pulse melts a given width of GeTe, and upon cooling crystalline material outside the melt region acts as a template for an inward-propagating crystalline growth front. The voids observed along the device centerline were correlated to increasing OFF state resistance and a relatively stable ON state with increasing pulse number via a series resistance model. As a result of this analysis, OFF state resistance was suggested as an early indicator of device reliability. An improved GeTe deposition process was implemented to limit void formation, which is shown to have a more stable OFF-state resistance with increasing pulse number.
Integration of pressure-sensitive paint with persistent phosphor: A light-charged pressure-sensing system
Authors: Peng Di , Zhong Zhe , Cai Tao , Guo Songtao , Zhao Xiaofeng , Liu Yingzheng
Published: November 2018

A novel pressure-sensitive paint has been developed by mixing phosphor Sr4Al14O25:Eu,Dy with pressure-sensitive luminophore PtTFPP in a polyethylene binder. The phosphor particles served as hosts for PtTFPP molecules while providing excitation light via their bright blue/green luminescence. The unique long afterglow of Sr4Al14O25:Eu,Dy allows the coating to be charged by a light source (UV-LED or even sunlight) in advance, and then the luminescent signals can be collected by using a color camera for pressure measurement (without an external light source). The persistent luminescence and the pressure-sensitive signal correspond to the green and red channels, respectively. The errors due to time-varying persistent luminescence can be removed by taking an intensity ratio between the two channels. The current formulation of this light-charged pressure-sensitive paint (LC-PSP) has been optimized for the maximum signal level. It showed similar pressure sensitivity to typical pressure-sensitive paints (PSPs), and its capability was demonstrated through a nitrogen jet impingement experiment. This light-charged PSP can be truly free of light source during measurement, which greatly simplifies the optical system and avoids errors due to the inconsistent illumination field, and thus provides a solution for PSP applications in facilities with limited optical access.
A miniaturized device for the measurement of sheet-metal formability using digital image correlation
Authors: Leonard M. E. , Ugo F. , Stout M. , Signorelli J. W.
Published: November 2018

A laboratory-scale device to obtain forming-limit diagram data was designed to utilize the Marciniak and Kuczynski (MK) sample geometry. The design uses a high-resolution photographic camera, automatic trigger, and light-emitting diode (LED) lighting to record the time history of deformation calculated with the digital-image correlation technique. Because the testing device was miniaturized, it was possible to halt the forming experiments at intermediate strains and recrystallize the MK carrier blank. This permits large formability strains to be obtained without cracks developing at the carrier blank’s central hole, an advantage over full-size specimens and conventional testing rates. A number of initial experiments were performed on a zinc alloy sheet (Zn-Cu-Ti) over the entire forming-limit range (−0.5 ≤ ε2/ε1 ≤ 1), and the strain fields reduced employing the Bragard criterion to obtain limit strains. These results are compared favorably to previous data of this material obtained with a hemispherical, Nakazima, punch and a circle-grid pattern.
Development of an ion beam detector for the atomic beam probe diagnostic
Authors: Hacek P. , Berta M. , Anda G. , Aradi M. , Bencze A. , Dunai D. , Krbec J. , Panek R. , Refy D. I. , Stockel J. , Weinzettl V. , Zoletnik S.
Published: November 2018

The atomic beam probe diagnostic concept aims at measuring the edge magnetic field and through that edge current distribution in fusion plasmas by observing trajectories of an ion beam stemming from a diagnostic neutral beam. The diagnostic potentially has microsecond scale time resolution and can thus prove to be a powerful option to study fast changes in the edge plasma. A test detector has been installed on the COMPASS tokamak as an extension of the existing lithium beam diagnostic system. It employs a relatively simple concept of an array of conductive detection plates measuring the incident ion current, which is then amplified and converted to a voltage signal. The aim of the test detector is to experimentally examine the idea of the diagnostic and provide background data for design and installation of a final detector. Also, a numerical code based on the CUDA parallel computing platform has been developed for modeling lithium ion trajectories in the given COMPASS plasma discharges. We present the developments of the detector design and test measurements of the diagnostic performed both in a laboratory beam system and on the COMPASS tokamak.
Power stabilization of a diode laser with an acousto-optic modulator
Authors: Tricot F. , Phung D. H. , Lours M. , Guérandel S. , de Clercq E.
Published: November 2018

Laser power fluctuations can significantly reduce the device performances in various applications. High frequency fluctuations impact the signal-to-noise ratio, while slow variations can reduce the device repeatability or accuracy. Here we report experimental investigations on the power stabilization of a diode laser with an acousto-optic modulator. In the frequency domain, the relative power noise is reduced at the level of 2.2 × 10−8 Hz−1/2 in the range 1-100 kHz. The slow variations are studied in the time domain. The relative Allan standard deviation is measured at the level of 6 × 10−7 at 100 s averaging time. Above 100 s, the instability increases and reaches 2 × 10−6 at 10 000 s.
On the use of a fluid’s elasticity for deliberate rise of Taylor cells in a rotating micro-filter separator
Authors: Pourjafar M. , Hejri A. , Bazargan S. , Sadeghy K.
Published: November 2018

The effect of radial throughflow on the instability of circular Couette flow is numerically studied for a viscoelastic fluid obeying the Giesekus model. An exact solution has been obtained for the base flow using the perturbation method with the cross-flow Reynolds number serving as the small parameter. The stability of the base flow to infinitesimally small, normal-mode, axisymmetric perturbations is studied using the linear temporal stability theory. An eigenvalue problem is obtained which is solved numerically using the pseudo-spectral, Chebyshev-based collocation method. The numerical results show that for small cross-flow Reynolds numbers, there exists a critical Weissenberg number at which the flow is at its most stable state. For sufficiently large cross-flow Reynolds numbers, however, it is predicted that the flow becomes monotonically less stable when the Weissenberg number is increased. These results suggest that elasticity can be used as an efficient means for the deliberate rise of Taylor cells in rotating micro-filter separators for self-cleaning purposes of the clogged pores.
Emulating dynamic synaptic plasticity over broad timescales with memristive device
Authors: Zhang Yishu , Zhong Shuai , Song Li , Ji Xinglong , Zhao Rong
Published: November 2018

Memristive devices have shown great potential in realizing artificial synapses efficiently for neuromorphic computing. However, emulation of various subtle forms of plasticity over broad timescales in a single device remains a challenge. In this paper, we designed a Ag/MgO/Pt memristive device exhibiting a volatile switching behavior and demonstrated various forms of synaptic plasticity from milliseconds to days in a single device. The volatile behaviors are owing to the formation and spontaneous rupture of silver nano-filaments with and without applying electrical stimuli. By manipulating the input voltage pulse strength, such as pulse amplitude, interval, and pulse number, several key features of biological synaptic plasticity including paired pulse facilitation, augmentation, post-tetanic potentiation, early long-term plasticity (LTP), and late-LTP were emulated. In addition, a reversible transition between short-term plasticity and LTP was also demonstrated. This work enables artificial synapses with rich plasticity in a single nano-device, providing a pathway to develop a large scale artificial neural network for brain inspired computing systems.
First harmonic measurements of the spin Seebeck effect
Authors: Chen Yizhang , Roy Debangsu , Cogulu Egecan , Chang Houchen , Wu Mingzhong , Kent Andrew D.
Published: November 2018

We present measurements of the spin Seebeck effect (SSE) by a technique that combines alternating currents (AC) and direct currents (DC). The method is applied to a ferrimagnetic insulator/heavy metal bilayer, Y3Fe5O12 (YIG)/Pt. Typically, SSE measurements use an AC current to produce an alternating temperature gradient and measure the voltage generated by the inverse spin-Hall effect in the heavy metal at twice the AC frequency. Here, we show that when Joule heating is associated with AC and DC bias currents, the SSE response occurs at the frequency of the AC current drive and can be larger than the second harmonic SSE response. We compare the first and second harmonic responses and show that they are consistent with the SSE. The field dependence of the voltage response is used to distinguish between the damping-like and field-like torques. This method can be used to explore nonlinear thermoelectric effects and spin dynamics induced by temperature gradients.
Communication: Gas phase vibrational spectroscopy of the azide-water complex
Authors: Kelly John T. , Ellington Thomas L. , Sexton Thomas More , Fortenberry Ryan C. , Tschumper Gregory S. , Asmis Knut R.
Published: November 2018

The vibrational spectra of the azide-water complex, N3−(H2O), and its fully deuterated isotopologue are studied using infrared photodissociation (IRPD) spectroscopy (800-3800 cm−1) and high-level ab initio computations. The IRPD spectrum of the H2-tagged complex exhibits four fundamental transitions at 3705, 3084, 2003, and 1660 cm−1, which are assigned to the free OH stretching, the hydrogen-bonded O–H stretching, the antisymmetric N3 stretching, and the water bending mode, respectively. The IRPD spectrum is consistent with a planar, singly hydrogen-bonded structure according to an MP2 and CCSD(T) anharmonic analysis via generalized second-order vibrational perturbation theory. The red-shift of the hydrogen-bonded OH stretching fundamental of 623 cm−1 associated with this structure is computed within 6 cm−1 (or 1%) and is used to estimate the proton affinity of azide (1410 kJ mol−1). Born-Oppenheimer molecular dynamics simulations show that large amplitude motions are responsible for the observed band broadening at cryogenic temperature. Temperature-dependent (6–300 K) IR multiphoton dissociation spectra of the untagged complex are also presented and discussed in the context of spectral diffusion observed in the condensed phase.
Strain induced enhancement of erasable domain wall current in epitaxial BiFeO3 thin films
Authors: Chen Dongfang , Bai Zilong , Zhang Yan , Jiang Anquan
Published: November 2018

The characteristic of electronic transport at the ferroelectric domain boundary is intensively studied for the potential application in random access memory due to its unique resistance switching mechanism along with polarization reversal. Such high conductivity in artificially created domain walls is not only affected by the material defect chemistry, such as oxygen vacancies, but also pertinent to the multiple polarization states of the sample. Here, we show the enhanced domain wall current in BiFeO3 thin films that could be obtained by the optimization of epitaxial strains from substrates. The leakage current analysis reveals the electronic transport of domain wall current in line with the space-charge-limited conduction mechanism. It is believed that the uncompensated polarization charge arouses the band bending at the domain boundary, which profoundly affects the wall current. Free carriers are easily concentrated in the domain boundary region for the compensation of the enhanced polarization by the strain, resulting in an abrupt increase of the conductivity.
Anisotropic nano-scale resolution in 3D Bragg coherent diffraction imaging
Authors: Cherukara Mathew J. , Cha Wonsuk , Harder Ross J.
Published: November 2018

We demonstrate that the resolution of three-dimensional (3D) real-space images obtained from Bragg coherent x-ray diffraction measurements is direction dependent. We propose and demonstrate the effectiveness of a metric to determine the spatial resolution of images that accounts for the directional dependence. The measured direction dependent resolution of ∼4–9 nm is higher than the best previously obtained 3D measurements. Finally, we quantify the relationship between the resolution of recovered real-space images and dosage and discuss its implications in the light of next generation synchrotrons.
Room-temperature magnetoresistance achieved in a metallic antiferromagnetic material
Authors: Cockbill Louisa
Published: November 2018

A new industrially relevant material, incorporating a nonmagnetic metal with an antiferromagnetic alloy, has been tested for spintronic capabilities.
Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice
Authors: Shen Hui , Marino Rosa Anna M. , McDevitt Ross A. , Bi Guo-Hua , Chen Kai , Madeo Graziella , Lee Pin-Tse , Liang Ying , De Biase Lindsay M. , Su Tsung-Ping , Xi Zheng-Xiong , Bonci Antonello
Published: November 2018

Significance

Parkinson’s disease (PD) is a chronic dopamine (DA) neuron degenerative disorder. Little is known about factors that impact vulnerability of DA neurons to pathological insults. In this study, we found that vesicular glutamate transporter 2 (VgluT2) expression may play an important role in protecting DA neurons. Selective deletion of VgluT2 in DA neurons led to a significant reduction in expression of brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B and a significant increase in DA neuron death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Restoration of VgluT2 expression in DA neurons reversed these alterations. These findings suggest that reduced VgluT2 expression in DA neurons may constitute a risk factor in the development of PD and suggest potential therapeutic strategies for boosting resilience of DA neurons.
Ubiquilin 2 modulates ALS/FTD-linked FUS–RNA complex dynamics and stress granule formation
Authors: Alexander Elizabeth J. , Ghanbari Niaki Amirhossein , Zhang Tao , Sarkar Jaya , Liu Yang , Nirujogi Raja Sekhar , Pandey Akhilesh , Myong Sua , Wang Jiou
Published: November 2018

Significance

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating neurodegenerative diseases for which there are few treatments. ALS/FTD has been genetically and pathologically linked to both protein quality control (PQC) factors and RNA homeostasis, but the molecular players that bridge these pathways are not well characterized. Here, we identify a role for the ALS/FTD-linked PQC protein ubiquilin 2 (UBQLN2) in maintaining the solubility of RNA binding protein FUS in response to stress. UBQLN2 increases the dynamics of FUS–RNA complex formation, resulting in the negative regulation of stress granule (SG) formation. Because SGs potentially seed toxic inclusions of patients with ALS/FTD, these findings have implications for understanding ALS/FTD pathogenesis and designing new treatments for these diseases.
Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function
Authors: McAlpine William , Sun Lei , Wang Kuan-wen , Liu Aijie , Jain Ruchi , San Miguel Miguel , Wang Jianhui , Zhang Zhao , Hayse Braden , McAlpine Sarah Grace , Choi Jin Huk , Zhong Xue , Ludwig Sara , Russell Jamie , Zhan Xiaoming , Choi Mihwa , Li Xiaohong , Tang Miao , Moresco Eva Marie Y. , Beutler Bruce , Turer Emre
Published: November 2018

Significance

Activation of Toll-like receptors by microbes or host-derived molecules triggers signaling that promotes inflammation and may contribute to the development of autoimmunity. Here we show that excessive signaling by the innate immune Toll-like receptors (TLRs) TLR3, TLR7, and TLR9 is causative for inflammatory disease in mice with mutations of
Smcr8
. The cellular mechanism for their hyperactivation is likely prolonged ligand–receptor contact in lysosomes and phagosomes, the trafficking of which is regulated by the SMCR8-WDR41-C9ORF72 complex in immune cells. We also show that
Smcr8
and
Wdr41
mutations sensitize mice to chemically induced colitis. Our findings reveal an important negative regulatory mechanism that limits endosomal TLR signaling and shed light on the mechanism by which deficiencies of C9ORF72 or SMCR8 cause inflammation.
Dynamic nanoscale morphology of the ER surveyed by STED microscopy
Authors: Schroeder Lena K. , Barentine Andrew E.S. , Merta Holly , Schweighofer Sarah , Zhang Yongdeng , Baddeley David , Bewersdorf Joerg , Bahmanyar Shirin
Published: November 2018

The endoplasmic reticulum (ER) is composed of interconnected membrane sheets and tubules. Superresolution microscopy recently revealed densely packed, rapidly moving ER tubules mistaken for sheets by conventional light microscopy, highlighting the importance of revisiting classical views of ER structure with high spatiotemporal resolution in living cells. In this study, we use live-cell stimulated emission depletion (STED) microscopy to survey the architecture of the ER at 50-nm resolution. We determine the nanoscale dimensions of ER tubules and sheets for the first time in living cells. We demonstrate that ER sheets contain highly dynamic, subdiffraction-sized holes, which we call nanoholes, that coexist with uniform sheet regions. Reticulon family members localize to curved edges of holes within sheets and are required for their formation. The luminal tether Climp63 and microtubule cytoskeleton modulate their nanoscale dynamics and organization. Thus, by providing the first quantitative analysis of ER membrane structure and dynamics at the nanoscale, our work reveals that the ER in living cells is not limited to uniform sheets and tubules; instead, we suggest the ER contains a continuum of membrane structures that includes dynamic nanoholes in sheets as well as clustered tubules.
CNBP controls IL-12 gene transcription and Th1 immunity
Authors: Chen Yongzhi , Sharma Shruti , Assis Patricia A. , Jiang Zhaozhao , Elling Roland , Olive Andrew J. , Hang Saiyu , Bernier Jennifer , Huh Jun R. , Sassetti Christopher M. , Knipe David M. , Gazzinelli Ricardo T. , Fitzgerald Katherine A.
Published: November 2018

An inducible program of inflammatory gene expression is a hallmark of antimicrobial defenses. Recently, cellular nucleic acid–binding protein (CNBP) was identified as a regulator of nuclear factor-kappaB (NF-κB)–dependent proinflammatory cytokine gene expression. Here, we generated mice lacking CNBP and found that CNBP regulates a very restricted gene signature that includes IL-12β. CNBP resides in the cytosol of macrophages and translocates to the nucleus in response to diverse microbial pathogens and pathogen-derived products. Cnbp-deficient macrophages induced canonical NF-κB/Rel signaling normally but were impaired in their ability to control the activation of c-Rel, a key driver of IL-12β gene transcription. The nuclear translocation and DNA-binding activity of c-Rel required CNBP. Lastly, Cnbp-deficient mice were more susceptible to acute toxoplasmosis associated with reduced production of IL-12β, as well as a reduced T helper type 1 (Th1) cell IFN-γ response essential to controlling parasite replication. Collectively, these findings identify CNBP as important regulator of c-Rel–dependent IL-12β gene transcription and Th1 immunity.
Final report, on-going key comparison BIPM.QM-K1, ozone at ambient level, comparison with FMI, November 2017
Authors: Viallon Joële , Idrees Faraz , Moussay Philippe , Wielgosz Robert , Walden Jari , Saarnio Karri
Published: November 2018

As part of the ongoing key comparison BIPM.QM-K1, a comparison has been performed between the ozone national standard of Finland maintained by the Finnish Meteorological Institute (FMI) and the common reference standard of the key comparison, maintained by the Bureau International des Poids et Mesures (BIPM). The instruments have been compared over a nominal ozone amount-of-substance fraction range from 0 nmol/mol to 500 nmol/mol.

KEY WORDS FOR SEARCH

Ozone, Standard Reference Photometer, BIPM, FMI, KCDB, CIPM MRA

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Final report, on-going key comparison BIPM.QM-K1, ozone at ambient level, comparison with DHMZ, August 2016
Authors: Viallon Joële , Idrees Faraz , Moussay Philippe , Wielgosz Robert , Zobaj Eugen , Lepri Petra , Norris James E , Hodges Joseph T
Published: November 2018

As part of the on-going key comparison BIPM.QM-K1, a comparison has been performed between the ozone national standard of Croatia maintained by the Meteorological and Hydrological Service (DHMZ) and the common reference standard of the key comparison, maintained by the Bureau International des Poids et Mesures (BIPM), via a transfer standard maintained by the National Institute of Standards and Technology (NIST). The instruments have been compared over a nominal ozone amount-of-substance fraction range of 0 nmol/mol to 500 nmol/mol.

KEY WORDS FOR SEARCH

Ozone, Standard Reference Photometer, BIPM, DHMZ, CIPM MRA, KCDB

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Neurons in the Macaque Dorsal Premotor Cortex Respond to Execution and Observation of Actions
Authors: Papadourakis Vassilis , Raos Vassilis
Published: November 2018

We identified neurons in dorsal premotor cortex (PMd) of the macaque brain that respond during execution and observation of reaching-to-grasp actions, thus fulfilling the mirror neuron (MirN) criterion. During observation, the percentage of grip-selective MirNs in PMd and area F5 were comparable, and the selectivity indices in the two areas were similar. During execution, F5-MirNs were more selective than PMd–MirNs for grip, which was reflected in the higher selectivity indices in F5 than in PMd. PMd displayed grip-related information earlier than F5 during both conditions. In both areas, the number of neurons exhibiting congruent visual and motor selectivity did not differ from that expected by chance. However, both the PMd and F5 neuronal ensembles provided observation–execution matching, suggesting that the congruency may be achieved in a distributed fashion across the selective elements of the population. Furthermore, representational similarity analysis revealed that grip encoding in PMd and F5 is alike during both observation and execution. Our study provides direct evidence of mirror activity in PMd during observation of forelimb movements, and suggests that PMd is a node of the MirN circuit.
Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption
Authors: Bowden Jack , Del Greco M Fabiola , Minelli Cosetta , Zhao Qingyuan , Lawlor Debbie A , Sheehan Nuala A , Thompson John , Davey Smith George
Published: November 2018

Background

Two-sample summary-data Mendelian randomization (MR) incorporating multiple genetic variants within a meta-analysis framework is a popular technique for assessing causality in epidemiology. If all genetic variants satisfy the instrumental variable (IV) and necessary modelling assumptions, then their individual ratio estimates of causal effect should be homogeneous. Observed heterogeneity signals that one or more of these assumptions could have been violated.

Methods

Causal estimation and heterogeneity assessment in MR require an approximation for the variance, or equivalently the inverse-variance weight, of each ratio estimate. We show that the most popular ‘first-order’ weights can lead to an inflation in the chances of detecting heterogeneity when in fact it is not present. Conversely, ostensibly more accurate ‘second-order’ weights can dramatically increase the chances of failing to detect heterogeneity when it is truly present. We derive modified weights to mitigate both of these adverse effects.

Results

Using Monte Carlo simulations, we show that the modified weights outperform first- and second-order weights in terms of heterogeneity quantification. Modified weights are also shown to remove the phenomenon of regression dilution bias in MR estimates obtained from weak instruments, unlike those obtained using first- and second-order weights. However, with small numbers of weak instruments, this comes at the cost of a reduction in estimate precision and power to detect a causal effect compared with first-order weighting. Moreover, first-order weights always furnish unbiased estimates and preserve the type I error rate under the causal null. We illustrate the utility of the new method using data from a recent two-sample summary-data MR analysis to assess the causal role of systolic blood pressure on coronary heart disease risk.

Conclusions

We propose the use of modified weights within two-sample summary-data MR studies for accurately quantifying heterogeneity and detecting outliers in the presence of weak instruments. Modified weights also have an important role to play in terms of causal estimation (in tandem with first-order weights) but further research is required to understand their strengths and weaknesses in specific settings.
Use of a pooled cohort to impute cardiovascular disease risk factors across the adult life course
Authors: Zeki Al Hazzouri Adina , Vittinghoff Eric , Zhang Yiyi , Pletcher Mark J , Moran Andrew E , Bibbins-Domingo Kirsten , Golden Sherita H , Yaffe Kristine
Published: November 2018

Background

In designing prevention strategies, it may be useful to understand how early and midlife cardiovascular disease risk factor (CVDRF) exposures affect outcomes that primarily occur in mid to late life. Few single US cohorts have followed participants from early adulthood to late life.

Methods

We pooled four prospective cohorts that represent segments of the adult life course, and studied 15 001 White and Black adults aged 18 to 95 years at enrollment. We imputed early and midlife exposure to body mass index (BMI), glucose, lipids and blood pressure (BP). CVDRF trajectories were estimated using linear mixed models. Using the best linear unbiased predictions, we obtained person-specific estimates of CVDRF trajectories beginning at age 20 until each participant’s end of follow-up. We then calculated for each CVDRF, summary measures of early and midlife exposure as time-weighted averages (TWAs).

Results

In the pooled cohort, 33.7% were Black and 54.8% were female. CVDRF summary measures worsened in midlife compared with early life and varied by sex and race. In particular, systolic and diastolic BP were consistently higher over the adult life course among men, and BMI was higher among Blacks, particularly Black women. Simulation studies suggested acceptable imputation accuracy, especially for the younger cohorts. Correlations of true and imputed CVDRF summary measures ranged from 0.53 to 0.99, and agreement ranged from 67% to 99%.

Conclusions

These results suggest that imputed CVDRFs may be accurate enough to be useful in assessing the effects of early and midlife exposures on later life outcomes.
Examining associations between physical activity and cardiovascular mortality using negative control outcomes
Authors: Hamer Mark , Bauman Adrian , Bell Joshua A , Stamatakis Emmanuel
Published: November 2018

Background

The purpose of a negative control is to reproduce a condition that cannot involve the hypothesized causal mechanism, but does involve the same sources of bias and confounding that may distort the primary association of interest. Observational studies suggest physical inactivity is a major risk factor for cardiovascular disease (CVD), although potential sources of bias, including reverse causation and residual confounding, make it difficult to infer causality. The aim was to employ a negative control outcome to explore the extent to which the association between physical activity and CVD mortality is explained by confounding.

Methods

The sample comprised 104 851 participants (aged 47 ± 17 years; 45.4% male) followed up over mean (SD) 9.4 ± 4.5 years, recruited from the Health Survey for England and the Scottish Health Survey.

Results

There were 10 309 deaths, of which 3109 were attributed to CVD and 157 to accidents (negative control outcome). Accidental death was related to age, male sex, smoking, longstanding illness and psychological distress, with some evidence of social patterning. This confounding structure was similar to that seen with CVD mortality, suggesting that our negative control outcome was appropriate. Physical activity (per SD unit increase in MET-hr-wk) was inversely associated with CVD [hazard ratio (HR) = 0.75; 95% confidence interval (CI), 0.70, 0.80]; the point estimate between physical activity and accidental death was in the same direction but of lesser magnitude (HR = 0.86; 95% CI: 0.69, 1.07). A linear dose–response pattern was observed for physical activity and CVD but not with the negative control.

Conclusions

Inverse associations between physical activity and risk of CVD mortality are likely causal but of a smaller magnitude than commonly observed. Negative control studies have the potential to improve causal inference within the physical activity field.
Early Surgical Management of Thermal Airway Injury: A Case Series
Authors: Jayawardena Asitha , Lowery Anne S , Wootten Christopher , Dion Gregory R , Summitt J Blair , McGrane Stuart , Gelbard Alexander
Published: November 2018

Inhalation injury is an independent risk factor in burn mortality, imparting a 20% increased risk of death. Yet there is little information on the natural history, functional outcome, or pathophysiology of thermal injury to the laryngotracheal complex, limiting treatment progress. This paper demonstrates a case series (n = 3) of significant thermal airway injuries. In all cases, the initial injury was far exceeded by the subsequent immune response and aggressive fibroinflammatory healing. Serial examination demonstrated progressive epithelial injury, mucosal inflammation, airway remodeling, and luminal compromise. Histologic findings in the first case demonstrate an early IL-17A response in the human airway following thermal injury. This is the first report implicating IL-17A in the airway mucosal immune response to thermal injury. Their second and third patients received Azithromycin targeting IL-17A and showed clinical responses. The third patient also presented with exposed tracheal cartilage and underwent mucosal reconstitution via split-thickness skin graft over an endoluminal stent in conjunction with tracheostomy. This was associated with rapid abatement of mucosal inflammation, resolution of granulation tissue, and return of laryngeal function. Patients who present with thermal inhalation injury should receive a thorough multidisciplinary airway evaluation, including early otolaryngologic evaluation. New early endoscopic approaches (scar lysis and mucosal reconstitution with autologous grafting over an endoluminal stent), when combined with targeted medical therapy aimed at components of mucosal airway inflammation (local corticosteroids and systemic Azithromycin targeting IL-17A), may have potential to limit chronic cicatricial complications.
Application of the Bacterial Meningitis Score for Infants Aged 0 to 60 Days
Authors: Rees Chris A , Cruz Andrea T , Freedman Stephen B , Mahajan Prashant , Uspal Neil G , Okada Pamela , Aronson Paul L , Thompson Amy D , Ishimine Paul T , Schmidt Suzanne M , Kuppermann Nathan , Nigrovic Lise E ,   HSV Study Group of the Pediatric Emergency Medicine Collaborative Research Committee
Published: November 2018

In 4292 infants aged ≤60 days with cerebrospinal fluid (CSF) pleocytosis, the bacterial meningitis score had excellent sensitivity (121 of 121 [100.0%] [95% confidence interval, 96.5%–100.0%]) but low specificity (66 of 4171 [1.6%] [95% confidence interval, 1.3%–2.0%]) and therefore should not be applied clinically to infants in this age group.
Growth of Lumbosacral Perineural (Tarlov) Cysts: A Natural History Analysis
Authors: Yang Andrew I , Rinehart Cole D , McShane Brendan J , Hitti Frederick L , Welch William C
Published: November 2018

BACKGROUND

Tarlov cysts (TC) are commonly found spinal perineural cysts. Symptomatic TCs are rare, however, and there is no consensus on their pathogenesis and optimal management.

OBJECTIVE

To characterize cyst growth in patients with symptomatic TCs.

METHODS

This is a retrospective cohort study of 28 subjects, evaluated for symptomatic TCs (2011-2017). Each of the subjects had multiple magnetic resonance imaging (MRIs) across time and was included in a natural history analysis.

RESULTS

A total of 42 TCs were identified across the 28 subjects, of which 7 cysts (17%) across 5 subjects demonstrated growth. Across a mean follow-up of 4.7 ± 1.8 years, TCs grew at a relative rate of 2.9 ± 2.6% in the anteroposterior, 4.3 ± 3.8% in the craniocaudal, and 1.4 ± 1.4% in the transverse dimensions per year. None of the cysts decreased in size between successive MRIs. Symptoms of cerebrospinal fluid (CSF) hypotension (positional headaches) were positive predictors of prior cyst growth on logistic regression (P = 0.02, odds ratio = 10). A total of 2 of the 5 subjects were initially asymptomatic from their TCs, and developed symptoms during the period of cyst growth, whereas 2 others experienced worsening of their symptoms during cyst growth.

CONCLUSION

We report on the growth of TCs, which is consistent with a widely-held theory that hydrostatic and pulsatile forces of CSF along with a ball-valve phenomenon allow for continuous dilation of TCs.
Free-Base and Total Nicotine, Reactive Oxygen Species, and Carbonyl Emissions From IQOS, a Heated Tobacco Product
Authors: Salman Rola , Talih Soha , El-Hage Rachel , Haddad Christina , Karaoghlanian Nareg , El-Hellani Ahmad , Saliba Najat A , Shihadeh Alan
Published: November 2018

Introduction

IQOS is an emerging heated tobacco product marketed by Philip Morris International (PMI). Because the tobacco in IQOS is electrically heated and not combusted, PMI claims that it generates significantly lower toxicant levels than combustible cigarettes. To date, a few independent studies have addressed IQOS toxicant emissions, and none have reported reactive oxygen species (ROS), and the form of the nicotine emitted by the device.

Methods

In this study, IQOS aerosol was generated using a custom-made puffing machine. Two puffing regimens were used: Health Canada Intense and ISO. ROS, carbonyl compounds (CCs), and total nicotine and its partitioning between free-base and protonated forms were quantified in the IQOS aerosol by fluorescence, high-performance liquid chromatography, and gas chromatography, respectively. The same toxicants were also quantified in combustible cigarette aerosols for comparison. In addition, propylene glycol and vegetable glycerin were also measured in the IQOS tobacco and aerosol.

Results

IQOS and combustible cigarettes were found to emit similar quantities of total and free-base nicotine. IQOS total ROS (6.26 ± 2.72 nmol H2O2/session) and CC emissions (472 ± 19 µg/session) were significant, but 85% and 77% lower than levels emitted by combustible cigarettes.

Conclusions

IQOS emits harmful constituents that are linked to cancer, pulmonary disease, and addiction in cigarette smokers. For a given nicotine intake, inhalation exposure to ROS and CCs from IQOS is likely to be significantly less than that for combustible cigarettes.

Implications

IQOS is PMI’s new heated tobacco product. PMI claims that because IQOS heats and does not burn tobacco it generates low toxicant yields. We found that one IQOS stick can emit similar free-base and total nicotine yields as a combustible cigarette. A pack-a-day equivalent user of IQOS may experience significant inhalation exposure of ROS and CCs compared to background air. However, substituting IQOS for combustible cigarettes will likely result in far lower ROS and carbonyl inhalation exposure for a given daily nicotine intake.
Web-Based Contingency Management for Adolescent Tobacco Smokers: A Clinical Trial
Authors: Harvanko Arit , Slone Stacey , Shelton Brent , Dallery Jesse , Fields Sherecce , Reynolds Brady
Published: November 2018

Introduction

Adolescence is a critical time when the majority of tobacco users initiate smoking. Contingency management for adolescent smoking cessation has shown promise in previous studies, but efficacy following removal of contingencies is not well understood. This study examined a remote form of contingency management among non-treatment-seeking adolescent smokers.

Methods

Participants (N = 127) submitted breath carbon monoxide (CO) three times daily throughout a 42-day program. For this randomized trial, participants in the active condition (n = 63) were reinforced for providing CO measurements on schedule and below a set criterion, whereas those in the control condition (n = 64) were reinforced for providing CO measurements on schedule. Self-reported smoking and urinary cotinine levels were collected at several timepoints.

Results

Active condition showed greater within-group reductions in CO levels relative to control condition, but not at 3- or 6-month follow-up. Active condition reported significantly less smoking during treatment compared to control condition, but not at follow-up. There were no significant differences for urinary cotinine. Overall treatment adherence was low, with only 37% and 51% of possible CO samples being submitted among active and control, respectively. Poor treatment adherence may explain the disparity between CO and cotinine results, and poor follow-up treatment efficacy.

Conclusions

This study replicates feasibility of a remote form of contingency management for adolescent smoking. CO results suggest active condition reduced smoking within group, but treatment adherence and posttreatment efficacy was poor. Future research should focus on increasing adherence for this type of program among adolescent smokers.

Implications

This study demonstrates feasibility of a remote form of contingency management therapy for smoking cessation among adolescents, while providing posttreatment efficacy data. Within-group efficacy of this form of treatment is suggested, but treatment adherence and follow-up efficacy were poor. This study underscores the need for further development of contingency management therapy for adolescent smoking cessation, which emphasizes better treatment adherence and posttreatment efficacy.
Property of young massive clusters in a galaxy–galaxy merger remnant
Authors: Matsui Hidenori , Tanikawa Ataru , Saitoh Takayuki R
Published: November 2018

We investigate the properties of young massive clusters (YMCs) in a galaxy–galaxy merger remnant by analyzing the data obtained by a gas-rich major merger simulation in Matsui et al. (2012, ApJ, 746, 26). We found that the YMCs are distributed at a few kpc and at ∼10 kpc from the galactic center; in other words, there are two components of their distribution. The former are formed in filamentary and turbulent gas generated at a few kpc from the center as a result of galaxy encounters, and the latter are formed in tidal tails which are far from the center. The YMCs are much less concentrated than galaxy stars. The mass function of the YMCs is dN/dM∝M−2. Most YMCs are formed between the second encounter and the final coalescence phase of the galactic cores, and their formation rate is especially high at the final coalescence phase. Most of them consist of single stellar population in age, but YMCs with multi-stellar populations in age are also formed. The multiple populations are produced by the following process: a YMC captures dense gas, and another generation of stars form within the cluster. There are several YMCs formed in an isolated disk before the encounter of galaxies. These candidates contain stars with various ages by capturing dense gas and forming stars. YMCs in a merger remnant have various orbits, but a large fraction of candidates have circular orbits.
Associations between smoking and extra-axial manifestations and disease severity in axial spondyloarthritis: results from the BSR Biologics Register for Ankylosing Spondylitis (BSRBR-AS)
Authors: Zhao Sizheng , Jones Gareth T , Macfarlane Gary J , Hughes David M , Dean Linda E , Moots Robert J , Goodson Nicola J
Published: November 2018

Objective

The effects of smoking on disease manifestations in axial SpA are inadequately described. Utilizing a large and well-characterized cohort, we investigated the association between smoking and extra-axial manifestations, and smoking and disease severity measures.

Methods

Baseline data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis were explored. Our analyses focused on extra-axial manifestations and other disease severity measures, including scales for fatigue, sleep, anxiety and depression. Logistic and linear models were used to quantify associations between disease characteristics according to smoking status (current/ex/never) and quantity (heavy/light), adjusting for age, gender, BMI, education, deprivation, comorbidities, symptom duration and alcohol status.

Results

A total of 2031 participants were eligible for the current analysis (68% male, mean age 49 years). Of these, 24% were current and 32% ex-smokers. When compared with non-smokers, current smokers had lower odds of uveitis [OR 0.7, 95% CI 0.5–0.9] and higher odds of psoriasis (ORadj 1.6, 95% CI 1.1–2.3). Ex- and current smokers had incrementally more severe disease than never smokers, with higher BASDAI (β = 0.3, 95% CI 0.1–0.6; β = 0.9, 95% CI 0.6–1.2) and BASFI (β = 0.5, 95% CI 0.2–0.8; β = 1.3, 95% CI 1.0–1.6); similar associations were observed for fatigue, sleep, anxiety and depression.

Conclusion

In this large cross-sectional study, we observed that smoking is independently associated with an adverse disease profile in axial SpA, including worse fatigue, sleep, anxiety and depression, and higher odds of psoriasis. The paradoxical association between current smoking and reduced odds of uveitis is interesting and warrants further investigation.
Three Lymphadenectomy Strategies in Low-Risk Endometrial Carcinoma: A Cost-effectiveness Analysis
Authors: Suidan Rudy S. , Sun Charlotte C. , Cantor Scott B. , Mariani Andrea , Soliman Pamela T. , Westin Shannon N. , Lu Karen H. , Giordano Sharon H. , Meyer Larissa A.
Published: November 2018

(Abstracted from Obstet Gynecol 2018;132:52–58)

There has been an ongoing debate on the optimal approach to lymph node dissection in women with endometrial cancer. Traditionally, routine lymph node dissection has been considered to be the standard of care for surgical management of endometrial cancer.
Different Patterns of Ovarian Recovery After Cancer Treatment Suggest Various Individual Ovarian Susceptibilities to Chemotherapy
Authors: Decanter Christine , Cloquet Marc , Dassonneville Audrey , D'Orazio Emmanuelle , Mailliez Audrey , Pigny Pascal
Published: November 2018

(Abstracted from Reprod Biomed Online 2018;36:711–718)

A late marker for the resumption of follicle growth after chemotherapy is the final recovery of menstrual activity. This can be monitored by measuring concentrations of anti–müllerian hormone (AMH), which is a real-time indicator of both follicular depletion and renewal of growth.