bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Train Energy Consumption on the Wear of Railroad Catenary Contact Conductor
Authors: Niringiyimana Egide , Nkundineza Celestin
Published: July 2021

With current rise of climate change worldwide, transport industry contributes up to 21% of the world’s total Green House Gases (GHG). In addition to that developing cities are facing great changes in urbanization, population growth and environmental concerns. In these instances, railway transportation is a top contender on land transport mode to achieve sustainable mobility in fast growing cities. For railway operation, apart from wheel-rail contact, the catenary system has a very high initial investment cost as well as associated maintenance cost. It is important to monitor the damage evolution of the catenary components for developing better maintenance strategies. This study utilizes a co-simulation between the railway catenary system dynamics and electrical power flow. With reference to Addis Ababa Light Rail Transit Service (AALRTS), the power and current drawn by the running train were calculated. Then the heat losses in the conductor wire were obtained with respect to train location on the line. This procedure was followed by thermal analysis that allowed us to obtain temperature rise in the conductor. The temperature results were used as some of the inputs in the dynamic explicit finite element model of the coupled catenary and sliding pantograph. From the finite element analysis, different quantities such as contact forces and pressures, temperature rise because of friction between sliding parts, and deflections of conductor were obtained. Furthermore, the fluctuations of train loads were taken into consideration in the calculation of power consumption and hence in temperature rise. Increase in loads resulted in increase of current drawn which increases the temperature of the mating parts, which in-turn affected frictional stresses and forces. The latter were the input parameters in Archard wear model for calculating wear volume from the catenary contact conductor. It was observed that at different scenarios of train passenger loadings, the train experiences an increase in energy consumption, which results in slight increase of contact conductor wear by material removal.
Near-Field and Far-Field Sampling of Aerosol Plumes to Evaluate Particulate Emission Rates From a Falling Particle Receiver During On-Sun Testing
Authors: Glen Andrew , Dexheimer Darielle , Sanchez Andres L. , Ho Clifford K. , China Swarup , Mei Fan , Lata Nurun Nahar
Published: July 2021

High-temperature falling particle receivers are being investigated for next-generation concentrating solar power applications. Small sand-like particles are released into an open-cavity receiver and are irradiated by concentrated sunlight from a field of heliostats. The particles are heated to temperatures over 700 °C and can be stored to produce heat for electricity generation or industrial applications when needed. As the particles fall through the receiver, particles and particulate fragments in the form of aerosolized dust can be emitted from the aperture, which can lower thermal efficiency, increase costs of particle replacement, and pose a particulate matter (PM) inhalation risk. This paper describes sampling methods that were deployed during on-sun tests to record near-field (several meters) and far-field (tens to hundreds of meters) concentrations of aerosol particles within emitted plumes. The objective was to quantify the particulate emission rates and loss from the falling particle receiver in relation to OSHA and EPA National Ambient Air Quality Standards (NAAQS). Near-field instrumentation placed on the platform in proximity to the receiver aperture included several real-time aerosol size distribution and concentration measurement techniques, including a TSI Aerodynamic Particle Sizers (APS), TSI DustTraks, Handix Portable Optical Particle Spectrometers (POPS), Alphasense Optical Particle Counters (OPC), TSI Condensation Particle Counters (CPC), Cascade Particle Impactors, 3D-printed prototype tipping buckets, and meteorological instrumentation. Far-field particle sampling techniques utilized multiple tethered balloons located upwind and downwind of the particle receiver to measure the advected plume concentrations using a suite of airborne aerosol and meteorological instruments including POPS, CPCs, OPCs and cascade impactors. The combined aerosol size distribution for all these instruments spanned particle sizes from 0.02 μm – 500 μm. Results showed a strong influence of wind direction on particle emissions and concentration, with preliminary results showing representative concentrations below both the OSHA and NAAQS standards.
Artificial Neural Network Based Optimized Control of Condenser Water Temperature Set-Point
Authors: Kim Tae Young , Lee Jong Man , Hong Sung Hyup , Choi Jong Min , Lee Kwang Ho
Published: July 2021

In this study, we developed an artificial neural network-based real-time predictive control and optimization model to compare and analyze the difference in total energy consumption when the condenser water outlet temperature coming out of the cooling tower is fixed and when real-time control of the condenser water outlet temperature through the optimal ANN model is applied. An ANN model was developed through MATLAB’s built-in neural network toolbox functionality to predict total energy consumption. The model accuracy of the ANN was examined by applying Cv(RMSE), a statistical concept that shows the overall accuracy of the predicted values, and as a result, it was found to have a Cv(RMSE) value of approximately 25%. In addition, the predictive control algorithm was able to reduce cooling energy consumption by about 5.6% compared to the conventional control strategy that fix condenser water temperature set-point to constantly 30°C.
A Study on Estimation Model of Incidence Factor of the Thermal Bridge Using In-Situ Measurement Infrared Thermography
Authors: Kang Eunho , Lee Hyomoon , Kim Dongsu , Yoon Jongho
Published: July 2021

Practical thermal bridge performance indicators (ITBs) of existing buildings may differ from calculated thermal bridge performance derived theoretically due to actual construction conditions, such as effect of irregular shapes and aging. To fill this gap in a practical manner, more realistic quantitative evaluation of thermal bridge at on-site needs to be considered to identify thermal behaviors throughout exterior walls and thus improve overall insulation performance of buildings. In this paper, the model of a thermal bridge performance indicator is developed based on an in-situ Infrared thermography method, and a case study is then carried out to evaluate thermal performance of an existing exterior wall using the developed model. For the estimation method in this study, the form of the likelihood function is used with the Bayesian method to constantly reflect the measured data. Subsequently, the coefficient of variation is applied to analyze required times for the assumed convergence. Results from the measurement for three days show that thermal bridge under the measurement has more heat losses, including 1.14 times, when compared to the non-thermal bridge. In addition, the results present that it takes about 40 hours to reach 1% of the variation coefficient. Comparison of the ITB estimated at coefficient of variation 1% (40 hours point) with the ITB estimated at end-of-experiment (72 hours point) results in 0.9% of a relative error.
A Flexible Thermal Model for Solar Cavity Receivers Using Analytical View Factors
Authors: Kerkhoff Jacob A. , Wagner Michael J.
Published: July 2021

This paper presents advances to a thermal model for a cavity-type receiver that will be integrated into NREL’s System Advisor Model (SAM) software. Traditional concentrated solar power towers make use of an external cylindrical receiver where all active surfaces are fully exposed to the environment, resulting in significant convective and radiative losses. Cavity-type receivers promise to mitigate these losses by instead accepting solar flux through an aperture. In order to allow detailed resolution of the temperature distribution across the cavity, it is necessary to create refined meshes for different cavity geometries and determine the view factor accurately and quickly between any two elements in the mesh. To accomplish this, an analytical function is written to precisely calculate view factors between arbitrary planar polygons without requiring the use of computationally expensive Monte Carlo ray tracing. These view factors are modified using the F-hat method and used as the basis for a two-band radiation heat transfer model. Heat transfer fluid routing is handled through an elemental connectivity matrix, which specifies the elemental fluid temperature variation from inlet to outlet and allows the cavity mesh to interact with the fluid elements. The model is solved iteratively for panel and then fluid temperatures in order to account simultaneously for all energy transfers (convective, long wavelength, short wavelength, and fluid). This approach offers a computationally efficient but still detailed simulation of cavity receiver configurations making it suitable for use in an annual-hourly time series simulation tool such as SAM.
Application Methods for Refractory Insulation in Hot Particle Storage Bins
Authors: Sment Jeremy N. , Lambert Matthew , Albrecht Kevin J. , Ho Clifford K. , Davidson Murphy
Published: July 2021

The National Solar Thermal Test Facility (NSTTF) at Sandia National Laboratories is conducting research on a Generation 3 Particle Pilot Plant (G3P3) that uses falling sandlike particles as the heat transfer medium. G3P3 proposes a system with 6 MWh of thermal energy storage in cylindrical bins made of steel that will be insulated internally using multiple layers of refractory materials[1]. The refractory materials can be applied by stacking pre-cast panels in a cylindrical arrangement or by spraying refractory slurry to the walls (shotcrete). A study on the two methods determined that shotcrete would be the preferred method in order to minimize geometric tolerance issues in the pre-cast panels, improve repairability, and to more closely resemble commercial-scale construction methods. Testing and analysis was conducted which showed shotcrete refractories could be applied with minimal damage and acceptable heat loss.
Adhesive performance enhancement of the mushroom-shaped microstructured elastomer by atmospheric plasma treatment
Authors: Kizilkan Emre , Kovalev Alexander , Gorb Stanislav N.
Published: July 2021

Bioinspired reversible adhesives that have been developed in the course of recent years have found several applications in robotics, transportation, and marine applications. One of their prominent features is strong reversible static adhesion. To fulfill the requirements of various applications, the static adhesive performance of these materials can be enhanced by modifying the material and surface properties. In this work, the mushroom-shaped adhesive microstructured surface was functionalized by atmospheric plasma treatment to enhance its adhesive performances. Through optimizing the duration of the treatment, the pull-off force increase of up to 60% can be reached after the treatment in comparison to the measurements performed on the same mushroom-shaped microstructured sample before the treatment. In comparison to the microstructured samples, the attachment of the unstructured sample made of the same silicone elastomer was enhanced by 16% after plasma treatment. The strong adhesion enhancement on the microstructured sample was attributed to the combination of the changed effective elastic modulus of the material and the specific detachment behavior of microstructures. These results are anticipated to contribute to the further development of bioinspired dry adhesives and may potentially widen their usage in various technological applications.
The developmental biology of
Charnia
and the eumetazoan affinity of the Ediacaran rangeomorphs
Authors: Dunn Frances S. , Liu Alexander G. , Grazhdankin Dmitriy V. , Vixseboxse Philip , Flannery-Sutherland Joseph , Green Emily , Harris Simon , Wilby Philip R. , Donoghue Philip C. J.
Published: July 2021

Rangeomorphs represent a long-extinct group of eumetazoans with a bodyplan unlike anything alive today.
Genomic signatures of the unjamming transition in compressed human bronchial epithelial cells
Authors: De Marzio Margherita , Kılıç Ayşe , Maiorino Enrico , Mitchel Jennifer A. , Mwase Chimwemwe , O’Sullivan Michael J. , McGill Maureen , Chase Robert , Fredberg Jeffrey J. , Park Jin-Ah , Glass Kimberly , Weiss Scott T.
Published: July 2021

Temporal RNA-seq data reveal genomic signatures of the unjamming transition in compressed human bronchial epithelial cells.
An integrated giant polyoxometalate complex for photothermally enhanced catalytic oxidation
Authors: Chen Xiaofei , Zhang Guohua , Li Bao , Wu Lixin
Published: July 2021

A polyoxometalate cluster integrating a photothermal and catalytic center is used to synergistically enhance olefin oxidation.
A DNA repair pathway can regulate transcriptional noise to promote cell fate transitions
Authors: Desai Ravi V. , Chen Xinyue , Martin Benjamin , Chaturvedi Sonali , Hwang Dong Woo , Li Weihan , Yu Chen , Ding Sheng , Thomson Matt , Singer Robert H. , Coleman Robert A. , Hansen Maike M. K. , Weinberger Leor S.
Published: July 2021

DNA repair amplifies transcriptional noise

The potential role of noise, or stochastic variations in rates of gene expression, remains to be elucidated. Desai
et al
. used screens to identify a compound, 5′-iodo-2–-deoxyuridine (IdU), that increased gene expression noise in mouse embryonic stem cells in culture without changing the overall rate of transcription of most genes. They propose a model by which the thymidine analog IdU promotes binding of the base excision repair protein AP endonuclease to DNA, thereby inducing helical distortion of DNA and modulating transcriptional bursting. Such modulation of noise enhanced reprogramming of the embryonic stem cells. Thus, variation in gene expression noise could influence developmental or disease processes. —LBR
Spatiotemporal characterization of the field-induced insulator-to-metal transition
Authors: del Valle Javier , Vargas Nicolas M. , Rocco Rodolfo , Salev Pavel , Kalcheim Yoav , Lapa Pavel N. , Adda Coline , Lee Min-Han , Wang Paul Y. , Fratino Lorenzo , Rozenberg Marcelo J. , Schuller Ivan K.
Published: July 2021

Watching a metal filament grow

Resistive switching is a process in which the electrical resistance of a sample changes abruptly in response to a voltage pulse, often by orders of magnitude. This process is at the heart of many neuromorphic computing approaches but visualizing it in both space and time is tricky. del Valle
et al
. monitored the resistive switching in three different vanadium oxide compounds by measuring time- and space-resolved optical reflectivity (see the Perspective by Hilgenkamp and Gao). A characteristic conducting filament was quickly nucleated on the inhomogeneities in the sample and then propagated due to Joule heating. —JS
Innovation and geographic spread of a complex foraging culture in an urban parrot
Authors: Klump Barbara C. , Martin John M. , Wild Sonja , Hörsch Jana K. , Major Richard E. , Aplin Lucy M.
Published: July 2021

Birds in the bin

It is by now well accepted that humans are not the only animal to have complex culture, and we have also found that ecological novelty can lead to cultural innovation. Klump
et al.
documented the emergence of an evolving set of behaviors in response to human-generated resources, specifically garbage bins, in sulphur-crested cockatoos. This finding both documents the existence and spread of complex foraging culture among parrots, a lineage known for high-level cognitive function, and illuminates how the spread of a cultural innovation can lead to regional distinct variations.

Science
, abe7808, this issue p.
456
Coherent manipulation of an Andreev spin qubit
Authors: Hays M. , Fatemi V. , Bouman D. , Cerrillo J. , Diamond S. , Serniak K. , Connolly T. , Krogstrup P. , Nygård J. , Levy Yeyati A. , Geresdi A. , Devoret M. H.
Published: July 2021

Superconducting spin qubit

To date, the most promising solid-state approaches for developing quantum information-processing systems have been based on the circulating supercurrents of superconducting circuits and manipulating the spin properties of electrons in semiconductor quantum dots. Hays
et al.
combined the desirable aspects of both approaches, the scalability of the superconducting circuits and the compact footprint of the quantum dots, to design and fabricate a superconducting spin qubit (see the Perspective by Wendin and Shumeiko). This so-called Andreev spin qubit provides the opportunity to develop a new quantum information processing platform.

Science
, abf0345, this issue p.
430
; see also abk0929, p.
390
Proximity and single-molecule energetics
Authors: Li Linfei , Jiang Nan
Published: July 2021

Scanning probes measure how nearby oxygen molecules affect triplet lifetimes of pentacene
Pax5 regulates B cell immunity by promoting PI3K signaling via PTEN down-regulation
Authors: Calderón Lesly , Schindler Karina , Malin Stephen G. , Schebesta Alexandra , Sun Qiong , Schwickert Tanja , Alberti Chiara , Fischer Maria , Jaritz Markus , Tagoh Hiromi , Ebert Anja , Minnich Martina , Liston Adrian , Cochella Luisa , Busslinger Meinrad
Published: July 2021

Pax5 controls the generation, proliferation, and survival of all mature B cells by promoting PI3K signaling via PTEN down-regulation.
Complete Genome Sequence of the
Anabaena
Myophage Elbi
Authors: Patel Ria , Chen Julia , Xu Julie , Erdmann Emily , Laughlin Zoephia , Alvey Richard M.
Published: July 2021

Here, we report the genome sequence of bacteriophage Elbi that infects the cyanobacterium
Anabaena
sp. strain PCC 7120, a model organism for prokaryotic multicellular development. The 68,626 bp encode 108 proteins, of which 31 can be assigned a function. Elbi is similar to two
Anabaena
myophages, namely, A-1 and N-1, isolated in the 1970s.
Translithospheric magma plumbing system of intraplate volcanoes as revealed by electrical resistivity imaging
Authors: Li Yabin , Weng Aihua , Xu Wenliang , Zou Zonglin , Tang Yu , Zhou Zikun , Li Shiwen , Zhang Yanhui , Ventura Guido
Published: July 2021

The magma plumbing systems of volcanoes in subduction and divergent tectonic settings are relatively well known, whereas those of intraplate volcanoes remain elusive; robust geophysical information on the magma pathways and storage zones is lacking. We inverted magnetotelluric data to image the magma plumbing system of an intraplate monogenetic volcanic field located above the stagnant Pacific slab in northeast China. We identified a complex, vertically aligned, low-resistivity anomaly system extending from the asthenosphere to the surface consisting of reservoirs with finger- to lens-like geometries. We show that magma forms as CO2-rich melts in a 150-km-deep asthenospheric plume crossing the whole lithosphere as hydrated melt, inducing underplating at 50 km depth, evolving in crustal reservoirs, and erupting along dikes. Intraplate volcanoes are characterized by low degrees of melting and low magma supply rates. Their plumbing systems have a geometry not so different from that of volcanoes in subduction settings.
Extreme fractionation of selenium isotopes and possible deep biospheric origin of platinum nuggets from Minas Gerais, Brazil
Authors: Cabral Alexandre Raphael , König Stephan , Eickmann Benjamin , Brauns Michael , Tupinambá Miguel , Lehmann Bernd , Varas-Reus María Isabel
Published: July 2021

Platinum-rich nuggets offer an opportunity for understanding how precious metals accumulate. We analyzed the selenium (Se) isotopic composition of Se-rich (102–103 µg g−1) platinum-palladium (Pt-Pd) nuggets from a recent placer deposit in Minas Gerais, Brazil, for which a biogenic origin has been inferred. We obtained Se isotopic values with a relatively narrow range (δ82/76SeNIST3149 = −17.4 to −15.4 ± 0.2, two standard deviations [2 SD]). The Pt-Os age of the nuggets is 181 ± 6 Ma (2 SD). The data indicate that the nuggets did not form in the recent placer deposit, but by replacement of hydrothermal vein minerals at ~70 °C and at least 800 m below the surface. The high abundance and extreme isotopic composition of Se as well as the presence of other biophilic elements like iodine, organic carbon, and nitrogen within the nugget matrix are consistent with a microbial origin. Although abiogenic reduction of Se oxyanions cannot be ruled out, the nuggets plausibly record Se-supported microbial activity in the deep biosphere.
Microstructure and Rheological Behavior of Stabilized Gold Nanoparticles Hydrosol
Authors: Kamyshinsky R. A. , Kuznetsov N. M. , Lebedev-Stepanov P. V. , Stepko A. S. , Chvalun S. N. , Vasiliev A. L.
Published: July 2021

A comprehensive analysis of an aqueous solution of gold nanoparticles with an average size of 6 nm in a citrate buffer has been carried out, with investigation of the solution rheology and structure by electron and atomic force microscopy. A deviation of the rheological behavior of hydrosol from the Newtonian properties is found even at low gold nanoparticle concentrations. The specific features of the rheological behavior of hydrosol are explained based on the transmission electron microscopy (TEM) data.
Auricular acupuncture induces FNDC5/irisin and attenuates obese inflammation in mice
Authors: Lu Yi , Li Guohua
Published: July 2021

Objective:

To investigate whether auricular acupuncture (AA) attenuates bodyweight and obese inflammation through the release of irisin from muscle tissue in mice.

Methods:

Sixty 4-week-old mice were fed a high fat diet (HFD) for 4 weeks. These animals were divided into six groups that remained untreated (HFD) or underwent electrical AA (HFD+EAA), sham EAA (HFD+SEAA), adrenalectomy (HFD+AD), adrenalectomy and EAA (HFD+AD+EAA), or adrenalectomy and injection of recombinant lentivirus expressing fibronectin type III domain-containing protein 5 (rFNDC) (HFD+AD+rFNDC) in the ninth week. The EAA and SEAA were performed at two traditional auricular acupuncture points daily for 4 weeks. An additional 10 mice fed a control diet were included as a normal control (NC) group. At the end of the study, norepinephrine (NE) in the serum, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β) in the serum and white adipose tissue, irisin in the serum and muscle, uncoupling protein-1 (UCP-1) in the brown adipose tissue (BAT), and FNDC5 in the muscle, were analysed.

Results:

The AD+EAA group exhibited better control of bodyweight and inflammation compared with the AD+SEAA and untreated HFD model groups (P<0.05), especially regarding the increased expression of NE, FNDC5, irisin and UCP-1 (P<0.05). After adrenalectomy, mice receiving EAA had less NE, FNDC5, irisin and UCP-1 as well as greater expression of inflammatory cytokines and bodyweight. However, lentiviral overexpression of rFNDC successfully reversed this situation in the AD mice and mimicked the effects of EAA on bodyweight, inflammation and expression of FNDC5, irisin and UCP-1, although it did not impact NE.

Conclusions:

EAA promoted NE release from the adrenal gland leading to further expression of FNDC5, irisin and UCP-1, which contributed to weight management and inflammatory inhibition.
Multi-valvular infective endocarditis fromGemella morbillorum
Authors: Desai Anish Kumar , Bonura Erin Murchan
Published: July 2021

Gemella morbillorumis increasingly implicated in infectious endocarditis. Our patient presented with anaemia and renal failure with evidence of infarcts and embolic disease. He was found to have endocarditis with an organism that could not speciate with standard culture methods requiring matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) for identification and susceptibilities. While involvement of mitral and aortic valves can be expected withGemella, he had rare involvement of the pulmonic valve in a structurally normal heart. Although bacteriological cure was achieved, due to the locally destructive nature ofGemella, he ultimately required valve replacements for heart failure resolution. Workup for commonly implicated pathologies associated withG. morbillorumled to suspicion of gastrointestinal malignancy with findings of occult bleeding prompting an ongoing evaluation. With improved access to advanced diagnostics,G. morbillorumhas been increasingly identified in infectious endocarditis. Given its destructive nature, it is important for clinicians to consider this organism is difficult to identify isolates.
Factors predictive of cystoid macular oedema following endothelial keratoplasty: a single-centre review of 2233 cases
Authors: Myerscough James , Roberts Harry William , Yu Angeli Christy , Mimouni Michael , Furiosi Luca , Mandrioli Matteo , Giannaccare Giuseppe , Busin Massimo
Published: July 2021

Aims

To describe the incidence of postoperative cystoid macular oedema (CMO) after endothelial keratoplasty (EK) and to identify its contributory risk factors.

Methods

2233 patients undergoing EK at Ospedali Privati Forlì ‘Villa Igea’, between January 2005 to October 2018 for Descemet stripping automated endothelial keratoplasty (DSAEK) and June 2014 to August 2018 for Descemet membrane endothelial keratoplasty (DMEK) with a minimum follow-up of 18 months were evaluated. Univariate and multivariate analyses were conducted to identify and quantify contributory risk factors. Receiver operating characteristic (ROC) curve analysis were performed to determine ideal cut-off points of continuous variables.

Results

CMO was identified in 2.82% (n=63) of the cases. CMO occurred in 2.36% of DSAEK eyes and in 5.56% of DMEK eyes (p=0.001). Average onset of CMO was 4.27±6.63 months (range: 1–34 months) postoperatively. Compared with those who did not develop CMO, a higher proportion of patients in the CMO group had diabetes (24.2% vs 9.8%, p<0.001) (OR=3.16, 95% CI: 1.72 to 5.81, p<0.001), a higher proportion of patients who underwent DMEK rather than DSAEK (28.6% vs 14.1%, p=0.001) (OR=2.42, 95% CI: 1.35 to 4.33, p=0.003) and were older (70.5±10.0 vs 67.1±14.3 years, p=0.01). Using the cut-off of 67 years as identified by ROC curve analysis, subjects aged >67 years (OR=2.35, 95% CI: 1.30 to 4.26, p=0.005) were more likely to develop CMO. There were no other significant differences between the groups.

Conclusions

Older age (>67 years), diabetes mellitus and DMEK have been identified as independent risk factors for postoperative CMO following EK. Close observation is necessary during the first postoperative year after EK, particularly in patients with risk factors.
Foveal structure and visual function in nanophthalmos and posterior microphthalmos
Authors: Müller Philipp L , Treis Tim , Alsaedi Abdulrahman , Webster Andrew R , Khaw Peng , Michaelides Michel , Wickham Louisa , Siriwardena Dilani , Foster Paul , Moosajee Mariya , Pavesio Carlos , Tufail Adnan , Egan Catherine
Published: July 2021

Background/aims

The reason for visual impairment in patients with nanophthalmos and posterior microphthalmos is not completely understood. Therefore, this study aims to investigate foveal structure, and the impact of demographic, clinical and imaging parameters on best-corrected visual acuity (BCVA) in these conditions.

Methods

Sixty-two eyes of 33 patients with nanophthalmos (n=40) or posterior microphthalmos (n=22), and 114 eyes of healthy controls with high-resolution retinal imaging including spectral-domain or swept-source optical coherence tomography images were included in this cross-sectional case–control study. Foveal retinal layer thickness was determined by two independent readers. A mixed-effect model was used to perform structure–function correlations and predict the BCVA based on subject-specific variables.

Results

Most patients (28/33) had altered foveal structure associated with loss of foveal avascular zone and impaired BCVA. However, widening of outer nuclear layer, lengthening of photoreceptor outer segments, normal distribution of macular pigment and presence of Henle fibres were consistently found. Apart from the presence of choroidal effusion, which had significant impact on BCVA, the features age, refractive error, axial length and retinal layer thickness at the foveal centre explained 61.7% of the variability of BCVA.

Conclusion

This study demonstrates that choroidal effusion, age, refractive error, axial length and retinal layer thickness are responsible for the majority of interindividual variability of BCVA as well as the morphological foveal heterogeneity in patients with nanophthalmos or posterior microphthalmos. This might give further insights into the physiology of foveal development and the process of emmetropisation, and support clinicians in the assessment of these disease entities.
Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK
Authors: Ogura Yuichiro , Jaffe Glenn J , Cheung Chui Ming Gemmy , Kokame Gregg T , Iida Tomohiro , Takahashi Kanji , Lee Won Ki , Chang Andrew A , Monés Jordi , D’Souza Divya , Weissgerber Georges , Gedif Kinfemichael , Koh Adrian
Published: July 2021

Purpose

To compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study.

Design

HAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration.

Methods

Of the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96.

Results

Mean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept.

Conclusion

In Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48.
Clinical and magnetic resonance study of a case of subacute sclerosing panencephalitis treated with ketogenic diet
Authors: Valente Mariarosaria , Del Negro Ilaria , Bagatto Daniele , Garbo Riccardo , Lettieri Christian , Bernardini Andrea , Nilo Annacarmen , Peri Maria Rosaria , Pecori Davide , Gigli Gian Luigi
Published: July 2021

Background

Subacute sclerosing panencephalitis is a progressive neurodegenerative disorder caused by a latent and mutant measles virus which is extremely rare in developed countries. The lack of effective treatments leads to the research of other anti-inflammatory and neuroprotective treatments.

Case

Here we present a case of a 17-year-old patient affected by subacute sclerosing panencephalitis who manifest a dramatic improvement in neurological and general clinical conditions, as well as an arrest in the progression of demyelinating process in the central nervous system, after the beginning of a high ratio ketogenic diet.

Conclusions

Given its anti-inflammatory, antioxidant and metabolic effects, we believe that ketogenic diet utilisation could be a rational approach, can be considered a safe add-on therapy, carrying on with only a minimal risk of adverse effects or interactions.
Prognostic value of proliferation, PD-L1 and nuclear size in patients with superior sulcus tumours treated with chemoradiotherapy and surgery
Authors: Blaauwgeers Hans , Lissenberg-Witte Birgit I , Dickhoff Chris , Duin Sylvia , Thunnissen Erik
Published: July 2021

Aims

The aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.

Methods

Proliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.

Results

Low proliferative activity (<20% MIB-1) was associated with better overall survival: 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%–50%) and high (MIB-1 >50%) proliferative activity (p=0.016). A negative PD-L1 status (<1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference −38.1; range −115.2 to 16.0; p<0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference −4.6; range −75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).

Conclusions

Low proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.
CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding study
Authors: Sanborn Rachel E , Hamid Omid , de Vries Elisabeth GE , Ott Patrick A , Garcia-Corbacho Javier , Boni Valentina , Bendell Johanna , Autio Karen A , Cho Daniel C , Plummer Ruth , Stroh Mark , Lu Lawrence , Thistlethwaite Fiona
Published: July 2021

Background

Probody® therapeutics are antibody prodrugs designed to be activated by tumor-associated proteases. This conditional activation restricts antibody binding to the tumor microenvironment, thereby minimizing ‘off-tumor’ toxicity. Here, we report the phase 1 data from the first-in-human study of CX-072 (pacmilimab), a Probody immune checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1), in combination with the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab.

Methods

Adults (n=27) with advanced solid tumors (naive to PD-L1/programmed cell death protein 1 or CTLA-4 inhibitors) were enrolled in the phase 1 combination therapy dose-escalation portion of this multicenter, open-label, phase 1/2 study (NCT03013491). Dose-escalation pacmilimab/ipilimumab followed a standard 3+3 design and continued until the maximum tolerated dose (MTD) was determined. Pacmilimab+ipilimumab was administered intravenously every 3 weeks for four cycles, followed by pacmilimab administered every 2 weeks as monotherapy. The primary objective was identification of dose-limiting toxicities and determination of the MTD. Other endpoints included the rate of objective response (Response Evaluation Criteria In Solid Tumors v.1.1).

Results

Twenty-seven patients were enrolled in pacmilimab (mg/kg)+ipilimumab (mg/kg) dose-escalation cohorts: 0.3+3 (n=6); 1+3 (n=3); 3+3 (n=3); 10+3 (n=8); 10+6 (n=6); and 10+10 (n=1). Dose-limiting toxicities occurred in three patients, one at the 0.3+3 dose level (grade 3 dyspnea/pneumonitis) and two at the 10+6 dose level (grade 3 colitis, grade 3 increased aspartate aminotransferase). The MTD and recommended phase 2 dose was pacmilimab 10 mg/kg+ipilimumab 3 mg/kg administered every 3 weeks. Pacmilimab-related grade 3–4 adverse events (AEs) and grade 3–4 immune-related AEs were reported in nine (33%) and six (22%) patients, respectively. Three patients (11%) discontinued treatment because of AEs. The overall response rate was 19% (95% CI 6.3 to 38.1), with one complete (anal squamous cell carcinoma) and four partial responses (cancer of unknown primary, leiomyosarcoma, mesothelioma, testicular cancer). Responses lasted for >12 months in four patients.

Conclusions

The MTD and recommended phase 2 dose of pacmilimab (10 mg/kg)+ipilimumab (3 mg/kg) every 3 weeks is active and has a favorable tolerability profile.
Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead
Authors: Kirtane Kedar , Elmariah Hany , Chung Christine H , Abate-Daga Daniel
Published: July 2021

While immune checkpoint inhibitors (ICIs) have ushered in major changes in standards of care for many solid tumor malignancies, primary and acquired resistance is common. Insufficient antitumor T cells, inadequate function of these cells, and impaired formation of memory T cells all contribute to resistance mechanisms to ICI. Adoptive cellular therapy (ACT) is a form of immunotherapy that is rapidly growing in clinical investigation and has the potential to overcome these limitations by its ability to augment the number, specificity, and reactivity of T cells against tumor tissue. ACT has revolutionized the treatment of hematologic malignancies, though the use of ACT in solid tumor malignancies is still in its early stages. There are currently three major modalities of ACT: tumor-infiltrating lymphocytes (TILs), genetically engineered T-cell receptors (TCRs), and chimeric antigen receptor (CAR) T cells. TIL therapy involves expansion of a heterogeneous population of endogenous T cells found in a harvested tumor, while TCRs and CAR T cells involve expansion of a genetically engineered T-cell directed toward specific antigen targets. In this review, we explore the potential of ACT as a treatment modality against solid tumors, discuss their advantages and limitations against solid tumor malignancies, discuss the promising therapies under active investigation, and examine future directions for this rapidly growing field.
Cushing’s disease presenting with psychosis
Authors: Mubarak Mohamed Ahmed Saeed , Iqbal Ahmed , Prasad Suveera , Hoggard Nigel , Blackburn Daniel
Published: July 2021

Cushing’s disease is a rare endocrine condition in which a pituitary corticotroph adenoma drives excess adrenal cortisol production, and is one cause of endogenous Cushing’s syndrome. We present a young woman with 3 weeks of headaches and cognitive disturbance who subsequently developed florid psychosis requiring multiple admissions under neurology and psychiatry. Her clinical stigmata of hypercortisolism and biochemical abnormalities prompted an MR scan of the pituitary, which confirmed a pituitary microadenoma. Treatment with metyrapone and subsequent surgery led to complete recovery within 2 months. Cushing’s disease commonly causes neuropsychiatric symptoms and can present with psychosis. Diagnosing Cushing’s disease can be challenging, but with early diagnosis and treatment it has an excellent prognosis.
Factors associated with receipt of intracranial pressure monitoring in older adults with traumatic brain injury
Authors: Ghneim Mira , Albrecht Jennifer , Brasel Karen , Knight Ariel , Liveris Anna , Watras Jill , Michetti Christopher P , Haan James , Lightwine Kelly , Winfield Robert D , Adams Sasha D , Podbielski Jeanette , Armen Scott , Zacko J Christopher , Nasrallah Fady S , Schaffer Kathryn B , Dunn Julie A , Smoot Brittany , Schroeppel Thomas J , Stillman Zachery , Cooper Zara , Stein Deborah M
Published: July 2021

Background

The Brain Trauma Foundation (BTF) Guidelines for the Management of Severe Traumatic Brain Injury (TBI) include intracranial pressure monitoring (ICPM), yet very little is known about ICPM in older adults. Our objectives were to characterize the utilization of ICPM in older adults and identify factors associated with ICPM in those who met the BTF guidelines.

Methods

We analyzed data from the American Association for the Surgery of Trauma Geriatric TBI Study, a registry study conducted among individuals with isolated, CT-confirmed TBI across 45 trauma centers. The analysis was restricted to those aged ≥60. Independent factors associated with ICPM for those who did and did not meet the BTF guidelines were identified using logistic regression.

Results

Our sample was composed of 2303 patients, of whom 66 (2.9%) underwent ICPM. Relative to Glasgow Coma Scale (GCS) score of 13 to 15, GCS score of 9 to 12 (OR 10.2; 95% CI 4.3 to 24.4) and GCS score of <9 (OR 15.0; 95% CI 7.2 to 31.1), intraventricular hemorrhage (OR 2.4; 95% CI 1.2 to 4.83), skull fractures (OR 3.6; 95% CI 2.0 to 6.6), CT worsening (OR 3.3; 95% CI 1.8 to 5.9), and neurosurgical interventions (OR 3.8; 95% CI 2.1 to 7.0) were significantly associated with ICPM. Restricting to those who met the BTF guidelines, only 43 of 240 (18%) underwent ICPM. Factors independently associated with ICPM included intraparenchymal hemorrhage (OR 2.2; 95% CI 1.0 to 4.7), skull fractures (OR 3.9; 95% CI 1.9 to 8.2), and neurosurgical interventions (OR 3.5; 95% CI 1.7 to 7.2).

Discussion

Worsening GCS, intraparenchymal/intraventricular hemorrhage, and skull fractures were associated with ICPM among older adults with TBI, yet utilization of ICPM remains low, especially among those meeting the BTF guidelines, and potential benefits remain unclear. This study highlights the need for better understanding of factors that influence compliance with BTF guidelines and the risks versus benefits of ICPM in this population.

Level of evidence

Prognostic and epidemiological, level III.
Dexmedetomidine upregulates the expression of miR-493-5p, inhibiting growth and inducing the apoptosis of lung adenocarcinoma cells by targeting RASL11B
Authors: Xu Bo , Qian Yiling , Hu Chunxiao , Wang Yongsheng , Gao Hong , Yang Jianping
Published: July 2021

Numerous studies have indicated that microRNAs (miRNAs) play critical roles in the development and progression of cancer. However, how changes to the expression levels of miRNAs in response to dexmedetomidine affects the progression of lung cancer remains poorly understood. In this study, we treated the lung adenocarcinoma cell line-A549 with dexmedetomidine and then examined the changes to the expression levels of miRNAs. We found that one of the most significantly upregulated miRNAs was miR-493-5p, which has an important role in the growth and apoptosis of lung adenocarcinoma (LUAD) cells. In addition, bioinformatics searches and luciferase reporter assays revealed that miR-493-5p targets RASL11B, which has a high degree of similarity to RAS. Finally, database searches revealed that RASL11B is associated with survival of LUAD cells. In conclusion, dexmedetomidine causes changes to the expression levels of miRNAs in LUAD, including significant upregulation of miR-493-5p. MiR-493-5p targets RASL11B, thereby inhibiting cell growth and inducing apoptosis in LUAD.
Effect of environmental factors on polyketide synthase gene expression, usnic acid biosynthesis, and ground cover of a lichen-fungus, Cladonia uncialis
Authors: Gunawardana W.G. Duleeka I. , Sveshnikova Natalia , Arsenault André , Piercey-Normore Michele D.
Published: July 2021

Lichens are composed of symbiotic slow-growing organisms and are often exposed to extreme microenvironmental conditions, resulting in the production of unique secondary metabolites. One of the most commonly produced secondary metabolites is usnic acid, which is thought to be produced by two genes. The objectives of the present study were to compare polyketide synthase (PKS) gene expression and usnic acid concentration in Cladonia uncialis (L.) Weber ex F.H. Wigg., with two environmental factors. Seventy-five lichen samples were collected from three locations in Newfoundland, Canada, using a strip transect method (×5 transects, ×5 quadrats). Usnic acid concentration was measured using the liquid chromatography tandem mass-spectrometric method and gene expression of two PKS genes (methylphloracetophenone oxidase (MPAO) and methylphloracetophenone synthase (MPAS)) was examined using quantitative real-time PCR. The results showed that percent ground cover of C. uncialis was affected by soil pH level but not soil moisture, and usnic acid concentration was not affected by either soil pH or soil moisture. MPAO gene expression level was significantly affected by soil pH level but not soil moisture, and MPAS gene expression level was not affected by either soil pH level or soil moisture. There was no significant relationship between MPAS and MPAO gene expression levels and usnic acid concentration. These findings suggest that soil pH may be important for the production of usnic acid by C. uncialis but the genes involved require further study.
Formwork systems selection criteria for building construction projects: a critical review of the literature
Authors: Terzioglu Taylan , Turkoglu Harun , Polat Gul
Published: July 2021

The formwork system (FWS) is one of the key components in reinforced concrete (RC) construction. Therefore, selection of the most appropriate FWS plays a critical role in the project success. Because selection of the FWS is affected by several compromising and conflicting criteria, since the early 1990s, numerous studies have been carried out to identify the FWS selection criteria and (or) have employed various multicriterion decision-making (MCDM) methods. However, there is no research to date that has conducted a critical review of the previous studies addressing the FWS selection criteria in construction projects. This study aims to fill this knowledge gap. For this purpose, a critical review of the relevant literature was carried out using an integrative approach, and the findings were validated through face-to-face interviews with professionals specialized in formwork engineering. The findings of this study should provide practitioners with a useful guide that can assist them in selecting the most appropriate FWS.
High-resolution remote sensing and multistate occupancy estimation identify drivers of spawning site selection in fall chum salmon (Oncorhynchus keta) across a sub-Arctic riverscape
Authors: Clawson Chelsea M. , Falke Jeffrey A. , Bailey Larissa L. , Rose Joshua , Prakash Anupma , Martin Aaron E.
Published: July 2021

Groundwater upwellings provide warmer, stable overwinter temperatures for developing salmon embryos, which may be particularly important in cold, braided, gravel-bed sub-Arctic rivers. We used a three-year time series of aerial counts and remote sensing to estimate the distribution of low and high aggregations of spawning fall chum salmon (Oncorhynchus keta), classify approximately 0.5 km long river segments by geomorphic channel type, and map thermal variability along a 25.4 km stretch of the Teedriinjik River, Alaska. We used a dynamic multistate occupancy model to estimate detectability, occupancy, and the dynamics of spawning aggregations among river segments. Detectability was higher for large (>150) relative to smaller aggregations. Unoccupied segments were likely to remain so from year to year; low abundance spawning segments were dynamic and rarely remained in that state for multiple years, while ∼20%–35% of high abundance segments remained stable, indicating the presence of high-quality spawning habitat. Spawning habitat use was associated with warmer water temperatures likely caused by groundwater upwellings. We identified spawning habitat characteristics and trends in usage by fall chum salmon, which will inform land management decisions and assist in evaluating impacts of shifting climate conditions and resource management on Arctic salmon populations.