bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmark studies of hydrogen bond governing reactivity of cephalosporins inL1metallo‐β‐lactamase: Efficient and reliableQSPRequations
Authors: Khrenova Maria G. , Levina Elena O. , Tsirelson Vladimir G.
Published: September 2020

The combined quantum mechanics/molecular mechanics (QM/MM) simulations of equilibrium geometry configurations followed by electron density analysis provide reliable quantitative structure‐property relationship equations to estimate the reactivity of compounds in the active sites of enzymes. The main drawback is high computational cost of such calculations. Here, we report on a benchmark study aiming to optimize computational protocol for the accuracy of predictions. We considered an important example of cephalosporin hydrolysis in the active site of L1 metallo‐β‐lactamase and found that it is important to consider contributions to the one‐electron part of the QM Hamiltonian from all MM system rather than using the cutoff of electrostatic interactions. Switching from the reference PBE0‐D3/6‐31G(d,p) QM protocol to the reduced PBE0‐D3/6‐31G scheme decreases the number of basis set functions by almost twice, increasing the error of the rate constant estimates up to 18 seconds−1compared with the reference 10 seconds−1. Therefore, the QM(PBE0‐D3/6‐31G)/MM(AMBER) level of theory can be recommended for estimates of cephalosporin reactivity in the search of new antibiotics.
Indirect adaptive model predictive control and its application to uncertain linear systems
Authors: Di Cairano Stefano , Danielson Claus
Published: September 2020

We consider constrained systems that are represented by uncertain models with unknown constant or slowly varying parameters. We propose an indirect adaptive model predictive control (IAMPC) approach where the prediction model can be adjusted during controller operation by a separately designed estimator that satisfies only a minimal set of assumptions. The controller guarantees constraint satisfaction despite the uncertainty in the parameters by means of a robust control invariant set, and input‐to‐state stability with respect to the estimation error by means of an appropriately designed method for adjusting the IAMPC prediction model and cost function based on the evolution of the parameter estimate. The controller has minimal computational overhead with respect to a nominal MPC and for the special case of uncertain linear systems, we obtain a constructive design procedure for the IAMPC which only solves quadratic programs during closed‐loop control.
Robust global stabilization of a class of underactuated mechanical systems of two degrees of freedom
Authors: Gutiérrez‐Oribio Diego , Mercado‐Uribe José A. , Moreno Jaime A. , Fridman Leonid
Published: September 2020

In this article, the global stabilization of a class of underactuated mechanical systems of two degrees of freedom (DoF) is addressed, despite the presence of Lipschitz disturbances and/or uncertainties and uncertain control coefficient in the model. Using two second‐order continuous sliding modes algorithms, the control task is performed, reaching finite‐time convergence in one part of the dynamics and generating a continuous control signal. The efficacy of the proposed controllers is illustrated via simulations for the reaction wheel pendulum (RWP) and the translational oscillator with rotational actuator (TORA) systems, and by means of experiments on the RWP system, comparing the presented algorithms with a linearizing controller.
It’s Time to Be Scientific About Dyslexia
Authors: Elliott Julian G.
Published: September 2020

Tha author argues that despite the vast proliferation of scientific research, our understanding of dyslexia is marked by serious weaknesses of conceptualization, definition, and operationalization that are not only unscientific but also result in impoverished practice in schools, social inequity in both understanding and provision for many struggling readers, and ultimately, reduced life chances for millions of students worldwide. Key to this problem is the inconsistency of the use of the term dyslexia in both scientific research and clinical and educational practice. Four different, common conceptions of dyslexia are outlined, and the implications that each of these have for work with struggling readers are discussed. Whereas it is often claimed that scientific understandings, derived from genetics, neuroscience, and cognitive science, enable clinicians to validly identify, from within a larger group of poor readers, those individuals with dyslexia, the author shows this to be not only misleading but also potentially deleterious to broader inclusive practice. The author argues that the seemingly scientifically based construction of the dyslexic individual, often buoyed by vested interests, typically favors more socially privileged students and often undermines attempts to identify and help all of those who struggle to learn to read. Common responses by proponents to challenges to the dyslexia construct are outlined and discussed. In conclusion, the author argues that scientists, researchers, clinicians, and educators have a responsibility to address and confront the real‐world consequences of much science but little wisdom in the field of reading disability.
Beyond Decoding: A Meta‐Analysis of the Effects of Language Comprehension Interventions on K–5 Students’ Language and Literacy Outcomes
Authors: Silverman Rebecca D. , Johnson Erika , Keane Kristin , Khanna Saurabh
Published: September 2020

The debate over the science of reading has focused primarily on decoding (i.e., connecting letters and sounds to read words) and whether to use phonics to teach it. However, research on reading has included much more than decoding. Language comprehension, which allows readers to derive meaning from text, is an equally critical component of reading. Research has suggested that explicit instruction on the components of language comprehension—vocabulary and semantics, morphology, and syntax—can support language and reading comprehension. To inform the field on the science of reading as it pertains to language comprehension, in this meta‐analysis of recent language comprehension interventions (n = 43) in U.S. elementary schools, the authors examined whether effects vary depending on participant and intervention characteristics. Findings suggest positive effects on custom measures of vocabulary, listening comprehension, and reading comprehension but not on standardized measures of these outcomes. Results also indicate positive effects for English learners and promise for multicomponent interventions and those that include technology. Much more research is needed on how best to support language comprehension for underserved populations (e.g., students from low‐income backgrounds) and how interventions can be optimized to support generalizable language and literacy outcomes. Implications for policy and practice are discussed.
Peridynamic modeling of prefabricated beams post‐cast with steelfiber reinforced high‐strength concrete
Authors: Xu Chen , Yuan Yong , Zhang Yiming , Xue Yuan
Published: September 2020

For connecting precast concrete members in prefabricated structures, steel fiber reinforced high‐strength concrete (HSFRC) shows greater bearing capacity and better durability than normal reinforced concrete. When these structures are continuously loaded, multiply micro and macro cracks will appear. The modeling of this process is challenging because the conventional finite element modeling commonly encounters numerical problems such as stress locking and overestimations of the damaging zones. On the other hand, the novel peridynamics‐based theory models the continuous and discontinuous processes in the same framework, showing robustness. In this work, based on the recently presented micropolar peridynamics with shear deformability, a numerical tool with implicit iteration scheme for quasi‐static loading condition is built. With the proposed numerical tool, the damage processes of prefabricated beam post‐cast with HSFRC are simulated. The interaction between precast, post‐cast concrete, and rebars are taken into consideration. For validations, the numerically obtained results are compared with the experimental results, indicating that this tool can provide agreeable crack patterns, initial cracking loads, and yield loads of the beams.
Experimental study on fabricated shear wall structure with energy‐dissipating vertical joint
Authors: Wang Yuliang , Zhang Yumin , Cui Hongjun , Cai Zhanjun , Xu Lixian
Published: September 2020

Based on the design concept of 'strong horizontal joint and weak vertical joint', an energy‐dissipating fabricated shear wall structure system with a steel damper is proposed. The wall limbs were connected using the damper to realize the rapid assembly and improve the seismic performance of the fabricated shear wall structure. Four fabricated shear wall specimens and one cast‐in‐place comparison specimen were prepared, and a low‐cycle repeated load test was carried out under an axial compression ratio of 0.1. Results show that the fabricated shear wall structure features slightly reduced bearing capacity but obviously improved ductility, and the energy dissipation of the damper improves the seismic performance of the structure. The damper can dissipate energy rapidly, reduce the damage degree of the wall limbs and work stably, suggesting its good performance as a connector.
D‐galactose‐induced toxicity associated senescence mitigated by alpinate oxyphyllae fructus fortified adipose‐derived mesenchymal stem cells
Authors: Lin Hung‐Jen , Ramesh Samiraj , Chang Yung‐Ming , Tsai Chuan‐Te , Tsai Chin‐Chuan , Shibu Marthandam Asokan , Tamilselvi Shanmugam , Mahalakshmi B. , Kuo Wei‐Wen , Huang Chih‐Yang
Published: September 2020

This study addresses the effect of D‐galactose‐induced toxicity associated senescence mitigated by alpinate oxyphyllae fructus (AOF; Alpinia oxyphylla Miq) extracts fortified with adipose‐derived mesenchymal stem cells (ADMSCs) in rats. Male 18 week‐old Wistar Kyoto (WKY) rats were used in this study. We analyzed cardiac fibrosis by Masson's trichrome staining. The tissue sections were dyed using hematoxylin and eosin (H&E). Tissue sections were stained for the restoration of Nrf2 expression in treatment groups by immunohistochemistry. Immunohistochemistry and western blotting analysis showed that AOF with ADMSCs could significantly reduce aging‐induced oxidative stress in D‐galactose‐induced aging rat hearts by inducing Nrf2 pathway. Reduction in ROS resulted in the suppression of inflammatory signals (p‐NF‐κB and IL‐6). Histopathological studies were showed an increased interstitium and collagen accumulation in aging‐induced heart sections. However, AOF and ADMSCs treated hearts were recovered from cardiac remodeling. Furthermore, hypertrophy and fibrosis associated markers were also significantly reduced (P < .05) in treatment groups. We speculate that ADMSCs might activate certain paracrine factors, which could target the upstream activator of aging associated cardiac complications and AOF might provide homing for these stem cells.
Incorporating Multimodal Literacies Into Classroom‐Based Reading Assessment
Authors: Serafini Frank , Moses Lindsey , Kachorsky Dani , Rylak Danielle
Published: September 2020

As literacy researchers continue to investigate how young students make sense of texts, specifically picture books, attention has expanded beyond the role that written language plays in reading comprehension to the various ways that visual images, typography, design elements, and digital devices support and challenge young readers during the act of reading. This article is a description of classroom‐based research that led to the development of an assessment instrument for classroom teachers designed to help teachers observe readers using a variety of semiotic resources to make sense of contemporary picture books. As the texts that young readers encounter continue to evolve from language‐dominant texts to more complex multimodal ensembles, classroom‐based assessments must evolve as well to account for the semiotic resources that young readers use in navigating and comprehending multimodal texts.
Investigation of reduction in risk from antibiotic resistance genes in laboratory wastewater by using O3, ultrasound, and autoclaving
Authors: Lan Lihua , Xie Yinglong , Kong Xianwang , Li Changwei , Liu Dezhao
Published: September 2020

Biological laboratory wastewater containing both antibiotic‐resistant bacteria (ARB) and antibiotics is a potential source of antibiotic resistance genes (ARGs). Thus, we determined the efficacy of autoclaving, a common disinfection method, in eliminating 5 ARGs (sul1, sul2, tetW, tetM, amp) and the integrase‐encoding gene intI1 from laboratory wastewater. Autoclaving (15 min, 121°C) inactivated all bacteria including ARB, whereas ARGs persisted in the wastewater with limited reduction even after 60 min of treatment. Ozonation (O3), ultrasound (US), O3/US, and autoclaving followed by O3 were investigated for their ability to reduce ARGs in laboratory wastewater. With O3 and O3/US, the reduction rate ranged from 5.44 to 7.13 log for all ARGs investigated. Wastewater treatment with US alone did not reduce ARGs under the present experimental conditions (150 W, 53 kHz). Among the four treatments, autoclaving followed by O3 treatment showed the highest reduction rates in the shortest time; however, further optimization and investigation are needed for the advanced treatment of bio‐laboratory wastewater. Overall, this study provides novel insights into ARG sources and demonstrates that advanced oxidation methods can be useful to optimize laboratory wastewater treatment for ARG inactivation.

Practitioner points

Bio‐laboratory wastewater is potential reservoir of ARGs.

Conventional autoclaving was not able to reduce ARGs to a low level.

Autoclaving‐O3 completely eliminate all the bacteria.

Autoclaving‐O3 reduced ARGs efficiently (6.12–7.86 logs removal in 60 min).
Effect of Lure on Detecting Mammals with Camera Traps
Authors: Fidino Mason , Barnas Gabriella R. , Lehrer Elizabeth W. , Murray Maureen H. , Magle Seth B.
Published: September 2020

Motion‐triggered camera traps are subject to imperfect detection and thus camera‐trapping surveys often try to increase species detectability as part of the study design. One possible way to increase detectability is to use lures, which may encourage a species to investigate a given area. Yet the effectiveness of lures is primarily grounded in anecdotal support. We quantified the effect of a common olfactory carnivore lure on the detectability of mammals near Chicago, Illinois, USA, during 27 August 2018–25 September 2018. We deployed 2 camera traps per site, spaced apart by 100 m, to assess whether lure can modify detectability both within and between sites. At each camera location, we changed lure treatments every 7 days and placed either a lure or a non‐lure control in view of each camera following a fully crossed design. For analysis, we developed single‐season occupancy models with 3 distinct observational models to quantify whether lure increased the number of days a species was detected, decreased the amount of time to first detection, and increased the number of images collected. Lure induced a subtle change in detectability. Virginia opossum (Didelphis virginiana) responded most to the presence of lure; their daily detection probability rose by roughly 5% and the number of opossum images nearly doubled. However, the effect of lure was often negative for prey species. When lure was present, eastern cottontail (Sylvilagus floridanus) daily detection probability decreased by 5% and they were photographed 63% less often. Likewise, eastern gray squirrel (Sciurus carolinensis) arrived 70% later to a camera trap if lure was present and were photographed 14% less. By using multiple criteria, we were able to better understand how wildlife respond to lure while camera‐trapping more thoroughly than would be possible with a single metric. Our results show that lure may not be as effective as expected in terms of increasing detectability, but the choice to use lure should depend on several factors, including the density of the study species, species life history, and the dynamics between the species studied. © 2020 The Wildlife Society.
Fermentation profiles of the yeast Brettanomyces bruxellensis in d‐xylose and l‐arabinose aiming its application as a second‐generation ethanol producer
Authors: da Silva Jackeline Maria , Ribeiro Karol Cristianne , Teles Gilberto Henrique , Ribeiro Ester , de Morais Junior Marcos Antonio , de Barros Pita Will
Published: September 2020

The yeast Brettanomyces bruxellensis is able to ferment the main sugars used in first‐generation ethanol production. However, its employment in this industry is prohibitive because the ethanol productivity reached is significantly lower than the observed for Saccharomyces cerevisiae. On the other hand, a possible application of B. bruxellensis in the second‐generation ethanol production has been suggested because this yeast is also able to use d‐xylose and l‐arabinose, the major pentoses released from lignocellulosic material. Although the latter application seems to be reasonable, it has been poorly explored. Therefore, we aimed to evaluate whether or not different industrial strains of B. bruxellensis are able to ferment d‐xylose and l‐arabinose, both in aerobiosis and oxygen‐limited conditions. Three out of nine tested strains were able to assimilate those sugars. When in aerobiosis, B. bruxellensis cells exclusively used them to support biomass formation, and no ethanol was produced. Moreover, whereas l‐arabinose was not consumed under oxygen limitation, d‐xylose was only slightly used, which resulted in low ethanol yield and productivity. In conclusion, our results showed that d‐xylose and l‐arabinose are not efficiently converted to ethanol by B. bruxellensis, most likely due to a redox imbalance in the assimilatory pathways of these sugars. Therefore, despite presenting other industrially relevant traits, the employment of B. bruxellensis in second‐generation ethanol production depends on the development of genetic engineering strategies to overcome this metabolic bottleneck.
Modular Hamiltonians in flat holography and (W)AdS/WCFT
Authors: Apolo Luis , Jiang Hongliang , Song Wei , Zhong Yuan
Published: September 2020

Abstract

We study several aspects of holographic entanglement in two models known as flat3/BMSFT and (W)AdS3/WCFT. These are two examples of holography beyond AdS/CFT where the boundary field theories are not Lorentz invariant but still feature an infinite set of local symmetries. In the first example, BMS-invariant field theories (BMSFTs) are conjectured to provide a holographic description of quantum gravity in asymptotically flat three-dimensional spacetimes; while in the second example, warped conformal field theories (WCFTs) are proposed to describe quantum gravity in warped AdS3 or AdS3 backgrounds with Dirichlet-Neumann boundary conditions. In particular, we derive the modular Hamiltonian for single intervals in both BMSFTs and WCFTs and find the holographic duals in the bulk using the covariant formulation of gravitational charges. We also extend the first law of entanglement entropy to these models of non-AdS holography and discuss the bound on “modular chaos” introduced recently in the context of the AdS/CFT correspondence.
Pure gravity and conical defects
Authors: Benjamin Nathan , Collier Scott , Maloney Alexander
Published: September 2020

Abstract

We revisit the spectrum of pure quantum gravity in AdS3. The computation of the torus partition function will — if computed using a gravitational path integral that includes only smooth saddle points — lead to a density of states which is not physically sensible, as it has a negative degeneracy of states for some energies and spins. We consider a minimal cure for this non-unitarity of the pure gravity partition function, which involves the inclusion of additional states below the black hole threshold. We propose a geometric interpretation for these extra states: they are conical defects with deficit angle 2π(1−1/N), whereNis a positive integer. That only integer values ofNshould be included can be seen from a modular bootstrap argument, and leads us to propose a modest extension of the set of saddle-point configurations that contribute to the gravitational path integral: one should sum over orbifolds in addition to smooth manifolds. These orbifold states are below the black hole threshold and are regarded as massive particles in AdS, but they are not perturbative states: they are too heavy to form multi-particle bound states. We compute the one-loop determinant for gravitons in these orbifold backgrounds, which confirms that the orbifold states are Virasoro primaries. We compute the gravitational partition function including the sum over these orbifolds and find a finite, modular invariant result; this finiteness involves a delicate cancellation between the infinite tower of orbifold states and an infinite number of instantons associated with PSL(2,ℤ) images.
Quantum geometry and θ-angle in five-dimensional super Yang-Mills
Authors: Haouzi Nathan
Published: September 2020

Abstract

Five-dimensional Sp(N) supersymmetric Yang-Mills admits a ℤ2 version of a theta angle θ. In this note, we derive a double quantization of the Seiberg-Witten geometry of $$ \mathcal{N} $$
N
= 1 Sp(1) gauge theory at θ = π, on the manifold S1× ℝ4. Crucially, ℝ4 is placed on the Ω-background, which provides the two parameters to quantize the geometry. Physically, we are counting instantons in the presence of a 1/2-BPS fundamental Wilson loop, both of which are wrapping S1. Mathematically, this amounts to proving the regularity of a qq-character for the spin-1/2 representation of the quantum affine algebra $$ {U}_q\left(\hat{A_1}\right) $$

U
q

A
1

̂

, with a certain twist due to the θ-angle. We motivate these results from two distinct string theory pictures. First, in a (p, q)-web setup in type IIB, where the loop is characterized by a D3 brane. Second, in a type I′ string setup, where the loop is characterized by a D4 brane subject to an orientifold projection. We comment on the generalizations to the higher rank case Sp(N) when N > 1, and the SU(N) theory at Chern-Simons level κ when N > 2.
Magnetophonons & type-B Goldstones from hydrodynamics to holography
Authors: Baggioli Matteo , Grieninger Sebastian , Li Li
Published: September 2020

Abstract

We perform a detailed analysis of a large class of effective holographic models with broken translations at finite charge density and magnetic field. We exhaustively discuss the dispersion relations of the hydrodynamic modes at zero magnetic field and successfully match them to the predictions from charged hydrodynamics. At finite magnetic field, we identify the presence of an expected type-B Goldstone boson Re[ω] ∼ k2, known as magnetophonon and its gapped partner — the magnetoplasmon. We discuss their properties in relation to the effective field theory and hydrodynamics expectations. Finally, we compute the optical conductivities and the quasinormal modes at finite magnetic field. We observe that the pinning frequency of the magneto-resonance peak increases with the magnetic field, in agreement with experimental data on certain 2D materials, revealing the quantum nature of the holographic pinning mechanism.
Two-loop HTL-resummed thermodynamics for $$ \mathcal{N} $$ = 4 supersymmetric Yang-Mills theory
Authors: Du Qianqian , Strickland Michael , Tantary Ubaid , Zhang Ben-Wei
Published: September 2020

Abstract

We compute the two-loop hard-thermal-loop (HTL) resummed thermodynamic potential for$$ \mathcal{N} $$N= 4 supersymmetric Yang-Mills (SYM). Our final result is manifestly gauge-invariant and was renormalized using only simple vacuum energy, gluon mass, scalar mass, and quark mass counter terms. The HTL mass parametersmD,MD, andmqare then determined self-consistently using a variational prescription which results in a set of coupled gap equations. Based on this, we obtain the two-loop HTL-resummed thermodynamic functions of$$ \mathcal{N} $$N= 4 SYM. We compare our final result with known results obtained in the weak- and strong-coupling limits. We also compare to previously obtained approximately self-consistent HTL resummations and Padé approximants. We find that the two-loop HTL resummed results for the scaled entropy density is a quantitatively reliable approximation to the scaled entropy density for 0 ≤ λ ≲ 2 and is in agreement with previous approximately self-consistent HTL resummation results for λ ≲ 6.
Interaction among bacterioplankton and macrophytes in shallow lakes with high macrophyte cover
Authors: Szabó-Tugyi Nóra , Tóth Viktor R.
Published: September 2020

Growth of submerged and emergent macrophytes was studied together with heterotrophic bacterioplankton abundance and production in two Hungarian shallow lakes with dominant macrophyte covers. It was expected that bacterioplankton numbers and activity would have an effect on macrophyte biomass accumulation. Bacterial production and abundance showed a strong seasonal pattern with maximum in the warmest months (July, August). It was found that macrophyte biomass increased with heterotrophic bacterial production and abundance up to 5.6 µg C l− 1 h− 1 and 5.30*106 cells, respectively, while over that value was negatively associated with macrophyte growth. It was also shown that the relationship between heterotrophic bacteria and macrophytes also varied seasonally, showing a multifaceted relationship. It was demonstrated that macrophytes are not only the most significant carbon and energy source for the bacteria in shallow, macrophyte-dominated lakes, but are also competing organisms that could be supressed by excessive bacterial activity. These findings could help better understand the interaction between macrophytes and bacterioplankton, and assist wetland managers in quantifying what may be a primary cause of reed die-back.
GNSS scale determination using calibrated receiver and Galileo satellite antenna patterns
Authors: Villiger Arturo , Dach Rolf , Schaer Stefan , Prange Lars , Zimmermann Florian , Kuhlmann Heiner , Wübbena Gerhard , Schmitz Martin , Beutler Gerhard , Jäggi Adrian
Published: September 2020

The reference frame of a global terrestrial network is defined by the origin, the orientation and the scale. The origin of the ITRF2014 is defined by the ILRS long-term solution, the orientation by no-net rotation conditions w.r.t. the previous reference frame (ITRF2008), and the scale by the mean values from global VLBI and SLR solution series (Altamimi et al. in J Geophys Res Solid Earth 121:6109–6131, 2016). With the release of the Galileo satellite antenna phase center offsets (PCO) w.r.t. the satellites center of mass (GSA in Galileo IOV and FOC satellite metadata, 2019) and the availability of new ground antenna calibrations for GNSS receivers, based on anechoic chamber measurements or on robot calibrations, GNSS global network solutions qualify to contribute to the scale determination of terrestrial networks, as well. Our analysis is based on global multi-GNSS solutions of the years 2017 and 2018 and may be seen as “proof of concept” for the contribution of GNSS data to the scale determination of the terrestrial reference frame. In a first step, the currently used Galileo PCO estimations (Steigenberger et al. in J Geod 90:773–785, 2016) are compared to the released PCO values, which show discrepancies on the decimeter-level. Eventually, the published Galileo PCOs are used in an experimental solution as known values. GNSS-specific PCOs are estimated, as well, for GPS and GLONASS, together with the “standard” parameters set up in global GNSS solutions. From the estimated network coordinates, a time series of daily scale parameters of the terrestrial network is extracted, which shows an offset of the order of 1 ppb (parts per billion, corresponding to a height difference of 6.4 mm on the Earth’s surface) w.r.t. to the ITRF2014 network and an annual variation with an amplitude of about 0.3 ppb.
Head-to-head comparison of DFO* and DFO chelators: selection of the best candidate for clinical 89Zr-immuno-PET
Authors: Chomet Marion , Schreurs Maxime , Bolijn Maria J. , Verlaan Mariska , Beaino Wissam , Brown Kari , Poot Alex J. , Windhorst Albert D. , Gill Herman , Marik Jan , Williams Simon , Cowell Joseph , Gasser Gilles , Mindt Thomas L. , van Dongen Guus A. M. S , Vugts Danielle J.
Published: September 2020

Purpose

Almost all radiolabellings of antibodies with 89Zr currently employ the hexadentate chelator desferrioxamine (DFO). However, DFO can lead to unwanted uptake of 89Zr in bones due to instability of the resulting metal complex. DFO*-NCS and the squaramide ester of DFO, DFOSq, are novel analogues that gave more stable 89Zr complexes than DFO in pilot experiments. Here, we directly compare these linker-chelator systems to identify optimal immuno-PET reagents.

Methods

Cetuximab, trastuzumab and B12 (non-binding control antibody) were labelled with 89Zr via DFO*-NCS, DFOSq, DFO-NCS or DFO*Sq. Stability in vitro was compared at 37 °C in serum (7 days), in formulation solution (24 h ± chelator challenges) and in vivo with N87 and A431 tumour-bearing mice. Finally, to demonstrate the practical benefit of more stable complexation for the accurate detection of bone metastases, [89Zr]Zr-DFO*-NCS and [89Zr]Zr-DFO-NCS-labelled trastuzumab and B12 were evaluated in a bone metastasis mouse model where BT-474 breast cancer cells were injected intratibially.

Results

[89Zr]Zr-DFO*-NCS-trastuzumab and [89Zr]Zr-DFO*Sq-trastuzumab showed excellent stability in vitro, superior to their [89Zr]Zr-DFO counterparts under all conditions. While tumour uptake was similar for all conjugates, bone uptake was lower for DFO* conjugates. Lower bone uptake for DFO* conjugates was confirmed using a second xenograft model: A431 combined with cetuximab. Finally, in the intratibial BT-474 bone metastasis model, the DFO* conjugates provided superior detection of tumour-specific signal over the DFO conjugates.

Conclusion

DFO*-mAb conjugates provide lower bone uptake than their DFO analogues; thus, DFO* is a superior candidate for preclinical and clinical 89Zr-immuno-PET.
Accurate Risk Stratification of Patients with Node‐Positive Gastric Cancer by Lymph Node Ratio
Authors: Nakamura Shunsuke , Kanda Mitsuro , Ito Seiji , Mochizuki Yoshinari , Teramoto Hitoshi , Ishigure Kiyoshi , Murai Toshifumi , Asada Takahiro , Ishiyama Akiharu , Matsushita Hidenobu , Tanaka Chie , Kobayashi Daisuke , Fujiwara Michitaka , Murotani Kenta , Kodera Yasuhiro
Published: September 2020

Background

We aimed to clarify the utility of lymph node ratio (LNR) for assessing the prognosis of patients with node‐positive gastric cancer after curative gastrectomy.

Methods

We retrospectively analyzed data of 973 patients with node‐positive gastric cancer who had undergone curative gastrectomy at nine institutions from 2010 to 2014. Survival analysis was performed by comparing LNR low and high groups according to the optimal cutoff value of LNR, which was determined using receiver operating characteristic curve analysis.

Results

LNR high was significantly associated with shorter disease‐free survival and was an independent predictor of recurrence in all patients. Moreover, we obtained the similar results from analysis of each N stage. The prevalence of lymph node and peritoneal recurrence appeared to be higher in the LNR high group. Correlation analysis showed that LNR was negatively correlated with the number of retrieved nodes within every N stage; however, disease‐free survival did not differ significantly between LNR low and high groups of each N stage with 16–30, 31–40, or >40 retrieved nodes.

Conclusions

LNR is a strong prognostic factor and predictor of recurrence in patients with node‐positive gastric cancer who have undergone curative gastrectomy. The combination of LNR and N staging permits more accurate prognostic stratification of patients with gastric cancer and may contribute to developing novel prognostic models.
Video‐Based Guided Simulation without Peer or Expert Feedback is Not Enough: A Randomized Controlled Trial of Simulation‐Based Training for Medical Students
Authors: Tejos Rodrigo , Crovari Fernando , Achurra Pablo , Avila Ruben , Inzunza Martín , Jarry Cristian , Martinez Jorge , Riquelme Arnoldo , Alseidi Adnan , Varas Julian
Published: September 2020

Background

Feedback is a pivotal cornerstone and a challenge in psychomotor training. There are different teaching methodologies; however, some may be less effective.

Methods

A prospective randomized controlled trial was conducted in 130 medical students to compare the effectiveness of the video‐guided learning (VLG), peer‐feedback (PFG) and the expert feedback (EFG) for teaching suturing skills. The program lasted 4 weeks. Students were recorded making 3‐simple stitches (pre‐assessment and post‐assessment). The primary outcome was a global scale (OSATS). The secondary outcomes were performance time, specific rating scale (SRS) and the impact of the intervention (IOI), defined as the variation between the final and initial OSATS and SRS scores.

Results

No significant differences were found between PFG and EFG in post‐assessment results of OSATS, SRS scores or in the IOI for OSATS and SRS scores. Post‐assessment results of PFG and EFG were significantly superior to VLG in OSATS and SRS scores [(19.8 (18.5–21); 16.6 (15.5–17.5)) and (20.3 (19.88–21); 16.8 (16–17.5)) vs (15.7 (15–16); 13.3 (12.5–14)) (p < 0.05)], respectively. The results of PFG and EFG were significantly superior to VLG in the IOI for OSATS [7 (4.5–9) and 7.4 (4.88–10) vs 3.5 (1.5–6) (p < 0.05)] and SRS scores [5.4 (3.5–7) and 6.3 (4–8.5) vs 3.1 (1.13–4.88) (p < 0.05)], respectively.

Conclusion

The video‐guided learning methodology without any kind of feedback is not enough for teaching suturing skills compared to expert or peer feedback. The peer feedback methodology appears to be a viable alternative to handling the emerging demands in medical education.
Latent likelihood ratio tests for assessing spatial kernels in epidemic models
Authors: Thong David , Streftaris George , Gibson Gavin J.
Published: September 2020

One of the most important issues in the critical assessment of spatio-temporal stochastic models for epidemics is the selection of the transmission kernel used to represent the relationship between infectious challenge and spatial separation of infected and susceptible hosts. As the design of control strategies is often based on an assessment of the distance over which transmission can realistically occur and estimation of this distance is very sensitive to the choice of kernel function, it is important that models used to inform control strategies can be scrutinised in the light of observation in order to elicit possible evidence against the selected kernel function. While a range of approaches to model criticism is in existence, the field remains one in which the need for further research is recognised. In this paper, building on earlier contributions by the authors, we introduce a new approach to assessing the validity of spatial kernels—the latent likelihood ratio tests—which use likelihood-based discrepancy variables that can be used to compare the fit of competing models, and compare the capacity of this approach to detect model mis-specification with that of tests based on the use of infection-link residuals. We demonstrate that the new approach can be used to formulate tests with greater power than infection-link residuals to detect kernel mis-specification particularly when the degree of mis-specification is modest. This new tests avoid the use of a fully Bayesian approach which may introduce undesirable complications related to computational complexity and prior sensitivity.
Impact of real-time angiographic co-registered optical coherence tomography on percutaneous coronary intervention: the OPTICO-integration II trial
Authors: Schneider Vera S. , Böhm Felix , Blum Katharina , Riedel Matthias , Abdelwahed Youssef S. , Klotsche Jens , Steiner Julia K. , Heuberger Andrea , Skurk Carsten , Mochmann Hans-Christian , Lauten Alexander , Fröhlich Georg , Rauch-Kröhnert Ursula , Haghikia Arash , Sinning David , Stähli Barbara E. , Landmesser Ulf , Leistner David M.
Published: September 2020

Aims

Longitudinal geographic mismatch (LGM) as well as edge dissections are associated with an increased risk of adverse events after percutaneous coronary intervention (PCI). Recently, a novel system of real-time optical coherence tomography (OCT) with angiographic co-registration (ACR) became available and allows matched integration of cross-sectional OCT images to angiography. The OPTICO-integration II trial sought to assess the impact of ACR for PCI planning on the risk of LGM and edge dissections.

Methods

A total of 84 patients were prospectively randomized to ACR-guided PCI, OCT-guided PCI (without co-registration), and angiography-guided PCI. Primary endpoint was a composite of major edge dissection and/or LGM as assessed by post-PCI OCT.

Results

The primary endpoint was significantly reduced in ACR-guided PCI (4.2%) as compared to OCT-guided PCI (19.1%; p = 0.03) and angiography-guided PCI (25.5%; p < 0.01). Rates of LGM were 4.2%, 17.0%, and 22.9% in the ACR-guided PCI, in the OCT-guided PCI, and the angiography-guided PCI groups, respectively (ACR vs. OCT p = 0.04; ACR vs. angiography p = 0.04). The number of major edge dissections was low and without significant differences among the study groups (0% vs. 2.1% vs. 4.3%).

Conclusion

This study for the first time demonstrates superiority of ACR-guided PCI over OCT- and angiography-guided PCI in reducing the composite endpoint of major edge dissection and LGM, which was meanly driven by a reduction of LGM.

Graphical abstract
Destructive and topical treatments of skin lesions in organ transplant recipients and relation to skin cancer
Authors: Green Adele C. , Way Mandy , Oster Mariella , Plasmeijer Elsemieke I. , Jiyad Zainab , O’Rourke Peter , Miura Kyoko , Campbell Scott , Isbel Nicole , Chambers Daniel C. , Hopkins Peter , Ferguson Lisa E. , Davis Marcia Batista , Whiteman David C. , Soyer H. Peter , Marquart Louise
Published: September 2020

Various treatments of keratotic skin lesions and early skin cancers are performed in organ transplant recipients (OTRs) at high risk of skin malignancies but the frequency of their use is unknown. We prospectively assessed the frequency of use of cryotherapy, diathermy, and topical therapies and also investigated their associations with background incidence of histologically-confirmed squamous-cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of OTRs in Queensland, Australia. Median follow-up ranged from 1.7 to 3.2 years across organ transplant groups. Among 285 kidney, 125 lung and 203 liver transplant recipients [382 (62%) male, 380 (62%) immunosuppressed > 5 years, 394 (64%) previously diagnosed with skin cancer], 306 (50%) reported treatment of skin lesions with major types of non-excision therapies during follow-up: 278 (45%) cryotherapy or diathermy; 121 (20%) topical treatments. Of these 306, 150 (49%) developed SCC at double the incidence of those who did not receive these treatments, as assessed by incidence rate ratio (IRR) adjusted for age, sex, type of organ transplant, skin color and history of skin cancer at baseline, calculated by multivariable Poisson regression (IRRadj = 2.1, 95% confidence interval (CI) 1.4–3.1). BCC incidence was not associated with these therapies. Skin lesions in OTRs that are treated with cryotherapy, diathermy, or topical treatment warrant judicious selection and careful follow-up.
Single-centre experience and practical considerations of the benefit of a second cochlear implant in bilaterally deaf adults
Authors: Péus Dominik , Pfluger Andreas , Häussler Sophia Marie , Knopke Steffen , Ketterer Manuel Christoph , Szczepek Agnieszka J. , Gräbel Stefan , Olze Heidi
Published: September 2020

Purpose

Bilateral cochlear implant (CI) implantation is increasingly used in the auditory rehabilitation of bilaterally deafened adults. However, after successful unilateral implantation, objective patient counselling is essential.

Methods

We investigated the extra benefit of a second CI in adults in terms of health-related quality of life, tinnitus, stress, anxiety, depression, quality of hearing, and speech recognition. Hearing ability was assessed by using the Freiburg monosyllable speech discrimination test (FB MS) and the Oldenburg sentence test with azimuth variations. In a prospective patient cohort, we administered validated questionnaires before a CI, after a first CI and after a second CI implantation.

Results

The study included 29 patients, made up of nine women and 20 men. The median time between the first and the second implantation was 23 months. The mean total NCIQ score and TQ before a CI improved significantly after both implantations. Stress, anxiety, and depression were stable over time and were not significantly affected by CI implantations. Speech recognition with noise significantly improved after the first and again after the second CI. Correlation analysis showed a strong connection between auditory performance and HRQoL.

Conclusion

We demonstrated that a unilateral CI benefitted many fields and that the second sequential CI leads again to additional improvement. Bilateral CI implantation should, therefore, be the standard form of auditory rehabilitation in deafened adults.
Correction to: Use of PerClot® in head and neck surgery: a Scottish centre experience
Authors: Rao Kanishka , Gomati Anas , Tong Edwin Yuen Hao , W Ah-See Kim , Shakeel Muhammad
Published: September 2020

In the original publication of the article, the third author name was published incorrectly. The correct name is Edwin Yuen Hao Tong.
Inter-hospital transfer for mechanical thrombectomy within the supraregional stroke network NEVAS
Authors: Feil Katharina , Rémi Jan , Küpper Clemens , Herzberg Moriz , Dorn Franziska , Kunz Wolfgang G. , Reidler Paul , Levin Johannes , Hüttemann Katrin , Tiedt Steffen , Heidger Wanja , Müller Katharina , Thunstedt Dennis C. , Dabitz Rainer , Müller Robert , Pfefferkorn Thomas , Hamann Gerhard F. , Liebig Thomas , Dieterich Marianne , Kellert Lars
Published: September 2020

Background

Telemedicine stroke networks are mandatory to provide inter-hospital transfer for mechanical thrombectomy (MT). However, studies on patient selection in daily practice are sparse.

Methods

Here, we analyzed consecutive patients from 01/2014 to 12/2018 within the supraregional stroke network “Neurovascular Network of Southwest Bavaria” (NEVAS) in terms of diagnoses after consultation, inter-hospital transfer and predictors for performing MT. Degree of disability was rated by the modified Rankin Scale (mRS), good outcome was defined as mRS ≤ 2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction (mTICI) was 2b-3.

Results

Of 5722 telemedicine consultations, in 14.1% inter-hospital transfer was performed, mostly because of large vessel occlusion (LVO) stroke. A total of n = 350 patients with LVO were shipped via NEVAS to our center for MT. While n = 52 recanalized spontaneously, MT-treatment was performed in n = 178 patients. MT-treated patients had more severe strokes according to the median National institute of health stroke scale (NIHSS) (16 vs. 13, p < 0.001), were more often treated with intravenous thrombolysis (64.5% vs. 51.7%, p = 0.026) and arrived significantly earlier in our center (184.5 versus 228.0 min, p < 0.001). Good outcome (27.5% vs. 30.8%, p = 0.35) and mortality (32.6% versus 23.5%, p = 0.79) were comparable in MT-treated versus no-MT-treated patients. In patients with middle cerebral artery occlusion in the M1 segment or carotid artery occlusion good outcome was twice as often in the MT-group (21.8% vs. 12.8%, p = 0.184). Independent predictors for performing MT were higher NIHSS (OR 1.096), higher ASPECTS (OR 1.28), and earlier time window (OR 0.99).

Conclusion

Within a telemedicine network stroke care can successfully be organized as only a minority of patients has to be transferred. Our data provide clinical evidence that all MT-eligible patients should be shipped with the fastest transportation modality as possible.
Effective elastic properties of composites with randomly distributed thin rigid fibres
Authors: Fedelinski Piotr
Published: September 2020

The aim of the work is to analyse the effective elastic properties of composites with randomly distributed thin rigid fibres. The matrix is linear-elastic, homogenous and isotropic, and the fibres are perfectly connected to the matrix. Two-dimensional models of composites are analysed using the boundary element method (BEM). The method requires division of fibres and external boundaries of the plate into boundary elements. The boundary quantities are interpolated using quadratic shape functions. The direct solutions are: displacements and tractions along the external boundaries, displacements of fibres and interaction forces between the fibres and the matrix. Three numerical examples are presented in the paper: a single fibre in a circular disc, uniformly distributed parallel fibres and randomly distributed and oriented fibres in a square plate. The influence of distribution and orientation of fibres on effective Young’s moduli, Poisson’s ratios and Kirchhoff’s moduli is analysed. The examples demonstrate the accuracy and efficiency of the method.
The mediating role of unhealthy behaviors and body mass index in the relationship between high job strain and self-rated poor health among lower educated workers
Authors: van Oostrom S. H. , Nachat A. , Loef B. , Proper K. I.
Published: September 2020

Objectives

The objective of this study is to examine the mediating role of unhealthy behaviors and body mass index (BMI) in the relationship between high job strain and self-rated poor health in workers with a low education.

Methods

A total of 8369 low educated workers, who participated in the Lifelines cohort study during the period 2012–2017, were included. Self-reported job strain, health behaviors (smoking, physical activity, and fruit and vegetable consumption), and BMI were assessed at baseline, and self-rated health after 2 years. To assess mediation by the health behaviors and BMI, structural equation modeling with logistic and multinomial regression analyses were performed.

Results

Workers with high job strain had a higher odds of poor health (OR 1.34; 95% CI 1.13–1.60) compared to those with low job strain. Workers with high job strain were more likely to have a lack of physical activity (OR 1.14; 95% CI 1.01–1.28), but were not more likely to smoke, to be overweight or obese, or to have a low fruit or vegetable consumption. Workers who smoke, have a lack of physical activity or are overweight or obese are more likely to report poor health (OR 1.37; 95% CI 1.16–1.60, OR 1.25; 95% CI 1.08–1.43, OR 1.37; 95% CI 1.16–1.61, OR 2.25; 95% CI 1.86–2.72). Indirect (mediating) effects of unhealthy behaviors and BMI in the relationship between high job strain and poor health were small and not statistically significant.

Conclusions

No mediating effects of unhealthy behaviors or BMI were found in the relationship between high job strain and self-rated poor health among workers with a low educational level.