bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Expanded Safe Zone for Reduction of Submental Fullness with ATX-101 Injection
Authors: Shridharani Sachin M. , Chandawarkar Akash A.
Published: November 2019

Background:

ATX-101 (deoxycholic acid injection; Kybella) provides an approved nonsurgical treatment option for reduction of submental fullness caused by submental fat. Current one-size-fits-all recommendations for the use of ATX-101 limit treatment to a central area, which may not provide complete resolution of submental fat for some patients. An expanded safe zone is described, allowing for individualized, comprehensive treatment of submental fat with ATX-101 according to each patient’s anatomy and desired outcomes.

Methods:

A retrospective review was conducted of patients treated with ATX-101 for excess submental fat between June of 2015 and December of 2016 at a single plastic surgery practice. The expanded safe zone was developed to isolate the distinct fat compartments of the submental area and includes a no-treatment zone to avoid the marginal mandibular nerve. The extent of ATX-101 treatment required in each zone was determined by assessment of subcutaneous adipose tissue. A 1-cm grid was used to mark the treatment area before injection of ATX-101 (2 mg/cm2). Improvement (defined as decreased palpable and/or visible submental fullness) was determined at least 4 months after the final treatment. Adverse events were recorded at each visit and reported by patients by means of telephone.

Results:

Overall, 167 patients were included in this analysis. Improvement in submental fullness was achieved in 160 of 167 patients (95.8 percent). The majority of adverse events consisted of temporary injection-site edema, numbness, and tenderness.

Conclusion:

An understanding of submental anatomy and careful assessment of each patient’s submental fat allows for individualized treatment with ATX-101 beyond the central region of the neck without increased risk of adverse events.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Measuring the contribution of γδ T cells to the persistent HIV reservoir
Authors: James Katherine S. , Trumble Ilana , Clohosey Matthew L. , Moeser Matthew , Roan Nadia R. , Adimora Adaora A. , Joseph Sarah B. , Archin Nancie M. , Hudgens Michael , Soriano-Sarabia Natalia
Published: November 2019

Objective:

To study the contribution of γδ T cells to the persistent HIV reservoir.

Design:

Fifteen HIV-seropositive individuals on suppressive ART were included. We performed parallel quantitative viral outgrowth assays (QVOA) of resting CD4+ T (rCD4) cells in the presence or absence of γδ T cells.

Methods:

Resting αβ+CD4+ T cells were magnetically isolated from PBMCs using two different custom cocktails, only one kit contained antibodies to deplete γδ T cells, resulting in two populations: rCD4 cells and rCD4 cells depleted of γδ cells. Frequency of infection was analyzed by QVOA and DNA measurements.

Results:

Recovery of replication-competent HIV from cultures of rCD4 cells was similar in 11 individuals despite the presence of γδ T cells. In four donors, HIV recovery was lower when γδ T cells were present. Expression of the cytotoxic marker CD16+ on Vδ2 cells was the only variable associated with the lower HIV recovery. Our results highlight the potency of those responses since a mean of 10 000 γδ T cells were present within 2.5 million rCD4 cells. However, despite the low frequency of γδ T cells, the presence of cytotoxic Vδ2 cells correlated with lower HIV recovery from cultures of rCD4 cells.

Conclusion:

Results of this study show that quantification of the contribution of γδ T cells to the reservoir is challenging because of their low numbers compared with conventional rCD4 cells and highlights the potent antiviral function of γδ T cells and the impact of their presence on the frequency of latent HIV infection.
Presence of Epstein–Barr virus DNA in cerebrospinal fluid is associated with greater HIV RNA and inflammation
Authors: Lupia Tommaso , Milia Maria Grazia , Atzori Cristiana , Gianella Sara , Audagnotto Sabrina , Imperiale Daniele , Mighetto Lorenzo , Pirriatore Veronica , Gregori Gabriella , Lipani Filippo , Ghisetti Valeria , Bonora Stefano , Di Perri Giovanni , Calcagno Andrea
Published: November 2019

Objective:

The current study aimed to investigate whether cerebrospinal fluid (CSF) Epstein–Barr virus (EBV) or cytomegalovirus (CMV) DNA was associated with viral, inflammatory and neuronal damage biomarkers in people living with HIV (PLWH).

Design:

A cross-sectional diagnostic study on CSF fluid samples in patients undergoing lumbar punctures for clinical reasons, to better understand the role of EBV and CMV in the CNS on HIV RNA replication, blood-brain-barrier (BBB) damage and biomarkers of neuronal damage/inflammation.

Methods:

EBV, CMV DNA and HIV RNA were measured on CSF, through real time (RT)-PCR, from PLWHs undergoing lumbar punctures for clinical reasons (excluding oncho-haematological comorbidities). Immune-enzymatic assays evaluated blood–brain barrier inflammation and damage. Patients were stratified according to plasma HIV RNA levels in viremic (≥50 copies/ml) and aviremic (<50 copies/ml).

Results:

We included 297 participants. Among 167 viremic patients CSF EBV and CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic individuals CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis (P < 0.001), higher CSF HIV RNA (P < 0.001) and neopterin levels (P = 0.002). In aviremic participants detectable EBV DNA was associated with pleocytosis (P = 0.056), higher neopterin (P = 0.027) and immune globulins (P = 0.016) in the CSF; CSF escape was more common in those with detectable EBV DNA (50 vs. 21.2%, P = 0.036).

Conclusion:

EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was associated with higher biomarkers levels of neuronal damage/inflammation. The role of EBV reactivation in HIV-associated central nervous system disorders warrants further studies.
Nonmineralized and Mineralized Silk Fibroin/Gelatin Hybrid Scaffolds: Chacterization and Cytocompatibility In Vitro for Bone-Tissue Engineering
Authors: Meng Xiangyun , Gong Kun , Sun Chao , Liu Dianwei , Du Pinggong , Xu Dapeng
Published: November 2019

In this study, nonmineralized silk fibroin/gelatin (SF/G) hybrid scaffolds and the mineralized SF/G/hydroxyapatite (SF/G/HA) hybrid scaffolds were fabricated using vacuum freeze-drying method and biomineralization technique. The morphology and mechanical properties of the 2 hybrid scaffolds were characterized. Furthermore, the cytotoxic profiles of the hybrid scaffolds were investigated in vitro by seeding the human osteoblast cells (hFOB1.19). The 2 hybrid scaffolds were both highly porous and the pore sizes of the SF/G as well as SF/G/HA hybrid scaffolds were 260 ± 58 μm and 210 ± 35 μm, respectively. Compared with the SF/G hybrid scaffold, the SF/G/HA hybrid scaffolds exhibited significantly enhanced compressive strength and modulus. Significant early cell adhesion and proliferation on the SF/G hybrid scaffolds were observed, while SF/G/HA hybrid scaffolds effectively improved osteogenic differentiation of hFOB1.19 after 10 days of coculture. The results confirmed that the 2 hybrid scaffolds were both cytocompatible and had almost no negative effects on the hFOB1.19 in vitro. However, the SF/G/HA hybrid scaffolds tended to be more promising for application in bone-tissue engineering with good mechanical property and osteogenic differentiation.
Modelling strain localization in Ti–6Al–4V at high loading rate: a phenomenological approach
Authors: Zhou Rongxin , Pang Ka Ho , Bisht Anuj , Roy Anish , Suwas Satyam , Silberschmidt Vadim V.
Published: November 2019

A phenomenological approach, based on a combination of a damage mechanism and a crystal plasticity model, is proposed to model a process of strain localization in Ti–6AI–4V at a high strain rate of 10
3
 s
−1
. The proposed model is first calibrated employing a three-dimensional representative volume element model. The calibrated parameters are then employed to investigate the process of onset of strain localization in the studied material. A suitable mesh size is chosen for the proposed model by implementing a mesh-sensitivity study. The influence of boundary conditions on the initiation of the strain localization is also studied. A variation of crystallographic orientation in the studied material after the deformation process is characterized, based on results for different boundary conditions. The study reveals that the boundary conditions significantly influence the formation of shear bands as well as the variation of crystallographic orientation in the studied material. Results also indicate that the onset of strain localization can affect considerably the material's behaviour.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
Fault-tolerant elastic–plastic lattice material
Authors: Ryvkin Michael , Slesarenko Viacheslav , Cherkaev Andrej , Rudykh Stephan
Published: November 2019

The paper describes a fault-tolerant design of a special two-dimensional beam lattice. The morphology of such lattices was suggested in the theoretical papers (Cherkaev and Ryvkin 2019Arch. Appl. Mech.89, 485–501; Cherkaev and Ryvkin 2019Arch. Appl. Mech.89, 503–519), where its superior properties were found numerically. The proposed design consists of beam elements with two different thicknesses; the lattice is macro-isotropic and stretch dominated. Here, we experimentally verify the fault-tolerant properties of these lattices. The specimens were three-dimensional-printed from the VeroWhite elastoplastic material. The lattice is subjected to uniaxial tensile loading. Due to its morphology, the failed beams are evenly distributed in the lattice at the initial stage of damage; at this stage, the material remains intact, preserves its bearing ability, and supports relatively high strains before the final failure. At the initial phase of damage, the thinner beams buckle; then another group of separated thin beams plastically yield and rupture. The fatal macro-crack propagates after the distributed damage reaches a critical level. This initial distributed damage stage allows for a better energy absorption rate before the catastrophic failure of the structure. The experimental results are supported by simulations which confirm that the proposed fault-tolerant material possesses excellent energy absorption properties thanks to the distributed damage stage phenomenon.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
Equilibration of energies in a two-dimensional harmonic graphene lattice
Authors: Berinskii I. , Kuzkin V. A.
Published: November 2019

We study dynamical phenomena in a harmonic graphene (honeycomb) lattice, consisting of equal particles connected by linear and angular springs. Equations of in-plane motion for the lattice are derived. Initial conditions typical for molecular dynamic modelling are considered. Particles have random initial velocities and zero displacements. In this case, the lattice is far from thermal equilibrium. In particular, initial kinetic and potential energies are not equal. Moreover, initial kinetic energies (and temperatures), corresponding to degrees of freedom of the unit cell, are generally different. The motion of particles leads to equilibration of kinetic and potential energies and redistribution of kinetic energy among degrees of freedom. During equilibration, the kinetic energy performs decaying high-frequency oscillations. We show that these oscillations are accurately described by an integral depending on dispersion relation and polarization matrix of the lattice. At large times, kinetic and potential energies tend to equal values. Kinetic energy is partially redistributed among degrees of freedom of the unit cell. Equilibrium distribution of the kinetic energies is accurately predicted by the non-equipartition theorem. Presented results may serve for better understanding of the approach to thermal equilibrium in graphene.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
Waves in elastic bodies with discrete and continuous dynamic microstructure
Authors: Mishuris Gennady S. , Movchan Alexander B. , Slepyan Leonid I.
Published: November 2019

This paper presents a unified approach to the modelling of elastic solids with embedded dynamic microstructures. General dependences are derived based on Green's kernel formulations. Specifically, we consider systems consisting of a
master
structure and continuously or discretely distributed oscillators. Several classes of connections between oscillators are studied. We examine how the microstructure affects the dispersion relations and determine the energy distribution between the master structure and microstructures, including the vibration shield phenomenon. Special attention is given to the comparative analysis of discrete and continuous distributions of the oscillators, and to the effects of non-locality and trapped vibrations.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
One-way interfacial waves in a flexural plate with chiral double resonators
Authors: Carta G. , Colquitt D. J. , Movchan A. B. , Movchan N. V. , Jones I. S.
Published: November 2019

In this paper, we demonstrate a new approach to control flexural elastic waves in a structured chiral plate. The main focus is on creating one-way interfacial wave propagation at a given frequency by employing double resonators in a doubly periodic flexural system. The resonators consist of two beams attached to gyroscopic spinners, which act to couple flexural and rotational deformations, hence inducing chirality in the system. We show that this elastic structure supports one-way flexural waves, localized at an interface separating two sub-domains with gyroscopes spinning in opposite directions, but with otherwise identical properties. We demonstrate that a special feature of double resonators is in the directional control of wave propagation by varying the value of the gyricity, while keeping the frequency of the external time-harmonic excitation fixed. Conversely, for the same value of gyricity, the direction of wave propagation can be reversed by tuning the frequency of the external excitation.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
Kappa (κ): Analysis of Curvature in Biological Image Data using B-splines
Authors: Mary Hadrien , Brouhard Gary J.
Published: November 2019

Curvature is a central morphological feature of tissues, cells, and sub-cellular structures. A challenge for computational biology is to measure the curvature of these structures from biological image data. We present an open-source Fiji plugin for measuring curvature using B-splines. The plugin is named Kappa after the Greek symbol for curvature, κ. Kappa is semi-automated: users create an initialization curve by a point-click method, and the initialization curve is fit to the underlying data using an iterative minimization algorithm. We demonstrate Kappa’s applicability on images of cytoskeletal filaments in vitro, the cell wall of budding yeast, and whole worms moving in an agar dish. In order to verify the accuracy and precision of Kappa, we created a bank of synthetic images of known curvature using sine waves and golden spirals, which we digitized with different signal-to-noise ratios (SNR), pixel sizes, and point-spread functions (PSF). For synthetic images with characteristics similar to real data, the measured curvatures of those images show a high correlation with the theoretical curvatures. Our fitting algorithms perform better with higher SNR, smaller pixel sizes, and especially PSFs equivalent to super-resolution microscopy data (surprise, surprise). Kappa is freely available under the MIT license for simple integration into Fiji-based workflows. The source code and documentation can be found on GitHub at https://github.com/brouhardlab/Kappa.
Learning to Fold RNAs in Linear Time
Authors: Rezaur Rahman Chowdhury F A , Zhang He , Huang Liang
Published: November 2019

RNA secondary structure is helpful for understanding RNA’s functionality, thus accurate prediction systems are desired. Both thermodynamics-based models and machine learning-based models have been used in different prediction systems to solve this problem. Compared to thermodynamics-based models, machine learning-based models can address the inaccurate measurement of thermodynamic parameters due to experimental limitation. However, the existing methods for training machine learning-based models are still expensive because of their cubic-time inference cost. To overcome this, we present a linear-time machine learning-based folding system, using recently proposed approximate folding tool LinearFold as inference engine, and structured SVM (sSVM) as training algorithm. Furthermore, to remedy non-convergence of naive sSVM with inexact search inference, we introduce a max violation update strategy. The training speed of our system is 41× faster than CONTRAfold on a diverse dataset for one epoch, and 14× faster than MXfold on a dataset with longer sequences. With the learned parameters, our system improves the accuracy of LinearFold, and is also the most accurate system among selected folding tools, including CONTRAfold, Vienna RNAfold and MXfold.
A human-specific modifier of cortical circuit connectivity and function improves behavioral performance
Authors: Schmidt Ewoud R.E. , Zhao Hanzhi T. , Park Jung M. , Dahan Jacob B. , Rodgers Chris C. , Hillman Elizabeth M. C. , Bruno Randy M. , Polleux Franck
Published: November 2019

The remarkable cognitive abilities characterizing humans are thought to emerge from our unique features of cortical circuit architecture, including increased feedforward and feedback connectivity. However, our understanding of the evolutionary origin and nature of these changes in circuit connectivity, and how they impact cortical circuit function and behavior is currently lacking. Here, we demonstrate that expression of the human-specific gene duplication SRGAP2C leads to a specific increase in feedforward and feedback cortico-cortical connectivity. Moreover, humanized SRGAP2C mice display improved cortical sensory coding, and an enhanced ability to learn a cortex-dependent sensory discrimination task. Our results identify a novel substrate for human brain evolution whereby the emergence of SRGAP2C led to increased feedforward and feedback cortico-cortical connectivity, improved cortical sensory processing and enhanced behavioral performance.
The ecology of cancer differentiation therapy
Authors: Solé Ricard , Aguadé-Gorgorió Guim
Published: November 2019

A promising, yet still under development approach to cancer treatment is based on the idea of differentiation therapy (DTH). Most tumours are characterized by poorly differentiated cell populations exhibiting a marked loss of traits associated to communication and tissue homeostasis. DTH has been suggested as an alternative (or complement) to cytotoxic-based approaches, and has proven successful in some specific types of cancer such as acute promyelocytic leukemia (APL). While novel drugs favouring the activation of differentiation therapies are being tested, several open problems emerge in relation to its effectiveness on solid tumors. Here we present a mathematical framework to DTH based on a well-known ecological model used to describe habitat loss. The models presented here account for some of the observed clinical and in vitro outcomes of DTH, providing relevant insight into potential therapy design. Furthermore, the same ecological approach is tested in a hierarchical model that accounts for cancer stem cells, highlighting the role of niche specificity in CSC therapy resistance. We show that the lessons learnt from metapopulation ecology can help guide future developments and potential difficulties of DTH.
Rapid antimicrobial susceptibility test using spatiotemporal analysis of laser speckle dynamics of bacterial colonies
Authors: Han SeungYun , No Hojun , Baek YoonSeok , Park Huijun , Lee KyeoReh , Yang Seungbum , Park YongKeun
Published: November 2019

Antimicrobial susceptibility testing (AST) is crucial for providing appropriate choices and doses of antibiotics to patients. However, standard ASTs require a time-consuming incubation of about 16-20 h for visual accumulation of bacteria, limiting the use of AST for an early prescription. In this study, we propose a rapid AST based on laser speckle formation (LSF) that enables rapid detection of bacterial growth, with the same sample preparation protocol as in solid-based ASTs. The proposed method exploits the phenomenon that well-grown bacterial colonies serve as optical diffusers, which convert a plane-wave laser beam into speckles. The generation of speckle patterns indicates bacterial growth at given antibiotic concentrations. Speckle formation is evaluated by calculating the spatial autocorrelation of speckle images, and bacterial growth is determined by tracking the autocorrelation value over time. We demonstrated the performance of the proposed method for several combinations of bacterial species and antibiotics to achieve the AST in 2-4.5 hours. Furthermore, we also demonstrated the sensitivity of the technique for low bacterial density. The proposed method can be a powerful tool for rapid, simple, and low-cost AST.

Abstract Figure
A simple computer vision algorithm as a clinical aid for the pathologist
Authors: Lázaro-Guevara J.M. , Flores-Robles B.J. , Murga A.E. , Garrido K.M.
Published: November 2019

Histological analysis for cancer detection or stratification is performed by observing and examining a small portion of a biopsied tissue under a microscope. Nevertheless, to assign clinical meaning to the findings, the analysis and interpretation of an experienced Pathologist is always necessary. Using high-resolution images, these experts visually examine the sample looking for specific characteristics on the cell shapes and tissue distributions, so they could decide whether tissue regions are cancerous, and establish the malignancy level of it. However, with the increasing demand for work for those pathologists and the importance of accuracy on diagnostics, multiple attempts to simplify their work have been performed. Current Imaging technologies allow novel horizons in the automatized selection of some of the characteristics that indicate malignancy in a biopsy. In this work, we propose a simple computer vision algorithm that can be implemented as a screening method for focusing in histological areas with higher risk of malignancy saving time to the pathologist and helping to perform a more standardized work, an easy observation with the potential to become in an aid to daily clinical work.
Push-to-open: The Gating Mechanism of the Tethered Mechanosensitive Ion Channel NompC
Authors: Wang Yang , Guo Yifeng , Liu Chunhong , Wang Lei , Zhang Aihua , Yan Zhiqiang , Song Chen
Published: November 2019

NompC was one of the earliest identified mechanosensitive ion channels responsible for the sensation of touch and balance in Drosophila melanogaster. A tethered gating model was proposed for NompC and the Cryo-EM structure has been solved. However, the atomistic mechano-gating mechanism still remains elusive. Here we show the atomistic details of the NompC channel opening in response to the compression of the intracellular domain while remaining closed under an intracellular stretch. This is demonstrated by all-atom molecular dynamics simulations and evidenced by electrophysiological experiments. Under intracellular compression, the ankyrin repeat region undergoes a significant conformational change and passes the mechanical force to the linker helices like a spring with a force constant of ~3.3 pN/nm. The linker helix region acts as a bridge between the ankyrin repeats and TRP domain, and most of the mutations breaking the hydrogen bonds around this region lead to the loss-of-function of the channel. Eventually, the compression-induced mechanical force is passed from the linker helices onto the TRP domain, which then undergoes a clockwise rotation that leads to the opening of the channel. This work provides a clear picture of how a pushing force opens the mechanosensitive ion channel NompC, which might be a universal gating mechanism of similar tethered mechanosensitive ion channels, enabling cells to feel and respond to compression or shrinking.
Ectopic HCN4 expression drives mTOR-dependent epilepsy
Authors: Hsieh Lawrence S. , Wen John H. , Nguyen Lena H. , Zhang Longbo , Torres-Reveron Juan , Spencer Dennis D. , Bordey Angélique
Published: November 2019

The causative link between focal cortical malformations (FCM) and epilepsy is well-accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we show that FCM neurons are responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide-gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP levels, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not that of control pyramidal neurons. Ectopic HCN4 expression was mTOR-dependent, preceded the onset of seizures, and was also found in diseased neurons in tissue resected for epilepsy treatment from TSC and FCDII patients. Finally, blocking HCN4 channel activity in FCM neurons prevented epilepsy in mice. These findings that demonstrate HCN4 acquisition as seizure-genic, identify a novel cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons provides opportunities for using HCN4 as a gene therapy target to treat epilepsy in individuals with FCDII or TSC.

One Sentence Summary

Our data provide a novel cAMP-dependent mechanism of seizure initiation in focal cortical dysplasia and tuberous sclerosis complex due to the unexpected ectopic expression of HCN4 channels only in diseased neurons. HCN4 channels are thus promising candidates for gene therapy to treat epilepsy generated by mTOR-driven focal malformations.
Face familiarity detection with complex synapses
Authors: Ji-An Li , Stefanini Fabio , Benna Marcus K. , Fusi Stefano
Published: November 2019

Synaptic plasticity is a complex phenomenon involving multiple biochemical processes that operate on different timescales. We recently showed that this complexity can greatly increase the memory capacity of neural networks when the variables that characterize the synaptic dynamics have limited precision, as in biological systems. These types of complex synapses have been tested mostly on simple memory retrieval problems involving random and uncorrelated patterns. Here we turn to a real-world problem, face familiarity detection, and we show that also in this case it is possible to take advantage of synaptic complexity to store in memory a large number of faces that can be recognized at a later time. In particular, we show that the familiarity memory capacity of a system with complex synapses grows almost linearly with the number of the synapses and quadratically with the number of neurons. Complex synapses are superior to simple ones, which are characterized by a single variable, even when the total number of dynamical variables is matched. We further show that complex and simple synapses have distinct signatures that are testable in proposed experiments. Our results indicate that a memory system with complex synapses can be used in real-world tasks such as face familiarity detection.

Significance

The complexity of biological synapses is probably important for enabling us to remember the past for a long time and rapidly store new memories. The advantage of complex synapses in terms of memory capacity is significant when the variables that characterize the synaptic dynamics have limited precision. This advantage has been estimated under the simplifying assumption that the memories to be stored are random and uncorrelated. Here we show that synaptic complexity is important also in a more challenging and realistic face familiarity detection task. We built a simple neural circuit that can report whether a face has been previously seen or not. This circuit incorporates complex synapses that operate on multiple timescales. The memory performance of this circuit is significantly higher than in the case in which synapses are simple, indicating that the complexity of biological synapses can be important also in real-world memory tasks.
Combined use of metagenomic sequencing and host response profiling for the diagnosis of suspected sepsis
Authors: Cheng Henry K. , Tan Susanna K. , Sweeney Timothy E. , Jeganathan Pratheepa , Briese Thomas , Khadka Veda , Strouts Fiona , Thair Simone , Dalai Sudeb , Hitchcock Matthew , Multani Ashrit , Aronson Jenny , Andermann Tessa , Yu Alexander , Yang Samuel , Holmes Susan P. , Lipkin W. Ian , Khatri Purvesh , Relman David A.
Published: November 2019

Background

Current diagnostic techniques are inadequate for rapid microbial diagnosis and optimal management of patients with suspected sepsis. We assessed the clinical impact of three powerful molecular diagnostic methods.

Methods

With blood samples from 200 consecutive patients with suspected sepsis, we evaluated 1) metagenomic shotgun sequencing together with a Bayesian inference approach for contaminant sequence removal, for detecting bacterial DNA; 2) viral capture sequencing; and 3) transcript-based host response profiling for classifying patients as infected or not, and if infected, with bacteria or viruses. We then evaluated changes in diagnostic decision-making among three expert physicians by unblinding the results of these methods in a staged fashion.

Results

Metagenomic shotgun sequencing confirmed positive blood culture results in 14 of 26 patients. In 17 of 200 patients, metagenomic sequencing and viral capture sequencing revealed organisms that were 1) not detected by conventional hospital tests within 5 days after presentation, and 2) classified as of probable clinical relevance by physician consensus. Host response profiling led at least two of three physicians to change their diagnostic decisions in 46 of 100 patients. The data suggested possible bacterial DNA translocation in 8 patients who were originally classified by physicians as noninfected and illustrate how host response profiling can guide interpretation of metagenomic shotgun sequencing results.

Conclusions

The integration of host response profiling, metagenomic shotgun sequencing, and viral capture sequencing enhances the utility of each, and may improve the diagnosis and management of patients with suspected sepsis.
Group-theoretical analysis of structural instability, vacancy ordering and magnetic transitions in the system troilite (FeS)–pyrrhotite (Fe1−xS)
Authors: Haines Charles R. S. , Howard Christopher J. , Harrison Richard J. , Carpenter Michael A.
Published: November 2019

A group-theoretical framework to describe vacancy ordering and magnetism in the Fe1−xS system is developed. This framework is used to determine the sequence of crystal structures consistent with the observed magnetic structures of troilite (FeS), and to determine the crystallographic nature of the low-temperature Besnus transition in Fe0.875S. It is concluded that the Besnus transition is a magnetically driven transition characterized by the rotation of the moments out of the crystallographic plane to which they are confined above the transition, accompanied by small atomic displacements that lower the symmetry from monoclinic to triclinic at low temperatures. Based on the phase diagram, magnetically driven phase transitions at low temperatures are predicted in all the commensurate superstructures of pyrrhotite. Based on the phase diagram, magnetically driven spin reorientations at low temperatures are predicted in all the commensurate superstructures of pyrrhotite. The exact nature of the spin rotation is determined by the symmetry of the vacancy-ordered state and based on this spin-flop transitions in 3C and 5C pyrrhotite and a continuous rotation akin to that seen in 4C pyrrhotite are predicted. A Besnus-type transition is also possible in 6C pyrrhotite. Furthermore, it is clarified that 3C and 4C pyrrhotite carry a ferrimagnetic moment whereas 5C and 6C are antiferromagnetic.
Five solvates of a multicomponent pharmaceutical salt formed by berberine and diclofenac
Authors: Sun Wei , Zuo Limin , Zhao Ting , Zhu Zhiling , Shan Guangzhi
Published: November 2019

A multicomponent pharmaceutical salt formed by the isoquinoline alkaloid berberine (5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium, BBR) and the nonsteroidal anti-inflammatory drug diclofenac {2-[2-(2,6-dichloroanilino)phenyl]acetic acid, DIC} was discovered. Five solvates of the pharmaceutical salt form were obtained by solid-form screening. These five multicomponent solvates are the dihydrate (BBR–DIC·2H2O or C20H18NO4
+·C14H10Cl2NO2
−·2H2O), the dichloromethane hemisolvate dihydrate (BBR–DIC·0.5CH2Cl2·2H2O or C20H18NO4
+·C14H10Cl2NO2
−·0.5CH2Cl2·2H2O), the ethanol monosolvate (BBR–DIC·C2H5OH or C20H18NO4
+·C14H10Cl2NO2
−·C2H5OH), the methanol monosolvate (BBR–DIC·CH3OH or C20H18NO4
+·C14H10Cl2NO2
−·CH3OH) and the methanol disolvate (BBR–DIC·2CH3OH or C20H18NO4
+·C14H10Cl2NO2
−·2CH3OH), and their crystal structures were determined. All five solvates of BBR–DIC (1:1 molar ratio) were crystallized from different organic solvents. Solvent molecules in a pharmaceutical salt are essential components for the formation of crystalline structures and stabilization of the crystal lattices. These solvates have strong intermolecular O...H hydrogen bonds between the DIC anions and solvent molecules. The intermolecular hydrogen-bond interactions were visualized by two-dimensional fingerprint plots. All the multicomponent solvates contained intramolecular N—H...O hydrogen bonds. Various π–π interactions dominate the packing structures of the solvates.
Organizational learning capability, innovation and organizational performance
Authors: Migdadi Mahmoud M.
Published: November 2019

Purpose

The purpose of this paper is to introduce a comprehensive, delineated and integrated conceptual model which includes organizational learning capability, innovation and organizational performance (OP). Then, an empirical investigation is undertaken to test the relationships among the proposed study model variables.

Design/methodology/approach

In total, 274 questionnaires were completed and returned. Statistical techniques employed included confirmatory factor analysis to examine the validity of the measurement model, and structural equation modeling to test the hypotheses.

Findings

The findings of this study suggest that OLC influences innovation and innovation affects OP. Finally, the results show that OLC affects OP indirectly through innovation (mediator).

Research limitations/implications

Future research should pay more attention to the influence of different mixture (variables) of influences on innovation and also examine other consequences of introducing innovation in organizations. In addition, more empirical papers supporting (or rejecting) the results in different contexts would be welcomed, especially longitudinal studies.

Practical implications

The results of this study help managers to ascertain the managerial practices that can be employed as well as determine the level of effort and resources necessary to enhance OLC. Additionally, managers should shed additional light on the innovation’s positive implications for OP.

Originality/value

This study focuses on the conceptualization of OLC and effects of these capabilities on innovation. It conceptualizes innovation as a multidimensional construct and tests its relationship with OP. Finally, the relationship between learning capability and OP, although implied, needs to be addressed empirically in the research literature, an objective that this study tries to achieve.
Decision making under uncertainty in the alarm systems response
Authors: Si Mohammed Antar , Smail Rachid , Chebila Mourad
Published: November 2019

Purpose

The purpose of this paper is to develop an advanced decision-making support for the appropriate responding to critical alarms in the hazardous industrial facilities.

Design/methodology/approach

A fuzzy analytical hierarchy process is suggested by considering three alternatives and four criteria using triangular fuzzy numbers to handle the associated uncertainty. A logarithmic fuzzy preference programming (LFPP)-based nonlinear priority method is employed to analyze the suggested model.

Findings

A quantitative decision-making support is not only a necessity in responding to critical alarms but also easy to implement even in a relatively short reaction time. Confirmation may not be the appropriate option to deal with a critical alarm, even with the availability of the needed resources.

Practical implications

A situation related to a flammable gas alarm in a gas plant is treated using the developed model showing its practical efficiency and practicality.

Originality/value

The proposed model provides a rational, simple and holistic fuzzy multi criteria tool with a refined number of criteria and alternatives using an LFPP method to handle process alarms.
Tourist experience, perceived authenticity, place attachment and loyalty when staying in a peer-to-peer accommodation
Authors: Souza Luis Henrique , Kastenholz Elisabeth , Barbosa Maria de Lourdes Azevedo , Carvalho Mariana Sousa e Silva Cabral
Published: November 2019

Purpose

The emergence of peer-to-peer accommodation (P2PA) introduces new values and meanings to the hospitality experience. Focusing on the diverse dimensions of the tourist experience, the purpose of this paper is to identify and assess the relative importance of the main dimensions of guests’ P2PA experience and its relationships with perception of authenticity, place attachment and loyalty to both the visited destination and the P2PA.

Design/methodology/approach

A qualitative netnographic approach with content analysis permitted the analysis of 250 reviews taken from the Airbnb platform, specifically focusing on P2PAs where guests stay with hosts in the same space.

Findings

The results of the study suggest that guests’ P2PA experiences are particularly influenced by the experience dimensions “aesthetic/sense”, “relate/social interaction”, “escape”, “act” and “feel”. P2PA experiences also result in loyalty intentions, to both the visited destination and the particular P2PA. The dimensions “aesthetic/sense”, “relate/social interaction” and “escape” stand out as most influential in determining perceived authenticity. In turn, place attachment is most influenced by the dimensions “feel” and “relate/social interaction”.

Research limitations/implications

Limitations of this research need to be acknowledged: the P2PA guest experience is explored from the restricted perspective of online reviews using passive netnography. Therefore, some criteria of data collection, for instance, gathering only reviews written in English and with more than 80 words, may be limitative in a more comprehensive assessment of the P2PA experience. Another point is, although P2PA platforms such as Airbnb encourage their guests to review the experience, some people are not inclined to do so; therefore, the published reviews may not reflect all possible experiences at these accommodations inclined to do so; therefore, the published reviews may not reflect all possible experiences at these accommodations.

Originality/value

This study suggests a comprehensive analytical framework for assessing the “holistic multidimensional tourist experience”, integrating Pine and Gilmore’s (1999) and Schmitt’s (1999) approaches, thus deepening the conceptual and methodological debate on the tourist experience. It further contributes to a better understanding of the dimensionality of the tourist experience in the context of shared accommodation. The dimensions under analysis and their association with perceived authenticity, loyalty and place attachment are both of theoretical and practical interest, suggesting approaches to improve the P2PA experience as well as the image and success of the destinations where these units are located.
Impact of anchor investors on IPO returns during pre-market and aftermarket: evidence from India
Authors: Gupta Vikas , Singh Shveta , Yadav Surendra S.
Published: November 2019

Purpose

The unique regulatory design of India provides us with the opportunity to disaggregate traditional initial public offering (IPO) underpricing into three categories: voluntary, pre-market and post-market. The presence of anchor investors in India makes it a compelling case to study. These individuals were introduced to bring transparency in the book building process, but their impact on pre-market and post-market underpricing was not foreseen. Therefore, the purpose of this paper is to evaluate the impact of anchor investors on the IPO underpricing after disaggregation and on the long-run performance of an IPO.

Design/methodology/approach

A sample covering 232 IPOs from a period of 2009–2018 is included. The empirical analysis explores the impact of various firm-specific as well as market-specific variables on IPO underpricing. The financial data for the empirical analysis are extracted from Prime database and websites of National Stock Exchange and Bombay Stock Exchange. To deal with the outliers effectively, this paper deploys “robust-regression.”

Findings

The study finds that investor’s subscription rate and voluntary underpricing impacts the pre-market but do not have any impact on the post-market while the age of the firm has a different impact on both the markets and the number of anchor investors have the same impact in both markets. Anchor investors’ participation increases the pre-market as well as post-market underpricing. Lastly, the long-term performance of IPOs backed by the anchor investors is high relative to the IPOs not subscribed to by the anchor investors.

Originality/value

This paper is believed to be the first attempt to study the impact of anchor investors on the disaggregated IPO underpricing. The findings of this study will have a great insight for the investors.
European academic libraries Key Performance Indicators (KPI)
Authors: Swiatek Cecile
Published: November 2019

Purpose

The French academic libraries directors association (ADBU) launched and updated a European comparative study on Key Performance Indicators (KPI) in Academic Libraries over the 2013–2017 period. The purpose of this paper is to briefly present the ADBU initiative; its main focus is how to use these figures to ground decision making process, notably so as to better assess the contribution of libraries in student success or research performance.

Design/methodology/approach

As universities and academic libraries are facing research evolutions and teaching/learning new models, a strong increase in students’ number is observed everywhere in Europe. This trend will most probably continue in the coming years and the pressure on academic libraries will grow. That is why the French ADBU took the initiative to launch a European comparative study on key and performance indicators in Academic Libraries over the 2013–2016 period. Data were updated in 2019, covering 2017 figures and including additional countries.

Findings

Thanks to the European partners and the help of a consultant firm, the first observations were updated with the 2017 figures and the country scope grew broader. Libraries buildings and equipment, space and seats per student, opening days and hours, frequentation rate, library services, users training, staff per student/documentary budgets/total expenditure, staff training, documentation loans/consultation/downloads: these KPI are gathered and can be compared in both relative and absolute value.

Originality/value

The ADBU initiative is unique, results are widely shared.
Illuminating microbial species‐specific effects on organic matter remineralization in marine sediments
Authors: Mahmoudi Nagissa , Enke Tim N. , Beaupré Steven R. , Teske Andreas P. , Cordero Otto X. , Pearson Ann
Published: November 2019

Marine microorganisms play a fundamental role in the global carbon cycle by mediating the sequestration of organic matter in ocean waters and sediments. A better understanding of how biological factors, such as microbial community composition, influence the lability and fate of organic matter is needed. Here, we explored the extent to which organic matter remineralization is influenced by species‐specific metabolic capabilities. We carried out aerobic time‐series incubations of Guaymas Basin sediments to quantify the dynamics of carbon utilization by two different heterotrophic marine isolates (Vibrio splendidus 1A01; Pseudoalteromonas sp. 3D05). Continuous measurement of respiratory CO2 production and its carbon isotopic compositions (13C and 14C) shows species‐specific differences in the rate, quantity and type of organic matter remineralized. Each species was incubated with hydrothermally‐influenced versus unimpacted sediments, resulting in a ~2‐fold difference in respiratory CO2 yield across the experiments. Genomic analysis indicated that the observed carbon utilization patterns may be attributed in part to the number of gene copies encoding for extracellular hydrolytic enzymes. Our results demonstrate that the lability and remineralization of organic matter in marine environments is not only a function of chemical composition and/or environmental conditions, but also a function of the microorganisms that are present and active.
Characterization of non‐canonical G beta‐like protein FvGbb2 and its relationship with heterotrimeric G proteins in Fusarium verticillioides
Authors: Yan Huijuan , Shim Won Bo
Published: November 2019

Fusarium verticillioides is a fungal pathogen that is responsible for maize ear rot and stalk rot diseases worldwide. The fungus also produces carcinogenic mycotoxins, fumonisins on infested maize. Unfortunately, we still lack clear understanding of how the pathogen responds to host and environmental stimuli to trigger fumonisin biosynthesis. The heterotrimeric G protein complex, consisting of canonical Gα, Gβ and Gγ subunits, is involved in transducing signals from external stimuli to regulate downstream signal transduction pathways. Previously, we demonstrated that Gβ protein FvGbb1 directly impacts fumonisin regulation but not other physiological aspects in F. verticillioides. In this study, we identified and characterized a RACK1 (Receptor for Activated C Kinase 1) homolog FvGbb2 as a putative Gβ‐like protein in F. verticillioides. The mutant exhibited severe defects not only in fumonisin biosynthesis but also vegetative growth and conidiation. FvGbb2 was positively associated with carbon source utilization and stress agents but negatively regulated general amino acid control. While FvGbb2 does not interact with canonical G protein subunits, it may associate with diverse proteins in the cytoplasm to regulate vegetative growth, virulence, fumonisin biosynthesis and stress response in F. verticillioides.