bluuebunny/crossref_metadata_2025 huggingface dataset:
Filipinos FrontToo! A Sociophonetic Analysis of Toronto English /u/-Fronting
Authors: Umbal Pocholo
Published: April 2021

The fronting of the back vowel /u/is an ongoing sound change in many varieties of English. While /u/-fronting is argued to be primarily phonetically constrained, many studies report the significant role of various social factors, including ethnicity. This article investigates the linguistic and social conditioning of /u/-fronting in Toronto English. A sociophonetic analysis of /u/, extracted from spontaneous speech data of second-generation Filipinos and age-matched Anglos, was conducted to determine whether Filipinos exhibit /u/-fronting and to what extent coarticulatory and social factors affect degree of fronting. Results of a multivariate analysis show that male and female Filipinos produce fronted realizations of /u/as often as their Anglo peers. However, Filipinos exhibit greater fronting than Anglos in coronal and palatal contexts, which may be explained by cross-language influence from Tagalog. Taken together, this study suggests that, although Filipinos join other Torontonians in /u/-fronting, they nonetheless exhibit finer-grained differences when phonetic conditioning is taken into account.
Cameralism asSonderwegof German Mercantilism?
Authors: Magnusson Lars
Published: April 2021

In recent years there has been a renewed interest in Cameralism, both as a discourse and as an administrative political economy, in both theory and practice. Attention has been drawn to how Cameralism—defined as thought and practice—should be understood. The aim of this article is to take a step back and focus on the historiography of Cameralism from the nineteenth century onwards. Even though many in recent times have challenged old and seemingly dated conceptualizations and interpretations, they are still very much alive. Most profoundly this has implied that Cameralism most often in the past has been acknowledged as an expression of—German. as it were—exceptionalism to the general history of economic doctrine and thinking.
The Magnificent Spruce
Authors: Wennerlind Carl
Published: April 2021

After its success in the Thirty Years’ War, Sweden harbored ambitions to establish an empire. To sustain its efforts, statesmen realized the need to generate more domestic wealth. The ensuing debates gave rise to an improvement discourse, centered on the harnessing of Sweden’s abundant natural resources. While most improvement writers were patronized by the state and offered state-centered analyses, the protagonist of this essay, Anders Kempe (1622–1689), was a staunch critic of Sweden’s warmongering state. In his mind, the state had become an obstacle to true human flourishing, which recent scientific development had put within humanity’s grasp. Free from wars, predatory taxation, and miseducation, the Swedish people would be in a position to create a society of abundance and righteousness. Kempe’s main recipe for progress was to use recent advancements in natural philosophy to transform nature into useable wealth. In his most famous publication, The Anatomized Spruce (1675), Kempe elaborated on the economic and medicinal benefits that a proper understanding of the spruce tree, its bark, branches, sap, roots, and needles might yield. In sharing the focus on the transformation of nature with other Swedish Cameralist writers, but wholeheartedly rejecting the state, Kempe can be categorized as an anarcho-Cameralist.
Land, People, and the Unused Economic Potential of Hungary
Authors: Hidvégi Mária
Published: April 2021

This article offers a case study about the importance of Staatenkunde (descriptive statistics) for Cameralism and the development of economic thought in Hungary, a country that has been rarely included into political economic studies about Cameralism. It aims at showing how the Hungarian statistical works and debates integrate and feed back into the broader European discourse of Cameralism and the role of “useful knowledge” in making the modern (industrial) economies. It points out the role of statistics in the assessment of the real production value and productivity of agriculture in the Kingdom of Hungary 1773–1848, at that time part of the Habsburg Monarchy. It displays the role of statistical knowledge production in the assessment of the position of Hungary in the monarchy and its importance for the national reform movement.
Serotonin syndrome in a patient with chronic pain taking analgesic drugs mistaken for psychogenic nonepileptic seizure: a case report
Authors: Boudier-Revéret Mathieu , Chang Min Cheol
Published: April 2021

Serotonin syndrome (SS) is a potentially life-threatening condition that is caused by the administration of drugs that increase serotonergic activity in the central nervous system. We report a case of serotonin syndrome in a patient with chronic pain who was taking analgesic drugs. A 36-year-old female with chronic pain in the lower back and right buttock area had been taking tramadol hydrochloride 187.5 mg, acetaminophen 325 mg, pregabalin 150 mg, duloxetine 60 mg, and triazolam 0.25 mg daily for several months. After amitriptyline 10 mg was added to achieve better pain control, the patient developed SS, which was mistaken for psychogenic nonepileptic seizure. However, her symptoms completely disappeared after discontinuation of the drugs that were thought to trigger SS and subsequent hydration with normal saline. Various drugs that can increase serotonergic activity are being widely prescribed for patients with chronic pain. Clinicians should be aware of the potential for the occurrence of SS when prescribing pain medications to patients with chronic pain.
Modeling the efficiency of project management of corporate innovation activity
Authors: Badykova Idelya
Published: April 2021

The role of innovation in the economy development is extremely significant. Within the framework of this work, the innovative activity of enterprises and its relation to corporate social responsibility (CSR) is of particular interest. This study is aimed at modeling the project management of corporate innovation activity on the basis of CSR.
The results obtained by the author for the Russian economy suggest that there is a positive relationship between the level of innovative development and CSR, both in general and in terms of investments in the transformation of human capital. In this regard, the model of project management of corporate innovation activity based on CSR is proposed. Author suggests, that this model's implementation for companies is promising, since transition to such a model should be resulted in an increase in the innovation activity of companies, regions and the whole country, as well as an increase in the economic, social and organizational effectiveness of innovative activity.
Fear and the importance of race-based data in COVID-19 policy implementation
Authors: Harper Leland
Published: April 2021

This paper distinguishes between the experiences of Black Americans and white Americans during the COVID-19 pandemic and how this different experience relates to fear. This paper ultimately argues that policymakers ought to fund the collection and analysis of race-based data, as it pertains to COVID-19, and that these policymakers ought to appeal to the findings of this race-based data to guide their policy and implementation strategy. Without gathering or appealing to such data, policymakers are being negligent in working to protect their constituents.
Laser curve extraction of a train wheelset based on an encoder-decoder network
Authors: Yang Kai , Luo Shuai , Wang Yong , Gao Xiaorong , Jiang Tianci , Li Chunjiang , Zhao Yanyu
Published: April 2021

An algorithm of laser curve segmentation for a train wheelset based on an encoder- decoder network is proposed. Aiming at the rich local features and simple semantic features of the train wheelset laser curve image, a neural network with shallow depth, high resolution, and good detail performance was designed. The proposed neural network makes full use of the dense connection mechanism and the upsampling module to enhance feature reuse and feature propagation. It can extract context semantic information at multiple scales with fewer parameters. Experimental results show that the encoder-decoder network has better performance than other neural networks in laser curve extraction of train wheelset. Based on the encoder-decoder neural network, mIOU, Recall, Accuracy, and F1_score of the laser curve dataset of the train wheelset, the score index reached 86.5%, 89.2%, 99.9%, and 85.0%, which can accurately extract the laser stripe of the train wheelset. Additionally, the encoder-decoder network can diminish the influence of noise on the extraction of laser fringes of a train wheelset to a certain extent. Therefore, it has good application in railway safety.
Prevention of laser damage precursors in spaceborne ultraviolet antireflection coatings
Authors: Alig Thimotheus , Bartels Nils , Allenspacher Paul , Balasa Istvan , Böntgen Tammo , Ristau Detlev , Jensen Lars
Published: April 2021

In order to enhance the reliability and performance of space-based Lidar systems, it is desirable to increase the damage resistance of ultraviolet antireflective coatings. For laser pulses with nanosecond pulse duration, laser-induced damage is known to be triggered by nano-sized defects embedded in the optical coating. In this work, we demonstrate the mitigation of damage precursors during the manufacturing of ion-beam sputtered (IBS) coatings using two approaches: ion bombardment with a secondary ion source and laser irradiation with a nanosecond-pulsed laser. Optical coatings produced with both technologies show a significantly increased damage threshold when tested in large-area raster scans.
Efficient terahertz generation scheme in a thin-film lithium niobate-silicon hybrid platform
Authors: Yang Jingwei , Wang Cheng
Published: April 2021

The terahertz (THz) spectral window is of unique interest for plenty of applications, yet we are still searching for a low-cost, continuous-wave, room-temperature THz source with high generation efficiency. Here, we propose and investigate a hybrid lithium niobate/silicon waveguide scheme to realize such an efficient THz source via difference-frequency generation. The multi-layer structure allows low-loss and strong waveguide confinements at both optical and THz frequencies, as well as a reasonable nonlinear interaction strength between the three associated waves. Our numerical simulation results show continuous-wave THz generation efficiencies as high as 3.5×10−4 W-1 at 3 THz with high tolerance to device fabrication variations, three orders of magnitude higher than current lithium-niobate-based devices. Further integrating the proposed scheme with an optical racetrack resonator could improve the conversion efficiency to 2.1×10−2 W-1. Our proposed THz source could become a compact and cost-effective solution for future spectroscopy, communications and remote sensing systems.
Interferometric scattering of a single plasmonic nanoparticle cluster assembled in a nanostructured template
Authors: Xu Ya , Meng Yan , Zhou Shuang , Zhang Weihua
Published: April 2021

In this work, we investigate the light scattering of a single Au nanoparticle cluster assembled in a nanostructured substrate and study how the substrate geometry influences the scattering spectrum. An explicit model was built with the help of the Green’s tensor theory, showing that there are two distinct types of substrate effects, namely, the interferometric scattering caused by the local corrugation and the spectral modulation caused by the global features (i.e., the layered substrate in this work). The result predicted by the model agrees with the experimental results well, providing a simple yet quantitative tool for the spectral interpretation of plasmonic nanostructures with complex substrates.
Design of a near-eye display measurement system using an anthropomorphic vision imaging method
Authors: Zhang Qingtian , Song Weitao , Hu Xiang , Hu Kaituo , Weng Dongdong , Liu Yue , Wang Yongtian
Published: April 2021

We developed a new near-eye display measurement system using anthropomorphic vision imaging to measure the key parameters of near-eye displays, including field-of-view (FOV), angular resolution, eye box, and virtual image depth. The characteristics of the human eye, such as pupil position, pupil size variation, accommodation function, and the high resolution of the fovea, are imitated by the proposed measurement system. A FOV scanning structure, together with a non-vignetting image-telecentric lens system, captures the virtual image from the near-eye display by imitating human eye function. As a proof-of-concept, a prototype device was used to obtain large-range, high-resolution measurements for key parameters of near-eye displays.
Efficient discontinuous Galerkin scheme for analyzing nanostructured photoconductive devices
Authors: Chen Liang , Sirenko Kostyantyn , Li Ping , Bagci Hakan
Published: April 2021

Incorporation of plasmonic nanostructures in the design of photoconductive devices (PCDs) has significantly improved their optical-to-terahertz conversion efficiency. However, this improvement comes at the cost of increased complexity for the design and simulation of these devices. Indeed, accurate and efficient modeling of multiphysics processes and intricate device geometries of nanostructured PCDs is challenging due to the high computational cost resulting from multiple characteristic scales in time and space. In this work, a discontinuous Galerkin (DG)-based unit-cell scheme for efficient simulation of PCDs with periodic nanostructures is proposed. The scheme considers two physical stages of the device and models them using two coupled systems: a system of Poisson and drift-diffusion equations describing the nonequilibrium steady state, and a system of Maxwell and drift-diffusion equations describing the transient stage. A “potential-drop” boundary condition is enforced on the opposing boundaries of the unit cell to mimic the effect of the bias voltage. Periodic boundary conditions are used for carrier densities and electromagnetic fields. The unit-cell model described by these coupled equations and boundary conditions is discretized using DG methods. Numerical results demonstrate that the proposed DG-based unit-cell scheme has the same accuracy in predicting the THz photocurrent as the DG framework that takes into account the whole device, while it significantly reduces the computational cost.
Sub-pixel registration of multi-resolution imagery by correlation matching of the bathymetry-related features
Authors: Zhang Kai , Wang Xin , Yang Fanlin , Ai Bo , Zhu Jinshan
Published: April 2021

Multispectral imaging plays a significant role in coastal mapping and monitoring applications. For tasks involving the integration of multiple overlapped images, precise co-registration of the multisource satellite images is a crucial preliminary step. However, due to the limited terrestrial area and insufficient landscape features, the traditional methods become less efficient or even invalid in offshore island environments. This study addresses the problem by exploring the feasibility of using bathymetry information for geometric registration of satellite imagery. Instead of using the ground control points (GCPs) or extracting the tie points from the landscape features, the band ratio values are extracted from the multispectral images and are subsequently matched between different images through a correlation-based similarity measure. By searching the optimum correlation within the positioning uncertainty radius, the translation between two satellite images is estimated. Thus, the geometric inconsistency between the multispectral images of different sources and resolutions is effectively reduced. This result is obtained by using the ample bathymetry features without the aid of the GCPs and the in-situ bathymetry data. The experimental results using GeoEye-1, Sentinel-2, and Landsat-8 images at Ganquan Island show that for an island setting with a limited terrestrial area, the developed method achieves sub-pixel registration accuracy (less than 2 m) in planimetry. The effect of the nonlinearity and outliers are accounted for using the Spearman correlation measure. The improvement in image alignment enables the integration of multispectral images of different sources and resolutions for producing an accurate and consistent interpretation for coastal comparative and synergistic applications.
Recurrent neural networks achieving MLSE performance for optical channel equalization
Authors: Kalla Sai-Chandra-Kumari , Gagné Christian , Zeng Ming , Rusch Leslie A.
Published: April 2021

We explore recurrent and feedforward neural networks to mitigate severe inter-symbol interference (ISI) caused by bandlimited channels, such as high speed optical communications systems pushing the frequency response of transmitter components. We propose a novel deep bidirectional long short-term memory (BiLSTM) architecture that strongly emphasizes dependencies in data sequences. For the first time, we demonstrate via simulation that for QPSK transmission the deep BiLSTM achieves the optimal bit error rate performance of a maximum likelihood sequence estimator (MLSE) with perfect channel knowledge. We assess performance for a variety of channels exhibiting ISI, including an optical channel at 100 Gbaud operation using a 35 GHz silicon photonic (SiP) modulator. We show how the neural network performance deteriorates with increasing modulation order and ISI severity. While no longer achieving MLSE performance, the deep BiLSTM greatly outperforms linear equalization in these cases. More importantly, the neural network requires no channel state information, while its performance is comparable to conventional equalizers with perfect channel knowledge.
Infrared broadband enhancement of responsivity in Ge photodetectors decorated with Au nanoparticles
Authors: Wang Liming , Wang Bo , Zhang Yichi , Meng Lingyao , Sun Hao , Liu Tao , Zhang Ningning , Jiang Zuimin , Hu Huiyong
Published: April 2021

A broadband, high-performance infrared Ge photodetector decorated with Au nanoparticles (NPs) is proposed. Photoelectronic characterization demonstrated that the responsivity of devices decorated with Au NPs is as high as 3.95 A/W at a wavelength of 1550 nm. Compared with a Ge photodetector without Au NPs, the responsivity of a device decorated with Au NPs is significantly increased, i.e., by more than 10 times in the entire range of infrared communication wavelengths, including the O, E, S, C, L, and U bands. The increase is ascribed to type-II energy-band alignment between Ge covered with Au NPs and bare Ge, instead of the localized surface-plasmon-resonance effect. The type-II energy-band alignment enhances the spatial electron-hole separation and restrains the electron-hole recombination, thus a larger photocurrent is observed. These results reflect the potential of this approach for achieving broadband, high-performance Ge photodetectors operating in the near-infrared communication band.
Photoswitchable stimulated Raman scattering spectroscopy and microscopy
Authors: Shou Jingwen , Ozeki Yasuyuki
Published: April 2021

Photoswitchable fluorescence is a powerful technique to realize super-resolution imaging, highlighting, and optical storage, while its multiplexing capability is limited. Raman scattering is attracting attention because it generates narrowband vibrational signatures, which are potentially useful for highly multiplexed detection of different constituents. Here, we demonstrate photoswitchable stimulated Raman scattering (SRS) spectroscopy and microscopy where narrowband vibrational signatures are switched with full reversibility at high speed. The demonstration of live-cell photoswitchable SRS imaging shows good sensitivity and compatibility with biological living systems.
Comparison of single- and dual-mode lasing states of a hybrid-cavity laser under optical feedback
Authors: Hao You-Zeng , Ma Chun-Guang , Shen Zheng-Zheng , Li Jian-Cheng , Xiao Jin-Long , Yang Yue-De , Huang Yong-Zhen
Published: April 2021

In this Letter, we design and realize a hybrid-cavity laser with single- or dual-mode lasing states and study the nonlinear states of the laser under external optical feedback (EOF). The laser at a dual-mode state easily and directly enters the chaotic state without periodic oscillation states and display chaos for a much wider range of the EOF magnitude than the laser at a single-mode state. A flat chaotic signal is obtained for the laser at a dual-mode lasing state under a weak EOF benefitting from the low-frequency energy enhancement caused by mode competition between the dual modes.
High efficiency and ultra-wideband polarization converter based on an L-shaped metasurface
Authors: Kamal Babar , Chen Jingdong , Yingzeng Ying , Ren Jian , Ullah Sadiq , Khan Wasi Ur Rehman
Published: April 2021

An ultra-wideband and efficient single layer polarization converting metasurface based on an L-shaped resonator is presented. The metasurface is based on an F4B dielectric substrate with relative permittivity of 2.65 and a loss tangent of 0.002. The size of the unit cell is 0.132λo × 0.132λo and the thickness of the metasurface is 0.05λo, where λo is the largest wavelength (corresponding to the lower frequency) in the operation band of interest. The proposed structure effectively transforms the linearly or circularly polarized incident wave to its orthogonal equivalent, which is justified by both simulated and measured results where the polarization conversion ratio (PCR) is greater than 90% in the frequency range from 8.6 GHz to 22 GHz with a fractional bandwidth of 88%. The polarization transformation process is illustrated in depth by the surface current distribution. Simulation results reveal that ultra-wideband is achieved because of strong electric and magnetic dipole resonances on the upper and the lower layer of the metasurface. Furthermore, the bandwidth and central frequency can be efficiently adjusted over a wide spectrum by changing the geometric aspects of the unit cell, thereby retaining high transformation proficiency. The designed converter can be used in applications such as antenna design, radar invisibility, imaging, microwave communications, and remote sensing.
Focus-tunable microscope for imaging small neuronal processes in freely moving animals
Authors: Bagramyan Arutyun , Tabourin Loïc , Rastqar Ali , Karimi Narges , Bretzner Frédéric , Galstian Tigran
Published: April 2021

Miniature single-photon microscopes have been widely used to image neuronal assemblies in the brain of freely moving animals over the last decade. However, these systems have important limitations for imaging in-depth fine neuronal structures. We present a subcellular imaging single-photon device that uses an electrically tunable liquid crystal lens to enable a motion-free depth scan in the search of such structures. Our miniaturized microscope is compact (10  mm×17  mm×12  mm) and lightweight (≈1.4  g), with a fast acquisition rate (30–50 frames per second), high magnification (8.7×), and high resolution (1.4 μm) that allow imaging of calcium activity of fine neuronal processes in deep brain regions during a wide range of behavioral tasks of freely moving mice.
Temporal dynamics of a CSF1R signaling gene regulatory network involved in epilepsy
Authors: Gérard Claude , De Mot Laurane , Cordi Sabine , van Eyll Jonathan , Lemaigre Frédéric P.
Published: April 2021

Colony Stimulating Factor 1 Receptor (CSF1R) is a potential target for anti-epileptic drugs. However, inhibition of CSF1R is not well tolerated by patients, thereby prompting the need for alternative targets. To develop a framework for identification of such alternatives, we here develop a mathematical model of a pro-inflammatory gene regulatory network (GRN) involved in epilepsy and centered around CSF1R. This GRN comprises validated transcriptional and post-transcriptional regulations involving STAT1, STAT3, NFκB, IL6R, CSF3R, IRF8, PU1, C/EBPα, TNFR1, CSF1 and CSF1R. The model was calibrated on mRNA levels of all GRN components in lipopolysaccharide (LPS)-treated mouse microglial BV-2 cells, and allowed to predict that STAT1 and STAT3 have the strongest impact on the expression of the other GRN components. Microglial BV-2 cells were selected because, the modules from which the GRN was deduced are enriched for microglial marker genes. The function of STAT1 and STAT3 in the GRN was experimentally validated in BV-2 cells. Further,in silicoanalysis of the GRN dynamics predicted that a pro-inflammatory stimulus can induce irreversible bistability whereby the expression level of GRN components occurs as two distinct states. The irreversibility of the switch may enforce the need for chronic inhibition of the CSF1R GRN in order to achieve therapeutic benefit. The cell-to-cell heterogeneity driven by the bistability may cause variable therapeutic response. In conclusion, our modeling approach uncovered a GRN controlling CSF1R that is predominantly regulated by STAT1 and STAT3. Irreversible inflammation-induced bistability and cell-to-cell heterogeneity of the GRN provide a theoretical foundation to the need for chronic GRN control and the limited potential for disease modification via inhibition of CSF1R.
Machine learning-based investigation of the cancer protein secretory pathway
Authors: Saghaleyni Rasool , Sheikh Muhammad Azam , Bangalore Pramod , Nielsen Jens , Robinson Jonathan L.
Published: April 2021

Deregulation of the protein secretory pathway (PSP) is linked to many hallmarks of cancer, such as promoting tissue invasion and modulating cell-cell signaling. The collection of secreted proteins processed by the PSP, known as the secretome, is often studied due to its potential as a reservoir of tumor biomarkers. However, there has been less focus on the protein components of the secretory machinery itself. We therefore investigated the expression changes in secretory pathway components across many different cancer types. Specifically, we implemented a dual approach involving differential expression analysis and machine learning to identify PSP genes whose expression was associated with key tumor characteristics: mutation of p53, cancer status, and tumor stage. Eight different machine learning algorithms were included in the analysis to enable comparison between methods and to focus on signals that were robust to algorithm type. The machine learning approach was validated by identifying PSP genes known to be regulated by p53, and even outperformed the differential expression analysis approach. Among the different analysis methods and cancer types, the kinesin family membersKIF20AandKIF23were consistently among the top genes associated with malignant transformation or tumor stage. However, unlike most cancer types which exhibited elevatedKIF20Aexpression that remained relatively constant across tumor stages, renal carcinomas displayed a more gradual increase that continued with increasing disease severity. Collectively, our study demonstrates the complementary nature of a combined differential expression and machine learning approach for analyzing gene expression data, and highlights key PSP components relevant to features of tumor pathophysiology that may constitute potential therapeutic targets.
Functional assessment of the “two-hit” model for neurodevelopmental defects in Drosophila and X. laevis
Authors: Pizzo Lucilla , Lasser Micaela , Yusuff Tanzeen , Jensen Matthew , Ingraham Phoebe , Huber Emily , Singh Mayanglambam Dhruba , Monahan Connor , Iyer Janani , Desai Inshya , Karthikeyan Siddharth , Gould Dagny J. , Yennawar Sneha , Weiner Alexis T. , Pounraja Vijay Kumar , Krishnan Arjun , Rolls Melissa M. , Lowery Laura Anne , Girirajan Santhosh
Published: April 2021

We previously identified a deletion on chromosome 16p12.1 that is mostly inherited and associated with multiple neurodevelopmental outcomes, where severely affected probands carried an excess of rare pathogenic variants compared to mildly affected carrier parents. We hypothesized that the 16p12.1 deletion sensitizes the genome for disease, while “second-hits” in the genetic background modulate the phenotypic trajectory. To test this model, we examined how neurodevelopmental defects conferred by knockdown of individual 16p12.1 homologs are modulated by simultaneous knockdown of homologs of “second-hit” genes inDrosophila melanogasterandXenopus laevis. We observed that knockdown of 16p12.1 homologs affect multiple phenotypic domains, leading to delayed developmental timing, seizure susceptibility, brain alterations, abnormal dendrite and axonal morphology, and cellular proliferation defects. Compared to genes within the 16p11.2 deletion, which has higherde novooccurrence, 16p12.1 homologs were less likely to interact with each other inDrosophilamodels or a human brain-specific interaction network, suggesting that interactions with “second-hit” genes may confer higher impact towards neurodevelopmental phenotypes. Assessment of 212 pairwise interactions inDrosophilabetween 16p12.1 homologs and 76 homologs of patient-specific “second-hit” genes (such asARID1BandCACNA1A), genes within neurodevelopmental pathways (such asPTENandUBE3A), and transcriptomic targets (such asDSCAMandTRRAP) identified genetic interactions in 63% of the tested pairs. In 11 out of 15 families, patient-specific “second-hits” enhanced or suppressed the phenotypic effects of one or many 16p12.1 homologs in 32/96 pairwise combinations tested. In fact, homologs ofSETD5synergistically interacted with homologs ofMOSMOin bothDrosophilaandX.laevis, leading to modified cellular and brain phenotypes, as well as axon outgrowth defects that were not observed with knockdown of either individual homolog. Our results suggest that several 16p12.1 genes sensitize the genome towards neurodevelopmental defects, and complex interactions with “second-hit” genes determine the ultimate phenotypic manifestation.
Antihypertensive treatment in a general uncontrolled hypertensive population in Belgium and Luxembourg in primary care: Therapeutic inertia and treatment simplification. The SIMPLIFY study
Authors: De Backer Tine , Van Nieuwenhuyse Bregt , De Bacquer Dirk
Published: April 2021

Background

Despite effective treatments, blood pressure (BP) control remains suboptimal.

Objective

The SIMPLIFY study aimed at identifying key factors related to therapeutic inertia in Belgium and Luxembourg, and evaluating how uncontrolled treated hypertension is managed in primary care.

Methods

In a 2017 cross-sectional survey, 245 general practitioners (GP) collected routine clinical data from 1,852 consecutive uncontrolled (Office SBP/DBP ≥ 140/90 mmHg) hypertensive adult patients taking at least one antihypertensive drug.

Results

Patients were 64 years old on average, 48% were women, 61% had dyslipidemia, 33% had diabetes mellitus and 22% had established cardiovascular disease. Half of the patients had 2 or more comorbidities. Patients had been treated for hypertension for an average period of 8 years, 40% of patients were in hypertensive stages 2–3, 44% were treated with monotherapy only, 28% with free combinations and 28% with at least one single pill combination (SPC). Therapeutic adherence was rated as ‘good’ in 62% of patients. AHT treatment was modified in 84% of patients.

In the group of patients with stage 2–3 hypertension, treatment remained unchanged in 5%. In the group of patients with stage 1 hypertension, treatment remained unchanged in 23% of patients. Patients treated for longer than 10 years were less likely to undergo treatment change (81%) compared to patients treated for less than 10 years (87%). Patients with 1 or 2 comorbidities were more likely to have their treatment modified (87%) compared to those with no comorbidities (61%) and those with ≥ 3 comorbidities (79%). If treatment was modified, a SPC was introduced in 90% of cases; 91% in stage 1–2 hypertension and 84% in stage 3 hypertension. SPCs were less frequently initiated in patients without comorbidities. Main reasons for the GPs to switch from a free association towards SPC were ‘better BP control’ (55%), ‘better therapeutic compliance’ (53%) and ‘simplicity for the patient’ (50%).

Conclusion

The SIMPLIFY study confirms therapeutic inertia in hypertension management. After an average of 8 years hypertension treatment, almost 1 in 2 uncontrolled treated patients are on monotherapy. The key inertia drivers seem to be age, mild grade hypertension, isolated systolic hypertension, longer duration of antihypertensive treatment and better therapeutic adherence. When treatment is updated by the GP, the currently preferred strategy is switching towards SPC based therapy to improve BP control, and enhance therapeutic compliance by simplifying treatment for the patient.

Trial registration

pharma.be visa number: VI 17/01/20/01

ISRCTN registered study: ISRCTN16199080.
Comparative analysis of various clinical specimens in detection of SARS-CoV-2 using rRT-PCR in new and follow up cases of COVID-19 infection: Quest for the best choice
Authors: Sharma Kuldeep , Aggarwala Pragya , Gandhi Deepa , Mathias Anuniti , Singh Priyanka , Sharma Somya , Negi Sanjay Singh , Bhargava Anudita , Das Padma , Gaikwad Ujjwala , Wankhede Archana , Behra Ajoy , Nagarkar Nitin M.
Published: April 2021

Background

An appropriate specimen is of paramount importance in Real Time reverse transcription-polymerase chain reaction (rRT-PCR) based diagnosis of novel coronavirus (nCoV) disease (COVID-19). Thus, it’s pertinent to evaluate various diversified clinical specimens’ diagnostic utility in both diagnosis and follow-up of COVID-19.

Methods

A total of 924 initial specimens from 130 COVID-19 symptomatic cases before initiation of treatment and 665 follow up specimens from 15 randomly selected cases comprising of equal number of nasopharyngeal swab (NPS), oropharyngeal swab (OPS), combined NPS and OPS (Combined swab), sputum, plasma, serum and urine were evaluated by rRT-PCR.

Results

Demographic analysis showed males (86) twice more affected by COVID-19 than females (44) (p = 0.00001). Combined swabs showed a positivity rate of 100% followed by NPS (91.5%), OPS (72.3%), sputum (63%), while nCoV was found undetected in urine, plasma and serum specimens. The lowest cycle threshold (Ct) values of targeted genes E, ORF1b and RdRP are 10.56, 10.14 and 12.26 respectively and their lowest average Ct values were found in combined swab which indicates high viral load in combined swab among all other specimen types. Analysis of 665 follow-up multi-varied specimens also showed combined swab as the last specimen among all specimen types to become negative, after an average 6.6 (range 4–10) days post-treatment, having lowest (15.48) and average (29.96) Ct values of ORF1b respectively indicating posterior nasopharyngeal tract as primary nCoV afflicted site with high viral load.

Conclusion

The combined swab may be recommended as a more appropriate specimen for both diagnosis and monitoring of COVID-19 treatment by rRT-PCR for assessing virus clearance to help physicians in taking evidence-based decision before discharging patients. Implementing combined swabs globally will definitely help in management and control of the pandemic, as it is the need of the hour.
Identification of gluten-like proteins in selected pod bearing leguminous tree seeds
Authors: Taghvaei Mostafa , Smith Brennan , Yazar Gamze , Bean Scott , Tilley Michael , Ioerger Brian
Published: April 2021

The protein composition, molecular weight distribution, and rheological properties of honey locust, mesquite, Kentucky coffee tree, and carob seed germs were compared against wheat gluten. Polymeric and Osborne fractionation protocols were used to assess biochemical properties. Dynamic oscillatory shear tests were performed to evaluate protein functionality. All samples had similar ratios of protein fractions as well as high molecular weight disulfide linked proteins except for the Kentucky coffee tree germ proteins, which were found to have lower molecular weight proteins with little disulfide polymerization. Samples were rich in acidic and polar amino acids (glutamic acid and arginine,). Rheological analyses showed that vital wheat gluten had the most stable network, while Kentucky coffee seed proteins had the weakest. High molecular weight disulfide linked glutenous proteins are a common, but not universal feature of pod bearing leguminous trees.
A metric learning method for estimating myelin content based on T2-weighted MRI from a de- and re-myelination model of multiple sclerosis
Authors: Pridham Glen , Hossain Shahnewaz , Rawji Khalil S. , Zhang Yunyan
Published: April 2021

Myelin plays a critical role in the pathogenesis of neurological disorders but is difficult to characterize in vivo using standard analysis methods. Our goal was to develop a novel analytical framework for estimating myelin content using T2-weighted magnetic resonance imaging (MRI) based on a de- and re-myelination model of multiple sclerosis. We examined 18 mice with lysolecithin induced demyelination and spontaneous remyelination in the ventral white matter of thoracic spinal cord. Cohorts of 6 mice underwent 9.4T MRI at days 7 (peak demyelination), 14 (ongoing recovery), and 28 (near complete recovery), as well as histological analysis of myelin and the associated cellularity at corresponding timepoints. Our MRI framework took an unsupervised learning approach, including tissue segmentation using a Gaussian Markov random field (GMRF), and myelin and cellularity feature estimation based on the Mahalanobis distance. For comparison, we also investigated 2 regression-based supervised learning approaches, one using our GMRF results, and another using a freely available generalized additive model (GAM). Results showed that GMRF segmentation was 73.2% accurate, and our unsupervised learning method achieved a correlation coefficient of 0.67 (top quartile: 0.78) with histological myelin, similar to 0.70 (top quartile: 0.78) obtained using supervised analyses. Further, the area under the receiver operator characteristic curve of our unsupervised myelin feature (0.883, 95% CI: 0.874–0.891) was significantly better than any of the supervised models in detecting white matter myelin as compared to histology. Collectively, metric learning using standard MRI may prove to be a new alternative method for estimating myelin content, which ultimately can improve our disease monitoring ability in a clinical setting.
Recipient pre-existing chronic hypotension is associated with delayed graft function and inferior graft survival in kidney transplantation from elderly donors
Authors: Dolla Caterina , Mella Alberto , Vigilante Giacinta , Fop Fabrizio , Allesina Anna , Presta Roberto , Verri Aldo , Gontero Paolo , Gobbi Fabio , Balagna Roberto , Giraudi Roberta , Biancone Luigi
Published: April 2021

Background

Pre-existing chronic hypotension affects a percentage of kidney transplanted patients (KTs). Although a relationship with delayed graft function (DGF) has been hypothesized, available data are still scarce and inconclusive.

Methods

A monocentric retrospective observational study was performed on 1127 consecutive KTs from brain death donors over 11 years (2003–2013), classified according to their pre-transplant Mean Blood Pressure (MBP) as hypotensive (MBP < 80 mmHg) or normal-hypertensive (MBP ≥ 80 mmHg, with or without effective antihypertensive therapy).

Results

Univariate analysis showed that a pre-existing hypotension is associated to DGF occurrence (p<0.01; OR for KTs with MBP < 80 mmHg, 4.5; 95% confidence interval [CI], 2.7 to 7.5). Chronic hypotension remained a major predictive factor for DGF development in the logistic regression model adjusted for all DGF determinants. Adjunctive evaluations on paired grafts performed in two different recipients (one hypotensive and the other one normal-hypertensive) confirmed this assumption. Although graft survival was only associated with DGF but not with chronic hypotension in the overall population, stratification according to donor age revealed that death-censored graft survival was significantly lower in hypotensive patients who received a KT from >50 years old donor.

Conclusions

Our findings suggest that pre-existing recipient hypotension, and the subsequent hypotension-related DGF, could be considered a significant detrimental factor, especially when elderly donors are involved in the transplant procedure.
Mortality and associated risk factors in patients with blood culture positive sepsis and acute kidney injury requiring continuous renal replacement therapy—A retrospective study
Authors: Järvisalo Mikko J. , Hellman Tapio , Uusalo Panu
Published: April 2021

Objectives

Septic acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) carries a mortality risk nearing 50%. Risk factors associated with mortality in AKI patients undergoing CRRT with blood culture positive sepsis remain unclear as sepsis has been defined according to consensus criteria in previous studies.

Methods

Risk factors associated with intensive care unit (ICU), 90-day and overall mortality were studied in a retrospective cohort of 126 patients with blood culture positive sepsis and coincident severe AKI requiring CRRT. Comprehensive laboratory and clinical data were gathered at ICU admission and CRRT initiation.

Results

38 different causative pathogens for sepsis and associated AKI were identified. ICU mortality was 30%, 90-day mortality 45% and one-year mortality 50%. Immunosuppression, history of heart failure, APACHE II and SAPS II scores, C-reactive protein and lactate at CRRT initiation were independently associated with mortality in multivariable Cox proportional hazards models. Blood lactate showed good predictive power for ICU mortality in receiver operating characteristic curve analyses with AUCs of 0.76 (95%CI 0.66–0.85) for lactate at ICU admission and 0.84 (95%CI 0.72–0.95) at CRRT initiation.

Conclusions

Our study shows for the first time that lactate measured at CRRT initiation is predictive of ICU mortality and independently associated with overall mortality in patients with blood culture positive sepsis and AKI requiring CRRT. Microbial etiology for septic AKI requiring CRRT is diverse.
Dynamic evolution and scenario simulation of habitat quality under the impact of land-use change in the Huaihe River Economic Belt, China
Authors: Tang Feng , Fu Meichen , Wang Li , Song Wanjuan , Yu Jiangfeng , Wu Yanbin
Published: April 2021

Habitat quality is an important indicator for evaluating the biodiversity provided by ecosystem. Estimating and scenario-simulating the dynamic evolution and future development trends of habitat quality under the influence of land-use change is significant in regional biodiversity conservation, formulating land-use planning, and maintaining the ecological environmental sustainability. In this article, we included the Huaihe River Economic Belt as the area of study because of its vital location in China and applied the CA–Markov and InVEST models to analyze the spatio-temporal evolution of habitat quality and to simulate the future development trends of habitat quality under three different land-use scenarios: fast urban growth scenario, farmland conservation-oriented scenario, and ecological conservation-oriented scenario. The results showed that the land-use change in the Huaihe River Economic Belt was mostly represented by the continuous increase of the built-up area, whereas other land types all declined in area from 1995 to 2015. The land-use changes under these three abovementioned alternative future scenarios with different development orientations were considerably different. The built-up area has been shown to expand rapidly to occupy other land types on a large scale under the fast urban growth scenario. Urban land increased slightly and a large area of rural residential land would be converted into farmland under the farmland conservation-oriented scenario. The built-up area and farmland might decrease while woodland, grassland and water would increase in extent of areas under the ecological conservation-oriented scenario. Habitat quality has been shown to be generally poor, continuing to decline from 1995 to 2015, while its spatial distribution was higher in the southwest and northeast areas and lower in the central regions. The future habitat quality would display a downward trend under the fast urban growth and farmland conservation-oriented scenarios with a further deterioration of the ecological environment, while the ecological conservation-oriented scenario predicted the converse trend that the ecological environment would be improved productively. This study may be useful for understanding the impact of land-use dynamics on biodiversity. The research results can provide a scientific basis for the decision-makers to formulate biodiversity conservation and land management policies.
Instrumental variable estimation of truncated local average treatment effects
Authors: Choi Byeong Yeob
Published: April 2021

Instrumental variable (IV) analysis is used to address unmeasured confounding when comparing two nonrandomized treatment groups. The local average treatment effect (LATE) is a causal estimand that can be identified by an IV. The LATE approach is appealing because its identification relies on weaker assumptions than those in other IV approaches requiring a homogeneous treatment effect assumption. If the instrument is confounded by some covariates, then one can use a weighting estimator, for which the outcome and treatment are weighted by instrumental propensity scores. The weighting estimator for the LATE has a large variance when the IV is weak and the target population, i.e., the compliers, is relatively small. We propose a truncated LATE that can be estimated more reliably than the regular LATE in the presence of a weak IV. In our approach, subjects who contribute substantially to the weak IV are identified by their probabilities of being compliers, and they are removed based on a pre-specified threshold. We discuss interpretation of the proposed estimand and related inference method. Simulation and real data experiments demonstrate that the proposed truncated LATE can be estimated more precisely than the standard LATE.
Clinical characteristics of COVID-19 patients with clinically diagnosed bacterial co-infection: A multi-center study
Authors: He Shengyang , Liu Wenlong , Jiang Mingyan , Huang Peng , Xiang Zhi , Deng Dingding , Chen Ping , Xie Lihua
Published: April 2021

Objective

To understand the clinical characteristics of COVID-19 patients with clinically diagnosed bacterial co-infection (CDBC), and therefore contributing to their early identification and prognosis estimation.

Method

905 COVID-19 patients from 7 different centers were enrolled. The demography data, clinical manifestations, laboratory results, and treatments were collected accordingly for further analyses.

Results

Around 9.5% of the enrolled COVID-19 patients were diagnosed with CDBC. Older patients or patients with cardiovascular comorbidities have increased CDBC probability. Increased body temperature, longer fever duration, anhelation, gastrointestinal symptoms, illness severity, intensive care unit attending, ventilation treatment, glucocorticoid therapy, longer hospitalization time are correlated to CDBC. Among laboratory results, increased white blood cell counting (mainly neutrophil), lymphocytopenia, increased procalcitonin, erythrocyte sedimentation rate, C-reaction protein, D-dimer, blood urea nitrogen, lactate dehydrogenase, brain natriuretic peptide, myoglobin, blood sugar and decreased albumin are also observed, indicating multiple system functional damage. Radiology results suggested ground glass opacity mixed with high density effusion opacities and even pleural effusion.

Conclusion

The aged COVID-19 patients with increased inflammatory indicators, worse lymphopenia and cardiovascular comorbidities are more likely to have clinically diagnosed bacterial co-infection. Moreover, they tend to have severer clinical manifestations and increased probability of multiple system functional damage.