bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPACTOS TRIBUTÁRIOS E FINANCEIROS DO LUCRO DA EXPLORAÇÃO: ANÁLISE DAS DEMONSTRAÇÕES FINANCEIRAS DA EMPRESA M. DIAS BRANCO S.A. INDÚSTRIA E COMÉRCIO DE ALIMENTOS
Authors: Freitas Narjara Rodrigues , Souza Jackeline Lucas , Alves Francisco Ivander Amado Borges
Published: January 2021

O lucro da exploração é uma metodologia de apuração dos tributos IRPJ e CSLL em bases incentivadas nas empresas optantes pelo regime de tributação do lucro real. Esta pesquisa tem por objetivo verificar os impactos financeiros e tributários decorrentes dos incentivos fiscais calculados com base no lucro da exploração na empresa M. Dias Branco S.A. Indústria e Comércio de Alimentos. Para tanto, procedeu-se à análise dos dados coletados nos demonstrativos contábeis e notas explicativas em três fases: (i) nos indicadores financeiros e econômicos, (ii) no confronto da relação custo-benefício, com e sem os incentivos fiscais e (iii) no comparativo da carga tributária, do fluxo de caixa e da distribuição de riquezas, em dois cenários (C1 e C2). Os resultados apontaram índices médios de liquidez corrente e geral de 3,97 e 2,52, respectivamente; indicador de endividamento médio de 0,37; indicadores médios de rentabilidade (margem líquida, rentabilidade do ativo e rentabilidade do PL) de 0,20, 0,17 e 0,23, respectivamente. No que tange ao custo-benefício do incentivo fiscal do lucro da exploração, verificou-se que os índices médios foram superiores a 1 (um) durante os anos da análise, indicando que o retorno da riqueza gerada pela M. Dias Branco à Sociedade foi superior ao montante recebido a título de subvenção governamental. Os índices médios, em R$, de custo-benefício geral (ICB Geral), social (ICB Social) e acionistas (ICB Acionistas) de 40,54, 25,78 e 5,91, respectivamente, sinalizam que a empresa possui boa capacidade de distribuir riqueza ao meio no qual está inserida a partir do recebimento de incentivos fiscais. Os cenários C1 e C2 evidenciaram carga tributária efetiva (IRPJ e CSLL) de 6,29% e 15,02%, respectivamente, e uma redução média de R$71.845 no montante de IRPJ e CSLL a pagar nos anos de 2014 a 2019. Conclui-se que os incentivos fiscais geram redução de carga tributária, ao longo do período analisado, de R$287.114,00 (71,51% a menos); consequentemente, isso gera maior disponibilidade de caixa, que promoveu uma maior distribuição de riquezas, esta última representada pelo ICB Social médio de R$25,78, nos gastos com pessoal e tributos, ou seja, para cada R$1,00 de incentivo fiscal, a empresa gera distribuição de riquezas de R$25,78.
From impact evaluation to decision-analysis: assessing the extent and quality of evidence on ‘value for money’ in health impact evaluations in low- and middle-income countries
Authors: Kreif Noemi , Mirelman Andrew J. , Love-Koh James , Kim Sangjun , Moreno-Serra Rodrigo , Revill Paul , Sculpher Mark , Suhrcke Marc
Published: January 2021

Background:Health impact evaluations (HIEs) are currently the main way of assessing policy changes in low-and middle-income countries (LMICs). However, evidence on effectiveness alone cannot reliably inform decisions over the allocation of limited resources. Health economic evaluation provides a suitable framework for ‘value for money’ assessments.

Methods:In this article we explore to what extent economic evaluations have been conducted alongside published health impact evaluations, then we assess the quality of these, using criteria from an economic evaluation reference case developed for use in LMICs.

Results:Among the 2419 HIEs stored in the International Initiative for Impact Evaluations (3ie) database, and among the 8155 studies identified by the Ovid Medline database search, only 70 studies included an economic evaluation. When measured against the quality assessment criteria, study quality showed great variation. Many studies did not fulfil the basic requirements for economic evaluation, such as stating the perspective of the budget holder, using generic health measures that can be compared across diseases, or suitably reflecting uncertainty.

Conclusions:Greater effort should be directed towards bringing the fields of impact evaluation and economic evaluation together to better inform resource allocation decisions in global health.
A simple ATAC-seq protocol for population epigenetics
Authors: Augusto Ronaldo de Carvalho , Rey Oliver , Cosseau Céline , Chaparro Cristian , Vidal-Dupiol Jérémie , Allienne Jean-François , Duval David , Pinaud Silvain , Tönges Sina , Andriantsoa Ranja , Luquet Emilien , Aubret Fabien , Dia Sow Mamadou , David Patrice , Thomson Vicki , Joly Dominique , Gomes Lima Mariana , Federico Déborah , Danchin Etienne , Minoda Aki , Grunau Christoph
Published: January 2021

We describe here a protocol for the generation of sequence-ready libraries for population epigenomics studies, and the analysis of alignment results. We show that the protocol can be used to monitor chromatin structure changes in populations when exposed to environmental cues. The protocol is a streamlined version of the Assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) that provides a positive display of accessible, presumably euchromatic regions. The protocol is straightforward and can be used with small individuals such as daphnia and schistosome worms, and probably many other biological samples of comparable size (~10,000 cells), and it requires little molecular biology handling expertise.
Contracting Beyond the Market
Authors: Odziemkowska Kate , Dorobantu Sinziana
Published: January 2021

Despite growing engagements between firms and nonmarket stakeholders—such as local communities and nongovernmental organizations —research has yet to examine the emergence of formal contracts between them. Given that a very large number of such contracts are theoretically possible but only a small number exist, we seek to understand what factors explain the use of contracts to govern some relationships between firms and nonmarket stakeholders but not others. We draw on transaction cost economics to study transactions wherein a nonmarket stakeholder provides a firm access to a valuable resource and to understand when these transactions are governed by formal contracts. We propose that, when a firm makes site-specific investments, a stakeholder’s use rights to the resource sought by the firm, the negative externalities generated by its use, and the stakeholder’s capacity for collective mobilization increase holdup risk for the firm and therefore the probability of a contract. We collect novel data on the location of indigenous communities and mines in Canada to identify a plausible exhaustive set of indigenous communities “at risk” of signing a contract with a mining firm. We test our hypotheses by relying, respectively, on historically assigned property rights over lands, the mine-community colocation in a watershed and proximity on transportation routes, and archival records of community mobilization events. We find support for our propositions by examining which of the 5,342 dyads formed by 459 indigenous communities and 98 firms signed 259 contracts between 1999 and 2013.
Integrated Data Bank Development as Supporting System of Civil Service Management in Middle Vocational School
Authors: Rosadi Dodi
Published: January 2021

The objectives of this study are: 1) Improved Integrated Data Bank services for staffing data and information; 2) Enhanced support system for data and information service server usage; 3) Improving data and information services that are accurate for Staffing Management. The research method used is Research and Development (R&D). Data collection techniques using questionnaires and interviews. Product trials were conducted twice, the first trial involved 15 people, the second trial involved 35 people. The results of the study are 1) Integrated Data Bank services for employee data and information can be used effectively and efficiently. This is based on system reliability with a success rate of 100%. In addition, the efficiency test using GTMetrix gives the results of the PageSpeed Grade B (85%) with a loading rate of the system page 7.4 seconds; 2) the support system for the use of data and information service servers runs according to the Integrated Data Bank application; 3) Personnel management data and information services can be used as an accurate staffing database and show that the Integrated Data Bank staffing management information system can be used as a supporting management system for staff at SMK Muhammadiyah Karangpucung; 4) Integrated Data Bank Products have gone through the process of design validation, instrument validation, and product validation through judgment experts and experts, which produce data in the form of Data Flow Diagrams (DFD), Unified Modeling Language (UML) design, and Entity Relationship Diagram Bank designs Integrated Data. Based on the results of the product design validity test showed that the layout (layout), interface (interface), and content (content) of the system itself obtained a final percentage of 84%. Suggestions in this study include 1) Socialization of the Integrated Data Bank system to employees about the existence of this system can be optimized so that all information can be conveyed properly; 2) Integrated Data Bank systems can be utilized optimally to integrate staffing data; 3) Integrated Data Bank System can be developed into a superior product as a staffing database system in the SMK environment.
A meta-analysis of COVID-19: Challenging Australias’ Vocational Education sector
Authors: Pearson Matthew
Published: January 2021

With the advent of the digital age, vocational education and associated policy documents can create an awkward marriage for the student and educator.  For the student, the move to an online platform of learning containing digital tools is more than just mastery of a program but requires support, to resolve the financial costs and connectivity issues associated with learning in isolation. For the educator, online platforms provide a challenge not only will they became a student to learn the new platform. The educator confronted with new or unfamiliar pedagogical practices vastly different from their past learning experiences. However, the digital divide is complexing with no one issue attributing or resolving the digital divide.
Investigating loyalty through CSR: The mediating role of brand image and brand trust
Authors: Abd-El-Salam Eman Mohamed
Published: January 2021

The purpose of this study is to investigate the effect of corporate social responsibility (CSR) activities on brand image, brand trust, brand loyalty, and purchase intention, based on consumers' perceptions in the context of the retail hypermarkets industry within the Egyptian market.
To address the objectives of the study, a quantitative research methodology was used; the data were collected through a questionnaire, resulting in 403 valid responses from customers. The collected data were analysed using SPSS 23 and structural equation modelling on AMOS. The study found
that CSR activities influence directly brand image and brand trust and indirectly brand loyalty and purchase intentions through the mediating role of brand image and brand trust. There was no significant direct relationship between CSR and brand loyalty as well as between CSR and purchase
intentions. The effect of brand image is stronger than brand trust on both brand loyalty and purchase intention. The effects of brand image and brand trust are stronger in brand loyalty than in purchase intention. The paper adds to the understanding of the pivotal role of CSR activities as
well as brand image and trust in affecting a consumer's intention to purchase decision, which has not been studied extensively in the Egyptian business to customer relationship markets in the retail industry. The study emphasises the importance of consumers' perceptions of CSR in achieving
the main outcomes of relationship marketing (brand image, brand trust, brand loyalty and purchase intention). Retailers are progressively anxious to contribute to social and environmental domestic and international markets. Marketers should develop more consistent and effective social responsibility
programmes to close any gaps between the retailer and the consumer perspective on CSR initiatives, and enhance the coordination between CSR activities incorporated into retailers' corporate strategic plans and their consumers' perceptions of these activities.
Characterization of physiological states of the suspended marine microalgae using polarized light scattering: erratum
Authors: Wang Yong , Dai Jincai , Liao Ran , Zhou Jin , Meng Fanqiang , Yao Yue , Chen Huirong , Tao Yi , Ma Hui
Published: January 2021

This publisher’s note corrects the author affiliations section of
Appl. Opt.
59, 1307 (2020)APOPAI0003-693510.1364/AO.377332.
Single-molecule orientation localization microscopy I: fundamental limits
Authors: Zhang Oumeng , Lew Matthew D.
Published: January 2021

Precisely measuring the three-dimensional position and orientation of
individual fluorophores is challenging due to the substantial photon
shot noise in single-molecule experiments. Facing this limited photon
budget, numerous techniques have been developed to encode 2D and 3D
position and 2D and 3D orientation information into fluorescence
images. In this work, we adapt classical and quantum estimation theory
and propose a mathematical framework to derive the best possible
precision for measuring the position and orientation of dipole-like
emitters for any fixed imaging system. We find that it is impossible
to design an instrument that achieves the maximum sensitivity limit
for measuring all possible rotational motions. Further, our vectorial
dipole imaging model shows that the best quantum-limited localization
precision is 4%–8% worse than that suggested by a scalar monopole
model. Overall, we conclude that no single instrument can be optimized
for maximum precision across all possible 2D and 3D localization and
orientation measurement tasks.
Analysis of X-ray multilayer Laue lenses made by masked deposition
Authors: Chapman Henry N. , Prasciolu Mauro , Murray Kevin T. , Lukas Dresselhaus J. , Bajt Saša
Published: January 2021

Multilayer Laue lenses are diffractive optics for hard X-rays. To achieve high numerical aperture and resolution, diffracting structures of nanometer periods are required in such lenses, and a thickness (in the direction of propagation) of several micrometers is needed for high diffracting efficiency. Such structures must be oriented to satisfy Bragg’s law, which can only be achieved consistently over the entire lens if the layers vary in their tilt relative to the incident beam. The correct tilt, for a particular wavelength, can be achieved with a very simple technique of using a straight-edge mask to give the necessary gradient of the layers. An analysis of the properties of lenses cut from such a shaded profile is presented and it is shown how to design, prepare, and characterize matched pairs of lenses that operate at a particular wavelength and focal length. It is also shown how to manufacture lenses with ideal curved layers for optimal efficiency.
Multiple guidance of light using asymmetric micro prism arrays for privacy protection of device displays
Authors: Lee H. , Heo S. G. , Bae Y. , Lee H. , Kim J. , Yoon H.
Published: January 2021

With increasing use of mobile displays outdoors, privacy-related issues have come to the fore. Therefore, in this study, we proposed a novel concept using directionally guided light transmission using double-sided asymmetric prism arrays for fabricating a privacy protection film for digital displays. The proposed film allows only the user in front of the display to see its contents using dual refraction in a prism array. Otherwise, when the display is viewed at an angle, it is difficult to recognize the contents due to the overlap of different letters. The optical path was analysed through ray-tracing simulations, and the performance of the film was quantified using an optical character recognition (OCR) method. To further enhance the effectiveness of the film, a metal film was applied on the vertical face of the micro prism arrays using an oblique deposition method. This metal-coated double-sided prism array film showed superior privacy-protecting performance compared to a conventional method based on the micro-louver structure.
In-situ non-contact high-temperature measurement of an optical fiber up to the glass softening point
Authors: Mühlberger K. , Harvey C. M. , Fokine M.
Published: January 2021

The optical fiber itself can function as a partially reflecting concentric cavity interferometer when transversely probed by a focused laser beam. In this study, the thermal response of the fiber heated by a CO2-laser beam was characterized by monitoring the back-scattered interference pattern. Simultaneous measurement of the Bragg wavelength shift of an inscribed, high-temperature stable fiber Bragg grating allowed for calibration of the temperature-dependent phase response of the interferometer. The presented technique allows for in-situ non-contact temperature measurements up to the glass softening point.
70 mJ nonlinear compression and scaling route for an Yb amplifier using large-core hollow fibers
Authors: Fan G. , Carpeggiani P. A. , Tao Z. , Coccia G. , Safaei R. , Kaksis E. , Pugzlys A. , Légaré F. , Schmidt B. E. , Baltuška A.
Published: January 2021

In this Letter, we investigate the energy-scaling rules of hollow-core fiber (HCF)-based nonlinear pulse propagation and compression merged with high-energy Yb-laser technology, in a regime where the effects such as plasma disturbance, optical damages, and setup size become important limiting parameters. As a demonstration, 70 mJ 230 fs pulses from a high-energy Yb laser amplifier were compressed down to 40 mJ 25 fs by using a 2.8-m-long stretched HCF with a core diameter of 1 mm, resulting in a record peak power of 1.3 TW. This work presents a critical advance of a high-energy pulse (hundreds of mJ level) nonlinear interactions platform based on high energy sub-ps Yb technology with considerable applications, including driving intense THz, X-ray pulses, Wakefield acceleration, parametric wave mixing and ultraviolet generation, and tunable long-wavelength generation via enhanced Raman scattering.
Controllable hybridization between localized and delocalized anisotropic borophene plasmons in the near-infrared region
Authors: Nong Jinpeng , Feng Fu , Min Changjun , Yuan Xiaocong , Somekh Michael
Published: January 2021

In this Letter, we theoretically propose a coupled borophene plasmonic system, where an anisotropic localized plasmonic (LP) mode and a delocalized guided plasmonic (DGP) mode can be simultaneously excited. This allows us to manipulate the optical response of the strong LP-DGP coupling with exceptional flexibility in the near-infrared region, which is not possible with the conventional metallic plasmonic structures, and overcomes some shortcomings of coupled structures based on the other 2D materials. Specifically, the spatially LP-DGP coupling can arise when the system is driven into the strong coupling regime; this gives rise to a transparency window which can be well described by a coupled oscillation model. The bandwidth of the window is governed by the coupling strength which can be passively adjusted by the spacer thickness, while the center wavelength and the number of windows can be actively modulated by tuning the borophene electron density and the incident angle.
Few-cycle optical pulse characterization under phase-mismatching
Authors: Mo Yunlong , Cao Wei , Xu Huiyao , Mi Kang , Sun Xuechun , Zhang Qingbin , Lu Peixiang
Published: January 2021

The phase-matching bandwidth of nonlinear crystal is of great significance in ultrashort laser pulse characterization. In order to satisfy the phase-matching bandwidth, ultra-thin nonlinear crystals are generally required. However, the significantly reduced conversion efficiency, as well as the machining difficulties, limits its applications. Here, we show that sufficient spectrum bandwidth response can be achieved for a thick crystal when the phase-matching wavelength is tuned outside of the spectral window of the measured pulse. By applying this phenomenon to a single-shot second-harmonic generation frequency resolved optical gating (SHG-FROG) device, we successfully characterized a few-cycle pulse using a

150

µ

m

β

-barium borate (BBO) crystal. The accuracy of the method was verified by comparing the conventional pulse retrieving approach with a

5

µ

m

BBO crystal, which has a sufficient phase-matching bandwidth.
High-Flux MHz Vacuum Ultraviolet Light Source
Authors: Couch David E. , Murnane Margaret M. , Hickstein Daniel D. , Kapteyn Henry C.
Published: January 2021

An ideal vacuum ultraviolet light source for applications in angle-resolved photoemission spectroscopy and photoionization mass spectrometry would have a high flux, a MHz repetition rate, a photon energy range from the UV to at least 15 eV, and variable energy and time resolution. This year, we reported a highly cascaded harmonic generation technique that addresses this challenge.
Nonreciprocal Devices in Silicon Photonics
Authors: Yang Ki Youl , Skarda Jinhie , Dutt Avik , Ahn Geun Ho , Sawaby Mahmoud , Vercruysse Dries , Arbabian Amin , Fan Shanhui , Vučković Jelena , Cotrufo Michele , Alù Andrea
Published: January 2021

Nonreciprocal devices are crucial components for optical communications, nonlinear signal processing and all-optical circuits in silicon-compatible photonic platforms, but traditional techniques for achieving nonreciprocity and isolation have lacked CMOS compatibility. In recent work, we combined state-of-the-art fabrication and inverse design to demonstrate bias-free, low-loss nonreciprocal transmission in silicon integrated devices.
Nanopainting with Light
Authors: Huo Pengcheng , Song Maowen , Lu Yanqing , Xu Ting , Zhu Wenqi , Lezec Henri J. , Agrawal Amit , Shimizu Motoko
Published: January 2021

Color is a primary attribute of human visual perception and plays a crucial role both in imaging and display technology and in the arts. In work this year, we demonstrated the ability to tune both color hue and brightness in transmitted light with a specially designed metasurface—at a level of detail sufficient to create a “nanopainting” that reproduces a celebrated artwork.
Natural Photonic Structures from Birefringent Core-Shell Nanoparticles
Authors: Yallapragada Venkata Jayasurya , Addadi Lia , Weiner Steve , Oron Dan , Palmer Benjamin
Published: January 2021

Photonic structures are responsible for the vivid colors of many animals, and also serve as reflectors and filters in vision. Our recent work has explored the core–shell photonic nanostructures involved in the eyes of several decapod crustaceans, and motivates further research into exploiting spatial variation of birefringence in designing ultrathin reflecting photonic structures.
Low-Cost Sorting of Plastic Waste
Authors: Junjuri Rajendhar , Gundawar Manoj Kumar
Published: January 2021

Plastics recycling can help tackle the vast problem of plastic waste pollution, but accurate identification of plastic type is a crucial step to make such schemes viable. Recently, we enlisted laser-induced breakdown spectroscopy (LIBS) and machine learning to create an approach for rapidly sorting plastic waste—at very low cost.
TMT-Opsins differentially modulate medaka brain function in a context-dependent manner
Authors: Fontinha Bruno M. , Zekoll Theresa , Al-Rawi Mariam , Gallach Miguel , Reithofer Florian , Barker Alison J. , Hofbauer Maximilian , Fischer Ruth M. , von Haeseler Arndt , Baier Herwig , Tessmar-Raible Kristin
Published: January 2021

Vertebrate behavior is strongly influenced by light. Light receptors, encoded by functional opsin proteins, are present inside the vertebrate brain and peripheral tissues. This expression feature is present from fishes to human and appears to be particularly prominent in diurnal vertebrates. Despite their conserved widespread occurrence, the nonvisual functions of opsins are still largely enigmatic. This is even more apparent when considering the high number of opsins. Teleosts possess around 40 opsin genes, present from young developmental stages to adulthood. Many of these opsins have been shown to function as light receptors. This raises the question of whether this large number might mainly reflect functional redundancy or rather maximally enables teleosts to optimally use the complex light information present under water. We focus ontmt-opsin1bandtmt-opsin2, c-opsins with ancestral-type sequence features, conserved across several vertebrate phyla, expressed with partly similar expression in non-rod, non-cone, non-retinal-ganglion-cell brain tissues and with a similar spectral sensitivity. The characterization of the single mutants revealed age- and light-dependent behavioral changes, as well as an impact on the levels of the preprohormonesst1band the voltage-gated sodium channel subunitscn12aa. The amount of daytime rest is affected independently of the eyes, pineal organ, and circadian clock intmt-opsin1bmutants. We further focused on daytime behavior and the molecular changes intmt-opsin1b/2double mutants, and found that—despite their similar expression and spectral features—these opsins interact in part nonadditively. Specifically, double mutants complement molecular and behavioral phenotypes observed in single mutants in a partly age-dependent fashion. Our work provides a starting point to disentangle the highly complex interactions of vertebrate nonvisual opsins, suggesting thattmt-opsin-expressing cells together with other visual and nonvisual opsins provide detailed light information to the organism for behavioral fine-tuning. This work also provides a stepping stone to unravel how vertebrate species with conserved opsins, but living in different ecological niches, respond to similar light cues and how human-generated artificial light might impact on behavioral processes in natural environments.
A multiscale model of complex endothelial cell dynamics in early angiogenesis
Authors: Stepanova Daria , Byrne Helen M. , Maini Philip K. , Alarcón Tomás
Published: January 2021

We introduce a hybrid two-dimensional multiscale model of angiogenesis, the process by which endothelial cells (ECs) migrate from a pre-existing vascular bed in response to local environmental cues and cell-cell interactions, to create a new vascular network. Recent experimental studies have highlighted a central role of cell rearrangements in the formation of angiogenic networks. Our model accounts for this phenomenon via the heterogeneous response of ECs to their microenvironment. These cell rearrangements, in turn, dynamically remodel the local environment. The model reproduces characteristic features of angiogenic sprouting that include branching, chemotactic sensitivity, the brush border effect, and cell mixing. These properties, rather than being hardwired into the model, emerge naturally from the gene expression patterns of individual cells. After calibrating and validating our model against experimental data, we use it to predict how the structure of the vascular network changes as the baseline gene expression levels of the VEGF-Delta-Notch pathway, and the composition of the extracellular environment, vary. In order to investigate the impact of cell rearrangements on the vascular network structure, we introduce the mixing measure, a scalar metric that quantifies cell mixing as the vascular network grows. We calculate the mixing measure for the simulated vascular networks generated by ECs of different lineages (wild type cells and mutant cells with impaired expression of a specific receptor). Our results show that the time evolution of the mixing measure is directly correlated to the generic features of the vascular branching pattern, thus, supporting the hypothesis that cell rearrangements play an essential role in sprouting angiogenesis. Furthermore, we predict that lower cell rearrangement leads to an imbalance between branching and sprout elongation. Since the computation of this statistic requires only individual cell trajectories, it can be computed for networks generated in biological experiments, making it a potential biomarker for pathological angiogenesis.
Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions
Authors: Rombouts Jan , Gelens Lendert
Published: January 2021

Bistability is a common mechanism to ensure robust and irreversible cell cycle transitions. Whenever biological parameters or external conditions change such that a threshold is crossed, the system abruptly switches between different cell cycle states. Experimental studies have uncovered mechanisms that can make the shape of the bistable response curve change dynamically in time. Here, we show how such a dynamically changing bistable switch can provide a cell with better control over the timing of cell cycle transitions. Moreover, cell cycle oscillations built on bistable switches are more robust when the bistability is modulated in time. Our results are not specific to cell cycle models and may apply to other bistable systems in which the bistable response curve is time-dependent.
Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria
Authors: Chatterjee Anushila , Willett Julia L. E. , Dunny Gary M. , Duerkop Breck A.
Published: January 2021

Bacteriophages (phages) are being considered as alternative therapeutics for the treatment of multidrug resistant bacterial infections. Considering phages have narrow host-ranges, it is generally accepted that therapeutic phages will have a marginal impact on non-target bacteria. We have discovered that lytic phage infection induces transcription of type VIIb secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Membrane damage during phage infection induces T7SS gene expression resulting in cell contact dependent antagonism of different Gram positive bystander bacteria. Deletion of essB, a T7SS structural component, abrogates phage-mediated killing of bystanders. A predicted immunity gene confers protection against T7SS mediated inhibition, and disruption of its upstream LXG toxin gene rescues growth of E. faecalis and Staphylococcus aureus bystanders. Phage induction of T7SS gene expression and bystander inhibition requires IreK, a serine/threonine kinase, and OG1RF_11099, a predicted GntR-family transcription factor. Additionally, sub-lethal doses of membrane targeting and DNA damaging antibiotics activated T7SS expression independent of phage infection, triggering T7SS antibacterial activity against bystander bacteria. Our findings highlight how phage infection and antibiotic exposure of a target bacterium can affect non-target bystander bacteria and implies that therapies beyond antibiotics, such as phage therapy, could impose collateral damage to polymicrobial communities.
A novel type of colistin resistance genes selected from random sequence space
Authors: Knopp Michael , Babina Arianne M. , Gudmundsdóttir Jónína S. , Douglass Martin V. , Trent M. Stephen , Andersson Dan I.
Published: January 2021

Antibiotic resistance is a rapidly increasing medical problem that severely limits the success of antibiotic treatments, and the identification of resistance determinants is key for surveillance and control of resistance dissemination. Horizontal transfer is the dominant mechanism for spread of resistance genes between bacteria but little is known about the original emergence of resistance genes. Here, we examined experimentally if random sequences can generate novel antibiotic resistance determinants de novo. By utilizing highly diverse expression libraries encoding random sequences to select for open reading frames that confer resistance to the last-resort antibiotic colistin in Escherichia coli, six de novo colistin resistance conferring peptides (Dcr) were identified. The peptides act via direct interactions with the sensor kinase PmrB (also termed BasS in E. coli), causing an activation of the PmrAB two-component system (TCS), modification of the lipid A domain of lipopolysaccharide and subsequent colistin resistance. This kinase-activation was extended to other TCS by generation of chimeric sensor kinases. Our results demonstrate that peptides with novel activities mediated via specific peptide-protein interactions in the transmembrane domain of a sensory transducer can be selected de novo, suggesting that the origination of such peptides from non-coding regions is conceivable. In addition, we identified a novel class of resistance determinants for a key antibiotic that is used as a last resort treatment for several significant pathogens. The high-level resistance provided at low expression levels, absence of significant growth defects and the functionality of Dcr peptides across different genera suggest that this class of peptides could potentially evolve as bona fide resistance determinants in natura.
Hospital-based evidence on cost-effectiveness of brucellosis diagnostic tests and treatment in Kenyan hospitals
Authors: Alumasa Lorren , Thomas Lian F. , Amanya Fredrick , Njoroge Samuel M. , Moriyón Ignacio , Makhandia Josiah , Rushton Jonathan , Fèvre Eric M. , Falzon Laura C.
Published: January 2021

Hospitals in Kenya continue to use the Febrile Antigen Brucella Agglutination Test (FBAT) to diagnose brucellosis, despite reports showing its inadequacy. This study generated hospital-based evidence on the performance and cost-effectiveness of the FBAT, compared to the Rose Bengal Test (RBT).Twelve hospitals in western Kenya stored patient serum samples that were tested for brucellosis using the FBAT, and these were later re-tested using the RBT. Data on the running time and cost of the FBAT, and the treatment prescribed for brucellosis, were collected. The cost-effectiveness of the two tests, defined as the cost in US Dollars ($) per Disability Adjusted Life Year (DALY) averted, was determined, and a basic sensitivity analysis was run to identify the most influential parameters. Over a 6-month period, 180 patient serum samples that were tested with FBAT at the hospitals were later re-tested with RBT at the field laboratory. Of these 24 (13.3%) and 3 (1.7%) tested positive with FBAT and RBT, respectively. The agreement between the FBAT and RBT was slight (Kappa = 0.12). Treatment prescribed following FBAT positivity varied between hospitals, and only one hospital prescribed a standardized therapy regimen. The mean $/DALY averted when using the FBAT and RBT were $2,065 (95% CI $481-$6,736) and $304 (95% CI $126-$604), respectively. Brucellosis prevalence was the most influential parameter in the cost-effectiveness of both tests. Extrapolation to the national level suggested that an estimated $338,891 (95% CI $47,000-$1,149,000) per year is currently spent unnecessarily treating those falsely testing positive by FBAT. These findings highlight the potential for misdiagnosis using the FBAT. Furthermore, the RBT is cost-effective, and could be considered as the mainstay screening test for human brucellosis in this setting. Lastly, the treatment regimens must be harmonized to ensure the appropriate use of antibiotics for treatment.
Mothers’ sleep deficits and cognitive performance: Moderation by stress and age
Authors: Deater-Deckard Kirby , Chary Mamatha , McQuillan Maureen E. , Staples Angela D. , Bates John E.
Published: January 2021

There are well-known associations between stress, poor sleep, and cognitive deficits, but little is known about their interactive effects, which the present study explored in a sample of mothers of toddlers. Since certain types of cognitive decline start during the 20s and continue into later ages, we also explored whether mothers’ age interacted with stress and sleep in the prediction of cognitive functioning. We hypothesized that poorer sleep [measured using one week of 24-hour wrist actigraphy data] and having more chronic stressors [e.g., life events, household chaos, work/family role conflict] would be linked with poorer cognitive performance [both executive function and standardized cognitive ability tasks], and that the interactive combination of poorer sleep and more stressors would account for the effect. We also explored whether this process operated differently for younger versus older women. In a socioeconomically and geographically diverse community sample of 227 women with toddler-age children [age,M= 32.73 yrs,SD= 5.15 yrs], poorer cognitive performance was predicted by greater activity during the sleep period, shorter sleep duration, and lower night-to-night consistency in sleep; it was not associated with higher levels of stress. The interactive effects hypothesis was supported for sleep activity [fragmented sleep] and sleep timing [when mothers went to bed]. The combination of more exposure to stressors and frequent night waking was particularly deleterious for older women’s performance. For younger women, going to bed late was associated with poorer performance if they were experiencing high levels of stress; for those experiencing low levels of stress, going to bed late was associated with better performance.
Balancing the brain of offenders with psychopathy? Resting state EEG and electrodermal activity after a pilot study of brain self-regulation training
Authors: Konicar Lilian , Radev Stefan , Silvoni Stefano , Bolinger Elaina , Veit Ralf , Strehl Ute , Vesely Christine , Plener Paul L. , Poustka Luise , Birbaumer Niels
Published: January 2021

Although investigation of the brains of criminals began quite early in the history of psychophysiological research, little is known about brain plasticity of offenders with psychopathy. Building on our preliminary study reporting successful brain self-regulation using slow cortical potential (SCP) neurofeedback in offenders with psychopathy, we investigated the central nervous and autonomic peripheral changes occurring after brain self-regulation in a group of severe male offenders with psychopathy. Regarding the central nervous system, an overall suppression of the psychopathic overrepresentation of slow frequency bands was found, such as delta and theta band activity, after EEG neurofeedback. In addition, an increase in alpha band activity could be observed after the SCP self-regulation training. Electrodermal activity adaptively changed according to the regulation task, and this flexibility improved over training time. The results of this study point towards a constructive learning process and plasticity in neural and peripheral measures of offenders with psychopathy.
Robust estimation of diagnostic rate and real incidence of COVID-19 for European policymakers
Authors: Català Martí , Pino David , Marchena Miquel , Palacios Pablo , Urdiales Tomás , Cardona Pere-Joan , Alonso Sergio , López-Codina David , Prats Clara , Alvarez-Lacalle Enrique
Published: January 2021

Policymakers need clear, fast assessment of the real spread of the COVID-19 epidemic in each of their respective countries. Standard measures of the situation provided by the governments include reported positive cases and total deaths. While total deaths indicate immediately that countries like Italy and Spain had the worst situation as of mid-April, 2020, reported cases alone do not provide a complete picture of the situation. Different countries diagnose differently and present very distinctive reported case fatality ratios. Similar levels of reported incidence and mortality might hide a very different underlying pictures. Here we present a straightforward and robust estimation of the diagnostic rate in each European country. From that estimation we obtain a uniform, unbiased incidence of the epidemic. The method to obtain the diagnostic rate is transparent and empirical. The key assumption of the method is that the infection fatality ratio of COVID-19 in Europe is not strongly country-dependent. We show that this number is not expected to be biased due to demography nor to the way total deaths are reported. The estimation protocol is dynamic, and it has been yielding converging numbers for diagnostic rates in all European countries as from mid-April, 2020. Using this diagnostic rate, policy makers can obtain Effective Potential Growth updated every day, providing an unbiased assessment of the countries at greater risk of experiencing an uncontrolled situation. The method developed has been and will be used to track possible improvements in the diagnostic rate in European countries as the epidemic evolves.
Assessment patient satisfaction towards emergency medical care and its determinants at Ayder comprehensive specialized hospital, Mekelle, Northern Ethiopia
Authors: Molalign Takele Goitom , Abreha Weldesenbet Negash , Girmay Nahom , Degefe Habtamu , Kinfe Rigbe
Published: January 2021

Background

As the healthcare industry shifts toward patient-centered models, providers will need to fully understand patient satisfaction and how they affect their practices. This study aimed to assess patient satisfaction towards the emergency medical care and factors associated with at Ayder specialized comprehensive hospital, Emergency room, Mekelle, Ethiopia.

Methods

An institution-based cross-sectional study was conducted from March 1–30, 2019. A systematic random sampling method was used to enroll 299 study participants. Data were collected using a standard Brief Emergency Department Patient Satisfaction Scale questionnaire by trained data collectors. Data was entered into EpiData 3.1 then exported and analyzed by SPSS version 22. Binary and multiple logistic regression were used to assess the factors associated with patient satisfaction. Where the p-value of <0.05 was considered significant.

Results

A total of 299 participants were enrolled in the study with a response rate of 99.3%. On overall patient satisfaction score majority (81.9%) of them were satisfied with the emergency medical care provided. The satisfaction rate towards emergency staff courtesy, emergency room environment, physician care satisfaction, general patient satisfaction, and patient family satisfaction was 80.3%, 37.5%, 75.9%, 70.9%, and 49.8% respectively. Those who arrived during the morning time of the day tend to be satisfied more with the emergency services (AOR = 4.8, 95% CI: 2.08, 11.4), while having low educational status (able to read and write) (AOR = 0.12, 95% CI: 0.03, 0.50) and waiting time till seen by a doctor (AOR = 1.3, 95% CI: 1.003, 1.4) was found to affect patient satisfaction negatively.

Conclusions

The total patient satisfaction score towards emergency medical care was found to be good. The hospital management and emergency room staff should act on the identified factors especially on minimizing the patients waiting time to improve the quality of care in the emergency department.
Evaluating antibiotic use and developing a tool to optimize prescribing in a family-centered HIV clinic in Eswatini
Authors: Ness Tara E. , Streatfield Ashish E. , Simelane Tandzile , Korsa Abiy , Dlamini Sandile , Guffey Danielle , Lukhele Bhekumusa , Kay Alexander W.
Published: January 2021

In a human immunodeficiency virus (HIV) clinic for children and their families in Eswatini, we sought to understand the use of antibiotics and identify specific areas for improvement. We performed a retrospective patient chart review as part of a quality improvement (QI) initiative to assess antimicrobial use before and after implementation of a standardized antimicrobial guide. For each prescribing period, 100 random patient encounters were selected for review if the indication for antibiotics, duration, and dose were consistent with World Health Organization (WHO) guidelines. Two physicians reviewed each encounter using a structured abstraction tool, with a third resolving discrepancies. Results were analyzed using a chi-square test of proportions and a structured survey was performed to assess perceptions of the guide. After the implementation of an antimicrobial guide, there was a significant decrease in the proportion of clinic visits with an antibiotic prescribed (p < 0.001). Incorrect indication for antimicrobial use decreased from 20.4% in the initial period to 10.31% and 10.2% but did not reach significance (p = .0621) in the subsequent periods after implementation. Incorrect dose/duration decreased from 10.47% in the initial period to 7.37% and 3.1% in the subsequent periods, but this was also was not significant (p = 0.139). All prescribers who completed the survey felt that it positively impacted their prescribing. Our study found that an antimicrobial guide reduced and improved the prescription of antimicrobials, demonstrating practical solutions can have a lasting impact on prescribing in low resource settings.
3D multi-scale deep convolutional neural networks for pulmonary nodule detection
Authors: Peng Haixin , Sun Huacong , Guo Yanfei
Published: January 2021

With the rapid development of big data and artificial intelligence technology, computer-aided pulmonary nodule detection based on deep learning has achieved some successes. However, the sizes of pulmonary nodules vary greatly, and the pulmonary nodules have visual similarity with structures such as blood vessels and shadows around pulmonary nodules, which make the quick and accurate detection of pulmonary nodules in CT image still a challenging task. In this paper, we propose two kinds of 3D multi-scale deep convolution neural networks for nodule candidate detection and false positive reduction respectively. Among them, the nodule candidate detection network consists of two parts: 1) the backbone network part Res2SENet, which is used to extract multi-scale feature information of pulmonary nodules, it is composed of the multi-scale Res2Net modules of multiple available receptive fields at a granular level and the squeeze-and-excitation units; 2) the detection part, which uses a region proposal network structure to determine region candidates, and introduces context enhancement module and spatial attention module to improve detection performance. The false positive reduction network, also composed of the multi-scale Res2Net modules and the squeeze-and-excitation units, can further classify the nodule candidates generated by the nodule candidate detection network and screen out the ground truth positive nodules. Finally, the prediction probability generated by the nodule candidate detection network is weighted average with the prediction probability generated by the false positive reduction network to obtain the final results. The experimental results on the publicly available LUNA16 dataset showed that the proposed method has a superior ability to detect pulmonary nodules in CT images.