bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Optimization Approach to Process Flexibility Designs with Contribution Margin Differentials
Authors: Wang Shixin , Wang Xuan , Zhang Jiawei
Published: October 2020

Problem definition: The theoretical investigation of the effectiveness of limited flexibility has mainly focused on a performance metric that is based on the maximum sales in units. However, this could lead to substantial profit losses when the maximum sales metric is used to guide flexibility designs while the products have considerably large profit margin differences. Academic/practical relevance: We address this issue by introducing margin differentials into the analysis of process flexibility designs, and our results can provide useful guidelines for the evaluation and design of flexibility configurations when the products have heterogeneous margins. Methodology: We adopt a robust optimization framework and study process flexibility designs from the worst-case perspective by introducing the dual margin group index (DMGI). Results and managerial implications: We show that a general class of worst-case performance measures can be expressed as functions of a design’s DMGIs and the given uncertainty set. Moreover, the DMGIs lead to a partial ordering that enables us to compare the worst-case performance of different designs. Applying these results, we prove that under the so-called partwise independently symmetric uncertainty sets and a broad class of worst-case performance measures, the alternate long-chain design is optimal among all long-chain designs with equal numbers of high-profit products and low-profit products. Finally, we develop a heuristic based on the DMGIs to generate effective flexibility designs when products exhibit margin differentials.
Diagnostic accuracy among trainees to safely confirm peripherally inserted central catheter (PICC) placement using bedside ultrasound
Authors: Furlong-Dillard Jamie , Aljabari Salim , Hirshberg Ellie
Published: October 2020

Background

Real-time utilization of ultrasound to confirm peripherally inserted central catheter (PICC) placement improves efficacy and reduces patient radiation exposure. We evaluated if novice ultrasound users could accurately confirm appropriate PICC tip location via ultrasound assessment.

Methodology

A prospective data collection study was conducted in an academic center with an established PICC team. Novice ultrasonography users performed 2 echocardiographic views (subcostal and apical 4 chamber) and noted position of visible wire. The presence of central bubbles (visualized in the heart) after a saline infusion, as well as time to bubbles (push-to-bubbles) seen in all patients, was also recorded. Image quality and confidence in imaging acquisition was also recorded.

Results

Twenty-eight patients between ages 0 and 18 were enrolled over the study period with mean patient age of 10 years and median weight of 34 kg. The quality of image acquisition was rated as great only 34–44%. The wire was visualized only 25% of the time. The median push-to-bubble time when the PICC was later confirmed to be in appropriate positioning was 1.5 seconds with a delay of greater than 3 seconds 40% of the time when the line was malpositioned. The overall positive predictive value of ultrasound identifying malpositioned lines in this study was 43%.

Conclusions

With this PICC placement technique, ultrasound confirmation of PICC placement by novice ultrasound users was not superior to confirmation with chest radiograph. There may remain potential for future ultrasound protocols, with pediatric-specific technology or echogenic catheter tips, to reduce radiation exposure from chest radiograph during PICC line positioning verification.
Managing CVADs in 2020
Authors: Oliver Gemma
Published: October 2020

Gemma Oliver Macmillan Head of Nursing, Cancer, Clinical Haematology and Haemophilia, East Kent Hospitals University NHS Foundation Trust
Survey of ultrasound-guided peripheral intravenous practices: a report of supply usage and variability between clinical roles and departments
Authors: Moureau Nancy , Gregory E. Gilbert
Published: October 2020

Background

The purpose of this study was to investigate ultrasound-guided peripheral intravenous (UGPIV) supply usage practices by clinicians working in vascular access, in emergency departments (EDs), or in other roles.

Methodology

In 2019, a voluntary cross-sectional descriptive survey was conducted via SurveyMonkey. Data collected included demographics, practice-oriented information, procedural activities, and supplies used for UGPIV insertions. Frequency distributions and results of Fisher's exact test and one-way analysis of variance were reported using R v.3.5.2.

Results

A total of 26,649 surveys were distributed with a response rate of 5.5% (n = 1475). Forty-eight percent of respondents (n = 709) indicated that they worked in a vascular access role, 310 (21%) worked in an ED, and 455 (31%) categorized their role as other. Clinically meaningful differences existed in all variables for UGPIV procedures and supplies between departments (P < 0.0001) and in all care settings. Using an investigatorconstructed overall metric of supplies used, important differences were demonstrated between personnel supply use in vascular access roles and other roles (P < 0.0001) and personnel in EDs and other roles (P < 0.0001).

Conclusions

Use of supplies for UGPIV insertions varies by department. The variability in supply usage for UGPIV insertions revealed by this survey suggests a need for clinical education on guideline application and evaluation of compliance with policies to promote standardization of supplies for UGPIV insertion.
Misplacement of piccs following power-injected CT contrast media
Authors: Wortley Val , Almerol Leo Andrew
Published: October 2020

Peripherally inserted central catheters (PICCs) may be used to administer contrast injection during CT (computed tomography) scans to improve diagnostic accuracy. This is usually done with the use of a power injector. Research has shown that misplacement of catheters following contrast injection can occur. The aim of this review was to analyse appropriately positioned pre-scan PICCs that malposition following injection of contrast media during a CT scan, evaluate whether tip location or right or left insertion plays a part in the displacement of PICCs after CT, and to ensure those involved are aware of the risks and the safety checks required following such procedures. A quantitative method was used, gathering information from the team's insertion database to review 2045 records of contrast-injectable PICCs between 1 January 2015 and 30 April 2020. Analysis of the data indicated that 1% of appropriately sited PICCs malposition following contrast CT injection and that the catheter is able to self-correct back to its original position at an average interval of 24–72 hours without any other intervention. Further research is needed to explore other factors that could influence the rate of self-correction and complications of prolonged catheter malposition.
SECUREment bundles to prevent peripheral intravenous catheter failure—the SECURE-PIVC trial: study protocol for a pilot randomized controlled trial
Authors: Corley Amanda , Ullman Amanda J , Marsh Nicole , Emily N. Larsen , Mihala Gabor , Harris Patrick N. A. , Rickard Claire M.
Published: October 2020

Introduction

Peripheral intravenous catheters (PIVCs) are widely used, but failure is unacceptably common with up to 69% failing before treatment is complete. PIVC securement reduces failure, but the optimal way to achieve this is unclear. Tapes and supplementary securement products are widely used, however rigorous testing of these to reduce PIVC failure remains unexplored.

Methods and analysis

In adult medical-surgical wards at a tertiary hospital, this pilot randomized controlled trial tests standard care (bordered polyurethane dressing plus nonsterile tape over the extension tubing) against two securement interventions (intervention one: standard care plus two sterile tape strips over the PIVC hub; intervention two: intervention one plus a tubular bandage). Patients >18 years of age requiring a PIVC for >24 hours are eligible. Patients with laboratory-confirmed positive blood cultures within 24 hours of screening, known allergy to study products, current or high-risk of skin tear, or non-English speaking without interpreter are excluded. Sample size is 35 per trial arm, and central randomization is computer-generated with allocation concealed until entry. Patients and clinical staff cannot be blinded to treatment allocation. However, infection outcomes are assessed by a blinded investigator. Primary outcome is study feasibility. Secondary outcomes (PIVC failure, dwell time, skin adverse events, PIVC colonization, and cost) are compared between groups. Feasibility outcomes are reported descriptively.

Ethics and trial commencement

Ethical approvals were received from Royal Brisbane and Women's Hospital (HREC/18/QRBW/44571) and Griffith University (2018/1000). Trial commencement was May 2019. Trial registration: ACTRN12619000026123.
Glenoid fractures of the shoulder
Authors: Ström Peter
Published: October 2020

Glenoid fractures of the shoulder are uncommon. Any scapular fracture involving the glenoid should be scrutinized carefully for a surgical treatment option. Classification is helpful in deciding the surgical tactic.

Cite this article: EFORT Open Rev 2020;5:620-623. DOI: 10.1302/2058-5241.5.190057
EFORT Open Reviews: Turbulence
Authors: Hoffmeyer Pierre
Published: October 2020

Cite this article: EFORT Open Rev 2020;5:568-569. DOI: 10.1302/2058-5241.5.200200
EFORT Open Reviews: The Editor-in-chief’s perspective
Authors: Bentley George
Published: October 2020

Cite this article: EFORT Open Rev 2020;5:571-573. DOI: 10.1302/2058-5241.5.200201
Dynamic Adjustment of Center Pivot Nozzle Height: An Evaluation of Center Pivot Water Application Pattern and the Coefficient of Uniformity
Authors: Al-agele Hadi A. , Mahapatra D. M. , Prestwich Clarence , Higgins Chad W
Published: October 2020

Abstract.

This study assesses the potential of dynamic nozzle height adjustment for overhead irrigation systems. This system would maintain the nozzle or emitter a constant distance above the crop canopy throughout the growing season and would dynamically respond to variability in canopy height across the field. Within such systems, nozzle height would no longer be fixed in space and time. Nozzle heights would instead vary across space and time. This dynamic system response may therefore have adverse impacts on water application uniformity. The impact of DESA on application uniformity was assessed in three steps. First, changes in individual sprinkler patterns for pressure, nozzle type, flow rate, and nozzle height were measured in controlled experiments. Next, parametrized equations of the individual sprinkler patterns and how they are altered by nozzle height are developed. Next, the Center Pivot Evaluation and Design software was used to simulate theoretical uniformity, and these simulations were tested against field measurements of the coefficient of uniformity. Finally, we use the parameterized equations within the Center Pivot Evaluation and Design software to simulate the coefficient of uniformity for pivots with constant nozzle heights with a random distribution of nozzle heights, which simulate a dynamic elevation system. It was found that the uniformity coefficient decreased by 4-6% as the distribution of heights throughout the pivot become more variable, due to localized dynamic height adjustment. Systems equipped with nozzles with triangular spray patterns were less impacted than systems equipped with nozzles with elliptical spray patterns. Keywords: Keyword. Center pivot, Center Pivot Elevation and Design (CPED), Nozzle height, Sensor, Sprinkler pattern, Uniformity coefficient.
Field Test and Economic Analysis of Energy-Saving Renovation for an Old Nursery Pig Building in Beijing, China
Authors: Zhao Wanying , Wang Meizhi , Li Hao , Li Guoming , Shi Zhengxiang
Published: October 2020

Highlights

An old nursery pig building was retrofitted to potentially improve envelope insulation capacity.

A mathematical theory based on coal consumption was established to evaluate energy efficiency of insulation renovation for a nursery pig building.

The heat loss of the nursery pig house with 90-mm-thick extruded polystyrene boards was 60% lower than that without the materials.

Ground source heat pump and air source heat pump are economical and environmental-friendly heating systems.

Abstract. Appropriate renovation of old buildings is critical for energy-efficient pig production. Currently, energy consumption, especially coal consumption, keeps on rising in the production. Therefore, it is essential to develop energy-saving renovation methods for old nursery pig buildings and use cleaner heating energies. A mathematical theory based on coal consumption was established to evaluate energy efficiency of insulation renovation. Two nursery pig houses were tested in this experiment. One was the retrofitted house with the 90-mm-thick extruded polystyrene boards embedded onto outer walls, and the other one was served as a control house without those insulation materials. The results show that the air temperature and inside surface temperature of the retrofitted house were significantly higher than those of the control house in winter. Therefore, though adding insulation layers to walls, the envelope insulation capacity was improved. Meanwhile, the heat loss of the retrofitted house was 60% lower than that of the control house (11.08 W m-2 vs. 27.93 W m-2), when the theoretical ventilation rate was 1560 m3 h-1. In addition, with the prohibition of the coal usage in forseeable future of China, the ground source heat pump and air source heat pump can be economical solutions for heating systems with clean and renewable energy. Keywords: Air source heat pump, Extruded polystyrene board, Ground source heat pump, Heating, Thermal insulation.
Transport and Retention of Cadmium in Biochar-Amended Sand Porous Media
Authors: Xiao Lurui , Wang Daojing , Sang Wenjing , Ji Mengyuan , Zhou Lei , Xu Shihong , Zhang Yalei
Published: October 2020

Highlights

Batch experiment indicated that sorption of Cd on biochar was highly pH-dependant.

The main mechanism of Cd-biochar sorption were surface precipitation and ion exchange.

Biochar affected the transportation of the attached Cd.

At the same ionic strength, the transportation is faster in the presence of Ca2+ than Na+.

Abstract. Cadmium (Cd) is toxic to plants and animals, leaching of Cd through soil profiles can affect its accumulation and pollute the ground-water. In this study, we performed batch and column experiments to study the effect of biochar on the retention and transport of Cd in saturated porous media under different solution chemistry. Specific factors were considered including pH, ionic strength, and biochar dosages. The results of batch experiment indicated that sorption of Cd on biochar was highly pH-dependant, but ionic strength had negligible effect on the adsorption of Cd to biochar. The mechanism of the adsorption process of biochar for Cd mainly involves surface precipitation and ion exchange. In the column experiment, the increase in pH and biochar dosages made the Cd more stable, whereas the increase in ionic strength improved the migration of Cd. The increased retention time of Cd was related to the greater retarded coefficient value (R) based on two-site kinetic retention model. The decrease of partitioning coefficient (ß) and fraction of instantaneous sorption sites (f) were in favor of the continuous and dynamic adsorption under column conditions. This study will provide a theoretical and scientific basis for the rational assessment of cadmium-related risks in biochar-modified environments. Keywords: Adsorption, Biochar, Cadmium, Porous media, Transport.
Designing flat optical devices for path and wave vector manipulation by space transformation along a fixed direction
Authors: Giloan M. , Gutt R.
Published: October 2020

The capability of flat devices to manipulate the wave paths and wave vectors of electromagnetic waves is studied. The devices consisting in a transformed medium delimited by two parallel planes are designed by transforming the original free space along a fixed direction by an arbitrary function. We present the general equations describing the wave path and wave vector evolution inside such flat devices. In order to validate the theoretical results, a flat convergent lens working at oblique incidence is designed and discussed through computer simulations.
Pulsed terahertz spectroscopy combined with hybrid machine learning approaches for structural health monitoring of multilayer thermal barrier coatings
Authors: Ye Dongdong , Wang Weize , Yin Changdong , Xu Zhou , Zhou Haiting , Fang Huanjie , Li Yuanjun , Huang Jibo
Published: October 2020

Structural health monitoring of multilayer thermal barrier coatings (TBCs) is very vital to ensure the structural integrity and service performance of the hot-section components of the aero-engine. In this paper, we theoretically and numerically demonstrated that the terahertz time domain spectrum and the terahertz reflectance spectrum could be adopted to estimate the structure parameters, based on the finite difference time domain (FDTD) algorithm, 64 samples which were imported with three kinds of 64 sets structure parameters had been calculated to obtain the time domain and terahertz reflectance signals. To mimic the actual test signals, the original FDTD simulation signals were processed by adding the Gaussian white noise and wavelet noise reduction. To reduce the data dimension and improve the calculation efficiency during modeling, the principal component analysis (PCA) algorithm was adopted to reduce the dimensions of time-domain data and reflectance data. Finally, these data after multiple signal processing and PCA feature extraction were used to train the extreme learning machine (ELM), combining the genetic algorithm (GA) could optimize the PCA-ELM model and further improve the prediction performance of the hybrid model. Our proposed novel and efficient terahertz nondestructive technology combined with the hybrid machine learning approaches provides great potential applications on the multilayer TBCs structural integrity evaluation.
Gbps physical random bit generation based on the mesoscopic chaos of a silicon photonics crystal microcavity
Authors: Shi Binglei , Luo Ciwei , Flor Flores Jaime G. , Lo Guoqiang , Kwong Dim-Lee , Wu Jiagui , Wong Chee Wei
Published: October 2020

We present an experimental and theoretical physical random bit (PRB) generator using the mesoscopic chaos from a photonic-crystal optomechanical microcavity with a size of ∼10µm and very low operating intracavity energy of ∼60 Femto-Joule that was fabricated with CMOS compatible processes. Moreover, two kinds of PRB generation were proposed with rates over gigabits per second (Gbps). The randomness of the large PRB strings was further veriﬁed using the NIST Special Publication 800-22. In addition, the Diehard statistical test was also used to confirm the quality of the obtained PRBs. The results of this study can offer a new generation of dedicated PRB solutions that can be integrated on Si substrates, which can speed up systems and eliminate reliance on external mechanisms for randomness collection.
General design principle for structured light lasers
Authors: Scholes Stirling , Sroor Hend , Ait-Ameur Kamel , Zhan Qiwen , Forbes Andrew
Published: October 2020

Using custom laser cavities to produce as the output some desired structured light field has seen tremendous advances lately, but there is no universal approach to designing such cavities for arbitrarily defined field structures within the cavity, e.g., at both the output and gain ends. Here we outline a general design approach for structured light from lasers which allows us to specify the required cavity for any selected structured light fields at both ends. We verify the approach by numerical simulation as well as by an unwrapped cavity experiment. The power of this approach is that the cavity can be designed to maximise the overlap with the available pump for higher powers, minimise thermal effects for higher brightness, and at the same time output a desired structured light field that may differ substantially from the gain-end profile. These benefits make this work appeal to the large laser communities interested in cavities for high brightness and/or customized output beams.
Realization of strong coupling between 2D excitons and cavity photons at room temperature
Authors: Zhao Xinchao , Yan Yanhong , Cui Zhuangzhuang , Liu Feng , Wang Shaowei , Sun Liaoxin , Chen Yuwei , Lu Wei
Published: October 2020

Two-dimensional (2D) semiconductors of graphene, as well as transition–metal dichalcogenides, have performed strong interaction with light. Here the strong light–matter interaction between monolayer tungsten disulphide (

W
S

2

) excitons and microcavity photons at room temperature is well studied by the introduction of a gain material embedded dielectric optical microcavity structure. A Rabi splitting of about 36 meV is observed in angle-resolved reflectance spectra at room temperature, which agrees well with the theoretical results simulated by using the transfer matrix method. Since the cavity structures and 2D semiconductors can be prepared, the cavity and the gain materials, respectively, can be optimized separately in this platform. An all-dielectric Fabry–Pérot microcavity provides a simple but effective way to study the room temperature strong coupling between cavity photons and 2D excitons.
Sequence heterochrony led to a gain of functionality in an immature stage of the central complex: A fly–beetle insight
Authors: Farnworth Max S. , Eckermann Kolja N. , Bucher Gregor
Published: October 2020

Animal behavior is guided by the brain. Therefore, adaptations of brain structure and function are essential for animal survival, and each species differs in such adaptations. The brain of one individual may even differ between life stages, for instance, as adaptation to the divergent needs of larval and adult life of holometabolous insects. All such differences emerge during development, but the cellular mechanisms behind the diversification of brains between taxa and life stages remain enigmatic. In this study, we investigated holometabolous insects in which larvae differ dramatically from the adult in both behavior and morphology. As a consequence, the central complex, mainly responsible for spatial orientation, is conserved between species at the adult stage but differs between larvae and adults of one species as well as between larvae of different taxa. We used genome editing and established transgenic lines to visualize cells expressing the conserved transcription factorretinal homeobox, thereby marking homologousgenetic neural lineagesin both the flyDrosophila melanogasterand the beetleTribolium castaneum. This approach allowed us for the first time to compare the development of homologous neural cells between taxa from embryo to the adult. We found complex heterochronic changes including shifts of developmental events between embryonic and pupal stages. Further, we provide, to our knowledge, the first example ofsequence heterochronyin brain development, where certain developmental steps changed their position within the ontogenetic progression. We show that through thissequence heterochrony, an immature developmental stage of the central complex gains functionality inTriboliumlarvae.
Significance of trends in gait dynamics
Authors: Kozlowska Klaudia , Latka Miroslaw , West Bruce J.
Published: October 2020

Trends in time series generated by physiological control systems are ubiquitous. Determining whether trends arise from intrinsic system dynamics or originate outside of the system is a fundamental problem of fractal series analysis. In the latter case, it is necessary to filter out the trends before attempting to quantify correlations in the noise (residuals). For over two decades, detrended fluctuation analysis (DFA) has been used to calculate scaling exponents of stride time (ST), stride length (SL), and stride speed (SS) of human gait. Herein, rather than relying on the very specific form of detrending characteristic of DFA, we adopt Multivariate Adaptive Regression Splines (MARS) to explicitly determine trends in spatio-temporal gait parameters during treadmill walking. Then, we use the madogram estimator to calculate the scaling exponent of the corresponding MARS residuals. The durations of ST and SL trends are determined to be independent of treadmill speed and have distributions with exponential tails. At all speeds considered, the trends of ST and SL are strongly correlated and are statistically independent of their corresponding residuals. The averages of scaling exponents of ST and SL MARS residuals are slightly smaller than 0.5. Thus, contrary to the interpretation prevalent in the literature, the statistical properties of ST and SL time series originate from the superposition of large scale trends and small scale fluctuations. We show that trends serve as the control manifolds about which ST and SL fluctuate. Moreover, the trend speed, defined as the ratio of instantaneous values of SL and ST trends, is tightly controlled about the treadmill speed. The strong coupling between the ST and SL trends ensures that the concomitant changes of their values correspond to movement along the constant speed goal equivalent manifold as postulated by Dingwell et al. 10.1371/journal.pcbi.1000856.
Gene expression noise can promote the fixation of beneficial mutations in fluctuating environments
Authors: Schmutzer Michael , Wagner Andreas
Published: October 2020

Nongenetic phenotypic variation can either speed up or slow down adaptive evolution. We show that it can speed up evolution in environments where available carbon and energy sources change over time. To this end, we use an experimentally validated model ofEscherichia coligrowth on two alternative carbon sources, glucose and acetate. On the superior carbon source (glucose), all cells achieve high growth rates, while on the inferior carbon source (acetate) only a small fraction of the population manages to initiate growth. Consequently, populations experience a bottleneck when the environment changes from the superior to the inferior carbon source. Growth on the inferior carbon source depends on a circuit under the control of a transcription factor that is repressed in the presence of the superior carbon source. We show that noise in the expression of this transcription factor can increase the probability that cells start growing on the inferior carbon source. In doing so, it can decrease the severity of the bottleneck and increase mean population fitness whenever this fitness is low. A modest amount of noise can also enhance the fitness effects of a beneficial allele that increases the fraction of a population initiating growth on acetate. Additionally, noise can protect this allele from extinction, accelerate its spread, and increase its likelihood of going to fixation. Central to the adaptation-enhancing principle we identify is the ability of noise to mitigate population bottlenecks, particularly in environments that fluctuate periodically. Because such bottlenecks are frequent in fluctuating environments, and because periodically fluctuating environments themselves are common, this principle may apply to a broad range of environments and organisms.
Tissue-specific isoforms of the single C. elegans Ryanodine receptor gene unc-68 control specific functions
Authors: Marques Filipe , Thapliyal Saurabh , Javer Avelino , Shrestha Priyanka , Brown André E. X. , Glauser Dominique A.
Published: October 2020

Ryanodine receptors (RyR) are essential regulators of cellular calcium homeostasis and signaling. Vertebrate genomes contain multiple RyR gene isoforms, expressed in different tissues and executing different functions. In contrast, invertebrate genomes contain a single RyR-encoding gene and it has long been proposed that different transcripts generated by alternative splicing may diversify their functions. Here, we analyze the expression and function of alternative exons in theC.elegansRyR geneunc-68. We show that specific isoform subsets are created via alternative promoters and via alternative splicing inunc-68Divergent Region 2 (DR2), which actually corresponds to a region of high sequence variability across vertebrate isoforms. The expression of specificunc-68alternative exons is enriched in different tissues, such as in body wall muscle, neurons and pharyngeal muscle. In order to infer the function of specific alternative promoters and alternative exons ofunc-68, we selectively deleted them by CRISPR/Cas9 genome editing. We evaluated pharyngeal function, as well as locomotor function in swimming and crawling with high-content computer-assisted postural and behavioral analysis. Our data provide a comprehensive map of the pleiotropic impact of isoform-specific mutations and highlight that tissue-specificunc-68isoforms fulfill distinct functions. As a whole, our work clarifies how theC.eleganssingle RyR geneunc-68can fulfill multiple tasks through tissue-specific isoforms, and provide a solid foundation to further developC.elegansas a model to study RyR channel functions and malfunctions.
Estimating indirect parental genetic effects on offspring phenotypes using virtual parental genotypes derived from sibling and half sibling pairs
Authors: Hwang Liang-Dar , Tubbs Justin D. , Luong Justin , Lundberg Mischa , Moen Gunn-Helen , Wang Geng , Warrington Nicole M. , Sham Pak C. , Cuellar-Partida Gabriel , Evans David M.
Published: October 2020

Indirect parental genetic effects may be defined as the influence of parental genotypes on offspring phenotypes over and above that which results from the transmission of genes from parents to their children. However, given the relative paucity of large-scale family-based cohorts around the world, it is difficult to demonstrate parental genetic effects on human traits, particularly at individual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at individual loci in principle using large-scale genome-wide association study (GWAS) data, even in the absence of parental genotypes. Our strategy involves creating “virtual” mothers and fathers by estimating the genotypic dosages of parental genotypes using physically genotyped data from relative pairs. We then utilize the expected dosages of the parents, and the actual genotypes of the offspring relative pairs, to perform conditional genetic association analyses to obtain asymptotically unbiased estimates of maternal, paternal and offspring genetic effects. We apply our approach to 19066 sibling pairs from the UK Biobank and show that a polygenic score consisting of imputed parental educational attainment SNP dosages is strongly related to offspring educational attainment even after correcting for offspring genotype at the same loci. We develop a freely available web application that quantifies the power of our approach using closed form asymptotic solutions. We implement our methods in a user-friendly software package IMPISH (IMputing Parental genotypes In Siblings and Half Siblings) which allows users to quickly and efficiently impute parental genotypes across the genome in large genome-wide datasets, and then use these estimated dosages in downstream linear mixed model association analyses. We conclude that imputing parental genotypes from relative pairs may provide a useful adjunct to existing large-scale genetic studies of parents and their offspring.
Modeling epistasis in mice and yeast using the proportion of two or more distinct genetic backgrounds: Evidence for “polygenic epistasis”
Authors: Rau Christoph D. , Gonzales Natalia M. , Bloom Joshua S. , Park Danny , Ayroles Julien , Palmer Abraham A. , Lusis Aldons J. , Zaitlen Noah
Published: October 2020

Background

The majority of quantitative genetic models used to map complex traits assume that alleles have similar effects across all individuals. Significant evidence suggests, however, that epistatic interactions modulate the impact of many alleles. Nevertheless, identifying epistatic interactions remains computationally and statistically challenging. In this work, we address some of these challenges by developing a statistical test for polygenic epistasis that determines whether the effect of an allele is altered by the global genetic ancestry proportion from distinct progenitors.

Results

We applied our method to data from mice and yeast. For the mice, we observed 49 significant genotype-by-ancestry interaction associations across 14 phenotypes as well as over 1,400 Bonferroni-corrected genotype-by-ancestry interaction associations for mouse gene expression data. For the yeast, we observed 92 significant genotype-by-ancestry interactions across 38 phenotypes. Given this evidence of epistasis, we test for and observe evidence of rapid selection pressure on ancestry specific polymorphisms within one of the cohorts, consistent with epistatic selection.

Conclusions

Unlike our prior work in human populations, we observe widespread evidence of ancestry-modified SNP effects, perhaps reflecting the greater divergence present in crosses using mice and yeast.
Spatiotemporal transmission dynamics of co-circulating dengue, Zika, and chikungunya viruses in Fortaleza, Brazil: 2011–2017
Authors: Kazazian Lilit , Lima Neto Antonio S. , Sousa Geziel S. , Nascimento Osmar José do , Castro Marcia C.
Published: October 2020

The mosquito-borne viruses dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV), now co-endemic in the Americas, pose growing threats to health worldwide. However, it remains unclear whether there exist interactions between these viruses that could shape their epidemiology. This study advances knowledge by assessing the transmission dynamics of co-circulating DENV, ZIKV, and CHIKV in the city of Fortaleza, Brazil. Spatiotemporal transmission dynamics of DENV, ZIKV, and CHIKV were analyzed using georeferenced data on over 210,000 reported cases from 2011 to 2017 in Fortaleza, Brazil. Local spatial clustering tests and space-time scan statistics were used to compare transmission dynamics across all years. The transmission of co-circulating viruses in 2016 and 2017 was evaluated at fine spatial and temporal scales using a measure of spatiotemporal dependence, the τ-statistic. Results revealed differences in the diffusion of CHIKV compared to previous DENV epidemics and spatially distinct transmission of DENV/ZIKV and CHIKV during the period of their co-circulation. Significant spatial clustering of viruses of the same type was observed within 14-day time intervals at distances of up to 6.8 km (p<0.05). These results suggest that arbovirus risk is not uniformly distributed within cities during co-circulation. Findings may guide outbreak preparedness and response efforts by highlighting the clustered nature of transmission of co-circulating arboviruses at the neighborhood level. The potential for competitive interactions between the arboviruses should be further investigated.
Therapeutic vaccination of SIV-infected, ART-treated infant rhesus macaques using Ad48/MVA in combination with TLR-7 stimulation
Authors: Bricker Katherine M. , Obregon-Perko Veronica , Uddin Ferzan , Williams Brianna , Uffman Emilie A. , Garrido Carolina , Fouda Genevieve G. , Geleziunas Romas , Robb Merlin , Michael Nelson , Barouch Dan H. , Chahroudi Ann
Published: October 2020

Globally, 1.8 million children are living with HIV-1. While antiretroviral therapy (ART) has improved disease outcomes, it does not eliminate the latent HIV-1 reservoir. Interventions to delay or prevent viral rebound in the absence of ART would be highly beneficial for HIV-1-infected children who now must remain on daily ART throughout their lifespan. Here, we evaluated therapeutic Ad48-SIV prime, MVA-SIV boost immunization in combination with the TLR-7 agonist GS-986 in rhesus macaque (RM) infants orally infected with SIVmac251at 4 weeks of age and treated with a triple ART regimen beginning 4 weeks after infection. We hypothesized immunization would enhance SIV-specific T cell responses during ART-mediated suppression of viremia. Compared to controls, vaccinated infants had greater magnitude SIV-specific T cell responses (mean of 3475 vs 69 IFN-γspot forming cells (SFC) per 106PBMCs, respectively, P = 0.01) with enhanced breadth of epitope recognition and increased CD8+and CD4+T cell polyfunctionality (P = 0.004 and P = 0.005, respectively). Additionally, SIV-specific gp120 antibodies against challenge and vaccine virus strains were significantly elevated following MVA boost (P = 0.02 and P < 0.001, respectively). GS-986 led to expected immune stimulation demonstrated by activation of monocytes and T cells 24 hours post-dose. Despite the vaccine-induced immune responses, levels of SIV DNA in peripheral and lymph node CD4+T cells were not significantly different from controls and a similar time to viral rebound and viral load set point were observed following ART interruption in both groups. We demonstrate infant RMs mount a robust immunological response to this immunization, but vaccination alone was not sufficient to impact viral reservoir size or modulate rebound dynamics following ART release. Our findings hold promise for therapeutic vaccination as a part of a combination cure approach in children and highlight the importance of a pediatric model to evaluate HIV-1 cure interventions in this unique setting of immune development.
Assessment of Pre-Service Teacher Dispositions
Authors: Bradley Elizabeth , Isaac Patricia , King Joseph
Published: October 2020

Measurement of pre-service teacher dispositions is an important part of teacher preparation programs. A strong correlation exists between dispositions of teachers and the quality of their student’s learning. Teachers, in addition to sharing content knowledge, are responsible for demonstrating and sharing core values relating to virtues such as honesty, justice, fairness, care, empathy, integrity, courage, respect, and responsibility, and these values must guide their own conduct and interpersonal relations. As teachers serve pupils who are minors, their conduct and potential to serve effectively and ethically in the profession must be evaluated. However, a thorough faculty-led instrument to assess pre-service teacher candidates’ disposition does not currently exist. The purpose of this research was to develop an assessment of pre-service teachers’ dispositions for use in teacher education programs. A 25-item instrument was created through assessment of teacher education program needs and review of best practices on building teacher evaluation instruments, national professional teaching standards, and existing assessment tools. Teacher education faculty completed the instrument assessing roughly 600 students in a masters-level teacher education program. Results indicate that this instrument is a valid and reliable tool that will allow teacher education faculty and administrators to assess teacher candidate professional skills and conduct.
Optimization of Pancreatic Juice Collection: A First Step Toward Biomarker Discovery and Early Detection of Pancreatic Cancer
Authors: Levink Iris J. M. , Nesteruk Kateryna , Visser Dido I. , Sieuwerts Anieta M. , Fernandes Celio J.C. , Jansen Maurice P.H.M. , van Driel Lydi M.J.W. , Poley Jan-Werner , Peppelenbosch Maikel P. , Cahen Djuna L. , Fuhler Gwenny M. , Bruno Marco J.
Published: October 2020

INTRODUCTION:

Imaging-based surveillance programs fail to detect pancreatic ductal adenocarcinoma at a curable stage, creating an urgent need for diagnostic biomarkers.

METHODS:

Secretin-stimulated pancreatic juice (PJ) was collected from the duodenal lumen during endoscopic ultrasound. The yield of biomarkers and organoids was compared for 2 collection techniques (endoscope suction channel vs catheter-based) and 3 periods (0–4 vs 4–8 vs 8–15 minutes).

RESULTS:

Collection through the endoscope suction channel was superior to collection with a catheter. Collection beyond 8 minutes reduced biomarker yield. PJ-derived organoid culture was feasible.

DISCUSSION:

The optimal protocol for secretin-stimulated PJ collection is through the endoscope suction channel for 8 minutes allowing biomarker detection and organoid culture.
Role of Locoregional Therapies in Patients With Hepatocellular Cancer Awaiting Liver Transplantation
Authors: Thuluvath Paul J. , To Chau , Amjad Waseem
Published: October 2020

Hepatocellular cancer (HCC) is the fifth most common cancer in the world and the third most common cause of cancer-related deaths. The United Network for Organ Sharing has its own staging criteria for organ allocation, which is a modification of tumor-node-metastasis staging of American Joint Committee on Cancer. For the purpose of clarity, United Network for Organ Sharing staging will be described as uT1, uT2 (Milan criteria), and uT3 (eligible for downstaging) in this review. For those with unresectable HCC or those with advanced liver disease and HCC but within the Milan criteria, liver transplantation is the treatment of choice. Because of prolonged waiting period on the liver transplant list in many parts of the world for deceased donor liver transplantation, there is a serious risk of dropout from the liver transplant list because of tumor progression. For those patients, locoregional therapies might need to be considered, and moreover, there is circumstantial evidence to suggest that tumor progression after locoregional therapies might be a surrogate marker of unfavorable tumor biology. There is no consensus on the role or type of locoregional therapies in the management of patients with uT1 and uT2 eligible for liver transplant and of those with lesions larger than uT2 but eligible for downstaging protocol (uT3 lesions). In this review, we examine the role of locoregional therapies in these patients stratified by staging and propose treatment options based on the current evidence of tumor progression rates while awaiting liver transplantation and tumor recurrence rates after liver transplantation.
Achalasia Is Associated With Atopy in Patients Younger Than 40 Years of Age
Authors: King Dominic , Thomas Tom , Chandan Joht Singh , Bhala Nij , Adderley Nicola J. , Nirantharakumar Krishnarajah , Trudgill Nigel
Published: October 2020

INTRODUCTION:

Case reports describe individuals with achalasia features subsequently diagnosed with eosinophilic esophagitis (an atopic disorder). We have examined associations between achalasia and atopic and autoimmune conditions.

METHODS:

This is a UK cohort study of 2,593 subjects with achalasia matched to 10,402 controls.

RESULTS:

At diagnosis, achalasia was associated with autoimmune conditions (odds ratio 1.39; 95% confidence interval 1.02–1.90) and atopic conditions (1.40; 1.00–1.95) in those aged younger than 40 years.

DISSCUSSION:

Our findings support an autoimmune etiology in achalasia but also suggest a possible atopic etiology in younger subjects.
Long-Term Incidence and Mortality of Colorectal Cancer After Endoscopic Biopsy With Normal Mucosa: A Swedish-Matched Cohort Study
Authors: Song Mingyang , Emilsson Louise , Hultcrantz Rolf , Roelstraete Bjorn , Ludvigsson Jonas F.
Published: October 2020

INTRODUCTION:

Endoscopic screening reduces colorectal cancer (CRC) incidence and mortality. Individuals with a negative result are recommended to undergo rescreening within a 10-year interval, but evidence supporting this advice is limited.

METHODS:

We performed a matched cohort study using prospectively collected data from 88,798 individuals in Sweden with normal mucosa at the first colorectal biopsy (aged ≥50 years) in the nationwide gastrointestinal epidemiology strengthened by histopathology reports (ESPRESSO) (1965–2016) and 424,150 matched reference individuals from the general population. Cox proportional hazards regression estimated multivariable hazard ratios and 95% confidence intervals (CIs) of CRC incidence and mortality of incident CRCs up to 44 years of follow-up.

RESULTS:

In the normal biopsy and reference groups, respectively, the 20-year incidences of CRC were 3.03% and 4.53% and the 20-year mortalities of incident CRC were 0.89% and 1.54%. The multivariable hazard ratio comparing the normal biopsy and reference groups was 0.62 for CRC incidence (95% CI = 0.58–0.66, P < 0.001) and 0.56 for mortality of incident CRC (95% CI = 0.49–0.64, P < 0.001). When assessed by time interval after biopsy, lower CRC incidence and mortality were observed throughout the follow-up. The association seemed weaker for proximal colon cancer than for rectal and distal colon cancer.

DISCUSSION:

A normal colorectal biopsy was associated with lower CRC incidence and mortality for at least 20 years after the examination. Our findings confirm previous data and suggest that the screening intervals after a normal colonoscopy could be longer than the commonly recommended 10 years. It may be time to open the discussion for a revision of the international guidelines.
Rapid Rectal Polyposis Development in a Patient With Familial Adenomatous Polyposis
Authors: Abrams Hannah R. , Lee Michelle , Dahdal Sami , Khalaf Natalia
Published: October 2020

Familial adenomatous polyposis (FAP) is a well-described genetic condition that results in the development of multiple benign and malignant lesions throughout the gastrointestinal tract. The development of colorectal cancer is nearly universal in classic FAP, and total proctocolectomy after polyp development is recommended. We present a patient with FAP who was unable to undergo proctectomy. Despite careful removal of all rectal polyps before subtotal colectomy with ileorectal anastomosis, he developed 12 rectal polyps, including 4 advanced neoplastic lesions, within 73 days after initial endoscopic removal. This case highlights the rapid regrowth rate of colorectal adenomas in FAP.
Assisted reproductive technologies: psychoneurological, moral-ethical, and socio-cultural aspects
Authors: Tyuvina N. A. , Nikolaevskaya A. O.
Published: October 2020

The paper provides a definition of sexual and reproductive health and infertility and also reflects modern ideas about ways to overcome infertility using assisted reproductive technologies, such as in vitro fertilization (IVF) and surrogacy. It shows the specificity of the impact of an IVF procedure on the mental health of a potential mother. The features of the neonatal health status, as well as neuropsychiatric disorders in babies born using the IVF procedure are described. The authors present two types of surrogacy (traditional and gestational ones) and the features of their use in different countries according to governmental legislative regulation, socioeconomic and religious factors, and cultural traditions in society. They unveil the features of a psychological relationship between the mother (surrogate and presumed one) and the fetus. The consequences of surrogacy for a surrogate mother, genetic parents, and a child himself/herself are noted to be little studied. It is shown that the development of assisted reproductive technologies (IVF and surrogacy), on the one hand, helps fight infertility and, on the other hand, entails a number of problems (moral and ethical, legal, cultural and religious, socioeconomic, and neuropsychiatric ones) that need to be solved in order to prevent psychological, neurological, and mental abnormalities in all the participants (a surrogate mother, an unborn child, and potential parents) in the assisted reproductive process: