bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-infrared frequency comb generation from a silicon microresonator
Authors: Zhang Yaojing , Kumar Rakesh Ranjan , Zhong Keyi , Tsang Hon Ki
Published: July 2021

Optical frequency combs (OFCs) have been widely explored in the silica and silicon nitride platforms, from visible light to mid-infrared wavelength. Although silicon has a larger nonlinear coefficient, it suffers from larger two-photon absorption and consequent free-carrier absorption. Therefore, microresonator-based OFCs have not been experimentally demonstrated in the silicon platform with a single pump in the near-infrared region. Here, we experimentally demonstrated the Kerr comb generation (KCG) in a high-quality-factor silicon microresonator using sub-milliwatt pump power without any reverse bias for removing the free carriers. We experimentally investigated the effects of pump powers and quality factors (Qs) on the comb output power and number of comb lines. Under low pump power, either larger pump power or larger Q can yield higher comb output power and more comb lines. However, at higher pump powers, the comb output power is limited by nonlinear absorptions. The KCG was well established by using pump wavelengths in the range from 1340 nm to 1650 nm. The further combination of this microresonator with a p-i-n diode is possible to obtain considerable comb output powers. This work shows the possibility of microresonator-based OFCs in silicon chips at telecom wavelengths.
Synthetic Control Methods for the Evaluation of Single-Unit Interventions in Epidemiology: A Tutorial
Authors: Bonander Carl , Humphreys David , Degli Esposti Michelle
Published: July 2021

Evaluating the impacts of population-level interventions (e.g., changes to state legislation) can be challenging as conducting randomized experiments is often impractical and inappropriate, especially in settings where the intervention is implemented in a single, aggregate unit (e.g., a country or state). A common nonrandomized alternative is to compare outcomes in the treated unit(s) with unexposed controls both before and after the intervention. However, the validity of these designs depends on the use of controls that closely resemble the treated unit on before-intervention characteristics and trends on the outcome, and suitable controls may be difficult to find because the number of potential control regions is typically limited. The synthetic control method provides a potential solution to these problems by using a data-driven algorithm to identify an optimal weighted control unit—a “synthetic control”—based on data from before the intervention from available control units. While popular in the social sciences, the method has not garnered as much attention in health research, perhaps due to a lack of accessible texts aimed at health researchers. We address this gap by providing a comprehensive, nontechnical tutorial on the synthetic control method, using a worked example evaluating Florida’s “stand your ground” law to illustrate methodological and practical considerations.
The Utility of the Test of Memory Malingering Trial 1 in Differentiating Neurocognitive, Emotional, and Behavioral Functioning in a Pediatric Concussion Population
Authors: Smith Alphonso , Thomas Julia , Friedhoff Claire , Chin Esther
Published: July 2021

Objective

In concussion populations, suboptimal task engagement detected by performance validity tests (PVTs) has been associated with poorer neuropsychological scores and greater post-concussive symptoms (PCS). This study examined if Pass/Fail status on the Test of Memory Malingering—TOMM Trial 1—differentiated the neurocognitive, emotional, and behavioral profile of pediatric patients with concussion.

Method

This study utilized archival data from 93 patients (mean age = 14.56 and SD = 2.01) with a history of concussion who were assessed at ~5–6 weeks post-injury (mean days = 40.27 and SD = 35.41). Individuals were divided into “Pass” and “Fail” groups based on TOMM Trial 1 performance. The testing battery included ACT, CPT-II and III, HVLT-R, WJ-III and IV ACH, ImPACT, BASC-2, and BRIEF.

Results

The overall pass rate on Trial 1 was 70% (mean = 46.04 and SD = 4.55). Findings suggested that a passing score on Trial 1 may be associated with adequate performance across the remaining two trials of the TOMM. The Fail group scored significantly lower across attention, memory, and processing speed measures when compared with the Pass group. On rating scales, significantly more concerns were endorsed with the Fail group for attention and executive functioning relative to the Pass group. Parents generally endorsed significantly more concerns for executive functioning when compared with their children’s self-reported symptoms. There was a trend for the Fail group to report more PCS; however, they did not significantly differ from the Pass group for depression, anxiety, or somatization.

Conclusions

This study highlights the importance of utilizing PVTs when evaluating concussion recovery.
Addressing data imbalance problems in ligand-binding site prediction using a variational autoencoder and a convolutional neural network
Authors: Nguyen Trinh-Trung-Duong , Nguyen Duc-Khanh , Ou Yu-Yen
Published: July 2021

Since 2015, a fast growing number of deep learning–based methods have been proposed for protein–ligand binding site prediction and many have achieved promising performance. These methods, however, neglect the imbalanced nature of binding site prediction problems. Traditional data-based approaches for handling data imbalance employ linear interpolation of minority class samples. Such approaches may not be fully exploited by deep neural networks on downstream tasks. We present a novel technique for balancing input classes by developing a deep neural network–based variational autoencoder (VAE) that aims to learn important attributes of the minority classes concerning nonlinear combinations. After learning, the trained VAE was used to generate new minority class samples that were later added to the original data to create a balanced dataset. Finally, a convolutional neural network was used for classification, for which we assumed that the nonlinearity could be fully integrated. As a case study, we applied our method to the identification of FAD- and FMN-binding sites of electron transport proteins. Compared with the best classifiers that use traditional machine learning algorithms, our models obtained a great improvement on sensitivity while maintaining similar or higher levels of accuracy and specificity. We also demonstrate that our method is better than other data imbalance handling techniques, such as SMOTE, ADASYN, and class weight adjustment. Additionally, our models also outperform existing predictors in predicting the same binding types. Our method is general and can be applied to other data types for prediction problems with moderate-to-heavy data imbalances.
Exploring the Impact of the First Wave of COVID-19 on Social Work Practice: A Qualitative Study in England, UK
Authors: Kingstone Tom , Campbell Paul , Andras Alina , Nixon Karen , Mallen Christian , Dikomitis Lisa ,   the Q-COVID-19 Group
Published: July 2021

The COVID-19 pandemic signalled a radical shift in health and social care services globally. In UK, many of the people with existing social care needs were identified as ‘clinically vulnerable’ to COVID-19. Those at greatest risk were encouraged to adhere to additional public health measures that inadvertently exacerbated social disadvantages. Social workers were challenged to ‘dig deep’ to continue to provide services as usual. However, problems implementing new ways of working were reported but not examined in-depth through research. Our study explored experiences and perceptions of social workers responding to the first wave (April–July 2020) of COVID-19, in England, UK. Interviews with thirteen social workers, all working in the West Midlands region, were conducted via telephone or online video. Transcripts were analysed using reflexive thematic analysis. We use ‘managing uncertainty’ as a central concept underpinning the four themes identified after analysis: (1) providing social care at a physical distance, (2) negotiating home/work boundaries, (3) managing emerging risks and (4) long-term implications for social work. We discuss our findings in the context of resilience and organisational adaptation. Social workers in our study demonstrated resilience in action and rapid adaptation to new practices, but equally expressed concern about short-term efficiencies being prioritised over individual service user needs.
Dedicated Representation of Others in the Macaque Frontal Cortex: From Action Monitoring and Prediction to Outcome Evaluation
Authors: Ferrucci Lorenzo , Nougaret Simon , Falcone Rossella , Cirillo Rossella , Ceccarelli Francesco , Genovesio Aldo
Published: July 2021

Social neurophysiology has increasingly addressed how several aspects of self and other are distinctly represented in the brain. In social interactions, the self–other distinction is fundamental for discriminating one’s own actions, intentions, and outcomes from those that originate in the external world. In this paper, we review neurophysiological experiments using nonhuman primates that shed light on the importance of the self–other distinction, focusing mainly on the frontal cortex. We start by examining how the findings are impacted by the experimental paradigms that are used, such as the type of social partner or whether a passive or active interaction is required. Next, we describe the 2 sociocognitive systems: mirror and mentalizing. Finally, we discuss how the self–other distinction can occur in different domains to process different aspects of social information: the observation and prediction of others’ actions and the monitoring of others’ rewards.
Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Induced by Natural Infection or Vaccination: A Systematic Review and Pooled Analysis
Authors: Chen Xinhua , Chen Zhiyuan , Azman Andrew S , Sun Ruijia , Lu Wanying , Zheng Nan , Zhou Jiaxin , Wu Qianhui , Deng Xiaowei , Zhao Zeyao , Chen Xinghui , Ge Shijia , Yang Juan , Leung Daniel T , Yu Hongjie
Published: July 2021

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection–mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6–4.7-fold), 1.8-fold (1.4–2.4-fold), and 3.2-fold (2.4–4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2–1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5–9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7–4.4-fold) for messenger RNA platform, and 2.5-fold (1.7–2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.
COVID-19 Outbreak Associated With a Fitness Center—Minnesota, September–November 2020
Authors: Suhs Tara , Gerlach Daniel , Garfin Jacob , Lorentz Alexandra , Firestone Melanie , Sherden Meaghan , Hackman Katie , Gray Talor , Siebman Samantha , Wienkes Haley , Vilen Kelley , Wang Xiong , Como-Sabetti Kathy , Danila Richard , Smith Kirk , Medus Carlota
Published: July 2021

The Minnesota Department of Health investigated a coronavirus disease 2019 (COVID-19) outbreak at a fitness center in Olmsted County, Minnesota. Twenty-three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections (5 employees and 18 members) were identified. An epidemiological investigation supported by whole genome sequencing demonstrated that transmission of SARS-CoV-2 occurred at the fitness center despite following recommended prevention strategies.
Risk factors for the occurrence of peptic esophagitis following laparoscopic Heller-Dor surgery for esophageal achalasia
Authors: Tsuboi Kazuto , Yano Fumiaki , Omura Nobuo , Hoshino Masato , Yamamoto Se-Ryung , Akimoto Shunsuke , Masuda Takahiro , Sakashita Yuki , Fukushima Naoko , Kashiwagi Hideyuki
Published: July 2021

Peptic esophagitis can occur as a complication of laparoscopic Heller-Dor surgery (LHD) among patients with esophageal achalasia. The goal of this study was to identify the characteristics of patients who have developed peptic esophagitis following LHD surgery along with the risk factors associated with the occurrence of peptic esophagitis. Among the 447 cases consisting of esophageal achalasia patients who underwent LHD as the primary surgery, we compared the patient background, pathophysiology, symptoms, and surgical outcomes according to whether or not peptic esophagitis occurred following surgery. We also attempted to use univariate and multivariate analyses to identify the risk factors for peptic esophagitis occurring following surgery. Esophagitis following surgery was confirmed in 67 cases (15.0%). With respect to the patient backgrounds for cases in which peptic esophagitis had occurred, a significantly higher number were male patients, with a significantly high occurrence of mucosal perforation during surgery in terms of surgical outcomes, along with a high occurrence of esophageal hiatal hernias in terms of postoperative course (P = 0.045, 0.041, and 0.022, respectively). However, there were no significant differences in terms of age, BMI, disease duration, preoperative symptoms, esophageal manometric findings, esophageal barium findings, and esophageal clearance. A multivariate analysis indicated independent risk factors for the occurrence of peptic esophagitis following LHD as being male, the occurrence of mucosal perforation during surgery, and the occurrence of esophageal hiatal hernias. Peptic esophagitis occurred following LHD in 15% of cases. Independent risk factors for the occurrence of peptic esophagitis following LHD included being male, the occurrence of mucosal perforation during surgery, and the occurrence of esophageal hiatal hernias following surgery.
A Nudge to Quit? The Effect of a Change in Pension Information on Annuitisation, Labour Supply and Retirement Choices Among Older Workers
Authors: Hagen Johannes , Hallberg Daniel , Lindquist Gabriella Sjögren
Published: July 2021

We study the effects of two exogenous modifications in the Swedish pension system application form nudging individuals towards a fixed-term payout. Meanwhile, the set of available options and the default option—life annuity—were unchanged during the period under study. We examine the effects on individuals’ payout decisions and the spillover effects on labour supply and other pensions using a difference-in-difference framework and detailed administrative data on actual payout decisions and a wide range of individual-level outcomes. Each modification increased the demand for the nudged payout by around 30 percentage points. The first modification also induced individuals to work less.
The temporal viscoelastic model of flexural isostasy for estimating the elastic thickness of the lithosphere
Authors: Eshagh Mehdi , Tenzer Robert
Published: July 2021

The (effective) elastic thickness of the lithosphere defines the strength of the lithosphere with respect to a load on it. Since the lithosphere is buoyant on a viscous mantle, its behaviour with respect to a load is not fully elastic, but rather viscoelastic. Fennoscandia is a well-known area in the world where the lithosphere has not yet reached its isostatic equilibrium due to the ongoing uplift after the last glacial period at the end of the Pleistocene. To accommodate for this changing property of the lithosphere in time, we present the flexural model of isostasy that accommodates temporal variations of the lithospheric flexure. We then define a theoretical model for computing the elastic thickness of the lithosphere based on combining the flexural and gravimetric models of isostasy. We demonstrate that differences between the elastic and viscoelastic models are not that significant in Fennoscandia. This finding is explained by a relatively young age of the glacial load when compared to the Maxwell relaxation time. The approximation of an elastic shell is then permissible in order to determine the lithospheric structure and its properties. In this way, the elastic thickness can be estimated based on combining gravimetric and flexural models of isostasy. This approach takes into consideration the topographic and ocean-floor (bathymetric) relief as well as the lithospheric structural composition and the post-glacial rebound. In addition, rheological properties of the lithosphere are taken into consideration by means of involving the Young modulus and the Poisson ratio in the model, both parameters determined from seismic velocities. The results reveal that despite changes in the Moho geometry attributed to the glacial isostatic adjustment in Fennoscandia are typically less than 1 km, the corresponding changes in the lithospheric elastic thickness could reach or even exceed ±50 km. The sensitivity analysis confirms that even small changes in input parameters could significantly modify the result (i.e. the elastic thickness estimates). The reason is that the elastic thickness estimation is an inverse problem. Consequently, small changes in input parameters can lead to large changes in the elastic thickness estimates. These findings indicate that a robust estimation of the elastic thickness by our method is possible if comprehensive information about structural and rheological properties of the lithosphere as input parameters are known with a relatively high accuracy. Otherwise, even small uncertainties in these parameters could result in large errors in the elastic thickness estimates.
Thermal conductivity of Triassic evaporites
Authors: Pauselli C , Gola G , Ranalli G , Mancinelli P , Trippetta F , Ballirano P , Verdoya M
Published: July 2021

Evaporites occur in various geological environments: sedimentary basins, orogenic belts, where they often act as tectonic decoupling layers, and as top-seals in hydrocarbon fields. In all cases, they affect the temperature distribution in the upper crust, as their thermal conductivity is relatively higher with respect to other sedimentary rocks. High heat conduction through evaporites enhances the geothermal gradient above the evaporitic layer and decreases it below, with potential consequences for surface heat flow, depth of the brittle–ductile transition and low-enthalpy geothermal exploitation. An accurate determination of their thermal conductivity is therefore necessary. We estimate the thermal conductivity of evaporitic rocks with a two-pronged method. First, an exhaustive review of the literature allows the determination of the conductivity for the main evaporitic minerals and of their variation with temperature. Secondly, in order to assess the effects of compositional variability, we select six samples of Triassic evaporites from the Apennines (from both outcrops and boreholes) and measure their mineralogical composition and thermal conductivity. The composition has a strong effect on conductivity, which goes from 5 W m–1 K–1 when anhydrite or dolomite are volumetrically predominant, to 2 W m–1 K–1 when gypsum is predominant. We also use various mixing models (where the rock conductivity is estimated from the mineralogical composition) and find sufficient agreement between measured and predicted values to justify the use of such models when direct measurements are not available. Finally, as an illustrative example of the thermal consequences of evaporites in the upper crust, we model the variations of temperature and surface heat flow caused by the occurrence of evaporitic layers of different thickness. The results show that the effects on crustal geotherms and the distribution of seismicity can be significant.
A Unifying Framework for Understanding Biological Structures and Functions Across Levels of Biological Organization
Authors: Herman M A , Aiello B R , DeLong J D , Garcia-Ruiz H , González A L , Hwang W , McBeth C , Stojković E A , Trakselis M A , Yakoby N
Published: July 2021

The relationship between structure and function is a major constituent of the rules of life. Structures and functions occur across all levels of biological organization. Current efforts to integrate conceptual frameworks and approaches to address new and old questions promise to allow a more holistic and robust understanding of how different biological functions are achieved across levels of biological organization. Here, we provide unifying and generalizable definitions of both structure and function that can be applied across all levels of biological organization. However, we find differences in the nature of structures at the organismal level and below as compared to above the level of the organism. We term these intrinsic and emergent structures, respectively. Intrinsic structures are directly under selection, contributing to the overall performance (fitness) of the individual organism. Emergent structures involve interactions among aggregations of organisms and are not directly under selection. Given this distinction, we argue that while the functions of many intrinsic structures remain unknown, functions of emergent structures are the result of the aggregate of processes of individual organisms. We then provide a detailed and unified framework of the structure–function relationship for intrinsic structures to explore how their unknown functions can be defined. We provide examples of how these scalable definitions applied to intrinsic structures provide a framework to address questions on structure–function relationships that can be approached simultaneously from all subdisciplines of biology. We propose that this will produce a more holistic and robust understanding of how different biological functions are achieved across levels of biological organization.
Using dagR to identify minimal sufficient adjustment sets and to simulate data based on directed acyclic graphs
Authors: Breitling Lutz P , Duan Chongyang , Dragomir Anca D , Luta George
Published: July 2021

Motivation

Directed acyclic graphs (DAGs) are causal diagrams that can be used to identify confounding or selection bias in observational studies, and are increasingly used in many areas of medical research. In the add-on package dagR for the statistical software R, a set of simple graphical rules was implemented to identify minimal sufficient adjustment sets or harmful adjustment.

General features

The dagR package allows an automated approach for realistic causal structures featuring numerous variables and dependencies, where a manual approach may be too tedious and error-prone. The algorithmic adherence to the graphical step-by-step approach often used in DAG theory introductory courses, together with functionalities for plotting and simulating data conforming to the causal structure of an arbitrary DAG, renders the dagR package particularly useful for both teaching purposes and methodological research.

Availability

dagR is available under the GNU general public licence (GPL-2) from within R or by download at [https://CRAN-R-project.org/package=dagR].
Case-Fatality Ratio of Enteric Fever: Estimates From Multitiered Surveillance in India
Authors: Samuel Prasanna , Njarekkattuvalappil Swathi Krishna , Kumar Dilesh , Raju Reshma , Andrews Jason R , Kang Gagandeep , John Jacob
Published: July 2021

Background

The case-fatality ratio (CFR) for enteric fever is essential for estimating disease burden and calibrating measures that balance the likely health gains from interventions against social and economic costs.

Methods

We aimed to estimate the CFR for enteric fever using multiple data sources within the National Surveillance System for Enteric Fever in India. This surveillance (2017–2020) was established as a multitiered surveillance system including community cohorts (tier 1), facility-based (tier 2), and tertiary care surveillance (tier 3) for estimating the burden of enteric fever in India. The CFR was calculated after accounting for healthcare-seeking behavior for enteric fever and deaths occurring outside the hospital.

Results

A total of 1236 hospitalized patients with blood culture–confirmed enteric fever were enrolled, of which 9 fatal cases were identified, for an estimated hospitalized CFR of 0.73% (95% confidence interval [CI], .33%–1.38%). After adjusting for severity, healthcare-seeking behavior, and deaths occurring out-of-hospital, the CFR was estimated to be 0.16% (95% CI, .07%–.29%) for all enteric fevers.

Conclusions

Our estimates of the CFR are relatively lower than previously estimated, accounting for care-seeking behavior and deaths outside the hospital.
Helicobacter urease suppresses cytotoxic CD8+ T-cell responses through activating Myh9-dependent induction of PD-L1
Authors: Wu Jian , Zhu Xiaowen , Guo Xia , Yang Ze , Cai Qinzhen , Gu Dongmei , Luo Wei , Yuan Chunhui , Xiang Yun
Published: July 2021

As a key virulence factor for persistent colonization, urease B subunit (UreB) is considered to be an ideal vaccine antigen against Helicobacter pylori infection. However, the role and molecular mechanisms of UreB involved in immune microenvironment dysregulation still remain largely unknown. In the present study, we evaluated the effects of UreB on macrophage activation and found that UreB induced PD-L1 accumulation on bone marrow-derived macrophages (BMDMs). Co-culture assays further revealed that UreB-induced PD-L1 expression on BMDMs significantly decreased the proliferation and secretion of cytolytic molecules (granzyme B and perforin) of splenic CD8+ T cells isolated from inactivated H. pylori-immunized mice. More importantly, using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation techniques, it has been confirmed that myosin heavy chain 9 (Myh9) is a direct membrane receptor for UreB and is required for PD-L1 up-regulation on BMDMs. Molecular studies further demonstrated that the interaction between UreB and Myh9 decreased GCN2 autophosphorylation and enhanced the intracellular pool of amino acids, leading to the up-regulation of S6K phosphorylation, a commonly used marker for monitoring activation of mTORC1 signaling activity. Furthermore, blocking mTORC1 activation with its inhibitor Temsirolimus reversed the UreB-induced PD-L1 up-regulation and the subsequent inhibitory effects of BMDMs on activation of cytotoxic CD8+ T-cell responses. Overall, our data unveil a novel immunosuppressive mechanism of UreB during H. pylori infection, which may provide valuable clues for the optimization of H. pylori vaccine.
Investigation of mechanisms responsible for decreased susceptibility of aztreonam/avibactam activity in clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019
Authors: Mendes Rodrigo E , Doyle Timothy B , Streit Jennifer M , Arhin Francis F , Sader Helio S , Castanheira Mariana
Published: July 2021

Background

The combination aztreonam/avibactam is currently under Phase 3 trials for the treatment of serious infections caused by Gram-negative bacteria including those with MBLs.

Objectives

To investigate the resistance mechanisms in Enterobacterales exhibiting aztreonam/avibactam MICs of ≥4 mg/L.

Methods

Among 8787 Enterobacterales, 17 (0.2%) isolates exhibited an aztreonam/avibactam MIC of ≥4 mg/L. Isolates were sequenced and screened for β-lactamases. Sequences of porins, penicillin-binding protein 3 (PBP3) and expression levels of AmpC and AcrA were evaluated.

Results

Eleven (11/4154 isolates; 0.26%) Escherichia coli, three (3/1981; 0.15%) Klebsiella pneumoniae and three (3/628; 0.5%) Enterobacter cloacae were identified. All E. coli showed either an ‘YRIK’ or ‘YRIN’ insertion in PBP3. In general, these isolates carried blaCMY and/or blaCTX-M variants, except for one isolate from Korea that also produced NDM-5 and one isolate from Turkey that produced OXA-48. Two DHA-1-producing K. pneumoniae overexpressed acrA and had a premature stop codon in either OmpK35 or OmpK36, whereas a third K. pneumoniae carried blaPER-2 and had a premature stop codon in OmpK35. All three E. cloacae expressed AmpC at levels ≥570-fold, but sequence analysis did not reveal known amino acid alterations associated with decreased avibactam binding or increased hydrolysis of β-lactams. Minor amino acid polymorphisms within OmpC, OmpF and PBP3 were noted among the E. cloacae.

Conclusions

A small number of isolates (0.2%) met the inclusion criteria. E. coli showed altered PBP3 as the most relevant resistance mechanism, whereas K. pneumoniae had multiple resistance mechanisms. Further investigations are needed to clarify resistance in E. cloacae.
Pharmacokinetic modelling to predict risk of ototoxicity with intravenous tobramycin treatment in cystic fibrosis
Authors: Dong Min , Rodriguez Anna V , Blankenship Chelsea A , McPhail Gary , Vinks Alexander A , Hunter Lisa L
Published: July 2021

Introduction

Further optimization of therapeutic drug monitoring (TDM) for aminoglycosides (AGs) is urgently needed, especially in special populations such as those with cystic fibrosis (CF), >50% of whom develop ototoxicity if treated with multiple courses of IV AGs. This study aimed to empirically test a pharmacokinetic (PK) model using Bayesian estimation of drug exposure in the deeper body tissues to determine feasibility for prediction of ototoxicity.

Materials and methods

IV doses (n = 3645) of tobramycin and vancomycin were documented with precise timing from 38 patients with CF (aged 8–21 years), including total doses given and total exposure (cumulative AUC). Concentration results were obtained at 3 and 10 h for the central (C1) compartment. These variables were used in Bayesian estimation to predict trough levels in the secondary tissue compartments (C2 trough) and maximum concentrations (C2max). The C1 and C2 measures were then correlated with hearing levels in the extended high-frequency range.

Results

Patients with more severe hearing loss were older and had a higher number of tobramycin C2max concentrations >2 mg/L than patients with normal or lesser degrees of hearing loss. These two factors together significantly predicted average high-frequency hearing level (r = 0.618, P < 0.001). Traditional metrics such as C1 trough concentrations were not predictive. The relative risk for hearing loss was 5.8 times greater with six or more tobramycin courses that exceeded C2max concentrations of 3 mg/L or higher, with sensitivity of 83% and specificity of 86%.

Conclusions

Advanced PK model-informed analysis predicted ototoxicity risk in patients with CF treated with tobramycin and demonstrated high test prediction.
Expectation, Disappointment, and Exit: Evidence on Reference Point Formation from an Online Marketplace
Authors: Backus Matthew , Blake Thomas , Masterov Dimitriy , Tadelis Steven
Published: July 2021

We study disappointment and platform exit among new bidders in an online auction marketplace. In particular, we study a hybrid auction format with a “Buy-It-Now” option, which, when executed, will abruptly end the auction and cancel any standing bids. When this happens, if the formerly leading bidder is new to the platform, then they are 6 percentage points more likely to exit the marketplace for every additional day they spent in the lead. This is rationalized by disappointment-averse bidders with outside options and rational expectations about the likelihood of winning. Our explanation is validated by three ancillary predictions: when expectations are lowered by higher competing bids, there is no effect; sensitivity of exit is declining in prior experience; and, for bidders who do not exit, time in the lead during the first experience predicts a subsequent preference for fixed-price, rather than auction, listings.
Deciphering the mechanism by which the yeastPhaffia rhodozymaresponds adaptively to environmental, nutritional, and genetic cues
Authors: Flores-Cotera Luis B , Chávez-Cabrera Cipriano , Martínez-Cárdenas Anahi , Sánchez Sergio , García-Flores Oscar Ulises
Published: July 2021

Phaffia rhodozyma is a basidiomycetous yeast that synthesizes astaxanthin (ASX), which is a powerful and highly valuable antioxidant carotenoid pigment. P. rhodozyma cells accrue ASX and gain an intense red-pink coloration when faced with stressful conditions such as nutrient limitations (e.g., nitrogen or copper), the presence of toxic substances (e.g., antimycin A), or are affected by mutations in the genes that are involved in nitrogen metabolism or respiration. Since cellular accrual of ASX occurs under a wide variety of conditions, this yeast represents a valuable model for studying the growth conditions that entail oxidative stress for yeast cells. Recently, we proposed that ASX synthesis can be largely induced by conditions that lead to reduction–oxidation (redox) imbalances, particularly the state of the NADH/NAD+ couple together with an oxidative environment. In this work, we review the multiple known conditions that elicit ASX synthesis expanding on the data that we formerly examined. When considered alongside the Mitchell's chemiosmotic hypothesis, the study served to rationalize the induction of ASX synthesis and other adaptive cellular processes under a much broader set of conditions. Our aim was to propose an underlying mechanism that explains how a broad range of divergent conditions converge to induce ASX synthesis in P. rhodozyma. The mechanism that links the induction of ASX synthesis with the occurrence of NADH/NAD+ imbalances may help in understanding how other organisms detect any of a broad array of stimuli or gene mutations, and then adaptively respond to activate numerous compensatory cellular processes.
Minimally invasive open surgery (MIOS) for clinical stage I lung cancer: diversity in minimally invasive procedures
Authors: Nakagawa Kazuo , Yoshida Yukihiro , Yotsukura Masaya , Watanabe Shun-ichi
Published: July 2021

Background

Many thoracic surgeons have tried to make lung cancer surgery less invasive. Among the minimally invasive approaches that are currently available, it is controversial which is optimal. Minimally invasive open surgery, i.e. hybrid video-assisted thoracic surgery, has been adopted for lung cancer surgery at our institute. The objective of this study was to evaluate minimally invasive open surgery in terms of perioperative outcomes over the most recent 5 years.

Methods

Between 2015 and 2019, 2738 patients underwent pulmonary resection for lung cancer at National Cancer Center Hospital, Japan. Among them, 2174 patients with clinical stage I lung cancer who underwent minimally invasive open surgery were included. Several perioperative parameters were evaluated.

Results

The patients consisted of 1092 men (50.2%) and 1082 women (49.8%). Lobectomy was performed in 1255 patients (57.7%), segmentectomy in 603 (27.7%) and wide wedge resection in 316 (14.5%). Median blood loss was 30 ml (interquartile range: 15–57 ml) for lobectomy, 17 ml (interquartile range: 10–31 ml) for segmentectomy and 5 ml (interquartile range: 2–10 ml) for wide wedge resection. Median operative time was 120 min (interquartile range: 104–139 min) for lobectomy, 109 min (interquartile range: 98–123 min) for segmentectomy and 59 min (interquartile range: 48–76 min) for wide wedge resection. Median length of postoperative hospital stay was 4 days (interquartile range: 3–5 days). The 30-day mortality rate was 0.08% for lobectomy, 0.17% for segmentectomy and 0.00% for wide wedge resection.

Conclusions

Minimally invasive open surgery for clinical stage I lung cancer is a feasible approach with a low mortality and a short hospital stay. Oncological outcomes need to be investigated.
Complying with Custom before the World Court: Towards a Relational Normativity
Authors: Vanhullebusch Matthias
Published: July 2021

Traditionally, institutional constraints informed the International Court of Justice’s ascertainment of the (non-) existence of customary norms in its decisions as it signals impartiality to uphold its legitimacy. Its reliance on (non-)legal elements underpinning the sources of the normativity of existing and future customary norms upon which it rules goes beyond the mutual acceptance of treaties and customs by the conflicting parties as well as shared (nascent) moral values of the international community. Its denial of the application of customary international law based on functional and equitable arguments gives further evidence of the Court’s relational and contextual approach towards the peaceful resolution of disputes. In addition to its rule-based governance function, the Court is actively pursuing relational governance. It seeks to reconcile competing relationships and interests inside and outside the courtroom and anticipates if a fertile soil is present in which existing and future customary norms can gain root.
Dan Pagis’ Bilingual Poem ‘Ein Leben’ – An Ophthalmologic Poetics of German–Hebrew Eye Contact
Authors: Kühne Jan
Published: July 2021

Hebrew–German homophonic translation as a poetic writing technique is a still largely unknown phenomenon in German–Hebrew Studies. In my research dedicated to mapping the diversity of multilingual modalities in modern German and Hebrew literature, I am particularly interested in German–Hebrew homophony. Thus, in my paper, I analyse German–Hebrew homophony in Pagis’ Hebrew poems ‘Ein Leben’ and ‘Written in Pencil in a Sealed Railway-Car’ (כתוב בעפרון בקרון החתום), while showing the deep impression that Ernst Jandl’s avant-garde poetry (‘oberflächenübersetzung’) has left upon Pagis’ oeuvre. In light of my homophonic analysis, I offer access to a hitherto unnoticed deep layer of German–Hebrew dialogue in Pagis’ poetry, which offers novel interpretations that are unique in the corpus of German-Jewish and Hebrew literature.
Clinical predictive models of invasive Candida infection: A systematic literature review
Authors: Rauseo Adriana M , Aljorayid Abdullah , Olsen Margaret A , Larson Lindsey , Lipsey Kim L , Powderly William G , Spec Andrej
Published: July 2021

Clinical predictive models (CPM) serve to identify and categorize patients into risk categories to assist in treatment and intervention recommendations. Predictive accuracy and practicality of models varies depending on methods used for their development, and should be evaluated. The aim of this study was to summarize currently available CPM for invasive candidiasis, analyze their performance, and assess their suitability for use in clinical decision making. We identified studies that described the construction of a CPM for invasive candidiasis from PubMed/MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane Library databases, and Clinicaltrials.gov. Data extracted included: author, data source, study design, recruitment period, characteristics of study population, outcome types, predictor types, number of study participants and outcome events, modelling method, and list of predictors used in the final model. Calibration and discrimination in the derivative datasets were used to assess the performance of each model. Ten articles were identified in our search and included for full text review. Five models were developed using data from ICUs, and five models included all hospitalized patients. The findings of this review highlight the limitations of currently available models to predict invasive candidiasis, including lack of generalizability, difficulty in everyday clinical use, and overly optimistic performance. There are significant concerns regarding predictive performance and usability in every day practice of existing CPM to predict invasive candidiasis.
The time-dependent distribution of optical polarization angle changes in blazars
Authors: Kiehlmann S , Blinov D , Liodakis I , Pavlidou V , Readhead A C S , Angelakis E , Casadio C , Hovatta T , Kylafis N , Mahabal A , Mandarakas N , Myserlis I , Panopoulou G V , Pearson T J , Ramaprakash A , Reig P , Skalidis R , Słowikowska A , Tassis K , Zensus J A
Published: July 2021

At optical wavelengths, blazar Electric Vector Position Angle (EVPA) rotations linked with gamma-ray activity have been the subject of intense interest and systematic investigation for over a decade. One difficulty in the interpretation of EVPA rotations is the inherent 180° ambiguity in the measurements. It is therefore essential, when studying EVPA rotations, to ensure that the typical time-interval between successive observations – i.e. the cadence – is short enough to ensure that the correct modulo 180° value is selected. This optimal cadence depends on the maximum intrinsic EVPA rotation speed in blazars, which is currently not known. In this paper, we address the following questions for the RoboPol sample: What range of rotation speeds for rotations greater than 90° can we expect? What observation cadence is required to detect such rotations? Have rapid rotations been missed in EVPA rotation studies thus far? What fraction of data is affected by the ambiguity? And how likely are detected rotations affected by the ambiguity? We answer these questions with three seasons of optical polarimetric observations of a statistical sample of blazars sampled weekly with the RoboPol instrument and an additional season with daily observations. We model the distribution of EVPA changes on time-scales from 1–30 d and estimate the fraction of changes exceeding 90°. We show that at least daily observations are necessary to measure ${\gt}96{{\ \rm per\ cent}}$ of optical EVPA variability in the RoboPol sample of blazars correctly and that intraday observations are needed to measure the fastest rotations that have been seen thus far.
Galaxy Zoo DECaLS: Detailed visual morphology measurements from volunteers and deep learning for 314 000 galaxies
Authors: Walmsley Mike , Lintott Chris , Géron Tobias , Kruk Sandor , Krawczyk Coleman , Willett Kyle W , Bamford Steven , Kelvin Lee S , Fortson Lucy , Gal Yarin , Keel William , Masters Karen L , Mehta Vihang , Simmons Brooke D , Smethurst Rebecca , Smith Lewis , Baeten Elisabeth M , Macmillan Christine
Published: July 2021

We present Galaxy Zoo DECaLS: detailed visual morphological classifications for Dark Energy Camera Legacy Survey images of galaxies within the SDSS DR8 footprint. Deeper DECaLS images (r = 23.6 versus r = 22.2 from SDSS) reveal spiral arms, weak bars, and tidal features not previously visible in SDSS imaging. To best exploit the greater depth of DECaLS images, volunteers select from a new set of answers designed to improve our sensitivity to mergers and bars. Galaxy Zoo volunteers provide 7.5 million individual classifications over 314 000 galaxies. 140 000 galaxies receive at least 30 classifications, sufficient to accurately measure detailed morphology like bars, and the remainder receive approximately 5. All classifications are used to train an ensemble of Bayesian convolutional neural networks (a state-of-the-art deep learning method) to predict posteriors for the detailed morphology of all 314 000 galaxies. We use active learning to focus our volunteer effort on the galaxies which, if labelled, would be most informative for training our ensemble. When measured against confident volunteer classifications, the trained networks are approximately 99 per cent accurate on every question. Morphology is a fundamental feature of every galaxy; our human and machine classifications are an accurate and detailed resource for understanding how galaxies evolve.
Discovery of a possible splashback feature in the intracluster light of MACS J1149.5+2223
Authors: Gonzalez Anthony H , George Tyler , Connor Thomas , Deason Alis , Donahue Megan , Montes Mireia , Zabludoff Ann I , Zaritsky Dennis
Published: July 2021

We present an analysis of the intracluster light (ICL) in the Frontier Field Cluster MACS J1149.5+2223 (z = 0.544), which combines new and archival Hubble WFC3/IR imaging to provide continuous radial coverage out to 2.8 Mpc from the brightest cluster galaxy (BCG). Employing careful treatment of potential systematic biases and using data at the largest radii to determine the background sky level, we reconstruct the surface brightness profile out to a radius of 2 Mpc. This radius is the largest to which the ICL has been measured for an individual cluster. Within this radius, we measure a total luminosity of 1.5 × 1013 L⊙ for the BCG plus ICL. From the profile and its logarithmic slope, we identify the transition from the BCG to ICL at r ∼ 70 kpc. Remarkably, we also detect an apparent inflection in the profile centred in the 1.2–1.7 Mpc (0.37–0.52 r200m) radial bin, a signature of an infall caustic in the stellar distribution. Based upon the shape and strength of the feature, we interpret it as potentially being at the splashback radius, although the radius is smaller than theoretical predictions. If this is the splashback radius, then it is the first such detection in the ICL and the first detection of the splashback radius for an individual cluster. Similar analyses should be possible with the other Frontier Field clusters, and eventually with clusters observed by the Euclid and Roman missions.
Early dynamics and violent relaxation of multimass rotating star clusters
Authors: Livernois Alexander , Vesperini Enrico , Tiongco Maria , Varri Anna Lisa , Dalessandro Emanuele
Published: July 2021

We present the results of a study aimed at exploring, by means of N-body simulations, the evolution of rotating multimass star clusters during the violent relaxation phase, in the presence of a weak external tidal field. We study the implications of the initial rotation and the presence of a mass spectrum for the violent relaxation dynamics and the final properties of the equilibria emerging at the end of this stage. Our simulations show a clear manifestation of the evolution towards spatial mass segregation and evolution towards energy equipartition during and at the end of the violent relaxation phase. We study the final rotational kinematics and show that massive stars tend to rotate more rapidly than low-mass stars around the axis of cluster rotation. Our analysis also reveals that during the violent relaxation phase, massive stars tend to preferentially segregate into orbits with angular momentum aligned with the cluster’s angular momentum, an effect previously found in the context of the long-term evolution of star clusters driven by two-body relaxation.