bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects and Potential Mechanisms of Alcohol Use Disorder on the Fate Determination of Newly Born Neurons in the Hippocampus
Authors: Shabani Zahra , Jafarzadeh Gharehziaaddin Mohsen
Published: July 2020

In the adult mammalian brain, new functional neurons are generated throughout life because of sustained proliferation and differentiation of neural stem cells (NSCs). The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus are the two major neurogenic regions in the adult brain. This process is not fixed but is highly modulated by numerous intrinsic and extrinsic factors. Neurogenesis has become in the focus of interest for its involvement in repairing the damaged brain and this motivates researchers to detect controlling mechanisms of this process. Recent evidence suggests that alcohol usage can directly influence adult hippocampal neurogenesis, but its mechanisms remain a matter for debate. Thus, this review summarizes in vivo/in vitro studies on the role of alcohol in hippocampal neurogenesis during adulthood and clarifies its underlying mechanisms by highlighting neurotransmitters and their receptors.
Quantitative Validation of Control Bands Using Bayesian Statistical Analyses
Authors: McCord Tyler A , Legaspi Matthew T , West Elaine A , Yung Priscilla K , Larson Diana L , Paik Samuel Y , Zalk David M
Published: July 2020

This study presents a quantitative validation of 15 Similar Exposure Groups (SEGs) that were derived via control bands inherent to the Risk Level Based Management System currently being used at the Lawrence Livermore National Laboratory. For 93% of the SEGs that were evaluated, statistical analyses of personal exposure monitoring data, through Bayesian Decision Analysis (BDA), demonstrated that the controls implemented from the initial control bands assigned to these SEGs were at least as protective as the controls from the control band outcomes derived from the quantitative data. The BDA also demonstrated that for 40% of the SEGs, the controls from the initial control bands were overly protective, thus allowing controls to be downgraded, which resulted in a significant saving of environmental safety and health (ES&H) resources. Therefore, as a means to both confirm existing controls and to identify candidate SEGs for downgrading controls, efforts to continuously improve the accuracy of Control Banding (CB) strategies through the routine quantitative validation of SEGs are strongly encouraged. Targeted collaborative efforts across institutions and even countries for both the development of CB strategies and the validation of discreetly defined SEGs of commonly performed tasks will not only optimize limited ES&H resources but will also assist in providing a simplified process for essential risk communication at the worker level to the benefit of billions of workers around the world.
PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection
Authors: Hölzer Martin , Marz Manja
Published: July 2020

PoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. By entering homologous sequences, PoSeiDon builds an alignment, estimates a best-fitting substitution model and performs a recombination analysis followed by the construction of all corresponding phylogenies. Finally, significantly positive selected sites are detected according to different models for the full alignment and possible recombination fragments. The results of PoSeiDon are summarized in a user-friendly HTML page providing all intermediate results and the graphical representation of recombination events and positively selected sites.

Availability and implementation

PoSeiDon is freely available at https://github.com/hoelzer/poseidon. The pipeline is implemented in Nextflow with Docker support and processes the output of various tools.
Differences in network controllability and regional gene expression underlie hallucinations in Parkinson’s disease
Authors: Zarkali Angeliki , McColgan Peter , Ryten Mina , Reynolds Regina , Leyland Louise-Ann , Lees Andrew J , Rees Geraint , Weil Rimona S
Published: July 2020

Visual hallucinations are common in Parkinson’s disease and are associated with poorer prognosis. Imaging studies show white matter loss and functional connectivity changes with Parkinson’s visual hallucinations, but the biological factors underlying selective vulnerability of affected parts of the brain network are unknown. Recent models for Parkinson’s disease hallucinations suggest they arise due to a shift in the relative effects of different networks. Understanding how structural connectivity affects the interplay between networks will provide important mechanistic insights. To address this, we investigated the structural connectivity changes that accompany visual hallucinations in Parkinson’s disease and the organizational and gene expression characteristics of the preferentially affected areas of the network. We performed diffusion-weighted imaging in 100 patients with Parkinson’s disease (81 without hallucinations, 19 with visual hallucinations) and 34 healthy age-matched controls. We used network-based statistics to identify changes in structural connectivity in Parkinson’s disease patients with hallucinations and performed an analysis of controllability, an emerging technique that allows quantification of the influence a brain region has across the rest of the network. Using these techniques, we identified a subnetwork of reduced connectivity in Parkinson’s disease hallucinations. We then used the Allen Institute for Brain Sciences human transcriptome atlas to identify regional gene expression patterns associated with affected areas of the network. Within this network, Parkinson’s disease patients with hallucinations showed reduced controllability (less influence over other brain regions), than Parkinson’s disease patients without hallucinations and controls. This subnetwork appears to be critical for overall brain integration, as even in controls, nodes with high controllability were more likely to be within the subnetwork. Gene expression analysis of gene modules related to the affected subnetwork revealed that down-weighted genes were most significantly enriched in genes related to mRNA and chromosome metabolic processes (with enrichment in oligodendrocytes) and upweighted genes to protein localization (with enrichment in neuronal cells). Our findings provide insights into how hallucinations are generated, with breakdown of a key structural subnetwork that exerts control across distributed brain regions. Expression of genes related to mRNA metabolism and membrane localization may be implicated, providing potential therapeutic targets.
Validated Liquid Chromatography–Tandem Mass Spectroscopic Method for Simultaneous Determination of Certain Drugs Used in Cataract Surgery in Rabbit Aqueous Humor
Authors: Nassar Mohammed W , Attia Khalid A , Mohamed Ahmed A , Said Ragab A , El-Olemy Ahmed , Hasan Mohamed A
Published: July 2020

A sensitive, selective, accurate and precise ultra-high performance liquid chromatography–Tandem mass spectrometry (MS/MS) method was developed and validated for the simultaneous determination of drugs used as eye drops in cataract surgery in aqueous humor. Cataract surgery requires a powerful mydriatic eye drops combination such as cyclopentolate hydrochloride and phenylephrine hydrochloride to dilate the pupil and facilitate eye lens replacement and also requires strong fluoroquinolone antibiotic such as lomefloxacin hydrochloride. The method was performed with positive ion electrospray ionization and the analytes were quantified and monitored on a triple quadrupole mass spectrometer using multiple reaction monitoring scanning mode. Liquid–liquid extraction was used for the purification and preconcentration of analytes from rabbit aqueous humor matrix. Chromatographic elution was performed using an Phenomenex Luna® C18 (150 mm × 2.1 mm, 1.6 μm) column and moxifloxacin hydrochloride as internal standard with a mobile phase consisting of methanol:water:formic acid (70:29:1, by volume) at flow rate of 0.2 mL/min. Satisfactory results regarding linearity, recovery, stability, accuracy and precision of the analytes were obtained. Full validation of the procedure was performed according to the US Food and Drug Administration guidance for industry: bioanalytical method validation and European Medicines Agency (EMA) guideline on bioanalytical method validation.
Preparative Separation and Purification of Liquiritin and Glycyrrhizic Acid from Glycyrrhiza uralensis Fisch by High-Speed Countercurrent Chromatography
Authors: Wang Hao , Shan Hu , Lü Haitao
Published: July 2020

The technique of high-speed countercurrent chromatography (HSCCC) was applied to the preparative isolation and purification of liquiritin and glycyrrhizic acid from a crude extract of Glycyrrhiza uralensis Fisch for the first time. Using single factor and orthogonal design experiments, the best extraction conditions were 70% ethanol, 1:25 ratio of solid-to-liquid (w/v) and extracted 1.5 h at 80°C. The contents of liquiritin and glycyrrhizic acid in the crude extract were 1.3 and 5.3%, respectively. Using the two-phase solvent system of ethyl acetate–methanol–water (5:2:5, v/v), 6.0 mg liquiritin (the purity was 96.7%, and the recovery was 89.3%), and 20.5 mg glycyrrhizic acid (the purity was 98.9%, and the recovery was 77.1%) were obtained from 500 mg crude extraction by HSCCC, respectively. The retention rate of stationary phase was 51.0%. Their structures were identified by high-performance liquid chromatography, melting points, ultraviolet radiation, Fourier transform infrared (FTIR), Electrospray ionization mass spectrometry (ESI-MS), 1H Nuclear Magnetic Resonance (NMR) and 13C NMR spectra. The scavenging abilities of glycyrrhizic acid to 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals were stronger than those of liquiritin.
Infectious Diseases Society of America Guidelines on Infection Prevention for Healthcare Personnel Caring for Patients With Suspected or Known COVID-19 (July 2020)
Authors: Lynch John B , Davitkov Perica , Anderson Deverick J , Bhimraj Adarsh , Cheng Vincent Chi-Chung , Guzman-Cottrill Judith , Dhindsa Jasmine , Duggal Abhijit , Jain Mamta K , Lee Grace M , Liang Stephen Y , McGeer Allison , Lavergne Valery , Murad M Hassan , Mustafa Reem A , Morgan Rebecca L , Falck-Ytter Yngve , Sultan Shahnaz
Published: July 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that can infect healthcare personnel (HCP) and patients in healthcare settings. Specific care activities, in particular, aerosol-generating procedures, may have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 has created significant challenges in healthcare facilities, particularly with severe shortages of personal protective equipment (PPE) used to protect HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care are needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators.

Objective

Our objective was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19).

Methods

The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel that included front-line clinicians, infectious diseases specialists, experts in infection control, and guideline methodologists with representation from the disciplines of preventive care, public health, medical microbiology, pediatrics, critical care medicine, and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then, a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence and make recommendations.

Results

The IDSA guideline panel agreed on 8 recommendations and provided narrative summaries of other interventions undergoing evaluations.

Conclusions

Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE for HCP who provide care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. Significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 remain, and PPE recommendations may need to be modified in response to new evidence.
Drug Resistance Mutations Among South African Children Living With HIV on WHO-recommended ART Regimens
Authors: Hackett Stephanie , Teasdale Chloe A , Pals Sherri , Muttiti Anthony , Mogashoa Mary , Chang Joy , Zeh Clement , Ramos Artur , Rivadeneira Emilia D , DeVos Joshua , Sleeman Katrina , Abrams Elaine J
Published: July 2020

Background

Children living with human immunodeficiency virus (HIV) (CLHIV) receiving antiretroviral therapy (ART) in resource-limited settings are susceptible to high rates of acquired HIV drug resistance (HIVDR), but few studies include children initiating age-appropriate World Health Organization (WHO)-recommended first-line regimens. We report data from a cohort of ART-naive South African children who initiated first-line ART.

Methods

ART-eligible CLHIV aged 0–12 years were enrolled from 2012 to 2014 at 5 public South African facilities and were followed for up to 24 months. Enrolled CLHIV received standard-of-care WHO-recommended first-line ART. At the final study visit, a dried blood spot sample was obtained for viral load and genotypic resistance testing.

Results

Among 72 successfully genotyped CLHIV, 49 (68.1%) received ABC/3TC/LPV/r, and 23 (31.9%) received ABC/3TC/EFV. All but 2 children on ABC/3TC/LPV/r were <3 years, and all CLHIV on ABC/3TC/EFV were ≥3 years. Overall, 80.6% (58/72) had at least one drug resistance mutation (DRM). DRMs to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were found among 65% and 51% of all CLHIV, respectively, with no statistical difference by ART regimen. More CLHIV on ABC/3TC/EFV, 47.8% (11/23), were found to have 0 or only 1 effective antiretroviral drug remaining in their current regimen compared to 8.2% (4/49) on ABC/3TC/LPV/r.

Conclusions

High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed mother-to-child transmission interventions on DRMs. However, drug susceptibility analysis reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least 2 effective agents on their current HIV regimen than those on ABC/3TC/EFV.
Why is the euro punching below its weight?
Authors: Ilzetzki Ethan , Reinhart Carmen M , Rogoff Kenneth S
Published: July 2020

On the twentieth anniversary of its inception, the euro has yet to expand its role as an international currency. We document this fact with a wide range of indicators including its role as an anchor or reference in exchange rate arrangements – which we argue is a portmanteau measure – and as a currency for the denomination of trade and assets. On all these dimensions, the euro comprises a far smaller share than that of the US dollar. Furthermore, that share has been roughly constant since 1999. By some measures, the euro plays no larger role than the Deutschemark and French franc that it replaced. We explore the reasons for this underperformance. While the leading anchor currency may have a natural monopoly, a number of additional factors have limited the euro’s reach, including lack of financial centre, limited geopolitical reach and US and Chinese dominance in technology research. Most important, in our view, is the comparatively scarce supply of (safe) euro-denominated assets, which we document. The European Central Bank’s (ECB's) lack of policy clarity may have also played a role. We show that the euro era can be divided into a ‘Bundesbank-plus’ period and a ‘Whatever it Takes’ period. The first shows a smooth transition from the European Exchange Rate Mechanism and continued to stabilize German inflation. The second period is characterized by an expanding ECB arsenal of credit facilities to European banks and sovereigns.
Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial
Authors: Szarek Michael , Bittner Vera A , Aylward Philip , Baccara-Dinet Marie , Bhatt Deepak L , Diaz Rafael , Fras Zlatko , Goodman Shaun G , Halvorsen Sigrun , Harrington Robert A , Jukema J Wouter , Moriarty Patrick M , Pordy Robert , Ray Kausik K , Sinnaeve Peter , Tsimikas Sotirios , Vogel Robert , White Harvey D , Zahger Doron , Zeiher Andreas M , Steg Ph Gabriel , Schwartz Gregory G ,   for the ODYSSEY OUTCOMES Investigators
Published: July 2020

Aims

Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.

Methods and results

Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio P  trend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median −5.0 [−13.6, 0] mg/dL) and corrected LDL-C (median −51.3 [−67.1, −34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.

Conclusion

Baseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.
Live births following fertility preservation using in-vitro maturation of ovarian tissue oocytes
Authors: Segers Ingrid , Bardhi Erlisa , Mateizel Ileana , Van Moer Ellen , Schots Rik , Verheyen Greta , Tournaye Herman , De Vos Michel
Published: July 2020

STUDY QUESTION

Can oocytes extracted from excised ovarian tissue and matured in vitro be a useful adjunct for urgent fertility preservation (FP)?

SUMMARY ANSWER

Ovarian tissue oocyte in-vitro maturation (OTO-IVM) in combination with ovarian tissue cryopreservation (OTC) is a valuable adjunct technique for FP.

WHAT IS KNOWN ALREADY

Despite the impressive progress in the field, options for FP for cancer patients are still limited and, depending on the technique, clinical outcome data are still scarce.

STUDY DESIGN, SIZE, DURATION

This was a retrospective cohort study conducted at a university hospital-affiliated fertility clinic between January 2012 and May 2019.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The study included 77 patients who underwent unilateral oophorectomy for OTC. Cumulus-oocyte complexes (COCs) obtained during ovarian tissue processing were matured in vitro for 28–42 h. Oocytes reaching metaphase II stage were vitrified or inseminated for embryo vitrification.

MAIN RESULTS AND THE ROLE OF CHANCE

Overall, 1220 COCs were collected. The mean oocyte maturation rate was 39% ± 23% (SD). There were 64 patients who had vitrification of oocytes (6.7 ± 6.3 oocytes per patient). There were 13 patients who had ICSI of mature oocytes after IVM, with 2.0 ± 2.0 embryos vitrified per patient. Twelve patients have returned to the clinic with a desire for pregnancy. For seven of these, OTO-IVM material was thawed. Two patients had OTO-IVM oocytes warmed, with survival rates of 86% and 60%. After ICSI, six oocytes were fertilised in total, generating three good quality embryos for transfer, leading to a healthy live birth for one patient. In five patients, for whom a mean of 2.0 ± 0.8 (SD) embryos had been vitrified, seven embryos were warmed in total: one embryo did not survive the warming process; two tested genetically unsuitable for transfer; and four were transferred in separate cycles to three different patients, resulting in two healthy babies. In this small series, the live birth rate per patient after OTO-IVM, ICSI and embryo transfer was 43%.

LIMITATIONS, REASONS FOR CAUTION

The retrospective study design and the limited sample size should be considered when interpreting results.

WIDER IMPLICATIONS OF THE FINDINGS

The results of the study illustrate the added value of OTO-IVM in combination with OTC. We report the first live birth following the use of this appended technique combined with oocyte vitrification.

STUDY FUNDING/COMPETING INTEREST(S)

No external funding was used for this study. M.D.V. reports honoraria for lectures in the last 2 years from MSD and Ferring, outside the submitted work, as well as grant support from MSD. The other authors have nothing to declare.

TRIAL REGISTRATION NUMBER

N/A
Comparison of nZEB indicators for hotel renovations under different European climatic conditions
Authors: Cunha Filipe O , Oliveira Armando C
Published: July 2020

Hotels hold an important role in the energy efficiency policies of the European Union (EU), as they are typically ranked among the top energy consumers in the non-residential sector. However, a significant amount of the energy used in hotels is wasted, leaving ample room for enhancing energy-efficiency and resource conservation. Indeed, energy refurbishment of the hotel building stock is crucial in order to reach the nearly zero energy building (nZEB) status imposed by EU Directives for energy efficiency, and also an important pillar to achieve the energy targets for 2030 and the transition towards climate-neutral levels by 2050.

A typical 4-star hotel in operation in Faro (Portugal) was used as a case study in order to establish energy performance indicators for nZEB hotels in three European cities, taking into account the influence of the climatic context, the technical feasibility and cost effectiveness of the best energy retrofit packages. The study started after the calibration of the building energy model by means of an energy audit and measured data, in order to have a baseline model that represents well the actual energy use of the hotel in the reference location. The building energy model was developed by using DesignBuilder/EnergyPlus software. The validated model was then used to assess the effect of the best retrofit interventions (energy efficiency measures and active solar systems) in order to set minimum energy performance requirements and to reach cost-optimal levels and nZEB levels for refurbished hotels. A significant energy-saving potential was found for the cost-optimal benchmarks, and the obtained nZEB levels can be achieved under technically and economically conditions for the selected cities: Faro, London and Athens.
Wavelet invariants for statistically robust multi-reference alignment
Authors: Hirn Matthew , Little Anna
Published: July 2020

We propose a nonlinear, wavelet-based signal representation that is translation invariant and robust to both additive noise and random dilations. Motivated by the multi-reference alignment problem and generalizations thereof, we analyze the statistical properties of this representation given a large number of independent corruptions of a target signal. We prove the nonlinear wavelet-based representation uniquely defines the power spectrum but allows for an unbiasing procedure that cannot be directly applied to the power spectrum. After unbiasing the representation to remove the effects of the additive noise and random dilations, we recover an approximation of the power spectrum by solving a convex optimization problem, and thus reduce to a phase retrieval problem. Extensive numerical experiments demonstrate the statistical robustness of this approximation procedure.
Oscillatory Asymptotics for the Airy Kernel Determinant on Two Intervals
Authors: Blackstone Elliot , Charlier Christophe , Lenells Jonatan
Published: July 2020

We obtain asymptotics for the Airy kernel Fredholm determinant on two intervals. We give explicit formulas for all the terms up to and including the oscillations of order $1$, which are expressed in terms of Jacobi $\theta $-functions.
Risk Factors for Cytomegalovirus Viremia following Liver Transplantation With a Seropositive Donor and Seronegative Recipient Receiving Antiviral Therapy
Authors: Singh Nina , Winston Drew J , Razonable Raymund R , Lyon G Marshall , Silveira Fernanda P , Wagener Marilyn M , Limaye Ajit P
Published: July 2020

Background

The risk factors for development of viremia in high-risk donor cytomegalovirus (CMV)-seropositive and recipient CMV-seronegative (D+R−) transplant recipients are incompletely defined.

Methods

The study population comprised patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus prophylaxis using valganciclovir in D+R− liver transplant recipients. Weekly surveillance monitoring for viremia for 100 days was performed using a sensitive CMV-DNA polymerase chain reaction assays. Risk factors for viremia and time to onset (≤4 vs >4 weeks) of viremia were examined using logistic regression models.

Results

Viremia developed in 84% (79/94) of recipients and older donor age was the only independent factor associated with viremia (odds ratio, 2.20 for each quartile increase in donor age; 95% confidence interval [CI], 1.07–4.52; P = .031). Recipients who developed early-onset viremia (within 4 weeks) also had significantly older donors than those with later-onset viremia (difference in age 10.1 years; 95% CI, 2–19; P = .03).

Conclusions

Older donor age was an independent predictor of viremia and earlier-onset of viremia in D+R− liver transplant recipients. Future studies should assess the mechanistic links underlying this novel association.

Clinical Trial Registration

NCT01552369.
Radiologic Technologist and Radiologist Knowledge Gaps about Breast Density Revealed by an Online Continuing Education Course
Authors: Seitzman Robin L , Pushkin JoAnn , Berg Wendie A
Published: July 2020

Objective

We sought to identify provider knowledge gaps and their predictors, as revealed by a breast density continuing education course marketed to the radiology community.

Methods

The course, continually available online during the study period of November 2, 2016 and December 31, 2018, includes demographics collection; a monograph on breast density, breast cancer risk, and screening; and a post-test. Four post-test questions were modified during the study period, resulting in different sample sizes pre- and postmodification. Multiple logistic regression was used to identify predictors of knowledge gaps (defined as > 25% of responses incorrect).

Results

Of 1649 analyzable registrants, 1363 (82.7%) were radiologic technologists, 226 (13.7%) were physicians, and 60 (3.6%) were other nonphysicians; over 90% of physicians and over 90% of technologists/nonphysicians specialized in radiology. Sixteen of 49 physicians (32.7%) and 80/233 (34.3%) technologists/nonphysicians mistakenly thought the Gail model should be used to determine “high-risk” status for recommending MRI or genetic testing. Ninety-nine of 226 (43.8%) physicians and 682/1423 (47.9%) technologists/nonphysicians misunderstood the inverse relationship between increasing age and lifetime breast cancer risk. Fifty-two of 166 (31.3%) physicians and 549/1151 (47.7%) technologists/nonphysicians were unaware that MRI should be recommended for women with a family history of BRCA1/BRCA2 mutations. Tomosynthesis effectiveness was overestimated, with 18/60 (30.0%) physicians and 95/272 (34.9%) technologists/nonphysicians believing sensitivity nearly equaled MRI. Knowledge gaps were more common in technologists/nonphysicians.

Conclusions

Important knowledge gaps about breast density, breast cancer risk assessment, and screening exist among radiologic technologists and radiologists. Continued education efforts may improve appropriate breast cancer screening recommendations.
Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy
Authors: Pitter Kenneth L , Casey Dana L , Lu Yue C , Hannum Margaret , Zhang Zhigang , Song Xinmao , Pecorari Isabella , McMillan Biko , Ma Jennifer , Samstein Robert M , Pei Isaac X , Khan Atif J , Braunstein Lior Z , Morris Luc G T , Barker Christopher A , Rimner Andreas , Alektiar Kaled M , Romesser Paul B , Crane Christopher H , Yahalom Joachim , Zelefsky Michael J , Scher Howard I , Bernstein Jonine L , Mandelker Diana L , Weigelt Britta , Reis-Filho Jorge S , Lee Nancy Y , Powell Simon N , Chan Timothy A , Riaz Nadeem , Setton Jeremy
Published: July 2020

Background

Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure.

Methods

We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided.

Results

Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors.

Conclusions

We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.
Involvement of Arabidopsis phospholipase D δ in regulation of ROS-mediated microtubule organization and stomatal movement upon heat shock
Authors: Song Ping , Jia Qianru , Chen Long , Jin Xin , Xiao Xingkai , Li Li , Chen Huatao , Qu Yana , Su Yinghua , Zhang Wenhua , Zhang Qun
Published: July 2020

Reactive oxygen species (ROS) are plant metabolic and signaling molecules involved in responses to various external stresses, but the existence of ROS receptors and how plants respond to ROS remain largely unknown. Here we report that the plasma membrane-localized phospholipase D δ (PLDδ) protein is crucial for sensing heat shock-induced ROS to initiate reorganization of guard cell microtubules in Arabidopsis cotyledons. Heat shock of wild-type Arabidopsis cotyledons stimulated ROS production which disrupted microtubule organization and induced stomatal closure, whereas this process was markedly impaired in pldδ mutants. Moreover, wild-type PLDδ, but not the Arg622-mutated PLDδ, complemented the pldδ phenotypes in heat shock-treated plants. ROS activated PLDδ by oxidizing cysteine residues, an action that was required for its functions in ROS-induced depolymerization of guard cell microtubules, stomatal closure, and plant thermotolerance. Additionally, lipid profiling reveals involvement of microtubule organization in the feedback regulation of glycerolipid metabolism upon heat stress. Together, our findings highlight a potential mechanosensory role for PLDδ in regulating the dynamic organization of microtubules and stomatal movement, as part of the ROS-sensing pathway, during the response to external stresses.
Searching for eclipsing binaries in the area of RA: 02h21m36s, Dec: +57○11′32″
Authors: Guo Di-Fu , Li Kai , Gao Xing , Gao Dong-Yang , Xu Zhi-Jian , Sun Guo-You , Liu Fen , Zhang Chang-Ming
Published: July 2020

By analysing the data observed by the Comet Search Programme telescope at Xingming Observatory from 2018 October 11 to 2018 December 19, 24 eclipsing binaries were identified. By cross-matching with the VSX (AAVSO) website, we found that four binaries are newly discovered. By analysing the Transiting Exoplanet Survey Satellite (TESS) data, the light curves of 17 binaries were obtained. First photometric solutions of 23 binaries were obtained by simultaneously analysing all the light curves, except for NSVS 1908107 (first analysed by Pan et al.). Based on the photometric solutions, nine binaries belong to detached binary systems, ten binaries belong to semidetached binary systems, and five binaries belong to contact binary systems. Two W-subtype low-mass ratio contact binaries (the less massive components are hotter), with total eclipsing light curves, were identified: Mis V1395 is a deep contact binary (q = 0.150, $f=80{{\ \rm per\ cent}}$), while NSVS 1917038 is a low-mass ratio binary with an unexpectedly marginal contact degree (q = 1/6.839 = 0.146, $f=4{{\ \rm per\ cent}}$). The total eclipsing detached binary GSC 03698-00022 has an extremely low mass ratio of q = 0.085. The Algol-type binary NSVS 1908107 is also found to have an extremely low mass ratio of q = 0.081. The Algol-type binary DK Per exhibits a continuous period decrease at a rate of dP/dt = −1.26 × 10−7 d yr−1, which may result from the orbital angular momentum loss. Based on the light curves obtained from the TESS data, a pulsating binary candidate (NSVS 1913053) was found.
The effect of the slit configuration on the H2 1-0 s(1) to Br γ line ratio of spatially resolved planetary nebulae
Authors: Aleman Isabel
Published: July 2020

The H2 1-0 S(1)/Br γ ratio (R(Br γ)) is used in many studies of the molecular content in planetary nebulae (PNe). As these lines are produced in different regions, the slit configuration used in spectroscopic observations may have an important effect on their ratio. In this work, observations and numerical simulations are used to demonstrate and quantify such effect in PNe. The study aims to assist the interpretation of observations and their comparison to models. The analysis shows that observed R(Br γ) ratios reach only values up to 0.3 when the slit encompasses the entire nebula. Values higher than that are only obtained when the slit covers a limited region around the H2 peak emission and the Br γ emission is then minimized. The numerical simulations presented show that, when the effect of the slit configuration is taken into account, photoionization models can reproduce the whole range of observed R(Br γ) in PNe, as well as the behaviour described above. The argument that shocks are needed to explain the higher values of R(Br γ) is thus not valid. Therefore, this ratio is not a good indicator of the H2 excitation mechanism as suggested in the literature.
Spiral density enhancements in Be binary systems
Authors: Cyr Isabelle H , Jones C E , Carciofi A C , Steckel C , Tycner C , Okazaki A T
Published: July 2020

We use a smoothed particle hydrodynamics (SPH) code to examine the effects of a binary companion on a Be star disc for a range of disc viscosities and misalignment angles, i.e. the angle between the orbital plane and the primary star’s spin axis. The density structures in the disc due to the tidal interaction with the binary companion are investigated. Expanding on our previous work, the shape and density structure of density enhancements due to the binary companion are analysed and the changes in observed interferometric features due to these orbiting enhancements are also predicted. We find that larger misalignment angles and viscosity values result in more tightly wound spiral arms with densities that fall-off more slowly with radial distance from the central star. We show that the orbital phase has very little effect on the structure of the spiral density enhancements. We demonstrate that these spiral features can be detected with an interferometer in H α and K-band emission. We also show that the spiral features affect the axis ratios determined by interferometry depending on the orientation of these features and the observer. For example, our simulations show that the axis ratios can vary by 20 per cent for our co-planar binary disc system depending on the location of the disc density enhancements.
Improving position accuracy for telescopes with small aperture and wide field of view utilizing point spread function modelling
Authors: Sun Rongyu , Yu Shengxian , Jia Peng , Zhao Changyin
Published: July 2020

Telescopes with a small aperture and a wide field of view are widely used and play a significant role in large-scale state-of-the-art sky survey applications, such as transient detection and near-Earth object observations. However, owing to the specific defects caused by optical aberrations, the image quality and efficiency of source detection are affected. To achieve high-accuracy position measurements, an innovative technique is proposed. First, a large number of raw images are analysed using principal component analysis. Then, the effective point spread function is reconstructed, which reflects the state of the telescope and reveals the characteristics of the imaging process. Finally, based on the point spread function model, the centroids of star images are estimated iteratively. To test the efficiency and reliability of our algorithm, a large number of simulated images are produced, and a telescope with small aperture and wide field of view is utilized to acquire the raw images. The position measurement of sources is performed using our novel method and two other common methods on these data. Based on a comparison of the results, the improvement is investigated, and it is demonstrated that our proposed technique outperforms the others on position accuracy. We explore the limitations and potential gains that may be achieved by applying this technique to custom systems designed specifically for wide-field astronomical applications.
Cosmological constraints from H ii starburst galaxy apparent magnitude and other cosmological measurements
Authors: Cao Shulei , Ryan Joseph , Ratra Bharat
Published: July 2020

We use H ii starburst galaxy apparent magnitude measurements to constrain cosmological parameters in six cosmological models. A joint analysis of H ii galaxy, quasar angular size, baryon acoustic oscillations peak length scale, and Hubble parameter measurements result in relatively model-independent and restrictive estimates of the current values of the non-relativistic matter density parameter $\Omega _{\rm m_0}$ and the Hubble constant H0. These estimates favour a 2.0–3.4σ (depending on cosmological model) lower H0 than what is measured from the local expansion rate. The combined data are consistent with dark energy being a cosmological constant and with flat spatial hypersurfaces, but do not strongly rule out mild dark energy dynamics or slightly non-flat spatial geometries.
PTF11rka: an interacting supernova at the crossroads of stripped-envelope and H-poor superluminous stellar core collapses
Authors: Pian E , Mazzali P A , Moriya T J , Rubin A , Gal-Yam A , Arcavi I , Ben-Ami S , Blagorodnova N , Bufano F , Filippenko A V , Kasliwal M , Kulkarni S R , Lunnan R , Manulis I , Matheson T , Nugent P E , Ofek E , Perley D A , Prentice S J , Yaron O
Published: July 2020

The hydrogen-poor supernova (SN) PTF11rka (z = 0.0744), reported by the Palomar Transient Factory, was observed with various telescopes starting a few days after the estimated explosion time of 2011 December 5 UT and up to 432 rest-frame days thereafter. The rising part of the light curve was monitored only in the RPTF filter band, and maximum in this band was reached ∼30 rest-frame days after the estimated explosion time. The light curve and spectra of PTF11rka are consistent with the core-collapse explosion of a ∼10 M⊙ carbon–oxygen core evolved from a progenitor of main-sequence mass 25–40 M⊙, that liberated a kinetic energy Ek≈4 × 1051 erg, expelled ∼8 M⊙ of ejecta, and synthesized ∼0.5 M⊙ of 56Ni. The photospheric spectra of PTF11rka are characterized by narrow absorption lines that point to suppression of the highest ejecta velocities (≳ 15 000 km s−1). This would be expected if the ejecta impacted a dense, clumpy circumstellar medium. This in turn caused them to lose a fraction of their energy (∼5 × 1050 erg), less than 2 per cent of which was converted into radiation that sustained the light curve before maximum brightness. This is reminiscent of the superluminous SN 2007bi, the light-curve shape and spectra of which are very similar to those of PTF11rka, although the latter is a factor of 10 less luminous and evolves faster in time. PTF11rka is in fact more similar to gamma-ray burst SNe in luminosity, although it has a lower energy and a lower Ek/Mej ratio.
Resonant-line radiative transfer within power-law density profiles
Authors: Lao Bing-Xin , Smith Aaron
Published: July 2020

Star-forming regions in galaxies are surrounded by vast reservoirs of gas capable of both emitting and absorbing Lyman α (Lyα) radiation. Observations of Lyα emitters and spatially extended Lyα haloes indeed provide insights into the formation and evolution of galaxies. However, due to the complexity of resonant scattering, only a few analytic solutions are known in the literature. We discuss several idealized but physically motivated scenarios to extend the existing formalism to new analytic solutions, enabling quantitative predictions about the transport and diffusion of Lyα photons. This includes a closed form solution for the radiation field and derived quantities including the emergent flux, peak locations, energy density, average internal spectrum, number of scatters, outward force multiplier, trapping time, and characteristic radius. To verify our predictions, we employ a robust gridless Monte Carlo radiative transfer (GMCRT) method, which is straightforward to incorporate into existing ray tracing codes but requires modifications to opacity-based calculations, including dynamical core-skipping acceleration schemes. We primarily focus on power-law density and emissivity profiles, however both the analytic and numerical methods can be generalized to other cases. Such studies provide additional intuition and understanding regarding the connection between the physical environments and observational signatures of galaxies throughout the Universe.
Exploring AGN and star formation activity of massive galaxies at cosmic noon
Authors: Florez Jonathan , Jogee Shardha , Sherman Sydney , Stevans Matthew L , Finkelstein Steven L , Papovich Casey , Kawinwanichakij Lalitwadee , Ciardullo Robin , Gronwall Caryl , Urry C Megan , Kirkpatrick Allison , LaMassa Stephanie M , Ananna Tonima Tasnim , Wold Isak
Published: July 2020

We investigate the relation between active galactic nucleus (AGN) and star formation (SF) activity at 0.5 < z < 3 by analysing 898 galaxies with X-ray luminous AGNs (LX > 1044 erg s−1) and a large comparison sample of ∼320 000 galaxies without X-ray luminous AGNs. Our samples are selected from a large (11.8 deg2) area in Stripe 82 that has multiwavelength (X-ray to far-IR) data. The enormous comoving volume (∼0.3 Gpc3) at 0.5 < z < 3 minimizes the effects of cosmic variance and captures a large number of massive galaxies (∼30 000 galaxies with M* > 1011 M⊙) and X-ray luminous AGNs. While many galaxy studies discard AGN hosts, we fit the SED of galaxies with and without X-ray luminous AGNs with Code Investigating GALaxy Emission and include AGN emission templates. We find that without this inclusion, stellar masses and star formation rates (SFRs) in AGN host galaxies can be overestimated, on average, by factors of up to ∼5 and ∼10, respectively. The average SFR of galaxies with X-ray luminous AGNs is higher by a factor of ∼3–10 compared to galaxies without X-ray luminous AGNs at fixed stellar mass and redshift, suggesting that high SFRs and high AGN X-ray luminosities may be fuelled by common mechanisms. The vast majority ($\gt 95 {{\ \rm per\ cent}}$) of galaxies with X-ray luminous AGNs at z = 0.5−3 do not show quenched SF: this suggests that if AGN feedback quenches SF, the associated quenching process takes a significant time to act and the quenched phase sets in after the highly luminous phases of AGN activity.
A complete view of the outskirts of the Coma cluster
Authors: Mirakhor M S , Walker S A
Published: July 2020

We present a new extended XMM–Newton mosaic of the nearby Coma cluster, which covers the cluster out to the virial radius with nearly complete azimuthal coverage. This large mosaic is combined with the Planck Sunyaev Zel’dovich effect observations to recover the thermodynamic properties of the intracluster medium in an azimuthally averaged profile and 36 angular sectors, producing the highest spatial resolution view of the thermodynamics of the outskirts of a galaxy cluster in its entirety. Beyond r500, our clumping-corrected entropy measurements along the less disturbed directions are statistically consistent with the power-law entropy profile predicted by non-radiative simulations, and the gas mass fraction agrees with the mean cosmic baryon fraction. However, there is a clear entropy deficit in the outskirts to the south-west, coinciding with where Coma connects to a cosmic web filament that joins it to Abell 1367. The low entropy to the south-west extends from 0.5 to 1.0r200, and is consistent with what is expected from simulations of a filamentary gas stream penetrating into the cluster as it continues to accrete matter from the cosmic web. We also find that the radial profiles of the recovered quantities become increasingly asymmetric in the outskirts, particularly along the more disturbed directions, consistent with the predictions of cosmological simulations.