bluuebunny/crossref_metadata_2025 huggingface dataset:
Using patient-reported outcome measures in psychiatric hospital care: an observational study describing an iterative implementation process in Denmark
Authors: Kristensen Solvejg , Holmskov Jens , Pølund Karen , Hjermitslev Anne-Louise Lind , Bergh-Hanssen Karin , Christensen Irene Hjortlund , Bonde Maria , Mainz Jan
Published: April 2021

Background

Patient-reported outcomes (PROs) are increasingly recognized as valuable sources of information to enhance our understanding of the quality of healthcare from the patient’s perspective.

Objective

This study aimed to describe the implementation process of the Danish nationwide PRO-Psychiatry project, including iterative tests of previously developed PRO measurement concept and an online data collection tool. Additional aims were to identify the ‘best practice’ for the routine use of PROs in hospital-based psychiatry and design information material about the project.

Methods

We conducted an action-oriented observational study to explore the pilot implementation of the PRO-Psychiatry project, which was initiated in February 2018. The study was based on an iterative plan-do-learn approach. An inpatient unit and an outpatient unit from the same psychiatric department in the North Denmark Region were selected for the pilot implementation. The implementation was anchored in multidisciplinary implementation teams at unit level. These teams managed the implementation process according to four tasks defined by the department management.

Results

The teams designed, tested, evaluated and adjusted the localized work practices relating to the use of PRO-Psychiatry. The comprehensibility of the predesigned PROs, the usability of the Information Technology(IT) system and the routine use of PROs during clinical consultations were repeatedly tested and adjusted until the functionality was satisfactory. Furthermore, the teams designed information material for patients (emails, posters, handouts and webpages) and clinicians (online clinical guidelines). The team members informed their colleagues about the progress of PRO-Psychiatry at staff meetings and rolled out the initiative through one-to-one teaching.

Conclusions

The pilot implementation was deemed successful. PRO-Psychiatry was rolled out to other units in the region, and a national decision was made to pilot implement the initiative in the other four Danish regions.
The effects of protein level on cytokines and chemokines in the uterine environment of beef heifers during development
Authors: Ault-Seay Taylor B , Harrison Taylor D , Brandt Kiernan J , Payton Rebecca R , Schneider Liesel G , Myer Phillip R , Rhinehart Justin D , Rispoli Louisa A , McLean Kyle J
Published: April 2021

The development of replacement heifers is crucial for breeding success and herd efficiency. Nutritional management can affect not only reproductive development but also the inflammatory status of the uterine environment, which may impact reproductive functions such as pregnancy establishment and development. The study herein evaluated the concentration of cytokines and chemokines in the uterus of heifers supplemented with different levels of protein. Angus heifers (n = 60) were blocked by body weight (BW) and randomly assigned to 1 of 3 treatments based on protein supplementation level: control of 10% crude protein (CON), 20% crude protein (P20), or 40% crude protein (P40). BW, body condition score, and blood samples were taken every 2 wk for 140 d to monitor development. Uterine flushes were performed monthly and concentrations of cytokines (IL-1α, IL-1β, TNF-α, IFN-γ, IL-10, VEGF-α, IL-17A, and IL-36RA) and chemokines (IL-8, MCP-1, MIP-1α, and MIP-1β) were quantified via ELISA multiplex. To test if there were mean differences in cytokines between the treatment groups or over time, PROC GLIMMIX (SAS v 9.4) was utilized. Concentrations of all cytokines and chemokines, except IL-1α, changed throughout heifer development (P < 0.05). Heifers in the P40 treatment group displayed reduced concentrations of MCP-1 (P = 0.007) and tended to have decreased concentrations of IFN-γ (P = 0.06). Cytokine IL-36RA tended (P = 0.06) to be affected by protein level, with the lowest concentrations observed in CON heifers. Most cytokines and chemokines increased following the initial month of supplementation (P < 0.05). The increase in concentrations after 1 mo may indicate an adaptive response in the uterus to diet change. Cytokines and chemokines fluctuated due to physiological changes occurring during development. Further research is needed to determine the influence of nutrition on uterine inflammation and long-term impacts on reproductive function.
Radiomics: A Primer for Breast Radiologists
Authors: Grimm Lars J
Published: April 2021

Radiomics has a long-standing history in breast imaging with computer-aided detection (CAD) for screening mammography developed in the late 20th century. Although conventional CAD had widespread adoption, the clinical benefits for experienced breast radiologists were debatable due to high false-positive marks and subsequent increased recall rates. The dramatic growth in recent years of artificial intelligence–based analysis, including machine learning and deep learning, has provided numerous opportunities for improved modern radiomics work in breast imaging. There has been extensive radiomics work in mammography, digital breast tomosynthesis, MRI, ultrasound, PET-CT, and combined multimodality imaging. Specific radiomics outcomes of interest have been diverse, including CAD, prediction of response to neoadjuvant therapy, lesion classification, and survival, among other outcomes. Additionally, the radiogenomics subfield that correlates radiomics features with genetics has been very proliferative, in parallel with the clinical validation of breast cancer molecular subtypes and gene expression assays. Despite the promise of radiomics, there are important challenges related to image normalization, limited large unbiased data sets, and lack of external validation. Much of the radiomics work to date has been exploratory using single-institution retrospective series for analysis, but several promising lines of investigation have made the leap to clinical practice with commercially available products. As a result, breast radiologists will increasingly be incorporating radiomics-based tools into their daily practice in the near future. Therefore, breast radiologists must have a broad understanding of the scope, applications, and limitations of radiomics work.
Interventions with Sticky Social Norms: A Critique
Authors: Dutta Rohan , Levine David K , Modica Salvatore
Published: April 2021

We study the consequences of policy interventions when social norms are endogenous but costly to change. In our environment, a group faces a negative externality that it partially mitigates through incentives in the form of punishments. In this setting, policy interventions can have unexpected consequences. The most striking is that when the cost of bargaining is high, introducing a Pigouvian tax can increase output—yet in doing so increase welfare. An observer who saw that an increase in a Pigouvian tax raised output might wrongly conclude that this harmed welfare and that a larger tax increase would also raise output. This counter-intuitive impact on output is demonstrated theoretically for a general model and found in case studies for public goods subsidies and cartels.
Sequence Analysis and Ontogenetic Expression Patterns of Cone Opsin Genes in the Bluefin Killifish (Lucania goodei)
Authors: Chang Chia-Hao , Catchen Julian , Moran Rachel L , Rivera-Colón Angel G , Wang Yu-Chun , Fuller Rebecca C
Published: April 2021

Sensory systems allow for the transfer of environmental stimuli into internal cues that can alter physiology and behavior. Many studies of visual systems focus on opsins to compare spectral sensitivity among individuals, populations, and species living in different lighting environments. This requires an understanding of the cone opsins, which can be numerous. The bluefin killifish is a good model for studying the interaction between environments and visual systems as they are found in both clear springs and tannin-stained swamps. We conducted a genome-wide screening and demonstrated that the bluefin killifish has 9 cone opsins: 1 SWS1 (354 nm), 2 SWS2 (SWS2B: 359 nm, SWS2A: 448 nm), 2 RH2 (RH2-2: 476 nm, RH2-1: 537 nm), and 4 LWS (LWS-1: 569 nm, LWS-2: 524 nm, LWS-3: 569 nm, LWS-R: 560 or 569 nm). These 9 cone opsins were located on 4 scaffolds. One scaffold contained the 2 SWS2 and 3 of the 4 LWS opsins in the same syntenic order as found in other cyprinodontoid fishes. We also compared opsin expression in larval and adult killifish under clear water conditions, which mimic springs. Two of the newly discovered opsins (LWS-2 and LWS-3) were expressed at low levels (<0.2%). Whether these opsins make meaningful contributions to visual perception in other contexts (i.e., swamp conditions) is unclear. In contrast, there was an ontogenetic change from using LWS-R to LWS-1 opsin. Bluefin killifish adults may be slightly more sensitive to longer wavelengths, which might be related to sexual selection and/or foraging preferences.
Seasonal Dynamics of Fleas (Siphonaptera: Pulicidae, Ceratophyllidae and Leptopsyllidae) onOryctolagus cuniculusin a Meso-Mediterranean Area of Central Spain
Authors: González M G , González J , Valcárcel F , Sánchez M , Tercero J M , Barrios L , Olmeda A S
Published: April 2021

Flea infestations of wild rabbits were examined monthly in central Spain in a meso-Mediterranean area for 5 yr. A total of 1,180 wild rabbits were trapped and 7,022 fleas were collected from them. Overall, the prevalence was 74.1% with a mean flea index of 5.95 fleas per rabbit. Four flea species were identified: Spilopsyllus cuniculi (Dale, 1878) was the most abundant species (accounting for 74.3% of fleas collected) followed by Xenopsylla cunicularis (Smit, 1957), Odontopsyllus quirosi (Gil Collado, 1934), and Nosopsyllus fasciatus (Bosc, 1800) (18.9, 6.7, and 0.1%, respectively). The highest prevalence was observed in S. cuniculi (48.6%) followed by X. cunicularis, O. quirosi, and N. fasciatus (34.3, 20.0, and 0.6%, respectively). Odontopsyllus quirosi and S. cuniculi were mainly collected from autumn to spring with the peak of infestation in winter, while X. cunicularis was mainly found from spring to autumn with maximum levels of infestation during the summer months. The relevance of these findings is discussed.
A Study of the Pupal Development of Five Forensically Important Flies (Diptera: Brachycera)
Authors: Barros-Cordeiro K B , Pujol-Luz J R , Báo S N
Published: April 2021

Holometabolous insects undergo complete metamorphosis, and hence, they have different phases of development (egg, larva, pupa, and adult), which occupy distinct ecological niches. The pupae of several fly species are surrounded by the puparium, which is a rigid structure, usually formed by the integument of the last larval instar. The puparium presents unique characteristics distinct from those of the larval and adult phases. During intrapuparial development, it is possible to distinguish at least four fundamental and continuous steps, namely: 1) larval–pupal apolysis, 2) cryptocephalic pupa, 3) phanerocephalic pupa, and 4) pharate adult. The objective of this work was to describe the external morphology of the distinct phase of development for five species that were collected, identified, and raised in the laboratory; intrapuparial development was studied by fixing immature specimens at regular intervals; the morphological analyses were performed with the aid of both light and scanning electron microscopy. Under the conditions established (27 ± 1.0 or 23 ± 1.0°C, 60 ± 10% relative humidity, 12 h of photoperiod), the minimum time for intrapuparial development was: 252 h for Megaselia scalaris (Loew 1966) (Phoridae), 192 h for Piophila casei (Linnaeus 1758) (Piophilidae), Fannia pusio (Wiedemann 1830) (Fanniidae), and Musca domestica (Linnaeus 1758) (Muscidae), and 96 h for Chrysomya megacephala (Fabricius 1794) (Calliphoridae). Intrapuparial development has defined steps, and distinct species responded differently to the same environmental conditions. In addition, it is possible to establish a sequential rule without ignoring the specific characteristics of each taxon.
Mosquito Identification From Bulk Samples Using DNA Metabarcoding: a Protocol to Support Mosquito-Borne Disease Surveillance in Canada
Authors: Mechai S , Bilodeau G , Lung O , Roy M , Steeves R , Gagne N , Baird D , Lapen D R , Ludwig A , Ogden N H
Published: April 2021

Approximately 80 species of mosquitoes (Diptera: Culicidae) have been documented in Canada. Exotic species such as Aedes albopictus (Skuse) (Diptera: Culicidae) are becoming established. Recently occurring endemic mosquito-borne diseases (MBD) in Canada including West-Nile virus (WNV) and Eastern Equine Encephalitis (EEE) are having significant public health impacts. Here we explore the use of DNA metabarcoding to identify mosquitoes from CDC light-trap collections from two locations in eastern Canada. Two primer pairs (BF2-BR2 and F230) were used to amplify regions of the cytochrome c oxidase subunit I (CO1) gene. High throughput sequencing was conducted using an Illumina MiSeq platform and GenBank-based species identification was applied using a QIIME 1.9 bioinformatics pipeline. From a site in southeastern Ontario, Canada, 26 CDC light trap collections of 72 to >300 individual mosquitoes were used to explore the capacity of DNA metabarcoding to identify and quantify captured mosquitoes. The DNA metabarcoding method identified 33 species overall while 24 species were identified by key. Using replicates from each trap, the dried biomass needed to identify the majority of species was determined to be 76 mg (equivalent to approximately 72 mosquitoes), and at least two replicates from the dried biomass would be needed to reliably detect the majority of species in collections of 144–215 mosquitoes and three replicates would be advised for collections with >215 mosquitoes. This study supports the use of DNA metabarcoding as a mosquito surveillance tool in Canada which can help identify the emergence of new mosquito-borne disease potential threats.
On the Child’s Right to Bodily Integrity: When Is the Right Infringed?
Authors: Mazor Joseph
Published: April 2021

This article considers two competing types of conceptions of the pre-autonomous child’s right to bodily integrity. The first, which I call encroachment conceptions, holds that any physically serious bodily encroachment infringes on the child’s right to bodily integrity. The second, which I call best-interests conceptions, holds that the child’s right to bodily integrity is infringed just in case the child is subjected to a bodily encroachment that substantially deviates from what is in the child’s best interests. I argue in this article that best-interests conceptions are more plausible than encroachment conceptions. They have more attractive implications regarding the permissibility of interventions in children’s bodies that are beneficial for the child but are not medically necessary. They are better able to explain the moral distinction between cases in which an encroachment on a child’s body is needed to benefit that child and cases in which an encroachment on one child’s body is needed to benefit another. Finally, best-interests conceptions are more consonant than encroachment conceptions with our understanding of adults’ right to bodily integrity.
EGFRAmplification in Metastatic Colorectal Cancer
Authors: Randon Giovanni , Yaeger Rona , Hechtman Jaclyn F , Manca Paolo , Fucà Giovanni , Walch Henry , Lee Jeeyun , Élez Elena , Seligmann Jenny , Mussolin Benedetta , Pagani Filippo , Germani Marco Maria , Ambrosini Margherita , Rossini Daniele , Ratti Margherita , Salvà Francesc , Richman Susan D , Wood Henry , Nanjangud Gouri , Gloghini Annunziata , Milione Massimo , Bardelli Alberto , de Braud Filippo , Morano Federica , Cremolini Chiara , Pietrantonio Filippo
Published: April 2021

Background

EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC.

Methods

In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided.

Results

EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002).

Conclusion

Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies.
Fundamentals of the Development of Connectivity in the Human Fetal Brain in Late Gestation: From 24 Weeks Gestational Age to Term
Authors: Kostović Ivica , Radoš Milan , Kostović-Srzentić Mirna , Krsnik Željka
Published: April 2021

During the second half of gestation, the human cerebrum undergoes pivotal histogenetic events that underlie functional connectivity. These include the growth, guidance, selection of axonal pathways, and their first engagement in neuronal networks. Here, we characterize the spatiotemporal patterns of cerebral connectivity in extremely preterm (EPT), very preterm (VPT), preterm and term babies, focusing on magnetic resonance imaging (MRI) and histological data. In the EPT and VPT babies, thalamocortical axons enter into the cortical plate creating the electrically-active, functional synapses. Additionally, the subplate zone gradually resolves in the preterm and term brain in conjunction with the growth of associative pathways leading to the activation of large-scale neural networks. We demonstrate that specific classes of axonal pathways within cerebral compartments are selectively vulnerable to temporally nested pathogenic factors. In particular, the radial distribution of axonal lesions, that is, radial vulnerability, is a robust predictor of clinical outcome. Furthermore, the subplate tangential nexus that we can visualize using MRI could be an additional marker as pivotal in the development of cortical connectivity. We suggest to direct future research toward the identification of sensitive markers of earlier lesions, the elucidation of genetic mechanisms underlying pathogenesis, and better long-term follow-up using structural and functional MRI.
SMARCB1-deficient sinonasal carcinoma: a case report and literature review
Authors: Yanagawa Naoki , Suzuki Masamichi , Sugimoto Ryo , Osakabe Mitsumasa , Uesugi Noriyuki , Shiga Kiyoto , Sugai Tamotsu
Published: April 2021

SWItch/Sucrose Non-Fermentable (SWI/SNF) -related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) deficient sinonasal carcinoma (SdSNC) is a rare variant of sinonasal undifferentiated carcinoma (SNUC). A 72-year-old man was referred to our hospital with complaints of left facial pain and nasal obstruction. Computed tomography (CI) revealed a tumor 5.5 cm in size in the left nasal cavity. Atypical cells with eosinophilic cytoplasm proliferating as solid nests and exhibiting necrosis were observed and diagnosed as poorly differentiated carcinoma. Carbon ion radiotherapy was performed. Follow-up CI revealed multiple masses in both lungs. Partial resection of the right lung was performed. Proliferating atypical cells with clear-to-eosinophilic cytoplasm were observed and resembled those in the paranasal sinus tumor. Immunohistochemical analysis indicated a metastatic lung tumor derived from the SNUC revealed completely negative SMARCB1 expression in the nuclei of the tumor cells. SdSNC is difficult to diagnose. However, molecular targeted therapy may be useful. Thus, it is necessary and important to recognize this rare cancer accurately.
The energy security and insecurity of Bangladesh: a critical analysis
Authors: Siddiky Chowdhury Ishrak Ahmed
Published: April 2021

The last five years have seen Bangladesh making good progress in adding various energy mixes to its supply of energy for domestic consumption. The GDP of the country grew at 8 per cent in the year before the pandemic. This was possible due to certain policy-level decisions by the government to increase the production of energy, implementing short-term projects for electricity generation and the flexibility of the industrial sector. The country now has a plan to increase its energy security and lower its reliability on imported energy. The purpose of this article is to discuss and analyse the various policies and the challenges that the government faces in order to ensure the country’s energy security.
The bacterial biocontrol agent Paenibacillus alvei K165 confers inherited resistance to Verticillium dahliae
Authors: Gkizi Danai , González Gil Anna , Pardal Alonso J , Piquerez Sophie J M , Sergaki Chrysi , Ntoukakis Vardis , Tjamos Sotirios E
Published: April 2021

The biocontrol agent Paenibacillus alvei K165 was previously shown to protect Arabidopsis thaliana plants against Verticillium dahliae. Here we show that K165 also confers inherited immune resistance to V. dahliae. By performing a histone acetyltransferases mutant screen, ChIP assays, and transcriptomic experiments, we were able to show that histone acetylation significantly contributes to the K165 biocontrol activity and establishment of inheritable resistance to V. dahliae. K165 treatment primed the expression of immune-related marker genes and the cinnamyl alcohol dehydrogenase gene CAD3 through the function of histone acetyltransferases. Our results reveal that offspring of plants treated with K165 have primed immunity and enhanced lignification, both contributing towards the K165-mediated inherited immune resistance. Thus, our study paves the way for the use of biocontrol agents for the establishment of inheritable resistance to agronomically important pathogens.
3D distribution models of Ca, Cr, and Fe in a magnetic CP star atmosphere with anisotropic wind
Authors: Alecian G , Stift M J
Published: April 2021

We present time-dependent atomic diffusion calculations for Ca, Cr, and Fe in a stellar magnetic atmosphere including an anisotropic wind. For three different models of mass-loss rates (or wind), we obtain a 3D description of the entire atmosphere. In two of these models, the mass-loss rate varies according to the magnetic field inclination, the assumed field geometry being non-axisymmetric. When the dipolar component of the magnetic field dominates, we find that ring-like abundance structures will be prominent. Spot-like distributions can also exist according to the field geometry. Abundance distributions turn out to be highly sensitive to the mass-loss model. The results are discussed and compared to an observational model of a real chemically peculiar star (θ Aurigae) that features parameters close to those of the model we have adopted for our calculations.
Planes of satellites around Milky Way/M31-mass galaxies in the FIRE simulations and comparisons with the Local Group
Authors: Samuel Jenna , Wetzel Andrew , Chapman Sierra , Tollerud Erik , Hopkins Philip F , Boylan-Kolchin Michael , Bailin Jeremy , Faucher-Giguère Claude-André
Published: April 2021

We examine the prevalence, longevity, and causes of planes of satellite dwarf galaxies, as observed in the Local Group. We use 14 Milky Way/Andromeda-(MW/M31) mass host galaxies from the Feedback In Realistic Environments-2 simulations. We select the 14 most massive satellites by stellar mass within $d_\mathrm{host}\le 300\mathrm{\, kpc}$ of each host and correct for incompleteness from the foreground galactic disc when comparing to the MW. We find that MW-like planes as spatially thin and/or kinematically coherent as observed are uncommon, but they do exist in our simulations. Spatially thin planes occur in 1–2 per cent of snapshots during z = 0−0.2, and kinematically coherent planes occur in 5 per cent of snapshots. These planes are generally transient, surviving for <500 Myr. However, if we select hosts with a Large Magellanic Cloud-like satellite near first pericentre, the fraction of snapshots with MW-like planes increases dramatically to 7–16 per cent, with lifetimes of  0.7–1 Gyr, likely because of group accretion of satellites. We find that M31’s satellite distribution is much more common: M31’s satellites lie within ∼1σ of the simulation median for every plane metric we consider. We find no significant difference in average satellite planarity for isolated hosts versus hosts in LG-like pairs. Baryonic and dark matter-only simulations exhibit similar levels of planarity, even though baryonic subhaloes are less centrally concentrated within their host haloes. We conclude that planes of satellites are not a strong challenge to ΛCDM cosmology.
Non-Kolmogorov turbulence in multiphase intracluster medium driven by cold gas precipitation and AGN jets
Authors: Wang C , Ruszkowski M , Pfrommer C , Oh S Peng , Yang H-Y K
Published: April 2021

Active galactic nuclei (AGNs) feedback is responsible for maintaining plasma in global thermal balance in extended haloes of elliptical galaxies and galaxy clusters. Local thermal instability in the hot gas leads to the formation of precipitating cold gas clouds that feed the central supermassive black holes, thus heating the hot gas and maintaining global thermal equilibrium. We perform 3D magnetohydrodynamical (MHD) simulations of self-regulated AGNs feedback in a Perseus-like galaxy cluster with the aim of understanding the impact of the feedback physics on the turbulence properties of the hot and cold phases of the intracluster medium (ICM). We find that, in general, the cold phase velocity structure function (VSF) is steeper than the prediction from Kolmogorov’s theory. We attribute the physical origin of the steeper slope of the cold phase VSF to the driving of turbulent motions primarily by the gravitational acceleration acting on the ballistic clouds. We demonstrate that, in the pure hydrodynamical case, the precipitating cold filaments may be the dominant agent driving turbulence in the hot ICM. The arguments in favour of this hypothesis are that: (i) the cold phase mass dominates over hot gas mass in the inner cool core; (ii) hot and cold gas velocities are spatially correlated; (iii) both the cold and hot phase velocity distributions are radially biased. We show that, in the MHD case, the turbulence in the ambient hot medium (excluding the jet cone regions) can also be driven by the AGN jets. The driving is then facilitated by enhanced coupling due to magnetic fields of the ambient gas and the AGN jets. In the MHD case, turbulence may thus be driven by a combination of AGN jet stirring and filament motions. We conclude that future observations, including those from high spatial and spectral resolution X-ray missions, may help to constrain self-regulated AGN feedback by quantifying the multitemperature VSF in the ICM.
Opposite roles of transcription elongation factors Spt4/5 and Elf1 in RNA polymerase II transcription through B-form versus non-B DNA structures
Authors: Xu Jun , Chong Jenny , Wang Dong
Published: April 2021

Transcription elongation can be affected by numerous types of obstacles, such as nucleosome, pausing sequences, DNA lesions and non-B-form DNA structures. Spt4/5 and Elf1 are conserved transcription elongation factors that promote RNA polymerase II (Pol II) bypass of nucleosome and pausing sequences. Importantly, genetic studies have shown that Spt4/5 plays essential roles in the transcription of expanded nucleotide repeat genes associated with inherited neurological diseases. Here, we investigate the function of Spt4/5 and Elf1 in the transcription elongation of CTG•CAG repeat using an in vitro reconstituted yeast transcription system. We found that Spt4/5 helps Pol II transcribe through the CTG•CAG tract duplex DNA, which is in good agreement with its canonical roles in stimulating transcription elongation. In sharp contrast, surprisingly, we revealed that Spt4/5 greatly inhibits Pol II transcriptional bypass of CTG and CAG slip-out structures. Furthermore, we demonstrated that transcription elongation factor Elf1 individually and cooperatively with Spt4/5 inhibits Pol II bypass of the slip-out structures. This study uncovers the important functional interplays between template DNA structures and the function of transcription elongation factors. This study also expands our understanding of the functions of Spt4/5 and Elf1 in transcriptional processing of trinucleotide repeat DNA.
Early Coagulopathy in Pediatric Traumatic Brain Injury: A Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Retrospective Study
Authors: Chong Shu-Ling , Ong Gene Yong-Kwang , Zheng Charles Qishi , Dang Hongxing , Ming Meixiu , Mahmood Maznisah , Chan Lawrence Chi Ngong , Chuah Soo Lin , Lee Olive Pei Ee , Qian Suyun , Fan Lijia , Konoike Yoshihiko , Lee Jan Hau ,   on behalf of the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN)
Published: April 2021

BACKGROUND

Although early coagulopathy increases mortality in adults with traumatic brain injury (TBI), less is known about pediatric TBI.

OBJECTIVE

To describe the prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet levels of children with moderate to severe TBI to identify predictors of early coagulopathy and study the association with clinical outcomes.

METHODS

Using the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) TBI retrospective cohort, we identified patients <16 yr old with a Glasgow Coma Scale (GCS) ≤13. We compared PT, APTT, platelets, and outcomes between children with isolated TBI and multiple trauma with TBI. We performed logistic regressions to identify predictors of early coagulopathy and study the association with mortality and poor functional outcomes.

RESULTS

Among 370 children analyzed, 53/370 (14.3%) died and 127/370 (34.3%) had poor functional outcomes. PT was commonly deranged in both isolated TBI (53/173, 30.6%) and multiple trauma (101/197, 51.3%). Predictors for early coagulopathy were young age (adjusted odds ratio [aOR] 0.94, 95% CI 0.88-0.99, P = .023), GCS < 8 (aOR 1.96, 95% CI 1.26-3.06, P = .003), and presence of multiple trauma (aOR 2.21, 95% confidence interval [CI] 1.37-3.60, P = .001). After adjusting for age, gender, GCS, multiple traumas, and presence of intracranial bleed, children with early coagulopathy were more likely to die (aOR 7.56, 95% CI 3.04-23.06, P < .001) and have poor functional outcomes (aOR 2.16, 95% CI 1.26-3.76, P = .006).

CONCLUSION

Early coagulopathy is common and independently associated with death and poor functional outcomes among children with TBI.
Should Health Care Institutions Mandate SARS-CoV-2 Vaccination for Staff?
Authors: Kates Olivia S , Diekema Douglas S , Blumberg Emily A
Published: April 2021

Health care workers have been prioritized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but vaccine hesitancy among workers may limit uptake. Institutions may wish to consider SARS-CoV-2 vaccine mandates for health care workers, but such proposals raise important ethical questions. Arguments supporting mandates emphasize the proposed favorable balance of harms and benefits for both individuals and communities, as well as moral duties of health care workers and organizations. Arguments in opposition seek to challenge some claims about utility and raise additional concerns about infringement on autonomy, damage to organizational relationships, and injustice. While available SARS-CoV-2 vaccines remain under an experimental designation, mandates may be excessively problematic, but following approval by the Food and Drug Administration mandates may be reconsidered. The authors summarize ethical arguments and practical considerations, concluding that mandates may be ethically permissible in select circumstances.
Effectiveness of the Cell-Derived Inactivated Quadrivalent Influenza Vaccine in Individuals at High Risk of Influenza Complications in the 2018–2019 United States Influenza Season
Authors: Boikos Constantina , Imran Mahrukh , Nguyen Van Hung , Ducruet Thierry , Sylvester Gregg C , Mansi James A
Published: April 2021

Background

Higher rates of influenza-related morbidity and mortality occur in individuals with underlying medical conditions. To improve vaccine effectiveness, cell-based technology for influenza vaccine manufacturing has been developed. Cell-derived inactivated quadrivalent influenza vaccines (cIIV4) may improve protection in seasons in which egg-propagated influenza viruses undergo mutations that affect antigenicity. This study aimed to estimate the relative vaccine effectiveness (rVE) of cIIV4 versus egg-derived inactivated quadrivalent influenza vaccines (eIIV4) in preventing influenza-related medical encounters in individuals with underlying medical conditions putting them at high risk of influenza complications during the 2018–2019 US influenza season.

Methods

An integrated dataset, linking primary care electronic medical records with claims data, was used to conduct a retrospective cohort study among individuals aged ≥4 years, with ≥1 health condition, vaccinated with cIIV4 or eIIV4 during the 2018–2019 season. Adjusted odds ratios (ORs) were derived using a doubly robust inverse probability of treatment-weighting (IPTW) model, adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness was estimated by (1 − OR) × 100 and presented with 95% confidence intervals (CIs).

Results

The study cohort included 471 301 cIIV4 and 1 641 915 eIIV4 recipients. Compared with eIIV4, cIIV4 prevented significantly more influenza-related medical encounters among individuals with ≥1 health condition (rVE, 13.4% [95% CI, 11.4%–15.4%]), chronic pulmonary disease (rVE, 18.7% [95% CI, 16.0%–21.3%]), and rheumatic disease (rVE, 11.8% [95% CI, 3.6%–19.3%]).

Conclusions

Our findings support the use of cIIV4 in individuals ≥4 years of age at high risk of influenza complications and provide further evidence supporting improved effectiveness of cIIV4 compared with eIIV4.
Discordance of the Repeat GeneXpert MTB/RIF Test for Rifampicin Resistance Detection Among Patients Initiating MDR-TB Treatment in Uganda
Authors: Ssengooba Willy , de Dieu Iragena Jean , Komakech Kevin , Okello Iginitius , Nalunjogi Joanitah , Katagira Winceslaus , Kimuli Ivan , Adakun Susan , Joloba Moses L , Torrea Gabriela , Kirenga Bruce J
Published: April 2021

Background

The Global Laboratory Initiative (GLI) guidelines recommend repeat for GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low pretest probability of rifampicin resistance (RR).

Methods

This was a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/multidrug-resistant (MDR) TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra, and MTBDRplus assays were done on sputum specimens. Culture-based drug susceptibility testing (DST) was performed on discordant specimens. We analyzed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA, or culture DST (reference comparator).

Results

A total of 126/130 patients had repeat XpertMTB/RIF results, of whom 97 (77.0%) had M. tuberculosis detected, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%), whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%).

Low–bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results (adjusted odds ratio [aOR], 0.04; 95% CI, 0.00–0.37; P = .01; aOR, 0.02; 95% CI, 0.01–0.35; P = .01, respectively).

Conclusions

Our findings show a high false-positive rifampicin resistance rate in low–TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti-MDR-TB therapy.
Perception of solar UV radiation by plants: photoreceptors and mechanisms
Authors: Rai Neha , Morales Luis Orlando , Aphalo Pedro José
Published: April 2021

About 95% of the ultraviolet (UV) photons reaching the Earth’s surface are UV-A (315–400 nm) photons. Plant responses to UV-A radiation have been less frequently studied than those to UV-B (280–315 nm) radiation. Most previous studies on UV-A radiation have used an unrealistic balance between UV-A, UV-B, and photosynthetically active radiation (PAR). Consequently, results from these studies are difficult to interpret from an ecological perspective, leaving an important gap in our understanding of the perception of solar UV radiation by plants. Previously, it was assumed UV-A/blue photoreceptors, cryptochromes and phototropins mediated photomorphogenic responses to UV-A radiation and “UV-B photoreceptor” UV RESISTANCE LOCUS 8 (UVR8) to UV-B radiation. However, our understanding of how UV-A radiation is perceived by plants has recently improved. Experiments using a realistic balance between UV-B, UV-A, and PAR have demonstrated that UVR8 can play a major role in the perception of both UV-B and short-wavelength UV-A (UV-Asw, 315 to ∼350 nm) radiation. These experiments also showed that UVR8 and cryptochromes jointly regulate gene expression through interactions that alter the relative sensitivity to UV-B, UV-A, and blue wavelengths. Negative feedback loops on the action of these photoreceptors can arise from gene expression, signaling crosstalk, and absorption of UV photons by phenolic metabolites. These interactions explain why exposure to blue light modulates photomorphogenic responses to UV-B and UV-Asw radiation. Future studies will need to distinguish between short and long wavelengths of UV-A radiation and to consider UVR8’s role as a UV-B/UV-Asw photoreceptor in sunlight.
The Economic Consequences of Increasing Sleep Among the Urban Poor
Authors: Bessone Pedro , Rao Gautam , Schilbach Frank , Schofield Heather , Toma Mattie
Published: April 2021

The urban poor in developing countries face challenging living environments, which may interfere with good sleep. Using actigraphy to measure sleep objectively, we find that low-income adults in Chennai, India, sleep only 5.5 hours a night on average despite spending 8 hours in bed. Their sleep is highly interrupted, with sleep efficiency—sleep per time in bed—comparable to those with disorders such as sleep apnea or insomnia. A randomized three-week treatment providing information, encouragement, and improvements to home sleep environments increased sleep duration by 27 minutes a night by inducing more time in bed. Contrary to expert predictions and a large body of sleep research, increased nighttime sleep had no detectable effects on cognition, productivity, decision making, or well being, and led to small decreases in labor supply. In contrast, short afternoon naps at the workplace improved an overall index of outcomes by 0.12 standard deviations, with significant increases in productivity, psychological well-being, and cognition, but a decrease in work time.
Gluing Non-commutative Twistor Spaces
Authors: Marcolli Matilde , Penrose Roger
Published: April 2021

We describe a general procedure, based on Gerstenhaber–Schack complexes, for extending to quantized twistor spaces the Donaldson–Friedman gluing of twistor spaces via deformation theory of singular spaces. We consider in particular various possible quantizations of twistor spaces that leave the underlying spacetime manifold classical, including the geometric quantization of twistor spaces originally constructed by the second author, as well as some variants based on non-commutative geometry. We discuss specific aspects of the gluing construction for these different quantization procedures.
Workforce Composition, Productivity, and Labour Regulations in a Compensating Differentials Theory of Informality
Authors: Haanwinckel Daniel , Soares Rodrigo R
Published: April 2021

We develop a search model of informal labour markets with realistic labour regulations, including minimum wage, and heterogeneous workers and firms. Smaller firms and lower wages in the informal sector emerge endogenously as firms and workers decide whether to comply with regulations. Because skilled and unskilled workers are imperfect substitutes in production, the model uniquely captures the informality consequences of shocks that affect returns to skill, such as rising educational levels. The model also reproduces empirical patterns incompatible with other frameworks: the presence of skilled and unskilled workers in the formal and informal sectors, the rising share of skilled workers by firm size, and formal and firm-size wage premiums that vary by skill level. We estimate the model using 2003 data from Brazil and show that it successfully predicts labour market changes observed between 2003 and 2012. Under a range of different assumptions, changes in workforce composition appear as the main drivers of the reduction in informality over this period. Policy simulations using the estimated model suggest that progressive payroll taxes are a cost-effective way to reduce informality.
The Macroeconomics of Epidemics
Authors: Eichenbaum Martin S , Rebelo Sergio , Trabandt Mathias
Published: April 2021

We extend the canonical epidemiology model to study the interaction between economic decisions and epidemics. Our model implies that people cut back on consumption and work to reduce the chances of being infected. These decisions reduce the severity of the epidemic but exacerbate the size of the associated recession. The competitive equilibrium is not socially optimal because infected people do not fully internalize the effect of their economic decisions on the spread of the virus. In our benchmark model, the best simple containment policy increases the severity of the recession but saves roughly half a million lives in the United States.
Relationships between sleep traits and lung cancer risk: a prospective cohort study in UK Biobank
Authors: Xie Junxing , Zhu Meng , Ji Mengmeng , Fan Jingyi , Huang Yanqian , Wei Xiaoxia , Jiang Xiangxiang , Xu Jing , Yin Rong , Wang Yuzhuo , Dai Juncheng , Jin Guangfu , Xu Lin , Hu Zhibin , Ma Hongxia , Shen Hongbing
Published: April 2021

Study objectives

To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer.

Methods

We included 469 691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable-adjusted hazard ratios (HRs) for lung cancer (2177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia, and snoring) and examined the interaction and joint effects with a lung cancer polygenic risk score.

Results

A U-shaped association was observed for sleep duration and lung cancer risk, with an 18% higher risk (95% confidence interval [CI]: 1.07 to 1.30) for short sleepers and a 17% higher risk (95% CI: 1.02 to 1.34) for long sleepers compared with normal sleepers (7–8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95% CI: 1.07 to 1.46), but no association was found for insomnia or snoring. Compared with participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (<7 hours or >8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HRsleep duration: 1.83; 95% CI: 1.47 to 2.27; HRchronotype: 1.85; 95% CI: 1.34 to 2.56).

Conclusions

Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk.
Endorsement of Religion–Science Conflict as an Expression of Group Solidarity among Graduate Students in the Sciences
Authors: Scheitle Christopher P , Corcoran Katie E
Published: April 2021

Why do some individuals perceive religion and science as being in conflict while others do not? Research suggests that individuals’ endorsement of religion–science conflict is often as much an expression of identity and group membership as it is an intellectual assessment of the relationship. This study examines this dynamic among graduate students in five science disciplines in the United States. An analysis of original survey data finds that students who both identify strongly with science and believe that others in their scientific discipline are hostile toward religion are more likely to say that religion and science are in conflict and that they are on the side of science. This suggests that endorsements of religion–science conflict are a way for students to express solidarity with a group that is important to their identity.
Retracted: Trends in mental health symptoms, service use, and unmet need for services among U.S. adults through the first 9 months of the COVID-19 pandemic
Authors: Coley Rebekah Levine , Baum Christopher F
Published: April 2021

Lay Summary

The myriad stressors imposed by the COVID-19 pandemic have impaired mental health and well-being. Although evidence from early in the pandemic revealed elevated rates of mental health conditions, research has not documented whether psychological disorders have continued to rise as the pandemic has persisted. In this research, we assess data from nearly 1.5 million U.S. adults who participated in cross-sectional surveys each week from April through November 2020 to track trends in mental health disorder symptoms and services. Our results show that reports of anxiety and depression rose significantly from April to November 2020 to rates six times higher than in 2019. We also found evidence of growing unmet need for mental health services. Rising mental health challenges are being borne largely by young, less advantaged people of color and women. Growing disparities in mental health disorders and treatment raise concerns for psychological, social, and economic recovery from COVID-19.