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Large H2O solubility in dense silica and its implications for the interiors of water-rich planets [Earth, Atmospheric, and Planetary Sciences]

Sub-Neptunes are common among the discovered exoplanets. However, lack of knowledge on the state of matter in H2O-rich setting at high pressures and temperatures (P−T) places important limitations on our understanding of this planet type. We have conducted experiments for reactions between SiO2 and H2O as archetypal materials for rock...




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Requirement of the Cep57-Cep63 Interaction for Proper Cep152 Recruitment and Centriole Duplication [Research Article]

Cep57 has been characterized as a component of a pericentriolar complex containing Cep63 and Cep152. Interestingly, Cep63 and Cep152 self-assemble into a pericentriolar cylindrical architecture, and this event is critical for the orderly recruitment of Plk4, a key regulator of centriole duplication. However, the way in which Cep57 interacts with the Cep63-Cep152 complex and contributes to the structure and function of Cep63-Cep152 self-assembly remains unknown. We demonstrate that Cep57 interacts with Cep63 through N-terminal motifs and associates with Cep152 via Cep63. Three-dimensional structured illumination microscopy (3D-SIM) analyses suggested that the Cep57-Cep63-Cep152 complex is concentrically arranged around a centriole in a Cep57-in and Cep152-out manner. Cep57 mutant cells defective in Cep63 binding exhibited improper Cep63 and Cep152 localization and impaired Sas6 recruitment for procentriole assembly, proving the significance of the Cep57-Cep63 interaction. Intriguingly, Cep63 fused to a microtubule (MT)-binding domain of Cep57 functioned in concert with Cep152 to assemble around stabilized MTs in vitro. Thus, Cep57 plays a key role in architecting the Cep63-Cep152 assembly around centriolar MTs and promoting centriole biogenesis. This study may offer a platform to investigate how the organization and function of the pericentriolar architecture are altered by disease-associated mutations found in the Cep57-Cep63-Cep152 complex.




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Svalbard ptarmigans don't prioritise fighting infection in winter [INSIDE JEB]

Kathryn Knight




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Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis

Background

Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis. Because macrophage-mediated inflammation plays an important role in the pathogenesis of cystinosis, biomarkers of macrophage activation could have potential for the therapeutic monitoring of cystinosis.

Methods

We conducted a 2-year prospective, longitudinal study in which 61 patients with cystinosis who were receiving cysteamine therapy were recruited from three European reference centers. Each regular care visit included measuring four biomarkers of macrophage activation: IL-1β, IL-6, IL-18, and chitotriosidase enzyme activity.

Results

A multivariate linear regression analysis of the longitudinal data for 57 analyzable patients found chitotriosidase enzyme activity and IL-6 to be significant independent predictors for white blood cell cystine levels in patients of all ages with cystinosis; a receiver operating characteristic analysis ranked chitotriosidase as superior to IL-6 in distinguishing good from poor therapeutic control (on the basis of white blood cell cystine levels of <2 nmol 1/2 cystine/mg protein or ≥2 nmol 1/2 cystine/mg protein, respectively). Moreover, in patients with at least one extrarenal complication, chitotriosidase significantly correlated with the number of extrarenal complications and was superior to white blood cell cystine levels in predicting the presence of multiple extrarenal complications.

Conclusions

Chitotriosidase enzyme activity holds promise as a biomarker for use in therapeutic monitoring of nephropathic cystinosis.




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Atorvastatin Reduces In Vivo Fibrin Deposition and Macrophage Accumulation, and Improves Primary Patency Duration and Maturation of Murine Arteriovenous Fistula

Background

Arteriovenous fistulas placed surgically for dialysis vascular access have a high primary failure rate resulting from excessive inward remodeling, medial fibrosis, and thrombosis. No clinically established pharmacologic or perisurgical therapies currently address this unmet need. Statins’ induction of multiple anti-inflammatory and antithrombotic effects suggests that these drugs might reduce arteriovenous fistula failure. Yet, the in vivo physiologic and molecular effects of statins on fistula patency and maturation remain poorly understood.

Methods

We randomized 108 C57Bl/6J mice to receive daily atorvastatin 1.14 mg/kg or PBS (control) starting 7 days before end-to-side carotid artery–jugular vein fistula creation and for up to 42 days after fistula creation. We then assessed longitudinally the effects of statin therapy on primary murine fistula patency and maturation. We concomitantly analyzed the in vivo arteriovenous fistula thrombogenic and inflammatory macrophage response to statin therapy, using the fibrin-targeted, near-infrared fluorescence molecular imaging agent FTP11-CyAm7 and dextranated, macrophage-avid nanoparticles CLIO-VT680.

Results

In vivo molecular-structural imaging demonstrated that atorvastatin significantly reduced fibrin deposition at day 7 and macrophage accumulation at days 7 and 14, findings supported by histopathologic and gene-expression analyses. Structurally, atorvastatin promoted favorable venous limb outward remodeling, preserved arteriovenous fistula blood flow, and prolonged primary arteriovenous fistula patency through day 42 (P<0.05 versus control for all measures).

Conclusions

These findings provide new in vivo evidence that statins improve experimental arteriovenous fistula patency and maturation, indicating that additional clinical evaluation of statin therapy in patients on dialysis undergoing arteriovenous fistula placement is warranted.




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Case 2: Mysterious Hyperkalemia in a Premature Infant of 25 Weeks Gestation




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The shear stiffness criterion for rock joints considering rock wear behaviour

Rock is a material that is affected by wear, and the curvature of the asperities on a rock joint surface increases with the degree of wear after shearing. Based on the Greenwood and Williamson (GW) model, a new model considering the change of asperity curvature is proposed to explain the wear behaviour of rock joints. First, the shear stiffness formula for a joint surface is derived when the asperity curvature is constant, which shows that the shear stiffness increases with increase of asperity curvature. According to the Mohr–Coulomb criterion, the yield position of a single asperity under normal force and tangential friction force is discussed. Then, the critical normal force for a single asperity at a specific friction coefficient is obtained, which shows that the normal force corresponds to the curvature radius of the asperity. A rough surface model with multi-level curvature radius is proposed. With increase of normal force, the higher-order asperities gradually fail and the curvature radius become larger. A specific pressure value excites a specific radius of curvature, and the larger the pressure, the larger the radius of curvature. The relation between the normal force and the curvature radius is proposed and a shear stiffness formula considering the change of curvature radius of the asperity is derived. The proposed model is verified on the basis of the published experimental results. The calculation results of the proposed model can reflect the test results well: for a given joint surface, with increase in normal force the joint surface gradually becomes smooth; for different joint surfaces, with increase in roughness, the joint surface is more easily smoothed.




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Fluorescent Hybridization of Mycobacterium leprae in Skin Samples Collected in Burkina Faso [Mycobacteriology and Aerobic Actinomycetes]

Leprosy is caused by Mycobacterium leprae, and it remains underdiagnosed in Burkina Faso. We investigated the use of fluorescent in situ hybridization (FISH) for detecting M. leprae in 27 skin samples (skin biopsy samples, slit skin samples, and skin lesion swabs) collected from 21 patients from Burkina Faso and three from Côte d’Ivoire who were suspected of having cutaneous leprosy. In all seven Ziehl-Neelsen-positive skin samples (four skin biopsy samples and three skin swabs collected from the same patient), FISH specifically identified M. leprae, including one FISH-positive skin biopsy sample that remained negative after testing with PCR targeting the rpoB gene and with the GenoType LepraeDR assay. Twenty other skin samples and three negative controls all remained negative for Ziehl-Neelsen staining, FISH, and rpoB PCR. These data indicate the usefulness of a microscopic examination of skin samples after FISH for first-line diagnosis of cutaneous leprosy. Accordingly, FISH represents a potentially useful point-of-care test for the diagnosis of cutaneous leprosy.




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High-Content Screening, a Reliable System for Coxiella burnetii Isolation from Clinical Samples [Bacteriology]

Q fever, caused by Coxiella burnetii, is a worldwide zoonotic disease that may cause severe forms in humans and requires a specific and prolonged antibiotic treatment. Although current serological and molecular detection tools allow a reliable diagnosis of the disease, culture of C. burnetii strains is mandatory to assess their susceptibility to antibiotics and sequence their genome in order to optimize patient management and epidemiological studies. However, cultivating this fastidious microorganism is difficult and restricted to reference centers, as it requires biosafety level 3 laboratories and relies on cell culture performed by experienced technicians. In addition, the culture yield is low, which results in a small number of isolates being available. In this work, we developed a novel high-content screening (HCS) isolation strategy based on optimized high-throughput cell culture and automated microscopic detection of infected cells with specifically designed algorithms targeting cytopathic effects. This method was more efficient than the shell vial assay, at the level of time dependency, when applied to both frozen specimens (7 isolates recovered by HCS only, sensitivity 91% versus 78% for shell vial) and fresh samples (1 additional isolate using HCS, sensitivity 7% versus 5% for shell vial), for which most strains were recovered more rapidly with the new technique. In addition, detecting positive cultures by an automated microscope reduced the need for expertise and saved 24% of technician working time. Application of HCS to antibiotic susceptibility testing of 12 strains demonstrated that it was as efficient as the standard procedure that combines shell vial culture and quantitative PCR.




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Evaluation of a Novel Multiplex PCR Panel Compared to Quantitative Bacterial Culture for Diagnosis of Lower Respiratory Tract Infections [Bacteriology]

Quantitative bacterial culture of bronchoalveolar lavage fluids (BALF) is labor-intensive, and the delay involved in performing culture, definitive identification, and susceptibility testing often results in prolonged use of broad-spectrum antibiotics. The Unyvero lower respiratory tract (LRT) panel (Curetis, Holzgerlingen, Germany) allows the multiplexed rapid detection and identification of 20 potential etiologic agents of pneumonia within 5 h of collection. In addition, the assay includes detection of gene sequences that confer antimicrobial resistance. We retrospectively compared the performance of the molecular panel to routine quantitative bacterial culture methods on remnant BALF. Upon testing 175 BALF, we were able to analyze positive agreement of 181 targets from 129 samples, and 46 samples were negative. The positive percent agreement (PPA) among the microbial targets was 96.5%, and the negative percent agreement (NPA) was 99.6%. The targets with a PPA of <100% were Staphylococcus aureus (34/37 [91.9%]), Streptococcus pneumoniae (10/11 [90.9%]), and Enterobacter cloacae complex (2/4 [50%]). For the analyzable resistance targets, concordance with phenotypic susceptibility testing was 79% (14/18). This study found the Unyvero LRT panel largely concordant with culture results; however, no outcome or clinical impact studies were performed.




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Genomic Investigation Reveals Contaminated Detergent as the Source of an Extended-Spectrum-{beta}-Lactamase-Producing Klebsiella michiganensis Outbreak in a Neonatal Unit [Bacteriology]

Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis. Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.




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Pooling Pharyngeal, Anorectal, and Urogenital Samples for Screening Asymptomatic Men Who Have Sex with Men for Chlamydia trachomatis and Neisseria gonorrhoeae [Bacteriology]

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae at the pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Combining the three individual-site samples into a single pooled sample could result in significant cost savings, provided there is no significant sensitivity reduction. The aim of this study was to examine the sensitivity of pooled samples for detecting chlamydia and gonorrhea in asymptomatic MSM using a nucleic acid amplification test. Asymptomatic MSM who tested positive for chlamydia or gonorrhoea were invited to participate. Paired samples were obtained from participants prior to administration of treatment. To form the pooled sample, the anorectal swab was agitated in the urine specimen transport tube and then discarded. The pharyngeal swab and 2 ml of urine sample were then added to the tube. The difference in sensitivity between testing of pooled samples and individual-site testing was calculated against an expanded gold standard, where an individual is considered positive if either pooled-sample or individual-site testing returns a positive result. All samples were tested using the Aptima Combo 2 assay. A total of 162 MSM were enrolled in the study. Sensitivities of pooled-sample testing were 86% (94/109; 95% confidence interval [CI], 79 to 92%]) for chlamydia and 91% (73/80; 95% CI, 83 to 96%) for gonorrhea. The sensitivity reduction was significant for chlamydia (P = 0.02) but not for gonorrhea (P = 0.34). Pooling caused 22 infections (15 chlamydia and 7 gonorrhoea) to be missed, and the majority were single-site infections (19/22). Pooling urogenital and extragenital samples from asymptomatic MSM reduced the sensitivity of detection by approximately 10% for chlamydia but not for gonorrhea.




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Multicenter Evaluation of the BD Phoenix CPO Detect Test for Detection and Classification of Carbapenemase-Producing Organisms in Clinical Isolates [Bacteriology]

Limited treatment options contribute to high morbidity/mortality rates with carbapenem-resistant, Gram-negative bacterial infections. New approaches for carbapenemase-producing organism (CPO) detection may help inform clinician decision-making on patient treatment and infection control. BD Phoenix CPO detect (CPO detect) detects and classifies carbapenemases in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa during susceptibility testing. The clinical performance of CPO detect is reported here. Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates were evaluated across three sites using CPO detect and a composite reference method (RM); the latter was comprised of the modified carbapenem inactivation method and a MIC screen for ertapenem, imipenem, and meropenem. Multiplex PCR testing was also utilized for Ambler class determination. Positive and negative percentages of agreement (PPA and NPA, respectively) between CPO detect and the RM were determined. The PPA and NPA for Enterobacterales were 98.5% (confidence intervals, 96.6%, 99.4%) and 97.2% (95.8%, 98.2%), respectively. The A. baumannii PPA and NPA, respectively, were 97.1% (90.2%, 99.2%) and 97.1% (89.9%, 99.2%). The P. aeruginosa PPA and NPA, respectively, were 95.9% (88.6%, 98.6%) and 92.3% (86.7%, 95.6%). The PPA values for carbapenemase class designations for all organisms combined and Enterobacterales alone, respectively, were 95.3% (90.2%, 97.8%) and 94.6% (88.8%, 97.5%) for class A, 94.0% (88.7%, 96.6%) and 96.4% (90.0%, 98.8%) for class B, and 95.0% (90.1%, 97.6%) and 99.0% (94.4%, 99.8%) for class D carbapenemases. NPA values for all organisms and Enterobacterales alone ranged from 98.5% to 100%. CPO detect provided accurate detection and classification of CPOs for the majority of isolates of Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa tested.




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Evaluation of Cycle Threshold, Toxin Concentration, and Clinical Characteristics of Clostridioides difficile Infection in Patients with Discordant Diagnostic Test Results [Bacteriology]

Clostridioides difficile infection (CDI) is one of the most common health care-associated infections that can cause significant morbidity and mortality. CDI diagnosis involves laboratory testing in conjunction with clinical assessment. The objective of this study was to assess the performance of various C. difficile tests and to compare clinical characteristics, Xpert C. difficile/Epi (PCR) cycle threshold (CT), and Singulex Clarity C. diff toxins A/B (Clarity) concentrations between groups with discordant test results. Unformed stool specimens from 200 hospitalized adults (100 PCR positive and 100 negative) were tested by cell cytotoxicity neutralization assay (CCNA), C. diff Quik Chek Complete (Quik Chek), Premier Toxins A and B, and Clarity. Clinical data, including CDI severity and CDI risk factors, were compared between discordant test results. Compared to CCNA, PCR had the highest sensitivity at 100% and Quik Chek had the highest specificity at 100%. Among clinical and laboratory data studied, prevalences of leukocytosis, prior antibiotic use, and hospitalizations were consistently higher across all subgroups in comparisons of toxin-positive to toxin-negative patients. Among PCR-positive samples, the median CT was lower in toxin-positive samples than in toxin-negative samples; however, CT ranges overlapped. Among Clarity-positive samples, the quantitative toxin concentration was significantly higher in toxin-positive samples than in toxin-negative samples as determined by CCNA and Quik Chek Toxin A and B. Laboratory tests for CDI vary in sensitivity and specificity. The quantitative toxin concentration may offer value in guiding CDI diagnosis and treatment. The presence of leukocytosis, prior antibiotic use, and previous hospitalizations may assist with CDI diagnosis, while other clinical parameters may not be consistently reliable.




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Direct Determination of Pyrazinamide (PZA) Susceptibility by Sputum Microscopic Observation Drug Susceptibility (MODS) Culture at Neutral pH: the MODS-PZA Assay [Mycobacteriology and Aerobic Actinomycetes]

Pyrazinamide (PZA) is considered the pivot drug in all tuberculosis treatment regimens due to its particular action on the persistent forms of Mycobacterium tuberculosis. However, no drug susceptibility test (DST) is considered sufficiently reliable for routine application. Although molecular tests are endorsed, their application is limited to known PZA resistance associated mutations. Microbiological DSTs for PZA have been restricted by technical limitations, especially the necessity for an acidic pH. Here, for the first time, MODS culture at neutral pH was evaluated using high PZA concentrations (400 and 800 μg/ml) to determine PZA susceptibility directly from sputum samples. Sputum samples were cultured with PZA for up to 21 days at 37°C. Plate reading was performed at two time points: R1 (mean, 10 days) and R2 (mean, 13 days) for each PZA concentration. A consensus reference test, composed of MGIT-PZA, pncA sequencing, and the classic Wayne test, was used. A total of 182 samples were evaluated. The sensitivity and specificity for 400 μg/ml ranged from 76.9 to 89.7 and from 93.0 to 97.9%, respectively, and for 800 μg/ml ranged from 71.8 to 82.1 and from 95.8 to 98.6%, respectively. Compared to MGIT-PZA, our test showed a similar turnaround time (medians of 10 and 12 days for PZA-sensitive and -resistant isolates, respectively). In conclusion, MODS-PZA is presented as a fast, simple, and low-cost DST that could complement the MODS assay to evaluate resistance to the principal first-line antituberculosis drugs. Further optimization of test conditions would be useful in order to increase its performance.




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Rapid acquisition through fast mapping: stable memory over time and role of prior knowledge [RESEARCH]

In recent years, there have been intensive debates on whether healthy adults acquire new word knowledge through fast mapping (FM) by a different mechanism from explicit encoding (EE). In this study, we focused on this issue and investigated to what extent retention interval, prior knowledge (PK), and lure type modulated memory after FM and EE. Healthy young participants were asked to learn novel word-picture associations through both FM and EE. Half of the pictures were from familiar categories (i.e., high PK) and the other half were from unfamiliar categories (i.e., low PK). After 10 min and 1 wk, the participants were tested by forced-choice (FC) tasks, with lures from different categories (Experiment 1) or from the same categories of the target pictures (Experiment 2). Pseudowords were used to denote names of the novel pictures and baseline performance was controlled for each task. The results showed that in both Experiments 1 and 2, memory performance remained stable after FM, while it declined after EE from 10 min to 1 wk. Moreover, the effect of PK appeared at 10 min after FM while at 1 wk after EE in Experiment 2. PK enhanced memory of word-picture associations when the lures were from the same categories (Experiment 2), rather than from different categories (Experiment 1). These results were largely confirmed in Experiment 3 when encoding condition was manipulated as a between-subjects factor, while lure type as a within-subjects factor. The findings suggest that different from EE, FM facilitates rapid acquisition and consolidation of word-picture knowledge, and highlight that PK plays an important role in this process by enhancing access to detailed information.




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A Conversation Between Ignasi Carrio and Ken Herrmann




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Advancing Biologics Development Programs with Legacy Cell Lines: Advantages and Limitations of Genetic Testing for Addressing Clonality Concerns Prior to Availability of Late Stage Process and Product Consistency Data

The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line "clonal origin" an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as "legacy cell lines," may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.




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Chitotriosidase: a marker and modulator of lung disease

Chitotriosidase (CHIT1) is a highly conserved and regulated chitinase secreted by activated macrophages; it is a member of the 18-glycosylase family (GH18). CHIT1 is the most prominent chitinase in humans, can cleave chitin and participates in the body's immune response and is associated with inflammation, infection, tissue damage and remodelling processes. Recently, CHIT1 has been reported to be involved in the molecular pathogenesis of pulmonary fibrosis, bronchial asthma, COPD and pulmonary infections, shedding new light on the role of these proteins in lung pathophysiology. The potential roles of CHIT1 in lung diseases are reviewed in this article.




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Prion protein deficiency impairs hematopoietic stem cell determination and sensitizes myeloid progenitors to irradiation

Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC regulates hematopoietic stem cell self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cell number during aging and their determination towards myeloid progenitors. Furthermore, PrPC protects myeloid progenitors against the cytotoxic effects of total body irradiation. This radioprotective effect was associated with increased cellular prion mRNA level and with stimulation of the DNA repair activity of the Apurinic/pyrimidinic endonuclease 1, a key enzyme of the base excision repair pathway. Altogether, these results show a previously unappreciated role of PrPC in adult hematopoiesis, and indicate that PrPC-mediated stimulation of BER activity might protect hematopoietic progenitors from the cytotoxic effects of total body irradiation.




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Use of the health care system by Ontario First Nations people with diabetes: a population-based study

Background:

First Nations people in Ontario have an increased prevalence of diabetes compared to other people in the province. This study examined use of health care services by First Nations people with diabetes and other people with diabetes in Ontario.

Methods:

Using linked health administrative databases, we identified all people in Ontario with diabetes as of Apr. 1, 2014. We identified First Nations people using the Indian Register. We looked at outcomes from Apr. 1, 2014, to Mar. 31, 2015. We determined the proportion of people with a regular family physician and their continuity of care with that physician. We also examined visits with specialists for diabetes care, hospital admissions for ambulatory-care–sensitive conditions, and emergency department visits for hypo- or hyperglycemia.

Results:

There were 1 380 529 people diagnosed with diabetes in Ontario as of Apr. 1, 2014, of whom 22 952 (1.7%) were First Nations people. First Nations people were less likely to have a regular family physician (85.3% v. 97.7%) and had lower continuity of care with that physician (mean score for continuity of care 74.6 v. 77.7) than other people in Ontario. They were also less likely to see specialists. First Nations people were more likely to be admitted to hospital for ambulatory-care–sensitive conditions (2.4% v. 1.2%) and to have an emergency department visit for hypo- or hyperglycemia (1.5% v. 0.8%). Disparities were particularly marked for those living in First Nations communities.

Interpretation:

First Nations people with diabetes in Ontario had poorer access to and use of primary care than other people with diabetes in the province. These findings may help explain continued disparities in the rates of complications related to diabetes.




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Emergency department use by pregnant women in Ontario: a retrospective population-based cohort study

Background:

Peripregnancy emergency department use may be common, but data specific to health care systems like that in Canada are lacking. As prior research was limited to livebirths, omitting pregnancies ending in miscarriage or induced abortion, the current study quantified and characterized emergency department use among women in Ontario with a recognized pregnancy.

Methods:

This retrospective population-based cohort study included all recognized pregnancies among Ontario residents aged 10–55 years with an estimated date of conception between Apr. 1, 2002, and Mar. 31, 2017. We defined peripregnancy emergency department use as any emergency department visit during pregnancy or within 42 days after pregnancy. We used modified Poisson regression with a robust error variance to generate relative risks (RRs) and 95% confidence intervals (CIs) for the outcome of any peripregnancy emergency department use in association with maternal age, parity, residential income quintile, location of residence, immigrant status, antenatal care provider and number of comorbidities within 120 days before the clinical start of the pregnancy (expressed as total number of Aggregated Diagnosis Groups [ADGs] obtained with the Johns Hopkins Adjusted Clinical Group System). All RRs, except for number of comorbidities, were further adjusted for number of ADGs.

Results:

Peripregnancy emergency department use occurred in 1 075 991 (39.4%) of 2 728 236 recognized pregnancies, including 35.8% of livebirths, 47.3% of stillbirths, 73.7% of miscarriages and 84.8% of threatened abortions. A peripregnancy emergency department visit was more likely among women who were less than 25 years of age (adjusted RR 1.16, 95% CI 1.16–1.17), were nulliparous (adjusted RR 1.13, 95% CI 1.13–1.13), resided in the lowest income quintile area (adjusted RR 1.16, 95% CI 1.15–1.16) or in a rural area (adjusted RR 1.50, 95% CI 1.50–1.51), were Canadian-born (adjusted RR 1.22, 95% CI 1.22–1.23), were not seen by an obstetrician (adjusted RR 1.66, 95% CI 1.54–1.80) or had a greater number of ADGs. Emergency department use peaked in the first trimester and in the first week postpartum. Compared to women residing in urban areas, those residing in rural areas had an odds ratio (OR) of 3.44 (95% CI 3.39–3.49) for 3 or more emergency department visits. Women with 3–4 (OR 1.99, 95% CI 1.97–2.01), 5–6 (OR 3.55, 95% CI 3.49–3.61), or 7 or more (OR 7.59, 95% CI 7.39–7.78) prepregnancy comorbidities were more likely to have 3 or more peripregnancy emergency department visits than were those with 2 or fewer comorbidities.

Interpretation:

Peripregnancy emergency department use occurred in nearly 40% of pregnancies, notably in the first trimester and early in the postpartum period. Efforts are needed to streamline rapid access to ambulatory obstetric care during these peak periods, when women are susceptible to miscarriage or a complication after a livebirth.




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A novel decision aid to help plan for serious illness: a multisite randomized trial

Background:

Recent studies have shown substantial deficiencies in the quality or quantity (or both) of communication and decision-making during serious illness. We evaluated the efficacy of a novel decision support intervention, the Plan Well Guide, in increasing completion of a standard medical order form for advance medical care planning and improving decisional outcomes in nonacademic primary care settings.

Methods:

We conducted a randomized trial in 3 primary care practices in Lethbridge, Alberta in 2017–2018. We recruited "patients at high risk" referred by the primary care doctor who required establishment or review of their Goals of Care Designation (GCD). Enrolled patients were randomly allocated to receive the Plan Well Guide, delivered by a trained facilitator, or usual care. Eight to 12 weeks after the intervention, a research assistant blinded to intervention assignment contacted the patients in both groups by telephone to do a final outcome assessment. The primary outcome was completion of GCD forms; secondary outcomes included decisional conflict scores and ratings of satisfaction.

Results:

A total of 123 patients (59 women [48.0%]; mean age 73.9 yr) were enrolled, 66 in the intervention arm and 57 in the usualcare arm; 119 patients completed the trial. After the intervention, GCD completion rates in the intervention and usual-care groups were 95.3% and 90.9%, respectively (risk difference [RD] 4%, 95% confidence interval [CI] –14% to 22%), and the rate of concordance between medical orders and expressed preferences on follow-up was 78% and 66%, respectively (RD 12%, 95% CI –7% to 30%). Significantly fewer patients in the intervention group than in the usual-care group had written medical orders for intensive care unit care and cardiopulmonary resuscitation (22 [34%] v. 33 [60%], RD –26%, 95% CI –42% to –8%). Patients in the intervention group had lower decisional conflict scores than those in the usual-care group (mean 30.9 v. 43.1, adjusted mean difference –12.0, 95% CI –23.2 to –0.8). Physicians considered patients in the intervention group to have lower decisional conflict than those in the usual-care group, although not significantly so (mean score 10.4 v. 14.9, adjusted mean difference –4.7, 95% CI –9.9 to 0.4) and spent less time with the former (mean 9.7 v. 13.2 min, adjusted mean difference –3.5, 95% CI –5.5 to –1.5 min).

Interpretation:

The decision-support intervention did not increase GCD completion rates but did seem to improve some aspects of decisional quality while reducing the physician’s time to accomplish GCD decisions. Trial registration: ClinicalTrials.gov, no. NCT01297946




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Diabetes-induced eye disease among First Nations people in Ontario: a longitudinal, population-based cohort study

Background:

In Canada, First Nations populations experience a higher incidence of diabetes and diabetes-related complications than other people. Given the paucity of information on use of preventive eye examinations and the need for interventional care for severe retinopathy among First Nations people, we carried out a population-based study to compare rates of eye examinations and interventional therapies to treat vision-threatening stages of diabetic retinopathy among First Nations people and other people with diabetes in Ontario.

Methods:

In collaboration with the Chiefs of Ontario, we carried out a population-based study to identify cohorts of First Nations people and other people with diabetes in Ontario from 1995/96 to 2014/15. We used linked health administrative databases to evaluate rates of eye examination (2005/06–2014/15) and severe diabetic retinopathy treatment and compared them between the 2 populations, and between First Nations people living in and outside of First Nations communities.

Results:

We identified 23 013 First Nations people and 1 364 222 other people diagnosed with diabetes from 1995/96 to 2014/15, of whom 49.8% (95% confidence interval [CI] 48.9%–50.7%) and 53.8% (95% CI 53.7%–54.0%), respectively, received an eye examination in 2014/15. Eye examination rates were similar for First Nations people regardless of whether they lived in or outside a First Nations community. First Nations people developed severe diabetic retinopathy at a faster rate than other people (hazard ratio 1.19, 95% CI 1.02–1.38). The gap between First Nations people and other people in the proportion requiring therapy for severe diabetic retinopathy was especially prominent among younger people. There were no significant differences in rates of diabetic retinopathy treatment in First Nations people stratified by place of residence.

Interpretation:

Eye examination rates remain suboptimal among people with diabetes in Ontario and were lower among First Nations people. This is particularly concerning in light of our other findings showing an increased risk of requiring treatment for advanced diabetic retinopathy and the accelerated rate of diabetic retinopathy progression among First Nations people with diabetes.




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Lactic Acidosis after Drinking Mysterious Beverage

ethylene glycol poisoninglactateanalytical interference




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Importation of Extensively Drug-Resistant Salmonella enterica Serovar Typhi Cases in Ontario, Canada [Susceptibility]

A strain of extensively drug-resistant (XDR) Salmonella enterica serovar Typhi has caused a large ongoing outbreak in Pakistan since 2016. In Ontario, Canada, 10 cases of mainly bloodstream infections (n = 9) were identified in patients who traveled to Pakistan. Whole-genome sequencing showed that Canadian cases were genetically related to the Pakistan outbreak strain. The appearance of XDR typhoid cases in Ontario prompted a provincial wide alert to physicians to recommend treatment with carbapenems or azithromycin in suspected typhoid cases with travel history to Pakistan.




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Facial Nerve Arterial Arcade Supply in Dural Arteriovenous Fistulas: Anatomy and Treatment Strategies [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Endovascular treatment of petrous dural AVFs may carry a risk of iatrogenic facial nerve palsy if the facial nerve arterial arcade, an anastomotic arterial arch that supplies the geniculate ganglion, is not respected or recognized. Our purpose was to demonstrate that the use of a treatment strategy algorithm incorporating detailed angiographic anatomic assessment allows identification of the facial nerve arterial arcade and therefore safe endovascular treatment.

MATERIALS AND METHODS:

This was a retrospective cohort study of consecutive petrous dural AVF cases managed at Toronto Western Hospital between 2006 and 2018. Our standard of care consists of detailed angiographic assessment followed by multidisciplinary discussion on management. Arterial supply, primary and secondary treatments undertaken, angiographic outcomes, and clinical outcomes were assessed by 2 independent fellowship-trained interventional neuroradiologists.

RESULTS:

Fifteen patients had 15 fistulas localized over the petrous temporal bone. Fistulas in all 15 patients had direct cortical venous drainage and received at least partial supply from the facial nerve arterial arcade. Following multidisciplinary evaluation, treatment was performed by endovascular embolization in 8 patients (53%) and microsurgical disconnection in 7 patients (47%). All patients had long-term angiographic cure, and none developed iatrogenic facial nerve palsy.

CONCLUSIONS:

By means of our treatment strategy based on detailed angiographic assessment and multidisciplinary discussion, approximately half of our patients with petrous AVFs were cured by endovascular treatment, half were cured by an operation, and all had preserved facial nerve function.




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Treatment Outcomes of Endovascular Embolization Only in Patients with Unruptured Brain Arteriovenous Malformations: A Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries.

MATERIALS AND METHODS:

We analyzed the rates and severity of stroke and death in patients who underwent embolization only. Events were identified through in-person neurologic follow-up visits performed at 6-month intervals during the first 2 years and annually, with telephone contact every 6 months thereafter. All event-related data were reviewed by independent adjudicators.

RESULTS:

Among 30 patients who had embolization planned, 26 underwent embolization only. A total of 13 stroke events were reported in the follow-up period among 26 subjects (ischemic, hemorrhagic, or both in 4, 7, and 2 subjects, respectively). The adverse event occurred after the first embolization in 11 of 13 patients. One patient had a major motor deficit, and 2 patients developed major visual field deficits. One event was fatal. The modified Rankin Scale score was 0–2 at last follow-up in 11 of the 12 stroke survivors. Estimated stroke-free survival was 46% at 12 months.

CONCLUSIONS:

Although the rates of stroke and/or death were high in patients treated with embolization only in ARUBA, the rates of favorable outcomes following stroke were high during follow-up.




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Complications of Endovascular Treatments for Brain Arteriovenous Malformations: A Nationwide Surveillance [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Embolization is widely performed to treat brain arteriovenous malformations, but little has been reported on factors contributing to complications. We retrospectively reviewed a nationwide surveillance to identify risk factors contributing to complications and short-term clinical outcomes in the endovascular treatment of brain arteriovenous malformations.

MATERIALS AND METHODS:

Data for endovascular treatment of brain arteriovenous malformations were extracted from the Japanese nationwide surveillance. Patient characteristics, brain arteriovenous malformation features, procedures, angiographic results, complications, and clinical outcomes at 30 days postprocedure were analyzed.

RESULTS:

A total of 1042 endovascular procedures (788 patients; mean, 1.43 ± 0.85 procedures per patient) performed in 111 institutions from 2010 to 2014 were reviewed. Liquid materials were used in 976 procedures (93.7%): to perform presurgical embolization in 638 procedures (61.2%), preradiosurgical embolization in 160 (15.4%), and as sole endovascular treatment in 231 (22.2%). Complete or near-complete obliteration of brain arteriovenous malformations was obtained in 386 procedures (37.0%). Procedure-related complications occurred in 136 procedures (13.1%), including hemorrhagic complications in 59 (5.7%) and ischemic complications in 57 (5.5%). Univariate analysis identified deep venous drainage, associated aneurysms, infratentorial location, and preradiosurgical embolization as statistically significant risk factors for complications. Multivariate analysis showed that embolization of brain arteriovenous malformations in the infratentorial location was significantly associated with complications. Patients with complications due to endovascular procedures had worse clinical outcomes 30 days after the procedures than those without complications.

CONCLUSIONS:

Complications arising after endovascular treatment of brain arteriovenous malformations are not negligible even though they may play a role in adjunctive therapy, especially in the management of infratentorial brain arteriovenous malformations.




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The FRED for Cerebral Aneurysms of the Posterior Circulation: A Subgroup Analysis of the EuFRED Registry [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Flow diversion for the posterior circulation remains a promising treatment option for selected posterior circulation aneurysms. The Flow-Redirection Intraluminal Device (FRED) system has not been previously assessed in a large cohort of patients with posterior circulation aneurysms. The purpose of the present study was to assess safety and efficacy of FRED in this location.

MATERIALS AND METHODS:

Consecutive patients with posterior circulation aneurysms treated at 8 centers participating in the European FRED study (EuFRED) between April 2012 and January 2019 were retrospectively reviewed. Complication and radiographic and functional outcomes were evaluated.

RESULTS:

Eighty-four patients (median age, 54 years) with 84 posterior circulation aneurysms were treated with the FRED. A total of 25 aneurysms (29.8%) had previously ruptured, even though most aneurysms were diagnosed incidentally (45.2%). The intradural vertebral artery was the most common location (50%), and saccular, the most common morphology (40.5%). The median size was 7 mm. There were 8 (9.5%) symptomatic thromboembolic and no hemorrhagic complications. Thromboembolic complications occurred mostly (90.9%) in nonsaccular aneurysms. On last follow-up at a median of 24 months, 78.2% of aneurysms were completely occluded. Functional outcome at a median of 27 months was favorable in 94% of patients. All mortalities occurred in patients with acute subarachnoid hemorrhage and its sequelae.

CONCLUSIONS:

The largest cohort of posterior circulation aneurysms treated with the FRED to date demonstrated favorable safety and efficacy profiles of the device for this indication. Treatment in the setting of acute subarachnoid hemorrhage was strongly related to mortality, regardless of whether procedural complications occurred.




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Glasgow Coma Scale on Presentation Predicts Outcome in Endovascular Treatment for Acute Posterior Large-Vessel Occlusion [INTERVENTIONAL]

SUMMARY:

Use of mechanical thrombectomy for stroke has increased since the publication of trials describing outcome improvement when used in the anterior circulation. These results, however, cannot be directly translated to the posterior circulation. While a high NIHSS score has demonstrated an association with poor outcomes in posterior stroke, the NIHSS is weighted toward hemispheric disease, and complex scores potentially delay definitive imaging diagnosis. We performed a retrospective analysis to ascertain whether any rapidly obtainable demographic or clinical and imaging data have a correlation with patient outcome postthrombectomy. Seventy-three cases were audited between September 2010 and October 2017. Presenting with a Glasgow Coma Scale score of >13 meant that the odds of reaching the primary end point of functional independence (defined as a 90-day modified Rankin Scale score of 0–2) were 5.70 times greater; similarly, presenting with a posterior circulation ASPECTS of >9 resulted in the odds of reaching the primary end point being 4.03 times greater. Older age correlated to a lower odds of independence (0.97, p = .04).




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CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error.

MATERIALS AND METHODS:

Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation.

RESULTS:

The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions.

CONCLUSIONS:

Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome.




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For sale apartment, Xi Riverview Palace 3BRs, 185m2 luxuriously designed.

Apartment for sale in Xi Riverview Palace, Xi, 103-xx.02, with an area of 185m2, architecture including 1 living room, 3 bedrooms, 3 bathrooms, dining room, kitchen, balcony.The apartment has been fully furnished with high-class furniture on the middle floor, tower 103, nice corn...




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City Garden apartment for sale with 2 bedrooms, 108m2, fully furnished luxurious

City Garden apartment for sale areas 108m2, located on the 19th-floor Phase 2 Promenade designed with 2 bedrooms and 2 bathrooms, is an ideal solution for families who want to work and study. near the center of District 1. The apartment is designed to be open modern, natural ligh...




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Palm Residence villa/townhouse for rent, 3 bedrooms, 2 floors, interior

Palm Residence villa/townhouse for rent, 3 bedrooms, beautifully arranged with luxurious design, and fully furnished with high-quality furniture, details: - Construction area 6x17m - Building 1 ground floor + 2 floors, each floor has a large state. - Including 3 bedrooms, 1 livin...




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Luxurious apartment at Midtown PMH District 7 for lease, 2BRs 2WCs, nice view. Tel: 0906.647.689

Design: 2 bedrooms & 2 WCs Area: 91 sqm The apartment is suitable for a person or couple to live. Price: 25,000,000vnd (~1100usd)Furniture: fully furnished, new, modern, luxurious- Location: at Nguyen Luong Bang street- Public amenities: SSIS school, Dinh Thien Ly school, Crescen...




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Why Interior Design Is Essential When Listing Your Home

The decision to list your home for resale is a big one. No doubt it came about after much thought, weighing pros and cons, and series of long discussions. However, once you decide to put your home on the market, get ready for the next big discussion: interior design.




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Công ty Thi công và Thiết kế nội thất Cogniplus Interiors




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Mysterious drone swarms flying at night are baffling US authorities

Swarms of drones have been seen flying over Colorado, Nebraska and Wyoming in the past few weeks, but no one has claimed responsibility




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Network Effect review: A glorious thought-provoking Murderbot tale

Martha Wells's action-packed novel Network Effect puts you inside the head of a Murderbot. It raises fascinating questions you will think about for a long time, says Sally Adee




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Somebody Is Furiously Uploading '90s Windows Desktop Themes to the Internet Archive

Please, I implore you: jump on this bandwagon.




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Mysterious radio signal from space seems to have suddenly vanished

Strange blasts from space called fast radio bursts continue to puzzle astronomers with their odd behaviour, as they seem to come from a variety of galaxies




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Mysteriously bright supernova may have smashed up a huge gas cloud

A strange supernova that’s 100 times brighter than it should be has long been a mystery, but it may be explained by the explosion slamming into a cloud of gas




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We’ve finally spotted a pattern in mysterious radio blasts from space

Strange, powerful blasts of radio waves from space called fast radio bursts sometimes flash repeatedly, but never with any discernible pattern – until now




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Mysterious crater on Mars could be a good place to look for life

Could life on Mars have hidden from extreme weather in a cavern on the Pavonis Mons volcano? This 2011 orbiter image of an otherworldly crater has NASA asking just that




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Mysterious ‘Planet Nine’ on the solar system’s edge may not be real

Strange orbits of distant space rocks have been used to infer that the solar system has an unseen ninth planet, but those orbits may be less strange than we thought, meaning there is no need for a new planet




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RoMeLa's Newest Robot Is a Curiously Symmetrical Dynamic Quadruped

With four legs but no back or front, ALPHRED 2 can run, jump, and punch through boards in any direction




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Second Extinction reveal: Xbox Series X game gives us serious Turok vibes



During Inside Xbox's special stream today, Systemic Reaction gave us our first taste of next-gen dino hunting glory




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RPGCast – Episode 310: “Mario Will Never Run Over A Hooker”

Another E3 comes to pass and we try to help you digest all of what happened and what it means to RPGamers. Chris and Anna...




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Why are period dramas so white? - video

Have you ever noticed that in film and on TV, period dramas tend to have almost entirely white casts? It’s almost as if, at least in film and TV land, black people do not feature in British history at all. The Guardian’s Josh Toussaint-Strauss finds out how accurate costume dramas are in terms of racial diversity, and looks into the reasons why period dramas might get whitewashed

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