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European stockpiles, better coordination: how would Josep Borrell federalise future health policy?

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Gov't to Stockpile 100 Million Masks

The government will stockpile 100 million face masks to prepare for a second wave of coronavirus but will also send them to about 70 countries in need."We've already allocated the budget necessary to stock up 100 million masks," Minister of Food and Drug Safety Lee Eui-kyung said Thursday. "Some 70 ...




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ADB Project in Henan, PRC to Pilot Integrated Approach to River Restoration

ADB today approved a $200 million loan to pilot an integrated approach to river restoration in one of the tributaries of the Yangtze River Basin in the PRC. The project in...




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MPLAB XC Compiler Functional Safety Manual

MPLAB XC Compiler Functional Safety Manual




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Baffling maths riddle that looks like a pile of worms almost solved

The Collatz conjecture is simple to state but has baffled mathematicians for 80 years. But a man dubbed the 'Mozart of maths' has now almost proved it




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Millions of hairy tarantula skins could be used to mop up oil spills

The dense, bristly hairs on the skins shed by tarantulas when they moult are naturally efficient sponges and could be used to soak up ocean oil spills




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Travel misery as Lufthansa pilots strike again

German flagship carrier Lufthansa cancels nearly half of scheduled services as pilots continue two-day strike, their ninth walkout this year




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Connectivity for pilots, passengers on display at Paris Airshow

Ground-breaking aviation technology is on display at this week's Paris Airshow. Jim Drury went to take a look.




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H&M's sales tumble as stockpiles grow

H&M, the world's second-biggest fashion retailer, said local currency sales have tumbled 57% since the start of March compared with a year ago. Ciara Lee reports




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Epilepsy Drug Linked to Low IQ

Title: Epilepsy Drug Linked to Low IQ
Category: Health News
Created: 5/4/2007 12:00:00 AM
Last Editorial Review: 5/4/2007 12:00:00 AM




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FDA Approves 'Morning-After' Pill Without a Prescription

Title: FDA Approves 'Morning-After' Pill Without a Prescription
Category: Health News
Created: 4/30/2013 8:36:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM




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White House to Challenge Ruling on Unlimited Access to 'Morning-After' Pill

Title: White House to Challenge Ruling on Unlimited Access to 'Morning-After' Pill
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM




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Implanted Device May Predict Epilepsy Seizures, Study Suggests

Title: Implanted Device May Predict Epilepsy Seizures, Study Suggests
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM




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Low-Dose 'Pill' Linked to Pain During Orgasm, Study Finds

Title: Low-Dose 'Pill' Linked to Pain During Orgasm, Study Finds
Category: Health News
Created: 5/3/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM




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Got Unwanted Pills? Drug Take-Back Day Is April 30

Title: Got Unwanted Pills? Drug Take-Back Day Is April 30
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




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Seizure Control Eases Life for Young Adults With Epilepsy

Title: Seizure Control Eases Life for Young Adults With Epilepsy
Category: Health News
Created: 4/28/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM




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Sleeping Pills Boost Danger of Falls, Fractures in Older Users

Title: Sleeping Pills Boost Danger of Falls, Fractures in Older Users
Category: Health News
Created: 5/2/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM




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Study Debunks Idea That Epilepsy Can Hamper Fertility

Title: Study Debunks Idea That Epilepsy Can Hamper Fertility
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions

Title: Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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More Evidence CBD Can Help Ease a Form of Epilepsy in Kids

Title: More Evidence CBD Can Help Ease a Form of Epilepsy in Kids
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM




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Pilates May Be Good Medicine for High Blood Pressure

Title: Pilates May Be Good Medicine for High Blood Pressure
Category: Health News
Created: 4/6/2020 12:00:00 AM
Last Editorial Review: 4/7/2020 12:00:00 AM




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Dupixent (dupilumab)

Title: Dupixent (dupilumab)
Category: Medications
Created: 2/26/2020 12:00:00 AM
Last Editorial Review: 2/26/2020 12:00:00 AM




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Birth Control Pill vs. Shot (Depo-Provera): Similarities and Differences

Title: Birth Control Pill vs. Shot (Depo-Provera): Similarities and Differences
Category: Diseases and Conditions
Created: 6/15/2017 12:00:00 AM
Last Editorial Review: 4/13/2020 12:00:00 AM




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Birth Control Pills (List of Oral Contraceptives and Side Effects)

Title: Birth Control Pills (List of Oral Contraceptives and Side Effects)
Category: Medications
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 1/30/2020 12:00:00 AM




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Aftermath of Seizures Troubling for Those With Epilepsy

Title: Aftermath of Seizures Troubling for Those With Epilepsy
Category: Health News
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/20/2020 12:00:00 AM




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The Additive Effects of Cell Phone Use and Dental Hygiene Practice on Finger Muscle Strength: A Pilot Study

Purpose: The purpose of this study was to determine strength of muscles involved with instrumentation (scaling) by dental hygienists and the additive effects of cellular (mobile) phone usage, as indicated by measurements of muscular force generation.Methods: A convenience sample of licensed dental hygienists currently in clinical practice (n=16) and an equal number of individuals not currently using devices/tools repetitively for work (n=16), agreed to participate in this pilot study. All participants completed a modified cell phone usage questionnaire to determine their use pattern and frequency. Upon completion of the questionnaire, participants' force production in six muscle groups was measured using a hand-held dynamometer. Descriptive statistics were used to analyze the data.Results: A total of 16 licensed dental hygienists (n=16) and 16 participants with no history of using tools/devices repetitively for work (n=16), comprised the experimental and control groups, repectively. The control group generated greater muscle force than the experimental group for the abductor pollicis longus (p=0.045). Significant differences were identified when comparing the low mobile phone users in the experimental group to the control group for the flexor pollicis brevis (p=0.031), abductor pollicis longus (p=0.031), and flexor digitorum (p=0.006), with the control group demonstrating higher muscle force. Years in clinical practice and mobile phone use was shown to have a significant effect on muscular force generation for the flexor pollicis brevis (F=3.645, df=3, p=0.020) and flexor digitorum (F=3.560, df=3, p=0.022); subjects who practiced dental hygiene the longest produced the least amount of muscle force.Conclusion: Results from this pilot study indicate there are no significant additive effects of cell phone use and dental hygiene practice on finger muscles used for instrumentation. However, results indicate that dental hygiene practice demonstrated significant effects on muscular strength as compared to individuals who do not use tools/devices repetitively for work. The small sample size may have impacted results and the study should be repeated with a larger sample.




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GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells [Images In Lipid Research]




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Species-Specific Recognition of Sulfolobales Mediated by UV-Inducible Pili and S-Layer Glycosylation Patterns

ABSTRACT

The UV-inducible pili system of Sulfolobales (Ups) mediates the formation of species-specific cellular aggregates. Within these aggregates, cells exchange DNA to repair DNA double-strand breaks via homologous recombination. Substitution of the Sulfolobus acidocaldarius pilin subunits UpsA and UpsB with their homologs from Sulfolobus tokodaii showed that these subunits facilitate species-specific aggregation. A region of low conservation within the UpsA homologs is primarily important for this specificity. Aggregation assays in the presence of different sugars showed the importance of N-glycosylation in the recognition process. In addition, the N-glycan decorating the S-layer of S. tokodaii is different from the one of S. acidocaldarius. Therefore, each Sulfolobus species seems to have developed a unique UpsA binding pocket and unique N-glycan composition to ensure aggregation and, consequently, also DNA exchange with cells from only the same species, which is essential for DNA repair by homologous recombination.

IMPORTANCE Type IV pili can be found on the cell surface of many archaea and bacteria where they play important roles in different processes. The UV-inducible pili system of Sulfolobales (Ups) pili from the crenarchaeal Sulfolobales species are essential in establishing species-specific mating partners, thereby assisting in genome stability. With this work, we show that different Sulfolobus species have specific regions in their Ups pili subunits, which allow them to interact only with cells from the same species. Additionally, different Sulfolobus species have unique surface-layer N-glycosylation patterns. We propose that the unique features of each species allow the recognition of specific mating partners. This knowledge for the first time gives insights into the molecular basis of archaeal self-recognition.




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Polygenic risk scores of several subtypes of epilepsies in a founder population

Objective

Polygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.

Methods

We first replicated previous single associations using 373 unrelated patients. We then calculated PRSs in the same French Canadian patients with epilepsy divided into 7 epilepsy subtypes and population-based controls. We fitted a logistic mixed model to calculate the variance explained by the PRS using pseudo-R2 statistics.

Results

We show that the PRS explains more of the variance in idiopathic generalized epilepsy than in patients with nonacquired focal epilepsy. We also demonstrate that the variance explained is different within each epilepsy subtype.

Conclusions

Globally, we support the notion that PRSs provide a reliable measure to rightfully estimate the contribution of genetic factors to the pathophysiologic mechanism of epilepsies, but further studies are needed on PRSs before they can be used clinically.




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Optimizing Human Papillomavirus Immunization: The Role of Centralized Reminder and Recall Systems




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The Transcriptional Cofactor VGLL1 Drives Transcription of Human Papillomavirus Early Genes via TEAD1 [Genome Replication and Regulation of Viral Gene Expression]

The TEAD family of transcription factors requires associating cofactors to induce gene expression. TEAD1 is known to activate the early promoter of human papillomavirus (HPV), but the precise mechanisms of TEAD1-mediated transactivation of the HPV promoter, including its relevant cofactors, remain unexplored. Here, we reveal that VGLL1, a TEAD-interacting cofactor, contributes to HPV early gene expression. Knockdown of VGLL1 and/or TEAD1 led to a decrease in viral early gene expression in human cervical keratinocytes and cervical cancer cell lines. We identified 11 TEAD1 target sites in the HPV16 long control region (LCR) by in vitro DNA pulldown assays; 8 of these sites contributed to the transcriptional activation of the early promoter in luciferase reporter assays. VGLL1 bound to the HPV16 LCR via its interaction with TEAD1 both in vitro and in vivo. Furthermore, introducing HPV16 and HPV18 whole genomes into primary human keratinocytes led to increased levels of VGLL1, due in part to the upregulation of TEADs. These results suggest that multiple VGLL1/TEAD1 complexes are recruited to the LCR to support the efficient transcription of HPV early genes.

IMPORTANCE Although a number of transcription factors have been reported to be involved in HPV gene expression, little is known about the cofactors that support HPV transcription. In this study, we demonstrate that the transcriptional cofactor VGLL1 plays a prominent role in HPV early gene expression, dependent on its association with the transcription factor TEAD1. Whereas TEAD1 is ubiquitously expressed in a variety of tissues, VGLL1 displays tissue-specific expression and is implicated in the development and differentiation of epithelial lineage tissues, where HPV gene expression occurs. Our results suggest that VGLL1 may contribute to the epithelial specificity of HPV gene expression, providing new insights into the mechanisms that regulate HPV infection. Further, VGLL1 is also critical for the growth of cervical cancer cells and may represent a novel therapeutic target for HPV-associated cancers.




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Correction for Pilat et al., Treg-mediated prolonged survival of skin allografts without immunosuppression [Corrections]

IMMUNOLOGY AND INFLAMMATION Correction for “Treg-mediated prolonged survival of skin allografts without immunosuppression,” by Nina Pilat, Mario Wiletel, Anna M. Weijler, Romy Steiner, Benedikt Mahr, Joanna Warren, Theresa M. Corpuz, Thomas Wekerle, Kylie E. Webster, and Jonathan Sprent, which was first published June 13, 2019; 10.1073/pnas.1903165116 (Proc. Natl. Acad. Sci....




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Diving apart together: call propagation in diving long-finned pilot whales [RESEARCH ARTICLE]

Annebelle C. M. Kok, Lisette van Kolfshoten, James A. Campbell, Alexander M. von Benda-Beckmann, Patrick J. O. Miller, Hans Slabbekoorn, and Fleur Visser

Group-living animals must communicate to stay in contact. In long-finned pilot whales, there is a trade-off between the benefits of foraging individually at depth and the formation of tight social groups at the surface. Using theoretical modelling and empirical data of tagged pairs within a group, we examined the potential of pilot whale social calls to reach dispersed group-members during foraging periods. Both theoretical predictions and empirical data of tag pairs showed a potential for communication between diving and non-diving group members over separation distances up to at least 385 m (empirical) and 1800 m (theoretical). These distances are at or exceeding pilot whale dive depths recorded across populations. Call characteristics and environmental characteristics were analysed to investigate determinants of call detectability. Longer calls with a higher sound pressure level (SPL) that were received in a quieter environment were more often detected than their shorter, lower SPL counterparts within a noisier environment. In a noisier environment, calls were louder and had a lower peak frequency, indicating mechanisms for coping with varying conditions. However, the vulnerability of pilot whales to anthropogenic noise is still of concern as the ability to cope with increasing background noise may be limited. Our study shows that combining propagation modelling and actual tag recordings provides new insights into the communicative potential for social calls in orientation and reunion with group members for deep-diving pilot whales.




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The major subunit of widespread competence pili exhibits a novel and conserved type IV pilin fold [Protein Structure and Folding]

Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species.




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Pilot Study of Return of Genetic Results to Patients in Adult Nephrology

Background and objectives

Actionable genetic findings have implications for care of patients with kidney disease, and genetic testing is an emerging tool in nephrology practice. However, there are scarce data regarding best practices for return of results and clinical application of actionable genetic findings for kidney patients.

Design, setting, participants, & measurements

We developed a return of results workflow in collaborations with clinicians for the retrospective recontact of adult nephrology patients who had been recruited into a biobank research study for exome sequencing and were identified to have medically actionable genetic findings.

Results

Using this workflow, we attempted to recontact a diverse pilot cohort of 104 nephrology research participants with actionable genetic findings, encompassing 34 different monogenic etiologies of nephropathy and five single-gene disorders recommended by the American College of Medical Genetics and Genomics for return as medically actionable secondary findings. We successfully recontacted 64 (62%) participants and returned results to 41 (39%) individuals. In each case, the genetic diagnosis had meaningful implications for the patients’ nephrology care. Through implementation efforts and qualitative interviews with providers, we identified over 20 key challenges associated with returning results to study participants, and found that physician knowledge gaps in genomics was a recurrent theme. We iteratively addressed these challenges to yield an optimized workflow, which included standardized consultation notes with tailored management recommendations, monthly educational conferences on core topics in genomics, and a curated list of expert clinicians for patients requiring extranephrologic referrals.

Conclusions

Developing the infrastructure to support return of genetic results in nephrology was resource-intensive, but presented potential opportunities for improving patient care.

Podcast

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_16_12481019.mp3




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Association of Anti-TNF with Decreased Survival in Steroid Refractory Ipilimumab and Anti-PD1-Treated Patients in the Dutch Melanoma Treatment Registry

Purpose:

Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.

Experimental Design:

Using data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients.

Results:

A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade ≥3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity [hazard ratio (HRadj) = 0.77; 95% confidence interval (CI), 0.63–0.93]. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF ± steroids for steroid-refractory toxicity compared with patients who were managed with steroids only (HRadj = 1.61; 95% CI, 1.03–2.51), with a median OS of 17 and 27 months, respectively.

Conclusions:

Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti-TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.

See related commentary by Weber and Postow, p. 2085




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Radiomics Study of Thyroid Ultrasound for Predicting BRAF Mutation in Papillary Thyroid Carcinoma: Preliminary Results [FUNCTIONAL]

BACKGROUND AND PURPOSE:

It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer.

MATERIALS AND METHODS:

The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013. BRAF mutation was positive in 48 nodules and negative in 48 nodules. For analysis, ROIs from the nodules were demarcated manually on both longitudinal and transverse sonographic images. We extracted a total of 86 radiomics features derived from histogram parameters, gray-level co-occurrence matrix, intensity size zone matrix, and shape features. These features were used to build 3 different classifier models, including logistic regression, support vector machine, and random forest using 5-fold cross-validation. The performance including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, of the different models was evaluated.

RESULTS:

The incidence of high-suspicion nodules diagnosed on ultrasound was higher in the BRAF mutation–positive group than in the mutation–negative group (P = .004). The radiomics approach demonstrated that all classification models showed moderate performance for predicting the presence of BRAF mutation in papillary thyroid cancers with an area under the curve value of 0.651, accuracy of 64.3%, sensitivity of 66.8%, and specificity of 61.8%, on average, for the 3 models.

CONCLUSIONS:

Radiomics study using thyroid sonography is limited in predicting the BRAF mutation status of papillary thyroid carcinoma. Further studies will be needed to validate our results using various diagnostic methods.




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Russian Humanoid Robot to Pilot Soyuz Capsule to ISS This Week

Skybot F-850 will spend a week on the ISS charming astronauts with its sense of humor




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Elastec scoops X prize for oil-spill clean-up

Skimming system tripled previous best effort at oil collection.




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Journeyman pilloried, superstar adored

Go ahead and applaud taking down a group of boorish hockey “bros” for their despicable behaviour. But you might want to hold off on a full-fledged victory lap. Brendan Leipsic said ...




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'I Was A Feminist Activist In The '70s When The Pill Was Legalized For All Women'

It has been 60 years since the FDA first approved the birth control pill on May 9, 1960. It emerged as an essential pillar of women's ability to have good quality of life.




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Our pupils move to the rhythm of the environment

Regular processes in the environment improve our eyesight.




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Come on, you can do it: Rugby stars cheer pupils at London school during coronavirus lockdown

Rugby stars have recorded inspirational messages for boys at a London school to help motivate them through the coronavirus lockdown.




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School closures leave poorest pupils at huge exams disadvantage, warns Grenfell head

Poorer children taking GCSEs and A-levels next year face an "impossible situation" because they have missed so much face-to-face teaching, a leading London headmaster has warned.




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Businesses offering lockdown pupils virtual work experience

Businesses are giving schoolchildren virtual work experience placements to prevent them from missing out on opportunities during the crisis.




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Pentagon releases 'UFO video footage' taken by US Navy pilots

Previously leaked videos of US Navy pilots encountering "unexplained aerial phenomena" have been released by the Pentagon.




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Key PPE items not in Government's pandemic stockpile when coronavirus hit UK, investigation finds

Key items of protective equipment were not included in the government's pandemic stockpile when coronavirus hit the UK, an investigation has found.




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Pilot sparks complaints for breaching lockdown after spelling 'NHS' with flightpath

A pilot has sparked complaints over an alleged breach of lockdown rules after spelling out "NHS" using his plane's flightpath.




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Pilot flouts lockdown to write 'f*** Covid-19' with flightpath




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British Airways to lay off a quarter of its pilots amid plans to make 12,000 workers redundant

More than 1,000 British Airways pilots are set to lose their jobs as part of major redundancy plans announced by the airline, it is reported.