Magnetic to the Core - Communicating paleomagnetism with hands-on activities

&amp;lt;p&amp;gt;With geoscience student numbers dwindling, there is a strong need for Earth scientists to enthuse a new generation of prospective students. We created several hands-on activities to introduce members of the general public of all ages to the fundamentals of, and current research in paleomagnetism. We developed these activities at different outreach events in the UK, such as a family science fair (at the Ness Gardens) and a holiday workshop (at the Victoria Gallery &amp;amp; Museum). In the first week of July, 2019, we contributed to the Royal Society Summer Science Exhibition, a science exhibition in London with almost 14,000 visitors of the general public, including many school groups. Visitors came from all educational backgrounds. We had a stand that consisted of 4 hands-on experiments, and an informative backdrop. The four activities allowed visitors to explore the range of tasks that a paleomagnetist does, from the collection and measurement of samples to understanding the behaviour of the Earth&amp;amp;#8217;s magnetic field. Visitors could measure real lavas from Iceland on a custom-built magnetometer that was designed specifically for outreach, and determine the magnetic polarity of the samples. We also created an information booklet with &amp;amp;#8217;10 things you might not know about Earth&amp;amp;#8217;s magnetic field&amp;amp;#8217;, which is openly available under a CC-license. To measure the impact of our stand on visitors&amp;amp;#8217; knowledge of paleomagnetism, we designed a quiz. Our results show that especially for school kids, our stand had a significant impact on their knowledge of the Earth&amp;amp;#8217;s magnetic field. In this contribution we share lessons learned through designing the &amp;amp;#8216;Magnetic to the Core&amp;amp;#8217; stand, hands-on activities and evaluations.&amp;lt;/p&amp;gt; </jats:p

Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice

Total body upstream stimulatory factor 1 (USF1) deficiency in mice is associated with brown adipose tissue activation and a marked protection against the development of obesity and atherosclerotic lesions. Functional expression of USF1 has also been detected in monocytes and monocyte-derived macrophages. In the current study we therefore tested whether selective hematopoietic USF1 deficiency can also beneficially impact the development of atherosclerosis. For this purpose, LDL receptor knockout mice were transplanted with bone marrow from USF1 knockout mice or their wild-type littermate controls and subsequently fed a Western-type diet for 20 weeks to stimulate atherosclerotic lesion development. Strikingly, absence of USF1 function in bone marrow-derived cells was associated with exacerbated blood leukocyte (+ 100%; P < 0.01) and peritoneal leukocyte (+ 50%; P < 0.05) lipid loading and an increased atherosclerosis susceptibility (+ 31%; P < 0.05). These effects could be attributed to aggravated hyperlipidemia, i.e. higher plasma free cholesterol (+ 33%; P < 0.001) and cholesteryl esters (+ 39%; P < 0.001), and the development of hepatosteatosis. In conclusion, we have shown that hematopoietic USF1 deficiency is associated with an increased atherosclerosis susceptibility in LDL receptor knockout mice. These findings argue against a contribution of macrophage-specific USF1 deficiency to the previously described beneficial effect of total body USF1 deficiency on atherosclerosis susceptibility in mice.Peer reviewe

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study) : A multicentre, randomised, double-blinded, placebo-controlled trial

Funding: MdB, LV, TN, BM, MO and CdG received funding from ZonMw, The Dutch Organisation for Health Research and Development (grant number 836041006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test_2-sided). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Identification of a second major tumor-specific antigen recognized by CTLs on mouse mastocytoma P815

Murine mastocytoma P815 induces CTL responses against at least four distinct Ags (AB, C, D, and E), Recent studies have shown that the main component of the CTL response against the P815 tumor is targeted against Ags P815AB and P815E, The gene PIA has been well characterized, It encodes the P815AB Ag in the form of a nonameric peptide containing two epitopes, P815A and P815B, which are recognized by different CTLs. Here, we report the identification of the P815E Ag, Using a cDNA library derived from tumor P815, we identified the gene coding for P815E. We also characterized the antigenic peptide that anti-P815E CTLs recognize on the MHC class I molecule H-2K(d), The P815E Ag results from a mutation within an ubiquitously expressed gene encoding methionine sulfoxide reductase, an enzyme that is believed to be important in the protection of proteins against the by-products of aerobic metabolism Surprisingly, immunizing mice i.p. with syngeneic tumor cells (L1210) that were constructed to express B7-1 and P815E did not induce resistance against live P815, even though a strong anti-P815E CTL response was observed with splenocytes from immunized animals

Magnetic to the Core – communicating palaeomagnetism with hands-on activities

Abstract. Palaeomagnetism is a relatively unknown part of Earth sciences that is not well integrated into the school curriculum in the UK. Throughout recent years, there has been a decline in the number of Earth science students in the UK. In 2018 and 2019, we developed outreach activities and resources to introduce the scientifically engaged general public to palaeomagnetism and raise awareness of how geomagnetism affects society today, thus putting palaeomagnetism, and Earth sciences, in the spotlight. We tested our ideas at local events that were visited mostly by families with small children, with tens to hundreds of participants. Our project culminated in the Magnetic to the Core stand at the Royal Society Summer Science Exhibition in 2019, which is visited by members of the general public, students and teachers, scientists, policymakers and the media. At this event, we communicated the fundamentals of palaeomagnetism through hands-on activities and presented our recent research advances in a fun and family- friendly way. To test the impact of our exhibit on knowledge of palaeomagnetism and Earth's magnetic field on visitors, we designed an interactive quiz and collected results from 382 participants over 8 d. The results show a significant increase in median quiz score of 22.2 % between those who had not yet visited the stand and those who had visited for more than 10 min. The results from school-aged respondents alone show a larger increase in the median score of 33.5 % between those who had not yet visited and those who had spent more than 10 min at the stand. These findings demonstrate that this outreach event was successful in impacting visitors' learning. We hope our Magnetic to the Core project can serve as an inspiration for other Earth science laboratories looking to engage a wide audience and measure the success and impact of their outreach activities. </jats:p

Lifetime Observation of Cognition and Physiological Parameters in Male Mice

Kahnau P, Günther A, Boon MN, et al. Lifetime Observation of Cognition and Physiological Parameters in Male Mice. Frontiers in Behavioral Neuroscience . 2021;15: 709775.Laboratory mice are predominantly used for one experiment only, i.e., new mice are ordered or bred for every new experiment. Moreover, most experiments use relatively young mice in the range of late adolescence to early adulthood. As a consequence, little is known about the day-to-day life of adult and aged laboratory mice. Here we present a long-term data set with three consecutive phases conducted with the same male mice over their lifetime in order to shed light on possible long-term effects of repeated cognitive stimulation. One third of the animals was trained by a variety of learning tasks conducted up to an age of 606 days. The mice were housed in four cages with 12 animals per cage; only four mice per cage had to repeatedly solve cognitive tasks for getting access to water using the IntelliCage system. In addition, these learner mice were tested in standard cognitive tests outside their home-cage. The other eight mice served as two control groups living in the same environment but without having to solve tasks for getting access to water. One control group was additionally placed on the test set-ups without having to learn the tasks. Next to the cognitive tasks, we took physiological measures (body mass, resting metabolic rate) and tested for dominance behavior, and attractivity in a female choice experiment. Overall, the mice were under surveillance until they died a natural death, providing a unique data set over the course of virtually their entire lives. Our data showed treatment differences during the first phase of our lifetime data set. Young learner mice showed a higher activity, less growth and resting metabolic rate, and were less attractive for female mice. These effects, however, were not preserved over the long-term. We also did not find differences in dominance or effects on longevity. However, we generated a unique and valuable set of long-term behavioral and physiological data from a single group of male mice and note that our long-term data contribute to a better understanding of the behavioral and physiological processes in male C57Bl/6J mice.</p