Dark Matter: Introduction

This short review was prepared as an introduction to the Royal Society's 'Dark Matter' conference. It addresses the embarrassing fact that 95% of the universe is unaccounted for. Favoured dark matter candidates are axions or weakly-interacting particles that have survived from the very early universe, but more exotic options cannot be excluded. Experimental searches are being made for the 'dark' particles but we have indirect clues to their nature too. Comparisons of data (from, eg, gravitational lensing) with numerical simulations of galaxy formation can constrain (eg) the particle velocities and collision cross sections. The mean cosmic density of dark matter (plus baryons) is now pinned down to be only about 30% of the critical density However, other recent evidence -- microwave background anisotropies, complemented by data on distant supernovae -- reveals that our universe actually is 'flat', and that its dominant ingredient (about 70% of the total mass-energy) is something quite unexpected -- 'dark energy' pervading all space, with negative pressure. We now confront two mysteries: (i) Why does the universe have three quite distinct basic ingredients -- baryons, dark matter and dark energy -- in the proportions (roughly) 5%, 25% and 70%? (ii) What are the (almost certainly profound) implications of the 'dark energy' for fundamental physics?Comment: 10 pages, 1 figure. Late

Evidence for Ordered Magnetic Fields in the Quasar Environment

At a distance of 20 pc from the purported supermassive black hole powering quasars, temperatures and densities are inferred from optical observations to be ~10**4 K and ~10**4 cm**-3. Here we present Very Long Baseline Interferometry radio observations revealing organized magnetic fields on the parsec scale in the hot plasma surrounding the quasar OQ172 (1442+101). These magnetic fields rotate the plane of polarization of the radio emission coming from the core and inner jet of the quasar. The derived rotation measure (RM) is 40,000 rad m**-2 in the rest frame of the quasar. Only 10 mas (a projected distance of 68 pc) from the nucleus the jet absolute values of RM fall to less than 100 rad m**-2.Comment: in press at ApJ Letters, 12 page LaTeX document includes 4 postscript figure

‘The worst day of my life’: Foster carers’ experiences of allegations

Appropriate allegation investigations within social care are paramount to protect children. However, many allegations are unsubstantiated (Biehal et al., 2014) and result in stress and anxiety for fostering families (Adams, Hassett and Lumsden, 2018), financial uncertainty (Boffey, Stanton and Thomas, 2019), unplanned endings and foster carers leaving their role (Adams, Hassett and Lumsden, 2018). There is little research into the prevalence, nature and outcomes of allegations against foster carers. This UK-based study uses The Fostering Network’s State of the Nation’s Foster Care (SOTN) 2021 survey and analyses responses from 3,352 UK foster carers and 99 fostering service staff. Qualitative findings reflect six themes: (1) emotional impacts, (2) financial implications, (3) independent support, (4) social services involvement, (5) understanding allegations, and (6) children being removed or foster carers leaving their role. Quantitative findings show only 25% of those experiencing an allegation believed they were sufficiently communicated with, only 20% believed specified timescales were adhered to, 57% did not receive independent support, and 36% said no support was offered to children in their home. Poor information-sharing and lack of support were found to have exacerbated the stress experienced

Postcolonial Transplants: Cinema, Diaspora and the Body Politic

This essay examines depictions of migrant workers in French and British postcolonial cinema as transplanted interlopers, 'exotic' or transgendered bodies that are perceived as a threat to the integrity of the body politic

The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial

OBJECTIVES: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. TRIAL DESIGN: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. PARTICIPANTS: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. INTERVENTION AND COMPARATOR: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. MAIN OUTCOMES: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. RANDOMISATION: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. BLINDING (MASKING): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. TRIAL STATUS: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Mechanism for the Suppression of Intermediate-Mass Black Holes

A model for the formation of supermassive primordial black holes in galactic nuclei with the simultaneous suppression of the formation of intermediate-mass black holes is presented. A bimodal mass function for black holes formed through phase transitions in a model with a "Mexican hat" potential has been found. The classical motion of the phase of a complex scalar field during inflation has been taken into account. Possible observational manifestations of primordial black holes in galaxies and constraints on their number are discussed.Comment: 12 pages, 2 figure

Feasibility study to assess the delivery of a novel isometric exercise intervention for people with stage 1 hypertension in the NHS: protocol for the IsoFIT-BP study including amendments to mitigate the risk of COVID-19.

BackgroundHypertension  (HTN) affects approximately 25% of the UK population and is a leading cause of mortality. Associated annual health care costs run into billions. National treatment guidance includes initial lifestyle advice, followed by anti-hypertensive medication if blood pressure (BP) remains high. However, adoption and adherence to recommended exercise guidelines, dietary advice and anti-hypertensive medication is poor. Four short bouts of isometric exercise (IE) performed 3 days per week (d/wk) at home elicits clinically significant reductions in BP in those with normal to high-normal BP. This study will determine the feasibility of delivering personalised IE to patients with stage 1 hypertension for whom lifestyle changes would be recommended before medication within NHS primary care.MethodsThis is a randomised controlled feasibility study. Participants were 18+ years, with stage 1 hypertension, not on anti-hypertensive medication and without significant medical contraindications. Trial arms will be standard lifestyle advice (control) or isometric wall squat exercise and standard lifestyle advice. Primary outcomes include the feasibility of healthcare professionals to deliver isometric exercise prescriptions in a primary care NHS setting and estimation of the variance of change in systolic BP. Secondary outcomes include accuracy of protocol delivery, execution of and adherence to protocol, recruitment rate, attrition, perception of intervention viability, cost, participant experience and accuracy of home BP. The study will last 18 months. Sample size of 100 participants (50 per arm) allows for 20% attrition and 6.5% incomplete data, based upon 74 (37 each arm) participants (two-sided 95% confidence interval, width of 1.33 and standard deviation of 4) completing 4 weeks. Ethical approval IRAS ID is 274676.DiscussionBefore the efficacy of this novel intervention to treat stage 1 hypertension can be investigated in any large randomised controlled trial, it is necessary to ascertain if it can be delivered and carried out in a NHS primary care setting. Findings could support IE viability as a prophylactic/alternative treatment option.Trial registrationISRCTN13472393 , registered 18 August 2020

A time-series of methane and carbon dioxide production from dairy cows during a period of dietary transition

Emissions from dairy farms are contributing to the increased concentrations of greenhouse gases which are linked to recent climate change. Altering diets has been proposed as a greenhouse gas mitigation strategy in dairy systems. The magnitude of mitigation and the time taken for cows to adapt to new diets has not been comprehensively quantified. Methane (CH4) and carbon dioxide (CO2) produced by dairy cows was measured for six weeks using the sulphur hexafluoride tracer technique following a change in diet; from barley straw and protein supplements to grazed grass. CH4 and CO2 production increased linearly as the animals adapted to their new diets, however, production did not reach an asymptote six weeks into the grazing period. This suggested that metabolic activity and greenhouse gas emissions may not have been at their maximum. There was substantial variation between individuals with high emitting cows producing four times more CH4 than low producing cows. Cows which produced greater amounts of CH4 consistently also produced greater CO2. We demonstrate that feeding regime plays an important role in determining greenhouse gas emissions and we highlight that transition periods in greenhouse gas models and future experiments must be sufficiently large to allow for adaptation

Fermion correlators in non-abelian holographic superconductors

We consider fermion correlators in non-abelian holographic superconductors. The spectral function of the fermions exhibits several interesting features such as support in displaced Dirac cones and an asymmetric distribution of normal modes. These features are compared to similar ones observed in angle resolved photoemission experiments on high T_c superconductors. Along the way we elucidate some properties of p-wave superconductors in AdS_4 and discuss the construction of SO(4) superconductors.Comment: 49 pages, 11 figure

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents