34 research outputs found
Tidal Heating: Lessons from Io and the Jovian System - Final Report
Tidal heating is key to the evolution and habitability of many worlds across our solar system and beyond. However, there remain fundamental gaps in our understanding of tidal heating and coupled orbital evolution, which motivated a Keck Institute for Space Studies (KISS) workshop on this topic. The Cassini mission has led to many recent results about ocean worlds and what may become a new paradigm for understanding orbital evolution with tidal heating, the model of resonance locking in the parent planet (Fuller et al., 2016). Resonance locking explains how subsurface oceans may persist over much of geologic time, even in tiny Enceladus. The discovery
of the Laplace resonance of Io, Europa, and Ganymede orbiting Jupiter led to the prediction of intense tidal heating of Io (Peale et al., 1979); this system provides the greatest potential for advances in the next few decades. Europa Clipper and JUpiter ICy moons Explorer (JUICE) will provide in-depth studies of Europa and Ganymede in the 2030s. The easily observed heat flow of Io, from hundreds of continually erupting volcanoes, makes it an ideal target for further investigation, and the missing linkâalong with missions in developmentâto understand the Laplace system.
We identified five key questions to drive future research and exploration: (Q1) What do volcanic eruptions tell us about the interiors of tidally heated bodies (e.g., Io, Enceladus, and perhaps Europa and Triton)? (Q2) How is tidal dissipation partitioned between solid and liquid materials? (Q3) Does Io have a melt-rich layer, or âmagma oceanâ, that mechanically decouples the lithosphere from the deeper interior? (Q4) Is the Jupiter/Laplace system in equilibrium (i.e., does the satelliteâs heat output equal the rate at which energy is generated)? (Q5) Can stable isotope measurements inform long-term evolution of tidally heated bodies?
The most promising avenues to address these questions include a new spacecraft mission making close flybys of Io, missions orbiting and landing on key worlds such as Europa and Enceladus, technology developments to enable advanced techniques, closer coupling between laboratory experiments and tidal heating theory, and advances in Earth-based telescopic observations of solar system and extrasolar planets and moons. All of these avenues would benefit from technological developments. An Io mission should: characterize volcanic processes (Q1); test interior models via a set of geophysical measurements coupled with laboratory experiments and theory (Q2 and Q3); measure the rate of Ioâs orbital migration (to complement similar measurements expected at Europa and Ganymede) to determine if the Laplace resonance is in equilibrium (Q4); and determine neutral compositions and measure stable isotopes in Ioâs atmosphere and plumes (Q5). No new technologies are required for such an Io mission following advances in radiation design and solar power realized for Europa Clipper and JUICE. Seismology is a promising avenue for future exploration, either from landers or remote laser reflectometry, and interferometric synthetic aperture radar (InSAR) could be revolutionary on these active worlds, but advanced power systems plus lower mass and power-active instruments are needed for operation in the outer solar system
Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors
Context
Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs).
Objective
To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients.
Design
12-year prospective, observational study.
Participants & Setting
We studied probands and family members of FIPA kindreds and sporadic patients with disease onset â€18 years or macroadenomas with onset â€30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases.
Interventions & Outcome
AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).
Results
Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650).
Conclusions
Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course
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Single-cell multi-omics analysis of the immune response in COVID-19
Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
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FRT - FONDATION RENE TOURAINEÂ An International Foundation For Dermatology
Brave new green world : consequences of a carbon economy for the conservation of Australian biodiversity
Pricing greenhouse gas emissions is a burgeoning and possibly lucrative financial means for climate change mitigation. Emissions pricing is being used to fund emissions-abatement technologies and to modify land management to improve carbon sequestration and retention. Here we discuss the principal land-management options under existing and realistic future emissions-price legislation in Australia, and examine them with respect to their anticipated direct and indirect effects on biodiversity. The main ways in which emissions price-driven changes to land management can affect biodiversity are through policies and practices for (1) environmental plantings for carbon sequestration, (2) native regrowth, (3) fire management, (4) forestry, (5) agricultural practices (including cropping and grazing), and (6) feral animal control. While most land-management options available to reduce net greenhouse gas emissions offer clear advantages to increase the viability of native biodiversity, we describe several caveats regarding potentially negative outcomes, and outline components that need to be considered if biodiversity is also to benefit from the new carbon economy. Carbon plantings will only have real biodiversity value if they comprise appropriate native tree species and provide suitable habitats and resources for valued fauna. Such plantings also risk severely altering local hydrology and reducing water availability. Management of regrowth post-agricultural abandonment requires setting appropriate baselines and allowing for thinning in certain circumstances, and improvements to forestry rotation lengths would likely increase carbon-retention capacity and biodiversity value. Prescribed burning to reduce the frequency of high-intensity wildfires in northern Australia is being used as a tool to increase carbon retention. Fire management in southern Australia is not readily amenable for maximising carbon storage potential, but will become increasingly important for biodiversity conservation as the climate warms. Carbon price-based modifications to agriculture that would benefit biodiversity include reductions in tillage frequency and livestock densities, reductions in fertiliser use, and retention and regeneration of native shrubs; however, anticipated shifts to exotic perennial grass species such as buffel grass and kikuyu could have net negative implications for native biodiversity. Finally, it is unlikely that major reductions in greenhouse gas emissions arising from feral animal control are possible, even though reduced densities of feral herbivores will benefit Australian biodiversity greatly
An AAAAâDDDD quadruple hydrogen-bond array
Secondary electrostatic interactions between adjacent hydrogen bonds can have a significant effect on the stability of a supramolecular complex. In theory, the binding strength should be maximized if all the hydrogen-bond donors (D) are on one component and all the hydrogen-bond acceptors (A) are on the other. Here, we describe a readily accessible AAAAâDDDD quadruple hydrogen-bonding array that exhibits exceptionally strong binding for a small-molecule hydrogen-bonded complex in a range of different solvents (Ka > 3 Ă 1012 Mâ1 in CH2Cl2, 1.5 Ă 106 Mâ1 in CH3CN and 3.4 Ă 105 Mâ1 in 10% v/v DMSO/CHCl3). The association constant in CH2Cl2 corresponds to a binding free energy (?G) in excess of â71 kJ molâ1 (more than 20% of the thermodynamic stability of a carbonâcarbon covalent bond), which is remarkable for a supramolecular complex held together by just four intercomponent hydrogen bonds