Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19

Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19

The Biomolecule Sequencer Project: Nanopore Sequencing as a Dual-Use Tool for Crew Health and Astrobiology Investigations

Human missions to Mars will fundamentally transform how the planet is explored, enabling new scientific discoveries through more sophisticated sample acquisition and processing than can currently be implemented in robotic exploration. The presence of humans also poses new challenges, including ensuring astronaut safety and health and monitoring contamination. Because the capability to transfer materials to Earth will be extremely limited, there is a strong need for in situ diagnostic capabilities. Nucleotide sequencing is a particularly powerful tool because it can be used to: (1) mitigate microbial risks to crew by allowing identification of microbes in water, in air, and on surfaces; (2) identify optimal treatment strategies for infections that arise in crew members; and (3) track how crew members, microbes, and mission-relevant organisms (e.g., farmed plants) respond to conditions on Mars through transcriptomic and genomic changes. Sequencing would also offer benefits for science investigations occurring on the surface of Mars by permitting identification of Earth-derived contamination in samples. If Mars contains indigenous life, and that life is based on nucleic acids or other closely related molecules, sequencing would serve as a critical tool for the characterization of those molecules. Therefore, spaceflight-compatible nucleic acid sequencing would be an important capability for both crew health and astrobiology exploration. Advances in sequencing technology on Earth have been driven largely by needs for higher throughput and read accuracy. Although some reduction in size has been achieved, nearly all commercially available sequencers are not compatible with spaceflight due to size, power, and operational requirements. Exceptions are nanopore-based sequencers that measure changes in current caused by DNA passing through pores; these devices are inherently much smaller and require significantly less power than sequencers using other detection methods. Consequently, nanopore-based sequencers could be made flight-ready with only minimal modifications

Posaconazole and midostaurin in patients with FLT3-mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

: Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3-mutated acute myeloid leukemia. Chemotherapy-induced neutropenia exposes these patients to a significant risk of invasive fungal infections (IFIs). International guidelines recommend primary antifungal prophylaxis with posaconazole (PCZ) but nested analysis of a phase III trial showed that strong PCZ inhibition of CYP3A4 diminished midostaurin metabolism and increased midostaurin plasma levels; however, midostaurin-related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real-life study to evaluate (i) how often concerns around PCZ-midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ-midostaurin interactions influenced hematologic and safety outcomes of induction therapy. Although the hematologists were blinded to pharmacokinetic findings, as many as 16 of 35 evaluable patients were prescribed antifungal prophylaxis with micafungin, weak CYP3A4 inhibitor, in place of PCZ (p < 0.001 for deviation from guidelines). In the 19 patients managed as per guidelines, PCZ-midostaurin interactions were more remarkable than previously characterized, such that at the end of induction therapy midostaurin minimum plasma concentration (Cmin ) was greater than three times higher than reported; moreover, midostaurin Cmin , maximum plasma concentration, and area under the curve were more than or equal to four times higher with PCZ than micafungin. Hematologic outcomes (complete remission and duration of severe neutropenia) and safety outcomes (midostaurin-related any grade or grade ≥3 AEs) were nonetheless similar for patients exposed to PCZ or micafungin, as was the number of breakthrough IFIs. In waiting for randomized phase III trials of new prophylaxis regimens, these findings show that PCZ should remain the antifungal of choice for the midostaurin-treated patient

Ethics for an uninhabited planet

Some authors argue that we have a moral obligation to leave Mars the way it is, even if it does not harbour any life. This claim is usually based on an assumption that Mars has intrinsic value. The problem with this concept is that different authors use it differently. In this chapter, I investigate different ways in which an uninhabited Mars is said to have intrinsic value. First, I investigate whether the planet can have moral standing. I find that this is not a plausible assumption. I then investigate different combinations of objective value and end value. I find that there is no way we can know whether an uninhabited Mars has objective end value and even if it does, this does not seem to imply any moral obligations on us. I then investigate whether an uninhabited Mars can have subjective end value. I conclude that this is very plausible. I also investigate whether an uninhabited Mars can have objective instrumental value in relation to some other, non-Mars related end value. I find also this very plausible. It is also highly plausible, however, that spreading (human or other) life to a presently uninhabited Mars can also have subjective end value, as well as objective instrumental value. I mention shortly two ways of prioritising between these values: (1) The utilitarian method of counting the number of sentient beings who entertain each value and determining the strength of the values to them. (2) Finding a compromise that allows colonisation on parts of the planet while leaving other parts untouched. These methods should be seen as examples, not as an exhaustive list. Also, I do not take a definitive stand in favour of any of the two approaches, though it seems at least prima facie that the second approach may have a better chance of actually leading to a constructive result

NASA's International Space Station: A Testbed for Planetary Protection Protocol Development

Wherever humans go, they inevitably carry along the critters that live in and on them. Conventional wisdom has long held that it is unlikely those critters could survive the space environment, but in 2007 some microscopic aquatic animals called Tardigrades survived exposure to space and in 2008 Cyanobacteria lived for 548 days outside the ISS. Unlike the Mars rovers that were cleaned once and sent on their way, crew members will provide a constantly regenerating contaminant source. Are we prepared to certify that we can meet forward contamination protocols as we search for life at new destinations? What about the organisms we might reasonably expect a crewed spacecraft to leak or vent? Do we even know what they are? How long might our tiny hitch-hikers survive in close proximity to a warm spacecraft that periodically leaks/vents water or oxygen and how might they mutate with long-duration exposure? How will these contaminants migrate from their source in conditions encountered in space or on other planetary surfaces? This project aims to answer some of these questions by bringing together key stakeholder communities to develop a human forward contamination test, analysis, and integration plan. A system engineering approach to identify the experiments, analysis, and modeling needed to develop the contamination control protocols required will be used as a roadmap to integrate the many different parts of this problem - from launch to landing, living, and working on another planetary surface

Nasa's International Space Station: A Testbed for Planetary Protection Protocol Development

Wherever humans go, they inevitably carry along the critters that live in and on them. Conventional wisdom has long held that it is unlikely those critters could survive the space environment, but in 2007 some microscopic aquatic animals called Tardigrades survived exposure to space and in 2008 Cyanobacteria lived for 548 days outside the ISS. Unlike the Mars rovers that were cleaned once and sent on their way, crew members will provide a constantly regenerating contaminant source. Are we prepared to certify that we can meet forward contamination protocols as we search for life at new destinations? What about the organisms we might reasonably expect a crewed spacecraft to leak or vent? Do we even know what they are? How long might our tiny hitch-hikers survive in close proximity to a warm spacecraft that periodically leaks/vents water or oxygen and how might they mutate with long-duration exposure? How will these contaminants migrate from their source in conditions encountered in space or on other planetary surfaces? This project aims to answer some of these questions by bringing together key stakeholder communities to develop a human forward contamination test, analysis, and integration plan. A system engineering approach to identify the experiments, analysis, and modeling needed to develop the contamination control protocols required will be used as a roadmap to integrate the many different parts of this problem - from launch to landing, living, and working on another planetary surface

Space Science Opportunities Augmented by Exploration Telepresence

Since the end of the Apollo missions to the lunar surface in December 1972, humanity has exclusively conducted scientific studies on distant planetary surfaces using teleprogrammed robots. Operations and science return for all of these missions are constrained by two issues related to the great distances between terrestrial scientists and their exploration targets: high communication latencies and limited data bandwidth. Despite the proven successes of in-situ science being conducted using teleprogrammed robotic assets such as Spirit, Opportunity, and Curiosity rovers on the surface of Mars, future planetary field research may substantially overcome latency and bandwidth constraints by employing a variety of alternative strategies that could involve: 1) placing scientists/astronauts directly on planetary surfaces, as was done in the Apollo era; 2) developing fully autonomous robotic systems capable of conducting in-situ field science research; or 3) teleoperation of robotic assets by humans sufficiently proximal to the exploration targets to drastically reduce latencies and significantly increase bandwidth, thereby achieving effective human telepresence. This third strategy has been the focus of experts in telerobotics, telepresence, planetary science, and human spaceflight during two workshops held from October 3–7, 2016, and July 7–13, 2017, at the Keck Institute for Space Studies (KISS). Based on findings from these workshops, this document describes the conceptual and practical foundations of low-latency telepresence (LLT), opportunities for using derivative approaches for scientific exploration of planetary surfaces, and circumstances under which employing telepresence would be especially productive for planetary science. An important finding of these workshops is the conclusion that there has been limited study of the advantages of planetary science via LLT. A major recommendation from these workshops is that space agencies such as NASA should substantially increase science return with greater investments in this promising strategy for human conduct at distant exploration sites

Space Science Opportunities Augmented by Exploration Telepresence

Since the end of the Apollo missions to the lunar surface in December 1972, humanity has exclusively conducted scientific studies on distant planetary surfaces using teleprogrammed robots. Operations and science return for all of these missions are constrained by two issues related to the great distances between terrestrial scientists and their exploration targets: high communication latencies and limited data bandwidth. Despite the proven successes of in-situ science being conducted using teleprogrammed robotic assets such as Spirit, Opportunity, and Curiosity rovers on the surface of Mars, future planetary field research may substantially overcome latency and bandwidth constraints by employing a variety of alternative strategies that could involve: 1) placing scientists/astronauts directly on planetary surfaces, as was done in the Apollo era; 2) developing fully autonomous robotic systems capable of conducting in-situ field science research; or 3) teleoperation of robotic assets by humans sufficiently proximal to the exploration targets to drastically reduce latencies and significantly increase bandwidth, thereby achieving effective human telepresence. This third strategy has been the focus of experts in telerobotics, telepresence, planetary science, and human spaceflight during two workshops held from October 3–7, 2016, and July 7–13, 2017, at the Keck Institute for Space Studies (KISS). Based on findings from these workshops, this document describes the conceptual and practical foundations of low-latency telepresence (LLT), opportunities for using derivative approaches for scientific exploration of planetary surfaces, and circumstances under which employing telepresence would be especially productive for planetary science. An important finding of these workshops is the conclusion that there has been limited study of the advantages of planetary science via LLT. A major recommendation from these workshops is that space agencies such as NASA should substantially increase science return with greater investments in this promising strategy for human conduct at distant exploration sites

Overview of a Preliminary Destination Mission Concept for a Human Orbital Mission to the Martial Moons

The National Aeronautics and Space Administration s Human Spaceflight Architecture Team (HAT) has been developing a preliminary Destination Mission Concept (DMC) to assess how a human orbital mission to one or both of the Martian moons, Phobos and Deimos, might be conducted as a follow-on to a human mission to a near-Earth asteroid (NEA) and as a possible preliminary step prior to a human landing on Mars. The HAT Mars-Phobos-Deimos (MPD) mission also permits the teleoperation of robotic systems by the crew while in the Mars system. The DMC development activity provides an initial effort to identify the science and exploration objectives and investigate the capabilities and operations concepts required for a human orbital mission to the Mars system. In addition, the MPD Team identified potential synergistic opportunities via prior exploration of other destinations currently under consideration