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The sustainable energy technologies that are required to achieve net-zero carbon emissions rely on critical metals. Pegmatite deposits are one of the world’s primary sources of these critical metals, which makes understanding their formation essential. The sustainable energy technologies that are required to achieve net-zero carbon emissions rely on critical metals. Pegmatite deposits are one of the world’s primary sources of these critical metals, which makes understanding their formation essential.

Building super-eruptive magma reservoirs in the cold, upper parts of Earth’s crust requires a significant influx of magma over an extended period, sufficient to allow the magma to accumulate, differentiate and periodically erupt. Some models favour magma storage in a cold non-eruptible state, requiring extensive reactivation of the reservoirs before eruption, whereas others suggest storage at higher temperature and lower crystallinity, implying that magma in such reservoirs is readily eruptible. Consequently, constraining volcanic hazards requires observations directly linking magma residence timescales to the thermal state and crystallinity of storage. Here we simultaneously determine crystallization temperatures and ages of magmatic crystals of zircon and titanite in the 900 km 3 Kneeling Nun Tuff (New Mexico, USA), which allows us to place tight constraints on the long-term thermal evolution of the magma reservoir. We show that zircon and titanite crystals record more than 600,000 years of magma assembly and constrain the dominant storage conditions to low temperatures, set between the granitic solidus (680 to 700 °C) and the temperature of the onset of titanite crystallization (about 720 to 730 °C). We apply the zircon–titanite systematics to a suite of other super-eruptions and suggest that protracted low-temperature storage culminating in late-stage reheating is a widespread feature of large crystal-rich eruptions. Super-eruptions are fed by large magma reservoirs. Geochemical analyses of volcanic rocks erupted in New Mexico suggest the magma was stored under cool conditions in the crust for 600,000 years, before late-stage heating triggered an eruption.

The Island Park-Mount Jackson series in the Yellowstone volcanic field, Wyoming (USA), is a suite of rhyolitic domes and lavas that erupted between the caldera-forming eruptions of the Mesa Fall Tuff (1.3 Ma) and the Lava Creek Tuff (0.6 Ma). Combined zircon U/Pb geochronology, Raman spectroscopy, oxygen isotopic and trace elemental compositions document storage conditions of these magmas between consecutive supereruptions. Based on comparison with co-erupted melt compositions and textural criteria, four zircon compositional groups are identified that record different stages along a continuous magmatic evolution from trace element-poor rhyolite at high temperatures to extremely fractionated rhyolite where zircon trace elements are highly enriched (e.g., > 1000 ppm U). These latter zircon domains are dark in cathodoluminescence images and show broadened Raman peaks relative to near-endmember zircon, indicating that substitution of non-stoichiometric trace elements into zircon leads to distortion of the crystal lattice. Some of these zircon domains contain inclusions of U-Th-REE-phases, likely originating from coupled dissolution–reprecipitation of metastable trace element-rich zircon in the presence of a fluid phase. Rhyolite-MELTS simulations indicate that at the conditions required to produce the observed enrichment in trace elements, a fluid phase is likely present. These findings illustrate that zircons can be assembled from a variety of co-existing magmatic environments in the same magma reservoir, including near-solidus volatile-rich melts close to the magmatic–hydrothermal transition.

Over the last ~267 ky, the island of Lipari has erupted magmas ranging in compositions from basaltic andesites to rhyolites, with a notable compositional gap in the dacite field. Bulk geochemical and isotopic compositions of the volcanic succession, in conjunction with major and trace elemental compositions of minerals, indicate that the rhyolites were dominantly generated via crystal fractionation processes, with subordinate assimilation. Radiogenic (Sr, Nd, and Pb) and stable (O) isotopes independently suggest ≤30 % of crustal contamination with the majority of it occurring in mafic compositions, likely relatively deep in the system. Within the rhyolites, crystal-rich, K 2 O-rich enclaves are common. In contrast to previous interpretations, we suggest that these enclaves represent partial melting, remobilization and eruption of cumulate fragments left-over from rhyolite melt extraction. Cumulate melting and remobilization is supported by the presence of (1) resorbed, low-temperature minerals (biotite and sanidine), providing the potassic signature to these clasts, (2) reacted Fo-rich olivine, marking the presence of mafic recharge, (3) An 38–21 plagioclase, filling the gap in feldspar composition between the andesites and the rhyolites and (4) strong enrichment in Sr and Ba in plagioclase and sanidine, suggesting crystallization from a locally enriched melt. Based on Sr-melt partitioning, the high-Sr plagioclase would require ~2300 ppm Sr in the melt, a value far in excess of Sr contents in Lipari and Vulcano magmas (50–1532 ppm) but consistent with melting of a feldspar-rich cumulate. Due to the presence of similar crystal-rich enclaves within the rhyolites from Vulcano, we propose that the eruption of remobilized cumulates associated with high-SiO 2 rhyolites may be a common process at the Aeolian volcanoes, as already attested for a variety of volcanic systems around the world.

Both Earth and Mars possess different styles of explosive basaltic volcanism. Distinguishing phreatomagmatic eruptions, driven by magma–water interaction, from ‘magmatic’ explosive eruptions (that is, strombolian and plinian eruptions) is important for determining the presence of near-surface water or ice at the time of volcanism. Here we show that eruption styles can be broadly identified by relative variations in groundmass or bulk crystallinity determined by X-ray diffraction. Terrestrial analogue results indicate that rapidly quenched phreatomagmatic ejecta display lower groundmass crystallinity (<35%) than slower cooling ejecta from strombolian or plinian eruptions (>40%). Numerical modelling suggests Martian plinian eruptive plumes moderate cooling, allowing 20–30% syn-eruptive crystallization, and thus reduce the distinction between eruption styles on Mars. Analysis of Mars Curiosity rover CheMin X-ray diffraction results from Gale crater indicate that the crystallinity of Martian sediment (52–54%) is similar to pyroclastic rocks from Gusev crater, Mars, and consistent with widespread distribution of basaltic strombolian or plinian volcanic ejecta. Although observations of volcanic deposits on Mars are more accessible than ever, constraining Martian eruption styles remains a challenge. Here, the authors show that volcanic eruption style can be characterized through X-ray diffraction analysis of groundmass crystallinity in basaltic volcanic deposits.

Three voluminous rhyolitic ignimbrites have been identified along the southern margin of the central Snake River Plain. As a result of wide-scale correlations, new volume estimates can be made for these deposits: ~350 km 3 for the Steer Basin Tuff and Cougar Point Tuff XI, and ~1,000 km 3 for Cougar Point Tuff XIII. These volumes exclude any associated regional ashfalls and correlation across to the north side of the plain, which has yet to be attempted. Each correlation was achieved using a combination of methods including field logging, whole rock and mineral chemistry, magnetic polarity, oxygen isotope signature and high-precision 40 Ar/ 39 Ar geochronology. The Steer Basin Tuff, Cougar Point Tuff XI and Cougar Point Tuff XIII have deposit characteristics typical of ‘Snake River (SR)-type’ volcanism: they are very dense, intensely welded and rheomorphic, unusually well sorted with scarce pumice and lithic lapilli. These features differ significantly from those of deposits from the better-known younger eruptions of Yellowstone. The ignimbrites also exhibit marked depletion in δ 18 O, which is known to characterise the SR-type rhyolites of the central Snake River Plain, and cumulatively represent ~1,700 km 3 of low δ 18 O rhyolitic magma (feldspar values 2.3–2.9‰) erupted within 800,000 years. Our work reduces the total number of ignimbrites recognised in the central Snake River Plain by 6, improves the link with the ashfall record of Yellowstone hotspot volcanism and suggests that more large-volume ignimbrites await discovery through detailed correlation work amidst the vast ignimbrite record of volcanism in this bimodal large igneous province.

Mouse models of breast carcinoma and other solid tumours show that selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors not only induce tumour cell cycle arrest but also promote anti-tumour immunity. Anti-tumour effect of CDK4/6 inhibitors CDK4/6 inhibitors are currently in clinical trials for breast cancer. They are known to induce cytostatic effects. Here, the authors uncover a novel effect of CDK4/6 inhibitors that could contribute to their therapeutic effect. By both increasing tumour cell antigen presentation and suppressing the proliferation of regulatory T cells, CDK4/6 inhibitors enhance anti-tumour immunity. These effects are each linked to reduced expression of DNMT1 after treatment. In vivo , combining CDK4/6 inhibitors and checkpoint blockade provides a more profound anti-tumour effect. Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies 1 , 2 . Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours 3 , 4 . Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells 5 . Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity. We confirm this phenomenon through transcriptomic analysis of serial biopsies from a clinical trial of CDK4/6 inhibitor treatment for breast cancer. The enhanced anti-tumour immune response has two underpinnings. First, CDK4/6 inhibitors activate tumour cell expression of endogenous retroviral elements, thus increasing intracellular levels of double-stranded RNA. This in turn stimulates production of type III interferons and hence enhances tumour antigen presentation. Second, CDK4/6 inhibitors markedly suppress the proliferation of regulatory T cells. Mechanistically, the effects of CDK4/6 inhibitors both on tumour cells and on regulatory T cells are associated with reduced activity of the E2F target, DNA methyltransferase 1. Ultimately, these events promote cytotoxic T-cell-mediated clearance of tumour cells, which is further enhanced by the addition of immune checkpoint blockade. Our findings indicate that CDK4/6 inhibitors increase tumour immunogenicity and provide a rationale for new combination regimens comprising CDK4/6 inhibitors and immunotherapies as anti-cancer treatment.

The impacts of global environmental change have precipitated numerous approaches that connect the health of ecosystems, non-human organisms and humans. However, the proliferation of approaches can lead to confusion due to overlaps in terminology, ideas and foci. Recognising the need for clarity, this paper provides a guide to seven field developments in environmental public health research and practice: occupational and environmental health; political ecology of health; environmental justice; ecohealth; One Health; ecological public health; and planetary health. Field developments are defined in terms of their uniqueness from one another, are historically situated, and core texts or journals are highlighted. The paper ends by discussing some of the intersecting features across field developments, and considers opportunities created through such convergence. This field guide will be useful for those seeking to build a next generation of integrative research, policy, education and action that is equipped to respond to current health and sustainability challenges.

Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Δ-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size=0.60; p =0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.