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Shocked quartz grains are an accepted indicator of crater-forming cosmic impact events, which also typically produce amorphous silica along the fractures. Furthermore, previous research has shown that shocked quartz can form when nuclear detonations, asteroids, and comets produce near-surface or “touch-down” airbursts. When cosmic airbursts detonate with enough energy and at sufficiently low altitude, the resultant relatively small, high-velocity fragments may strike Earth’s surface with high enough pressures to generate thermal and mechanical shock that can fracture quartz grains and introduce molten silica into the fractures. Here, we report the discovery of shocked quartz grains in a layer dating to the Younger Dryas (YD) onset (12.8 ka) in three classic archaeological sequences in the Southwestern United States: Murray Springs, Arizona; Blackwater Draw, New Mexico; and Arlington Canyon, California. These sites were foundational in demonstrating that the extinction or observed population bottlenecks of many megafaunal species and the coeval collapse/reorganization of the Clovis technocomplex in North America co-occurred at or near the YD onset. Using a comprehensive suite of 10 analytical techniques, including electron microscopy (TEM, SEM, CL, and EBSD), we have identified grains with glass-filled fractures similar to shocked grains associated with nuclear explosions and 27 accepted impact craters of different ages (e.g., Meteor Crater, 50 ka; Chesapeake Bay, 35 Ma; Chicxulub, 66 Ma; Manicouagan, 214 Ma) and produced in 11 laboratory shock experiments. In addition, we used hydrocode modeling to explore the temperatures, pressures, and shockwave velocities associated with the airburst of a 100-m fragment of a comet and conclude that they are sufficient to produce shocked quartz. These shocked grains co-occur with previously reported peak concentrations in platinum, meltglass, soot, and nanodiamonds, along with microspherules, similar to those found in ~28 microspherule layers that are accepted as evidence for cosmic impact events, even in the absence of a known crater. The discovery of apparently thermally-altered shocked quartz grains at these three key archaeological sites supports a cosmic impact as a major contributing factor in the megafaunal extinctions and the collapse of the Clovis technocomplex at the YD onset.

The Younger Dryas Impact Hypothesis (YDIH) posits that ~12,800 years ago Earth encountered the debris stream of a disintegrating comet, triggering hemisphere-wide airbursts, atmospheric dust loading, and the deposition of a distinctive suite of extraterrestrial (ET) impact proxies at the Younger Dryas Boundary (YDB). Until now, evidence supporting this hypothesis has come only from terrestrial sediment and ice-core records. Here we report the first discovery of similar impact-related proxies in ocean sediments from four marine cores in Baffin Bay that span the YDB layer at water depths of 0.5–2.4 km, minimizing the potential for modern contamination. Using scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) and laser ablation ICP-MS, we detect synchronous abundance peaks of metallic debris geochemically consistent with cometary dust, co-occurring with iron- and silica-rich microspherules (4–163 μm) that are predominantly of terrestrial origin with minor (<2 wt%) ET contributions. These microspherules were likely formed by low-altitude touchdown airbursts and surface impacts of comet fragments and were widely dispersed. In addition, single-particle ICP-TOF-MS analysis reveals nanoparticles (<1 μm) enriched in platinum, iridium, nickel, and cobalt. Similar platinum-group element anomalies at the YDB have been documented at dozens of sites worldwide, strongly suggesting an ET source. Collectively, these findings provide robust support for the YDIH. The impact event likely triggered massive meltwater flooding, iceberg calving, and a temporary shutdown of thermohaline circulation, contributing to abrupt Younger Dryas cooling. Our identification of a YDB impact layer in deep marine sediments underscores the potential of oceanic records to broaden our understanding of this catastrophic event and its climatological impacts.

Shocked quartz grains are an accepted indicator of crater-forming cosmic impact events, which also typically produce amorphous silica along the fractures. Furthermore, previous research has shown that shocked quartz can form when nuclear detonations, asteroids, and comets produce near-surface or \"touch-down\" airbursts. When cosmic airbursts detonate with enough energy and at sufficiently low altitude, the resultant relatively small, high-velocity fragments may strike Earth's surface with high enough pressures to generate thermal and mechanical shock that can fracture quartz grains and introduce molten silica into the fractures. Here, we report the discovery of shocked quartz grains in a layer dating to the Younger Dryas (YD) onset (12.8 ka) in three classic archaeological sequences in the Southwestern United States: Murray Springs, Arizona; Blackwater Draw, New Mexico; and Arlington Canyon, California. These sites were foundational in demonstrating that the extinction or observed population bottlenecks of many megafaunal species and the coeval collapse/reorganization of the Clovis technocomplex in North America co-occurred at or near the YD onset. Using a comprehensive suite of 10 analytical techniques, including electron microscopy (TEM, SEM, CL, and EBSD), we have identified grains with glass-filled fractures similar to shocked grains associated with nuclear explosions and 27 accepted impact craters of different ages (e.g., Meteor Crater, 50 ka; Chesapeake Bay, 35 Ma; Chicxulub, 66 Ma; Manicouagan, 214 Ma) and produced in 11 laboratory shock experiments. In addition, we used hydrocode modeling to explore the temperatures, pressures, and shockwave velocities associated with the airburst of a 100-m fragment of a comet and conclude that they are sufficient to produce shocked quartz. These shocked grains co-occur with previously reported peak concentrations in platinum, meltglass, soot, and nanodiamonds, along with microspherules, similar to those found in ~28 microspherule layers that are accepted as evidence for cosmic impact events, even in the absence of a known crater. The discovery of apparently thermally-altered shocked quartz grains at these three key archaeological sites supports a cosmic impact as a major contributing factor in the megafaunal extinctions and the collapse of the Clovis technocomplex at the YD onset.

Shocked quartz grains are an accepted indicator of crater-forming cosmic impact events, which also typically produce amorphous silica along the fractures. Furthermore, previous research has shown that shocked quartz can form when nuclear detonations, asteroids, and comets produce near-surface or \"touch-down\" airbursts. When cosmic airbursts detonate with enough energy and at sufficiently low altitude, the resultant relatively small, high-velocity fragments may strike Earth's surface with high enough pressures to generate thermal and mechanical shock that can fracture quartz grains and introduce molten silica into the fractures. Here, we report the discovery of shocked quartz grains in a layer dating to the Younger Dryas (YD) onset (12.8 ka) in three classic archaeological sequences in the Southwestern United States: Murray Springs, Arizona; Blackwater Draw, New Mexico; and Arlington Canyon, California. These sites were foundational in demonstrating that the extinction or observed population bottlenecks of many megafaunal species and the coeval collapse/reorganization of the Clovis technocomplex in North America co-occurred at or near the YD onset. Using a comprehensive suite of 10 analytical techniques, including electron microscopy (TEM, SEM, CL, and EBSD), we have identified grains with glass-filled fractures similar to shocked grains associated with nuclear explosions and 27 accepted impact craters of different ages (e.g., Meteor Crater, 50 ka; Chesapeake Bay, 35 Ma; Chicxulub, 66 Ma; Manicouagan, 214 Ma) and produced in 11 laboratory shock experiments. In addition, we used hydrocode modeling to explore the temperatures, pressures, and shockwave velocities associated with the airburst of a 100-m fragment of a comet and conclude that they are sufficient to produce shocked quartz. These shocked grains co-occur with previously reported peak concentrations in platinum, meltglass, soot, and nanodiamonds, along with microspherules, similar to those found in ~28 microspherule layers that are accepted as evidence for cosmic impact events, even in the absence of a known crater. The discovery of apparently thermally-altered shocked quartz grains at these three key archaeological sites supports a cosmic impact as a major contributing factor in the megafaunal extinctions and the collapse of the Clovis technocomplex at the YD onset.

The Younger Dryas Impact Hypothesis (YDIH) posits that ~12,800 years ago Earth encountered the debris stream of a disintegrating comet, triggering hemisphere-wide airbursts, atmospheric dust loading, and the deposition of a distinctive suite of extraterrestrial (ET) impact proxies at the Younger Dryas Boundary (YDB). Until now, evidence supporting this hypothesis has come only from terrestrial sediment and ice-core records. Here we report the first discovery of similar impact-related proxies in ocean sediments from four marine cores in Baffin Bay that span the YDB layer at water depths of 0.5-2.4 km, minimizing the potential for modern contamination. Using scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) and laser ablation ICP-MS, we detect synchronous abundance peaks of metallic debris geochemically consistent with cometary dust, co-occurring with iron- and silica-rich microspherules (4-163 [mu]m) that are predominantly of terrestrial origin with minor (<2 wt%) ET contributions. These microspherules were likely formed by low-altitude touchdown airbursts and surface impacts of comet fragments and were widely dispersed. In addition, single-particle ICP-TOF-MS analysis reveals nanoparticles (<1 [mu]m) enriched in platinum, iridium, nickel, and cobalt. Similar platinum-group element anomalies at the YDB have been documented at dozens of sites worldwide, strongly suggesting an ET source. Collectively, these findings provide robust support for the YDIH. The impact event likely triggered massive meltwater flooding, iceberg calving, and a temporary shutdown of thermohaline circulation, contributing to abrupt Younger Dryas cooling. Our identification of a YDB impact layer in deep marine sediments underscores the potential of oceanic records to broaden our understanding of this catastrophic event and its climatological impacts.

Students were asking critical legal questions early that semester raised by this event, such as: \"If the Cubans, with Soviet help, were acting within their legal right of selfdefense, what could the United States legally do to counter this move?\"' The discussions and focus on international law in the wake of the Cuban Missile Crisis led to student interest and discussion that exceeded the time available in class, and students soon chartered the Texas International Law Society to explore these issues and others in earnest. In describing the impact the Journal and its students left on him, he remarked, \"the results of these student initiatives, as seen thirty years later, make me realize that teaching at the University of Texas School of Law was the high point of an exciting and rewarding fifty years of professional life.\"

Conventional external beam radiotherapy is the standard palliative treatment for spinal metastases; however, complete response rates for pain are as low as 10–20%. Stereotactic body radiotherapy delivers high-dose, ablative radiotherapy. We aimed to compare complete response rates for pain after stereotactic body radiotherapy or conventional external beam radiotherapy in patients with painful spinal metastasis. This open-label, multicentre, randomised, controlled, phase 2/3 trial was done at 13 hospitals in Canada and five hospitals in Australia. Patients were eligible if they were aged 18 years and older, and had painful (defined as ≥2 points with the Brief Pain Inventory) MRI-confirmed spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0–2, a Spinal Instability Neoplasia Score of less than 12, and no neurologically symptomatic spinal cord or cauda equina compression. Patients were randomly assigned (1:1) with a web-based, computer-generated allocation sequence to receive either stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions or conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions using standard techniques. Treatment assignment was done centrally by use of a minimisation method to achieve balance for the stratification factors of radiosensitivity, the presence or absence of mass-type tumour (extraosseous or epidural disease extension, or both) on imaging, and centre. The primary endpoint was the proportion of patients with a complete response for pain at 3 months after radiotherapy. The primary endpoint was analysed in the intention-to-treat population and all safety and quality assurance analyses were done in the as-treated population (ie, all patients who received at least one fraction of radiotherapy). The trial is registered with ClinicalTrials.gov, NCT02512965. Between Jan 4, 2016, and Sept 27, 2019, 229 patients were enrolled and randomly assigned to receive conventional external beam radiotherapy (n=115) or stereotactic body radiotherapy (n=114). All 229 patients were included in the intention-to-treat analysis. The median follow-up was 6·7 months (IQR 6·3–6·9). At 3 months, 40 (35%) of 114 patients in the stereotactic body radiotherapy group, and 16 (14%) of 115 patients in the conventional external beam radiotherapy group had a complete response for pain (risk ratio 1·33, 95% CI 1·14–1·55; p=0·0002). This significant difference was maintained in multivariable-adjusted analyses (odds ratio 3·47, 95% CI 1·77–6·80; p=0·0003). The most common grade 3–4 adverse event was grade 3 pain (five [4%] of 115 patients in the conventional external beam radiotherapy group vs five (5%) of 110 patients in the stereotactic body radiotherapy group). No treatment-related deaths were observed. Stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions was superior to conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions in improving the complete response rate for pain. These results suggest that use of conformal, image-guided, stereotactically dose-escalated radiotherapy is appropriate in the palliative setting for symptom control for selected patients with painful spinal metastases, and an increased awareness of the need for specialised and multidisciplinary involvement in the delivery of end-of-life care is needed. Canadian Cancer Society and the Australian National Health and Medical Research Council.

Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, which is licensed to kill following phosphorylation by its upstream regulator, RIPK3 kinase. The precise molecular details underlying MLKL activation are still emerging and, intriguingly, appear to mechanistically-diverge between species. Here, we report the structure of the human RIPK3 kinase domain alone and in complex with the MLKL pseudokinase. These structures reveal how human RIPK3 structurally differs from its mouse counterpart, and how human RIPK3 maintains MLKL in an inactive conformation prior to induction of necroptosis. Residues within the RIPK3:MLKL C-lobe interface are crucial to complex assembly and necroptotic signaling in human cells, thereby rationalizing the strict species specificity governing RIPK3 activation of MLKL. The pseudokinase MLKL is activated by the upstream kinase RIPK3 in the necroptotic pathway but the structural basis of MLKL activation is not well understood yet. Here, the authors present the crystal structures of the human RIPK3:MLKL complex and human RIPK3 kinase alone, which reveal structural differences between human and murine RIPK3 and they discuss mechanistic implications.

In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB binds to this new site and recruits its H3K27 acetylase–binding partner CBP, as well as core components of a major leukemogenic transcriptional complex that contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super-enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a general role for MYB in super-enhancer initiation. Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells.