The Paisley Caves in Oregon record the oldest directly dated human remains (DNA) in the Western Hemisphere. More than 100 high-precision radiocarbon dates show that deposits containing artifacts and ...coprolites ranging in age from 12,450 to 2295 ¹⁴C years ago are well stratified. Western Stemmed projectile points were recovered in deposits dated to 11,070 to 11,340 ¹⁴C years ago, a time contemporaneous with or preceding the Clovis technology. There is no evidence of diagnostic Clovis technology at the site. These two distinct technologies were parallel developments, not the product of a unilinear technological evolution. "Blind testing" analysis of coprolites by an independent laboratory confirms the presence of human DNA in specimens of pre-Clovis age. The colonization of the Americas involved multiple technologically divergent, and possibly genetically divergent, founding groups.
To better understand the formation conditions of ferromagnesian chondrules from the Renazzo‐like carbonaceous (CR) chondrites, a systematic study of 210 chondrules from 15 CR chondrites was ...conducted. The texture and composition of silicate and opaque minerals from each observed FeO‐rich (type II) chondrule, and a representative number of FeO‐poor (type I) chondrules, were studied to build a substantial and self‐consistent data set. The average abundances and standard deviations of Cr2O3 in FeO‐rich olivine phenocrysts are consistent with previous work that the CR chondrites are among the least thermally altered samples from the early solar system. Type II chondrules from the CR chondrites formed under highly variable conditions (e.g., precursor composition, redox conditions, cooling rate), with each chondrule recording a distinct igneous history. The opaque minerals within type II chondrules are consistent with formation during chondrule melting and cooling, starting as S‐ and Ni‐rich liquids at 988–1350 °C, then cooling to form monosulfide solid solution (mss) that crystallized around olivine/pyroxene phenocrysts. During cooling, Fe,Ni‐metal crystallized from the S‐ and Ni‐rich liquid, and upon further cooling mss decomposed into pentlandite and pyrrhotite, with pentlandite exsolving from mss at 400–600 °C. The composition, texture, and inferred formation temperature of pentlandite within chondrules studied here is inconsistent with formation via aqueous alteration. However, some opaque minerals (Fe,Ni‐metal versus magnetite and panethite) present in type II chondrules are a proxy for the degree of whole‐rock aqueous alteration. The texture and composition of sulfide‐bearing opaque minerals in Graves Nunataks 06100 and Grosvenor Mountains 03116 suggest that they are the most thermally altered CR chondrites.
AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ ...6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy.
During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 CRP) < 2.6, were assessed. For patients achieving early sustained SDAI remission at weeks 24/40/52, flow between disease activity categories and individual trajectories was evaluated; flow was also evaluated for later remitters (weeks 40/52 but not week 24).
Among patients treated with abatacept + methotrexate (n/N = 451/752) at IP week 24, 22% achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved DAS28 (CRP) < 2.6; of these, 56%, 58%, and 74%, respectively, sustained a response throughout IP weeks 40/52. Among patients with a sustained response at IP weeks 24/40/52, 82% (14/17) on weekly abatacept + methotrexate, 81% (13/16) on abatacept monotherapy, 63% (12/19) who de-escalated/withdrew abatacept, and 65% (11/17) on abatacept placebo + methotrexate were in SDAI remission at end of the DE period; rates were higher than for later remitters in all arms except abatacept placebo + methotrexate.
A high proportion of individual patients achieving clinical endpoints at IP week 24 with abatacept + methotrexate sustained their responses through week 52. Of patients achieving early and sustained SDAI remission through 52 weeks, numerically more maintained remission during the DE period if weekly abatacept treatment continued.
NCT02504268 (ClinicalTrials.gov), registered July 21, 2015.
Three evolutionarily distinct families of replicative DNA polymerases, designated polymerase B (Pol B), Pol C, and Pol D, have been identified. Members of the Pol B family are present in all three ...domains of life, whereas Pol C exists only in Bacteria and Pol D exists only in Archaea. Pol B enzymes replicate eukaryotic chromosomal DNA, and as members of the Pol B family are present in all Archaea, it has been assumed that Pol B enzymes also replicate archaeal genomes. Here we report the construction of Thermococcus kodakarensis strains with mutations that delete or inactivate key functions of Pol B. T. kodakarensis strains lacking Pol B had no detectable loss in viability and no growth defects or changes in spontaneous mutation frequency but had increased sensitivity to UV irradiation. In contrast, we were unable to introduce mutations that inactivated either of the genes encoding the two subunits of Pol D. The results reported establish that Pol D is sufficient for viability and genome replication in T. kodakarensis and argue that Pol D rather than Pol B is likely the replicative DNA polymerase in this archaeon. The majority of Archaea contain Pol D, and, as discussed, if Pol D is the predominant replicative polymerase in Archaea, this profoundly impacts hypotheses for the origin(s), evolution, and distribution of the different DNA replication enzymes and systems now employed in the three domains of life.
Tidal marshes (including saltmarshes) provide remarkable value for many social (cultural, recreational) and environmental (fish production, water quality, shoreline protection, carbon sequestration) ...services. However, their extent, condition, and capacity to support these services are threatened by human development expansion, invasive species, erosion, altered hydrology and connectivity, and climate change. The past two decades have seen a shift toward working with managers to restore tidal marshes to conserve existing patches or create new marshes. The present perspective examines key features of recent tidal marsh restoration projects. Although optimism about restoration is building, not all marshes are the same; site-specific nuances require careful consideration, and thus, standard restoration designs are not possible. Restoration projects are effectively experiments, requiring clear goals, monitoring and evaluation, and adaptive management practices. Restoration is expensive; however, payment schemes for ecosystem services derived from restoration offer new ways to fund projects and appropriate monitoring and evaluation programs. All information generated by restoration needs to be published and easily accessible, especially failed attempts, to equip practitioners and scientists with actionable knowledge for future efforts. We advocate the need for a network of tidal marsh scientists, managers, and practitioners to share and disseminate new observations and knowledge. Such a network will help augment our capacity to restore tidal marsh, but also valuable coastal ecosystems more broadly.
Cougar Mountain Cave is located in Oregon's Fort Rock Basin. In 1958, avocationalist John Cowles excavated most of the cave's deposits and recovered abundant fiber, lithic, wood, and osseous ...artifacts. A crew from the University of California, Davis returned to the site in 1966 to evaluate the potential for further research, collecting additional lithic and fiber artifacts from disturbed deposits and in situ charcoal from apparently undisturbed deposits. Because Cowles took few notes or photographs, the Cougar Mountain Cave collection—most of which is housed at the Favell Museum in Klamath Falls, Oregon—has largely gone unstudied even though it contains diagnostic artifacts spanning the Holocene and, potentially, the terminal Pleistocene. We recently submitted charcoal and basketry from the site for radiocarbon dating, providing the first reliable sense of when Cougar Mountain Cave was first occupied. Our results indicate at least a Younger Dryas age for initial occupation. The directly dated basketry has provided new information about the age ranges and spatial distributions of diagnostic textile types in the northwestern Great Basin. La Cueva de Cougar Mountain se encuentra en la Cuenca de Fort Rock, en Oregón. En 1958, el arqueólogo vocacional John Cowles excavó la mayor parte de los depósitos de la cueva y recuperó abundantes artefactos de fibra, piedra tallada, madera y hueso. Un equipo de la Universidad de California, Davis, regresó al sitio en 1966 para evaluar su potencial investigativo. Durante esta visita también se recolectaron nuevos artefactos líticos y de fibra de los depósitos perturbados y se tomaron muestras de carbón in situ de depósitos aparentemente intactos. Debido a que Cowles tomó pocas notas o fotografías, la colección de la Cueva de Cougar Mountain, la mayoría de la cual está almacenada en el Museo Favell en Klamath Falls, Oregón, ha quedado sin estudiar, a pesar de que contiene artefactos que abarcan el Holoceno y, potencialmente, el Pleistoceno terminal. Hace poco sometimos muestras de carbón y cestería del sitio a datación por radiocarbono, lo que nos proporcionó una primera estimación confiable de la ocupación inicial en la Cueva de Cougar Mountain. Nuestros resultados indican que la ocupación inicial ocurrió por lo menos en el Dryas Reciente. La cestería, que fue fechada directamente, nos proporciona nueva información sobre los rangos de edad y la distribución espacial de tipos de textiles diagnósticos en el noroeste de la Gran Cuenca.
Background and objective
Functional outcome after spontaneous intracerebral hemorrhage (ICH) may vary depending on hematoma volume and location. We assessed the interaction between hematoma volume ...and location, and modified the original ICH score to include such an interaction.
Methods
Consecutive ICH patients were enrolled in the Intracerebral Hemorrhage Outcomes Project from 2009 to 2017. Inclusion criteria were age≥18 years, baseline modified Rankin Scale (mRS) score 0–2, neuroimaging, and follow-up. Functional dependence and mortality were defined as 90-day mRS>2 and death, respectively. A location ICH score was developed using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses.
Results
The study cohort comprised 311 patients, and the derivation and validation cohorts comprised 209 and 102 patients, respectively. Interactions between hematoma volume and location predicted functional dependence (p = 0.008) and mortality (p = 0.025). The location ICH score comprised age≥80 years (1 point), Glasgow Coma Scale score (3–9 = 2 points; 10–13 = 1 point), volume–location (lobar:≥24 mL=2 points, 21–24 mL=1 point; deep:≥8 mL=2 points, 7–8 mL=1 point; brainstem:≥6 mL=2 points, 3–6 mL=1 point; cerebellum:≥24 mL=2 points, 12–24 mL=1 point), and intraventricular hemorrhage (1 point). AUROC of the location ICH score was higher in functional dependence (0.883 vs. 0.770, p = 0.002) but not mortality (0.838 vs. 0.841, p = 0.918) discrimination compared to the original ICH score.
Conclusions
The interaction between hematoma volume and location exerted an independent effect on outcomes. Excellent discrimination of functional dependence and mortality was observed with incorporation of location-specific volume thresholds into a prediction model. Therefore, the volume–location relationship plays an important role in ICH outcome prediction.
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