Silurian plutonism in the Trinity terrane (Neoproterozoic and Ordovician), Klamath Mountains, California, United States

New data indicate that the Trinity terrane of northern California is a polygenetic composite terrane rather than a single slice of oceanic lithosphere. We suggest approximately one third of the Trinity terrane consists of Silurian intrusive rocks that represent the roots of a previously unrecognized Silurian magmatic arc. Crosscutting relations and U‐Pb zircon isotopic data document at least one early Paleozoic deformation in the Trinity terrane of northern California. A ductile shear zone between Neoproterozoic metagabbro and Ordovician(?) harzburgite is intruded by the Upper Silurian China Mountain pluton. This evidence indicates a major early Paleozoic shear zone formed in the eastern Klamath Mountains after the Middle Ordovician but prior to Late Silurian plutonism

A summary of ODP leg 141 hydrogeologic, geochemical and thermal results

The subduction of the oceanic spreading center at the Chile Triple Junction is marked by a substantial thermal perturbation and marked changes in the hydrogeologic and aqueous geochemical regimes in the overthrust plate. Ridge subduction substantially changes the fluid chemistry in the wedge through variably hydrating the oceanic basement, accretionary wedge, and continental backstop. This generates positive anomalies in salinity and chloride values with respect to sea water. The wedge immediately above the subducted ridge also experiences greatly enhance diagenesis and cementation together with the influx of primordial mantle derived ⁴He. Linear temperature and pore fluid chemistry profiles suggest a predominantly diffusive/conductive regime predominates in the interior eastern portion of the wedge and continental backstop region. In contrast, a vigorous and transient hydrogeolgic system within 5 km of the toe of the wedge at both Sites 859 and 863 generates spatially narrow, large, and complex anomalies in temperature and fluid chemistry. At the toe the vigorous hydrogeologic system may be variably influenced by the episodic expulsion of fluid from both the deeper parts of the wedge and oceanic basement driven convection systems. Structural and diagenetic observations are also consistent with a hydrogeologic regime that both evolves with time and that is dominated by episodic processes. In particular, studies of cements, mineralized veins, deformation bands, and Fe sulfide distribution suggest that above the subducting ridge (i.e., Site 863) the lithification in the wedge is greatly enhanced and that and periods of enhanced fluid expulsion are associated with local hydrofracture and dilation episodes

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery.Chemistry and Chemical Biolog

Medical Student Attitudes toward USMLE Step 1 and Health Systems Science–A Multi-Institutional Survey

© 2020 Taylor & Francis Group, LLC. Phenomenon: Because of its importance in residency selection, the United States Medical Licensing Examination Step 1 occupies a critical position in medical education, stimulating national debate about appropriate score use, equitable selection criteria, and the goals of undergraduate medical education. Yet, student perspectives on these issues and their implications for engagement with health systems science-related curricular content are relatively underexplored. Approach: We conducted an online survey of medical students at 19 American allopathic medical schools from March-July, 2019. Survey items were designed to elicit student opinions on the Step 1 examination and the impact of the examination on their engagement with new, non-test curricular content related to health systems science. Findings: A total of 2856 students participated in the survey, representing 23.5% of those invited. While 87% of students agreed that doing well on the Step 1 exam was their top priority, 56% disagreed that studying for Step 1 had a positive impact on engagement in the medical school curriculum. Eighty-two percent of students disagreed that Step 1 scores should be the top item residency programs use to offer interviews. When asked whether Step 1 results should be reported pass/fail with no numeric score, 55% of students agreed, while 33% disagreed. The majority of medical students agreed that health systems science topics were important but disagreed that studying for Step 1 helped learn this content. Students reported being more motivated to study a topic if it was on the exam, part of a course grade, prioritized by residency program directors, or if it would make them a better physician in the future. Insights: These results confirm the primacy of the United States Medical Licensing Examination Step 1 exam in preclinical medical education and demonstrate the need to balance the objectives of medical licensure and residency selection with the goals of the broader medical profession. The survey responses suggest several potential solutions to increase student engagement in health systems science curricula which may be especially important after Step 1 examination results are reported as pass/fail