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Rock art compels interest from both researchers and a broader public, inspiring many hypotheses about its cultural origin and meaning, but it is notoriously difficult to date numerically. Barrier Canyon-style (BCS) pictographs of the Colorado Plateau are among the most debated examples; hypotheses about its age span the entire Holocene epoch and previous attempts at direct radiocarbon dating have failed. We provide multiple age constraints through the use of cross-cutting relations and new and broadly applicable approaches in optically stimulated luminescence dating at the Great Gallery panel, the type section of BCS art in Canyonlands National Park, southeastern Utah. Alluvial chronostratigraphy constrains the burial and exhumation of the alcove containing the panel, and limits are also set by our related research dating both a rockfall that removed some figures and the rock’s exposure duration before that time. Results provide a maximum possible age, a minimum age, and an exposure time window for the creation of the Great Gallery panel, respectively. The only prior hypothesis not disproven is a late Archaic origin for BCS rock art, although our age result of A.D. ∼1–1100 coincides better with the transition to and rise of the subsequent Fremont culture. This chronology is for the type locality only, and variability in the age of other sites is likely. Nevertheless, results suggest that BCS rock art represents an artistic tradition that spanned cultures and the transition from foraging to farming in the region.Archaeology is focused upon material records, contextualized in time. Rock art is a record with the potential to provide unique insight into the dynamics and evolution of culture, but it generally lacks stratigraphic or chronologic context. Interpretation of the origin and meaning of rock art is indirect at best, or simply speculative. In the case of some pictographs, pigments may include or have enough accessory carbon for accelerator mass spectrometry (AMS) radiocarbon dating (14). In other special situations, such as caves, minimum age constraints have been obtained by various techniques of dating material that overlies or entombs rock art (57). However, most rock art remains undatable and researchers rely upon stylistic comparison and indirect associations with artifacts at nearby sites (8, 9). The case in point for this study is arguably the most compelling and debated rock art in the United States—the Barrier Canyon style (BCS) of the Colorado Plateau. Previous attempts to derive an absolute chronology have failed and its age remains unknown, with widely ranging hypotheses that have remained untested until now.The continued development of dating techniques offers new possibilities for hypothesis testing. The optically stimulated luminescence (OSL) signals from mineral grains make it possible to date the deposition of most sediment that is exposed to a few seconds of full sunlight before burial, and its use in the earth and cultural sciences has greatly increased (10, 11). Among the latest applications of OSL are techniques dating the outer surfaces of rock clasts that have become shielded from light, including those with archaeological context (1215). Recent work has furthermore used the “bleaching” profile of decreasing luminescence signal toward the surface of rock to estimate exposure time to sunlight (16, 17). Using these dating tools, we can constrain the age of rock art and gain new insight into past cultures and landscapes.Here, we synthesize results from three approaches to dating the type section of BCS art, the Great Gallery in Canyonlands National Park of southeastern Utah. Through dating the full alluvial stratigraphy and a rockfall event that both have incontrovertible cross-cutting relations with the rock art, and then by determining the exposure duration of a painted rock surface, we greatly narrow the window of time when the rock art was created. These approaches do not require direct sampling of rock art and have strong potential for application to other archaeological and surface processes research. Although our results are only for the type section of BCS art, and chronological variability should be expected for the style across the region, they suggest that BCS art coincides with the transition to agriculture in the northern Colorado Plateau and may not have been limited to a specific archaeological culture.  相似文献   
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Systemic lupus erythematosus (SLE) is a chronic, relapsing autoimmune connective tissue disease, primarily affecting the skin, joints, kidneys, heart, lungs, nervous system, blood elements, and serosal membranes. SLE is characterized by cytokine dysregulation, polyclonal B-cell activation, autoantibody production, and increased immune complex formation due to aberrations involving hyperactive B cells, T cells, and cells of the monocytic lineage. The symptoms of SLE are often diverse and nonspecific, and timely identification of SLE and associated comorbidities in patients is critical as aggressive monitoring and therapy may be warranted, especially in patients with poor prognoses. Based on the up-to-date understanding of the pathophysiology of SLE, the first targeted biological agent belimumab has been approved by the US Food and Drug Administration (FDA) in more than 50 years, and many targeted agents are being evaluated in late-stage clinical trials. There is a clear need to discuss how and when to incorporate new and emerging biological agents in managing patients with SLE. Additionally, the potential for increased risk of infections is a factor that heavily influences the rheumatologist?s decision to use biological agents in managing patients with SLE. Hence, in this roundtable educational activity, expert faculty will review and discuss the strategies for timely diagnosis of SLE and associated comorbidities. They will also discuss the current understanding of the pathophysiology of SLE and how new and emerging biological agents help address the underlying pathophysiological aberrations in patients with SLE. The faculty will also review strategies to minimize the risk of infections and other toxicities in patients with SLE.  相似文献   
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Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non‐validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non‐validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country‐specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross‐checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors.  相似文献   
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Introduction

Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing.

Materials/Methods

This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/− trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes.

Results/Conclusion

Women with MHV (N = 4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N = 12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P < 0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.  相似文献   
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Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV-treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca(2+) influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV(-/-) mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV(-/-) mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes.  相似文献   
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