Vascular remodeling of the mouse yolk sac requires hemodynamic force

The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a^(–/–)). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sa

On a Sea of Sand: A Comparative Analysis of the Challenges to Beached Wreck Site Stability and Management

The archaeological remains of ships in the beach zone are part of a complex and dynamic system, being periodically exposed and reburied, they vary between being both visible and frequently forgotten features of the physical and cultural coastal landscape. These limited and nonrenewable resources play an important informational role as tangible pieces of maritime heritage that also document dynamic coastal processes. Shipwreck remains in the beach zone are highly susceptible to instability within the landscape. This instability in turn, affects decisions regarding importance and management strategies. The challenges to certain management strategies may result in these resources being damaged, ignored or forgotten, leading to a potential loss of pertinent social, economic, and physical information. Although little can be done to prevent natural coastal processes, a better understanding of them allows for their mitigation and management. At the same time, an understanding of perceptions toward the beached wreck resource and associated management practices may guide practitioner decision-making and allow for the development of appropriate and innovative strategies of management

A Discourse on Drawings: Amateurs and Connoisseurs and the graphic arts in early eighteenth-century Paris

This study looks at a group of art collectors whose interests in the graphic arts contributed to the status of drawings in Paris in the first half of the eighteenth century. The collection of 19,000 drawings formed by Pierre Crozat (1665 – 1740) provided the locus for a discourse on the graphic arts that developed outside of the Royal Academy of Painting and Sculpture. The print-making initiatives of the members of this circle and their writings helped to elevate the status of drawings from a secondary art form in service to the noble arts of painting or sculpture to one wherein drawings were appreciated in their own right. Pierre-Jean Mariette (1694 – 1775) and Anne-Claude-Philippe de Tubières, le comte de Caylus (1692 – 1765) and Antoine-Joseph Dezallier d’Argenville (1680 – 1765) among others brought a focus and attention to the graphic arts which had a profound effect on the developing connoisseurship and critical discourse on prints and drawings in the first half of the eighteenth century

Scattered to the Wind : An Evaluation of the Disaster Landscape of Coastal North Carolina

Coastal North Carolina has had a long and intimate relationship with severe weather events, the outcome of which has affected the physical, economical, and social structures of the State. The primary objective of this thesis is to investigate historical storm occurrences in coastal North Carolina in order to determine a correlation between weather disasters and the initial settlement, sustained occupation, or abandonment of occupied lands. Utilizing geographic information systems (GIS) to explore historical hurricane tracks and shipwreck and land site loss, spatial and temporal analysis can provide insight into how the disaster landscape is reflected in settlement patterns and loss versus survivability, as well as the social, economic, or environmental factors that have shaped continued and subsequent settlement and trade in coastal North Carolina.  M.A

Cost-Effectiveness of an Emergency Department Based Early Sepsis Resuscitation Protocol

Background Guidelines recommend that sepsis be treated with an early resuscitation protocol, such as early goal directed therapy (EGDT). Our objective was to assess the cost-effectiveness of implementing EGDT as a routine protocol. Design Prospective before and after study. Setting Large urban hospital ED with >110,000 visits/year. Patients The target population was patients with consensus criteria for septic shock. We excluded those with age <18 yrs, no aggressive care desired, or need for immediate surgery. Interventions Clinical and cost data were prospectively collected on two groups: 1) patients from 1 yr before and 2) 2 yrs after implementing EGDT as standard-of-care. Before phase patients received nonprotocolized care at attending discretion. The primary outcomes were one year mortality, discounted life expectancy, and quality adjusted life years (QALYs). Using costs and QALYs, we constructed an incremental cost-effectiveness ratio and performed a net monetary benefit (NMB) analysis, producing the probability that the intervention was cost-effective given different values for the willingness to pay for a QALY. Results 285 subjects, 79 in the before and 206 in the after phases, were enrolled. Treatment with EGDT was associated with an increased hospital cost of $7028 and an increase in both discounted sepsis-adjusted life expectancy and QALYs of 1.5 and 1.3 yrs, respectively. EGDT use was associated with a cost of$5397 per QALY gained and the NMB analysis indicates a 98% probability (p = .038) that EGDT is cost-effective at a willingness to pay of $50,000 per QALY. Conclusion Implementation of EGDT in the ED care of severe sepsis patients is cost effective

Immediate replacement of fishing with dairying by the earliest farmers of the NE Atlantic archipelagos

The appearance of farming, from its inception in the Near East around 12 000 years ago, finally reached the northwestern extremes of Europe by the fourth millennium BC or shortly thereafter. Various models have been invoked to explain the Neolithization of northern Europe; however, resolving these different scenarios has proved problematic due to poor faunal preservation and the lack of specificity achievable for commonly applied proxies. Here, we present new multi-proxy evidence, which qualitatively and quantitatively maps subsistence change in the northeast Atlantic archipelagos from the Late Mesolithic into the Neolithic and beyond. A model involving significant retention of hunter–gatherer–fisher influences was tested against one of the dominant adoptions of farming using a novel suite of lipid biomarkers, including dihydroxy fatty acids, ω-(o-alkylphenyl)alkanoic acids and stable carbon isotope signatures of individual fatty acids preserved in cooking vessels. These new findings, together with archaeozoological and human skeletal collagen bulk stable carbon isotope proxies, unequivocally confirm rejection of marine resources by early farmers coinciding with the adoption of intensive dairy farming. This pattern of Neolithization contrasts markedly to that occurring contemporaneously in the Baltic, suggesting that geographically distinct ecological and cultural influences dictated the evolution of subsistence practices at this critical phase of European prehistory