#35 - Enamel isotopes reveal late Pleistocene ecosystem dynamics in southeastern North America

The end of the late Pleistocene (~10,000 years ago) witnessed the extinction of over seventy percent of North America’s megafaunal genera. Although this pattern has been extensively investigated, its causal mechanisms remain elusive. Much of this difficulty is related to the spatial and temporal discontinuity of sites dating to the period leading up to the extinctions. Due to its removal from glacial conditions, southeastern North America provides a unique window into ecosystem dynamics just prior to human arrival in the region. In this study, we present new stable carbon and oxygen isotope data from Mammuthus columbiand Bison latifronsteeth collected from a well-dated Last Glacial Maximum (~20,000 rcybp) locality called Clark Quarry in coastal Georgia, USA. We compare these data to those from similarly aged (middle and late Rancholabrean) localities from Florida and demonstrate the presence of a vegetation gradient with elevated levels of C3vegetation at higher latitudes. We hypothesize that this pattern may have contributed to previously described migratory patterns of mastodon (Mammut) populations in southeastern North America. Serially-sampled δ13C and δ18O values suggest that Clark Quarry Mammuthus and Bison changed their diet seasonally with the incorporation of elevated quantities of C4vegetation during warmer periods. Our data indicate more exaggerated seasonal dietary variability in these taxa at Clark Quarry relative to those collected from the interglacial locality of Waccasassa River in Florida, providing additional evidence for the significant influence of glacial dynamics in structuring North American ecosystems

Improving the use of research evidence in guideline development: 13. Applicability, transferability and adaptation

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the thirteenth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on applicability, transferability, and adaptation of guidelines. METHODS: We searched five databases for existing systematic reviews and relevant primary methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We used the definition "coming from, concerning or belonging to at least two or all nations" for the term international. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not identify systematic reviews addressing the key questions. We found individual studies and projects published in the peer reviewed literature and on the Internet. Should WHO develop international recommendations? • Resources for developing high quality recommendations are limited. Internationally developed recommendations can facilitate access to and pooling of resources, reduce unnecessary duplication, and involve international scientists. • Priority should be given to international health problems and problems that are important in low and middle-income countries, where these advantages are likely to be greatest. • Factors that influence the transferability of recommendations across different settings should be considered systematically and flagged, including modifying factors, important variation in needs, values, costs and the availability of resources. What should be done centrally and locally? • The preparation of systematic reviews and evidence profiles should be coordinated centrally, in collaboration with organizations that produce systematic reviews. Centrally developed evidence profiles should be adaptable to specific local circumstances. • Consideration should be given to models that involve central coordination with work being undertaken by centres located throughout the world. • While needs, availability of resources, costs, the presence of modifying factors and values need to be assessed locally, support for undertaking these assessments may be needed to make guidelines applicable. • WHO should provide local support for adapting and implementing recommendations by developing tools, building capacity, learning from international experience, and through international networks that support evidence-informed health policies, such as the Evidence-informed Policy Network (EVIPNet). How should recommendations be adapted? • WHO should provide detailed guidance for adaptation of international recommendations. • Local adaptation processes should be systematic and transparent, they should involve stakeholders, and they should report the key factors that influence decisions, including those flagged in international guidelines, and the reasons for any modifications that are made

Stigma and Fear: the 'Psy Professional' in Cultural Artifacts

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The loss of reason called madness provokes perhaps the greatest human fear, for it is reason that dignifies humanity and separates us from beasts. The ‘psy professionals’ - those who prescribe and administer treatments for madness - are frequently portrayed in fiction, film, comics, computer games and entertainments, along with the mad themselves and the asylums that confine them. Overall, these depictions are malign: the reader/watcher/player is encouraged to fear the mad, the madhouse and the mad-doctor. Choosing to use less abrasive vocabulary to name the condition of madness makes no difference to the terror the condition arouses, for the content of many books and games aims to inspire fear. In spite of considerable efforts over many years, the stigma which attaches to mental illness remains firmly in place for patients, while psy professionals also carry their share of “some of the discredit of the stigmatized” (Goffman 1968, p 43) and join patients in a stigmatized group. Popular belief often equates the psy professions with madness (Walter, 1989). This paper explores ways in which the fear of madness, and the stigma which clings to sufferers and their professional carers, is perpetuated by a constant stream of popular cultural artifacts

CD9 Tetraspanin Interacts with CD36 on the Surface of Macrophages: A Possible Regulatory Influence on Uptake of Oxidized Low Density Lipoprotein

CD36 is a type 2 scavenger receptor with multiple functions. CD36 binding to oxidized LDL triggers signaling cascades that are required for macrophage foam cell formation, but the mechanisms by which CD36 signals remain incompletely understood. Mass spectrometry analysis of anti-CD36 immuno-precipitates from macrophages identified the tetraspanin CD9 as a CD36 interacting protein. Western blot showed that CD9 was precipitated from mouse macrophages by anti-CD36 monoclonal antibody and CD36 was likewise precipitated by anti-CD9, confirming the mass spectrometry results. Macrophages from cd36 null mice were used to demonstrate specificity. Membrane associations of the two proteins on intact cells was analyzed by confocal immunofluorescence microscopy and by a novel cross linking assay that detects proteins in close proximity (<40 nm). Functional significance was determined by assessing lipid accumulation, foam cell formation and JNK activation in wt, cd9 null and cd36 null macrophages exposed to oxLDL. OxLDL uptake, lipid accumulation, foam cell formation, and JNK phosphorylation were partially impaired in cd9 null macrophages. The present study demonstrates that CD9 associates with CD36 on the macrophage surface and may participate in macrophage signaling in response to oxidized LDL

Intranasal Immunization with an Archaeal Lipid Mucosal Vaccine Adjuvant and Delivery Formulation Protects against a Respiratory Pathogen Challenge

Archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) is a safe mucosal adjuvant that elicits long lasting and memory boostable mucosal and systemic immune responses to model antigens such as ovalbumin. In this study, we evaluated the potential of the AMVAD system for eliciting protective immunity against mucosal bacterial infections, using a mouse model of intranasal Francisella tularensis LVS (LVS) challenge. Intranasal immunization of mice with cell free extract of LVS (LVSCE) adjuvanted with the AMVAD system (LVSCE/AMVAD) induced F. tularensis-specific antibody responses in sera and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IL-17 production. More importantly, the AMVAD vaccine partially protected the mice against a lethal intranasal challenge with LVS. Compared to LVSCE immunized and naïve mice, the LVSCE/AMVAD immunized mice showed substantial to significant reduction in pathogen burdens in the lungs and spleens, reduced serum and pulmonary levels of proinflammatory cytokines/chemokines, and longer mean time to death as well as significantly higher survival rates (p<0.05). These results suggest that the AMVAD system is a promising mucosal adjuvant and vaccine delivery technology, and should be explored further for its applications in combating mucosal infectious diseases

National Standards for Diabetes Self-Management Education and Support

By the most recent estimates, 18.8 million people in the U.S. have been diagnosed with diabetes and an additional 7 million are believed to be living with undiagnosed diabetes. At the same time, 79 million people are estimated to have blood glucose levels in the range of prediabetes or categories of increased risk for diabetes. Thus, more than 100 million Americans are at risk for developing the devastating complications of diabetes (1). Diabetes self-management education (DSME) is a critical element of care for all people with diabetes and those at risk for developing the disease. It is necessary in order to prevent or delay the complications of diabetes (2–6) and has elements related to lifestyle changes that are also essential for individuals with prediabetes as part of efforts to prevent the disease (7,8). The National Standards for Diabetes Self-Management Education are designed to define quality DSME and support and to assist diabetes educators in providing evidence-based education and self-management support. The Standards are applicable to educators in solo practice as well as those in large multicenter programs—and everyone in between. There are many good models for the provision of diabetes education and support. The Standards do not endorse any one approach, but rather seek to delineate the commonalities among effective and excellent self-management education strategies. These are the standards used in the field for recognition and accreditation. They also serve as a guide for nonaccredited and nonrecognized providers and programs. Because of the dynamic nature of health care and diabetes-related research, the Standards are reviewed and revised approximately every 5 years by key stakeholders and experts within the diabetes education community. In the fall of 2011, a Task Force was jointly convened by the American Association of Diabetes Educators (AADE) and the American Diabetes Association