Rapid turnover of the recirculating lymphocyte pool in vivo

Lymphocytes are unique among blood cells in their capacity to continually recirculate between blood and the tissues via the lymph. Previous estimates of lymphocyte lifespan in vivo and the turnover of the recirculating lymphocyte pool have been deduced from indirect labeling techniques. Using the fluorescent dye PKH-26, individual labeled cells have been tracked in sheep for periods >2 months. By direct measurement their lifespan was calculated. This label was found to be stable in vivo, allowing long-term analysis of the characteristics of the recirculating lymphocyte pool. It Is possible to calculate the rate of turnover of cells of the recirculating pool based on the rate at which labeled cells disappear from the lymphatic circulation. The recirculating lymphocyte pool was found to repopulate itself every 16.5 ± 3.0 days. Using this label, it was estimated that recirculating lymphocytes divide on average once every 29.8 ± 6.8 days. Labeled erythrocytes were also examined and found to have an average lifespan of 153 days, demonstrating no dye loss over the 2 month period of observation. These data suggest that the recirculating lymphocyte pool is a highly dynamic compartment, with a high rate of turnover and peripheral cell division in vivo. This is the first report of the direct measurement of the in vivo turnover of recirculating lymphocyte pools, and this method may now be used to further analyze the lifespan of individual lymphocyte subsets and the in vivo lifespan of other cell types in viv

Tracking dendritic cells: use of an in situ method to label all blood leukocytes

Here we describe an in situ procedure with a labeling index (percent of labeled blood leukocytes) >98%, which is high enough to permit the direct tracking of dendritic cell (DC) precursors from blood into lymphoid tissues, while circumventing the pitfalls associated with in vitro labeling. DC and lymphocytes have similar blood to afferent lymph migratory capabilities. This method has additional applications in tracking other rare cell populations in both normal and pathological state

Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control

Background: Genetically-modified (GM) mosquitoes have been proposed as part of an integrated vector control strategy for malaria control. Public acceptance is essential prior to field trials, particularly since mosquitoes are a vector of human disease and genetically modified organisms (GMOs) face strong scepticism in developed and developing nations. Despite this, in sub-Saharan Africa, where the GM mosquito effort is primarily directed, very little data is available on perspectives to GMOs. Here, results are presented of a qualitative survey of public attitudes to GM mosquitoes for malaria control in rural and urban areas of Mali, West Africa between the months of October 2008 and June 2009. Methods: The sample consisted of 80 individuals - 30 living in rural communities, 30 living in urban suburbs of Bamako, and 20 Western-trained and traditional health professionals working in Bamako and Bandiagara. Questions were asked about the cause of malaria, heredity and selective breeding. This led to questions about genetic alterations, and acceptable conditions for a release of pest-resistant GM corn and malaria-refractory GM mosquitoes. Finally, participants were asked about the decision-making process in their community. Interviews were transcribed and responses were categorized according to general themes. Results: Most participants cited mosquitoes as one of several causes of malaria. The concept of the gene was not widely understood; however selective breeding was understood, allowing limited communication of the concept of genetic modification. Participants were open to a release of pest-resistant GM corn, often wanting to conduct a trial themselves. The concept of a trial was reapplied to GM mosquitoes, although less frequently. Participants wanted to see evidence that GM mosquitoes can reduce malaria prevalence without negative consequences for human health and the environment. For several participants, a mosquito control programme was preferred; however a transgenic release that satisfied certain requirements was usually acceptable. Conclusions: Although there were some dissenters, the majority of participants were pragmatic towards a release of GM mosquitoes. An array of social and cultural issues associated with malaria, mosquitoes and genetic engineering became apparent. If these can be successfully addressed, then social acceptance among the populations surveyed seems promising

The Third wave in globalization theory

This essay examines a proposition made in the literature that there are three waves in globalization theory—the globalist, skeptical, and postskeptical or transformational waves—and argues that this division requires a new look. The essay is a critique of the third of these waves and its relationship with the second wave. Contributors to the third wave not only defend the idea of globalization from criticism by the skeptics but also try to construct a more complex and qualified theory of globalization than provided by first-wave accounts. The argument made here is that third-wave authors come to conclusions that try to defend globalization yet include qualifications that in practice reaffirm skeptical claims. This feature of the literature has been overlooked in debates and the aim of this essay is to revisit the literature and identify as well as discuss this problem. Such a presentation has political implications. Third wavers propose globalist cosmopolitan democracy when the substance of their arguments does more in practice to bolster the skeptical view of politics based on inequality and conflict, nation-states and regional blocs, and alliances of common interest or ideology rather than cosmopolitan global structures

A comparative framework: how broadly applicable is a 'rigorous' critical junctures framework?

The paper tests Hogan and Doyle's (2007, 2008) framework for examining critical junctures. This framework sought to incorporate the concept of ideational change in understanding critical junctures. Until its development, frameworks utilized in identifying critical junctures were subjective, seeking only to identify crisis, and subsequent policy changes, arguing that one invariably led to the other, as both occurred around the same time. Hogan and Doyle (2007, 2008) hypothesized ideational change as an intermediating variable in their framework, determining if, and when, a crisis leads to radical policy change. Here we test this framework on cases similar to, but different from, those employed in developing the exemplar. This will enable us determine whether the framework's relegation of ideational change to a condition of crisis holds, or, if ideational change has more importance than is ascribed to it by this framework. This will also enable us determined if the framework itself is robust, and fit for the purposes it was designed to perform — identifying the nature of policy change

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

Biosurveillance in Central Asia: Successes and Challenges of Tick-Borne Disease Research in Kazakhstan and Kyrgyzstan

Central Asia is a vast geographic region that includes five former Soviet Union republics: Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. The region has a unique infectious disease burden, and a history that includes Silk Road trade routes and networks that were part of the anti-plague and biowarfare programs in the former Soviet Union. Post Soviet Union biosurveillance research in this unique area of the world has met with several challenges, including lack of funding and resources to independently conduct hypothesis driven, peer-review quality research. Strides have been made, however, to increase scientific engagement and capability. Kazakhstan and Kyrgyzstan are examples of countries where biosurveillance research has been successfully conducted, particularly with respect to especially dangerous pathogens. In this review we describe in detail the successes, challenges and opportunities of conducting biosurveillance in Central Asia as exemplified by our recent research activities on ticks and tick-borne diseases in Kazakhstan and Kyrgyzstan

Geographic Market Definition in an International Context

Market definition is generally regarded as a key step in antitrust analysis. Market definition has two components. Product market definition seeks to include all products that are meaningful substitutes. Geographic market definition seeks to incorporate all relevant sources of the product in question. This paper is concerned with geographic market definition and, in particular, how geographic markets are defined in situations where competition may, at least to some extent, transcend national boundaries. The subject of the paper may be of some current interest for two reasons. First, the perception is widespread that, over the past twenty or so years, competition in many products and services has become increasingly international in scope and that this trend will continue. Second, the way in which foreign competition is taken into account in performing the antitrust analysis can have a dramatic impact on the legal or policy conclusions that are reached in a particular instance. The legality of a proposed merger, for example, may turn entirely on how competition from foreign sellers is treated. For antitrust purposes, when we say that competition has become more international in scope, we mean primarily that the range of possible suppliers for many goods and services to U.S. consumers increasingly includes sellers who do not produce or are not primarily headquartered in the United States or that an increasing portion of sales by American-based firms are to customers abroad. Many aspects of antitrust are potentially affected by these changes. Some of the more complex issues involve jurisdictional considerations and these will not be discussed here. As we will see, however, the subject of market definition exposes almost all of the substantive (as opposed to jurisdictional) considerations that come into play when we take account of the international aspect of certain markets. The paper has three main parts. The first focuses on the role market definition plays in antitrust analysis and, in particular, the link between market definition and market power. The second explores the particular issues that are raised with respect to market definition when there is an international aspect to competition. The final section addresses some of the empirical questions raised by the largely theoretical analysis of the first two parts of the paper