The Microbial Ecology of Bacterial Vaginosis: A Fine Scale Resolution Metagenomic Analysis

The vaginal microbiota play an important protective role in maintaining the health of women. Disruption of the mutualistic relationship that exists between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic acid producing bacteria are supplanted by a diverse array of strictly anaerobic bacteria. BV has been shown to be an independent risk factor for adverse outcomes including preterm delivery and low infant birth weight, acquisition of sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29.2%, and yet, despite considerable effort, the etiology of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV, and reoccurrence is common. In the proposed research we will test the overarching hypothesis that vaginal microbial community dynamics and activities are indicators of risk to BV. To do this, we propose to conduct a high resolution prospective study in which samples collected daily from 200 reproductive-age women over two menstrual cycles are used to capture molecular events that take place before, during, and after the spontaneous remission of BV episodes. We will use modern genomic technologies to obtain the data needed to correlate shifts in vaginal microbial community composition and function, metabolomes, and epidemiological and behavioral metadata with the occurrence of BV to better define the syndrome itself and identify patterns that are predictive of BV. The three specific aims of the research are: (1) Evaluate the association between the dynamics of vaginal microbial communities and risk to BV by characterizing the community composition of vaginal specimens archived from a vaginal douching cessation study in which 33 women self-collected vaginal swabs twice-weekly for 16 weeks; (2) Enroll 135 women in a prospective study in which self-collected vaginal swab samples and secretions are collected daily along with data on the occurrence of BV, vaginal pH, and information on time varying habits and practices; (3) Apply model-based statistical clustering and classification approaches to associate the microbial community composition and function, with metadata and clinical diagnoses of BV. The large body of information generated will facilitate understanding vaginal microbial community dynamics, the etiology of BV, and drive the development of better diagnostic tools for BV. Furthermore, the information will enable a more personalized and effective treatment of BV and ultimately help prevent adverse sequelae associated with this highly prevalent disruption of the vaginal microbiome

The Consequences of Repealing Health Care Reform in Early 2013

This Article evaluates the consequences of an early 2013 repeal of the enacted Health Care Reform. We consider the Act\u27s significant provisions that will have taken effect by 2013. For implemented provisions, we review their current effect on coverage, costs, and care. We then evaluate the practical consequence of the loss of those provisions. For provisions that have not yet taken effect, but will before 2013, we evaluate their projected effects in considering the consequences of repeal. Finally, for provisions that will not take effect before 2014, but where significant funds and effort will be expended prior to 2014, we evaluate those costs in considering the consequences of repeal. We conclude that the loss of many provisions would cause a significant impact. However, not all segments of the population would be equally affected by a pre-2014 repeal. Americans with basic coverage stand to lose the most. For example, changes such as the extension of dependent coverage and restrictions on annual limits have greatly increased the value of basic coverage for those who have it. Medicare recipients would similarly stand to lose from a 2013 repeal. But for those unable to afford basic comprehensive coverage, a 2013 repeal would comparatively have less effect-though a repeal after 2014 would significantly impact this group

The Consequences of Repealing Health Care Reform in Early 2013

This Article evaluates the consequences of an early 2013 repeal of the enacted Health Care Reform. We consider the Act\u27s significant provisions that will have taken effect by 2013. For implemented provisions, we review their current effect on coverage, costs, and care. We then evaluate the practical consequence of the loss of those provisions. For provisions that have not yet taken effect, but will before 2013, we evaluate their projected effects in considering the consequences of repeal. Finally, for provisions that will not take effect before 2014, but where significant funds and effort will be expended prior to 2014, we evaluate those costs in considering the consequences of repeal. We conclude that the loss of many provisions would cause a significant impact. However, not all segments of the population would be equally affected by a pre-2014 repeal. Americans with basic coverage stand to lose the most. For example, changes such as the extension of dependent coverage and restrictions on annual limits have greatly increased the value of basic coverage for those who have it. Medicare recipients would similarly stand to lose from a 2013 repeal. But for those unable to afford basic comprehensive coverage, a 2013 repeal would comparatively have less effect-though a repeal after 2014 would significantly impact this group

Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Radio Detection of Cosmic Ray Air Showers with Codalema

Studies of the radio detection of Extensive Air Showers is the goal of the demonstrative experiment CODALEMA. Previous analysis have demonstrated that detection around $5.10^{16}$ eV was achieved with this set-up. New results allow for the first time to study the topology of the electric field associated to EAS events on a event by event basis.Comment: 6 pages, 4 figures Proceedings of the Rencontres de Moriond, Very High Energy Phenomena in the Universe, La Thuile, Italy (March 12-19, 2005

Cryptic diversity within the major trypanosomiasis vector Glossina fuscipes revealed by molecular markers

Background: The tsetse fly Glossina fuscipes s.l. is responsible for the transmission of approximately 90% of cases of human African trypanosomiasis (HAT) or sleeping sickness. Three G. fuscipes subspecies have been described, primarily based upon subtle differences in the morphology of their genitalia. Here we describe a study conducted across the range of this important vector to determine whether molecular evidence generated from nuclear DNA (microsatellites and gene sequence information), mitochondrial DNA and symbiont DNA support the existence of these taxa as discrete taxonomic units. Principal Findings: The nuclear ribosomal Internal transcribed spacer 1 (ITS1) provided support for the three subspecies. However nuclear and mitochondrial sequence data did not support the monophyly of the morphological subspecies G. f.fuscipes or G. f. quanzensis. Instead, the most strongly supported monophyletic group was comprised of flies sampled fromEthiopia. Maternally inherited loci (mtDNA and symbiont) also suggested monophyly of a group from Lake Victoria basin and Tanzania, but this group was not supported by nuclear loci, suggesting different histories of these markers. Microsatellite data confirmed strong structuring across the range of G. fuscipes s.l., and was useful for deriving the interrelationship of closely related populations. Conclusion/Significance: We propose that the morphological classification alone is not used to classify populations of G. fuscipes for control purposes. The Ethiopian population, which is scheduled to be the target of a sterile insect release (SIT) programme, was notably discrete. From a programmatic perspective this may be both positive, given that it may reflect limited migration into the area or negative if the high levels of differentiation are also reflected in reproductive isolation between this population and the flies to be used in the release programme

Radio Detection of Extensive Air Showers with CODALEMA

The principle and performances of the CODALEMA experimental device, set up to study the possibility of high energy cosmic rays radio detection, are presented. Radio transient signals associated to cosmic rays have been identified, for which arrival directions and shower's electric field topologies have been extracted from the antenna signals. The measured rate, about 1 event per day, corresponds to an energy threshold around 5.10^16 eV. These results allow to determine the perspectives offered by the present experimental design for radiodetection of UHECR at a larger scale.Comment: 4 pages and 3 figures. To appear in the Proceedings of the 29th ICRC, Pune (2005