Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

The role of anti-malarial drugs in eliminating malaria

Abstract Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and transmissibility coincides with peak asexual parasite densities. Mature Plasmodium falciparum gametocytes are more drug resistant and affected only by artemisinins and 8-aminoquinolines. The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection. Radical treatment with primaquine plays a key role in the eradication of vivax and ovale malaria. More evidence is needed on the safety of primaquine when administered without screening for G6PD deficiency to inform individual and mass treatment approaches in the context of malaria elimination programmes.</p

Occupation of racial grief, loss as a resource : learning from ‘The Combahee River Collective Black Feminist Statement'

The methodology of ‘occupation’ through rereading The Combahee River Collective Black Feminist Statement (The Combahee River Collective, in: James, Sharpley-Whiting (eds) The Black Feminist Reader. Blackwell Publishers Ltd., Oxford, pp 261–270, 1977) demonstrates the necessity of temporal linkages to historical Black feminist texts and the wisdom of Black feminist situated knowers. This paper argues that racism produces grief and loss and as long as there is racism, we all remain in racial grief and loss. However, in stark contrast to the configuration of racial grief and loss as something to get over, perhaps grief and loss can be thought about differently, for example, in terms of racial grief and loss as a resource. This paper questions Western Eurocentric paternalistic responses to Black women’s ‘talk about their feelings of craziness… [under] patriarchal rule’ (The Combahee River Collective 1977: 262) and suggests alternative ways of thinking about the psychological impact of grief and loss in the context of racism. In this paper, a Black feminist occupation of racial grief and loss includes the act of residing within, and the act of working with the constituent elements of racial grief and loss. The proposal is that an occupation of racial grief and loss is a paradoxical catalyst for building a twenty-first century global intersectional Black feminist movement

Deconstructing the outsider puzzle: The legitimation journey of novelty

The proposition that outsiders often are crucial carriers of novelty into an established institutional field has received wide empirical support. But an equally compelling proposition points to the following puzzle: the very same conditions that enhance outsiders' ability to make novel contributions also hinder their ability to carry them out. We seek to address this puzzle by examining the contextual circumstances that affect the legitimation of novelty originating from a noncertified outsider that challenged the status quo in an established institutional field. Our research case material is John Harrison's introduction of a new mechanical method for measuring longitude at sea-the marine chronometer- which challenged the dominant astronomical approach.We find that whether an outsider's new offer gains or is denied legitimacy is influenced by (1) the outsider's agency to further a new offer, (2) the existence of multiple audiences with different dispositions toward this offer, and (3) the occurrence of an exogenous jolt that helps create a more receptive social space. We organize these insights into a multilevel conceptual framework that builds on previouswork but attributes a more decisive role to the interplay between endogenous and exogenous variables in shaping a field's shifting receptiveness to novelty. The framework exposes the interdependencies between the micro-, meso-, and macro-level processes that jointly affect an outsider's efforts to introduce novelty into an existing field

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background: Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method: In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results: We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion: We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values