Effect of transmission setting and mixed species infections on clinical measures of malaria in Malawi

<p>Background: In malaria endemic regions people are commonly infected with multiple species of malaria parasites but the clinical impact of these Plasmodium co-infections is unclear. Differences in transmission seasonality and transmission intensity between endemic regions have been suggested as important factors in determining the effect of multiple species co-infections.</p> <p>Principal Findings: In order to investigate the impact of multiple-species infections on clinical measures of malaria we carried out a cross-sectional community survey in Malawi, in 2002. We collected clinical and parasitological data from 2918 participants aged >6 months, and applied a questionnaire to measure malaria morbidity. We examined the effect of transmission seasonality and intensity on fever, history of fever, haemoglobin concentration ([Hb]) and parasite density, by comparing three regions: perennial transmission (PT), high intensity seasonal transmission (HIST) and low intensity seasonal transmission (LIST). These regions were defined using multi-level modelling of PCR prevalence data and spatial and geo-climatic measures. The three Plasmodium species (P. falciparum, P. malariae and P. ovale) were randomly distributed amongst all children but not adults in the LIST and PT regions. Mean parasite density in children was lower in the HIST compared with the other two regions. Mixed species infections had lower mean parasite density compared with single species infections in the PT region. Fever rates were similar between transmission regions and were unaffected by mixed species infections. A history of fever was associated with single species infections but only in the HIST region. Reduced mean [Hb] and increased anaemia was associated with perennial transmission compared to seasonal transmission. Children with mixed species infections had higher [Hb] in the HIST region.</p> <p>Conclusions: Our study suggests that the interaction of Plasmodium co-infecting species can have protective effects against some clinical outcomes of malaria but that this is dependent on the seasonality and intensity of malaria transmission.</p&gt

Tripartite ATP-Independent Periplasmic (TRAP) Transporters and Tripartite Tricarboxylate Transporters (TTT): From Uptake to Pathogenicity

The ability to efficiently scavenge nutrients in the host is essential for the viability of any pathogen. All catabolic pathways must begin with the transport of substrate from the environment through the cytoplasmic membrane, a role executed by membrane transporters. Although several classes of cytoplasmic membrane transporters are described, high-affinity uptake of substrates occurs through Solute Binding-Protein (SBP) dependent systems. Three families of SBP dependant transporters are known; the primary ATP-binding cassette (ABC) transporters, and the secondary Tripartite ATP-independent periplasmic (TRAP) transporters and Tripartite Tricarboxylate Transporters (TTT). Far less well understood than the ABC family, the TRAP transporters are found to be abundant among bacteria from marine environments, and the TTT transporters are the most abundant family of proteins in many species of β-proteobacteria. In this review, recent knowledge about these families is covered, with emphasis on their physiological and structural mechanisms, relating to several examples of relevant uptake systems in pathogenicity and colonization, using the SiaPQM sialic acid uptake system from Haemophilus influenzae and the TctCBA citrate uptake system of Salmonella typhimurium as the prototypes for the TRAP and TTT transporters, respectively. High-throughput analysis of SBPs has recently expanded considerably the range of putative substrates known for TRAP transporters, while the repertoire for the TTT family has yet to be fully explored but both types of systems most commonly transport carboxylates. Specialized spectroscopic techniques and site-directed mutagenesis have enriched our knowledge of the way TRAP binding proteins capture their substrate, while structural comparisons show conserved regions for substrate coordination in both families. Genomic and protein sequence analyses show TTT SBP genes are strikingly overrepresented in some bacteria, especially in the β-proteobacteria and some α-proteobacteria. The reasons for this are not clear but might be related to a role for these proteins in signaling rather than transport

How to Undertake a Clinically Relevant Systematic Review in a Rapidly Evolving Field: Magnetic Resonance Angiography

Objectives: The aim was to determine which generations of the evolving technology of magnetic resonance angiography (MRA) are currently of clinical relevance in two clinical applications. Our purpose was to plan a systematic review that would be valuable both to purchasers driven by cost-effectiveness and to practicing clinicians. Methods: Information was gathered from a search of major bibliographic databases, from a short questionnaire sent to 500 U.K. vascular radiologists and vascular surgeons, and from local clinical The authors thank A. Jackson and all those who completed a questionnaire. This work was carried out with the financial support of the Secretary of State for Health under the NHS Health Technology Assessment Programme, project 97/13/04. The views and opinions expressed do not necessarily reflect those of the Secretary of State for Health. In part, this work was undertaken by the Leeds Teaching Hospitals NHS Trust, which received funding from the NHS Executive. The views expressed in this publication are those of the authors and not necessarily those of the NHS Executive.experts. We asked which of the MRA techniques were currently used and, assuming availability, what would be their technique of choice. Results: There were 206 published articles that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162 questionnaires returned (60 radiologists, 102 surgeons). Of the total respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis; 47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use MRA, contrast-enhanced techniques were the method of choice. Conclusions: The TOF methods that represent earlier generations of the technology remain clinically relevant, and will therefore be included in our systematic review. To ensure complete and relevant coverage in reviews of other evolving technologies, it would be advisable to obtain data for guidance in a similar way

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review

Objective To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. Design Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. Main outcome measures Performance characteristics of diagnostic test. Results 126 potentially relevant articles were identified, but many articles failed to examine die performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. Conclusions Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes

Massive over-representation of solute-binding proteins (SBPs) from the tripartite tricarboxylate transporter (TTT) family in the genome of the α-proteobacterium Rhodoplanes sp. Z2-YC6860.

Lineage-specific expansion (LSE) of protein families is a widespread phenomenon in many eukaryotic genomes, but is generally more limited in bacterial genomes. Here, we report the presence of 434 genes encoding solute-binding proteins (SBPs) from the tripartite tricarboxylate transporter (TTT) family, within the 8.2 Mb genome of the α-proteobacterium Rhodoplanes sp. Z2-YC6860, a gene family over-representation of unprecedented abundance in prokaryotes. Representing over 6 % of the total number of coding sequences, the SBP genes are distributed across the whole genome but are found rarely in low-GC islands, where the gene density for this family is much lower. This observation, and the much higher sequence identity between the 434 Rhodoplanes TTT SBPs compared with the average identity between homologues from different species, is indicative of a key role for LSE in the expansion. The TTT SBP genes were found in the vicinity of genes encoding membrane components of transport systems from different families, as well as regulatory proteins such as histidine-kinases and transcription factors, indicating a broad range of functions around the sensing, response and transport of organic compounds. A smaller expansion of TTT SBPs is known in some species of the β-proteobacteria Bordetella and we observed similar expansions in other β-proteobacterial lineages, including members of the genus Comamonas and the industrial biotechnology organism Cupriavidus necator, indicating that strong environmental selection can drive SBP duplication and specialisation from multiple evolutionary starting points

Building an Improved Drought Climatology Using Updated Drought Tools: A New Mexico Food-Energy-Water (FEW) Systems Focus

Drought is a familiar climatic phenomenon in the United States Southwest, with complex human-environment interactions that extend beyond just the physical drought events. Due to continued climate variability and change, droughts are expected to become more frequent and/or severe in the future. Decision-makers are charged with mitigating and adapting to these more extreme conditions and to do that they need to understand the specific impacts drought has on regional and local scales, and how these impacts compare to historical conditions. Tremendous progress in drought monitoring strategies has occurred over the past several decades, with more tools providing greater spatial and temporal resolutions for a variety of variables, including drought impacts. Many of these updated tools can be used to develop improved drought climatologies for decision-makers to use in their drought risk management actions. In support of a Food-Energy-Water (FEW) systems study for New Mexico, this article explores the use of updated drought monitoring tools to analyze data and develop a more holistic drought climatology applicable for New Mexico. Based upon the drought climatology, droughts appear to be occurring with greater frequency and magnitude over the last two decades. This improved drought climatology information, using New Mexico as the example, increases the understanding of the effects of drought on the FEW systems, allowing for better management of current and future drought events and associated impacts

Long-term quality of life and cost-effectiveness of treatment of partial thickness burns: A randomized controlled trial comparing enzyme alginogel vs silver sulfadiazine (FLAM study)

The clinical effectiveness and scar quality of the randomized controlled trial comparing enzyme alginogel with silver sulfadiazine (SSD) for treatment of partial thickness burns were previously reported. Enzyme alginogel did not lead to faster wound healing (primary outcome) or less scar formation. In the current study, the health-related quality of life (HRQoL), costs, and cost-effectiveness of enzyme alginogel compared with SSD in the treatment of partial thickness burns were studied. HRQoL was evaluated using the Burn Specific Health Scale-Brief (BSHS-B) and the EQ-5D-5L questionnaire 1 week before discharge and at 3, 6, and 12 months postburn. Costs were studied from a societal perspective (health care and nonhealth-care costs) for a follow-up period of 1 year. A cost-effectiveness analysis was performed using cost-effectiveness acceptability curves and comparing differences in societal costs and Quality Adjusted Life Years (QALYs) at 1 year postburn. Forty-one patients were analyzed in the enzyme alginogel group and 48 patients in the SSD group. None o

Breaking of general rotational symmetries by multi-dimensional classical ratchets

We demonstrate that a particle driven by a set of spatially uncorrelated, independent colored noise forces in a bounded, multidimensional potential exhibits rotations that are independent of the initial conditions. We calculate the particle currents in terms of the noise statistics and the potential asymmetries by deriving an n-dimensional Fokker-Planck equation in the small correlation time limit. We analyze a variety of flow patterns for various potential structures, generating various combinations of laminar and rotational flows.Comment: Accepted, Physical Review

Neutrino Quasielastic Scattering on Nuclear Targets: Parametrizing Transverse Enhancement (Meson Exchange Currents)

We present a parametrization of the observed enhancement in the transverse electron quasielastic (QE) response function for nucleons bound in carbon as a function of the square of the four momentum transfer ($Q^2$) in terms of a correction to the magnetic form factors of bound nucleons. The parametrization should also be applicable to the transverse cross section in neutrino scattering. If the transverse enhancement originates from meson exchange currents (MEC), then it is theoretically expected that any enhancement in the longitudinal or axial contributions is small. We present the predictions of the "Transverse Enhancement" model (which is based on electron scattering data only) for the $\nu_\mu, \bar{\nu}_\mu$ differential and total QE cross sections for nucleons bound in carbon. The $Q^2$ dependence of the transverse enhancement is observed to resolve much of the long standing discrepancy in the QE total cross sections and differential distributions between low energy and high energy neutrino experiments on nuclear targets.Comment: Revised Version- July 21, 2011: 17 pages, 20 Figures. To be published in Eur. Phys. J.

Boost operators in Coulomb-gauge QCD: the pion form factor and Fock expansions in phi radiative decays

In this article we rederive the Boost operators in Coulomb-Gauge Yang-Mills theory employing the path-integral formalism and write down the complete operators for QCD. We immediately apply them to note that what are usually called the pion square, quartic... charge radii, defined from derivatives of the pion form factor at zero squared momentum transfer, are completely blurred out by relativistic and interaction corrections, so that it is not clear at all how to interpret these quantities in terms of the pion charge distribution. The form factor therefore measures matrix elements of powers of the QCD boost and Moeller operators, weighted by the charge density in the target's rest frame. In addition we remark that the decomposition of the eta' wavefunction in quarkonium, gluonium, ... components attempted by the KLOE collaboration combining data from phi radiative decays, requires corrections due to the velocity of the final state meson recoiling against a photon. This will be especially important if such decompositions are to be attempted with data from J/psi decays.Comment: 14 pages, 4 figure