Focus–specific clinical profiles in human African trypanosomiasis caused by <i>Trypanosoma brucei rhodesiense</i>

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Diverse clinical features have been reported in human African trypanosomiasis (HAT) foci caused by &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; (&lt;i&gt;T.b.rhodesiense&lt;/i&gt;) giving rise to the hypothesis that HAT manifests as a chronic disease in South-East African countries and increased in virulence towards the North. Such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. Our molecular tools allow us to study the role of host and parasite genotypes, but obtaining matched extensive clinical data from a large cohort of HAT patients has previously proved problematic.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods/Principal Findings:&lt;/b&gt; We present a retrospective cohort study providing detailed clinical profiles of 275 HAT patients recruited in two northern foci (Uganda) and one southern focus (Malawi) in East Africa. Characteristic clinical signs and symptoms of &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection were recorded and the degree of neurological dysfunction determined on admission. Clinical observations were mapped by patient estimated post-infection time. We have identified common presenting symptoms in &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection; however, marked differences in disease progression and severity were identified between foci. HAT was characterised as a chronic haemo-lymphatic stage infection in Malawi, and as an acute disease with marked neurological impairment in Uganda. Within Uganda, a more rapid progression to meningo-encephaltic stage of infection was observed in one focus (Soroti) where HAT was characterised by early onset neurodysfunction; however, severe neuropathology was more frequently observed in patients in a second focus (Tororo).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; We have established focus-specific HAT clinical phenotypes showing dramatic variations in disease severity and rate of stage progression both between northern and southern East African foci and between Ugandan foci. Understanding the contribution of host and parasite factors in causing such clinical diversity in &lt;i&gt;T.b.rhodesiense&lt;/i&gt; HAT has much relevance for both improvement of disease management and the identification of new drug therapy.&lt;/p&gt

FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel

Hair cells in mouse cochlear cultures are selectively labeled by brief exposure to FM1-43, a styryl dye used to study endocytosis and exocytosis. Real-time confocal microscopy indicates that dye entry is rapid and via the apical surface. Cooling to 4°C and high extracellular calcium both reduce dye loading. Pretreatment with EGTA, a condition that breaks tip links and prevents mechanotransducer channel gating, abolishes subsequent dye loading in the presence of calcium. Dye loading recovers after calcium chelation with a time course similar to that described for tip-link regeneration. Myo7a mutant hair cells, which can transduce but have all mechanotransducer channels normally closed at rest, do not label with FM1-43 unless the bundles are stimulated by large excitatory stimuli. Extracellular perfusion of FM1-43 reversibly blocks mechanotransduction with half-blocking concentrations in the low micromolar range. The block is reduced by high extracellular calcium and is voltage dependent, decreasing at extreme positive and negative potentials, indicating that FM1-43 behaves as a permeant blocker of the mechanotransducer channel. The time course for the relief of block after voltage steps to extreme potentials further suggests that FM1-43 competes with other cations for binding sites within the pore of the channel. FM1-43 does not block the transducer channel from the intracellular side at concentrations that would cause complete block when applied extracellularly. Calcium chelation and FM1-43 both reduce the ototoxic effects of the aminoglycoside antibiotic neomycin sulfate, suggesting that FM1-43 and aminoglycosides enter hair cells via the same pathway

Permeability of compacting porous lavas

The highly transient nature of outgassing commonly observed at volcanoes is in part controlled by the permeability of lava domes and shallow conduits. Lava domes generally consist of a porous outer carapace surrounding a denser lava core with internal shear zones of variable porosity. Here we examine densification using uniaxial compression experiments on variably crystalline and porous rhyolitic dome lavas from the Taupo Volcanic Zone. Experiments were conducted at 900°C and an applied stress of 3MPa to 60% strain, while monitoring acoustic emissions to track cracking. The evolution of the porous network was assessed via X-ray computed tomography, He-pycnometry, and relative gas permeability. High starting connected porosities led to low apparent viscosities and high strain rates, initially accompanied by abundant acoustic emissions. As compaction ensued, the lavas evolved; apparent viscosity increased and strain rate decreased due to strain hardening of the suspensions. Permeability fluctuations resulted from the interplay between viscous flow and brittle failure. Where phenocrysts were abundant, cracks had limited spatial extent, and pore closure decreased axial and radial permeability proportionally, maintaining the initial anisotropy. In crystal-poor lavas, axial cracks had a more profound effect, and permeability anisotropy switched to favor axial flow. Irrespective of porosity, both crystalline samples compacted to a threshold minimum porosity of 17–19%, whereas the crystal-poor sample did not achieve its compaction limit. This indicates that unconfined loading of porous dome lavas does not necessarily form an impermeable plug and may be hindered, in part by the presence of crystals

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn’s disease

Background: The faecal calprotectin (FC) test is a non-invasive marker for gastrointestinal inflammation. Aim: To determine whether higher FC levels in individuals with quiescent Crohn’s disease are associated with clinical relapse over the ensuing 12 months.&lt;p&gt;&lt;/p&gt; Methods: A single centre prospective study was undertaken in Crohn's disease patients in clinical remission attending for routine review. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan-Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse.&lt;p&gt;&lt;/p&gt; Results: Of 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) had relapsed by 12 months. The median FC was lower for non-relapsers, 96µg/g (IQR 39-237), than for relapsers, 414µg/g (IQR 259-590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240µg/g to predict relapse of quiescent Crohn’s had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%. FC≥240μg/g was associated with likelihood of relapse 5.7 (95% CI 1.9-17.3) times higher within 2.3 years than lower values (p=0.002).&lt;p&gt;&lt;/p&gt; Conclusions: In this prospective dataset, FC appears to be a useful, non-invasive tool to help identify quiescent Crohn’s disease patients at a low risk of relapse over the ensuing 12 months. FC of 240µg/g was the optimal cutoff in this cohort.&lt;p&gt;&lt;/p&gt

Infrared Features of the Landau Gauge QCD

The infrared features of Landau gauge QCD are studied by the lattice simulation of $\beta=6.0, 16^4, 24^4, 32^4$ and $\beta=6.4, 32^4, 48^4$. We adopt two definitions of the gauge field; 1) $U-$linear 2) $\log U$ and measured the gluon propagator and ghost propagator. Infrared singularity of the gluon propagator is less than that of tree level result but the gluon propagator at 0 momentum remains finite. The infrared singularity of ghost propagator is stronger than the tree level. The QCD running coupling measured by using the gluon propagator and the ghost propagator has a maximum $\alpha_s(p)\simeq 1$ at around $p=0.5GeV$ and decreases as $p$ approaches 0. The data are analyzed in use of formula of the principle of minimal sensitivity(PMS), the effective charge method and the contour-improved perturbation method, which suggest necessity of the resummation of perturbation series in the infrared region together with existence of the infrared fixed point. Kugo-Ojima parameter saturates at about -0.8 in contrast to the theoretically expected value -1.Comment: RevTex4, 9 pages, 10 eps figures, Typos corrected. To be published in Phys. Rev. D(2004

Thermodynamic studies of the two dimensional Falicov-Kimball model on a triangular lattice

Thermodynamic properties of the spinless Falicov-Kimball model are studied on a triangular lattice using numerical diagonalization technique with Monte-Carlo simulation algorithm. Discontinuous metal-insulator transition is observed at finite temperature. Unlike the case of square lattice, here we observe that the finite temperature effect is not able to smear out the discontinuous metal-insulator transition seen in the ground state. Calculation of specific heat (C_v) shows single and double peak structures for different values of parameters like on-site correlation strength (U), f-electron energy (E_f) and temperature.Comment: 6 pages, 7 figure

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect