Test characteristics of the SD FK80 Plasmodium falciparum/Plasmodium vivax malaria rapid diagnostic test in a non-endemic setting

<p>Abstract</p> <p>Background</p> <p>The SD FK80 P.f/P.v Malaria Antigen Rapid Test (Standard Diagnostics, Korea) (FK80) is a three-band malaria rapid diagnostic test detecting <it>Plasmodium falciparum </it>histidine-rich protein-2 (HRP-2) and <it>Plasmodium vivax</it>-specific lactate dehydrogenase (Pv-pLDH). The present study assessed its performance in a non-endemic setting.</p> <p>Methods</p> <p>Stored blood samples (n = 416) from international travellers suspected of malaria were used, with microscopy corrected by PCR as the reference method. Samples infected by <it>Plasmodium falciparum </it>(n = 178), <it>Plasmodium vivax </it>(n = 99), <it>Plasmodium ovale </it>(n = 75) and <it>Plasmodium malariae </it>(n = 24) were included, as well as 40 malaria negative samples.</p> <p>Results</p> <p>Overall sensitivities for the diagnosis of <it>P. falciparum </it>and <it>P. vivax </it>were 91.6% (95% confidence interval (CI): 86.2% - 95.0%) and 75.8% (65.9% - 83.6%). For <it>P. falciparum</it>, sensitivity at parasite densities ≥ 100/μl was 94.6% (88.8% - 97.6%); for <it>P. vivax</it>, sensitivity at parasite densities ≥ 500/μl was 86.8% (75.4% - 93.4%). Four <it>P. falciparum </it>samples showed a Pv-pLDH line, three of them had parasite densities exceeding 50.000/μl. Two <it>P. vivax </it>samples, one <it>P. ovale </it>and one <it>P. malariae </it>sample showed a HRP-2 line. For the HRP-2 and Pv-pLDH lines, respectively 81.4% (136/167) and 55.8% (43/77) of the true positive results were read as medium or strong line intensities. The FK80 showed good reproducibility and reliability for test results and line intensities (kappa values for both exceeding 0.80).</p> <p>Conclusion</p> <p>The FK80 test performed satisfactorily in diagnosing <it>P. falciparum </it>and <it>P. vivax </it>infections in a non-endemic setting.</p

Predictive feedback control and Fitts' law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”

From planning the port/city to planning the port-city : exploring the economic interface in European port cities

In last three decades, planning agencies of most ports have institutionally evolved into a (semi-) independent port authority. The rationale behind this process is that port authorities are able to react more quickly to changing logistical and spatial preferences of maritime firms, hence increasing the competitiveness of ports. Although these dedicated port authorities have proven to be largely successful, new economic, social, and environmental challenges are quickly catching up on these port governance models, and particularly leads to (spatial) policy ‘conflicts’ between port and city. This chapter starts by assessing this conflict and argue that the conflict is partly a result of dominant—often also academic—spatial representations of the port city as two separate entities. To escape this divisive conception of contemporary port cities, this chapter presents a relational visualisation method that is able to analyse the economic interface between port and city. Based on our results, we reflect back on our proposition and argue that the core challenge today for researchers and policy makers is acknowledging the bias of port/city, being arguably a self-fulfilling prophecy. Hence, we turn the idea of (planning the) port/city conflicts into planning the port-city’s strengths and weaknesses

Heat and dehydration induced oxidative damage and antioxidant defenses following incubator heat stress and a simulated heat wave in wild caught four-striped field mice Rhabdomys dilectus

This is the final version. Available on open access from the Public Library of Science via the DOI in this recordData Availability: All relevant data are within the manuscript and its Supporting information files.Heat waves are known for their disastrous mass die-off effects due to dehydration and cell damage, but little is known about the non-lethal consequences of surviving severe heat exposure. Severe heat exposure can cause oxidative stress which can have negative consequences on animal cognition, reproduction and life expectancy. We investigated the current oxidative stress experienced by a mesic mouse species, the four striped field mouse, Rhabdomys dilectus through a heat wave simulation with ad lib water and a more severe temperature exposure with minimal water. Wild four striped field mice were caught between 2017 and 2019. We predicted that wild four striped field mice in the heat wave simulation would show less susceptibility to oxidative stress as compared to a more severe heat stress which is likely to occur in the future. Oxidative stress was determined in the liver, kidney and brain using malondialdehyde (MDA) and protein carbonyl (PC) as markers for oxidative damage, and superoxide dismutase (SOD) and total antioxidant capacity (TAC) as markers of antioxidant defense. Incubator heat stress was brought about by increasing the body temperatures of animals to 39–40.8 C for 6 hours. A heat wave (one hot day, followed by a 3-day heatwave) was simulated by using temperature cycle that wild four striped field mice would experience in their local habitat (determined through weather station data using temperature and humidity), with maximal ambient temperature of 39 C. The liver and kidney demonstrated no changes in the simulated heat wave, but the liver had significantly higher SOD activity and the kidney had significantly higher lipid peroxidation in the incubator experiment. Dehydration significantly contributed to the increase of these markers, as is evident from the decrease in body mass after the experiment. The brain only showed significantly higher lipid peroxidation following the simulated heat wave with no significant changes following the incubator experiment. The significant increase in lipid peroxidation was not correlated to body mass after the experiment. The magnitude and duration of heat stress, in conjunction with dehydration, played a critical role in the oxidative stress experienced by each tissue, with the results demonstrating the importance of measuring multiple tissues to determine the physiological state of an animal. Current heat waves in this species have the potential of causing oxidative stress in the brain with future heat waves to possibly stress the kidney and liver depending on the hydration state of animals.University of PretoriaDST-NR

Global networks, cities and economic performance: Observations from an analysis of cities in Europe and the USA

The network paradigm has been highly influential in spatial analysis in the globalisation era. As economies across the world have become increasingly integrated, so-called global cities have come to play a growing role as central nodes in the networked global economy. The idea that a city’s position in global networks benefits its economic performance has resulted in a competitive policy focus on promoting the economic growth of cities by improving their network connectivity. However, in spite of the attention being given to boosting city connectivity little is known about whether this directly translates to improved city economic performance and, if so, how well connected a city needs to be in order to benefit from this. In this paper we test the relationship between network connectivity and economic performance between 2000 and 2008 for cities with over 500,000 inhabitants in Europe and the USA to inform European policy

European Cities in Globalization: A Comparative Analysis Based on the Location Strategies of Advanced Producer Services

Today there is a key question that lurks behind any consideration of Europe and its cities: is this foundation core zone of the modern world-system showing symptoms of dropping out of the contemporary core zone? It certainly appears that in the period of crises since 2008, Europe has been falling behind other major world-regions. Dubbed the “austerity region” of the world, such an interpretation sees Europe as the first part of the world-economy core to be subject to what are effectively structural adjustment programmes, largely self-imposed but still resulting in a process of peripheralization. Although uneven in impact, this is clearly a result of Europe’s states failing to adequately manage and regulate the economic activities within their territories. However it is far too soon to say whether such a monumental global economic shift is happening but we can investigate the current unevenness of economic globalization amongst European states. We compare three of these states that represent different degrees of potential peripheralization: Spain showing the stronger symptoms, Germany with least symptoms, and Britain somewhere in between. Our study is based upon an original analysis of advanced producer services that combines comparisons between countries and relations between cities

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Sox2 Sustains Recruitment of Oligodendrocyte Progenitor Cells following CNS Demyelination and Primes Them for Differentiation during Remyelination.

UNLABELLED: The Sox family of transcription factors have been widely studied in the context of oligodendrocyte development. However, comparatively little is known about the role of Sox2, especially during CNS remyelination. Here we show that the expression of Sox2 occurs in oligodendrocyte progenitor cells (OPCs) in rodent models during myelination and in activated adult OPCs responding to demyelination, and is also detected in multiple sclerosis lesions. In normal adult white matter of both mice and rats, it is neither expressed by adult OPCs nor by oligodendrocytes (although it is expressed by a subpopulation of adult astrocytes). Overexpression of Sox2 in rat OPCs in vitro maintains the cells in a proliferative state and inhibits differentiation, while Sox2 knockout results in decreased OPC proliferation and survival, suggesting that Sox2 contributes to the expansion of OPCs during the recruitment phase of remyelination. Loss of function in cultured mouse OPCs also results in an impaired ability to undergo normal differentiation in response to differentiation signals, suggesting that Sox2 expression in activated OPCs also primes these cells to eventually undergo differentiation. In vivo studies on remyelination following experimental toxin-induced demyelination in mice with inducible loss of Sox2 revealed impaired remyelination, which was largely due to a profound attenuation of OPC recruitment and likely also due to impaired differentiation. Our results reveal a key role of Sox2 expression in OPCs responding to demyelination, enabling them to effectively contribute to remyelination. SIGNIFICANCE STATEMENT: Understanding the mechanisms of CNS remyelination is central to developing effective means by which this process can be therapeutically enhanced in chronic demyelinating diseases such as multiple sclerosis. In this study, we describe the role of Sox2, a transcription factor widely implicated in stem cell biology, in CNS myelination and remyelination. We show how Sox2 is expressed in oligodendrocyte progenitor cells (OPCs) preparing to undergo differentiation, allowing them to undergo proliferation and priming them for subsequent differentiation. Although Sox2 is unlikely to be a direct therapeutic target, these data nevertheless provide more information on how OPC differentiation is controlled and therefore enriches our understanding of this important CNS regenerative process.This work was mainly supported by the UK Multiple Sclerosis Society.This is the final version of the article. It first appeared from the Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.3655-14.201

Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets