Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania.

BACKGROUND\ud \ud Malaria transmission in Africa occurs predominantly inside houses where the primary vectors prefer to feed. Human preference and investment in blocking of specific entry points for mosquitoes into houses was evaluated and compared with known entry point preferences of the mosquitoes themselves.\ud \ud METHODS\ud \ud Cross-sectional household surveys were conducted in urban Dar es Salaam, Tanzania to estimate usage levels of available options for house proofing against mosquito entry, namely window screens, ceilings and blocking of eaves. These surveys also enabled evaluation of household expenditure on screens and ceilings and the motivation behind their installation.\ud \ud RESULTS\ud \ud Over three quarters (82.8%) of the 579 houses surveyed in Dar es Salaam had window screens, while almost half (48.9%) had ceilings. Prevention of mosquito entry was cited as a reason for installation of window screens and ceilings by 91.4% (394/431) and 55.7% (127/228) of respondents, respectively, but prevention of malaria was rarely cited (4.3%, 22/508). The median cost of window screens was between US $21-30 while that of ceilings was between US$301-400. The market value of insecticide-treated nets, window screening and ceilings currently in use in the city was estimated as 2, 5 and 42 million US$. More than three quarters of the respondents that lacked them said it was too expensive to install ceilings (82.2%) or window screens (75.5%).\ud \ud CONCLUSION\ud \ud High coverage and spending on screens and ceilings implies that these techniques are highly acceptable and excellent uptake can be achieved in urban settings like Dar es Salaam. Effective models for promotion and subsidization should be developed and evaluated, particularly for installation of ceilings that prevent entry via the eaves, which are the most important entry point for mosquitoes that cause malaria, a variety of neglected tropical diseases and the nuisance which motivates uptake

Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects

A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study

Experimental Evolution of an Oncolytic Vesicular Stomatitis Virus with Increased Selectivity for p53-Deficient Cells

Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53−/− MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53−/− cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy

Group-Conditional Conformal Prediction via Quantile Regression Calibration for Crop and Weed Classification

As deep learning predictive models become an integral part of a large spectrum of precision agricultural systems, a barrier to the adoption of such automated solutions is the lack of user trust in these highly complex, opaque and uncertain models. Indeed, deep neural networks are not equipped with any explicit guarantees that can be used to certify the system's performance, especially in highly varying uncontrolled environments such as the ones typically faced in computer vision for agriculture.Fortunately, certain methods developed in other communities can prove to be important for agricultural applications. This article presents the conformal prediction framework that provides valid statistical guarantees on the predictive performance of any black box prediction machine, with almost no assumptions, applied to the problem of deep visual classification of weeds and crops in real-world conditions. The framework is exposed with a focus on its practical aspects and special attention accorded to the Adaptive Prediction Sets (APS) approach that delivers marginal guarantees on the model's coverage. Marginal results are then shown to be insufficient to guarantee performance on all groups of individuals in the population as characterized by their environmental and pedo-climatic auxiliary data gathered during image acquisition.To tackle this shortcoming, group-conditional conformal approaches are presented: the ''classical'' method that consists of iteratively applying the APS procedure on all groups, and a proposed elegant reformulation and implementation of the procedure using quantile regression on group membership indicators. Empirical results showing the validity of the proposed approach are presented and compared to the marginal APS then discussed

Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed

Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)

DO PARADIGMA DO VER AO DO TOCAR. O DEVIR HÁPTICO NA CRIAÇÃO ARTÍSTICA CONTEMPORÂNEA

[EN] The issue of the primacy of the visual perception of new technologies and the role of the haptic perception, through the intensification of sensory stimulation of digital culture, constitute a landmark reference in analysis and critical reflection in the field of aesthetics. A large part of the contemporary artistic discourses operates on the body, in search of new dimensions through the senses, promoting a cognitive agency out of the interstices of the rational-mediation logic. This research assumes that the digital image leaves the Cartesian tradition and demand a response in which the phenomenological technological images find their primary sense in the body. In this way, the body appears as a center of the most avant-garde arrangements of artistic objects in the video art and contemporary visual arts. Of the time-image, image-body, fluid and interactive. It is in this framework that the concepts linked to the speech has undergone a profound Visual recontextualization in contemporary art and that new approaches claim in rupture with the models of representation based on realism of the image. Thus, video art has questioned the perception of reality through sensory consciousness and is a preferred mean of exploration of the new regime of haptic Visuality, as a ultimate symbol of the apotheosis of postmodernism. Emerges from the metamorphosis of the body and of the visual objects a proposition video-body, which integrates the experiences of transgressive haptic arrangements of the new media. The video- haptic arises, in this context, as promoter of the perceptive interweaving of synesthetic intertranslations of the sensory modalities within the contemporary art. The haptic territories of the video are therefore seen as instances that establish their own construction video processing. This research focuses on the current scenario of haptic perception in contemporary art and the new fields of action on the border of the video-haptics and outlines the relocation to a haptic aesthetics in contemporary art.[ES] La cuestión de la primacía de la percepción visual con las nuevas tecnologías y el papel de la percepción háptica mediante la intensificación de los estímulos sensoriales de la cultura digital, se constituyen como un marco referencial en análisis y reflexiones críticas en el ámbito de la estética. Gran parte de los discursos artísticos contemporáneos trabajan sobre el cuerpo, en busca de nuevas dimensiones a través de los sentidos, promoviendo una apropiación cognitiva fuera de los límites de la mediación racional-lógica. Esta investigación parte de ese presupuesto, de que la imagen digital abandona la tradición cartesiana y busca una respuesta fenomenológica en la cual las imágenes tecnológicas encuentran su sentido primario en el cuerpo. De este modo, el cuerpo se nos aparece como el centro de los logros más vanguardistas en prácticas artísticas, tanto en los discursos del videoarte como en las artes visuales contemporáneas. De la imagen-tiempo pasamos a la imagen-interfaz, una imagen-cuerpo, fluida e interactiva. Es en este marco, donde los conceptos vinculados al discurso videográfico han sufrido una profunda recontextualización en el arte contemporáneo y donde las nuevas propuestas se plantean como forma de ruptura con los modelos de representación basados en el no-realismo de la imagen. Así, el videoarte ha cuestionado la percepción de la realidad a través de la consciencia sensorial y se constituye como un medio privilegiado de exploración del nuevo régimen de visualidad háptica, como un símbolo máximo de apoteosis del pos-modernismo. Emerge de la metamorfosis del cuerpo y de los objetos virtuales una proposición de video-cuerpo que integra las experiencias transgresivas de la potencialidad háptica de los nuevos media. Lo video-háptico surge, en este contexto, como promotor del cruce perceptivo y de las inter-traducciones sinestésicas de las modalidades sensoriales en el seno del arte contemporáneo. Los territorios hápticos del video son, por tanto, vistos como instancias que se establecen en el procesamiento de la propia construcción videográfica. Esta investigación incide sobre el actual escenario de la percepción háptica en el arte contemporáneo y los nuevos campos de actuación en la frontera de lo video-háptico y anuncia la deslocalización para una estética háptica en el arte contemporáneo.[CA] La qüestió de la primacia de la percepció visual amb les noves tecnologies i el paper de la percepció hàptica mitjançant la intensificació dels estímuls sensorials de la cultura digital, es constitueixen com un marc referencial en anàlisi i reflexions crítiques en l'àmbit de l'estètica. Gran part dels discursos artístics contemporanis treballen sobre el cos, a la recerca de noves dimensions a través dels sentits, promovent una apropiació cognitiva fos dels límits de la mediació racional-lògica. Aquesta recerca parteix d'aquest pressupost, que la imatge digital abandona la tradició cartesiana i busca una resposta fenomenològica en la qual les imatges tecnològiques troben el seu sentit primari en el cos. D'aquesta manera, el cos se'ns apareix com el centre dels assoliments més avantguardistes en pràctiques artístiques, tant en els discursos del videoart com en les arts visuals contemporànies. De la imatge-temps passem a la imatge-interfície, una imatge-cos, fluïda i interactiva. És en aquest marc, on els conceptes vinculats al discurs videogràfic han sofert una profunda recontextualització en l'art contemporani i on les noves propostes es plantegen com a forma de ruptura amb els models de representació basats en el no-realisme de la imatge. Així, el videoart ha qüestionat la percepció de la realitat a través de la consciència sensorial i es constitueix com un mitjà privilegiat d'exploració del nou règim de visualitat hàptica, com un símbol màxim d'apoteosi del postmodernisme. Emergeix de la metamorfosi del cos i dels objectes virtuals una proposició de video-cos que integra les experiències transgressives de la potencialitat hàptica dels nous mitjans. El video-hàptic sorgeix, en aquest context, com a promotor de l'encreuament perceptiu i de les inter-traduccions sinestésiques de les modalitats sensorials en el si de l'art contemporani. Els territoris hàptics del video són, per tant, vists com a instàncies que s'estableixen en el processament de la pròpia construcció videogràfica Aquesta recerca incideix sobre l'actual escenari de la percepció hàptica en l'art contemporani i els nous camps d'actuació a la frontera del video-hàptic i anuncia la deslocalització per a una estètica hàptica en l'art contemporani.Aguês Da Cruz Silva, SD. (2016). DO PARADIGMA DO VER AO DO TOCAR. O DEVIR HÁPTICO NA CRIAÇÃO ARTÍSTICA CONTEMPORÂNEA [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/61441TESI

Childhood Cryptosporidiosis: A Case Report

Cryptosporidium has emerged as an important cause of diarrheal illness worldwide, especially amongst young children and patients with infectious or iatrogenic immune deficiencies. The authors describe a case of mild cryptosporidiosis in a well-nourished, immunocompetent, one-year-old child. Rapid clinical and parasitological improvement was observed after a 3-day course of nitazoxanide

Nova crise nos Grandes Lagos da África Central: o surgimento da Segunda Guerra Mundial Africana?

A new crisis in Central Africa has recently emerged, involving the rise of a Congolese armed group accused of being supported by Rwanda. The crisis brings fears of the outbreak of a new conflagration in the proportions of the so-called Africa’s World War. The article discusses the crisis and its possible outcomes and solutions.  Uma nova crise na África Central surgiu recentemente, envolvendo a ascensão de um grupo armado congolês acusado de ser apoiado por Ruanda. A crise traz temores da explosão de uma nova conflagração nas proporções da chamada Guerra Mundial Africana. O artigo discute a crise e seus possíveis desfechos e soluções

A narrative review of methods and findings on recent studies on the carriage of meningococci and other Neisseria species in the African meningitis belt

Objective To review the findings of studies of pharyngeal carriage of Neisseria meningitidis and related species conducted in the African meningitis belt since a previous review published in 2007. Methods PubMed and Web of Science were searched in July 2018 using the terms “meningococcal OR Neisseria meningitidis OR lactamica AND carriage AND Africa”, with the search limited to papers published on or after 1st January 2007. We conducted a narrative review of these publications. Results 113 papers were identified using the search terms described above, 20 of which reported new data from surveys conducted in an African meningitis belt country. These papers described 40 surveys conducted before the introduction of the group A meningococcal conjugate vaccine (MenAfriVac R) during which 66,707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from <1% to 24%. The mean pharyngeal carriage prevalence of N. meningitidis across all surveys was 4.5% [95% CI 3.4%, 6.8%] and that of capsulated N. meningitidis 2.8% [95% CI 1.9%; 5.2%]. A study of households provided strong evidence for meningococcal transmission within and outside households. The introduction of MenAfriVac® led to marked reductions in carriage of the serogroup A meningococcus in Burkina Faso and Chad. Conclusions Recent studies employing standardised methods confirm the findings of older studies that carriage of N. meningitidis in the African meningitis belt is highly variable over time and place, but generally occurs with a lower prevalence and shorter duration than reported from industrialised countries