Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: the role of inadequate secondary prophylaxis.

OBJECTIVES: Cryptococcal meningitis is the commonest cause of adult meningitis in Southern Africa. A sizeable proportion of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We carried out a study to examine the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal meningitis. DESIGN: A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town. OUTCOME MEASURES: Relapse episodes were categorized into 1) patients not taking fluconazole prophylaxis, 2) immune reconstitution inflammatory syndrome (IRIS) and 3) relapses occurring prior to ART in patients taking fluconazole. In-hospital mortality was recorded. RESULTS: There were 69 relapse episodes, accounting for 23% of all cases of cryptococcal meningitis. 43%(n=30) of relapse episodes were in patients not taking fluconazole prophylaxis, 45%(31) were due to IRIS and 12%(8) were in patients pre-ART taking fluconazole. Patients developing relapse due to inadequate secondary prophylaxis had severe disease and high in-hospital mortality (33%). Of the 30 patients not taking fluconazole, 47% (14) had not been prescribed secondary prophylaxis by their healthcare providers. Importantly, we documented no relapses due to fluconazole resistance in this cohort of patients who has received amphotericin B as initial therapy. CONCLUSIONS: Large numbers of relapses of cryptococcal meningitis are due to failed prescription, dispensing, referral for or adherence to secondary fluconazole prophylaxis. Interventions to improve the use of secondary fluconazole prophylaxis are essential

Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial.

BACKGROUND: Interferon-gamma (IFNγ) is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis remains high, and novel treatment strategies are needed. We performed a randomized controlled trial to determine whether addition of IFNγ to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated cryptococcal meningitis. METHODS: Patients were randomized to amphotericin B 1 mg/kg per day and 5FC 100 mg/kg per day for 2 weeks (standard therapy), standard therapy and IFNγ1b 100 μg days 1 and 3 (IFNγ two doses), or standard therapy and IFNγ1b 100 μg days 1, 3, 5, 8, 10 and 12 (IFNγ six doses). Primary outcome was rate of clearance of cryptococcus from the cerebrospinal fluid (CSF) (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival. RESULTS: Rate of fungal clearance was significantly faster in IFNγ containing groups than with standard treatment. Mean EFA [log colony forming unit (CFU)/ml per day] was -0.49 with standard treatment, -0.64 with IFNγ two doses, and -0.64 with IFNγ six doses. Difference in EFA was -0.15 [confidence interval (95% CI) -0.02 to -0.27, P=0.02] between standard treatment and IFNγ two doses, and -0.15 (95% CI -0.05 to -0.26, P=0.006) between standard treatment and IFNγ six doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated. CONCLUSION: Addition of short-course IFNγ to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFNγ are as effective as six doses

On-chip food safety monitoring: multi-analyte screening with imaging surface plasmon resonance-based biosensor

Food safety is an increasing health concern, recognised and promoted by many institutions across the globe. Food products can be contaminated with pathogenic microorganisms, environmental pollutants, veterinary drug residues, allergens and toxins. Public health concerns which have been raised in relation to hazardous agents found in food include, among others, increased cancer risk, endocrine, reproductive and neurobehavioral systems disruption, teratogenesis, antibiotic resistance and even death in cases of allergic reactions and acute poisoning. Some of the food hazardous agents (e.g. pathogenic microorganisms and toxins) can even be used as biological warfare, spread through food and agricultural chains. Thus, an adequate detection of these compounds is also important for biosecurity. In order to safeguard consumers’ health, legislations have been put in place both in the US and the EU. These laws specify for each health threatening compound the maximal acceptable amounts in different food products. Besides health issues, food safety and quality has an economical impact on the food industry, where quality control expenses amount to about 1.5 – 2 % of the total sales. Since more and more food products nowadays contain multiple and processed ingredients, which are often shipped from different parts of the world, and share common production lines and storage spaces, food safety and quality monitoring becomes a challenging task. Traditional analytical methods require dedicated laboratories, equipment and highly trained personnel for detection and identification of each type of hazardous agent (e.g. antibiotics, bacteria, allergens). These techniques are also time-consuming and often expensive. There is a growing need for multi-analyte screening methods, which will enable rapid and simultaneous detection of multiple compounds in complex food samples. In recent years, biosensors have been applied successfully to food analysis, incorporating the same bioassay principals as traditional methods with transducers (optical, electrochemical, etc) in novel, usually miniaturized, integrated analytical devices. However, most of these biosensors still lack the desired level of the multiplexicity. Recent developments in the field of Surface Plasmon Resonance (SPR) technology in the direction of high-throughput systems and multi-analyte measurements present a promising alternative for the existing systems. One of such systems is imaging SPR (iSPR); it enables real-time and label free read-out of spatially modified surfaces (e.g. microarrays). The aim of this study was to develop an iSPR–based biosensor, for simultaneous and quantitative detection of different health-threatening compounds in food. To obtain a comprehensive overview on the analytical applicability of such a system, several points were addressed. The intrinsic sensor properties, such as optical sensitivity and robustness, of the iSPR instrument were studied. Further on, both direct and competitive immunoassay formats for high and low molecular weight compounds detection using the iSPR platform were evaluated. Then, the iSPR-based biosensor was applied for detection of regulated substances in food such as antibiotic residues in milk and allergens in cookies and chocolates. Finally, the most common drawback of using SPR for screening in complex biological matrices, the nonspecific binding to the sensor chip surface, was tackled. The sensitivity of both high and low molecular weight compounds was proven to be sufficient for some of the hazardous agents detection at the maximum residue levels, established in the EU legislation, as was demonstrated by simultaneous detection of seven antibiotic residues in milk and twelve allergens in cookies and dark chocolates. The analysis time takes about 10 minutes and provides quantitative information on multiple targets, producing a fingerprint (allergenic fingerprint for instance) of the tested food. This detailed food profile contributes to the decision making process on the quality and safety of foods, basing it on the total picture of all target compounds present. In order for iSPR-based biosensing to reach its full potential and to become a widely applied routine analytical tool, the instrumental cost needs to be reduced and the analysis further simplified, becoming cost-effective and approachable to non-trained personnel. An additional drawback in analytical applications of a SPR sensor is the nonspecific binding of the matrix components of complex samples to the sensor surface. Many assays based on SPR fail due to inapplicability to measure in “real” samples. As a possible solution to this problem, sensor chip surface engineering was suggested in this thesis. A nanopatterned filter layer covering the sensor chip surface was found to be effective in reducing nonspecific binding when the measurements were performed in “raw” samples by keeping the non-soluble aggregates and big sample matrix components beyond the sensing region of the SPR. With respect to other existing biosensors, iSPR still lags behind in terms of sensitivity and portability. In summary, the results of this study demonstrate that iSPR-based biosensor is a versatile platform, which can be applied for a wide variety of fundamentally different analytes and offers several advantages over already existing methods. SPR detection principle eliminates the need in labelling and the instrumental set-up allows automated analysis. High multiplexing capabilities and short measurement times are obtained with no need for complex and time consuming sample preparation steps. By using iSPR-based biosensor, one can obtain robust and quantitative information on the target analyte concentration, in real time and with high specificity (or broad spectrum, depending on the assay). In conclusion, on-chip screening using iSPR, described here, presents a powerful analytical approach towards food safety and quality monitoring which satisfies the current need in rapid and multi-analytical devices. <br/

Unexplained fever — an approach to defining the aetiology

No Abstract

The control of the dioxin contents in foodstuffs: are routine methods of analysis able to implement the European regulation?

This article reviews the current rules and regulations which apply to laboratories. It also gives the structure of dioxins, furans and dioxin-like PCB, along with a summary description of the method of analysis, and the information required to understand analysis results. The aspects of the European regulation which may be problematic for laboratories are described, using the results provided by the Rouen Laboratory as an example. The authors conclude by saying that a lot of work and investment will be required for the laboratories to comply with the new European regulation.Après un rappel du cadre réglementaire qui s'impose aujourd'hui aux laboratoires d'analyse, la structure des dioxines, furanes et PCB de type dioxines est décrite, les informations nécessaires à la compréhension de l'expression des résultats sont fournies, suivies d'un résumé de la méthode d'analyse. Les points qui, dans la réglementation européenne, sont susceptibles de créer des difficultés aux laboratoires d'analyse sont développés, documentés à l'aide des résultats des essais du Laboratoire de Rouen. Il apparaît en conclusion que les laboratoires devront réaliser un gros travail de mise au point et un investissement en matériel important pour suivre les évolutions de la réglementation européenne

Lepidoptera stem borers on cultivated and wild host plants : implications of insect-plant interactions for pest management

Please read the abstract in the section 00front of this documentThesis (PhD (Entomology))--University of Pretoria, 2005.Zoology and Entomologyunrestricte

The evolution of regional planning and regional economic development in Malaysia

This article explains the evolution of regional planning and policy in Malaysia and discusses the implications of the underlying regional economic theories and regional policies for the socio-economic development of Malaysia. Regional economic development in Malaysia is due to several factors, including the integration of geography and physical features, the need for cooperation beyond local jurisdictions, and the needs of local and national economic development. A review of the literature suggests that the achievement and development of regional planning would differ depending on the country’s pattern of development and growth. However, the basis of regional planning remains the same: to promote competitiveness, create economic opportunities, and achieve balance in the socio-economic development of a country. In a way, regional planning is a tool to achieve sustainable development in a countr

Perpignan – Ruscino

Le sondage a été motivé par un projet de réfection du mur très dégradé soutenant le talus du site archéologique, en bordure nord de la parcelle DV143 (à une dizaine de mètres de la limite des fouilles programmées du quartier d’habitat antique menées de 1976 à 1990 par G. Barruol puis R. Marichal). Le mur surplombe le chemin d’accès au Mas Ramon où les fouilles de D. Henry révélèrent au milieu du xixe s. la présence de bassins interprétés comme les thermes publics. Long d’environ 35 m, il s’ap..

Finlandiako hezkuntza sistema: kudeaketa eredua

[EU]Lan honen helburua Finlandiako Hezkuntza Sistemaren kudeaketa ikertzea da; alde batetik, hezkuntzaren inguruko gai desberdinak jorratuz, eta beste aldetik, herrialdeko eta hezkuntza sistemako egoerak eta ezaugarriak aztertuz. Izan ere, Finlandiako Hezkuntzaren arrakasta oro har didaktika eta pedagogia ikuspuntutik aztertua izan da, eta lan honen bitartez, bere barne funtzionamendua eta eragile desberdinen rolak ezagutu nahi dira. Amaitzeko, Finlandiako Hezkuntza Kudeaketa ereduaren indarguneak aipatuz, gaur egun Euskal Hezkuntza Sisteman aplikatzeko proposamenak aurkeztuko dira.[ES]El objetivo de este proyecto consistirá en investigar la gestión del Sistema Educativo de Finlandia; por un lado, se van a tratar diferentes temas sobre la educación, y por otra parte, se analizaran las características y situaciones del país y del Sistema Educativo. De hecho, el éxito de la Educación en Finlandia normalmente se ha analizado por un enfoque didáctico y pedagógico, y mediante este trabajo, se quiere conocer su funcionamiento interno y los roles de las diferentes influencias. Para terminar, mencionando los puntos fuertes de la Gestión Educativo de Finlandia, se van a presentar diferentes propuestas para aplicar en el Sistema Educativo Vasco.[EN]The aim of this Project will be to investigate the management of the Finnish Education System; On the one hand, different topics on education will be discussed, and on the other hand, the characteristics and situations of the country and the Educational System will be analyzed. In fact, the success of Education in Finland has usually been analyzed by a didactic and pedagogical approach, and through this work, we want to know its internal operation and the roles of the different influences. Finally, mentioning the strengths of the Education Management of Finland, they will be presented different proposals to apply in the Basque Educational System