80 research outputs found
Highly selective recovery of medium chain carboxylates from co-fermented organic wastes using anion exchange with carbon dioxide expanded methanol desorption
No full textThe aim of this work was to recover a mixture of carboxylates ranging from 2 to 7 carbon atoms using a strong anion exchange resin, followed by desorption with CO2-expanded methanol. Medium chain carboxylates hexanoate and heptanoate adsorbed better than acetate, and the corresponding medium chain carboxylic acids desorbed easier than acetic acid. Consequently, hexanoate and heptanoate were concentrated up to 14.6 and 20.7 times, respectively. These findings will enable effective separation and purification of the produced carboxylic acids. Notably, the presence of inorganic ions in the sample, such as chloride, decreased the adsorption affinity compared to a synthetic mixture only of carboxylates.BT/Bioprocess Engineerin
Recovery of acetate by anion exchange with consecutive CO<sub>2</sub>-expanded methanol desorption: A model-based approach
No full textProduction of bio-based acetate is commonly hindered by the high costs of the downstream processing. In this paper, a model is developed to describe a new method that recovers acetate salts using anion exchange resins, and subsequently desorbs and upgrades them using CO2-expanded alcohol. The model consists of equilibrium parameters for both the adsorption and desorption step. The calculated parameters are: for the adsorption KCl- Ac- =0.125, KCl- HCO3 - =0.206 and KOV,HAc=0.674[Formula presented], and for the desorption pKMeCO3 - Ac- =3.71. The maximum experimental concentration of acetic acid obtained in CO2-expanded methanol is 0.427 mol/kg (20 g/LMeOH) at an operating pressure of 31 bar. The model represents the expected trends for all species, and can be used to design a multicolumn system for the recovery and upgrading of carboxylates.BT/Bioprocess EngineeringApplied Science
Productivity growth and the returns from public investment in R&D in Australian broadacre agriculture
No full textInvestment in R&D has long been regarded as an important source of productivity growth in Australian agriculture. Perhaps because research lags are long, current investment in R&D is monitored closely. Investment in R&D has been flat while productivity growth has remained strong, relative both to other sectors of the Australian economy and to the agricultural sectors of other countries. Such productivity growth, at a time when the decline in terms of trade facing Australian farmers has slowed, may have enhanced the competitiveness of Australian agriculture. The econometric results presented here suggest no evidence of a decline in the returns from research from the 15 to 40 per cent per annum range estimated by Mullen and Cox. In fact the marginal impact of research increases with research over the range of investment levels experienced from 1953 to 2000, a finding which lends support to the view that there is underinvestment in agricultural research. These results were obtained from econometric models which maintain strong assumptions about how investments in research and extension translate into changes in TFP. Hence some caution in interpreting the results is warranted.productivity, research and development, research evaluation, Productivity Analysis, Research and Development/Tech Change/Emerging Technologies,
Semi-supervised linear spectral unmixing using a hierarchical Bayesian model for hyperspectral imagery
No full textThis paper proposes a hierarchical Bayesian model that can be used for semi-supervised hyperspectral image unmixing. The model assumes that the pixel reflectances result from linear combinations of pure component spectra contaminated by an additive Gaussian noise. The abundance parameters appearing in this model satisfy positivity and additivity constraints. These constraints are naturally expressed in a Bayesian context by using appropriate abundance prior distributions. The posterior distributions of the unknown model parameters are then derived. A Gibbs sampler allows one to draw samples distributed according to the posteriors of interest and to estimate the unknown abundances. An extension of the algorithm is finally studied for mixtures with unknown numbers of spectral components belonging to a know library. The performance of the different unmixing strategies is evaluated via simulations conducted on synthetic and real data
Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy
No full textBackground
The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy.
Methods
In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation.
Results
Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89·6 per cent) compared with that in countries with a middle (753 of 1242, 60·6 per cent; odds ratio (OR) 0·17, 95 per cent c.i. 0·14 to 0·21, P < 0·001) or low (363 of 860, 42·2 per cent; OR 0·08, 0·07 to 0·10, P < 0·001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high‐HDI countries (risk difference −9·4 (95 per cent c.i. −11·9 to −6·9) per cent; P < 0·001), but the relationship was reversed in low‐HDI countries (+12·1 (+7·0 to +17·3) per cent; P < 0·001). In multivariable models, checklist use was associated with a lower 30‐day perioperative mortality (OR 0·60, 0·50 to 0·73; P < 0·001). The greatest absolute benefit was seen for emergency surgery in low‐ and middle‐HDI countries.
Conclusion
Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low‐HDI countries was half that in high‐HDI countries
Aplicação e validação do modelo WTox para avaliar risco ambiental toxicológico de misturas complexas: estudo de caso em amostras de resíduos industriais
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia AmbientalA contaminação do ecossistema aquático acontece de diversas maneiras, por exemplo, o corpo d'água pode ser atingido por esgotos domésticos, efluentes industriais, arraste de agrotóxicos e fertilizantes, e lixiviação de resíduos perigosos. Os modelos matemáticos são importantes ferramentas de gestão ambiental e gerenciamento de riscos. Modelos sobre a previsão da toxicidade de componentes químicos já estão bastante desenvolvidos, e são comumente utilizados quando um acidente ambiental já aconteceu, ou então para estimar riscos em locais previamente determinados. Mas previsões sobre a toxicidade de misturas químicas ainda devem ser aprimoradas, devido à complexidade dos efeitos que podem causar aos seres vivos. A dificuldade de se estimar a toxicidade com base nos resultados de análises físico-químicas é um fato esperado, pois desde que a toxicidade é um fenômeno biológico, a utilização de testes baseados em respostas biológicas parece ser mais apropriada. Assim, neste trabalho avaliou-se o risco ambiental, abordando a necessidade do estudo da relação entre o organismo e os xenobióticos. Para isto, foram aplicados seis tipos de testes toxicológicos através do Modelo WTox (software). Utilizando esta metodologia foi possível realizar uma avaliação e obter a classificação do risco de substâncias ou compostos potencialmente tóxicos. Ensaios de toxicidade aguda foram realizados com os organismos Daphnia magna e Vibrio fischeri. Ensaios de toxicidade crônica foram realizados com o organismo Daphnia magna. Os testes de citotoxicidade e genotoxicidade foram realizados com o organismo Oreochromis niloticus (lipoperoxidação, frequência de micronúcleos e metilação do DNA). Um estudo de caso foi realizado com resíduos sólidos provenientes da indústria têxtil, metal-mecânica e de papel e celulose. Os resultados obtidos com a avaliação dos parâmetros toxicológicos demonstraram que diversos resíduos industriais induziram mortalidade, efeitos na reprodução, aumentos na taxa de lipoperoxidação, mutações e alterações na metilação do DNA dos organismos testados. Estes resultados, analisados em conjunto através do Modelo WTox, e validados através da comparação com outros modelos de avaliação de risco ambiental, permitiram a classificação de risco ambiental toxicológico dos resíduos industriais. A avaliação demonstrou que as amostras analisadas podem ser classificadas como de risco ambiental toxicológico significativo ou crítico.The contamination of the aquatic ecosystem can happen in many ways, for example, ponds or rivers can be contaminated by domestic sewage, industrial effluents, drag of pesticides and fertilizers, and leaching of hazardous waste. Mathematical models are important tools for environmental management. Models about prediction of toxicity of chemical components are already well developed, and are commonly used when an environmental accident has happened, or to estimate risks at sites previously determined. Predictions about the toxicity of chemical mixtures must be enhanced due to the complexity of effects that can be caused to the living species. The difficulty to estimate the toxicity based only in physical-chemical parameters is an expected fact, because since the toxicity is a biological phenomenon, it seems more suitable to use tests based on biological responses. In this work, the environmental risk was accessed addressing the need to study the relationship between the organism and xenobiotics. Therefore, six toxicological endpoints were applied through the WTox Model (software). Using this methodology it was possible to make an evaluation and to obtain the risk classification of potentially toxic substances. Acute toxicity tests were performed with the organisms Daphnia magna and Vibrio fischeri. Chronic toxicity tests were performed with the organism Daphnia magna. Citotoxicity and genotoxicity tests were performed with the organism Oreochromis niloticus (lipid peroxidation, micronucleus frequency and DNA methylation). A case study was conducted with solid wastes from textile, metal-mechanic and pulp and paper industries. The results obtained with the evaluation of toxicological parameters have shown that several industrial wastes induced mortality, reproductive effects, increases in the rate of lipid peroxidation, mutations and changes in DNA methylation of the organisms tested. These results, analyzed together through the WTox Model, and validated by comparison with other models of environmental risk assessment, allowed the classification of the environmental risk of industrial wastes. The evaluation showed that the toxicological environmental risk of the samples analyzed can be classificated as significant or critical
Estratigrafía y geocronología de los depósitos de corrientes de densidad piroclástica en el río El Barranco, Complejo Volcánico Galeras, Colombia
No full textIlustraciones, fotos, mapasspa:El Complejo Volcánico Galeras (CVG) es un volcán compuesto que se localiza en el el valle Cauca-Patía, entre lascordillerasCentral yOccidental, en el departamento deNariño, al sur de Colombia. Su última etapa eruptiva, el volcán Galeras sensu stricto, se considera como uno de los volcanesmás activosde Colombia, con erupcionestípicamente vulcanianas, desde hace ca. 4500 años. En este trabajo se exponen losresultadosdel análisisestratigráfico, geocronológico, de vesicularidad y morfológico en fragmentos de pómez, de componentes y granulométrico, de ocho depósitosde corrientesdedensidadpiroclásticas(CDPs) que afloran a lo largo del valle del río El Barranco, en el municipio de La Florida, al NW del CVG. Los depósitos de CDPs sobreyacen discordantemente a depósitos de flujos de lava andesíticos de la etapa Genoy(150 – 40 ka) del CVG y fueron denominados desde Unidad U1 hasta Unidad U8. Las unidades U1 (8303 ± 97 y 8284,5 ± 90,5 cal AP), U2 (7667 ± 78 cal AP), U3 (5082 ± 198, 5096,5 ± 226,5, 5801,5 ± 481,5 y 5966 ± 235 cal AP, edades tomadas de investigaciones anteriores), U4 (4625 ± 181 cal AP), y U6 (2215,5 ± 101,5 y 2033 ± 91 cal AP) se componen, en orden de abundancia, de fragmentos de pómez, líticos volcánicos, y cristales libres de anfíbol y plagioclasa, mientras que las unidades U5 (3201,5 ± 129 cal AP), U7 (1066,5 ± 109,5 y 944,5 ± 115,4 cal AP) y U8 (390,5 ± 80,5 cal AP), se componen de líticosvolcánicos, fragmentosde pómez y cristalesde plagioclasa yanfíbol. Intercalado entre U3 y U4, un depósito de caída piroclástica muestra un alto contenido de biotita que sirvió de nivel guía, mientras que un depósito de lahar de tipo flujo de escombros, separa las unidades U6 y U7. Con base en su composición, las unidades U1, U2, U3, y U6, se clasifican como depósitos de flujos piroclásticos de pómez generadas por el colapso de pequeñas columnas, lo cual se relaciona con eventos eruptivos de tipo pliniano, específicamente subpliniano, mientras que la Unidad U4 se asocia a un evento tipo “blast”, causado por la sobrepresión ejercida por los gases de un magma viscoso. Finalmente, las unidades U5, U7 y U8 se clasifican como depósitos de bloques y ceniza generados por la destrucción de domos intracratéricos y colapso de columnas eruptivas vulcanianas. Las unidades U3, U4, U5, U6 y U7 se correlacionan estratigráfica y geocronológicamente con depósitos estudiados previamente en el CVG, sin embargo, las unidades U1, U2 yU8, se consideran como eventos aúnnoregistrados en lahistoriaeruptivadel volcán Galeras. Ladatación ycaracterizacióndela Unidad U1, permite proponer que la historia eruptiva del volcán Galeras inició a principios del Holoceno (~8300 años AP), y no hace 4500 AP, como se ha establecido hasta el momento. Adicionalmente, el registro de la Unidad U8 en el pueblo de La Florida, ratifica la amenaza alta por CDPs para esta población. De esta manera, esta investigación mejora la resolución de la información vulcanológica de la zona y contribuye al entendimiento de la evolución eruptiva del volcán Galeras.eng:Abstract The Galeras Volcanic Complex (GVC) is a composite volcano located in the CaucaPatía valley, between the Central and Western mountain ranges, in the department of Nariño, in southern Colombia. Its last eruptive stage, the Galeras volcano sensu stricto, is considered one of the most active volcanoes in Colombia, with typically Vulcanian eruptions, since ca. 4500 years. This study presents the results of stratigraphic, and geochronological, vesicularity and morphological in pumice fragments, and components and granulometric analyses of eight pyroclastic density current deposits (PDCs), which outcrop along the El Barranco river valley, in the town of La Florida, to the NW of the GVC. The PDCs deposits have a cumulative thickness of 14.67 m and discordantly overlie to andesitic lava flows deposits of the Genoy stage (150 – 40 ka) from the GVC and werenamed from Unit U1 to Unit U8. The units U1 (8303 ± 97 and 8284.5 ± 90.5 cal BP), U2 (7667 ± 78 cal BP), U3 (5082 ± 198, 5096.5 ± 226.5, 5801.5 ± 481.5 and 5966 ± 235 cal BP, ages taken from previous investigations), U4 (4625 ± 181 cal BP), and U6 (2215.5 ± 101.5 and 2033 ± 91 cal BP) are composed, in order of abundance, of pumice fragments, volcanic lithics, and free amphibole and plagioclase crystals, while units U5 (3201.5 ± 129 cal BP), U7 (1066.5 ± 109.5 and 944.5 ± 115.4 cal BP) and U8 (390.5 ± 80.5 cal BP), are composed of volcanic lithics, pumice fragments and plagioclase and amphibole crystals. Within U3 and U4, a pyroclastic fall deposit shows a high biotite content that served as a guide level, while a debris flow-type lahar deposit separates units U6 and U7. Based on their composition, units U1, U2, U3, and U6 are classified as pumice pyroclastic flow deposits generated by the collapse of small columns, which is related to Subplinian eruptive events, while Unit U4 is associated with a "blast" type event, caused by the overpressure exerted by the gases of a viscous magma. Finally, units U5, U7 and U8 are classified as block and ash deposits generated by the destruction of intracrateric domes and collapse of Vulcanian eruptive columns. Units U3, U4, U5, U6 and U7 are stratigraphically and geochronologically correlated with deposits previously studied in the GVC; however, units U1, U2 and U8 are considered as events not yet recorded in the eruptive history of the Galeras volcano. The dating and characterization of Unit U1 allows us to propose that the eruptive history of the Galeras volcano began at the beginning of the Holocene (~8300 years BP), and not 4500 BP, as it has been established until now. Additionally, the record of Unit U8 in the town of La Florida ratifies the high PDCs threat for this population. Thus, this research improves the resolution of the volcanological information in the area, and contributes to the understanding of the eruptive evolution of the Galeras volcano.Tabla de contenido Resumen Abstract 1. Introducción / 1.1 Objetivos / 1.1.1. Objetivo general / 1.2.1 Objetivos específicos / 2. Margen geológico y estructural / 2.1 Los Andes colombianos / 2.2 Complejo Volcánico Galeras / 2.2.1 Volcán Galeras / 3. Marco teórico / 3.1 Estilo eruptivo / 3.1.1 Erupciones vulcanianas / 3.1.2 Erupciones plinianas / 3.1.2.1 Erupciones subplinianas / 3.2 Corrientes de densidad piroclástica / 3.2.1 Subtipos de corrientes de densidad piroclástica / 3.2.1.1 Corrientes de densidad piroclástica de tipo flujo de bloques y ceniza / 3.2.1.2 Corrientes de densidad piroclástica de tipo flujo de pómez / 3.2.1.3 Corrientes de densidad piroclástica de tipo “blast” 4. Metodología / 4.1. Fotointerpretación / 4.2 Distribución de depósitos y definición de facies / 4.3 Granulometría, vesicularidad, microtexturas, y componentes / 4.3.1 Análisis granulométrico / 4.3.1.1 Análisis textural por el método del tamizado por vía seca / 4.3.1.2 Parámetros estadísticos / 4.3.2 Análisis de vesicularidad / 4.3.2 Análisis de componentes / 4.3.3 Análisis microtextural y/o morfológico en Microscopio Electrónico de Barrido (MEB) / 4.4. Análisis geocronológicos / 5. Resultados / 5.1 Estratigrafía de los depósitos / 5.1.1 Caracterización de las unidades estratigráficas / 5.1.1.1 Etapa Genoy / 5.1.1.2 Unidad U1 / 5.1.1.3 Unidad U2 / 5.1.1.4 Unidad U3 / 5.1.1.5 Marcador de Biotita (MB) / 5.1.1.6 Unidad U4 / 5.1.1.7 Unidad U5 / 5.1.1.8 Unidad U6 / 5.1.1.9 Depósito volcaniclástico secundario / 5.1.1.10 Unidad U7 / 5.1.1.11 Unidad U8 / 5.1.2 Edad de los depósitos / 5.1.3 Relaciones estratigráficas / 5.2 Análisis de vesicularidad y morfológico en fragmentos de pómez / 5.2.1 Unidad U1 / 5.2.2 Unidad U2 / 5.2.3 Unidad U3 / 5.2.4 Unidad U4 / 5.2.5 Unidad U5 / 5.2.6 Unidad U6 / 5.2.7 Unidad U7 / 5.2.8 Unidad U8 / 5.3 Análisis de componentes / 5.3.1 Unidad U1 / 5.3.2 Unidad U2 / 5.3.3 Unidad U3 / 5.3.4 Unidad U4 / 5.3.5 Unidad U5 / 5.3.6 Unidad U6 / 5.3.7 Unidad U7 / 5.3.8 Unidad U8 / 5.4 Análisis de granulometría por el método del tamizado seco / 5.4.1 Unidad U5 / 5.4.2 Unidad U7 / 5.4.3 Unidad U8 / 6. Discusión / 6.1 Estratigrafía / 6.1.1. Correlaciones estratigráficas / 6.1.1.1. Etapa Galeras vs. Etapa Urcunina / 6.1.1.2. Unidades (a.k.a. miembros) en la microcuenca / 6.2. Modelo eruptivo y distribución de los depósitos volcaniclásticos / 6.2.1. Análisis de componentes / 6.2.2. Vesicularidad / 6.2.3. Erupciones vulcanianas vs. Erupciones subplinianas / 6.3. Fragmentos agregados / 6.3.1. Agente adhesivo / 6.4 Alteración de los fragmentos volcánicos / 6.5 Amenaza volcánica en la microcuenca del río El Barranco / 7. Conclusiones / 8. BibliografíaUniversitarioGeólogo(a)Vulcanologí
Molecular epidemiology and population genetics of "Plasmodium vivax" in Papua New Guinea
No full textAbstract: In recent years a new focus has been put on malaria, and elimination and eradication of this disease has been brought back to the agenda. While Plasmodium falciparum causes most of the disease in Africa, P. vivax is predominant in malaria endemic regions in Latin America, Asia and the South Pacific. In the last 10 years increasing reports of severe disease and even mortality caused by P. vivax raised new awareness for this parasite. Forty percent of the world population lives in areas of P. vivax transmission, and severe disease is caused especially in infants and young children. P. vivax has the ability to form semi-dormant liver hypnozoites that can relapse and lead to clinical disease after an extended period of time. As most currently applied drugs are not effective against hypnozoites, they present a mayor obstacle towards malaria control.
In the lowlands of Papua New Guinea (PNG), malaria prevalence reaches levels similar to those in sub-Saharan Africa. Both P. falciparum and P. vivax are frequent, and P. vivax reaches prevalence higher than anywhere else in the world. Individuals from these regions are often co-infected by both parasite species. Multiple concurrent infections with different strains of P. falciparum or P. vivax are common. For this thesis I have genotyped over 3000 P. vivax positive blood samples collected in a cohort study of 264 children. These children, aged 1 to 4.5 years, were followed over 16 months and visited every 8 weeks for collection of two blood samples taken 24 hours apart. Additional samples were collected whenever the children presented sick to the local health centre. In parallel morbidity data was collected. P. vivax was genotyped using two size polymorphic markers, which both distinguished individual parasite clones. Genotyping data of P. falciparum clones was available from a previous study.
Extensive diversity of the genotyping markers and high multiplicity of infection (MOI, the number of co-occurring clones per carrier) was observed. Each P. vivax positive child carried a mean of 2.7 concurrent infections, mean MOI was nearly twice as high as P. falciparum multiplicity in the cohort. We did not detect a seasonal trend in MOI, and only a moderate increase of MOI with age, most pronounced in very young children up to 3 years. Most likely relapses increase P. vivax mean MOI, and they also lead to high MOI during seasons of less transmission.
The detection of parasitemia in field surveys is imperfect owing to parasite densities below or fluctuating around the detection limit of light microscopy or PCR. We have compared >1000 pairs of samples collected 24 hours apart. The collection of a second sample was found to have a limited effect on parasite prevalence: a single PCR missed only 6 to 9% of the combined parasite positivity. The proportion of individual clones missed was more pronounced. Depending on the marker, 19% or 31% of all P. vivax clones were missed when sampling on a single day. As a consequence, mean MOI increased from 2.7 to 3.4 when combining results from paired samples. Detectability does not differ between P. vivax and P. falciparum or between age groups. Thus comparisons of prevalence and MOI between species and age trends are not biased by detectability.
To investigate structuring of P. vivax population in PNG, we have typed a subset of samples with 13 additional markers. Allele frequencies and haplotypes were compared to those from samples collected at other sites in PNG. No differences were detected between parasite populations, most likely because of high gene flow between sites. This is in contrast to the situation in countries of lower endemicity, and differs from the earlier observed moderate structuring in P. falciparum populations from PNG.
In this cohort study, the incidence of P. vivax malaria decreased with age, whereas the incidence of P. falciparum peaked later at the age of 3.5 years. These contrasting trends are in line with results from other countries were both parasites are co-endemic. Differences in the parasite biology, e.g. a more limited reservoir of surface antigens of P. vivax compared to P. falciparum, might cause faster immunization against P. vivax and thus the different age trends in incidence. But also differences in transmission intensity might be responsible. Our typing of clones over an extended period of time allowed estimations of the molecular force of infection (molFOI), i.e. the number of infections per child per year. Each child acquired 14 P. vivax clones per year, but only 6 P. falciparum clones. molFOI did not change with age, suggesting that acquired immunity builds up gradually with each new clone, leading to a decrease in P. vivax incidence over time. This does not rule out that biological differences between P. vivax and P. falciparum also play a role.
PNG is among the countries with the poorest health infrastructure and the highest prevalence of malaria. P. vivax prevalence is in some regions as high as P. falciparum prevalence. High MOI and molFOI, as well as high levels of gene flow imply great resilience of P. vivax towards antimalarial interventions. Fast acquisition of semi-immunity leads to a large number of asymptomatic P. vivax carriers, potentially contributing to transmission, and control is further complicated by relapses, occurring in the blood weeks or months after transmission from the mosquito. The high proportion of P. vivax will be a major challenge towards malaria control and elimination in PNG. ---------- Zusammenfassung: In den letzten Jahren erhielt die Krankheit Malaria neue Aufmerksamkeit, und ihre Ausrottung in einzelnen Ländern oder gar weltweit wird wieder als realistisches Ziel angesehen. Plasmodium falciparum verursacht die meisten Krankheitsfälle in Afrika, dagegen ist P. vivax der vorherrschende Parasit in Malariagebieten in Lateinamerika, Asien und dem Südpazifik. In den letzten zehn Jahren haben Forschungen gezeigt, dass P. vivax häufig schwere Krankheit bis hin zum tödlichen Verlauf verursachen kann, insbesondere bei Kleinkindern. Dadurch geriet der Parasit nach Jahren mit wenig Beachtung erneut in den Fokus der Forschung. Vierzig Prozent der Weltbevölkerung leben in Gebieten mit P.vivax-Übertragung. P. vivax hat die Fähigkeit, Ruhestadien zu bilden, welche längere Zeit nach der Übertragung zum erneuten Krankheitsausbruch führen können. Die meisten der heute vorhandenen Medikamente sind wirkungslos gegen Leberstadien, darum sind diese eine grosse Hürde auf dem Weg zur Bekämpfung von Malaria.
In tief liegenden Gebieten von Papua Neuguinea erreicht die Malariaprävalenz Werte ähnlich der in Afrika südlich der Sahara. P. falciparum wie auch P. vivax sind häufig, und die P. vivax Prävalenz ist höher als irgendwo sonst auf der Welt. Bewohner dieser Gegenden sind häufig gleichzeitig mit beiden Spezies infiziert, sowie mit verschiedenen Linien derselben Art. Für diese Arbeit wurden die P. vivax Stämme in über 3'000 positiven Blutproben analysiert, die im Rahmen einer Kohortenstudie mit 264 Kindern gesammelt wurden. Diese Kinder im Alter von 1 bis 4.5 Jahren wurden während 16 Monaten alle 2 Monate besucht um im Abstand von 24 Stunden zwei Blutproben zu sammeln. Zusätzliche Proben wurden gesammelt, wann immer ein Kind eines der Gesundheitszentren aufsuchte. Parallel dazu wurden alle Erkrankungen der Kinder registriert. P. vivax Stämme wurden aufgrund von zwei molekularen Markern, bei welchen sich die Allele in der Grösse unterscheiden, typisiert. Im Rahmen einer vorhergehenden Studie wurden die P. falciparum Stämme in der Kohorte typisiert.
Die gewählten Marker wiesen eine hohe Diversität auf, und die Multiplizität (die Anzahl verschiedener Stämme pro Träger) war hoch. Jedes infizierte Kind trug im Schnitt 2.7 P. vivax Stämme, dieser Wert ist fast doppelt so hoch wie derjenige von P. falciparum. Es gab keine saisonalen Unterschiede in der Multiplizität, und nur einen geringen Anstieg der Multiplizität mit dem Alter der Kinder; dieser war am deutlichsten in sehr jungen Kindern unter 3 Jahren. Es ist davon auszugehen, dass wiederausbrechende Leberstadien die Multiplizität erhöhen, dies auch während Jahreszeiten mit geringerer Übertragung durch Mücken.
In Feldstudien ist die Detektion von Parasiten häufig unvollständig, d.h. die Dichte eines Teils der Parasiten liegt unter der Nachweisgrenze von Mikroskopie oder molekularen Methoden wie PCR. Wir haben über 1000 Blutproben-Paare verglichen, welche im Abstand von 24 Stunden gesammelt wurden. Die zusätzliche zweite Blutprobe hatte einen eher geringen Einfluss auf die Prävalenz, mittels PCR wurden nur 6 bis 9% der Proben falsch negativ diagnostiziert. Der Anteil der Stämme, die in einer einzelnen Proben nicht detektiert wurden, war dagegen ausgeprägter. Je nach Marker wurden 19 oder 31% aller P. vivax Stämme, die an mindestens einem der 2 Tage nachgewiesen wurden, am Tag 1 nicht entdeckt. Als Folge stieg die Multiplizität von 2.7 auf 3.4 wenn die Resultate von beiden Tagen kombiniert wurden. Die Wahrscheinlichkeit, einen Stamm zu detektieren, unterscheidet sich nicht zwischen P. vivax und P. falciparum oder in verschiedenen Altersklassen, folglich werden Vergleiche der Prävalenz und Multiplizität nicht beeinflusst.
Um die Populationsstruktur von P. vivax in Papua Neuguinea zu untersuchen haben wir einen Teil der Proben aus unserer Kohorte mit 13 weiteren molekularen Markern untersucht. Die Allele-Frequenzen und die Haplotypen wurden verglichen mit den-jenigen von drei anderen Orten in Papua Neuguinea. Es wurden keine Unterschiede zwischen diesen Parasitenpopulationen festgestellt, sehr wahrscheinlich aufgrund eines häufigen genetischen Austauschs zwischen den Populationen. Im klaren Gegensatz dazu wurden in Gebieten mit geringer P. vivax Prävalenz ausgeprägte Unterschiede zwischen Populationen beobachtet, und in früheren Studien wurde auch eine moderat ausgeprägte Populationsstruktur von P. falciparum in Papua Neuguinea festgestellt.
Die Inzidenz von P. vivax, also die Anzahl Erkrankungen, nahm in der Kohorte mit dem Alter deutlich ab, dagegen stieg die P. falciparum Inzidenz bis zu einem Alter von 3.5 Jahren. Diese gegensätzlichen Trends bestätigen Beobachtungen aus anderem Gebieten, wo beide Parasiten endemisch sind. Als mögliche Ursache kommen Unterschiede in der Biologie der Parasiten in Frage, z.B. eine kleinere Diversität von Oberflächenproteinen von P. vivax, wodurch die Immunisierung schneller verlaufen sollte. Auch sind Unterschiede in der Übertragungsrate von P. vivax und P. falciparum möglich. Unsere Typisierung von Stämmen über einen längeren Zeitraum ermöglicht, die „molekulare Infektionshäufigkeit“ zu bestimmen, also die Anzahl Infektionen pro Kind pro Jahr. Jedes Kind wurde im Schnitt mit über 14 P. vivax-Stämmen pro Jahr infiziert, aber nur mit etwa 6 P. falciparum-Stämmen. Die Infektionshäufigkeit änderte sich nicht mit dem Alter, dies lässt darauf schliessen, dass die Kinder mit der Zeit allmählich Immunität erlangten, und dadurch die Anzahl Erkrankungen zurückging. Dies schliesst natürlich nicht aus, dass auch Unterschiede in der Biologie eine Rolle spielt im Erlangen von Immunität.
Papua Neuguinea ist eines der Länder mit dem schlechtesten Gesundheitswesen und gleichzeitig einem hohen Auftreten von Malaria. Die Prävalenz von P. vivax ist manchen Gegenden gleich hoch wie diejenige von P. falciparum. Die hohe Multiplizität und Infektionshäufigkeit, wie auch der hohe Grad von genetischem Austausch zwischen Parasitenpopulationen, lässt auf einen hohen Widerstandsgrad gegenüber Massnahmen zur Malariakontrolle schliessen. Die schnelle Immunisierung gegen P. vivax führt dazu, dass es eine grosse Zahl von asymptomatischen Trägern gibt, die vermutlich immer noch zur Übertragung beitragen. Die Bekämpfung von P. vivax wird weiter erschwert durch die Leberstadien, welche noch Wochen oder Monate nach der Übertragung zu Krankheitsausbrüchen führen können. Der hohe Anteil von P. vivax an allen Malariafällen wird Papua Neuguinea vor grosse Herausforderungen stellen auf dem Weg zur Kontrolle und Elimination von Malaria
O papel dos receptores 5-HT1A nas respostas ingestivas e hipnogênica provocadas pela injeção intracerebroventricular de serotonina em pombos (Columba livia): discriminação entre receptores pré e pós-sinápticos
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2014.Introdução: diversos estudos demonstram que os circuitos serotonérgicos inibem a ingestão de alimentos e o sono em aves e mamíferos. A injeção intracerebroventricular (ICV) de 5-HT em pombos, entretanto, provoca efeitos diferentes: aumento na ingestão de água e na duração do sono. Nós associamos estas respostas à atuação de receptores 5-HT1A, pois a ativação destes receptores produz respostas similares. No entanto, os receptores 5-HT1A podem estar localizados no neurônio serotonérgico (autorreceptores) ou em outros neurônios (heterorreceptores). Dependendo da sua localização, a ativação destes receptores produz efeitos diferentes. Portanto, o nosso objetivo foi avaliar a participação dos receptores 5-HT1A nas respostas dipsogênica e hipnogênica provocadas pela 5-HT, na tentativa de especificar as respostas desencadeadas pela 5-HT à atuação de auto ou heterorreceptores. Métodos: os animais (pombos adultos, Columba lívia, de ambos os sexos, pesando entre 400-550 g) foram divididos em 5 grupos/experimentos diferentes. Experimento 1: 16 pombos foram divididos em dois grupos de acordo com o pré-tratamento e receberam: MM77 (antagonista de heterorreceptores 5-HT1A; 0, 23 ou 69 nmol), ou WAY100635 (WAY, antagonista de auto e heterorreceptores 5-HT1A; 0, 0,1, 0,3 ou 1 nmol) e 20 min. após foram tratados com 5-HT (50 e 150 nmol) ou 8-OH-DPAT (30 nmol; agonista de receptores 5-HT1A/7). Logo após o tratamento, o registro comportamental começou e a ingestão de alimentos foi verificada 60 min. após a última injeção. Experimento 2: 12 pombos foram divididos em 2 grupos e submetidos à cirurgia para injeção ICV (bilateral) da neurotoxina de neurônios serotonérgicos 5,7-dihidroxitriptamina (5,7-DHT, 200µg/injeção) ou de seu veículo. Após 12 dias, os animais começaram a ser testados com 5-HT (150 nmol), 8-OH-DPAT (30 nmol) ou veículo (ácido ascórbico 1% em NaCl 0,9%) com intervalo de 7 dias entre as injeções. Estes animais foram mortos 28 dias após a cirurgia e o conteúdo encefálico de 5-HT foi analisado para verificar os efeitos da lesão. Adicionalmente, nós utilizamos outros 18 animais divididos em três grupos, a) 6 animais naïve que foram mortos para servir como controle para os níveis basais de 5-HT e outros dois grupos (N: 6/grupo) que foram submetidos à cirurgia (injeção de 5,7-DHT ou do veículo) e perfundidos 12 dias após a cirurgia para verificar os efeitos da toxina sobre a densidade de neurônios serotonérgicos. Experimento 3: Secções do tronco e do hipotálamo de 6 animais não submetidos a qualquer manipulação experimental foram processados pela técnica de autorradiografia para detectar a distribuição dos sítios de ligação ao agonista tritiado [3H] 8-OH-DPAT. Experimento 4: 15 pombos com cânulas guia direcionadas ao ventrículo lateral direito foram divididos em 3 grupos e tratados com: 8-OH-DPAT (30 nmol) e tiveram livre acesso (N:5) ou foram privados de água após a injeção (N:5) e veículo (N:5). 90 min. após a injeção os animais foram perfundidos e as secções do tronco encefálico processadas para detecção da proteína Fos em neurônios serotonérgicos e não serotonérgicos, e secções do hipotálamo processadas para detectar somente a expressão da proteína Fos. Experimento 5: 10 pombos com cânulas guia direcionadas ao ventrículo lateral direito foram divididos em 3 grupos e tratados com: 5-HT (150 nmol) e tiveram livre acesso (N:5) ou foram privados de água após a injeção (N:5). 90 min. após, os animais foram perfundidos e secções contendo o hipotálamo foram processadas para a detecção da proteína Fos. Resultados: tanto a 5-HT como o 8-OH-DPAT provocaram intensa ingestão de água e aumento na duração do sono. O 8-OH-DPAT ainda aumentou a ingestão de alimento. Os efeitos ingestivos e hipnogênico dos tratamentos foram parcial ou totalmente afetados pelos antagonistas evidenciando a participação dos receptores 5-HT1A nas alterações comportamentais provocadas pela 5-HT. Entretanto, os dados farmacológicos não nos permitiram especificar entre a ação de auto ou heterorreceptores, mas indicam que a interação entre os dois receptores parece ser um importante aspecto do controle exercido pelos circuitos serotonérgicos sobre os comportamentos ingestivos. Apesar de diminuir drasticamente a densidade de neurônios serotonérgicos, a lesão não afetou as alterações provocadas pelos tratamentos o que sugere que em animais com a função serotonérgica prejudicada, receptores 5-HT1A localizados em neurônios não serotonérgicos parecem ser os responsáveis pelos efeitos dos tratamentos. Além disso, os antagonistas e a lesão dos neurônios serotonérgicos também aumentaram o sono dos animais indicando um efeito inibitório tônico dos neurônios serotonérgicos sobre o sono. Os tratamentos também aumentaram a atividade Fos em regiões hipotalâmicas ricas em receptores 5-HT1A e que parecem estar envolvidas com o controle da ingestão de alimento, dos fluídos corporais e do sono. Conclusão: As respostas dipsogênica e hipnogênica desencadeadas pela injeção de 5-HT parecem ser mediadas parcialmente tanto por auto como por heterorreceptores 5-HT1A. Aparentemente, estas respostas são mediadas por receptores 5-HT1A localizados em estruturas encefálicas (no tronco e no hipotálamo) envolvidas com o controle dos comportamentos ingestivos e de sono em aves. Nossos resultados revelaram sutis diferenças na atividade celular produzidas pela 5-HT e pelo 8-OH-DPAT que sugerem que outros receptores serotonérgicos também participam das respostas comportamentais organizadas pela 5-HT. Além disso, os resultados obtidos com a lesão sugerem que os receptores 5-HT1A parecem apresentar diferenças funcionais espécie-específicas, o que pode ser reflexo de diferentes pressões seletivas experimentadas por aves e mamíferos ao longo da evolução dos vertebrados.Abstract : Introduction: several studies have demonstrated the inhibitory role of serotonergic circuits on ingestive and sleep behaviors both in mammals and birds. Intracerebroventricular (ICV) injections of serotonin (5-HT), however, evoked oposite effects: increased water intake and sleep. We associated these responses to 5-HT1A receptors, because the activation of these receptors caused similar responses. However, the 5-HT1A receptor is located on serotonergic neurons (as autoreceptor) as well as on different neurons (as heteroreceptor), and produces different effects based on its location. Therefore, we decided to investigate the participation of 5-HT1A receptor on dipsogenic and hypnogenic 5-HT-mediated responses to try discriminate the role of auto and heteroreceptors. Methods: the animals (adult pigeons, Columba lívia, both sex, 400-550g of body weight) were divided in 5 groups. Each group represented one different experiment. Experiment 1: 16 pigeons were divided in two groups according on the antagonist used as pretreatment and were injected with: MM77 (0, 23 or 69 nmol, heteroreceptor antagonist), or WAY100635 (WAY, 0, 0.1, 0.3 or 1 nmol, 5-HT1A auto and heterorreceptor antagonist) and 20 min. afterwards injected with 5-HT (0, 50 or 150 nmol) or 8-OH-DPAT (30 nmol). The animals behaviors were registered during the first hour after the last injection and the food and water intake was evaluated at the end of this period. Experiment 2: 12 pigeons were divided in 2 groups and were stereotaxically implanted with an ICV cannula guide (bilateral) to receive the serotonergic neurotoxin 5,7-Dihydroxytryptamine (5,7-DHT, 200µg/injection) or its vehicle. Past 12 days the tests with 5-HT (150 nmol), 8-OH-DPAT (30 nmol) or vehicle (1% ascorbic acid in 0.9 NaCl) started, with seven days apart each other. These animals were killed 28 days after the surgery and the encephalic levels of 5-HT were analised to verify possible degenerative effects of 5,7-DHT. Moreover, we used other 18 animals divided in three groups, a) six naïve pigeons that were killed to be used as reference of the basal levels of 5-HT and another 2 groups that were inject with 5.7-DHT (N: 6) or its vehicle (N:6) and were perfused 12 days later to verify the 5,7-DHT effects on serotonergic neurons. Experiment 3: six naïve pigeons were killed and had their brains dissecated and brainstem and hypothalamic sections reacted by autoradiographic approach to demonstrate the distribution of 5-HT1A binding sites with the selective radioligand [3H] 8-OH-DPAT. Experiment 4: 15 pigeons with ICV cannula guide implanted were divided in three groups and treated with: 8-OH-DPAT (30 nmol) withfree (N:5) or without acess to water after the injection (N:5), and vehicle (N:5). 90 min. later the animals were perfused and brainstem sections reacted to detect Fos protein expression in serotonergic and in non-serotonergic neurons, and hypothalamic sections processed to detect Fos activation. Experiment 5: 10 pigeons with ICV cannula guide implanted were divided in three groups and treated with: 5-HT (150 nmol) with free (N:5) or without acess to water after the injection (N:5). 90 min. later the animals were perfused and hypothalamic sections processed to detect the Fos activation. Results: both 5-HT and 8-OH-DPAT evoked huge increase in water intake and sleep duration. The 8-OH-DPAT injection also produce hyperphagic responses. The ingestive and hypnogenic effects of the treatments were partially or totally inhibited by the antagonists, sugesting the participation of 5-HT1A receptors on behavioral changes produced by 5-HT. However, the pharmacologic data did not permit specify between the action of 5-HT1A auto or heteroreceptors, but indicate the interaction between these two receptors as an important aspect of serotonergic control upon ingestive behavior. Besides its impressive effects on serotonergic neurons density, the 5,7-DHT lesion did not affect the behavioral changes caused by the treatments, suggesting that in animals with anormal serotonergic function, 5-HT1A receptors located in non-serotonergic neurons seem to be related to the treatments effects. Additionally, the antagonists and the 5,7-DHT lesion increased the sleep, indicating one tonic inhibitory effect of serotonergic circuits on sleep. The treatments also increased the Fos protein activation in hypothalamic regions with high 5-HT1A binding sites density that seem to be involved with food, body fluid and sleep regulation. Conclusion: the dipsogenic and hypnogenic responses evoked by 5-HT seem to be mediated partially by both 5-HT1A auto and heteroreceptors. Apparently, these responses are regulated by 5-HT1A receptors located on encephalic (hypothalamic and brainstem) regions directly or indirectly involved with ingestive and sleep/wake cycle regulation in birds. Our results also indicate small differences in the neuronal activity evoked by 5-HT and by 8-OH-DPAT suggesting that other serotonergic receptor also participate in behavioral responses organized by 5-HT. Moreover, the results produced by 5,7-DHT lesion indicate that 5-HT1A receptors seem present specie-specific functional differences that could represent different seletive pressions experimented by birds and mammal during vertebrate evolution
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