Ecology and Epidemiology of Integrated Malaria Vector Management in Dar es Salaam, Tanzania

Malaria remains one of the major contributors to the global burden of disease with approximately 70% of the clinical malaria attacks occurring in sub-Saharan Africa. Sub- Saharan Africa has the highest risk as ideal climatic conditions for transmission coincide with occurrence of some of the most efficient malaria vectors, namely Anopheles gambiae s.s., Anopheles arabiensis and Anopheles funestus.. Even though it is estimated that by the year 2030 more than 50% of the African population will live in towns and cities, relatively little is known about urban malaria epidemiology, larval ecology and adult mosquito behaviour. Although integrated malaria control programs including environmental management and larviciding have proven successful before the Global Eradication Campaign started in 1955, they were neglected after the invention of DDT. Lately interest into these control measures has revived but it remains to be determined whether they are feasible and cost-effective in urban Africa. The overall goal of the research presented in this thesis was to enhance current understanding of urban malaria epidemiology and ecology and to take an in-depth look at the effectiveness of larviciding with Bacillus thuringiensis (Bti) in the context of the Urban Malaria Control Program (UMCP) in Dar es Salaam, Tanzania. Our findings are based on data derived from the first 3 years of the UMCP, where data collection started in March 2004. The project area includes 5 wards in each of the 3 municipalities which consist of 67 mitaa covering an area of 55 km2 in which 611,871 people lived during the population census of 2002. Achieving the UMCPs objectives fundamentally relies on three component activities: 1) Mapping and surveillance of potential Anopheles breeding sites, 2) Monitoring of adult mosquito densities, and 3) Household surveys with questionnaires and blood smears testing for malaria parasite infection. In the third year of the UMCP, beginning in March 2006, the routine application of the microbial larvicides Bti in open habitats and Bs in closed habitats was initiated in 3 of the 15 wards in the study area, adding to existing interventions such as bednets, house screening, ceiling boards, repellents, spray and coils. At the same time a detailed survey of mosquito biting behaviour, human behaviour and domestic protection measures was conducted in 12 Ten Cell Units (TCU), the smallest subunit of local government in Tanzania, which presented the highest An. gambiae s.l. densities during the early period of the UMCP surveillance system. Human landing catch (HLC) was conducted in 216 houses on an hourly basis indoors and outdoors from 6 pm till 7 am and residents were interviewed about their sleeping behaviour, where they spend their evenings and what kind of preventive measures against malaria they use. Personal protection of an insecticide treated net (ITN) was evaluated using an extension of a recently developed mathematical model. Overall An. gambiae s.l. exhibited a classical hourly biting pattern. In contrast one of the complex’s component sibling species, namely An. arabiensis, had an early biting peak before 10 pm. Both sibling species, namely An. gambiae s.s. and An. arabiensis, as well as An. funestus and An. coustani were highly exophagic. This behaviour led to a reduced personal protection against exposure to An. gambiae s.s. by ITNs which conferred 59% reduction of exposure in Dar es Salaam compared to 70% in rural Tanzania. An. arabiensis is a vector of only modest importance in Dar es Salaam which is fortunate because ITNs only conferred 38% protection against exposure to this species of mosquito. ITNs conferred slightly less protection against exposure to malaria vectors in good quality houses. This is mainly because people living in good houses tend to spend more time indoors before they go to bed. An. gambiae s.l. is the most important vector in Dar es Salaam , responsible for an EIR (entomological inoculation rate) of 1.00 infectious bites per person per year whereas An. funestus has an EIR of 0.13. Surprisingly, An. coustani also acts as a notable vector in Dar es Salaam with an EIR of 0.20 infectious bites per person per year. Malaria transmission is seasonal with two peaks of malaria prevalence during and after the two rainy seasons. Malaria prevalence was only related to EIR in children under 5 years of age, with a classical ageprevalence distribution similar to most of rural Africa. Malaria prevalence steadily declined from 2004 onwards as the use of window screenings, ceiling boards and more effective drugs like amodiaquine and artemisin-based drugs increased. ITNs (prevalence reduction estimate 20%, 95% CI 0%-36%; P=0.060; year 1) and ceiling boards (prevalence reduction estimate 22%, 95% CI 3%-38%; P=0.026; year 2) conferred modest personal protection and reduced malaria prevalence by approximately one fifth. By comparison, a much greater reduction (prevalence reduction estimate 50%, 95% CI 20%-64%; P=0.002) of malaria prevalence was achieved by larviciding with Bti. This was mainly achieved through major reductions of An. gambiae during July and August when most of the sporozoite infected mosquitoes were caught, combined with all-year-round suppression of the secondary vectors, namely An. funestus and An. coustani. This major achievement was only possible through the novel surveillance and staff management procedures developed by the UMCP to enable effective community based implementation in a decentralized manner. Standards of the surveillance improved greatly after the onset of the program with realized reaction times to vector surveillance at observations being one day, week and month at ward, municipality and city level, respectively. These results of changing biting behaviour of the main malaria vectors in urban settings and the therefore lower but still useful personal protection offered by ITNs call for additional complementary vector control methods such as environmental management or larviciding. The UMCP demonstrated that major reductions in malaria prevalence can be achieved through routine application of microbial larvicides with its new practical management and surveillance system. As these represent the early results of the program, we expect substantial improvement with time and investment. Here we demonstrated for the first time since before the Global Eradication Campaign era, a success story of a malaria control program integrating larviciding, which could be easily adapted by other African cities as a cost-effective option for malaria prevention

Does direct democracy really work? A review of the empirical evidence from Switzerland

Discussions about direct democracy and its advantages and risks are often superficial, invoke stereotypes and ignore empirical data. This article tests seven common criticisms of direct democracy by referring to the Swiss experience. Evidently, Swiss democracy is not a copy/paste model, but has developed in a specific historical and institutional setting. It is obvious that both conservative as well as left-wing critics overemphasize their case against direct democracy by (wilfully) neglecting the evidence. Direct democracy does not lead to anarchy. The common people can make reasonable decisions. Minorities are not more discriminated against in direct democratic systems than in representative ones. Money plays a role in direct democracy, as it does in representative systems. Direct democracy slows down reforms, but it also makes them steadier and more sustainable. Direct democracy brings contentment to its citizens. Finally, direct democracy is not ideologically predisposed. It is a mechanism to revert policies back to the median voter.Dyskusje o demokracji bezpośredniej, jej zaletach i zagrożeniach są często powierzchowne, odwołujące się do stereotypów i pomijające dane empiryczne. Niniejszy artykuł, odwołując się do doświadczeń szwajcarskich, analizuje siedem czynników dotyczących demokracji bezpośredniej. Oczywistym jest fakt, iż szwajcarska demokracja nie jest łatwym do powielenia modelem, m.in. ze względu na to, że rozwinęła się w bardzo specyficznych warunkach historycznych i instytucjonalnych. Odpowiadając na krytykę demokracji bezpośredniej, zaznaczyć należy, iż demokracja bezpośrednia nie prowadzi do anarchii, a zwykli obywatele mogą podejmować racjonalne decyzje. Ponadto, w demokracji bezpośredniej mniejszości nie są dyskryminowane bardziej niż w demokracji przedstawicielskiej, a pieniądze odgrywają w obu formach demokracji podobną rolę. Pamiętać należy, iż demokracja bezpośrednia spowalnia reformy, ale jednocześnie czyni je stabilniejszymi i bardziej zrównoważonymi, co z kolei przekłada się na zadowolenie wśród obywateli

Double Field Theory and N=4 Gauged Supergravity

Double Field Theory describes the NS-NS sector of string theory and lives on a doubled spacetime. The theory has a local gauge symmetry generated by a generalization of the Lie derivative for doubled coordinates. For the action to be invariant under this symmetry, a differential constraint is imposed on the fields and gauge parameters, reducing their possible dependence in the doubled coordinates. We perform a Scherk-Schwarz reduction of Double Field Theory, yielding electric gaugings of half-maximal supergravity in four dimensions when integrability conditions are assumed. The residual symmetries of the compactified theory are mapped with the symmetries of the effective theory and the differential constraints of Double Field Theory are compared with the algebraic conditions on the embedding tensor. It is found that only a weaker form of the differential constraint has to be imposed on background fields to ensure the local gauge symmetry of the reduced action.Comment: 25 pages; v2: typos corrected, published versio

Zukunft des Berufsbildes Berufs-, Studien- und Laufbahnberatung : Thesen aus Sicht von Studierenden sowie Absolventinnen und Absolventen des MAS ZFH in Berufs-, Studien- und Laufbahnberatung

Die vorliegende Arbeit widmet sich dem Thema «Zukunft des Berufsbildes Berufs-, Studien- und Laufbahnberatung». Die Fragestellung wurde von aussen an das IAP Institut für Angewandte Psychologie herangetragen zur Bearbeitung in einer Masterarbeit im Rahmen des MAS ZFH in Berufs-, Studien- und Laufbahnberatung. Nach einer Einleitung sowie Festlegung und Präzisierung der Fragestellung erfolgt eine Auseinandersetzung mit der geschichtlichen Entwicklung des Berufsfelds. Auf dieser Basis werden wichtige normative Eckpunkte des Berufsbildes erläutert, es erfolgt eine Berufssoziologische Auseinandersetzung mit den Begriffen «Beruf», «Profession» sowie «Berufsbild» und das Tätigkeitsfeld wird unter einer systemischen Perspektive beleuchtet. Die Überlegungen bilden die Grundlage zur Bestimmung wichtiger Aspekte zum Berufsbild Berufs-, Studien- und Laufbahnberatung. Zu ausgewählten Dimensionen wurde schliesslich mittels Fragebogen und Einzelgesprächen eine qualitative Befragung von Studierenden sowie Absolventinnen und Absolventen der Ausbildung am IAP Institut für Angewandte Psychologie durchgeführt. Nach der Darstellung der Ergebnisse erfolgt eine Verdichtung zu Thesen bezüglich der Zukunft des Berufsbildes. Die abschliessenden Kapitel widmen sich einem Fazit, einer kritischen Reflexion der Arbeit sowie einem Ausblick

Tiers garant, tiers payant (42 LAMal) – Un point de vue de droit des obligations

Dans la relation entre assureurs, assurés et fournisseurs, chacun exploite le peu de liberté contractuelle qui lui est consentie pour sauvegarder ses intérêts. C'est donc tout naturellement que les parties se tournent vers le droit des obligations. Celui-ci peut avoir deux usages: moduler les rapports entre parties, avec ou sans le consentement des autres, ou aider à l'interprétation des normes légales. Mais, au-delà d'un simple outil, il peut offrir des pistes d'évolution pour le droit des assurances sociales

Cadmium selenide nanocrystals for specific interactions with biomolecules

The goal of this work was to produce water-soluble fluorescent semiconductor nanocrystals suitable to interact specifically with biomolecules and thereby creating hybrid supramolecular structures composed of nanocrystals and proteins. Hydrophobic TOPO-coated cadmium selenide (CdSe) nanocrystals (NCs) were synthesized using published protocols (TOP/TOPO method). The challenge was to find a novel procedure to solubilize and functionalize the NCs in water for further specific interactions with biomolecules. We therefore coated the NCs with a lipid mono-layer (lipid-NCs) in a one-step process. The lipid monolayer made the NCs water soluble and simultaneously allowed to decorate the NCs surface with different functional groups. The resulting lipid-NCs are functionalized, fluorescent and stable; they can thus be used for further interaction with biomolecules. The ability of the functionalized lipid-NCs to bind specifically to biomolecules was demonstrated for His6-NCs, biotin-NCs and NTA-NCs (hexahistidine, biotin and nitrilotriacetic acid NCs) using fluorescence resonance energy transfer (FRET). Multifunctional NCs were also produced by decorating the NCs with biotin and NTA simultaneously; these NCs showed specific interactions toward to the complementary partner molecules. The properties of the lipid monolayer coat on the NCs surface were characterized by investigating its interaction with the peripheral membrane protein cytochrome c. This protein bound to the lipid-NCs only in the presence of negatively charged lipids, very similarly as in the case of lipid vesicles and mitochondrial membranes. The functionalized-NCs could also be immobilized on micro-patterned surfaces for creation of a photostable, fluorescent patterned surface for biosensor applications. We could observe via FRET the specific binding of a fluorescent protein on the NCs patterns

Novel Concepts for Functional High Resolution Microscopy

Functional imaging of biological cells and organs is one of the key techniques that drives new discoveries in life science research and medicine. In this thesis novel concepts for functional imaging at high spatial and temporal resolution are presented. In the first part, an imaging modality named Triplet Lifetime Imaging is developed. The technique allows oxygen consumption within single cells to be monitored at sub-cellular resolution. Measurement of tissue and cell oxygenation is important in order to understand cell metabolism. The method exploits oxygen induced triplet lifetime changes. The technique is applied to a biological cell system, employing as reporter a cytosolic fusion protein of -galactosidase SNAP-tag labeled with TMR. Oxygen consumption in single smooth muscle cells A7r5 during an [Arg8]-vasopressin (AVP) induced contraction is measured. The results indicate a consumption leading to an intracellular oxygen concentration that decays mono-exponentially with time. The proposed method has the potential to become a new tool for investigating oxygen metabolism at the single cell and sub-cellular level. The method is further applied to various other biological systems, demonstrating its versatility and the usefulness of this novel imaging modality. In the second part of this thesis, a concept for optical spectroscopy named nonlinear correlation spectroscopy (NLCS) is developed. The method allows monitoring of diffusing and flowing nanoparticles made of nonlinear optical material. NLCS is a method related to fluorescence correlation spectroscopy (FCS), but instead of fluorescence intensity fluctuations, NLCS analyses coherent field fluctuations of the second and third harmonic light. In bulk material, the third harmonic contribution vanishes due to the destructive interference of the third harmonic light generated in front of and behind of the focal field (Guoy phase shift). On the other hand, nanoparticles with dimensions comparable or smaller than the focal volume can generate strong higher harmonic signals. Particles based on non-centrosymmetric non-linear materials such as KNbO3 have been found to show a strong second and third harmonic signal. The method and the theory are introduced and NLCS results for diffusing polystyrene spheres (PS) as well as KNbO3 particles are presented. These spectroscopic results open the door for future extension into imaging concepts