Evaluation of personal protection afforded by repellent-treated sandals against mosquito bites in south-eastern Tanzania

Outdoor and early evening mosquito biting needs to be addressed if malaria elimination is to be achieved. While indoor-targeted interventions, such as insecticide-treated nets and indoor residual spraying, remain essential, complementary approaches that tackle persisting outdoor transmission are urgently required to maximize the impact. Major malaria vectors principally bite human hosts around the feet and ankles. Consequently, this study investigated whether sandals treated with efficacious spatial repellents can protect against outdoor biting mosquitoes. Sandals affixed with hessian bands measuring 48 cm treated with 0.06 g, 0.10 g and 0.15 g of transfluthrin were tested in large cage semi-field and full field experiments. Sandals affixed with hessian bands measuring 240 cm and treated with 0.10 g and 0.15 g of transfluthrin were also tested semi field experiments. Human landing catches (HLC) were used to assess reduction in biting exposure by comparing proportions of mosquitoes landing on volunteers wearing treated and untreated sandals. Sandals were tested against insectary reared Anopheles arabiensis mosquitoes in semi-field experiments and against wild mosquito species in rural Tanzania. In semi-field tests, sandals fitted with hessian bands measuring 48 cm and treated with 0.15 g, 0.10 g and 0.06 g transfluthrin reduced mosquito landings by 45.9%, (95% confidence interval (C.I.) 28-59%), 61.1% (48-71%), and 25.9% (9-40%), respectively compared to untreated sandals. Sandals fitted with hessian bands measuring 240 cm and treated with 0.15 g and 0.10 g transfluthrin reduced mosquito landings by 59% (43-71%) and 64% (48-74%), respectively. In field experiments, sandals fitted with hessian bands measuring 48 cm and treated with 0.15 g transfluthrin reduced mosquito landings by 70% (60-76%) against Anopheles gambiae sensu lato, and 66.0% (59-71%) against all mosquito species combined. Transfluthrin-treated sandals conferred significant protection against mosquito bites in semi-field and field settings. Further evaluation is recommended for this tool as a potential complementary intervention against malaria. This intervention could be particularly useful for protecting against outdoor exposure to mosquito bites. Additional studies are necessary to optimize treatment techniques and substrates, establish safety profiles and determine epidemiological impact in different settings

Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania

Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania. In this exploratory qualitative study, Focus group discussions were held with policy-makers, regulators, research scientists and community members. Malaria control interventions discussed were: (a) improved housing, (b) larval source management, (c) mass drug administration (MDA) with ivermectin to reduce vector densities, (d) release of modified mosquitoes, including genetically modified or irradiated mosquitoes, (e) targeted spraying of mosquito swarms, and (f) spatial repellents. Larval source management and spatial repellents were widely supported across all stakeholder groups, while insecticide-spraying of mosquito swarms was the least preferred. Support for MDA with ivermectin was high among policy makers, regulators and research scientists, but encountered opposition among community members, who instead expressed strong support for programmes to improve housing for poor people in high transmission areas. Policy makers, however, challenged the idea of government-supported housing improvement due to its perceived high costs. Techniques of mosquito modification, specifically those involving gene drives, were viewed positively by community members, policy makers and regulators, but encountered a high degree of scepticism among scientists. Overall, policy-makers, regulators and community members trusted scientists to provide appropriate advice for decision-making. Stakeholder opinions regarding alternative malaria interventions were divergent except for larval source management and spatial repellents, for which there was universal support. MDA with ivermectin, housing improvement and modified mosquitoes were also widely supported, though each faced concerns from at least one stakeholder group. While policy-makers, regulators and community members all noted their reliance on scientists to make informed decisions, their reasoning on the benefits and disadvantages of specific interventions included factors beyond technical efficiency. This study suggests the need to encourage and strengthen dialogue between research scientists, policy makers, regulators and communities regarding new interventions

A Logical Verification Methodology for Service-Oriented Computing

We introduce a logical verification methodology for checking behavioural properties of service-oriented computing systems. Service properties are described by means of SocL, a branching-time temporal logic that we have specifically designed to express in an effective way distinctive aspects of services, such as, e.g., acceptance of a request, provision of a response, and correlation among service requests and responses. Our approach allows service properties to be expressed in such a way that they can be independent of service domains and specifications. We show an instantiation of our general methodology that uses the formal language COWS to conveniently specify services and the expressly developed software tool CMC to assist the user in the task of verifying SocL formulae over service specifications. We demonstrate feasibility and effectiveness of our methodology by means of the specification and the analysis of a case study in the automotive domain

Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam

Software Model Checking with Explicit Scheduler and Symbolic Threads

In many practical application domains, the software is organized into a set of threads, whose activation is exclusive and controlled by a cooperative scheduling policy: threads execute, without any interruption, until they either terminate or yield the control explicitly to the scheduler. The formal verification of such software poses significant challenges. On the one side, each thread may have infinite state space, and might call for abstraction. On the other side, the scheduling policy is often important for correctness, and an approach based on abstracting the scheduler may result in loss of precision and false positives. Unfortunately, the translation of the problem into a purely sequential software model checking problem turns out to be highly inefficient for the available technologies. We propose a software model checking technique that exploits the intrinsic structure of these programs. Each thread is translated into a separate sequential program and explored symbolically with lazy abstraction, while the overall verification is orchestrated by the direct execution of the scheduler. The approach is optimized by filtering the exploration of the scheduler with the integration of partial-order reduction. The technique, called ESST (Explicit Scheduler, Symbolic Threads) has been implemented and experimentally evaluated on a significant set of benchmarks. The results demonstrate that ESST technique is way more effective than software model checking applied to the sequentialized programs, and that partial-order reduction can lead to further performance improvements.Comment: 40 pages, 10 figures, accepted for publication in journal of logical methods in computer scienc

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Service Renaming in Component Composition

In component-based systems, the behavior of components is usually described at component interfaces and the components are characterized as requester (active) and provider (reactive) components. Two interacting components are considered compatible if all possible sequences of services requested by one component can be provided by the other component. This concept of component compatibility can be extended to sets of interacting components, however, in the case of several requester components interacting with one or more provider components, as is typically the case of cleint-server applications, the requests from different components can be interleaved and then verifying component compatibility must take into account all possible interleavings of requests. Such interleaving of requests can lead to unexpected behavior of the composed system, e.g. a deadlock can occur. Service renaming is proposed as a method of systematic eliminating of such unexpected effects and streamlining component compositions

Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to chronic airway infections, male infertility, and situs abnormalities. Multiple causative PCD mutations account for only 65% of cases, suggesting that many genes essential for cilia function remain to be discovered. By using zebrafish morpholino knockdown of PCD candidate genes as an in vivo screening platform, we identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility. c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is a flagellar matrix protein that accumulates specifically when cilia motility is impaired. The Chlamydomonas ida6 mutant identifies CCDC65/FAP250 as an essential component of the nexin-dynein regulatory complex. Analysis of 295 individuals with PCD identified recessive truncating mutations of C21orf59 in four families and CCDC65 in two families. Similar to findings in zebrafish and planaria, mutations in C21orf59 caused loss of both outer and inner dynein arm components. Our results characterize two genes associated with PCD-causing mutations and elucidate two distinct mechanisms critical for motile cilia function: dynein arm assembly for C21orf59 and assembly of the nexin-dynein regulatory complex for CCDC65

Electronic Structure and Bonding of Icosahedral Core-Shell Gold-Silver Nanoalloy Clusters Au_(144-x)Ag_x(SR)_60

Atomically precise thiolate-stabilized gold nanoclusters are currently of interest for many cross-disciplinary applications in chemistry, physics and molecular biology. Very recently, synthesis and electronic properties of "nanoalloy" clusters Au_(144-x)Ag_x(SR)_60 were reported. Here, density functional theory is used for electronic structure and bonding in Au_(144-x)Ag_x(SR)_60 based on a structural model of the icosahedral Au_144(SR)_60 that features a 114-atom metal core with 60 symmetry-equivalent surface sites, and a protecting layer of 30 RSAuSR units. In the optimal configuration the 60 surface sites of the core are occupied by silver in Au_84Ag_60(SR)_60. Silver enhances the electron shell structure around the Fermi level in the metal core, which predicts a structured absorption spectrum around the onset (about 0.8 eV) of electronic metal-to-metal transitions. The calculations also imply element-dependent absorption edges for Au(5d) \rightarrow Au(6sp) and Ag(4d) \rightarrow Ag(5sp) interband transitions in the "plasmonic" region, with their relative intensities controlled by the Ag/Au mixing ratio.Comment: 4 figure