Should New Anti-Malarial Drugs be Subsidized?

We use analytical and numerical models to explain and quantify the welfare effects of subsidies for artemisinin combination treatments (ACTs), a valuable new class of antimalarial drugs. There are two (second-best) efficiency rationales for such subsidies: by expanding drug use, they reduce infection transmission from one individual to another, and they slow the evolution of drug resistance by deterring use of substitute monotherapy drugs for which resistance emerges more rapidly than for ACTs. Our analysis merges epidemiological models of malaria transmission among individuals and mosquitoes, evolution of drug resistance, and economic models of the demand for alternative drugs; parameter values for the simulations are representative of malaria prevalence in sub-Saharan Africa. We find that large subsidies for ACT are welfare improving across many plausible scenarios for malaria transmission, drug-demand elasticities, and evolution of drug resistance; the benefits of the policy are often several times larger than the costs.antimalarial drugs, resistance externality, transmission externality, subsidies, welfare effects

Elastomer Reinforced with Carbon Nanotubes

Elastomers are reinforced with functionalized, single-walled carbon nanotubes (SWNTs) giving them high-breaking strain levels and low densities. Cross-linked elastomers are prepared using amine-terminated, poly(dimethylsiloxane) (PDMS), with an average molecular weight of 5,000 daltons, and a functionalized SWNT. Cross-link densities, estimated on the basis of swelling data in toluene (a dispersing solvent) indicated that the polymer underwent cross-linking at the ends of the chains. This thermally initiated cross-linking was found to occur only in the presence of the aryl alcohol functionalized SWNTs. The cross-link could have been via a hydrogen-bonding mechanism between the amine and the free hydroxyl group, or via attack of the amine on the ester linage to form an amide. Tensile properties examined at room temperature indicate a three-fold increase in the tensile modulus of the elastomer, with rupture and failure of the elastomer occurring at a strain of 6.5

A GIT interpretration of the Harder-Narasimhan filtration

An unstable torsion free sheaf on a smooth projective variety gives a GIT unstable point in certain Quot scheme. To a GIT unstable point, Kempf associates a "maximally destabilizing" 1-parameter subgroup, and this induces a filtration of the torsion free sheaf. We show that this filtration coincides with the Harder-Narasimhan filtration.Comment: 19 pages; Comments of the referees and references added. The construction for holomorphic pairs (Sections 6 and 7 from previous version) will appear in a further publication. To appear in Rev. Mat Complutens

Clinically immune hosts as a refuge for drug-sensitive malaria parasites

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>Plasmodium falciparum </it>that confer resistance to first-line antimalarial drugs have spread throughout the world from a few independent foci, all located in areas that were likely characterized by low or unstable malaria transmission. One of the striking differences between areas of low or unstable malaria transmission and hyperendemic areas is the difference in the size of the population of immune individuals. However, epidemiological models of malaria transmission have generally ignored the role of immune individuals in transmission, assuming that they do not affect the fitness of the parasite. This model reconsiders the role of immunity in the dynamics of malaria transmission and its impact on the evolution of antimalarial drug resistance under the assumption that immune individuals are infectious.</p> <p>Methods</p> <p>The model is constructed as a two-stage susceptible-infected-susceptible (SIS) model of malaria transmission that assumes that individuals build up clinical immunity over a period of years. This immunity reduces the frequency and severity of clinical symptoms, and thus their use of drugs. It also reduces an individual's level of infectiousness, but does not impact the likelihood of becoming infected.</p> <p>Results</p> <p>Simulations found that with the introduction of resistance into a population, clinical immunity can significantly alter the fitness of the resistant parasite, and thereby impact the ability of the resistant parasite to spread from an initial host by reducing the effective reproductive number of the resistant parasite as transmission intensity increases. At high transmission levels, despite a higher basic reproductive number, <it>R</it>₀, the effective reproductive number of the resistant parasite may fall below the reproductive number of the sensitive parasite.</p> <p>Conclusion</p> <p>These results suggest that high-levels of clinical immunity create a natural ecological refuge for drug-sensitive parasites. This provides an epidemiological rationale for historical patterns of resistance emergence and suggests that future outbreaks of resistance are more likely to occur in low- or unstable-transmission settings. This finding has implications for the design of drug policies and the formulation of malaria control strategies, especially those that lower malaria transmission intensity.</p

Polymerization initated at sidewalls of carbon nanotubes

The present invention is directed to aryl halide (such as aryl bromide) functionalized carbon nanotubes that can be utilized in anionic polymerization processes to form polymer-carbon nanotube materials with improved dispersion ability in polymer matrices. In this process the aryl halide is reacted with an alkyllithium species or is reacted with a metal to replace the aryl-bromine bond with an aryl-lithium or aryl-metal bond, respectively. It has further been discovered that other functionalized carbon nanotubes, after deprotonation with a deprotonation agent, can similarly be utilized in anionic polymerization processes to form polymer-carbon nanotube materials. Additionally or alternatively, a ring opening polymerization process can be performed. The resultant materials can be used by themselves due to their enhanced strength and reinforcement ability when compared to their unbound polymer analogs. Additionally, these materials can also be blended with pre-formed polymers to establish compatibility and enhanced dispersion of nanotubes in otherwise hard to disperse matrices resulting in significantly improved material properties. The resultant polymer-carbon nanotube materials can also be used in drug delivery processes due to their improved dispersion ability and biodegradability, and can also be used for scaffolding to promote cellular growth of tissue

Seasonal and Temperature-Associated Increases in Gram-Negative Bacterial Bloodstream Infections among Hospitalized Patients

BACKGROUND: Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels. METHODS: A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases. RESULTS: A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2-15.4) to 51.8% for Acinetobacter (95% CI 41.1-63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0-5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6°C (10°F) rise in mean monthly temperature corresponded to increases in gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1-4.9) to 10.8% for Acinetobacter (95% CI 6.9-14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3-3.2) but no significant change in Enterococcus BSI frequency. CONCLUSIONS: Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important gram-negative bacteria

The effective bandwidth problem revisited

The paper studies a single-server queueing system with autonomous service and $\ell$ priority classes. Arrival and departure processes are governed by marked point processes. There are $\ell$ buffers corresponding to priority classes, and upon arrival a unit of the $k$th priority class occupies a place in the $k$th buffer. Let $N^{(k)}$, $k=1,2,...,\ell$ denote the quota for the total $k$th buffer content. The values $N^{(k)}$ are assumed to be large, and queueing systems both with finite and infinite buffers are studied. In the case of a system with finite buffers, the values $N^{(k)}$ characterize buffer capacities. The paper discusses a circle of problems related to optimization of performance measures associated with overflowing the quota of buffer contents in particular buffers models. Our approach to this problem is new, and the presentation of our results is simple and clear for real applications.Comment: 29 pages, 11pt, Final version, that will be published as is in Stochastic Model